SYNTHESI S O F NE W SEPARATIN G AGENT S FO RNUCLEA RMATERIAL S

b y JAEWOO K

NAM , B.S . A DISSERTATIO N I N CHEMISTR Y Submitte dt o th e Graduat e Facult y o f Texa s Tec h Universit y i n Partia l Fulfillmen t

o f th e Requirement s fo r th e Degre e o f DOCTO RO F PHILOSOPH Y

Approve d

Accepte d

August , 199 8ACKNOWLEDGMENT S

First , I wis h t o expres s m

y deepes t appreciatio n t o Dr . Richar dA . Bartsch , m y supervisin g professor , fo

r hi s guidance , encouragement , an dprofessional advic e throughou t

m y graduat e programa

t Texa s Tec h University . I woul dals o like t o than k to m y doctora l committe e members , Dr . Davi dM . Bimey , Dr . Alla n D . Headley , an dDr . Joh n N . Marx , for

thei r encouragemen t

an dadvice . I wis h t o expres s m y thank s t o pas t an dpresen t

member s o

f th e Bartsc h Researc h Group , fo r thei r advic e an dfriendship . Secondly , I a

mplease dt o acknowledg e suppor t b y th e Nuclea

r Material s Technolog y Divisio n of

Lo s Alamo s National Laborator y fo r th e researc h on bifunctiona l anion-exchang e resin s fo

r plutonium(rV ) sorptio n an db y th e Chemistr y Divisio n o

f Argonn e Nationa l Laboratory fo r th e researc h on ne w cycli c polyethe r compound s fo

r cesiu mio n extraction . Finally , I woul dlike t o giv e special thank s t o m y wif e Seulhe e fo

r he r lov e an d support . Withou t

he r understandin g an ddevotion , m y study woul dno t

hav e been completed . I als o wis h t o expres s special thank s to m y aunt an d uncle , Dr . He e Soo k Ki mChon g an dDr . Key Ra y Chong , fo

r thei r lov e an d support . I coul dno t finis h m y acknowledgmen t

withou t a n expressio n of

gratitud e t o m

y mothe r fo r he r lov e an d support .TABLE O F CONTENT S

ACKNOWLEDGMENT S i i ABSTRAC T xiv LIS T O F TABLE S x v LISTOFnOURE S xvi i LIS T O F SCHEME S xvii i CHAPTE R 1 . INTRODUCTIO N 1 1.1 . Backgroun dfor

Nuclea r Wast e Managemen t

1 1.2 . Plutoniu mSeparatio n b y Ion-Exchang e Resin s 3 1.3 . Cesiu mSeparatio n b y Cycli c Polyethe r Extractant s 4 1.4 . Statemen t

of Researc h Goal s 6 1.5 . Reference s 8 2 . SYNTHESI S O F POLYMER-BOUN D SEPARATIN G AGENT S 1 0 2.1 . Result s an dDiscussio n 1 0 2.1.1 . Synthesi s o

f Bifunctiona

l Anion-Exchang e Resin s 1 0 2.1.1.1 . Trimethylammonium-Containin g Bifunctional Anion-Exchang e Resin s 1 3 2.1.1.2 . Pyridinium-Containin g Bifunctiona l Anion-Exchang e Resin s 1 6 2.1.1.3 . Trimethylphosphonium-Containin g Bifunctional Anion-Exchang e Resin s 2 1 2.1.1.4 . N-Methylpicolinium-Containin g Bifunctional Anion-Exchang e Resin s 2 3

ii i2.1.2 . Evaluatio n of Bifunctional Anion-Exchang e Resin s 2 5 2.1.3 . Synthesi s of

Water-Solubl e Poly(vinylpyridines ) 3 0 2.1.3.1 . Hydroxyethyl-Substitute dWater-Solubl e Polymer s 3 1 2.1.3.2 . 3-(Trimethylammonio)propyl-Substitute d Water-Solubl e Polymer s 3 3 2.2 . Chapte r

Summar y 3 5 2.3 . Experimenta l Procedure s 3 6 2.3.1 . Source s of

Reagent s 3 6 2.3.2 . Purificatio n o

f Reagent s 3 6 2.3.3 . General 3 6 2.3.4 . General Procedur e fo r th e Synthesi s of (co-Bromoalkyl)trimethylammoniu m Bromide s 8-1 3 3 7 2.3.4.1 . (3-Bromopropyl)trimethylammoniu mBromid e (8 ) 3 7 2.3.4.2 . (4-Bromobutyl)trimethylammoniu mBromid e (9 ) 3 8 2.3.4.3 . (5-Bromopentyl)trimethylammoniu mBromid e (10 ) 3 8 2.3.4.4 . (6-Bromohexyl)trimethylammoniu mBromid e (11 ) 3 8 2.3.4.5 . (7-Bromoheptyl)trimethylammoniu mBromid e (12 ) 3 8 2.3.4.6 . (8-Bromooctyl)trimethylammoniu mBromid e (13 ) 3 9 2.3.5 . Preparatio n o

f [2-(2'-Bromoethoxy)ethyl]

- trimethylammoniu mBromid e (21 ) 3 9 2.3.6 . General Procedur e fo r th e Synthesi s of Poly[N-(co-Trimethylammonioalkyl ) 4-Vinylpyridiniu m Dibromides ] 14-1 9 4 0 2.3.6.1 . Poly[N-(2-Trimethylammonioethyl ) 4-Vinylpyridiniu mDibromide ] (14 ) 4 0 iv2.3.6.2 . Poly[N-(3-Trimethylammoniopropyl ) 4-Vinylpyridiniu mDibromide ] (15 ) 4 0 2.3.6.3 . Poly[N-(4-Trimethylammoniobutyl ) 4-Vinylpyridiniu mDibromide ] (16 ) 4 0 2.3.6.4 . Poly[N-(5-Trimethylammoniopentyl ) 4-Vinylpyridiniu mDibromide ] (17 ) 4 1 2.3.6.5 . Poly[N-(6-Trimethylammoniohexyl ) 4-Vinylpyridiniu mDibromide ] (18 ) 4 1 2.3.6.6 . Poly[N-(8-Trimethylammoniooctyl ) 4-Vinylpyridiniu mDibromide ] (19 ) 4 1 2.3.7

- Preparatio n of

Poly[2-(N-2'-Trimethylammonioethoxy)ethy l 4-Vinylpyridiniu mDibromide ] (22 ) 4 1 2.3.8 . Preparatio n of

N-(2-Bromoethyl)pyridiniu m Bromid e (23 ) 4 2 2.3.9 . General Procedure fo r th e Synthesi s of N-(o>Bromoalkyl)pyridiniu mBromide s 25-2 8 4 2 2.3.9.1 . N-(3-Bromopropyl)pyridiniu mBromid e (25 ) 4 3 2.3.9.2 . N-(4-Bromobutyl)pyridiniu mBromid e (26 ) 4 3 2.3.9.3 . N-(5-Bromopentyl)pyridiniu mBromid e (27 ) 4 4 2.3.9.4 . N-(6-Bromohexyl)pyridiniu mBromid e (28 ) 4 4 2.3.10 . Preparatio n o

f N-[2-(2'-Bromoethoxy)ethyl]pyridiniu m Bromid e (29 ) 4 4 2.3.11 . General Procedur e fo r th e Synthesi s o

f Poly[N-co-(N'-Pyridinio)alky l 4-Vinylpyridiniu m Dibromides ] 30-3 4 4 5 2.3.11.1 . Poly[N-2-(N'-Pyridinio)ethy l 4-Vinylpyridiniu m Dibromide ] (30 ) 4 5 2.3.11.2 . Poly[N-3-(N'-Pyridinio)propy l 4-Vinylpyridiniu m Dibromide ] (31 ) 4 62.3.11.3 . Poly[N-4-(^N'-Pyridinio)buty l 4-Vinylpyridiniu m Dibromide ] (32 ) 4 6 2.3.11.4 . Poly[N-5-(N'-Pyridinio)penty l 4-Vinylpyridiniu m Dibromide ] (33 ) 4 6 2.3.11.5 . Poly[N-6-(N'-Pyridinio)hexy l 4-Vinylpyridiniu m Dibromide ] (34 ) 4 6 2.3.12 . Genera l Procedur e fo r th e Synthesi s o f (O-Bromoalkyltrimethylphosphoniu m Bromide s 35-3 9 4 7 2.3.12.1 . (2-Bromoethyl)trimethylphosphoniu m Bromid e (35 ) 4 7 2.3.12.2 . (3-Bromopropyl)trimethylphosphoniu m Bromid e (36 ) 4 7 2.3.12.3 . (4-Bromobutyl)trimethylphosphoniu m Bromid e (37 ) 4 7 2.3.12.4 . (5-Bromopentyl)trimethylphosphoniu m Bromid e (38 ) 4 8 2.3.12.5 . (6-Bromohexyl)trimethylphosphoniu m Bromid e (39 ) 4 8 2.3.13 . Genera l Procedur e fo r th e Synthesi s o f Poly[N-(co-Trimethylphosphonioalkyl ) 4-Vinylpyridiniu mDibromides ] 40-4 3 4 8 2.3.13.1 . Poly[N-(^2-Trimethylphosphonioethyl ) 4-Vinylpyridiniu mDibromide ] (40 ) 4 9 2.3.13.2 . Poly[N-(3-Trimethylphosphoniopropyl ) 4-Vinylpyridiniu mDibromide ] (41 ) 4 9 2.3.13.3 . Poiy[N-(4-Trimethylphosphoniobutyl ) 4-Vinylpyridiniu mDibromide ] (42 ) 4 9 2.3.13.4 . Poly[N-(5-Trimethylphosphoniopentyl ) 4-Vinylpyridiniu mDibromide ] (43 ) 4 9

V I2.3.14 . General Procedur e fo r th e Synthesi s of Poly[N-(Picolyl ) 4-Vinylpyridiniu m Chlorides ] 47-4 9 5 0 2.3.14.1 . Poly[N-(2-Picolyl ) 4-Vinylpyridiniu m Chloride ] (47 ) 5 0 2.3.14.2 . Poly[N-(3-Picolyl ) 4-Vinylpyridiniu m Chloride ] (48 ) 5 0 2.3.14.3 . Poly[N-(4-Picolyl ) 4-Vinylpyridiniu m Chloride ] (49 ) 5 1 2.3.15 . Preparatio n of

Poly(N-Methy l 4-Vinylpyridiniu m Iodide ) (50 ) 5 1 2.3.16 . General Procedur e fo r th e Synthesi s o

f Poly[N-(N'-Methylpicolinio ) 4-Vinylpyridiniu m Diiodides ] 51-5 3 5 2 2.3.16.1 . Poly[N-(2-N'-Methylpicolinio ) 4-Vinylpyridiniu mDiiodide ] (51 ) 5 2 2.3.16.2 . Poly[N-(3-N'-Methylpicolinio ) 4-Vinylpyridiniu mDiiodide ] (52 ) 5 2 2.3.16.3 . Poly[N-(4-N'-Methylpicolinio ) 4-Vinylpyridiniu mDiiodide ] (53 ) 5 3 2.3.17 . Preparatio n of

Partiall y Substitute d Poly[N-(2'-Hydroxy)ethy l 4-Vinylpyridine ] 5 5 5 3 2.3.18 . Preparatio n o

f Partiall y Substitute d Poly[N-(2'-Hydroxy)ethy l 2-Vinylpyridine ] 5 9 5 4 2.3.19 . Preparatio n o

f Partiall y Substitute d Poly[N-(3-Trimethylammonio)propy l 4-Vinylpyridiniu mDibromide ] 6 3 5 4 2.3.20 . Preparatio n o

f Partiall y Substitute d Poly[N-(3-Trimethylammonio)propy l 2-Vinylpyridiniu mDibromide ] 6 5 5 5 2.4 . Reference s 5 6

Vl l

### 3 . SYNTHESI S O F CYCLI C POLYETHE R EXTRAC T ANT S 5 8

3.1 . Result s an dDiscussio n 5 8 3.1.1 . Synthesi s o

f Carbo n Atom-Linke dSid e Ar mCycli c Polyether s 5 8 3.1.1.1 . Preparatio n o

f Bis(l-hydroxyalkyl)

- Substitute dCrow n Ether s 5 9 3.1.1.2 . Preparatio n of

Bis(2-hydroxyalkyl)

- Substitute dCrow n Ether s 6 3 3.1.1.2.1 . B y Isomerizatio n 6 4 3.1.1.2.2 . B y Oxymercuration-Demercuratio n 6 6 3.1.1.2.3 . B y Hydroboration-Oxidatio n 7 0 3.1.2 . Synthesi s o

f Oxyge n Atom-Linke dSid e Ar mCycli c Polyether s 7 1 3.1.2.1 . Elaboratio n o

f th e Sid e Ar

mi n aCatecho l Derivativ e an dSubsequen t Cyclizatio n 7 2 3.1.2.2 . Cyclizatio n o

f aProtecte dCatecho l an d Subsequen t

Deprotectio n an dElaboratio n of th e Sid e Ar

m7 4 3.1.2.3 . Modificatio n o

f Dibenzo-18-crown- 6 an d Subsequen t

Elaboratio n of

th e Sid e Arm s 7 6 3.1.2.3.1 . Synthesi s of

Dihydroxy-Substitute d Dibenzo-18-crown- 6 7 6 3.1.2.3.2 . Synthesi s of

Di[(2-hydroxy)alkoxybenzo]

- 18-crown- 6 Involvin g Alkylatio n of Di(hydroxybenzo)- l 8-crown- 6 7 9 3.1.2.3.2.1 . Reactio n wit

h Epoxide s 8 0 3.1.2.3.2.2 . Reactio n wit

h Cycli c Sulfate Este r

8 3 3.1.2.3.2.3 . Reactio n wit

h Benzy l Bromid e 8 7

Vll l3.1.2.3.3 . Synthesi s o f Di[(2-hydroxyalkoxy)benzo]

- 18-crown- 6 Involvin g aGrignar dReactio n 8 8 3.1.2.3.3.1 . GrignardReactio n of a n Aci dChlorid e Followe db y Reductio n 8 8 3.1.2.3.3.2 . Grignar dReactio n of a n Aldehyd e 9 1 3.2 . Chapte r

Summar y 9 5 3.3. Experimenta l Procedure s 9 6 3.3.1 . Source s o

f Reagent s 9 6 3.3.2 . Purificatio n of

Reagent s 9 6 3.3.3 . General 9 7 3.3.4 . General Procedur e fo r th e Synthesi s o

f Dibenzo-18-crown- 6 Diketone s 66-6 9 9 7 3.3.4.1 . 4,4'(5')-Di[(butanoyl)benzo]-18-crown- 6 (66 ) 9 8 3.3.4.2 . 4,4'(5')-Di[(hexanoyl)benzo]-l8-crown- 6 (67 ) 9 8 3.3.4.3 . 4,4'(5')-Di[(decanoyl)benzo]-l8-crown- 6 (68 ) 9 8 3.3.4.4 . 4,4'(5')-Di[(2-ethylhexanoyl)benzo]-18-crown- 6 (69 ) 9 9 3.3.5 . General Procedur e fo r th e Synthesi s o

f Dibenzo-18-crown- 6 Diol s 70-7 2 9 9 3.3.5.1 . 4,4'(5')-Di[(l-hydroxybutyl)benzo]-18-crown- 6 (70 ) 9 9 3.3.5.2 . 4.4(5')-Di[(l-hydroxyhexyl)benzo]-18-crown- 6 (71 ) 100 3.3.5.3 . 4,4'(5')-Di[ ( 1 -hydroxydecyl)benzo]-18-crown- 6 (72 ) 10 0 3.3.6 . Preparatio n of

4,4'(5')-Di[(2-ethyl-l-hydroxyhexyl)benzo]

- 18-crown-6(73 ) 1003.3.7 . Preparatio n o f 4,4'(5')-Di[(2-ethyl-l

- (2-hydroxyethoxy)hexyl)benzo]- l 8-crown- 6 (74 ) 10 1 3.3.8 . Preparatio n of

4,4'(5>Di[(2-ethyl-l-(5-hydroxy

3-oxapentoxy)hexyl)benzo]-18-crown- 6 (75 ) 10 2 3.3.9 . Preparatio n o

f 4,4'(5')-Di[(2-ethylhexanoyl)benzo]

- 21-crown-7(77 ) 10 2 3.3.10 . Preparatio n o

f 4,4'(5')-Di[(2-ethyl-1-hydroxyhexyl)benzo]

- 21-crown-7(78 ) 10 3 3.3.11 . Preparatio n o

f 4,4'(5')-Di[(2-ethyl-l-(5-hydroxy

3-oxapentoxy)hexyl)benzo]-21-crown- 7 (79 ) 10 4 3.3.12 . Attempte dSynthesi s o f 4,4'(5')-Di[(2-ethyl-2

- hydroxyhexyl)benzo]-18-crown- 6 (82 ) from4,4'(5')

- Di[(2-ethyl-l-hydroxyhexyl)benzo]-18-crown- 6 (73 ) B y Isomerizatio n 10 5 3.3.12.1 . Isomerizatio n wit h Sulfuri c Aci d 10 5 3.3.12.2 . Isomerizatio n wit h Hydrochlori c Aci d10 6 3.3.13 . Attempte dSynthesi s o f Alkene-Substitute d Dibenzo-18-crown- 6 8 3 fro mDibenzo-18-crown- 6 Dio l 7 3 Givin g aMixtur e of Six Isomer s 83-8 8 10 1 3.3.14 . Preparatio n o

f 4,4'(5')-Di[(l-decenyl)benzo]

- l 8-crown- 6 (90 ) 10 7 3.3.15 . Attempte dSynthesi s of 4,4'(5')-Di[(2-ethyl-2

- hydroxyhexyl)benzo]-18-crown- 6 (82 ) fromth e Mixtur e of

Si x Alkene-Substitute dIsomer s 83-8 8 Givin g aMixtur e of

Thre e Isomer s 73 , 8 2 an d8 9 10 8 3.3.16 . Attempte dSynthesi s of 4,4'(5')-Di[(2-hydroxydecyl)benzo]

- 18-crown- 6 (91 ) fro

m4,4'(5')-Di[(l-decenyl)benzo]

- 18-crown- 6 (90 ) Givin g aMixtur e of th e Thre e Isomer s 72 , 9 1 an d9 2 10 9 3.3.16.1 . B y Hydroboration-Oxidatio n 109 3.3.16.2 . B y Oxymercuration-Demercuratio n 11 03.3.17 . Preparatio n of l-(2'-Hydroxy)hexoxy-3,4

- methylenedioxybenzen e (93 ) Il l 3.3.17.1 . Wit

h Cesiu mCarbonat e Il l 3.3.17.2 . Wit

h Sodiu mHydroxid e Il l 3.3.18 . Preparatio n of

3,4-Dihydroxy-l

- (2'-hydroxy)hexoxybenzen e (94 ) 11 2 3.3.19 . Attempte dSynthesi s o f 4,4'(5')

- Di[(2-hydroxyhexoxy)benzo]-18-crown- 6 (95 ) from 3,4-Dihydroxy- 1 -(2'-hydroxy)hexoxybenzen e (94 ) 11 3 3.3.20 . Attempte dSynthesi s of 1-Benzyloxy-3,4

- methylenedioxybenzen e (96 ) fromSesamo l 11 4 3.3.20.1 . Metho dA 11 4 3.3.20.2 . Metho dB 11 5 3.3.21 . Attempte dSynthesi s o f l-Benzyloxy-3,4

- dihydroxybenzen e (97 ) fro ml-Benzyloxy-3,4

- methylenedioxybenzen e (96 ) 11 5 3.3.22 . Preparatio n of

4,4'(5')-Di(nitrobenzo)-18-crown- 6 (98 ) 11 6 3.3.23 . Preparatio n of

4,4'(5')-Di(aminobenzo)-18-crown- 6 (99 ) 11 7 3.3.24 . Preparatio n o

f 4,4'(5')-Di(hydroxybenzo)-18-crown- 6 (101 ) from4,4'(5')-Di(aminobenzo)-18-crown- 6 (99 ) 11 7 3.3.24.1 . 4,4'(5')-Di[(diazoniu mtetrafluoroborato)benzo]

- 18-crown-6(100 ) 11 7 3.3.24.2 . 4,4'(5')-Di(hydroxybenzo)-18-crown- 6 (101 ) 11 8 3.3.25 . Preparatio n of

4,4'(5')-Di(acetylbenzo)

- 18-crown-6(102 ) 11 9 3.3.26 . Preparatio n o

f 4,4'(5')-Di(acetatobenzo)

- 18-crown- 6 (103 ) 11 9

X I3.3.27 . Preparatio n o f 4,4'(5')-Di(hydroxybenzo)

- 18-crown- 6 (101 ) from4,4'(5')-Di(acetatobenzo)

- 18-crown-6(103 ) 12 0 3.3.28 . Preparatio n of

l-(2'-Hydroxyoctoxy)-3,4

- methylenedioxybenzen e (104 ) 12 1 3.3.28.1 . Wit

h Cesiu mCarbonate 12 1 3.3.28.2 . Wit

h Sodiu mHydroxid e 12 2 3.3.29 . Attempte dSynthesi s o f 4,4'(5')

- Di[(2-hydroxy)octoxybenzo]-18-crown- 6 (105 ) from4,4'(5>Di(hydroxybenzo)-18-crown- 6 (101 ) 12 2 3.3.30 . Preparatio n o

f 4-Octyl-2,2-dioxo-1,3,2

- dioxathiolan e (107 ) 12 3 3.3.30.1 . 4-Octyl-2-oxo-l,3,2-dioxathiolan e (106 ) 12 3 3.3.30.2 . 4-Octyl-2.2-dioxo-l,3,2-dioxathiolan e (107 ) 12 4 3.3.31 . Attempte dSynthesi s of l-(2'-Hydroxydecyloxy)-3,4

- methylenedioxybenzen e (108 ) fro mSesamo l Givin g a Mixtur e of

Tw o Isomer s 10 8 and10 9 12 4 3.3.31.1. 1 -(2'-Hydroxydecyloxy)-3,4

-

methylenedioxybenzen e (108 ) 12 5 3.3.31.2 . l-[l'-(Hydroxymethyl)nonyloxy]-3,4

-

methylenedioxybenzen e (109 ) 12 5 3.3.32 . Preparatio n o

f 4,4'(5')-Di[(2-hydroxydecyloxy)benzo]

- 18-crown-6(110 ) 12 6 3.3.33 . Preparatio n o

f (2-Hydroxydecyloxy)benzen e (112 ) 12 7 3.3.34 . Preparatio n o

f 4,4'(5')-Di(benzyloxybenzo)

- 18-crown-6(115 ) 12 7 3.3.35 . Preparatio n o

f (3,4-Methylenedioxy)phenoxyaceti c Aci d (118 ) 12 8

Xl l3.3.36 . Attempte dSynthesi s of 1 -(3',4'-Methylenedioxy)phenoxy-2-decanon e (118 ) from(3,4-Methylenedioxy)phenoxyaceti c Aci d(119 ) Givin g th e Este r

12 0 12 9 3.3.37 . Preparatio n of

(3.4-Methylenedioxy)phenoxyacetaldehyd e Diethy l Acetal (123 ) 13 0 3.3.38 . Attempte dSynthesi s o f (3,4-Methylenedioxy)phenoxyacetaldehyd e (124 ) from(3,4-Methylenedioxy)phenoxyacetaldehyd e Diethy l Aceta

l (123 ) 13 1 3.3.39 . Attempte dSynthesi s o f (3,4-Methylenedioxy)phenoxyacetaldehyd e (124 ) from(3,4-Methylenedioxy)phenoxyacetaldehyd e Diethy l Acetal (123 ) Givin g th e Benzofura n Derivativ e 12 5 13 1 3.4 . Reference s 13 3

Xll lABSTRAC T

Syntheti c method s fo

r th e preparatio n o

f complexin g agent s fo

r th e separatio n o

f radionuclid e material s are describe di n thi s dissertation . Several serie s of ne w bifunctional anion-exchang e resin s wer e prepare db y reactio n o

f Reillex TM 40 2 po]y(4

- vinylpyridine ) resi n wit

h alkylatin g agent s CL>-Br(CH2)nQ ^ i n Q" ^ = trimethylammonio . trimethylphosphonio , an dpyridiniu mgroups . B y variatio n o f th e numbe r

o f methylen e group s i n th e spacer , th e distanc e betwee n th e tw o anion-exchang e site s wa s systematicall y varied . Th e structural variation s i n thes e bifunctional anion-exchang e resin s wer e mad e t o investigat e thei r Pu(IV ) sorptio n behavio r fromnitri c aci dmedia . Partial substitutio n of

linea r poly(vinylpyridine ) wit

h hydrophili c group s provide d ne w water-solubl e polymer s whic h hav e potential fo r us e i n metal separatio n usin g ultrafiltratio n membranes . Fo r th e cesiu mextractio n fro

macidi c nitrat e media , several serie s o f macrocycli c polyethe r compound s whic h hav e oxygenated , aliphati c sid e arm s were prepared . Acylatio n o f

dibenzo-18-crown- 6 (o r

dibenzo-21-crown-7 ) an dsubsequen t reductio n provide dne w carbo n atom-linke dsid e arme dcycli c polyethe r extractants . Several approache s t o th e synthesi s o f oxyge n atom-linke d sid e arme dcycli c polyethe r extractant s wer e explore dwit h th e mode l compoun dSesamol . Althoug h result s of th e mode l studie s wer e promising , all attempt s t o exten dth e method s t o th e preparatio n o f oxyge n atom-linke dsid e arme dcrow n ether s were unsuccessful .

XI VLIS T O F TABLE S

1.1 . Component s o

f High-Leve l Nuclea

r Waste .

- » - ) -s 2.1 . Preparatio n of

N-(a)-Bromoalkyl)pyridiniu mBromide s 25-2 8 fro mVaryin g Amount s of th e 1 ,Ci>-Dibromoalkane s 1 9 Measure dK<

i (mL/g ) Value s fo

r Pu(IV ) Sorptio n from Nitri c Aci db y Reillex TM HP Q andTrimethylammonium

Containin g Bifunctional Anion-Exchang e Resin s 2 6 2.3 . Measure dK

d(mUg ) Value s fo

r Pu(IV ) Sorptio n fro mNitri c Aci db y Trimethylpyridinium-Containin g Bifunctional Anion-Exchang e Resin s 27 2.4 . Measure dI Q (mL/g ) Value s fo r Pu(IV ) Sorptio n fro mNitri c Aci db y Trimethylphosphonium-Containin g Bifunctional Anion-Exchang e Resin s 2 8 2.5 . Measure dK^(mL/g ) Value s fo r Pu(rV ) Sorptio n fro mNitri c Aci db y Picolinium

- an dN-Methylpicolinium

Containin g Bifunctional Anion-Exchang e Resin s 2 9 2.6 . Synthesi s o f

Partiall y Substitute dPoly(4-vinylpyridines ) 54-5 8 an dThei r Wate r Solubilitie s 3 2 2.7 . Synthesi s o f

Partiall y Substitute dPoly(2-vinylpyridines ) 5 9 an d6 0 an dThei r Wate r Solubilitie s 3 3 2.8 . Synthesi s o f

Partiall y Substitute dPoly(4-vinylpyridines ) 61-6 3 an dThei r Wate r Solubilitie s 3 4 2.9 . Synthesi s o f

Partiall y Substitute dPoly(2-vinylpyridines ) 6 4 an d6 5 an dThei r Wate r Solubilitie s 3 5 3.1 . Attempte dSynthesi s o f Crow n Ethe r

Dio l 8 2 b y Oxymercuration-Demercuratio n 6 8 3.2 . Reaction s of

Sesamo l wit

h Epoxide s 8 0 3.3. Attempte dReaction s of Di(hydroxybenzo)-18-crown- 6 (101 ) wit h Epoxide s 8 2

X V3.4 . Reaction s o f Sesamo l wit

h Cycli c Sulfat

e Este r 10 7 8 4 3.5 . Attempte dSynthesi s o f (3,4-Methylenedioxy)phenoxyacetaldehyd e (124 ) 9 4

XV ILIS T O F FIGURE S

1.1 . Structur e of

Targete dNe w Bifunctiona l Anion-Exchang e Resin s 6 1.2 . Structur e of

aTargete dNe w Cycli c Polyethe r Extractan t

7 2.1 . Structur e o f

Reillex TM HP Q Resi n 1 1 2.2 . Structure s of

th e Ne w Type s of

Anion-Exchang e Resin s 1 2 2.3 . Schemati c Diagramof a n Ultrafiltratio n Proces s wit h Macromolecular

Complexe s fo

r th e Separatio n o

f Metal Ion s 3 1 3.1 . Possibl e Reactio n Pathway s upo n Treatmen t o f aCrow n Ethe r Alcoho l wit

h Aci d6 4 3.2 . Pathway s t o th e Alken e Isomer s 83-8 8 6 7 3.3. Propose dMechanis mfo r th e Formatio n o

f Benzofura

n Derivativ e 12 5 9 3

XVl lLIS T O F SCHEME S

2.1 . Synthesi s of

(co-Bromoalkyl)trimethylammoniu mBromide s 8-1 3 1 4 2.2 . Synthesi s of

Tetraalkylammonium-Containin g Bifunctional Anion-Exchang e Resin s 14-1 9 1 5 2.3 . Synthesi s of

[2-(2'-Bromoethoxy)ethyl]trimethylammoniu m Bromid e (21 ) 1 6 2.4 . Synthesi s o f

Anion-Exchang e Resi n 2 2 1 6 2.5 . Synthesi s of

N-(2-Bromoethyl)pyridiniu mBromid e (23 ) 1 7 2.6 . Reactio n of

1,2-Dibromoethan e wit

h Pyridin e i

n Benzen e 1 7 2.7 . Preparatio n of

N-(CL)-Bromoalkyl)pyridiniu mBromide s 25-2 8 1 8 2.8 . Synthesi s o f

N-[2-(2'-Bromoethoxy)ethyl]pyridiniu m Bromid e (29 ) 2 0 2.9 . Synthesi s of

Pyridinium-Containin g Bifunctiona l Anion-Exchang e Resin s 30-3 4 2 1 2.10 . Synthesi s of

(o>Bromoalkyl)trimethylphosphoniu m Bromide s 35-3 9 2 2 2.11 . Synthesi s of

Trimethylphosphonium-Containin g Bifunctional Anion-Exchang e Resin s 40-4 3 2 2 2.12 . Synthesi s of

Picoly l Substitute dPoly(4-vinylpyridines ) 47-4 9 2 3 2.13 . Synthesi s o f

Poly(N-Methy l 4-Vinylpyridiniu mIodide ) (50 ) 2 4 2.14 . Synthesi s of

N-Methylpicolinium-Containin g Bifunctiona l Anion-Exchang e Resin s 51-5 3 2 5 3.1 . Synthesi s of

Dibenzo-18-crown- 6 Diketone s 66-6 9 5 9 3.2 . Synthesi s o f

Dibenzo-18-crown- 6 Diol s 70-7 3 6 0 3.3 . Synthesi s o f

Dibenzo-18-crown- 6 Diol s 7 4 an d7 5 6 1

xvn i3.4 . Synthesi s of Di[(2-ethyl-l-hydroxyhexyl)benzo]-21-crown- 7 (78 ) 6 2 3.5 . Synthesi s of

4,4'(5')-Di[(2-ethyl-l-(5-hydroxy-3-oxapentoxy)

- hexyl)benzo]-21-crown- 7 (79 ) 6 3 3.6 . Attempte dSynthesi s of 4,4'(5')-Di[(2-ethyl-2-hydroxyhexyl)benzo]

- 18-crown-6(82 ) 6 5 3.7 . Dehydratio n of

Crow n Ethe r

Dio l 7 3 6 6 3.8 . Synthesi s of

4,4'(5')-Di[(l-decenyl)benzo]-18-crown- 6 (90 ) 6 9 3.9 . Attempte dSynthesi s of 4,4'(5')-Di[(2-hydroxydecyl)benzo]

- 18-crown- 6 (91 ) b y Oxymercuration-Demercuratio n 7 0 3.10 . Attempte dSynthesi s of 4,4'(5')-Di[(2-hydroxydecyl)benzo]

- 18-crown- 6 (91 ) b y Hydroboration-Oxidatio n 7 1 3.11 . Synthesi s of

th e Protecte dCatecho l Derivativ e 9 3 7 2 3.12 . Synthesi s o f

Catecho l Derivativ e 9 4 7 3 3.13 . Attempte dSynthesi s of 4,4'(5')-Di[(2-hydroxyhexoxy)benzo]

- 18-crown-6(95 ) 7 4 3.14 . Attempte dSynthesi s of th e Catecho l Derivativ e 9 7 7 5 3.15 . Synthesi s of

4,4'(5')-Di(hydroxybenzo)-18-crown- 6 (101 ) 7 7 3.16 . Attempte dSynthesi s of 4,4'(5')-Di(hydroxybenzo)

- 18-crown-6(101 ) 7 7 3.17 . Alternativ e Synthesi s of 4,4'(5')-Di(hydroxybenzo)

- 18-crown-6(101 ) 7 9 3.18 . Synthesi s o f

Cycli c Sulfate Este r

107 8 3 3.19 . Synthesi s o f

4,4'(5')-Di[(2-hydroxydecyloxy)benzo]

- 18-crown-6(110 ) 8 5 3.20 . Synthesi s o f

2-Hydroxydecyloxybenzen e (112 ) 8 5 3.21 . Synthesi s o f

1 -(2'-Hydroxydecyloxy)-3,4-methylenedioxybenzen e (108 ) 8 6

xi x3.22 . Attempte dSynthesi s o f Crow n Ethe r

Dio l 11 0 8 7 3.23 . Synthesi s of

Di(benzyloxybenzo)-18-crown- 6 (115 ) 8 8 3.24 . Strateg y fo

r Crow n Ethe r

Dio l Synthesi s Involvin g a Grignar dReactio n of

a n Aci dChlorid e 8 9 3.25 . Synthesi s of

(3,4-Methylenedioxy)phenoxyaceti c Aci d(118 ) 9 0 3.26 . Attempte dSynthesi s of l-(3',4'-Methylenedioxy)phenoxy-2

- decanon e (119 ) 9 0 3.27 . Strateg y for

Crow n Ethe r

Dio l Synthesi s Involvin g a Grignar dReactio n of

a n Aldehyd e 9 1 3.28 . Synthesi s o f

(3,4-Methylenedioxy)phenoxyacetaldehyd e Diethy l Acetal (123 ) 9 2 3.29 . Attempte dSynthesi s of (3,4-Methylenedioxy)phenoxyacetaldehyd e (124 ) 9 3 3.30 . Attempte dSynthesi s of (3,4-Methylenedioxy)phenoxyacetaldehyd e (124 ) 9 5

XXCHAPTE R1 INTRODUCTIO N

1.1 . Backgroun dfo

r Nuclea r Wast e Managemen t Sinc e th e U.S . Arm

y Corp s o f Engineer s buil t

th e firs t plutoniu mreactor s an d processin g facilitie s in 194 3 a s par t o f th e Manhattan Project , nuclea r waste s hav e bee n accumulatin g fro mnuclea r powe r production , national defens e activities , an dnuclea r medicin e ove r

fiv e decades . An

y activit y tha t use s radioactiv e material s inevitabl y generate s nuclear

waste s a s by-product s o

f thei r operation . Also , th e managemen t o f nuclea r waste s ha s receive dmuc h more attentio n tha n other type s o f waste s du e to thei r special handlin g an dhighe r radiotoxicity . Currently , anumbe r

of facilitie s withi n th e U . S . Departmen t of Energ y (DOE ) hav e bee n involve di

n th e managemen t

of nuclea r waste . Acros s th e DO E complex , undergroun dstroag e tank s hav e bee n use dt o capture , process , an dstor e hazardou s nuclea r wastes . Th e majorit

y of thes e waste s are store da

t fiv e DO E sites : th e Hanfor d sit e i n Richland , Washington ; th e Femal dsite i n Femald , Ohio ; th e Idah o National Engineerin g Laboratory (INEL ) nea r Idah o Falls , Idaho ; th e Oa k Ridg e Reservatio n i

n Oa k Ridge , Tennessee ; an dth e Savanna h River site i n Savanna h River , Sout

h Carolina . Th e nuclear

wast e ca n b e broadl y divide d int o tw o categories , low-leve l wast e (LLW ) an dhigh-leve l wast e (HLW) . A low-leve l wast e generall y ha s smal l amount s o f radioactiv e materia l i

n larg e volume s of

materials . Th e low-leve l wast e wil l b e converte dt o grou t

an ddispose di

n shallo w lan dburial site s a t controlle dlocations . A high-leve l waste , on th e othe r hand , ha s larg e quantitie s of radioactiv e materia lconcentrate di n asmal l mass . Th e radioactiv e material s foun di n high-leve l nuclea

r 137 , wast e are transurani c element s an dfissio n products , primaril y S r an dCs , a s show n i

n Tabl e 1.1 . Thi s high-leve l wast e wil l b e vitrifie dint o borosilicat e glas s an dremove dto a dee p geologi c repository . Tabl e 1.1 . Component s of High-Leve l Nuclea

r Waste . Elemen t Half-lif e Specifi c Activit y (Curies/gram ) Fissio n Product s 13 7 C s 129 i 8 5 K r 14 4 P r n oA g 9 0 S r 99 , T c 3 0 year s 5,900,00 0 year s 1 1 year s 1 7 minute s 2 4 second s 2 9 year s 213,00 0 year s 8 7 0.0001 7 39 0 75,500,00 0 4,300,000,00 0

14 0 0.01 7 Transuranic s 24 3 A m 24 2 C m 23 9 P u 7,38 0 year s 16 3 day s 24,11 0 year s 0. 2 3,30 0 0. 6Th e nuclea r wast e store di

n undergroun d storag e tank a t several DOE s site s usuall y contain s larg e amount s of alow-leve l radioactiv e fractio n an dnon-radioactiv e element s mixe dwit

h lesse r amount s o

f ahigh-leve l radioactiv e fraction . Therefore , pretreatmen t

o f high-leve l wast e i s performe dt o minimiz e th e volum e of high-leve l uast e becaus e of

th e hig h cos t

of virtrificatio n an d geologi c disposal . Minimizatio n o f th e high-leve l wast e ca

n b e achieve db y separatin g th e high-leve l fraction s fromth e other material s an drecyclin g a s many o f th e useful component s a s possible . A numbe r o f chemical method s ca

n b e utilize dfo

r th e separatio n of

high-leve l waste : (1 ) solven t extraction ; (2 ) ion-exchang e chromatography ; (3 ) precipitation ; (4 ) dissolution ; (5 ) solven t leaching ; (6 ) filtratio n an dmembran e processes ; an d (7 ) combustio n an d degradatio n processes. "

1.2 . Plutoniu mSeparatio n b v Ion-Exchang e Resin s Ion-exchang e processe s hav e bee n use dfo r th e recover

y an dpurificatio n o

f plutoniu mfromvariou s waste forms . Bot h cation-exchang e andanion-exchang e system s are employe dfo

r th e plutoniu mseparation . Th e cation-exchang e proces s ha s bee n foun dt o b e mor e useful fo r th e concentratio n o

f larg e volume s o f

dilut e solution s whe n moderat e decontaminatio n an dlo w waste losse s are desired . Th e anion-exchang e process , on th e othe r

hand , i s easil y adapte dto concentrate daci dan dsal t solution s an d allow s highe r

decontamination. ^ Th e anion-exchang e proces s i s rendere dattractiv e for th e recovery an d purificatio n of

plutoniu mb y tw o factor s an dahig h degre e of purificatio n i s expected . First , plutoniu mreadil y form s a n anioni c hexanitrat e complex , Pu(N03)6*^ , i n nitri c acid. ^Second , th e anioni c Pu(IV ) nitrat e comple x i s ver y strongl y sorbe do

n astrong-bas e anion-exchang e resins. ^ A n earlie r study ^ a t Lo s Alamo s National Laborator y indicate dtha

t macroporou s LewatitTM MP-500-F K

resi n showe dadramati c improvemen t i n anion-exchang e proces s efficienc y compare dwit

h th e gel-typ e Dowex TM 1 X 4 resin . Also , polyvinylpyridin e anion-exchang e resin s were reporte dt o b e more resistan t t o radiatio n tha

n th e conventiona l polystyren e resins. ^ I n addition , thes e polyvinylpyridin e resin s hav e greate r stability agains t

attac k b y nitri c acid. ^ Th e basicit y o f nitroge n i

n th e pyridin e rin g make s polyvinylpyridin e highl y resistan t to electrophili c aromati c substitution . Thi s chemical resistanc e i s importan t facto r i n many nuclea

r industr y processes . Anothe r study reveale dthat

Reillex^ ^ HP Q anion-exchang e resin , whic h wa s acopolyme r of 1 - methyl-4-vinylpyridin e an ddivinylbenzene , showe dimprove dsorptio n kinetic s an d greate r stability. ^

1.3 . Cesiu mSeparatio n b v Cvcli c Polyethe r Extractant s Solven t extractio n i s on e of

th e major area s o f application s of

cycli c polyethe r compound s an da

n efficient metho dfo

r th e separatio n o

f metal ion s froma

n aqueou s phas e int o a

n organi c phase. ^ Crow n ether s an dthei r analog s ca

n serv e a s extractant s du e t o thei r

ability t o transfe r

metal ion s betwee n tw o different liqui dphases.' ^ Durin g th e las t

tw o decades , muc h effor

t ha s been mad e towar dth e developmen t of improve dsolven t

extractio n system s o

f C s fo r it s recover

y fromnuclea

r wast e streams . Th e remova l of thi s radionuclide , whic h i s amajor biologica l hazar dan dhea t produce r i n waste , woul dsimplif

y th e handlin g an dfina

l disposa l o f

nuclear waste . 41 1* 7

Also , th e recovere dC s ca n b e use dfo

r disinfestatio n an dpreservatio n o f variou s agricultura l product s or

sterilizatio n o

f medical supplies.' ' Du e t o th e lo w charg e densit y o f cesiu mion , th e energ y associate dwit h bon d formatio n betwee n larg e cesiu mcatio n an d th e functiona l group s o f

organi c extractant s i s insufficient

to completel y dehydrat e suc h alarg e cation.' ' T o compensate , macrocycli c polyethe r compound s are selecte da s extractants . Th e energetic s o f cesiu mio n extractio n b y cycli c polyethe r extractant s i s favorabl e becaus e litti e o r n o chang e i

n th e conformational energ y o

f th e extractan t

molecul e i s involved . Anothe r proble mof

cesiu mextractio n fro

macidi c medi ai s th e difficult y o f solubilizin g th e mineral-aci danion s (NOs" , CI" , SO 4 ' ) i n anonpola

r organi c phase . A numbe r o f approache s were mad e t o enhanc e th e transfer suc h anion s int o organi c phases . First , mixe dsolven t

extractio n systems'^"* ^ wit h crow n ethe r

extractant s an dorganic

phase-solubl e carboxylic , phosphoric , an dsulfoni c aci da s liqui dcatio n exchanger s were employed . Second , crow n ether s wit h attache dproton-ionizabl e group s were use da s extractan t i n th e cesiu mextractio n fro macidi c media.' ^ Althoug h thes e approache s sometime s permi t

satisfactor

y cesiu mion extraction , the y ofte n fail t o provid e complet e recovery . I n anothe r study,'^' ^ i

t wa s reporte dtha

t th e extractio n an drecovery o f strontiu m fromstrongl y acidi c wast e stream s coul db e effecte db y th e us e o f certai n cycli c polyethe r extractant s i

n variou s oxygenated , aliphati c organi c phases .1.4 . Statemen t o f Researc h Goal s Th e separatio n of

radionuclid e material fro

mnuclea r wast e b y variou s syntheti c separatin g agent s ha s bee n studie dextensivel y sinc e th e 1940's . Th e investigation s o f thes e separatin g agent s hav e focuse dmainl y upo n achievin g hig h stability an dhig h selectivity for

certai n radionuclid e materials . Th e firs t portio n o f thi s dissertatio n deal s wit h th e synthesi s of

ne w polymer

boun dseparatin g agents . Thi s include s th e synthese s o f novel , bifunctional anion

exchang e resin s an dof

water-solubl e polymers . Ne w bifunctional anion-exchang e resin s (Figur e 1.1 ) ar e designe dan dsynthesize dfo r determinatio n of

th e influenc e of

variatio n i n thei r structure s upo n th e efficienc y an dselectivit y of plutoniu mseparatio n fro

mnitri c aci dmedia . Structural variatio n withi n th e bifunctiona l anion-exchang e resin s wil l include : (1 ) th e identit

y o f th e secon danion-exchang e group ; (2 ) th e lengt h of th e spacer betwee n tw o anion-exchang e sites ; an d(3 ) th e rigidit y of th e anion-exchang e resin .

4CH2CH ^

Figur e 1.1 . Structur e of

Targete dNew Bifunctiona l Anion-Exchang e Resins .Water-solubility o f linea r polyvinylpyridine s wil l b e achieve d b y introducin g aminimu m leve l of hydrophili c group s int o th e polymer . Th e secon dportio n of

thi s dissertatio n will involv e th e synthesi s of cycli c polyethe r extractant s for

further investigatio n o

f th e influenc e of

structural variatio n upo n th e efficienc y an dselectivity of cesiu mio n extractio n fromacidi c nitrat e media . Structural variatio n withi n th e cycli c polyether s includes : (i ) th e identity o f pivo t atom ; (ii ) th e crow n ethe r

ring size ; an d(iii ) th e lengt h an dbranchin g of

th e sid e arms . Fo r example , preparatio n of

new cycli c polyethe r

extractan t

show n i n Figur e 1.

2 i s propose d for study o f it s efficienc y an dselectivit y i n cesiu mion extraction .

H O I C6H13CHCH2O

— ^

O ^ O ^ O H

, 0 0^^rs.^^OCH2CHC6Hi 3 O 

# 0^ 0

Figur e 1.2 . Stmctur e o

f aTargete dNe w Cycli c Polyethe r Extractant .1.5 . Reference s

1 . G . D . Russ , Jr. , Nuclear Waste Disposal: Closing the Circle. Atomi c Industria l Forum , Inc. . Maryland , 1984 . p 11 . 2 . J . T . Bel l an dL . H . Bell , Chemical Pretreatment

of Nuclear Waste for

Disposal Plenum , Ne w York . 1994 , p 1 . 3 . J . L . Ryan . Chemistry of Plutonium in Anion Exchange Applications. U.S . Atomi c Energ y Commissio n Repor t TID-7607 . 1961 . p p 2-20 . 4 . J . L . Rya n an dE . J . Wheelwright . Ind. Eng. Chem., 1959 , 57 . 60 . 5 . J . P . Fari s an dR . F . Buchanan . Some Application of Anion ExchangeSpectrographic Procedures in a Nitric Acid Medium. U . S . Atomi c Energ > Commissio n Repor t

TID-7606 , 1960 , p p 185-194 . 6 . S . F . Marsh , Improved Recover, and

Purification of

Plutonium at

Los Alamos Using Macroporous Anion Exchange Resin, Lo s Alamo s Nationa l Laborator y Repor t LA-10906 . Ma y 1987 . 7 . S . F . Mars h an dK . K . S . Pillay , Effects of Ionizing Radiation on Modem Ion Exchange Materials. Lo s Alamo s Nationa l Laborator y Repor t LA-12655-MS , Octobe r 1993 . 8 . S . F . Marsh , Evaluation of a New, Macroporous Polyvinylpyridine Resin for Processing Plutonium Using Nitrate Anion Exchange. Lo s Alamo s Nationa l Laborator y Repor t

LA-11490 , Apri l 1989 . 9 . H . Nakamura , M . Takagi . an dK . Ueno . Anal. Chem., 1980 , 52. 1668 . 10 . Y . hioue , K . Wada , Y . Liu . M . Ouchi . A . Tai , an dT . Hakshi . J. Org. Chem., 1989 , 54, 5268 . 11 . W . W . Schul z an dL . A . Bray , Sep. Sci. Technol. 1987 . 22 . 191 . 12 . W . F . Kinar dan dW . J . McDowell , J. Inorg. Nucl Chem.. 1981 . 43, 2947 . 13 . W . J . McDowell , G . N . Case , an dD . W . Aldrup . Sep. Sci. Technol, 1983 , 75 , 1483 . 14 . W . F . Kinard , W . J . McDowell , an dR . R . Shoun , Sep. Sci Technol, 1980 , 75 , 1013 . 15 . W . J . McDowell . G . N . Case , J . A . McDonough , an dR . A . Bartsch , Anal Chem., 1992.6^.3013 . 816 . J . Strzelbicki an dR . A . Bartsch , Anal Chem., 1981 , 53, 1894 . 17 . E . P . Horwitz , M . L . Dietz , an dD . E . Fisher , Solvent Extr Ion Exch., 1991 . 9 . 1 18 . E . P . Horwitz , M . L . Dietz , an dD . E . Fisher , Solvent Extr. Ion Exch., 1990 , 8, 557 . 19 . E . P . Horwitz , M . L . Dietz , an dD . E . Fisher , Solvent Extr. Ion Exch., 1990 , 8. 199 .CHAPTER2 SYNTHESI S O F POLYMER-BOUN D SEPARATIN G AGENT S

2.1 . Result s an dDiscussio n Separatio n of

metal ion s wit

h polymer-boun dcomplexin g agent s ca n b e applie d i n variou s fiel do f

chemistry . Syntheti c ion-exchang e resin s are usefu l organi c compound s for

th e separatio n o

f heav y metals ' an dare rendere dinsolubl e i n all solvent s b y presenc e o f

2-12 % divinylbenzen e a s acrosslinkin g agent i n th e polymer-formin g mixture . Crosslinkin g influence s no t onl y th e solubility , bu t

als o th e chemical , thermal , an dmechanica l stability of th e polymer . A

n anion-exchang e resin , on e typ e of ion

exchang e resin , i s apolyme r tha t ha s positivel y charge dsites , suc h a s ammoniu mor phosphoniu mgroups , a s integral part s of th e polyme r

matri x an da

n equivalen t

numbe r o f replaceabl e anions , suc h a s chloride , sulfate , o r hydroxid e ions . T o alesse r extent , water-solubl e polymeri c reagent s wit h stron g complexin g propertie s hav e bee n synthesize dan duse dt o separat e metal ion s i n ahomogeneou s phase . I n thi s chapter , th e synthesi s o f avariet y of th e new bifunctional anion-exchang e resin s wil l b e described . Th e synthesi s o f water-soluble , anion-exchang e polymer s wil l b e als o described .

2.1.1 . Synthesi s o

f Bifunctional Anion-Exchang e Resin s Sinc e a n anion-exchang e proces s i s mos t frequentl y use dt o recove r plutoniu m fro mawid e rang e o f

impur e nuclea

r materials , avariet

y of anion-exchang e resin s hav e 1 0bee n evaluated . Researc h conducte da t Lo s Alamo s National Laboratory" ^ reporte dtha t resi n porosity an dbea dsiz e were th e tw o propertie s tha t mos t influenc e plutoniu m sorptio n kinetics . Replacemen t o f th e traditional polystyren e gel resi n wit h th e macroporou s resi n resulte di n adramati c improvemen t i n proces s efficiency . Also , polyvinylpyridin e anion-exchang e resin s hav e bee n reporte dto hav e greatl y increase d stability t o chemica l an dradiolyti c degradation. ^ Recently , th e macroporou s anion

exchang e resi n Reillex^" ^ HP Q wa s reporte dt o exhibi t Pu(IV ) sorptio n kinetic s comparabl e o r

superio r t o tha t of conventional polystyren e resin . Thi s resi n als o ha d greate r stability t o chemica l an dradiolyti c degradation . Reille x HP Q i s a n anion

exchang e resi n base do

n apartiall y methylate dcopolyme r of 4-vinylpyridin e an d divinylbenzen e a s show n i n Figure 2.1 . f CHsCHi meCH2CH-) n eCHsCH^ p eCH2CH ^



# Q

- e CHCHr ^

T M Figur e 2.1 . Structur e of

Reillex'" ' HP Q Resin . Althoug h th e anion-exchang e proces s wit h Reille x HP Q resi n wa s improved , it s Pu(IV ) sorptio n kinetic s were stil l slo w compare dt o th e relate dsolven t extractio n system . Thi s slowe r

exchang e proces s might

b e du e t o th e nee d of

th e mono-anioni c Pu(rV ) nitrat e comple x t o locat e asecon dsit e where it ca n absor b anothe r nitrat e anion . 1 1Therefore , it wa s postulate dthat

eve n bette r

sorptio n of

th e anioni c Pu(rV ) nitrat e comple x migh t

b e obtaine db y introducin g more ioni c group s int o th e repeat uni t i n th e anion-exchang e resin . On th e basi s of thi s proposal , th e synthesi s of avariet y o f ne w type s of anion-exchang e resins , whic h hav e tw o ion-exchang e site s per repeat unit , wa s envisioned . I n thi s dissertatio n research , th e synthese s o f new type s o

f bifunctional anion

exchang e resin s (Figur e 2.2 ) are explored . Thes e resin s consis t of poly(4-vinylpyridine ) resi n that i s modifie db y attachin g asecon danion-exchang e grou p to th e pyridin e nitroge n o f

th e bas e resi n vi aa

n alkylen e spacer . Th e secon danion-exchang e site include s trimethylammonium , pyridinium , trimethylphosphonium , an dN-methyl

picoliniu mgroups . Th e ne w bifunctiona l anion-exchang e resin s hav e bee n evaluate da t Lo s Alamo s Nationa l Laborator y t o determin e th e effect

o f structural variatio n o

f th e anion-exchang e resin s upo n th e sorptio n of th e anioni c Pu(rV ) nitrat e complex. ^

-fCH,—CH- b

N^ 2X - (CH2)^ Y CH,—CH

2X I CH2

- /

\ N

I CH 3 •CH2—CH4J ^ 2X I CH2

- CH i -CH2—CH

2X N I CH 2 '

N-CH 3

X = CI , Br , I Y = — N^CH3)3 , —P*(CH3)3 , — N J Figur e 2.2 . Structure s of th e Ne w Type s of

Anion-Exchang e Resins .

1 2Fo r th e synthesi s o

f new type s o

f anion-exchang e resins , Reille x 40 2 polymer , acommerciall y availabl e poly(4-vinylpyridine ) crosslinke dwit h 2 % o f 1,4-divinyl

benzen e wa s used . Thi s approac h ha s th e advantag e tha t th e polyme r

backbon e i s alread y formed . A potentia l rout e fo r th e synthesi s o

f suc h anion-exchang e resin s i s the preparatio n o

f appropriat e ammonium , phosphonium , o r pyridiniu msalt s fo

r us e a s alkylatin g agent s followe db y thei r couplin g wit

h poly(4-vinylpyridine) . 2.1.1.1 . Trimethylammonium-Containin g Bifunctiona l Anion-Exchang e Resin s Two-ste p processe s accomplishe dth e synthesi s of trimethylammonium

containin g bifunctional anion-exchang e resins . Th e firs t ste p wa s th e preparatio n of (co

bromoalkyl)trimethylammoniu mbromides^' ^ fo r us e a s th e alkylatin g agent s an dth e secon dste p wa s th e couplin g reactio n o f Reille x 40 2 polyme r

wit h th e (co-bromo

alkyl)trimethylammoniu mbromides . A serie s of

(co-bromoalkyl)trimethylammoniu mbromide s wa s prepare da s show n i n Schem e 2.1 . (co-Bromoalkyl)trimethylammoniu mbromide s 8-1 3 wer e obtaine dfrom th e commerciall y availabl e 1 ,a>dibromoalkane s 1-6 , respectively , b y reactio n wit h trimethylamin e i

n benzene . Trimethylamin e ga s wa s bubble dint o th e solutio n fo r 4 hour s an dthe n th e reactio n mixtur e wa s stirre dovernigh t a t roo mtemperature . Th e quaternary ammoniu mbromide s 8 an d1 0 were only slightl y contaminate dwit h th e correspondin g di-substitute dproducts . Th e (7-bromoheptyl)trimethylammoniu m bromid e (12 ) an d(8-bromooctyl)-trimethylammoniu mbromid e (13 ) wer e contaminate d wit h 55 % an d69 % o f

di-substitute dproducts , respectively , a s determine db y ' H NM R

1 3spectroscopy . Thes e mixture s of mono - an ddi-substitute dproduct s were use dwithou t purification , sinc e th e undesire ddi-substitute dproduc t shoul dno t

affect th e couplin g reactio n of

poly(4-vinylpyridine ) wit h th e (co-bromoalkyl)trimethylammoniu mbromide . Th e reactan t

(2-bromoethyl)trimethylammoniu mbromid e (7 ) wa s commerciall y available . Br(CH2)mB r N(CH3) 3

PhH,r t bubblin g fo

r 4 h then , stirrin g overnigh t Br(CH2)mNtCH3) 3 Br " (CH3)3N'(CH2)niNtCH3) 3 2 Br '

1 2 3 4 5 6 i n 3 4 5 6 7 8 Yiel do f Mono

substitutio n Produc t 8 9 1 0 1 1 1 2 1 3 76 %

83 % 83 % 85 % 37 % 29 % Schem e 2.1 . Synthesi s of (co-Bromoalkyl)trimethylammoniu mBromide s 8-13 . A ne w typ e of

anion-exchang e resi n wa s prepare da s show n i n Schem e 2.2 . T M Anion-exchang e resin s 14-1 9 were obtaine dfro mth e reactio n of

Reille x 40 2 polyme r wit h th e appropriat e (a>-bromoalkyl)trimethylammoniu mbromide s 7-13 , respectively , i n 1 1 ethano l a t reflux . I n earlie r wor k fro mBartsch' s group , Jon g Seun g Ki mfoun dtha t swellin g o f

thi s poly(4-vinylpyridine ) wa s muc h greate r i n ethano l tha

n i n DMF . Therefore , ethano l wa s use da s asolven t fo r th e couplin g reaction . Couplin g yield s fo r 1 4th e anion-exchang e resin s 14-1 9 were calculate dfro mth e percen t

of bromin e i

n th e elementa l analysi s dat aan dconfirme db y th e CH N analyse s data . iCH2CHi n 

# o N +. . + Br(CH2)niNTCH3) 3 B r

7 8 9 1 0 1 1 1 3 EtO H

reflux .



### m 2 3 4 5 6 8 lO d —t'- ' _ 1 1 ; n 2B f

• > - r (CH2)niNtCH3) . Couplin g viel d 1 4 59 % 1 5 91 % 1 6 87 % 1 7 99 % 1 8 100 % 1 9 38 % Schem e 2.2 . Synthesi s o f Tetraalkylammonium-Containin g Bifunctional Anion

Exchang e Resin s 14-19 . T o prob e th e effec t

o f replacin g th e central methylen e grou p i n th e spacer

o f anion-exchang e resi n 1 7 wit h a n oxyge n atom , th e preparatio n of anion-exchang e resi n 2 2 wa s envisioned . Th e presenc e of a n oxyge n ato mi

n th e spacer

shoul denhanc e th e flexibility of

th e space r

i n th e anion-exchang e resin . First , [2-(2'-bromoethoxy)ethyl]

- trimethylammoniu mbromid e (21 ) wa s prepare di n 80 % yiel dfro

mth e commerciall y availabl e bis(2-bromoethyl)ethe r (20 ) b y reactio n wit

h trimethylamin e i

n benzen e (Schem e 2.3) . Th e obtaine d[2-(2'-bromoethoxy)ethyl]trimethylammoniu mbromid e

1 5BrCH2CH20CH2CH2B r 2 0 N(CH3) 3

PhH,rt bubblin g fo r 4 h then , stirring ovemigh

t BiCH2CH20CH2CH2N'(CH3) 3 Br '

2 1 (80% ) Schem e 2.3 . Synthesi s of [2-(2'-Bromoethoxy)ethyl]trimethylammoniu m Bromid e (21 ) (21 ) wa s a100 % mono-substitute dproduct . Th e subsequen t couplin g reactio n o

f .T M Reille x 40 2 poly(4-vinylpyridine ) wit h alkylatin g agent

2 1 produce danion-exchang e resi n 2 2 wit

h a68 % couplin g yiel d(Schem e 2.4) .

•CH2CHi n + BrCH2CH20CH2CH2 N (CH3) 3 B r EtO H reflux , 1 0 d

2 1 CH2CH ^ }s-yj2Br

' CH2CH20CH2CH2Nr'(CH3) 3 2 2 (68 % Couplin g yield ) Schem e 2.4 . Synthesi s of Anion-Exchang e Resi n 22 . 2.1.1.2 . Pvridinium-Containin g Bifunctiona l Anion-Exchang e Resin s T o investigat e th e effec t

of changin g th e secon danion-exchang e site , th e synthesi s o f

pyridinium-containin g bifunctiona l anion-exchang e resin s wa s envisioned . N-(co-Bromoalkyl)pyridiniu mbromide s are th e requisit e alkylatin g agen t fo r th e couplin g 1 6.T M 12.1 3

reactio n wit

h Reille x 40 2 poly(4-vinylpyridine) . Several method s fo r th e preparatio n o f

N-(co-bromoalkyl)pyridiniu mbromide s were examine dt o optimiz e th e reactio n conditions . N-(2-Bromoethyl)pyridiniu mbromid e (23 ) wa s obtaine di n 25 % yiel dfro mpyridin e b y reactio n wit h 1,2-dibromoethan e i

n aceton e unde r

reflux fo r 1 5 hour s (Schem e 2.5) , whil e th e reactio n o f pyridin e wit

h 5. 0 equivalent s of

1,2-dibromo



# O N + BrCH2CH2B r aceton e reflux , 1 5 h 

# © Br " CH2CH2B r 2 3 (25% ) Schem e 2.5 . Synthesi s of A^-(2-Bromoethyl)pyridiniumBromid e (23) . ethan e i n benzen e unde r

reflu x fo r 6 hour s produce dmostl y th e bis-pyridiniu msal t 2 4 a s th e majo r produc t (Schem e 2.6) . 

# O N + BrCH2CH2B r Ph H reflux , 6 h 

# Q"- CH2CH2 — 2 Br " 2 4 

# -~0 >

Schem e 2.6 . Reactio n of 1,2-Dibromoethan e wit

h Pyridin e i

n Benzene .

1 7N-(co-Bromoalkyl)pyridiniu mbromide s 25-2 8 were obtaine dfromth e reactio n o f pyridin e wit

h l,(o-dibromoalkane s 1-4 , respectively , i n benzene , a s show n i

n Schem e 2.7 . I n contras t t o th e synthesi s of

N-(2-bromoethyl)pyridiniu mbromid e (23) , thes e reaction s i n benzen e gav e bette r

yield s an dselectivit

y fo r th e mono-substitute dproduct s

+ Br(CH2)mB r Ph H

reflux , 6 h 

# d

N- , Br

- (CH2)mB r 

# ©" - -(CH2)rir^NQ ^

^ 2 Br "

1 2 3 4 m

3 4 5 6 2 5

2 6 2 7 2 8 Yiel dof

Mono

substitutio n Produc t 94 % 99 % 83 % 82 % Schem e 2.7 . Preparatio n of N-(co-Bromoalkyl)pyridiniu mBromide s 25-28 . than thos e conducte di

n acetone . Several attempt s t o optimiz e th e reactio n condition s wer e performed , a s show n i n Tabl e 2.1 . Us e of

alarg e exces s of

1 ,co-dibromoalkan e (1 0 equivalents ) wa s foun dt o improv e bot h th e yiel dan dselectivity .

1 8Tabl e 2.1 . Preparatio n o f N-(co-Bromoalkyl)pyridiniu mBromide s 25-2 8 fro mV aryin g Amount s o f

th e l.co-Dibromoalkanes . C)]+ Br(CH2)inB r Ph H reflux , 6 h 

# Q

N : Br

- (CH2)mB r 

### ^N^_<CH:)-N;P ) 2 B r

Mola r equivalent s o f Rati o o f mono - t o Dibromoalkan e l,co-dibromoalkan e Yiel d(% ) di-substitutio n produc t Br(CH2)3B r Br(CH2)4B r

Br(CH2)5B r 2. 5

5. 0 2. 5 5. 0 10. 0 2. 5

Br(CH2)6B r 5. 0

10. 0 2. 5 10. 0 4 9 9 4 3 2 8 6 9 9 4 8 7 4 9 1 4 4 9 0 100: 0

100: 0 29:7 1 71:2 9 100: 0 40:6 0 65:3 5 88:1 2 29:7 1 88:1 2

1 9N-[2-(2'-Bromoethoxy)ethyl]pyridiniu mbromid e (29 ) wa s obtaine dfro mth e reactio n of

pyridin e wit

h bis(2-bromoethyl)ethe r

(20 ) i n aceton e unde r

reflux fo r 1 5 hour s (Schem e 2.8 ) wit

h arati o of

mono - t o di-substitutio n product s o f 96: 4 a s determine db \ H NM Rspectroscopy . 

# O N -I

- BrCH2CH20CH2CH2B r aceton e reflux , 1 5 h 

# d

N ; Br ' CH2CH20CH2CH2B r 2 0 2 9 (46% ) Schem e 2.8 . Synthesi s of N-[2-(2'-Bromoethoxy)ethyl]pyridiniu m Bromid e (29) . Th e pyridinium-containin g bifunctiona l anion-exchang e resin s 30-3 4 were T M synthesize dfro mth e reactio n of Reille x 40 2 poly(4-vinylpyridine ) wit h N-(co

bromoalkyOpyridiniu mbromide s 2 3 an d25-28 , respectively , i n ethano l a

t reflu x fo r 1 0 days , a s show n i

n Schem e 2.9 . Th e couplin g yield s were calculate dfromth e combustio n analysi s dat ab y th e sam e metho da s tha t describe dpreviousl y for

anion-exchang e resin s 14-19 .

2 0CH2CH-)n

- - f CH2CH ^

N 

# Q

^NC ^ 

### B r (CH2)mB r EtO H

reflux , 1 0 d 

# Q

N + 2 Br ' (CH2 ) . . / 

# -< o \ C 2 3 2 5 2 6 2 7 2 8 i n

2 3 4 5 6 Couplin g viel d

3 0 67 % 3 1 79 % 3 2 86 % 3 3 78 % 3 4 88 % Schem e 2.9 . Synthesi s o f Pyridinium-Containin g Bifunctiona l Anion-Exchang e Resin s 30-34 . 2.1.1.3 . Trimethvlphosphonium-Containin g Bifunctiona l Anion-Exchang e Resin s T o explor e th e effec t

of replacin g th e nitroge n ato mwit h aphosphoru s ato ma

t th e cente r o f th e secon danion-exchang e group , th e synthesi s of trimethylphosphonium

containin g bifunctional anion-exchang e resin s wa s performed . Th e co-bromoalkyltrimethylphosphoniu mbromide s 35-3 9 were obtaine dfro mth e reaction'' * of

trimethylphosphin e wit

h 1 ,co-dibromoalkane s 2 3 an d1-4 . respectively , i n toluene , a s show n i

n Schem e 2.10 . Trimethylphosphoniu mbromide s 35-3 8 wer e obtaine da s pur e mono-substitute dproduct s an dcompoun d3 9 wa s obtaine da s amixture of mono - an ddi-substitute dproduct s wit h arati o of

76:2 4 a s determine db y ' H NM R .T M spectroscopy . Subsequen t couplin g reaction s o f

Reille x 40 2 poly(4-vinylpyridine ) 2 1P(CH3) 3 + Br(CH2)mB r toluen e rt,4d Br(CH2)mPtCH3) 3 Br "

<f . (CH3)3PlCH2)ni P (CH3) 3 2 B r 2 3 1 2 3 4 m

2 3 4 5 6 3 5

3 6 3 7 3 8 3 9 Yiel dof

Mono

substitutio n Produc t 47 % 89 % 89 % 77 % 51 % Schem e 2.10 . Synthesi s o f (co-Bromoalkyl)trimethylphosphoniu mBromide s 35

- 39 . wit h th e co-(bromoalkyl)trimethylphosphoniu mbromide s 35-3 8 i n ethano l produce d trimethylphosphonium-containin g bifunctiona l anion-exchang e resin s 40-43 , respectively , a s show n i n Schem e 2.11 . •fCH2CH ^ •fCH2CH ^ r j l + Br(CH2)mP'(CH3) 3 B r N

3 6

3 7 3 8 3 9 EtO H

reflux , 1 0 d

m 2 3 4 5 4 0 4 1 4 2 4 3 2 B r N ; (CH2)n,PtCH3) 3 Couplin g viel d 11 % 58 % 52 % 45 % Schem e 2.1 1 Synthesi s o f Trimethylphosphonium-Containin g Bifunctiona l Anion-Exchang e Resin s 40-43 .

2 22.1.1.4 . N-Methvlpicolinium-Containin g Bifunctiona l Anion-Exchang e Resin s T o prob e th e effec t

of more rigidl y define dgeometrie s i n th e bifunctional anion

exchang e resin , a

n N-methylpicoliniu mgroup wa s incorporate dint o th e hos t poly(4

- vinylpyridine ) resin . Th e synthesi s o f N-methylpicolinium-containin g bifunctional anion-exchang e resin s wa s atwo-ste p process . However , th e syntheti c sequenc e wa s different fro mthat

of th e bifunctional anion-exchang e resin s discusse dpreviously . First , apicoly l grou p wa s attache dt o th e poly(4-vinylpyridine ) resi n an dsubsequentl y th e secon dpyridin e nitroge n wa s methylate dt o provid e th e secon danion-exchang e site . Th e picolyl-substitute dpoly(4-vinylpyridines ) were synthesize da s show n i n Schem e 2.12 . Th e couplin g reactio n o f Reille x 40 2 poly(4-vinylpyridine ) an d2

- picoly l chlorid e hydrochlorid e wit h K2CO3 i

n ethano l unde r

reflux fo r 1 0 day s produce d poly[N-(2-picolyl)-4-vinylpyridiniu mchloride ] (47) . Th e reaction s of poly(4-vinyl

- -eCH2CH ^

N N

•HCl K2CO 3

EtO H reflux , 1 0 d •fCH2CH ^ 

# 0 C

I N ; CH2 ^ N

4 4 (ortho) 4 5 (meta) 4 6 (para) Couplin g viel d 4 7 66 % 4 8 60 % 4 9 93 % Schem e 2.12 . Synthesi s of Picoly l Substitute dPoly(4-vinylpyridines ) 47-49 . 2 3pyridine ) wit h 3

- an d4-picoly l chlorid e hydrochlorid e wer e performe dunde r

th e sam e conditions . Th e bifunctional anion-exchang e resin s were synthesize db y methylatio n o f th e picolyl-substitute dpoly(4-vinylpyridines) . A s amode l reaction . poly(N-methy l 4

- vinylpyridiniu miodide ) (50 ) wa s synthesize dfro mReillex TM 40 2 poly(4-vinylpyridine ) b y th e reactio n wit

h CH3 I i n ethano l a s show n i

n Schem e 2.13 . Th e reactio n o f pico K 1 substitute dpoly(4-vinylpyridines ) 47-4 9 wit h iodomethan e i

n ethano l produce d

•fCH2CHin

- —eCH2CH ^

CH3 I EtO H reflux , 2 d CH3

5 0 (99 % Couplin g yield ) Schem e 2.13 . Synthesi s o f Poly(N-Methy l 4-Vinylpyridiniu mIodide ) (50) . N-methylpicolinium-containin g bifunctional anion-exchang e resin s 51-53 , respectively , a s show n i

n Schem e 2.14 . A ver

y lo w leve l of

chlorid e io n i

n thes e bifunctional anion

exchang e resin s 51-5 3 wa s foun db y elemental analysis . Also , th e leve l o f iodid e ion wa s highe r

than that for th e 1(X) % substitute dN-methylpicolinium-containin g bifunctional anion-exchang e resin s 51-53 . Therefore , it appear s tha

t chlorid e ion wa s replace dwit

h iodid e io n durin g th e reaction . Th e couplin g yield s for th e anion-exchang e resin s 51-5 3 wer e calculate dfro mth e combustio n analysi s dat awit h th e assumptio n tha

t al l chlorid e ion s i

n bot h reactan t an dproduc t

wer e replace dwit

h iodid e ions . 2 4CH2CH ^ CH3 I EtO H reflux , 3 d ^CH2CH ^ 

# 0 2 1 N + C H 

# t). N ^ 

### I CH i 4 7 {ortho) 4 8 {meta) 4 9 ipara) 5 1 5 2 5 3 Couplin g viel d

40 % 71 % 85 % Schem e 2.14 . Synthesi s of N-Methylpicolinium-Containin g Bifunctional Anion

Exchang e Resin s 51-53 . 2.1.2 . Evaluatio n of

Bifunctiona

l Anion-Exchang e Resin s Th e ne w bifunctional resin s were evaluate dfo r th e separatio n o

f Pu(IV ) fro

m nitri c aci da

t Lo s Alamo s Nationa l Laboratory.^' ^ Eac h bifunctiona l anion-exchang e resi n wa s evaluate db y measurin g th e distributio n coefficient s (K j values ) of

Pu(rV ) fro

m 1 , 3 , 5 , 7 , an d9 M nitri c acid . Th e Pu(IV ) distributio n coefficient s were calculate dby procedure s develope da

t Lo s Alamo s National Laboratory.' ^ T o obtai n informatio n abou t th e sorptio n kinetics , I Q value s fo r dynami c contac t

period s o f 3 0 minutes , 2 hours , an d6 hour s wer e measured . Initial contac t solution s containe d 3 g/

L of plutonium .

2 5Th e Pu(IV ) sorptio n behavio r of th e trimethylammonium-containin g bifunctiona l anion-exchang e resin s i s show n i n Tabl e 2.2 . Th e K

dvalue s fo

r thes e bifunctional anion-exchang e resin s surpas s thos e observe dfo r Reillex TM HP Q resin . Tabl e 2.2 . Measure dK

d(mL/g ) Value s fo

r Pu(IV ) Sorptio n fro

mNitri c Aci dby Reillex TM HP Q an dTrimethylammonium-Containin g Bifunctional Anion

Exchang e Resins. ^ HN0 3 (M ) 1

3

5

7

9 Contac t

Tim e (h ) 0. 5 2 6 0. 5 2 6 0. 5 2 6 0. 5 2 6 0. 5 2 6 Reillex TM

HP Q 6. 7 7. 1 6. 8 6 9 9 7 10 0 23 0 41 0 37 0 49 0 85 0 68 0 38 0 1,20 0 1,50 0 2

1. 3 1. 4 1. 3 3 0 3 0 2 9 39 0 41 0 40 0 2,10 0 2,70 0 2,30 0 2,90 0 4,00 0 3,10 0 K dValu e o f

n 3 2. 5 1. 5 1.7 3 7 3 9 3 8 54 0 57 0 57 0 3,00 0 4,00 0 3,30 0 3,20 0 3,30 0 3,80 0 1 fo r

-(CH2)n

4 1. 2 1. 5 1.4 4 0 4 1 4 1 60 0 65 0 66 0 3,50 0 3,50 0 3,70 0 3,90 0 2,00 0 2,70 0 • Space r

5 1.7 1. 1 1. 3 6 1 6 3 6 0 69 0 91 0 1,00 0 3,50 0 4,30 0 3,80 0 3,60 0 3,30 0 3,20 0 6

1. 6 1.7 1. 3 7 3 7 9 8 1 77 0 99 0 1,00 0 2,10 0 2,60 0 2,40 0 2,10 0 3,80 0 4,20 0 2 6Th e Pu(IV ) sorptio n behavio r o f th e trimethylpyridinium-containin g bifunctional anion

exchang e resin s i s show n i n Tabl e 2.3 . Tabl e 2.3 . Measure dK

d(mL/g ) Value s fo

r Pu(rV ) Sorptio n fro

mNitri c Aci dby Trimethylpyridinium-Containin g Bifunctiona l Anion-Exchang e Resins . HNO 3 Contact

K

d Valu e o f n fo r -(CHi),,

- Space

r (M) Tim

e (h) 2 3 4 5~ ~

~ 1 0 5 T o 0 9 T s 2 T 1. 7 2. 2

3

5

7

9 2

6 0. 5 2 6 0. 5 2 6 0. 5 2 6 0. 5 2 6 1. 0

0. 9 3 9 5 7 6 3 17 0 56 0 71 0 38 0 2,40 0 4,10 0 85 0 1,00 0 1,00 0 1. :

1 . 5 2 5 4 5 6 79 0 79 0 82 0 5,10 0 4,70 0 5,60 0 5,90 0 9,40 0 9,60 0 O 1

o -) 1. 5 2. 1 2. 1

12 2 12 0 9 2 14 0 16 0 10 0 15 0 16 0

1,40 0 1,30 0 1,00 0 1,70 0 1,90 0 1,40 0 2,00 0 2,10 0

5,70 0 4.50 0 4,70 0 8,80 0 6,80 0 11,00 0 11,00 0 13,00 0

7,00 0 6,60 0 6,20 0 13,00 0 9,00 0 7,70 0 13,00 0 11,00 0

2 7Th e Pu(rV ) sorptio n behavio r of th e trimethylphosphonium-containin g bifunctiona l anion-exchang e resin s i s show n i n Tabl e 2.3 . Tabl e 2.4 . Measure dK

d(mL/g ) Value s fo

r Pu(rV ) Sorptio n fro

mNitri c Aci db \ Trimethylphosphonium-Containin g Bifunctiona l Anion-Exchang e Resins . HN0 3 (M ) 1

3

5

7

9 Contac t

Tim e (h ) 0. 5 1 6 0 5 2 6 0 5 0 6 0. 5 2 6 0. 5 2 6 2

1. 5 1. 2 1. 2 4 4 6 7 7 2 23 0 65 0 83 0 80 0 2,90 0 3,70 0 1,30 0 3,70 0 5,50 0 K

dValu e o f

n 3 0 7 0 7 0 7 3 7 4 3 4 3 45 0 57 0 68 0 2,20 0 3,30 0 3,90 0 3.10 0 5,30 0 7.70 0 fo r

-(CH2)n

- Space r 4 0. 6 0 7 0. 6 4 8 5 3 7 7 72 0 84 0 1,00 0 3,10 0 3.70 0 6,60 0 5,50 0 6,10 0 9,60 0 5

1. 1 0 9 1. 0 7 8 8 3 5 7 1.100 1.200 1,400 5,80 0 5,40 0 8,30 0 6,80 0 9,50 0 12,00 0

2 8Th e Pu(rV ) sorptio n behavio r of th e picolinium

- an dmethylate dpicolinium-containin g bifunctional anion-exchang e resin s i s show n i n Tabl e 2.5 . Tabl e 2.5 . Measure dK

d(mL/g ) Value s fo

r Pu(rV ) Sorptio n fromNitri c Aci db \ Picolinium

- an dN-Methylpicolinium-Containin g Bifunctional Anion

Exchang e Resins.' ^

HN0 3 (M ) 1

3

5

7

9 Contac t

Tim e (h ) 0. 5 2 6 0. 5 2 6 0. 5 2 6 0 5 2 6 0. 5 2 6 3-picoly l

1. 9 1. 5 1. 6 6 1 7 2 7 4 66 0 95 0 1,00 0 3,10 0 4,30 0 5,30 0 4,30 0 7.70 0 8,70 0 K dValu e 4-picoly l 1. 2 1. 3 1. 2 5 1 6 0 6 0 58 0 75 0 89 0 3,80 0 4,40 0 4,80 0 4,90 0 5,60 0 7,50 0 Methylate d

3-picoly l 1. 2 1. 2 1.7

- 6 2 6 4 72 0 82 0 85 9 3,80 0 5.90 0 6,90 0 7,80 0 7,70 0 9.10 0 Methylate d

4-picoly l

-

-

-

-

- 4 5 64 0 78 0 79 0 4,00 0 5,40 0 6,40 0 8,00 0 8,50 0 12,00 0

2 9It

wa s foun dtha

t th e ne w bifunctional anion-exchang e resin s exhibite dbette r plutoniu mdistributio n coefficient value s an dsorptio n kinetic s compare dt o Reillex TM HP Q resin . Amon g thos e bifunctional anion-exchang e resins , resin s wit h five-carbo n spacer s showe dth e bes t

performance . Th e K

dvalue s fo

r Pu(rV ) wer e highe r

i n 5- 9 M nitri c aci dan dlowe r

in 1-3 M nitri c aci dsinc e plutoniu measil y form s th e dianioni c species , Pu(N03)6'" , i

n 7 M nitri c acid . Thi s phenomeno n make s it possibl e t o perfor

m th e sorption-strippin g proces s b y changin g th e nitri c aci dconcentration .

2.1.3 . Synthesi s of

Water-Solubl e Poly(vinylpyridines ) Th e combinatio n o f

amacromolecula

r metal io n complexin g agen t wit h ultrafiltratio n i s a

n attractiv e concep t

fo r th e selectiv e remova

l o f metal ion s fro

m aqueou s solutions . Ultrafiltratio n i s aseparatio n metho dfo r ahomogeneou s phas e an d ha s becom e astandar dprocedur e fo r th e separatio n of

biomolecules . I

n ultrafiltration , th e differen t

chemica l component s are separate dexclusivel y accordin g t o thei r molecula r dimensions.' ^ Metal ion s ca n b e separate dfromaqueou s solution s by us e o f awater solubl e chelatin g polyme r whic h selectivel y bind s th e desire dmeta l io n specie s or

group s i n a n ultrafiltratio n process , a s show n i n Figur e 2.3 . Fo r

thi s process , th e macromolecular

compound s shoul dhav e water-solubility an d hig h bindin g capacity fo r th e metal ions . Poly(vinylpyridine ) resi n wa s reporte dt o exhibi t metal io n complexatio n betwee n meta l ion s an dth e pyridin e group s i n th e polymer . ' However , Reillin e 420 0 an d220 0 polymers , commerciall y availabl e linea r poly(4-vinylpyridine ) and poly(2-vinylpyridine) , are insolubl e i n water . 3 0Soli

d Polyme r METAL-CONTAININ G EFFLUEN

T

J 4 1 POLYME R SOLUTIO N ULTRAFILTRATIO N Loade

d an d Concentrate

d Polyme r REACTO R METAL-FRE E EFFLUEN

T Figur e 2.3 . Schemati c Diagram o f a n Ultrafiltratio n Proces s with Macromolecula r Complexe s fo r th e Separatio n o f Metal Ions . I n thi s dissertatio n research , th e synthesi s o f water-solubl e poly(vinylpyridines ) b y th e partial quatemizatio n wil l b e explored . A minimu m leve l o f quatemizatio n i s require d t o maximiz e th e ability fo r chelatio n o f meta l ion s b y th e pyridin e units i n th e polymer . 2.1.3.1 . Hydroxvethvl-Substitute d Water-Solubl e Polymer s Th e synthesi s o f

partiall y substitute d poly(4-vinylpyridines ) an d thei r water TV/ f solubilitie s ar

e show n i n Tabl e 2.2 . Reactio n o f Reillin e 420 0 polyme r with varyin g mola r equivalent s o f

2-bromoethano l i n methano l wa s performed . Solubilit y o f th e partiall y substitute d poly(4-vinylpyridine ) in wate r wa s evaluate d bot h with heatin g an

d withou theating . Base d upo n th e solubilit y tests , 20 % substitute d poly(4-vinylpyridine ) 5 5 wa s selecte d a s th e desire d product . Eve n thoug h th e polymer s 5 7 and 5 8 wer e solubl e i n ho twater , the y appeare d t o for m supersaturate d solution s upo n bein g allowe d t o coo l t o roo m temperature . 3 1Tabl e 2.6 . Synthesi s o f Partiall y Substitute dPoly(4-vinylpyridines ) 54-5 8 an d Thei r Wate r Solubilities . fCH2CH ^ ( ^ j + BrCH2CH20 H MeO H reflux , 1 d CH2CH^x eCH2CH ^ 

# Q N 

# Q

N B r CH2CH2O

H Partiall y substitute d Wate r solubilit y poly(4-vinylpyridine ) 5 4 5 5 5 6 5 7 5 8

^ No t determined . X

0.6 5 08 0 08 5 0.9 0 0.9 5 y

03 5 0.2 0 01 5 01 0 0.0 5 Withou t

heatin g ND' ^ Ye s N o N o ND ' Wit

h heatin g Ye s ND ' Ye s Ye s N o

Th e synthesi s of

partiall y substitute dpoly(2-vinylpyridines ) wa s performe db y usin g th e sam e procedur e a s tha t give n previousl y fo

r th e partiall y substitute dpoly(4

- vinylpyridines ) compound s 54-58 . Th e solubility tes t result s ar e show n i n Tabl e 2.3 . Th e 15 % substitute dpoly(2-vinylpyridine ) 5 9 wa s selecte d a s th e desire dproduct .

3 2Tabl e 2.7 . Synthesi s of Partiall y Substitute dPoly(2-vinylpyridines ) 5 9 an d6 0 an d Thei r Wate r Solubilkies . 4CH2CH ^ r ^ \ + BrCH2CH20H MeO H reflux , 1 d CH2CH ^

Partiall y substitute d poly(2-vinylpyridine ) Wate r solubility Withou t heatin g Wit

h heatin g 5 9 6 0 08 5 0.9 0 01 5

Ol O Ye s

N o ND "

Ye s No t determined . 2.1.3.2 . 3-(Trimethvlammonio)propvl-Substitute d Water-Soluble Polymer s T o investigat e th e effec t

o f combinin g a

n anion-exchang e proces s wit h awater solubl e polymer , th e synthesi s o f partiall y 3-(trimethylammonio)propyl-substitute d poly(vinylpyridine ) wa s envisioned . Th e partiall y substitute dpoly(4-vinylpyridine ) wa s synthesize dfro mth e reactio n of Reilline TM 420 0 polyme r wit h (3-bromopropyl)trimethylammoniu mbromid e i n methanol , a s show n i

n Tabl e 2.4 . Solubility test s fo r thes e water-solubl e polymer s were conducte din wate r

an di n aqueou s NaN0 3 solutio n a t roo mtemperatur e t o chec k thei r feasibility a s potentia l meta l io n separatin g agent s fromnuclea r waste . Poly(4

- vinylpyridine ) 6 3 wit

h 30 % substitutio n wa s selecte da s th e desire dproduct .

33Tabl e 2.8 . Synthesi s of Partiall y Substitute dPoly(4-vinylpyridines ) 61-63 an dThei r Wate r Solubilities . CHsCHi n -eCH2CH ^

+ Br(CH2)3 N (CH3) 3 Br

" MeOH reflux , 1 d -eCH2CH ^



# Q N 2 B r (CH2)3NYCH3) 3 Partiall y substitute d poly(4-vinylpyridine ) Wate r solubility Withou t NaNO . Wit

h NaN0 3 6 1 6 2 6 3 0.9 0 0.8 0 0.7 0 Ol O

0.2 0 O3 0 Ye s

Ye s Ye s N o

N o Ye s

Th e reactio n of

Reillin e 220 0 polyme r wit h (3-bromopropyl)trimethyl

ammoniu mbromid e i

n methano l wa s performe da s show n i n Tabl e 2.5 . Th e synthesi s an dsolubility testin g followe dth e same procedure s a s thos e fo r th e water-solubl e polymer s 61-63 . Poly(2-vinylpyridine ) 6 5 wit h 30 % substitutio n wa s selecte da s th e desire dproduct .

3 4Tabl e 2.9 . Synthesi s o f Partiall y Substitute dPoly(2-vinylpyridines ) 6 4 an d6 5 an dThei r Wate r Solubilities . CHjCH ^ N + + Br(CH2)3 N (CH3) 3 B r f CH2CH^ x ^ CH2C H

MeO H reflux , 1 d N^(CH2)3NtCH3) 3 2 Br '

Partiall y substitute d poly(2-vinylpyridine ) Wate r solubility Withou t NaN0 3 Wit

h NaNO ? 6 4 6 5 O8 0 0.7 0 0.2 0

0.3 0 Ye s

Ye s N o

Ye s

2.2 . Chapter

Summar y Th e synthesi s of

several serie s o f

ne w bifunctional anion-exchang e resin s wa s accomplishe db y modificatio n of commerciall y availabl e Reillex TM 40 2 poly(4-vinyl

pyridine ) resin . Structural variation s i n thes e bifunctiona

l anion-exchang e resin s were accomplishe db y changin g th e identit y of th e secon danion-exchang e group , th e lengt h o f th e space r betwee n tw o anion-exchang e sites , an dth e rigidity o f th e anion-exchang e resin . Investigation s of

th e sorptio n behavio r

of thes e ne w bifunctional anion-exchang e resin s for Pu(IV ) fromnitri c aci dwere performe da t Lo s Alamo s National Laboratory . A serie s of

water-solubl e polymer s wa s synthesize d by th e partia l substitutio n o f commerciall y available , linea r poly(4-vinylpyridine ) (Reilline TM 4200 ) an dpoly(2

- vinylpyridine ) (Reilline TM 2200 ) wit h hydrophili c group s whic h include d2-hydroxyethy l 3 5an d3-(trimethylammonio)propy l groups . Thes e polymeri c reagent s hav e potential fo r meta l io n separatio n fro mahomogeneou s aqueou s phase . 2.3 . Experimental Procedure s 2.3.1 . Source s o

f Reagent s Commerciall y availabl e reagent s were use da s receive dunles s otherwis e specified . Reillex'^ ^ 40 2 polymer , a2 % crosslinke dcopolyme r of 4-vinylpyridin e and 1,4-divinylbenzene , wa s obtaine dfromth e Aldric h Chemical Co . an duse dwithou t further purification . Reilline^ ^ 420 0 polymer , a60 % methano l solutio n of linea r poly(4

- vinylpyridine) , an dReilline TM 220 0 polymer , a65 % methano l solutio n of linea r poly(2

- vinylpyridine), wer e obtaine dfro mth e Reill y Industries , Inc . an d use dwithou t furthe r purification . 2.3.2 . Purificatio n o f Reagent s Dry solvent s wer e prepare da s follows : benzen e wa s store dove r activate d4 A molecular sieves ; aceton e wa s distilled . 2.3.3 . General Meltin g point s wer e obtaine dwit h aMel-Tem

p (capillar

y tube ) meltin g poin t apparatus . Infrare d(IR ) spectr awer e recorde d wit h aPerkin-Elme r

160 0 Serie s FT-I R o n NaC l plate s (fil mdeposite dfromsolution ) o r a s KB r pellet s an dare reporte di

n wavenumber s (cm') . Proto n nuclea r magneti c resonanc e (' H NMR ) spectr awer e recorde dwit

h a n IB M AF-20 0 spectromete r wit h th e chemica l shift s (6 ) reporte d 3 6downfiel dfromth e internal standar dtetramethylsilan e (TMS , presen t a t ca . 0.05 % i

n CDCI3) . Splittin g pattern s i n th e ' H NM Rspectr aare identifie das : s , singlet ; d , doublet : t , triplet ; q , quartet ; p , pentet ; b r s , broadsinglet ; dd , double t o f doublet ; an dm , multiplet . Elementa l analyse s wer e performe db y Deser t Analytic s Laboratory of

Tucson , Arizona . Fo r

th e synthesize danion-exchang e resins , th e percen t substitutio n wa s calculate dfro mth e percen t o f chloride , bromide , or

iodid e counte r

ion(s ) an dconfirme d b y th e CH N analysi s results .

2.3.4 . General Procedure fo r th e Synthesi s o

f (co-Bromoalkyl)trimethylammoniu mBromide s 8-1 3 Int o a100-mL , three-necked , round-bottome dflask equippe dwit

h CaC b dryin g tub e an damagneti c stirre r were adde dth e appropriat e 1 ,co-dibromoalkan e (2.(X ) g ) an d dr y benzen e (3 0 mL) . Int o th e reactio n mixture wa s bubble drapidl y (abou t 4 bubbles/second ) anhydrou s trimethylamin e fo r 4 hour s ( 8 hour s fo

r 10.0 0 g ) wit

h stirrin g a t roo mtemperature . Afte r th e completio n o

f th e addition , th e reactio n mixture wa s allowe dt o sti r

ovemight

a t roo mtemperature . Th e precipitate d soli dwa s filtere dand washe dwit

h col dbenzen e (1 0 mL ) t o giv e th e product . Sometimes , th e desire dmono sal t produc t wa s contaminate dwit

h th e bis-sal t

product . Th e rati o of

mono-sal t

t o bis

sal t wa s determine db y compariso n of th e integrate darea s fo

r th e -N"^(CH3) 3 absorption s fro mth e mono - an dbis-sal t i n th e ' H NM Rspectrum . 2.3.4.1 . (3-BromopropyI)trimethyIammoniu m Bromid e (8 ) wa s obtaine di n 76 % yiel da s awhit e soli dwit h m p 204-20 6 °C

(lit. ^ m p 20 5 ° C dec) . IR(deposi t fro m

37MeO H solutio n on aNaC l plate) : 147 9 (C- H bendin g i n -CHj-N^ ) cm"' . ' H NMR (CDCl3:DMSO-d 6 (lOl)) : 5 2.41-2.4 3 (m , 2H) ; 3.3 6 (s , 9H , mono-salt) ; 3.4 3 (s . 18H . bis-salt) ; 3.5 5 (t , 7 = 6. 2 Hz , 2H) ; 3.73-3.8 1 (m , 2H) . Mono-salt:Bis-sal t = 96:4 . 2.3.4.2 . (4-Bromobutyl)trimethylammoniu m Bromid e (9 ) wa s obtaine di n 83 % yiel da s awhit e soli dwit

h m p 134-13 6 ° C (ht.' ° m

p 131-13 4 °C) . I

R(deposi t

fro m MeO H solutio n o n aNaC l plate) : 148 2 (C- H bendin g i n -CH2-N'^

) cm"' . ' H NMR (CDCl3:DMSO-d 6 (10:1)) : 6 1.96-2.0 1 (m , 4H) ; 3.3 6 (s , 9H , mono-salt) ; 3.5 3 (t , 7 = 6. 0 Hz , 2H) ; 3.65-3.7 4 (m , 2H) . Mono-salt:Bis-sa k = 100:0 . 2.3.4.3 . (5-Bromopentyl)trimethylammoniu m Bromid e (10 ) wa s obtaine di n 83 % yiel da s awhit e soli dwit h m p 141-14 2 " C (ht.' ^ m

p 141-14 2 °C) . I

R(deposi t

fro m MeO H solutio n o n aNaC l plate) : 148 4 (C- H bendin g i n -CH2-N^) cm"' . ' H NMR (CDCl3:DMSO-d 6 (10:1)) : 6 1.56-1.5 9 (m , 2H) ; 1.84-2.00 (m , 4H) ; 3.3 6 (s , 9H , mono salt) ; 3.3 9 (s , 18H , bis-salt) ; 3.4 7 (t , 7 = 6. 5 Hz , 2H) ; 3.59-3.6 7 (m , 2H) . Mono-salt:Bis

sal t = 94:6 . 2.3.4.4 . (6-Bromohexyl)trimethylammoniu m Bromid e (11 ) wa s obtaine di n 85 % yiel da s awhit e soli dwit h m p 109-11 0 ° C (lit.' ° m

p 107-10 9 °C). I

R(deposi t

fro m MeO H solutio n o n aNaC l plate) : 148 0 (C- H bendin g i n -CH2-N^) cm' . ' H NM R (CDCl3:DMSO-d 6 (10:1)) : 6 1.46-1.5 1 (m , 4H) ; 1.82-1.9 0 (m , 4H) ; 3.3 4 (s , 9H , mono salt) ; 3.4 4 (t , 7 = 6. 6 Hz , 2H) ; 3.55-3.6 3 (m , 2H) . Mono-salt:Bis-sal t = 100:0 . 2.3.4.5 . (7-Bromoheptyl)trimethylammoniu m Bromid e (12 ) wa s obtaine di n 37 % yiel da s awhit e soli dwit h m p 24 0 ° C (dec) . I

R(deposi t

fromMeO H solutio n o

n a NaC l plate) : 148 3 (C- H bendin g i n -CH2-N"' ) cm"' . ' H NM R(DMSO-d6) : 6 1.13-1.4 9

3 8(m , 6H) ; 1.52-1.8 9 (m , 4H) ; 3.0 6 (s , 9H , mono-salt) ; 3.0 8 (s , 18H , bis-salt) ; 3.30-3.3 8 (m .

2H) ; 3.5 4 (t , 7 = 6. 7 Hz , 2H) . Mono-salt:Bis-sal t = 45:55 . 2.3.4.6 . (8-Bromooctyl)trimethylammoniu m Bromid e (13 ) wa s obtaine di n 29 % yiel da s awhit e soli dwit h m p 21 0 ° C (dec) . I

R(deposi t fromMeO H solutio n o

n a NaC l plate) : 148 2 (C- H bendin g i n -CH2-N^) cm"' . ' H NM R(DMSO-d6) : 6 1.13-1.47 (m , lOH) ; 1.57-1.7 6 (m , 2H) ; 3.0 5 (s , 9H , mono-salt) ; 3.0 6 (s , 18H , bis-salt) ; 3.26-3.3 5 (m , 2H) ; 3.5 4 (t , 7 = 6. 6 Hz , 2H) . Mono-salt:Bis-sak = 31:69 . 2.3.5 . Preparatio n of [2-(2'-Bromoethoxy)ethyl]trimethylammoniu m

Bromid e (21 ) Int o a100-mL , three-necked , round-bottome d flask equippe dwit

h CaCl2 dryin g tub e an damagneti c stirre r were adde dbis(2-bromoethyl)ethe r (2.0 0 g , 8.6 2 mmol ) an d dr y benzen e (3 0 mL) . Int o th e reactio n mixtur e wa s bubble drapidl y (abou t 4 bubbles/second ) anhydrou s trimethylamin e fo r 2 hour s wit

h stirrin g a

t roo mtemperature . Afte r th e completio n of

th e addition , th e reactio n mixture wa s allowe dt o sti r ovemigh t a t roo mtemperature . Th e precipitate dsoli dwa s filtere dan dwashe dwit h col dbenzen e (1 0 mL ) t o giv e 2.0 1 g (80% ) of th e produc t

a s awhite soli dwit

h m p 105-10 7 °C . I

R (deposi t fro mMeO H solutio n o

n aNaC l plate) : 147 9 (C- H bendin g i n -CH2-N^) ; 128 9 an d111 7 (C-0 ) cm' . ' H NM R(CDCl3:DMSO-d 6 (10:1)) : 6 3.3 5 (s , 9H) ; 3.55-3.6 0 (m , 2H) ; 3.79-3.9 7 (m , 6H) . Anal . Cacld . fo r C7Hi7Br2NO : C , 28.89 ; H , 5.89 . Found : C , 29.28 ; H , 5.83 .

3 92.3.6 . General Procedure fo r th e Synthesi s o

f Poly[N-(co-Trimethylammonioalkyl ) 4-Vinylpyridiniu m

Dibromides ] 14-1 9 Int o a1000-mL , one-necked , round-bottome d flask were adde dReillex^ ^ 40 2 poly(4-vinylpyridine ) (5.0 0 g , 47. 6 mmol) , a n appropriat e (co-bromoalkyl)trimethyl

ammoniu mbromid e (8-13 ) (47. 6 mmol) , an dabsolute ethano l (38 0 mL) . Th e reactio n mixtur e wa s refluxe dfor

1 0 day s unde r

nitrogen . Afte

r coolin g to roo mtemperature , th e reactio n mixtur e wa s filteredan dth e soli dwa s washe do n th e funnel wit

h ethano l ( 3 X 2 0 mL ) an dwate r

( 2 X 2 0 mL) . Th e soli dwa s drie dwit h benzen e i

n aDean-Star

k apparatu s t o giv e th e desire dproduct . 2.3.6.1 . Poly[N-(2-Trimethylammonioethyl ) 4-Vinylpyridiniu m Dibromide ] (14 ) wa s obtaine din 60 % yiel db y weigh t a s awhite soli d wit

h m p > 30 0 °C. I

R(KBr) : 163 7 (C=N) ; 147 8 (C- H bendin g i n -CH2-N"' ) cm"' . Elemental analysi s calculate dfo r (Ci2H2oBr2N2)o.59(C7H7N)o.4i : Br , 37.59 ; C , 47.64 ; H , 5.89 ; N , 8.88 . Found : Br , 37.83 ; C,47.99;H , 5.58 ; N , 8.61 . 2.3.6.2 . Poly[N-(3-Trimethylammoniopropyl ) 4-Vinylpyridiniu m Dibromide ] (15 ) wa s obtaine di

n 77 % yiel db y weigh t

a s awhite soli dwit

h m p > 30 0 °C . I

R(KBr) : 163 8 (C=N) ; 147 5 (C- H bendin g i n -CH2-N'' ) cm' . Elemental analysi s calculate dfo r (Ci3H22Br2N2)o.9i(C7H7N)o.o9 : Br , 42.44 ; C , 43.68 ; H , 6.07 ; N , 7.81 . Found : Br , 42.48 ; C , 43.99 ; H , 5.93 ; N , 7.60 . 2.3.6.3 . Poly[N-(4-Trimethylammoniobutyl ) 4-Vinylpyridiniu m Dibromide ] (16 ) wa s obtaine di

n 8 1 % yiel db y weigh t

a s awhite soli dwit

h m p > 30 0 °C . I

R(KBr) : 163 8 (C=N) ; 147 4 (C- H bendin g i n -CH2-N"' ) cm"' . Elemental analysi s calculate dfo r 4 0(Ci4H24Br2N2)o.87(C7H7N)o.,3 : Br , 40.37 ; C , 45.65 ; H , 6.38 ; N , 7.61 . Found : Br . 40.06 :

C , 46.02 ; H , 6.68 ; N , 7.24 . 2.3.6.4 . Poly[N-(5-Trimethylammoniopentyl ) 4-Vinylpyridiniu m Dibromide ] (17 ) wa s obtaine din 69 % yiel db y weight a s awhite soli d wit

h m p > 30 0 °C . I

R(KBr) : 163 8 (C=N) ; 147 4 (C- H bendin g i n -CH2-N^ ) cm"' . Elemental analysi s calculate dfo r (Ci5H26Br2N2)o.99(C7H7N)o.oi : Br , 40.43 ; C , 45.80 ; H , 6.65 ; N , 7.12 . Found : Br . 40.05 ; C , 46.06 ; H , 6.79 ; N , 7.11 . 2.3.6.5 . Poly[N-(6-Trimethylammoniohexyl ) 4-Vinylpyridiniu m Dibromide ] (18 ) wa s obtaine din 67 % yiel db y weigh t a s awhite soli dwit

h m p > 30 0 °C . I

R(KBr) : 163 8 (C=N) ; 147 4 (C- H bendin g i n -CH2-N^ ) cm"' . Elemental analysi s calculate dfo r Ci6H28Br2N2 : Br , 39.15 ; C , 47.08 ; H , 6.91 ; N , 6.86 . Found : Br , 39.41 ; C , 46.87 ; H , 6.66 ; N , 7.06 . 2.3.6.6 . Poly[N-(8-Trimethylammoniooctyl ) 4-Vinylpyridiniu m Dibromide ] (19 ) wa s obtaine di

n 47 % yiel db y weight

a s awhite soli dwit

h m p > 3(X ) °C. I R(KBr) : 163 7 (C=N) ; 147 4 (C- H bendin g i n -CH2-N'' ) cm' . Elemental analysi s calculate dfo r (C,8H32Br2N2)o.38(C7H7N)o.62 : Br , 26.29 ; C , 58.14 ; H , 7.20 ; N , 8.37 . Found : Br , 26.62 ; C , 58.54 ; H , 6.73 ; N , 8.12 . 2.3.7 . Preparatio n of

Poly[2-(N-2'-Trimethylammonioethoxy)ethy l 4-Vinylpyridiniu mDibromide ] (22 ) Int o a1000-mL , one-necked , round-bottome d flask were adde dReillex^ ^ 40 2 poly(4-vinylpyridine) (7.0 0 g , 66. 6 mmol) , [2-(2'-bromoethoxy)ethyl]trimethyl

ammoniu mbromid e (21 ) (19.3 8 g , 66. 6 mmol) , an d absolut e ethano l (53 0 mL) . Th e 4 1reactio n mixtur e wa s refluxe dfo r 1 0 day s unde r

nitrogen . Afte

r coolin g t o roo m temperature , th e reactio n mixtur e wa s filtere dan dth e soli dwa s washe do n th e funne

l wit h ethano l ( 3 X 5 0 mL ) an dwater ( 2 X 5 0 mL) . Th e soli dwa s drie dwit h benzen e i

n a Dean-Star k apparatu s t o giv e 19.3 1 g (73% ) o f th e produc t

a s awhite soli dwit

h m p > 30 0 °C . I R(KBr) : 163 9 (C=N) ; 147 4 (C- H bendin g i n -CH2-N^ ) cm"' . Elemental analysi s calculate dfor

(Ci4H24Br2N20)o.68(C7H7N)o.32 : Br , 35.86 ; C , 46.61 ; H , 6.17 ; N . 7.77 . Found : Br , 35.54 ; C , 46.68 ; H , 6.33 ; N , 7.42 . 2.3.8 . Preparatio n o

f N-(2-Bromoethyl)pyridiniu mBromid e (23 ) Int o a1000-mL , three-necked , round-bottome dflask were adde dpyridin e (16.0 0 g , 20. 0 mmol) , 1,2-dibromoethan e (187.8 6 g , l.(X ) mol) , an ddr

y aceton e (50 0 mL ) unde r nitrogen . Th e reactio n mixtur e wa s refluxe dfo r 1 5 hours . Th e precipitate dsoli d wa s filtere dan dwashe dwit h col daceton e (5 0 mL ) t o giv e 13.5 1 g (25% ) of th e produc t a s asoli dwit

h mp 125-13 0 °C

(lit.' ^ m p 11 1 °C) . I

R(deposi t fro mMeO H solutio n o

n a NaC l plate) : 163 2 (C=N) ; 148 7 (C- H bendin g i n -CH2-N^ ) cm"' . ' H NM R(DMSO-de) : 54.1 4 (t , 7 = 5. 9 Hz , 2H) ; 5.06-5.1 2 (m , 2H) ; 8.2 5 (t , 7 = 7. 1 Hz , 2H) ; 8.7 0 (t , 7 = 7. 8 Hz , IH) ; 9.1 7 (d , 7 = 5. 8 Hz , 2H) .

2.3.9 . General Procedur e for th e Synthesi s of N-(o>-Bromoalkyl)pyridiniu mBromid e 25-2 8 Int o a100-mL , three-necked , round-bottome dflask were adde dpyridin e (1.6 0 g , 20. 0 mmol ) an ddr

y benzen e (1 0 mL ) unde r

nitrogen . A solutio n of

th e 1 ,o>-dibromo

alkan e (10. 0 equivalent , 5. 0 equivalen t for 1,3-dibromopropane ) i

n 1 0 mL of

dr y benzen e 4 2wa s added . Th e reactio n mixtur e wa s refluxe dfo r 6 hour s an dthe n stirre dovemigh t a t roo mtemperatur e unde r

nitrogen . Th e precipitate dsoli dwa s filtered, washe dwit h col d benzen e (1 0 mL) , an ddrie dove r phosphorou s pentoxid e t o giv e th e product . Sometimes , th e desire dmono-sal t produc t wa s contaminate dwit

h th e bis-sal t

product . Th e -CH2-N

^ absorption s for

th e mono - an d bis-sal t

overlappe d i

n th e ' H NM Rspectru m an dcoul dno t

b e utilize ddirecti y t o determin e th e leve l o f bis-sal t contaminatio n i

n th e mono-salt . Integratio n of th e absorptio n fo

r -CH2-B r i n th e mono-sal t

an dth e absorptio n for

-CH2-N" ^ fromth e mono-sal t an dbis-sal t

allowe dth e mono-salt:bis-sal t rati o t o be calculate dfrom ; mono-salt integratio n o f -CH2-B r bis-sal t [(integratio n o

f -CH2-N"*' ) - (integratio n o

f -CH2-Br) ]

2.3.9.1 . N-(3-Bromopropyl)pyridiniu m Bromid e (25 ) wa s obtaine di n 94 % yiel da s asoli dwit

h mp 133-13 6 ° C (lit.' ° m p 13 6 °C) . I

R(deposi t

fromMeO H solutio n o n aNaC l plate) : 163 5 (C=N) ; 148 8 (C- H bendin g i n -CHz-N^ ) cm"' . ' H NM R(DMSO

d6) : 5 2.49-2.5 6 (p , 2H) ; 3.5 9 (t , 7 = 6. 6 Hz , 2H) ; 4.7 7 (t , 7 = 7. 1 Hz , 2H) ; 8.1 9 (t , 7 = 6. 8 Hz , 2H) ; 8.6 3 (t , 7 = 7. 8 Hz , IH) ; 9.08-9.2 9 (m , 2H) . Mono-sak:Bis-sak = 100:0 . 2.3.9.2 . N-(4-Bromobutyl)pyridiniu m Bromid e (26 ) wa s obtaine di n 99 % yiel d a s agum-lik e solid . IR(deposi t fromMeO H solutio n o

n aNaC l plate) : 163 4 (C=N) ; 148 8 (C- H bendin g i

n -CH2-N-' ) cm"' . ' H NM R(DMSO-de) : 5 1.78-2.1 0 (m , 4H) ; 3.5 8 (t , 7 = 6. 5 Hz , 2H) ; 4.6 9 (t , 7 = 7. 1 Hz , 2H) ; 8.2 0 (t , 7=7. 1 Hz , 2H) ; 8.6 4 (t , 7 = 7. 8 Hz , IH) ; 9.1 5 (d , 7 = 5. 2 Hz , 2H) . Mono-salt:Bis-sal t = 100: 0

4 32.3.9.3 . N-(5-Bromopentyl)pyridiniu m Bromid e (27 ) wa s obtaine di n 83 % yiel d a s agum-lik e soli dfro malarger-scal e m n wit h 3.9 6 g (50. 0 mmol ) o

f pyridine . I

R (deposi t fro mMeO H solutio n on aNaC l plate) : 163 3 (C=N) ; 148 7 (C- H bendin g i n -CH2-N^ ) cm"' . ' H NM R(DMSO-de) : 5 1.80-2.4 6 (m , 6H) ; 3.9 6 (t . 7 = 6. 6 Hz , 2H , -CH2-Br) ; 4.99-5.4 8 (m , 2H , -CH2-N^) ; 8.67 (t , 7 = 6. 9 Hz , 2H) ; 9.1 2 (t , 7 = 7. 7 Hz , IH) : 9.8 0 (t , 7 = 6. 7 Hz , 2H) . Mono-sak:Bis-sah = 88:12 . 2.3.9.4 . N-(6-Bromohexyl)pyridiniu m Bromid e (28 ) wa s obtaine di n 82 % yiel d a s asoli dwit

h mp 128-13 3 ° C (lit.' ^ m p 127-12 8 °C ) fro

malarger-scal e run wit

h 3.9 6 g (50. 0 mmol ) o f

pyridine . I

R(deposi t

fro mMeO H solutio n o

n aNaC l plate) : 163 2 (C=N) ; 148 5 (C- H bendin g i n -CH2-N'' ) cm"' . ' H NM R(DMSO-de) : 5 1.30-1.4 3 (m , 4H) ; 1.76-1.9 7 (m , 4H) ; 3.5 3 (t , 7 = 6. 6 Hz , 2H , -CH2-Br) ; 4.54-4.8 0 (m , 2H , -CH2-N^) : 8.2 0 (t , 7 = 6. 5 Hz , 2H) ; 8.64 (t , 7 = 7. 5 Hz , IH) ; 9.2 2 (t , 7 = 7. 3 Hz , 2H) . Mono

salt:Bis-sak

= 88:12 . 2.3.10 . Preparatio n o f N-[2-(2'-Bromoethoxy)ethyl]pyridiniu m

Bromid e (29 ) Int o alOO-mL , three-necked , round-bottome dflask were adde dpyridin e (0.7 9 g , 10. 0 mol) , bis(2-bromoethyl)ethe r (11.6 0 g , 50. 0 mmol) , an ddr y aceton e (2 5 mL ) unde r nitrogen . Th e reactio n mixtur e wa s refluxe d fo r 1 5 hours . Th e solven t

wa s evaporate d in vacuo t o giv e 1.4

9 g (46% ) of

produc t a s ayellow , viscou s liquid . Th e desire dmono sal t produc t wa s contaminate dwit

h th e bis-sal t

product . Th e -CH2-N

^ absorption s fo

r th e mono - an dbis-sal t

overiappe di

n th e ' H NM Rspectmman dcoul dno t b e utilize d directi y t o determin e th e leve l o f bis-sal t contaminatio n i

n th e mono-salt . Integratio n o f 4 4th e absorptio n for -CH2-B r in th e mono-sal t

an dth e absorptio n fo

r -CH2-N ^ fro mth e mono-sal t an dbis-sal t

allowe dth e mono-salt:bis-sal t rati o t o b e calculate dfrom : mono-salt integratio n o f -CH2-B r bis-sal t [(integratio n o

f -CH2-N"^ ) - (integratio n o

f -CH2-Br) ]

I R(depos k

fro mMeO H solutio n o

n aNaC l plate) : 163 4 (C=N) ; 148 7 (C- H bendin g i n -CH2-N^ ) cm"' . ' H NM R(DMSO-de) : 5 3.53-3.5 9 (m , 2H) ; 3.7 7 (t , 7 = 5. 4 Hz , 2H , -CH2-Br) ; 3.98-4.0 3 (m , 2H) ; 4.91-4.9 6 (m , 2H , -CH2-N^) ; 8.18-8.2 7 (m , 2H) ; 8.65-8.6 9 (m , IH) ; 9.12-9.2 0 (m , 2H) . Mono-salt:Bis-sak = 94:6 . 2.3.11 . General Procedure fo r th e Synthesi s of Poly[N-(0-(N'-Pyridinio)alky l 4-Vinylpyridiniu m

Dibromides ] 30-3 4 Int o a1000-mL , one-necked , round-bottome dflask were adde dReillex^ ^ 40 2 poly(4-vinylpyridine ) (5.0 0 g , 47. 6 mmol) , th e appropriat e N-(o>bromoalkyl)pyridiniu m bromid e 15-1 9 (47. 6 mmol) , an dabsolut e ethano l (38 0 mL) . Th e reactio n wa s refluxe d for 1 0 day s unde r

nitrogen . Afte

r coolin g to roo mtemperature , th e reactio n mixtur e wa s filteredan dth e soli dwa s washe don th e funne l wit h ethano l ( 3 X 2 0 mL ) an dwater ( 2 X 2 0 mL) . Th e soli dwa s drie dwit h benzen e i

n aDean-Star

k apparatu s t o giv e th e polymeri c product . 2.3.11.1 . Poly[N-2-(N'-Pyridinio)ethy l 4-Vinylpyridiniu m Dibromide ] (30 ) wa s obtaine din 55 % yiel db y weigh t a s apal e brow n soli dwit h m p > 30 0 °C . I

R(KBr) : 163 6 (C=N) ; 145 8 (C- H bendin g i n -CH2-N'^ ) cm"' . Elemental analysi s calculate dfo r 4 5(Ci4Hi6Br2N2)o.67(C7H7N)o.33 : Br , 37.70 ; C , 49.44 ; H , 4.62 ; N , 8.24 . Found : Br , 37.52 :

C , 49.73 ; H , 4.79 ; N , 7.97 . 2.3.11.2 . Poly[N-3-(N'-Pyridinio)propy l 4-Vinylpyridiniu m Dibromide ] (31 ) wa s obtaine di

n 76 % yiel db y weigh t

a s awhite soli dwit

h m p > 30 0 °C. I

R(KBr) : 163 7 (C=N) ; 145 8 (C- H bendin g i n -CH2-N"^

) cm"' . Elemental analysi s calculate dfo r (Ci5Hi8Br2N2)o.79(C7H7N)o.2i : Br , 38.59 ; C , 48.91 ; H , 4.83 ; N , 7.66 . Found : Br , 38.23 ; C , 48.99 ; H, 5.34 ; N , 7.44 . 2.3.11.3 . Poly[N-4-(N'-Pyridinio)buty l 4-Vinylpyridiniu m Dibromide ] (32 ) wa s obtaine di

n 60 % yiel db y weigh t

a s apal e brow n soli dwit

h m p > 30 0 °C. I

R(KBr) : 163 7 (C=N) ; 145 8 (C- H bendin g i n -CH2-N"' ) cm"' . Elemental analysi s calculate dfo r (Ci6H2oBr2N2)o.86(C7H7N)o.i4 : Br , 38.30 ; C , 49.34 ; H , 5.11 ; N , 7.26 . Found : Br , 37.98 ; C , 49.63 ; H , 5.36 ; N , 7.03 . 2.3.11.4 . Poly[N-5-(N'-Pyridinio)penty l 4-Vinylpyridiniu m Dibromide ] (33 ) wa s obtaine di

n 61 % yiel db y weigh t

a s apal e brow n soli dwit h m p > 30 0 °C . I

R(KBr) : 163 7 (C=N) ; 145 3 (C- H bendin g i n -CH2-N'' ) cm"' . Elemental analysi s calculate dfo r (C,7H22Br2N2)o.78(C7H7N)o.22 : Br , 36.01 ; C , 51.35 ; H , 5.44 ; N , 7.20 . Found : Br , 35.71 ; C , 51.42 ; H , 5.73 ; N , 7.14 . 2.3.11.5 . Poly[N-6-(N'-Pyridinio)hexy l 4-Vinylpyridiniu m Dibromide ] (34 ) wa s obtaine di

n 60 % yiel db y weigh t

a s apal e brow n soli dwit h m p > 30 0 °C . I

R(KBr) : 163 7 (C=N) ; 145 8 (C- H bendin g i n -CH2-N^ ) cm"' . Elemental analysi s calculate dfo r (Ci8H24Br2N2)o.88(C7H7N)o.i2 : Br , 36.11 ; C , 51.44 ; H , 5.68 ; N , 6.76 . Found : Br , 35.80 ; C , 51.26 ; H , 5.95 ; N , 7.0 0 4 62.3.12 . General Procedure fo r th e Synthesi s of co-Bromoalkyltrimethylphosphoniu mBromide s 35-3 9 Int o a250-niL , three-necked , round-bottome d flask were adde dtrimethyl

phosphin e (6 0 nti:. , o f

a1. 0 M solutio n i

n toluene , 60. 0 mmol ) an dth e appropriat e 1 .codibromoalkan e (1.6 7 equivalent ) unde r nitrogen . Th e reactio n mixtur e wa s stirre dfo r 4 day s a t roo mtemperature . Th e precipitate dsoli dwa s filteredan dwashe dwit h col d benzen e (1 0 mL ) t o giv e th e product . Sometimes , th e desire dmono-sal t produc t wa s contaminate dwit

h th e bis-sal t

product . Th e rati o o

f mono-sal t

t o bis-sal t

wa s determine db y th e compariso n of th e integrate darea s fo

r th e -P^(CH3) 3 absorption s fro m th e mono - an dbis-sal t

i n th e ' H NM Rspectmm . 2.3.12.1 . (2-Bromoethyl)trimethylphosphoniu m Bromid e (35 ) wa s obtaine di n 47 % yiel da s awhit e soli dwit h m p 250-25 5 °C . I

R(deposi t fromMeO H solutio n o

n a NaC l plate) : 1427 (C- H bendin g i n -CH2-P^) ; 129 3 an d97 5 (C- H bendin g i n CHB-P^ ) cm"' . ' H NM R(DMS0-d6): 5 1.9 3 (d , 7 = 15. 2 Hz , 9H) ; 2.88-3.0 3 (m , 2H) ; 3.73-3.8 6 (m , 2H) . Anal . Cacld . Fo r C5H,3Br2P : C , 22.75 ; H , 4.89 . Found : C , 22.99 ; H , 4.89 . 2.3.12.2 . (3-Bromopropyl)trimethylphosphoniu m Bromid e (36 ) wa s obtaine d i n 89 % yiel da s awhit e soli dwit h m p 173-17 5 °C

(lit. " m p 16 4 "C) . I R(deposi t

fro m MeO H solutio n o n aNaC l plate) : 144 0 (C- H bendin g i n -CH2-P^) ; 1298 , 100 1 an d98 1 (C- H bendin g i

n CH3-P^ ) cm"' . ' H NM R(DMS0-d6) : 5 1.8 8 (d . 7 = 14. 9 Hz . 9H) ; 2.05

- 2.1 2 (m , 2H) ; 2.27-2.3 4 (m , 2H) ; 3.6 2 (t , 7 = 6. 2 Hz . 2H) . Mono-salt:Bis-sak = 100:0 . 2.3.12.3 . (4-Bromobutyl)trimethylphosphoniu m Bromid e (37 ) wa s obtaine di n 89 % yiel da s awhit e soli dwit h m p 135-13 9 ° C (lit. " m

p 13 2 °C). I

R(deposi t

from MeO H solutio n o n aNaC l plate) : 143 3 (C- H bendin g i n -CH2-P^) ; 130 0 an d97 1 (C- H 4 7bendin g i

n CH3-P"' ) cm"' . ' H NM R(DMSO-d6) : 5 1.57-1.7 0 (m . 2H) ; 1.8 7 (d,7 = 14. 9 Hz , 9H) ; 1.83-1.9 9 (m , 2H) ; 2.20-2.3 5 (m , 2H) ; 3.5 9 (t , 7 = 6. 5 Hz , 2H) . Mono-salt:Bis

sak = 100:0 . 2.3.12.4 . (5-Bromopentyl)trimethylphosphoniu m Bromid e (38 ) wa s obtaine d in 77 % yiel da s awhit e soli dwit h m p 126-12 8 ° C (lit.' ^ m

p 38 6 "C) . I

R(deposi t

fro m MeO H solutio n o n aNaC l plate) : 142 6 (C- H bendin g i n -CH2-P^) ; 130 1 an d98 6 (C- H bendin g in CH3-P^ ) cm"' . ' H NM R(CDC13) : 5 1.63-1.67 (m , 4H) ; 1.91-1.9 7 (m , 2H) ; 2.2 3 (d , 7 = 14. 3 Hz , 9H) ; 2.48-2.7 3 (m , 2H) ; 3.4 6 (t , 7 = 6. 4 Hz , 2H) . Mono-salt:Bis

sak = 100:0 . 2.3.12.5 . (6-Bromohexyl)trimethylphosphoniu m Bromid e (39 ) wa s obtaine di n 5 1 % yiel da s awhit e soli dwit h m p 26 0 ° C (dec. ) (ht.^

^ m p 19 0 °C). I

R(deposi t fro m MeO H solutio n o n aNaC l plate) : 142 3 (C- H bendin g i n -CH2-P'') ; 130

4 an d97 1 (C- H bendin g in CHB-P"" ) cm"' . ' H NM R(DMSO-de) : 5 1.48-1.64 (m . 4H) ; 1.8 6 (d , 7 = 14. 9 Hz , 9H , mono-salt) ; 1.8 3 (d , 7 = 14. 8 Hz , 18H , bis-salt) ; 2.14-2.2 6 (m , 6H) ; 3.5 5 (t , 7 = 6. 6 Hz , 2H) . Mono-salt:Bis-sal t = 76:24 .

2.3.13 . General Procedur e fo r th e Synthesi s o f Poly[N-(co-Trimethylphosphonioalkyl ) 4-Vinylpyridiniu m

Dibromides ] 40-4 3 Int o a1000-mL , one-necked , round-bottome dflask were adde dReillex^ ^ 40 2 poly(4-vinylpyridine ) (5.0 0 g , 47. 6 mmol) , th e appropriat e (O-bromoalkyltrimethyl

phosphoniu mbromid e 35-3 8 (47. 6 mmol) , an dabsolut e ethano l (38 0 mL) . Th e reactio n mixtur e wa s refluxe dfo

r 1 0 day s unde r

nitrogen . Afte

r coolin g t o roo mtemperature , th e 4 8reactio n mixtur e wa s filteredan dth e soli dwa s washe do n th e funnel wit

h ethano l ( 3 X 2 0 mL ) an dwate r

( 2 X 2 0 mL) . Th e soli dwa s drie d wit h benzen e i

n aDean-Star

k apparatu s t o giv e th e desire dproduct . Th e percen t substitutio n fo

r th e poly(N-co

trimethylphosphonioalky l 4-vinylpyridiniu mdibromide ) wa s calculate dfromth e percent of bromin e a s determine db y combustio n analyses . 2.3.13.1 . Poly[N-(2-Trimethylphosphonioethyl ) 4-VinyIpyridiniu m Dibromide ] (40 ) wa s obtaine di n 51 % yiel db y weight

a s apal e yello w soli dwit h m p > 30 0 °C . IR(KBr) : 163 7 (C=N) ; 147 4 (C- H bendin g i n -CH2-N'' ) cm' . Elemental analysi s calculate dfo

r (Ci2H2oBr2NP)o.65(C7H7N)o.35 : Br , 37.54 ; C , 44.49 ; H , 5.63 : N , 5.06 ; P , 7.28 . Found : Br , 37.30 ; C , 47.95 ; H, 5.46 ; N , 7.09 ; P , 2.20 . 2.3.13.2 . Poly[N-(3-Trimethylphosphoniopropyl ) 4-Vinylpyridiniu m Dibromide ] (41 ) wa s obtaine di n 77 % yiel db y weight

a s awhite soli dwit

h m p > 3(X ) °C. I R(KBr) : 163 7 (C=N) ; 147 4 (C- H bendin g i n -CH2-N^ ) cm"' . Elemental analysi s calculate dfor

(Ci3H22Br2NP)o.75(C7H7N)o.25 : Br , 38.22 ; C , 44.04 ; H , 5.87 ; N , 4.47 ; P , 7.4 1 Found : Br , 37.97 ; C , 44.41 ; H , 6.84 ; N , 4.43 ; P , 6.36 . 2.3.13.3 . Poly[N-(4-Trimethylphosphoniobutyl ) 4-Vinylpyridiniu m Dibromide ] (42 ) wa s obtaine di n 74 % yiel db y weight

a s awhite soli dwit

h m p > 3(X ) °C . I R(KBr) : 163 8 (C=N) ; 147 4 (C- H bendin g i n -CH2-N^ ) cm"' . Elemental analysi s calculate dfor

Ci4H24Br2NP : Br , 40.24 ; C , 42.34 ; H , 6.09 ; N , 3.53 ; P , 7.8 0 Found : Br , 40.42 ; C , 43.03 ; H , 6.40 ; N , 4.25 ; P , 5.90 . 2.3.13.4 . Poly[N-(5-Trimethylphosphoniopentyl ) 4-Vinylpyridiniu m Dibromide ] (43 ) wa s obtaine di n 7 1 % yiel d b y weigh t

a s awhit e soli dwit

h m p > 30 0 4 9°C . IR(KBr) : 163 8 (C=N) ; 146 6 (C- H bendin g i n -CHz-N^ ) cm"' . Elemental analysi s calculate dfor

(C,5H26Br2NP)o.82(C7H7N)o.,8 : Br , 36.80 ; C , 45.74 ; H , 6.39 : N . 3.93 ; P . 7.1 3 Found : Br , 36.47 ; C , 46.89 ; H , 6.85 ; N , 4.44 ; P , 5.35 .

2.3.14 . General Procedure fo r th e Synthesi s o

f Poly[N-(Picolyl ) 4-Vinylpyridiniu m Chlorides ] 47-4 9 Int o alOOO-mL

, one-necked , round-bottome d flask were adde dReillex^ ^ 40 2 poly(4-vinylpyridine ) (10.0 0 g , 95. 1 mmol) , th e appropriat e co-picolyl chlorid e hydrochlorid e (95. 1 mmol) , anhydrou s potassiu mcarbonat e (50. 1 mmol) , an dabsolute ethano l (65 0 mL) . Th e reactio n wa s refluxe dfo r 1 0 day s unde r

nitrogen . Afte

r coolin g t o roo mtemperature , th e reactio n mixtur e wa s filtere dan dth e soli dwa s washe do n th e funne l wit

h ethano l ( 3 X 2 0 mL ) an dwater ( 2 X 2 0 mL) . Th e soli dwa s drie dwit h benzen e i n aDean-Star

k apparatu s t o giv e th e polymeri c product . Th e percen t substitutio n for

th e poly[N-(co-picolyl ) 4-vinylpyridiniu mchloride ] wa s calculate dfro m th e percen t

o f chlorin e a s determine db y combustio n analyses . 2.3.14.1 . Poly[N-(2-Picolyl ) 4-Vinylpyridiniu m Chloride ] (47 ) wa s obtaine di n 79 % yiel db y weigh t

a s ared-brow n soli dwit

h m p > 30 0 °C . I

R(KBr) : 163 7 (C=N) ; 147 4 (C- H bendin g i

n -CH2-N^ ) cm"' . Elemental analysi s calculate dfo r (Ci3Hi3ClN2)o.66(C7H7N)o.34 : CI , 12.36 ; C , 69.53 ; H , 5.84 ; N , 12.28 . Found : CI , 12.54 ; C , 69.87 ; H , 6.00 ; N , 11.59 . 2.3.14.2 . Poly[N-(3-Picolyl ) 4-Vinylpyridiniu m Chloride ] (48 ) wa s obtaine di n 68 % yiel db y weigh t

a s ata n soli dwit

h m p > 30 0 °C . I

R(KBr) : 163 7 (C=N) ; 145 8 (C- H 5 0bendin g i

n -CH2-N"' ) cm"' . Elemental analysi s calculate dfo r (Ci3Hi3ClN2)o.6o(C7H7N)o.4o : CI , 11.71 ; C , 7O08 ; H , 5.88 ; N , 12.34 . Found : CI . 11.73 : C , 70.26 ; H , 6.55 ; N , 11.46 . 2.3.14.3 . Poly[N-(4-Picolyl ) 4-Vinylpyridiniu m Chloride ] (49 ) wa s obtaine di n 79 % yiel db y weigh t

a s ared-brow n soli dwit

h m p > 30 0 °C . I

R(KBr) : 163 7 (C=N) ; 145 8 (C- H bendin g i

n -CH2-N^ ) cm"' . Elemental analysi s calculate dfo r (C,3Hi3ClN2)o.93(C7H7N)o.o7 : CI , 14.73 ; C , 67.52 ; H , 5.67 ; N , 12.08 . Found : CI , 15.09 : C , 67.87 ; H , 5.88 ; N , 11.16 . 2.3.15 . Preparatio n o f Poly(N-Methy l 4-Vinylpyridiniu mIodide ) (50 ) Int o a500-mL , one-necked , round-bottome dflask were adde dReillex^ ^ 40 2 poly(4-vinylpyridine ) (2.0 0 g , 19. 0 mmol) , methy l iodid e (2.7 0 g , 19. 0 mmol) , an d absolut e ethano l (15 0 mL) . Th e reactio n wa s refluxe dfo r 2 day s unde r

nitrogen . Afte

r coolin g t o roo mtemperature , th e reactio n mixture wa s filtere dandth e soli dwa s washe d on th e funne l wit

h ethano l ( 3 X 2 0 mL ) an dwater ( 2 X 2 0 mL) . Th e soli dwa s drie d wit h benzen e i

n aDean-Star

k apparatu s to giv e 4.2 1 g (90% ) o f th e produc t

a s ayello w soli dwit h mp > 30 0 °C . I

R(KBr) : 163 7 (C=N) ; 145 8 (C- H bendin g i n CH3-N^) cm"' . Elementa l analysi s calculate dfor (C8H,oIN)o.99(C7H7N)o.oi : I , 51.14 ; C , 39.07 ; H , 4.09 ; N , 5.7 0 Found : I , 5074 ; C , 39.34 ; H , 4.35 ; N , 5.58 .

5 12.3.16 . General Procedure fo r th e Synthesi s o

f Poly[N-(N'-Methylpicolinio ) 4-Vinylpyridiniu m

Diiodide ] 51-5 3 Int o alOOO-mL

, one-necked , round-bottome d flask were adde dth e appropriate poly[N-(o>-picolyl ) 4-vinylpyridiniu mchloride ] 47-4 9 (7.0 0 g , 30. 1 mmol) , methy l iodid e (9.4 5 g , 66. 6 mmol) , an dabsolut e ethano l (53 0 mL) . Th e reactio n mixtur e wa s refluxe d fo r 3 day s unde r

nitrogen . Afte

r coolin g t o roo mtemperature , th e reactio n mixture wa s filtere dan dth e soli dwa s washe don th e funnel wit h ethano l ( 3 X 2 0 mL) . Th e soli dwa s drie dwit h benzen e i

n aDean-Star

k apparatu s t o giv e th e desire dproduct . Th e percent substitutio n for

th e poly[N-(co-N'-methylpicolinio ) 4-vinylpyridiniu mdiiodide ] wa s calculate dfro mth e percen t of iodin e a s determine d b y combustio n analyses . Note : I f on e assume s tha

t th e weigh t

of th e partiall y substitute dpoly[N-(co

picolyl ) 4-vinylpyridiniu mchloride ] i s th e weight o f th e unsubstitute dReillex TM 40 2 poly(4-vinylpyridine) , the n reactio n wit h 1.0 equivalen t

o f methy l iodid e base do

n th e unsubstitute dReillex''"' ^ 40 2 poly(4-vinylpyridine ) woul dguarante e a n exces s o

f methy l iodide . 2.3.16.1 . Poly[N-(2-N'-Methylpicolinio ) 4-Vinylpyridiniu m Diiodide ] (51 ) wa s obtaine di n 56 % yiel db y weigh t

a s adar k re dsoli dwit

h m p > 30 0 °C . I

R(KBr) : 163 7 (C=N) ; 145 8 (C- H bendin g i n -CH2-N^ ) cm"' . Elemental analysi s calculate dfo r (Ci4Hi6l2N2)o.4o(Ci3H,3lN2)o.6o : I , 46.64 ; C , 42.75 ; H , 3.76 ; N , 7.35 . Found : I , 46.35 ; C , 42.70 ; H , 4.27 ; N , 6.68 . 2.3.16.2 . Poly[N-(3-N'-Methylpicolinio ) 4-Vinylpyridiniu m Diiodide ] (52 ) wa s obtaine di n 91 % yiel db y weigh t

a s ayello w soli dwit

h m p > 30 0 °C . I

R(KBr) : 5 2163 4 (C=N) : 146 9 (C- H bendin g i n -CH2-N" ) cm"' . Elementa l analysi s calculate d fo r

(Ci4Hi6l2N2)o.7i(Ci3Hi3lN2)o.29:1 , 51.07 ; C , 38.75 : H . 3.59 ; N . 6.59 . Found : L 51.27 : C . 38.77 ; H , 3.99 : N , 5.98 . 2.3.16.3 . Poly[N-(4-N'-Methylpicolimo ) 4-Vinylpyridiniu m Diiodide ] (53 ) wa s obtaine di n 96 % yiel db y weigh t a s ayello w soli dwit h m p > 30 0 °C . I R(KBr) : 163 7 (C=N) ; 145 8 (C- H bendin g i n -CHi-N^ ) cm"' . Elementa l analysi s calculate dfo r (Ci4Hi6l2N2)o.85(Ci3Hi3lN2)o.i5:1 , 52.78 : C , 37.40 ; H , 3.52 : N , 6.30 . Found : I . 52.75 : C . 37.79 ; H , 3.79 ; N , 5.67 . 2.3.17 . Preparatio n o f Partiall y Substitute d Poly[N-(2'-Hydroxy)ethy l 4-Vinylpyridine ] 5 5 Int o a100-mL , one-necked , round-bottome dflask wer e adde dReilline TM 42(X ) polyme r (5.0 0 g , o f

a60 % MeO H solution , 28. 5 mmol) , 2-bromoethano l (0.7 1 g , 5.7 1 equivalent , 0.2 0 equivalent) , an dmethano l (2 5 mL) . Th e reactio n mixtur e wa s refluxe d fo r 1 day . Th e produc t

wa s isolate db y precipitatio n with Et^ O (5 0 mL) . Th e solven t wa s decante dfro mth e precipitate dsoli dan dth e precipitate dsoli dwa s drie din vacuo t o giv e 0.6 4 g (17% ) o f

th e produc t

a s ayello w soli dwith m p > 3(X ) °C. I R(deposi t

fro m MeO H solutio n o n aNaC l plate) : 164 0 (C=N) ; 145 4 (C- H bendin g i n -CH2-N^ ) cm"' . Note : Th e precipitate dsoli dwa s ver y sticky . Therefore , filtration coul dno t b e conducted .

5 32.3.18 . Preparatio n of Partiall y Substitute d Poly[N-(2'-Hydroxy)ethy l 2-Vinylpyridine ] 5 9 Int o alOO-mL , one-necked , round-bottome dflask wer e adde dReillin TM 220 0 polyme r (5.0 0 g , o f

a65 % MeO H solution , 30. 9 mmol) , 2-bromoethano l (0.5 8 g , 4.6 4 mmol , 0.1 5 equivalent) , an dmethano l (2 5 mL) . Th e reactio n mixtur e wa s refluxe dfo r 1 days . Th e produc t

wa s isolate db y precipitatio n wit h Et2 0 (5 0 mL) . Th e solven t wa s decante dfro mth e precipitate dsoli dan dth e precipitate dsoli dwa s drie din vacuo to giv e 0.7 4 g (19% ) of

th e produc t

a s ayello w soli dwit

h m p > 30 0 °C . I

R(deposi t

fro m MeO H solutio n o n aNaC l plate) : 164 1 (C=N) ; 145 4 (C- H bendin g i n -CH2-N"' ) cm"' . Note : Th e precipitate dsoli dwa s ver y sticky . Therefore , filtratio n coul dno t b e conducted . 2.3.19 . Preparatio n of Partiall y Substitute d Poly[N-(3-Trimethylammonio)propy l 4-Vinylpyridiniu mDibromide ] 6 3 Int o a100-mL , one-necked , round-bottome d flask were adde dReilline TM 420 0 polyme r (5.0 0 g , of

a60 % MeO H solution , 28. 5 mmol) , 3-bromopropyltrimethyl

ammoniu mbromid e (2.2 3 g , 8.5 5 mmol , 0.3 0 equivalent) , an dmethano l (2 5 mL) . Th e reactio n mixtur e wa s refluxe dfo r 1 day . Th e produc t

wa s isolate db y precipitatio n wit h Et2 0 (10 0 mL) . Th e solven t wa s decante dfromth e precipitate dsoli dan dth e precipitate dsoli dwa s drie din vacuo t o giv e 2.7 5 g (53% ) of th e produc t

a s asoli dwit

h mp > 30 0 °C . I

R(deposi t

fro mMeO H solutio n o

n aNaC l plate) : 163 7 (C=N) ; 147 4 (C- H bendin g i n -CH2-N"^

) cm"' .

5 4Note : Th e precipitate dsoli dwa s ver y sticky . Therefore , filtration coul dno t b e conducted . 2.3.20 . Preparatio n of Partiall y Substitute d Poly[N-(3-Trimethylammonio)propy l 2-Vinylpyridiniu mDibromide ] 6 5 Int o a100-mL , one-necked , round-bottome d flask were adde dReilline^ ^ 220 0 polyme r (5.0 0 g , of

a65 % MeO H solution , 30. 9 mmol) , 3-bromopropyltrimethyl

ammoniu mbromid e (2.4 2 g , 9.2 7 mmol , 0.3 0 equivalent) , an dmethano l (2 5 mL) . Th e reactio n mixtur e wa s refluxe dfo r 1 day . Th e produc t

wa s isolate db y precipitatio n wit h Et2 0 (10 0 mL) . Th e solven t wa s decante dfro

mth e precipitate dsoli dan dth e precipitate dsoli dwa s drie din vacuo t o giv e 1.8 4 g (32% ) of

th e produc t

a s asoli dwit

h m p > 30 0 °C . I

R(deposi t

fro mMeO H solutio n o

n aNaC l plate) : 163 7 (C=N) ; 147 4 (C

H bendin g in -CH2-N^ ) cm"' . Note : Th e precipitate dsoli dwa s ver y sticky . Therefore , filtratio n coul dno t b e conducted .

5 52.4 . Reference s

1 . A . K . De , Separation of Heavy Metals, Pergamon , Oxford , 1961 , Par t II . 2 . F . Helfferich , Ion Exchange, McGraw-Hill , Ne w York , 1962 , p 10 . 3 . R . Kunin , Ion Exchange Resins, Wiley , Ne w York , 1958 , p 73 . 4 . S . F . Marsh , Improved Recovery and

Purification of

Plutonium at

Los Alamos Using Macroporous Anion Exchange Resin, Lo s Alamo s Nationa l Laborator y Repor t LA-10906 , Ma y 1987 . 5 . S . F . Mars h an dT . D . Gallegos , The Infiuence of Plutonium Concentration and Solution Flow Rate on the Effective Capacity of Macroporous Anion Exchange Resin, Lo s Alamo s Nationa l Laborator y Repor t LA-10990 , Jul y 1987 . 6 . T . E . Gangwer , M . Goldstein , an dK . K . S . Pillay , Radiation Effects on Ion Exchange Materials, Brookhave n Nationa l Laborator y Repor t BNL-50781 , 1977 , p . 88 . 7 . S . F . Marsh , Evaluation of a New, Macroporous Polyvinylpyridine Resin for Processing Plutonium Using Nitrate Anion Exchange, Lo s Alamo s Nationa l Laborator y Repor t

LA-11490 , Apri l 1989 . 8 . S . F . Marsh , G . D . Jarvinen , J . S . Kim , J . Nam , an dR . A . Bartsch , React. Fund. Polymers, 1997 , 35, 75 . 9 . A . P . Gray , D . C . Schlieper , E . E . Spinner , an dC . J . Cavallito , 7 . Am. Chem. Soc, 1955 , 77, 3648 . 10 . J . Bielavsky , J . Vachek , an dF . Omst , Coll. Czech. Chem. Commun., 1972 , 37, 1044 . 11 . J . S . Kim , unpublishe dresults . 12 . A . N . Kost , M . A . Yurovskaya , A . S . Vyazgin , an dA . Z . Afanas'ev , Khim. Geterotsikl

Soedin., 1980 , 1222 . 13 . A . P . Gray , R . D . Platz , T . C . P . Chang , T . R . Leverone , D . A . Ferrick , an dD . N . Kramer , 7 Med

Chem., 1985 , 28,\\\. 14 . E . Renaud , R . B . Russell , S . Fortier , S . J . Brown , an dM . C . Baird , 7 . Organomet. Chem.,1991, 419, AQi3. 15 . S . F . Marsh , G . D . Jarvinen , R . A . Bartsch , J . Nam , an dM . E . Barr , 7 . Radioanal Nucl Chem., i n press . 5 616 . S . F . Marsh , Z . V . Svitra , an dS . M . Bowen , Distributions of 14 Elements on 3 Absorbers from Three Simulant Solutions (Acid-Dissolved Sludge, Acidified Supemate, and

Alkaline Supemate) from Hanford HLW Tank 102-Y. Lo s Alamo s Nationa l Laboratory repor t LA-1265 4 rev. , Augus t

1994 . 17 . H . Strathman n an dK . Kock , Recent Developments in Separation Sciences. CR C Press , Inc. , Florida , 1978 , Vol . TV , Chapte r 3 . 18 . H . Nishid e an dE . Tsuchida , Makromol Chem., 1976 , 777 , 2295 . 19 . A . Sugii , N , Ogawa , Y . linuma , an dH . Yamamura , Talanta, 1981 , 28, 551 . 20 . Y . T . Ba o an dC . G . Pitt , 7 . Polym. ScL Part A: Polym. Chem., 1990 , 28, 741 . 21 . P . Thanei-Wys s an dP . G . Waser , Helv. Chim. Acta, 1983 , 66, 2198 . 22 . H . Schmidbau r

an dH . P . Scherm , Chem. Ber., 1977 , II0. 1576 . 23 . H . Schmidbau r

an dH . P . Scherm , Z . Naturforsch. B: Anorg. Chem. Org. Chem., 1919,34b, 1347

-

5 7CHAPTER3 SYNTHESI S O F CYCLI C POLYETHE REXTRACTANT S

3.1 . Result s an dDiscussion s Separatio n o f

metal ion s wit

h macrocycli c polyether s usin g variou s method s continue s t o receiv e agrea t dea l of attentio n du e to thei r

application s i

n man y chemical an dbiologica l systems . Fo r example , th e extractio n o f cesiu mion s fro

macidi c nitrat e medi awit h macrocycli c polyether s i s a n importan t

proces s fo

r th e removal an drecover

y o f radioactiv e cesiu mfromnuclea r waste streams. ' I n thi s chapter , th e synthesi s o f avariet y o f new macrocycli c polyether s whic h ar e potentia l complexin g agent s fo r cesiu mio n will b e described . Th e attempte dsynthesi s o f othe r macrocycli c polyether s wil l b e als o described .

3.1.1 . Synthesi s o

f Carbo n Atom-Linke d Sid e Ar mCycli c Polyether s Solven t extractio n processe s fo

r th e remova

l an drecover

y o f radioactiv e cesiu m ion s fro macidic , hig h activity nuclea r waste wit h aserie s of

macrocycli c polyether s hav e bee n reported."^""^ Recently , it wa s reporte dtha

t th e extractio n o

f cesiu mio n fro

macidi c nitrat e solutio n b y macrocycli c polyether s ca n b e enhance d b y th e us e of th e oxygenated . aliphati c solvent s (e.g. , alcohol s an dketones ) whic h are abl e t o dissolv e sufficient amount s o f

water. ^ I

n thes e oxygenate dsolvents , ahighe r concentratio n o

f wate r facilitate dbot

h catio n an danio n solvatio n an dresulte di n th e more efficient

cesiu mion extraction . Althoug h aromati c macrocycli c polyether s yiel d highe r level s of cesiu mio n extractio n than d o aliphati c macrocycli c polyethers , the y usuall y hav e limite dsolubilitie s 5 8i

n oxygenated , aliphati c solvents. ^ I n anothe r repor t b y Bartsc h et

al.,^ several crow n ethe r alcohol s wit

h ahydrox y o r

hydroxyalky l grou p attache dto th e polyethe r rin g serve d a s bifunctional ligand s fo

r simultaneou s anio n solvatio n an dcatio n complexation . In thi s dissertatio n research , th e synthesi s of ne w macrocycli c polyether s into whic h th e oxygenated , aliphati c sid e arm s ar e incorporate di s a

n importan t

objective . Suc h compound s wit

h systemati c structural variatio n are t o b e examine da t Argonn e Nationa l Laboratory for

cesiu mio n extractio n fro macidi c nitrat e media . 3.1.1.1 . Preparatio n of

Bis(l-hydroxyalkyl)

- Substitute dCrow n Ether s Fo r th e synthesi s of

th e crow n ethe r

diols , correspondin g crow n ethe r diketone s were neede da s syntheti c precursors . A serie s of crow n ether

diketone s were prepare da s show n i n Schem e 3.1 . Th e dibenzo-18-crown- 6 diketone s 66-6 9 were obtaine d

O 7 RCO2

H ^ ^"^^yi^^^^^Eaton' s reagen t O O O -> -

5 0 oC , 4- 6 h

6 6 6 7 6 8 6 9 79 % 55 % 49 % 92 % RYiel d C3H 7 C5H1 1 C9H1 9 CHC4H 9 C2H 5 Schem e 3.1 . Synthesi s of Dibenzo-18-crown- 6 Diketone s 66-69 . 5 9fro mcommerciall y availabl e dibenzo-18-crown- 6 b y diacylation^' ^ wit h th e appropriat e carboxyli c aci dan dEaton' s reagen t (prepare dfro

mmethanesulfoni c aci dan d phosphorou s pentoxide). ^ Th e serie s of

crow n ethe r

diol s 70-7 3 wa s prepare di n hig h yield s fromth e dibenzo-18-crown- 6 diketone s 66-69 , respectively , b y reduction''- ^ wit h NaBH 4 i n EtOH

CH2CI 2 a s show n i

n Schem e 3.2 . Sinc e th e crow n ethe r diketone s 66-6 8 were neari y insolubl e i

n EtO H a t roo mtemperature , CH2CI 2 wa s use da s aco-solven t for th e reductio n reaction s t o provid e bette r solubilit y of th e reactant . Fo r

th e preparatio n o

f crow n ethe r

dio l 73 , EtO H wa s th e onl y solvent .

» • R C EtOH-CH2Cl 2 "^^-"^^ O rt,4 h O > O H

O O RYiel d 6 6 C3H 7 7 0 Quantitativ e 6 7 C5H1 , 7 1 90 % 6 8 C9H, 9 7 2 80 % 6 9 CHC4H 9 7 3 87 % C2H 5 Schem e 3.2 . Synthesi s of Dibenzo-18-crown- 6 Diol s 70-73 . T o determin e th e effec t

upo n cesiu mio n extractio n of th e presenc e of

on e o r more ethyleneox y unit s betwee n th e aromati c rin g an dth e hydroxy l grou p i n compoun d73 , th e synthesi s o f

ne w crow n ethe r

diol s wa s accomplishe da s show n i n Schem e 3.3 . Ne w 6 0dibenzo-18-crown- 6 diol s 7 4 an d7 5 were obtaine di n hig h yield s fromth e precurso r dio l 7 3 b y th e reactio n wit

h acatalyti c amount

o f sulfuri c aci dan da

n exces s o

f th e appropriat e ethylen e glyco l i n CH2CI2 .

H O I C4H9CHC H C2H 5 O H

O^^^^^CHCHC4H 9

C2H 5 H O O O H

cat . H2SO4 CH2CI2 rt , 1 5 h 7 3

H O O O

I C4H9CHC H C2H 5 O O O H I C H C HC 4H

9 C2H 5

7 4 7 5 n 0 1 Yiel d 83 % 76 % Schem e 3.3 . Synthesi s of Dibenzo-18-crown- 6 Diol s 7 4 an d75 . T o investigat e th e effec t

of th e siz e of

th e polyethe r

rin g on cesiu mion extraction , th e synthesi s o f

dibenzo-2 1 -crown- 7 derivative s wa s performed . Dibenzo-2 1 -crown- 7 dio l 7 8 wa s prepare db y th e metho ddevelope db y Bradsha w et alJ'^a s show n i

n Schem e 3.4 . First , dibenzo-21-crown- 7 diketon e 7 7 wa s obtaine dfromdibenzo-21

- crown- 7 (76 ) b y reactio n wit h 2-ethylhexanoi c aci d an dEaton' s reagent . Subsequen t

6 1reductio n of dibenzo-21-crown- 7 diketon e 7 7 wit h NaBYU i n EtO H gav e di[(2-ethyl- l hydroxyhexyl)benzo]-21-crown- 7 (78 ) i n quantitativ e yield . 

# a ° o 

### ^^f" ^ o o C4H9CHCO2 H C2H5 Eaton' s reagen t y^^/ " 30-3 5 OC . 4- 6 h

7 6 7 7 (83% )

NaBH4 EtO H rt , 24 h H O

I C4H9CHC H C2H5 O O H

u o

7 8 (Quantitativ e yield ) Schem e 3.4 . Synthesi s of Di[(2-ethyl-l-hydroxyhexyl)benzo]-21-crown- 7 (78) . A dibenzo-21-crown- 7 dio l 7 9 wa s prepare d b y same metho da s wa s utilize dfo r th e synthesi s of

th e dibenzo-18-crown- 6 dio l 7 5 a s show n i n Schem e 3.5 . Reactio n o f th e dibenzo-21-crown- 7 dio l 7 8 wit h a n exces s o

f diethylen e glyco l an dacatalyti c amoun t o f sulfuri c aci di

n CH2CI 2 gav e 4,4'(5')-di[(2-ethyl-l-(5-hydroxy-3-oxapentoxy)

- hexyl)-benzo]-21-crown- 7 (79 ) i n hig h yield .

6 2H O

C4H9CHCH

C2H 5 O H CHCHC4H

9 H O O C H . O H

cat . H2SO 4 CH2CI2 rt, 1 5 h 7 8 

## /^A/— \ O O O H I CHCHC4H9 I C2H 5

7 9 (84% ) Schem e 3.5 . Synthesi s o f 4,4•(5')-Di[(2-ethyl-l-(5-hydroxy-3-oxapentoxy)

- hexyl)benzo]-21-crown- 7 (79) . 3.1.1.2 . Synthesi s of

Bis(2-hydroxyalkyl)

- Substitute dCrow n Ether s Sinc e cesiu mio n extractio n wa s to take plac e fro macidi c nitrat e media , th e stability o f

polyethe r extractant s t o acidi c condition s ha s to b e take n int o accoun t alon g wit h thei r extractio n ability fo

r cesiu mion . Treatmen t

o f bis ( 1 -hydroxyalkyl)

- substitute dcrow n ether s wit h aqueou s nitri c aci dcoul dleadt o several pathway s a s show n i n Figur e 3.1 . Th e hydroxy l grou p o n th e sid e ar

mo f th e crow n ethe r

ca n reac t wit h aci dt o generat e a

n oxoniu mion , whic h ca

n then dissociat e t o produc e abenzyli c

6 3H ® -H^ O

7 3 8 0

8 1 eliminatio n rearrangement combinatio n Figur e 3.1 . Possibl e Reactio n Pathway s upo n Treatmen t of aCrow n Ethe r Alcoho l wit

h Acid . carbocatio n an dwater . Thi s benzyli c carbocatio n i s apotential intermediat e fo r avariet y of reactions , includin g eliminatio n t o for ma n alkene , rearrangemen t

t o for mamore stabl e carbocation , o r

combinatio n wit

h nucleophiles . Th e stabilit y of th e polyethe r extractant s coul db e enhance di f formatio n of

th e benzyli c carbocatio n were prevented . Therefore , movemen t

of th e hydroxy l grou p fro

mth e firs t

t o th e secon dcarbo n ato mi n th e sid e ar

mwa s envisioned . T o thi s end , th e synthesi s o f bis(2-hydroxyalkyl)

- substitute dcrow n ether s wa s attempted . 3.1.1.2.1 . B y Isomerizatio n Fo r th e preparatio n of

bis(2-hydroxyalkyl)-substitute dcrow n ethers , th e reactio n o f bis(l-hydroxyalkyl)-substitute dcrow n ether s wit h hydrochlori c aci do r

sulfuri c aci d 6 4wa s conducte da s show n i n Schem e 3.6 . Wit

h 5 % hydrochlori c acid , th e reactio n gav e th e unreacte dstartin g materia l 73 . Reactio n wit h concentrate dHC l yielde dth e unreacte dstartin g materia l 7 3 wit h asmal l amount

of eliminatio n produc t

83 . Reactio n wit h sulfuri c aci d(5 % o r

concentrated ) gav e amixtur e of eliminatio n product s 83-88 . instea dof th e desire dproduc t

82 .

O H H O ' O O^^^^^CHCHCH, Aci d H O

. f^^V

- u.^^^uHY"^"" ^ Aci d" V ^^- ^ C4H9CHCH-|- ^ I

I 1

^ I I CaH . X ^ C4H<,CCH2-[

- ^

CH2CI 2 r t 7 3 ^ O ^ O H O 0,^^;f>^^CH2CC4H ^

8 2

, 0 0^^^fSs.CH=CC4H ^ C4H^=CH-|- : 11 ^ J ^C,H 5 C, H 2" 5 8 3 + C3H7CH=CC H C2H 5 - ^ y 8 4

.CH2C^IHCH 3 CH3CH=CC:H.^ ^ OA J ^^" ^

8 5 C4H9C=C H C2H5 

# OC . X^ - '

K 6

C4H9C=C H C2H 5 O

o o o o 8 7 .CH2C=CHCH 3

I C4H , + C3H7CH=CCH : C2H 5 ^tr^^y^O 0.^^^;;v^CH2C=CHCH 3 !~r : I I o 8 8 o ^ C4H y

Schem e 3.6 . Attempte dSynthesi s of 4,4'(5*)-Di[(2-ethyl-2

- hydroxyhexyl)benzo]-18-crown- 6 (82) .

6 53.1.1.2.2 . B y Oxymercuration-Demercuratio n

Fo r th e synthesi s of

bis(2-hydroxyalkyl)-substitute dcrow n ethers , abis-alkene

substitute dcrow n ethe r

wa s prepare da s aprecurso r fo r a n oxymercuration-demercuratio n proces s (Schem e 3.7) . Th e dehydratio n o f bis ( 1 -hydroxyalkyl)-substitute dcrow n ether 7 3 wit h p-toluenesulfoni c acid' ^ yielde damixtur e o f si x alken e isomer s 83-8 8 wit h a rati o of 1-alken e t o 2-alken e sid e group s = 83:1 7 a s determine dfromth e H NM R spectru mof

th e mixture . Alken e isomer s 8 4 an d8 5 resulte dfromth e rearrangemen t o f th e benzyli c carbocatio n a s show n i n Figur e 3.2 . 

# r o O H H O ^-j^v^ O 0^rs...^CHCHC4H , C4H9CHCH- P |

T T I

j C2H 5 C2H 5 ^^"^ 0 o-"^* ^

7 3

^?\.^ 0 0...^^v^CH=CC4H y

8 3

8 5

^^^ 00.^^s^CH2C=CHCH 3 C4H9C=CH4

- I

J L J C4H y *

8 7 TsO H ph H reflux , 3 0 min .

^J^V^ O 0^^;^^^CH2C=CHC3H 7

8 4

^J?^ 0 O.^^^CH2C=CHC,H 7

K 6 ^?\^ 0 0^^v,^^CH2C=CHCH 3 C3H7CH=CCH2- + I

X ^ J C4H , C2H 5 ^^-^ 0 0^^^= ^

8 8 Schem e 3.7 . Dehydratio n of Crow n Ethe r

Dio l 73 . 6 6OH H C-C-CH2C3H 7 H CH2CH 3 H + 7 3 -H2 O (a) H ® ^ 1 CMZ-CH^Ct H I I 2C3H

7 -H + H CH2CH 3 1,2-Hydrid e Shif

t (via a )

0 (b) H CH2-C^HC3H 7 -H + ;CHCH 3 (c)( ^ H (via b )

-H + (via c ) C H— C C 4 H 9 C2H5

CH.C=CHC^H 7 " I C2H S

CH2C=CHCH 3 C4H 9 Figur e 3.2 . Pathway s t o th e Alken e Isomer s 83-88 . Th e synthesi s o f

bis(2-hydroxyalkyl)-substitute d crow n ethe r 8 2 wa s attempte dby oxymercuration-demercuratio n a s show n i n Tabl e 3.1 . Oxymercuratio n o f th e bis

alkene-substitute dcrow n ethe r mixtur e 83-8 8 wit

h mercury(n ) acetate " (o r mercury(II ) trifluoroacetate'^ ) in H2O-THF followe db y demercuratio n wit h NaOH-NaBH4 gav e a mixtur e o f

crow n ethe r

diol s 73 , 8 2 an d89 . I

t i s envisione dtha

t bis-alkene-substitute d crow n ether s 8 4 an d8 5 gav e asingl e product , crow n ethe r dio l 82 , a s expecte dfo

r a Markovniko v addition . O n th e othe r hand , additio n t o th e doubl e bon di n crow n ethe r

8 3 migh t giv e th e tw o isomer s 7 3 an d8 2 du e to th e possibl e competitio n of benzyli c an d tertiary carbocations . Also , bis-alkene-substitute dcrow n ether s 86-8 8 woul dgiv e a mixtur e o f

crow n ethe r

diol s 8 2 an d89 .

6 7Tabl e 3.1 . Attempte dSynthesi s of Crow n Ethe r

Dio l 8 2 b y Oxymercuration

Demercuration .

Bis-alkene-substitute d Crow n Ethe r

Mixtur e 83-8 8 l)Hg(0Ac) 2 H2O-TH F rt , 1 d 2 ) NaOH-NaBH 4 C4H9CHC H C2H 5 O

o o o o o O H

I CHCHC4 H I 4n 4

73

H O C4H9CCH 2 C2H 5 O

o o O Q O O H I CH2CC4H 9 C2H 5 H O I C4H9CHC H C2H 5 O

o o o o o O H I CH.CCjH u " I

8 2 8 9 Rati o of sid e groups ^ Mercury reagen t Yield , % (1-alcoho l :2-alcohol ) Hg(OAc) : 33 65:3 5 Hg(OCOCF3) 2 6 3 64:3 6 Determinedfro

mthe H NM

Rspectru mo f th e produc t mixture . T o preven t

th e possibl e competitio n o f benzyli c an dtertiar

y carbocation s i

n th e additio n of

wate r t o th e doubl e bond , th e synthesi s o f a n alkene-substitute dcrow n ethe r wit h unbranche dsid e arm s wa s performe da s show n i n Schem e 3.8 . Th e dehydratio n of 4,4'(5')-di[(l-hydroxydecyl)benzo]-18-crown- 6 (72 ) wit h p-toluenesulfuri c aci d produce d4,4'(5')-di[(l-decenyl)benzo]-18-crown- 6 (90) . 1 0

6 8^ O ^ O H ^ O H(j ) ^v^^ O 0^^:^..CHCH2C«H n TsO H ,^^"-^* ^ d^^^^CH=CHC, H C«H.^H2CH^ ^ ,X J 7; ^C«H.^H=CH^ ^ ^Xj

L^O^reflux , 2 h C^O ^ 7 2 9 0 (59% ) Schem e 3.8 . Synthesi s of 4,4'(5*)-Di[(l-decenyl)benzo]-18-crown- 6 (90) . Th e synthesi s o f

4,4'(5')-di[(2-hydroxydecyl)benzo]-18-crown- 6 (91 ) fromth e alken e substitute dcrow n ethe r 9 0 b y oxymercuration-demercuratio n wit h mercury(II ) trifluoroacetat e wa s attempte da s show n in Scheme 3.9 . However , th e reactio n gav e a mixtur e o f

th e isomeri c 1

- an d2-hydroxyalkyl-substitute dcrow n ether s 72 , 9 1 an d92 . Fro mth e result s discusse dabove , oxymercuration-demecuratio n o f alkene

substitute dcrow n ether s wa s judge dt o b e unabl e t o produc e th e desire dbis(2

- hydroxyalkyl)-substitute dcrow n ethe r selectively .

6 9^ o ^

C8H,7CH=CH- ^ 1

1 p o o 9 0 CH=CHCg H 1 7 l)Hg(OCOCF3) 2

H2O-TH F rt . 1 d 2 ) NaOH-NaHH 4

H O I CSHITCHZC H o

o 7 2 O H

CHCH2C8H1 7 HO

+ CsHnCHCH j o o

o o o 9 1 O H I CHiCHCjfH p

+ CgHnCHzC H O

o o o o o 9 2 O H I CH2CHCgHi 7

(28% , l-alcohol:2-alcoho l = 45:55 ) Schem e 3.9 . Attempte dSynthesi s of 4,4'(5')-Di[(2-hydroxydecyl)benzo]-18

- crown- 6 (91 ) b y Oxymercuration-Demercuration . 3.1.1.2.3 . B y Hydroboration-Oxidatio n Sinc e th e oxymercuration-demercuratio n proces s of th e crow n ethe r

alkene s gav e amixtur e of

tw o crow n ethe r

dio l isomers , anothe r

synthesi s o

f bis[2-hydroxyalkyl ] 1 3 substitute dcrow n ethe r

b y hydroboration-oxidatio n wa s attempte da s show n i n Schem e 3.10 . Hydroboratio n of

4,4'(5')-di[(l-decenyl)benzo]-18-crown- 6 (90 ) wit h sodiu m borohydrid e an dboro n trifluorid e etherat e an dsubsequen t oxidatio n wit

h hydroge n peroxid e gav e amixtur e of crow n ethe r

diol s 72 , 9 1 an d92 . Hydroboration-oxidatio n gav e a n eve n lowe r

proportio n of

th e desire dcrow n ethe r

dio l 9 1 tha

n di d oxymercuration-demercuration . 7 0

# C O

C8H,7CH=CH-

P I I o o o 9 0 CH=CHC8 H S"! ? l)NaBH4,TH F

BF30Et2 , OoC , 2 0 mi n then , rt, lO h 2 ) OH- . H2O2 , Oo

C then , rt, 3 h

H O I CgHi7CH2C H 

# ^ Y ° 

# r^° ^

^*'*-''^^ I 72 O H I CHCH2CgH| 7 H O

+ CRHHCHCH Z o

o o o o o 9 1 O H I CH^CHCgHf

H O + C8H,7CH2C H O O O O o 9 2 O H

I .CH2CHCjjHi 7

(28% , 1-alcohol . 2-alcohol = 66:34 ) Schem e 3.10 . Attempte dSynthesi s of 4,4'(5')-Di[(2-hydroxydecyl)benzo]-18

- crown- 6 (91 ) b y Hydroboration-Oxidation . 3.1.2 . Synthesi s of

Oxyge n Atom-Linke d Sid e Ar mCycli c Polyether s I n additio n t o th e attempte dsynthesi s o f bis(2-hydroxyalkyl)-substitute ddibenzo

18-crown- 6 compounds , th e preparatio n of oxyge n ato mlinke dsid e ar mcycli c polyether s i

n whic h th e sid e arm s are joine d t o th e benzen e rings of th e dibenzo-18

- crown- 6 throug h a

n oxyge n ato mwa s attempted . A benzyli c carbocatio n coul dno t b e forme dfro msuc h diol s unde r acidi c conditions . Thre e strategie s fo r th e preparatio n of a n "O-linked " sid e ar

mdibenzo-18-crown- 6 were explored : (i ) elaboratio n of th e sid e 7 1ar mi n acatecho l derivativ e an dsubsequen t cyclizatio n t o formadisubstitute ddibenzo

18-crown-6 ; (ii ) cyclizatio n o f aprotecte dcatecho l derivativ e t o formadisubstitute d dibenzo-18-crown- 6 an dsubsequen t deprotectio n an delaboratio n o f th e sid e arm : an d (iii ) modificatio n o f

commerciall y availabl e dibenzo-18-crown- 6 t o formadisubstitute d dibenzo-18-crown- 6 an dsubsequen t elaboratio n o f

th e sid e arms . 3.1.2.1 . Elaboratio n o f

th e Sid e Ar mi n aCatecho l Derivativ e an dSubsequen t Cyclizatio n Fo r us e i n th e preparatio n o f a n "O-linked " sid e ar mdibenzo-18-crown- 6 compound , th e catecho l derivativ e 9 4 wa s synthesize di n tw o step s fro mth e commerciall y availabl e Sesamol . Th e protecte dcatecho l derivativ e 9 3 wa s obtaine d fro mth e reactio n o f

Sesamo l wit h cesiu mcarbonat e an d1,2-epoxyhexan e i n acetonitril e a s show n i n Schem e 3.11 . Reactio n o f Sesamo l with sodiu mhydroxid e an d1,2

- epoxyhexan e i n r-butano l at reflu x fo r

3 day s gav e sam e 9 3 i n alowe r yiel do f 45% .

O H

Sesamo l 1)CS2C0 3 CH3C N reflux , 3 h 2 ) O Z_A-—-•C4H

9 reflux , 6 0 h O H I OCH2CHC4H 9

9 3 (78% ) Schem e 3.11 . Synthesi s o f th e Protecte dCatecho l Derivativ e 93 .

7 2Attempt s t o us e sodiu mhydrid e o r potassiu mhydrid e a s th e bas e i n tetrahydrofura

n di d no t giv e th e desire dproduct . Subsequently , th e protectin g grou p wa s remove d b y th e reactio n of th e protecte d catecho l derivativ e 9 3 wit h boro n trichlorid e i

n dichloromethane" ^ t o giv e acatecho l derivativ e 9 4 a s show n i

n Schem e 3.12 . Attempte d deprotectio n wit h Dowex-50W-X 8 io n exchang e resi n in wate r (o r THF-water ) a

t 70° C fo r 2 4 hour s gav e onl y th e recovere d reactant .

OH O H I I OCH2CHC4H

9 Bc i HO.,^^?s..,^OCH2CHC4H 9 

# X J CH2CI 2 HO ' rt, 1 h 9 3 9 4 (50% ) Schem e 3.12 . Synthesi s o f Catecho l Derivativ e 94 . Th e synthesi s of

4,4'(5')-di[(2-hydroxyhexoxy)benzo]-18-crown- 6 (95 ) by th e 2+ 2 typ e o f cyclizatio n develope db y Pedersen' ^ fo r th e preparatio n of

dibenzo-18-crown- 6 wa s attempte da s show n i n Schem e 3.13 . Th e reactio n of th e catecho l derivativ e 9 4 wit h sodiu mhydroxid e an dbis(2-chloroethyl ) ethe r i n w-butano l gav e onl y ver y smal l amount s of

th e desire ddisubstitute ddibenzo-18-crown- 6 9 5 contaminate dwit h unidentifie dimpurities . Several attempt s t o purif y th e cmd e produc t

b y column chromatogarph y o r

recrystallizatio n di dno t

giv e th e pur e compoun d95 .

739 4 O H I OCH2CHC4H 9 C I NaO H O C I Ai-BuO H reflux , 1 6 h ^

H O C4H9CHCH2 O O O O H I 0..^^^s^OCH2CHC4H 9 O O ' O , 9 5 Schem e 3.13 . Attempte dSynthesi s of 4,4'(5')-Di[(2-hydroxyhexoxy)benzo]-18

- crown- 6 (95) . 3.1.2.2 . Cyclizatio n of

aProtecte dCatecho l an d Subsequen t

Deprotectio n an dElaboratio n o f th e Sid e Ar

m Th e assumptio n tha

t th e functionalize dsid e ar mi n th e catecho l derivativ e 9 4 wa s detrimenta l t o th e cyclizatio n reactio n le d t o th e anothe r syntheti c approac h whic h include s cyclizatio n an dsubsequen t elaboratio n of

th e sid e arm . Th e benzy l grou p wa s chose n a s aprotectin g grou p sinc e it shoul db e unaffecte db y th e basi c condition s t o b e use din th e cyclizatio n t o for mth e dibenzo-18-crown- 6 compound . Th e synthesi s of

th e benzy l grou p protecte dcatecho l 9 7 wa s attempte da s show n i n Schem e 3.14 . Th e synthesi s of th e benzyl-protecte dSesamo l 9 6 wa s attempte db y tw o different

methods . Th e reactio n of Sesamo l wit

h sodiu mhydroxid e an dbenzy l 74O H

Sesamo l BnCl , NaO H dioxane , lOOoC , 1 d o r BnCl , NaO H C6H5CH2N"(C2H5) 3 C r CH2CI2-H2O . rt , 1 d OCH.P h

9 6 BCI3 . CH2CI

2 rt, 3 0 mi n ) ( OCHzP

h

9 7 Schem e 3.14 . Attempte dSynthesi s o f th e Catecho l Derivativ e 97 .

16 chlorid e i n dioxan e wa s performed . Th e H NM Rspectr aindicate dtha t produc t 9 6 obtaine dfro mcolum n chromatograph y wa s contaminate dwith a n unidentifie dimpurity , whic h wa s no t

indicate db y thi n laye r

chromatographi c analysis . Anothe r synthesi s usin g aphas e transfer-catalyze dreactio n wa s attempted . Sesamo l wa s reacte dwit h sodiu mhydroxid e an dbenzy l chlorid e in th e presenc e o f aphas e transfe r

catalys t an d gav e th e sam e resul t

a s th e first

method . Despit e th e presenc e o f th e impurit y in compoun d96 , deprotectio n o f methylen e grou p wa s attempted . I t wa s though t

tha t th e impurit y migh t

b e separabl e afte r

th e deprotectio n o f

compoun d96 . Th e reactio n o f th e 7 5impur e benzylate dSesamo l 9 6 wit h boro n trichlorid e i

n dichloromethan e di dno t giv e th e desire dproduc t

97 , bu t a n unidentifie dmixtur e o

f products . 3.1.2.3 . Modificatio n o

f Dibenzo-18-crown- 6 an d Subsequen t

Elaboratio n of

th e Sid e Arm s 3.1.2.3.1 . Synthesi s of

Dihydroxy-Substitute d Dibenzo-18-crown- 6 Fo r th e synthesi s of

di(hydroxybenzo)-18-crown-6 , tw o method s wer e explored . Th e firs t preparativ e sequenc e fo

r th e dihydrox y substitute ddibenzo-18-crown- 6 i s show n i n Schem e 3.15 . Reactio n o f dibenzo-18-crown- 6 wit

h nitri c aci di

n aceti c aci d an dchloroforma

t roo mtemperature' ^ gav e adi(nitrobenzo)-18-crown- 6 (98) . Subsequen t

hydrogenatio n wit

h 10 % Pd- C i

n dimethylformamid e a

t roo mtemperature' ^ provide ddi(aminobenzo)-18-crown- 6 (99) . Th e di(hydroxybenzo)-18-crown- 6 (101 ) wa s obtaine db y two-ste p processes.' ^ Th e reactio n o f di(aminobenzo)-l8-crown- 6 (99 ) wit h NaN0 2 i

n aqueou s fluoroboric aci dgav e abis-diazoniu mtetrafluoroborat e 100 . Subsequen t

reactio n wit

h trifluoroaceti c aci dan dpotassiu mcarbonat e produce d di(hydroxybenzo)-18-crown- 6 (101) . Another attemp t fo r th e preparatio n o

f dihydroxy

substitute ddibenzo-18-crown- 6 wa s performe da s show n i n Schem e 3.16 . Th e reactio n o f di(aminobenzo)-18-crown- 6 (99 ) wit h NaN0 2 i

n aqueou s sulfuri c aci da

t 0 ° C to for

m th e bis-diazoniu msulfate in situ followe dby refluxing' ^ gav e a n unidentifie dmixtur e of products .

7 6O '

^ O 

### o ,

O ' HN0 3 O '



### o ACOH-CH3C 1

rt, 24 h - ^ O9 N O 

### o 

### o ,

O ' .NO . O , 9 8 (79% )

H2 , Pd- C DM F rt, 24 h H9N

O

^ O 

### o o 

### o . 9 9 (99% ) l)NaN02 . HBF 4

NH 2 H2O , OOC

, 3 0 mi n 2 ) K2CO 3 CF3CO2 H reflux , 2 4 h

HO-

- O

, 0 O

^ O 

### o 10 1 (40% ) Schem e 3.15 . Synthesi s of 4,4'(5')-Di(hydroxybenzo)-18-crown- 6 (101) .

H2N-

- 

### o o

Q O O 9 9 l)NaN02 , H2SO 4

NH 2 H2O , 0 O

C 2 ) H2SO4 , H2 O reflux , 5 mi

n ^ H0-

- O O O O 0 O 10 1 O H

Schem e 3.16 . Attempte dSynthesi s of 4,4'(5')-Di(hydroxybenzo)-18-crown- 6 (101) . 

### 7

7An alternativ e syntheti c rout e t o di(hydroxybenzo)-18-crown- 6 wa s develope d

(Schem e 3.17 ) du e t o th e lo w yiel dfo r th e las t step i n th e metho dshow n i

n Scheme 3.15 . I n thi s ne w syntheti c sequence , di(acetylbenzo)-18-crown- 6 (102 ) wa s obtaine dfro mth e reactio n o f

dibenzo-18-crown- 6 wit

h aceti c aci dan dEaton' s reagen t a t 50°C . Severa

l attempt s for

th e preparatio n of

di(acetatobenzo)-18-crown- 6 (103 ) b y aBaeyer-Villige r reactio n wer e performed . A n attemp t wit h w-CPBA-TsOH^ ^ gav e a n unidentifie d mixtur e o f

product s an dth e startin g material remaine dunreacte dfromth e attemp t wit h H202-CF3CH20H.^ ' Othe r attempt s wit

h w-CPBA " or

m-CPBA-CF3C02H-

- gav e lo w yields . Reactio n of

crow n ethe r

diketon e 10 2 wit

h m-chloroperoxybenzoi c aci di n dichloromethan e i n th e presenc e of Na2HP04^'^ gav e th e crow n ethe r dieste r 10 3 i n high yield . Hydrolysis^' * of

th e crow n ethe r

dieste r 10 3 wit h sodiu mhydroxid e i

n methanol

dichloromethan e yielde ddi(hydroxybenzo)-18-crown- 6 (101 ) i n hig h yield .

7 8CH3C02 H Eaton' s reagen t 5 0 OC , 6 h 10 2 (64% )

m-CPB A Na2HP0 4 CH2CI 2 rt, 2 d O

I I •^CH3CO — 

### o o 0.^^\^0CCH 3 NaO H Me0H-CH2Cl 2 rt, 24 h 10 3 (78% )

10 1 (83% ) Schem e 3.17 . Alternativ e Synthesi s o f o f 4,4'(5')-Di(hydroxybenzo)-18-crown- 6 (101) . 3.1.2.3.2 . Synthesi s o f

Di[(2-hydroxy)alkoxybenzo]-18-crown- 6 Involvin g Alkylatio n o f

Di(hydroxybenzo)-18-crown- 6 Fo r th e synthesi s o f

"O-linked " sid e ar

mcrow n ethers , sid e ar

melaboratio n reaction s o f

di(hydroxybenzo)- l 8-crown- 6 were performed . Analogou s reaction s o f Sesamo l a s amode l study wer e perfome di n advanc e of

th e reactio n wit

h di(hydroxybenzo)-18-crown-6 . 7 93.1.2.3.2.1 . Reactio n wit h Epoxides . Reaction s of Sesamo l wit

h 1,2

- epoxyhexan e o r

1,2-epoxyoctan e usin g different base-solven t

combination s wer

e performe da s show n i

n Tabl e 3.2 . Th e reaction s provide dth e desire dproduct s i n 39

- 8 1 % yields . Th e cesiu mcarbonate-acetonitril e combinatio n a t reflu x fo r 3 day s gav e th e bes t results . A

n analogou s reactio n wit

h potassiu mcarbonat e i

n acetonitril e wa s Tabl e 3.2 . Reaction s o f

Sesamo l wit

h Epoxides . O H O

R C4H 9 C6H13 9 3

10 4 O H

I OCH2CHR

R Bas e (equiv. ) Solven t Temp . Time , dYield , % C4H 9 C4H 9 C4H 9 C4H 9 CeH n CeH n CeH n CeH n C6H1 3 CS2CO 3 (2.5 )

K2CO 3 (2.5 ) CS2CO 3 (2.5 ) CS2CO 3 (2.5 ) CS2CO 3 (2.5 ) CS2CO 3 (2.5 ) Li2C0 3 (2.5 ) NaO H (2.0 ) NaO H (2.0 ) CH3C N

CH3C N DM F DM F CH3C N DM F DM F ?-BuO H /-BuO H reflu x

reflu x 80° C 115° C reflu x 80° C reflu x reflu x reflu x 3

3 3 3 3 3 3 3 7 7 8

a 6 2 6 2 8 1 5 1 5 8 3 9 4 0 Th e reaction was incomplete . 8 0incomplet e afte r refluxin g fo

r 3 days . Reaction s wit

h hydrid e bas e (Na

H o r KH ) i n acetonitril e o r

dimethylformamid e di dno t giv e th e desire dproduct . Reaction s o f

di(hydroxybenzo)-18-crown- 6 (101 ) wit h 1,2-epoxyhexan e or

1.2

- epoxyoctan e usin g different base-solven t

combination s wer

e attempte da s show n i

n Tabl e 3.3 . Non e of

th e reaction s produce dth e desire d product s 9 5 an d 105 , respectively . Reaction s usin g carbonat e base s (CS2CO3 , K2CO3 , or Li2C03 ) i n acetonitril e o r dimethylformamid e gav e aver y lo w mas s balance , wit

h th e isolate dproduct s bein g only abou t 1/1 0 o f th e startin g material b y weight . Thes e inorgani c base s were replace db y th e organi c base s o f

l,8-diazabicyclo[5,4,0]undec-7-en e (DBU ) an dproto n sponge , sinc e complexatio n o f

deprotonate ddi(hydroxybenzo)-18-crown- 6 wit h metal cation s coul d conceivabl y deactivat e th e nucleophile . However , reaction s wit h DB U o r proto n spong e gav e onl y th e unreacte dstartin g material . Also , mode l reaction s o f Sesamo l wit

h organi c base s (DBU , proto n sponge , o r triethylamine ) produce donl y th e unreacte d startin g material . Reactio n wit h sodiu mhydroxid e a s th e bas e gav e smal l amount s of th e desire dproduc t

10 5 tha t wa s contaminate dwit

h th e unidentifie dimpurity . However , th e obtaine dproduc t

10 5 wa s stil l contaminate dwit h thi s unidentifie dimpurit y eve n afte

r several attempt s o f

purificatio n b y colum

n chromatograph y an drecrystallization . Analysi s of

th e ' H NM Rspectr ao f

th e product s fromthes e reaction s indicate dtha t th e dibenzo-18-crown- 6 dialkoxid e whic h wa s initiall y forme dfromth e reactio n o f di(hydroxybenzo)-18-crown- 6 wit h th e epoxid e reacte dfurther wit h mor e epoxid e t o giv e elongate dsid e arms .

8 1Tabl e 3.3 . Attempte d Reaction s of Di(hydroxybenzo)-18-crown- 6 (101 ) wit h Epoxides .

o 

# Horr ° o

O 0 o O H O ^ RCHCH2 O o o o o o o O H I OCH.CH R

10 1 R C4H 9 CeH n 9 5 10 5 Epoxid e (equiv. ) Bas e (equiv. ) Solven t Temp . Time , d ,2-epoxyhexan e (2.0 ) CS2CO 3 (5.0 ) ,2-epoxyhexan e (2.0 ) K2CO3 (5.0 ) ,2-epoxyhexan e (2.2 ) CS2CO 3 (5.0 ) ,2-epoxyoctan e (2.2 ) CS2CO 3 (5.0 ) ,2-epoxyoctan e (5.0 ) CS2CO 3 (5.0 ) ,2-epoxyoctan e (2.2 ) CS2CO 3 (5.0 ) ,2-epoxyoctan e (2.0 ) Li2C0 3 (5.0 ) ,2-epoxyoctan e (2.0 ) NaO H (4.0 ) ,2-epoxyoctan e (2.0 ) NaO H (4.0 ) ,2-epoxyoctan e (2.0 ) DB U (4.0 ) CH3C N CH3C N DM F CH3C N CH3C N DM F DM F /-BuO H r-BuO H CH^CN ,2-epoxyoctan e (2.0 ) Proto n spong e (4.0 ) CH3C N reflu x reflu x 115° C reflu x reflu x 8 0 ° C reflux reflux reflu x reflu x reflu x 7

3 3 3 3 3 3 7 3

8 23.1.2.3.2.2 . Reactio n wit h Cvcli c Sulfate Ester . T o circumven t th e formatio n o

f multi-additio n product s postulate di n th e reactio n of

di(hydroxybenzo)-18-crown- 6 wit h epoxides , th e synthesi s of di[(2-hydroxyalkoxy)benzo]-18-crown- 6 b y th e reactio n o f di(hydroxybenzo)-18-crown- 6 wit h acycli c sulfat

e este r wa s envisioned . Th e cycli c sulfate este r

10 7 wa s prepare db y reactio n o f 1,2-decanedio l wit

h thiony l chlorid e and triethylamin e in dichloromethan e a t 0 ° C an dsubsequen t

oxidatio n o

f cycli c sulfit

e este r 10 6 wit h sodiu mperiodat e i

n th e presenc e o

f ruthenium(ni ) chlorid e hydrat e i n CCU

CH3CN-H2 O a

t 0 °C^^a s show n Schem e 3.18 .

OHO H ?\ 0 0 I I SOCl2,Et3 N ^S ^ RuCl3-H20 , NaI0 4 ^S ^ CH3(CH2)7CHCH 2 • O p • O O

CH2CI2 ^' CCI4-CH3CN-H2 O ^ ) f OOC , 1 5 mi n ^^"' ^ OoC , I h ^^^^^ 10 6 10 7 (95 % overall ) Schem e 3.18 . Synthesi s of Cycli c Sulfate Ester

107 . Elaboratio n o f

th e sid e ar

mb y reactio n o

f a n aryloxid e wit

h th e cycli c sulfat

e este r wa s investigate dusin g a

n adaptatio n o

f aliteratur e method.'^"^^ Th e subsequen t reactio n wa s t o b e hydrolysi s of th e sulfate group . Mode l reaction s wit h Sesamo l were performe da s show n i

n Tabl e 3.4 . Unde r

all of th e condition s employed , th e reaction s produce dth e desire dproduc t 10 8 togethe r

wit h it s structural isomer

109 . Variation s of base-solven t

combinatio n an dreactio n temperatur e di dno t appreciabl y affect

th e rati o o

f th e desire dproduc t

10 8 t o it s structural isome r 109 . 8 3Tabl e 3.4 . Reaction s o f Sesamo l with Cycli c Sulfat e Este r 107 .

o < o O H

Sesamo l DBas e CgH n

3 ) H2SO4 , H2

O TH F rt , 1 h OH O^^^^^^OCHzCHCgH n 

# <oX T

10 8 O < O ,OCHC8H, 7

CHoO H 10 9 Yield ' o f 108:10 9 Bas e (equiv. ) Solven t Temp . Time , d10 8 + 109 , % Rati o CS2CO 3 (2.5 ) CH3C N CS2CO 3 (2.5 )

DB U (2.5 ) DM F CS2CO 3 (2.5 ) CH3C N

CH3C N CS2CO3(1.0 ) CH3C N CS2CO 3 (2.5 ) CH3C N reflu x 8 0 ° C 5 0 ° C 5 0 ° C 5 0 ° C 5 0 ° C 2 6 9 (56 ) 6 2 (48 ) 49(44 ) 4 5 (39 ) 75(47 ) 7 7 (46 ) -4: 1

-6: 1 -5: 1 -6: 1 -4: 1 -4: 1 Th e yield s o

f 10 8 an d10 9 ar

e combined . Th e isolate dyiel do f 10 8 i s shown i

n th e parenthesis . Reactio n o f

di(hydroxybenzo)-18-crown- 6 with cycli c sulfat e este r 10 7 an d cesiu mcarbonat e i n acetonitril e wa s attempte da s show n i n Schem e 3.19 . Fro mthi s reaction , 4,4'(5')-di[(2-hydroxydecyloxy)benzo]-18-crown- 6 (110 ) wa s obtaine di n 21 % yiel db y recrystallizatio n fro mmethanol . Anothe r attemp t usin g 1,8-diazabicyclo

- [5,4,0]undec-7-en e (DBU ) a s th e bas e gav e th e compoun d11 0 in 17 % yiel db y colum n chromatography . However , th e obtaine dproduc t fro mth e reactio n wit h DB U wa s stil l contaminate dwit h smal l amount s o f impurity . 8 4H

O p O ' O H l)Cs2C0 3 CH3C N reflux , 3 h 0"^ 0 Cs H 1 7 reflux , 1 d 3)H2S04 , H2O THF rt , 1 h H O

C8H,7CHCH2 0 ^ o o O O O H I OCH.CHC^Hl

10 1 110(21% ) Schem e 3.19 . Synthesi s o f 4,4'(5')-Di[(2-hydroxydecyloxy)benzo]-18-crown- 6 (110) . I n a n attemp t t o increas e th e reactivity of th e aryloxid e nucleophile , reactio n o f th e isolate dpotassiu mphenoxid e compound s wit h th e cycli c sulfate este r

wa s attempted . A s amode l study , potassiu mphenoxid e (111 ) wa s prepare dan dreacte dwit h cycli c sulfate este r

10 7 followe db y hydrolysi s t o giv e (2-hydroxydecyloxy)benzen e (112 ) i n 45 % yiel da s show n i

n Schem e 3.20 . Anothe r

mode l reactio n wa s performe dwit h

O H KO H

MeO H rt O'K^

11 1 o^^ o Cg H 17 CH3C N rt,2 h then , reflux , 5 mi n 2 ) I N HC l reflux , 3 h O H 

# a OCHjCHCgH p

11 2 (45 % overall ) Schem e 3.20 . Synthesi s of 2-Hydroxydecyloxybenzen e (112) . 8 5Sesamo l a s show n i n Schem e 3.21 . Potassiu m3,4-methylenedioxy-phenoxid e (113 ) wa s prepare dusin g sam e metho da s th e preparatio n o f potassiu mphenoxid e (111) . Reactio n o f 11 3 wit h th e cycli c sulfate este r

10 7 followe dby hydrolysi s o f th e sulfate grou p gav e l-(2'-hydroxydecyloxy)-3,4-methylenedioxybenzen e (108 ) i n 68 % yield . Th e reactio n

o < O H KO H O C Sesamo l MeO H

n < 11 3 OK * 1 ) o<>.-^ o O^^ O CgH n CH3C N rt , 2 h then , reflux , 5 mi n 2 ) I N HC l reflux , 3 h O < O O H

OCH.CHCsH n

10 8 (68 % overall ) Schem e 3.21 . Synthesi s of 1 -(2'-Hydroxydecyloxy)-3,4-niethylenedioxybenzen e (108) .

wa s the n attempte dwit

h th e di-potassiu msal t

o f di(hydroxybenzo)-18-crown- 6 11 4 a s show n i n Schem e 3.22 . Althoug h th e same metho dwa s employe da s i n th e mode l reactions , th e obtaine dproduc t 11 0 wa s stil l contaminate dwit h unidentifie dimpuritie s afte r attempte dpurification .

8 6KO H MeO H rt OK ^

10 1 11 4

CH3C N ^ ^ rt,2h then , reflux , 5 mi n 2 ) I N HC l reflux , 3 h H O ^ ^ C8H,7CHCH20- h

11 0 (30% ) O H 1 .OCH2CHC8H, 7 

# 1

Schem e 3.22 . Attempte dSynthesi s of Crow n Ether

Dio l 110 . Althoug h reactio n o f

di(hydroxybenzo)-18-crown- 6 wit h th e cycli c sulfate este r

produce d th e desire dproduc t

i n 21 % yield , th e metho ddoe s no t seempromisin g sinc e it

give s a comple x mixtur e of

product s whic h include s asmal l amount of th e desire dproduc t

and significan t amount s of

unidentifie dimpurities . 3.1.2.3.2.3 . Reactio n wit

h Benzy l Bromide . Sinc e th e reactio n o f di(hydroxybenzo)-18-crown- 6 wit h epoxide s an dcycli c sulfat e este r often produce da comple x mixtur e o f

products , i

t seeme dworthwhil e t o ascertai n tha t th e alkylatio n o

f di(hydroxybenzo)-18-crown- 6 wa s achievable . Benzylatio n o f di(hydroxybenzo)-18

- crown- 6 wa s attempte da s show n i n Schem e 3.23 . Reactio n o f di(hydroxybenzo)-18

- crown- 6 (101 ) wit

h cesiu mcarbonat e an dbenzy l bromid e i n acetonitril e gav e 8 7di(benzyloxybenzo)-18-crown- 6 (115 ) i n 80 % yield . Thu s reactio n wit h a n activ e alkylatin g agen t

di dindee dgiv e th e desire dproduc t o f di-alkylation . 1)CS2C0 3 \ ^I

CH3CN ( o 

# a O OY=:^O H reflux . 3 h ff^V' ^ °Y^> ^ O 0"^^====:^ 2)PhCH2B r ^^"'^^Jk ^ Q'^ ^ OCH^P h 

# O ^ reflux , 1 d O 10 1 11 5 (80% ) Schem e 3.23 . Synthesi s of Di(benzyloxybenzo)-18-crown- 6 (115) . 3.1.2.3.3 . Synthesi s o f

Di[(2-hydroxyalkoxy)benzo]-18-crown- 6 Involvin g aGrignar dReactio n Whil e th e synthesi s of

di[(2-hydroxyalkoxy)benzo]-18-crown- 6 describe dabov e wa s accomplishe db y alkylatio n of di(hydroxybenzo)-18-crown-6 , anothe r syntheti c route t o di[(2-hydroxyalkoxy)benzo]-18-crown- 6 involvin g aGrignardreactio n a s akey ste p wa s explored . 3.1.2.3.3.1 . Grignar dReactio n of a n Aci dChlorid e Followe db y Reduction . Fo r th e synthesi s o f

di[(2-hydroxyalkoxy)benzo]-18-crown-6 , afou r step synthesi s startin g fromdi(hydroxybenzo)-18-crown- 6 (101 ) wa s propose d(Schem e 3.24) . Th e hydrox y group s o f di(hydroxybenzo)-18-crown- 6 (101 ) wa s t o b e converte dint o oxyaceti c aci d sid e arms . Then , crow n ethe r dicarboxyli c aci d11 6 wa s t o b e converte dt o crow n ethe r diketon e vi aaGrignar dreactio n of th e aci dchlorid e derivativ e 117 . Subsequen t reductio n woul dprovid e crow n ethe r diol . 8 8H O O o o o o o O H O I I HOCCH. O O O O O O O O I I OCH-,CO H

10 1 11 6

O I I RCCH-- 0 O

O O o o O o I I OCH.C R o C1CCH2 0 .0

o^ o o o I I OCHoCC l

11 7

H O I RCHCH2 O O O O O O O O H I OCH2CH R

Schem e 3.24 . Strateg y fo r Crow n Ethe r

Dio l Synthesi s Involvin g aGrignard Reactio n o

f a n Aci dChloride . T o prob e th e viability o f

thi s syntheti c strategy , amode l reactio n wit h Sesamo l wa s performed . Reactio n of Sesamo l wit

h bromoaceti c aci d an

dsodiu mhydrid e i

n tetrahydrofuran produce d(3,4-methylenedioxy)phenoxyaceti c aci d(118 ) i n 57 % yiel da s show n i n Schem e 3.25 . Wit

h carboxyli c aci dderivativ e 11 8 i n hand , th e synthesi s of

1 - (3',4'-methylenedioxy)phenoxy-2-decanon e (119 ) wa s attempte da s show n i n Schem e 3.26 . Reactio n o f

carboxyli c aci d11 8 wit

h oxaly l chlorid e i

n benzen e followe db y a

8 9< Sesamo l l)Na H TH F rt, 2 h 2 ) BrCH2C02 H rt, ovemigh t 3 ) H3O+ OCH2CO2H

11 8 (57% ) Schem e 3.25 . Synthesi s of (3,4-Methylenedioxy)phenoxyaceti c aci d(118) . Grignar dreactio n ' wit

h octylmagnesiu mbromid e i n th e presenc e of

iron(ni ) acetylacetonat e in tetrahydrofuran gav e th e desire dproduc t 11 9 (a s identifie db y appropriat e peak s i

n th e ' H NM Rspectmmof th e product ) togethe r

wit h th e unexpecte d este r produc t 120 . Isolatio n of

th e desire d produc t

11 9 coul dno t

b e achieve dan donly a

o < o OCH2CO2 H

11 8 1)(C0C1) 2 benzen e reflux , 2 h 2)C8Hi7MgB r 3 % Fe(acac) 3 TH F rt , 4 0 mi n O

< o

I I OCH2CC8 H 1

7 o

< o o

1 1 OCH2COC8 H 1

7

11 9 12 0 Schem e 3.26 . Attempte dSynthesi s o f l-(3',4'-Methylenedioxy)phenoxy-2

- decanon e (119) .

ver y smal l amoun t

of este r produc t 12 0 wa s isolate d i

n 4 % yiel d b

y recrystallization . Th e detaile dmechanis mfo r th e formatio n of

th e unexpecte d este r

produc t 12 0 wa s unclear . Remova l o f

oxyge n b y anitroge n swee p of th e reactio n di dno t

suppres s formatio n o f

th e este r product . 9 03.1.2.3.3.2 . Grignar dReactio n o f a n Aldehyde . Secondar

y alcohol s ca

n b e generate db y Grignar dreaction s o f aldehydes . Incorporatio n of a n aldehyd e grou p into th e sid e ar

mo f crow n ethe r

dio l 10 1 woul dmake it

possibl e t o synthesiz e di[(2

- hydroxyalkoxy)benzo]-18-crown- 6 a s show n i n Schem e 3.2 7 Di(hydroxybenzo)-18

- crown- 6 (101 ) i s treate dt o conver t t o crow n ethe r

12 1 followe db y deprotectio n of diethy l aceta l grou p t o giv e crow n ethe r dialdehyd e 122 . A subsequen t Grignar d reactio n o f

this produc t

12 2 woul dproduc e th e desire dcrow n ethe r diol .

(ElO)2CHCH20 + .OCH2CH(OEl) ;

H O RCHCH2 O 10 1

o o 

## C o ^ O H I OCH2CH R 12 1

HCCH2O-I - I

I O O O I I OCH,C H

12 2 Schem e 3.27 . Strateg y fo r Crow n Ethe r

Dio l Synthesi s Involvin g aGrignar d Reactio n of

a n Adehyde . A mode l reactio n wit

h Sesamo l wa s use dt o investigat e th e feasibilit y of thi s syntheti c strategy . Fo r

incorporatio n of

th e aldehyd e grou p int o th e sid e arm , commerciall y availabl e bromoacetaldehyd e diethy l acetal wa s chosen . Th e reactio n of Sesamo l wit

h cesiu mcarbonat e an dbromoacetaldehyd e diethy l acetal i n acetonitril e gav e 9 1(3,4-methylenedioxy)phenoxyacetaldehyd e diethy l acetal (123 ) i n hig h yiel da s show n i

n Schem e 3.28 . 1)CS2C0 3 CH3C N reflux , 3 h 2 ) BrCH2CH(OEt) 2 reflux , 1 d 0 ^ 0 ^ 

# 0 0CH2CH(0Et )

Sesamo l 12 3 (93% ) Schem e 3.28 . Synthesi s of (3,4-Methylenedioxy)phenoxyacetaldehyd e Diethy l Acetal (123) . Fo r th e (3,4-methylenedioxy)phenoxyacetaldehyd e (124 ) t o b e use dfo r i n a Grignar dreaction , deprotectio n o f th e diethy l aceta

l grou p wa s needed . Reactio n o f th e protecte daldehyd e 12 3 wit h boro n trifluorid e etherat e an d sodiu miodid e i n acetonitril e 3 0 gav e a n unexpecte dbenzofura

n derivativ e 12 5 i

n 50 % yiel d(Schem e 3.29) .

9 2

### o

< 

### o OCH2CH(Oa) 2

12 3 ^ BF3.(OEt) 2 Na l CH3C N reflux , 2 h O I I OCH.C H

12 4

125 (50% ) Schem e 3.29 . Attempte dSynthesi s o f (3,4-Methylenedioxy)

- phenoxyacetaldehyd e (124) . A possibl e mechanis mfo

r th e formatio n of

benzofura

n derivativ e 12 5 i s presente d in Figur e 3.3 . Initia l Lewi s aci dcomplexatio n wit h th e carbony l oxyge n an dsubsequen t

o I I 0^,^^\^°^"2C H BF3(OEt) 2 O 

## < 1 1 124 0

r O z-^ - ^l l t^OCHz—C H O < 

## Co. O e H O-BF 3 

# iX)^

- H®

12 5 H ® O ^ ^ H © 0 Cp-BF 3 H Figur e 3.3 . Propose dMechanis mfor th e Formatio n of

Benzofura

n Derivativ e 125 . 9 3attac k

o f 7C-bon di n benzen e t o carbony l carbo n ato mwoul dfor mafiv e membere dring . Th e abstractio n of

proto n an dth e releas e of

th e positiv e charg e on oxyge n ato mi n fura n woul dgiv e th e aromaticity bac k t o molecul e wit

h th e formatio n of

benzene . Then , dehydratio n woul dproduc e th e benzofura n derivativ e 125 . Othe r attempt s t o deprotec t

th e diethy l acetal grou p i n (3,4-methylenedioxy)

- phenoxyacetaldehyd e diethy l acetal (123 ) wit h 50 % aqueou s trifluoroaceti c aci di n chloroform' o r

ferri c chlorid e hexahydrate^ ^ were conducte d a s show n i n Tabl e 3.5 . Tabl e 3.5 . Attempte dSynthesi s o f (3,4-methylenedioxy)phenoxyacetaldehyd e (124) . OCH2CH(OEt) 2 50 % CF3CO2 H O

12 3 o r FeCl3-6H2 0 124 O I I OCH2C H 

# <Xi ^

12 5 Reagen t Solven t

Temp . Tim e Product s CF3CO2 H CHCI 3 CF3CO2 H CHCI 3 CF3CO2 H CHCI 3 CF3CO2 H CHCI 3 FeCl36H2 0 CH2CI

2 0° C rt 5 0 ° C 5 0 ° C rt 1.5 h

ovemigh t 2 h ovemigh t 1 h Unreacte d12 3

Unreacte d12 3 12 4 an dunrea

c 12 4 an d12 5 124,12 5 an du

Fro mattempte ddeprotectio n wit h trifluoroaceti c aci da

t 0 °C o r roo m temperature , th e unreacte dstartin g material 12 3 wa s recovered . Raisin g th e reactio n temperatur e t o 5 0 ° C fo

r 2 hour s produce donl y a

n 18 % conversio n t o th e aldehyd e 124 . 9 4hicreasin g th e reactio n tim e a t 5 0 °C gav e significant

amount s of

th e benzofura

n derivativ e 12 5 togethe r

wit h th e desire daldehyd e 124 . Attempte ddeprotectio n of (3.4

- methylenedioxy)phenoxyacetaldehyd e diethy l acetal (123 ) wit h ferri c chlorid e hexahydrat e in dichloromethane^ ^ gav e amixtur e o f unreacte d123 , th e desire daldehyd e 124 , an dth e benzofua

n derivativ e 125 . Treatmen t

of (3,4-methylenedioxy)phenoxyacetaldehyd e diethy l acetal (123 ) wit h hydrochlori c aci di

n tetrahydrofuran^ ^ di dno t produc e th e desire dproduc t 12 4 a s show n i n Schem e 3.30 . A

n unidentifie dmixtur e o

f product s wa s obtained . O 0^^^;;^\^OCH2CH(OEt) 2 2 N HC l 0^.^^\^OCH2C H 

# <XJ -^ —X—<„X

J rt,24h 12 3 12 4 Schem e 3.30 . Attempte dSynthesi s of (3,4-Methylenedioxy)

- phenoxyacetaldehyd e (124) .

3.2 . Chapter

Summar y Several serie s o f

bis(l-hydroxyalkyl)-substitute dcrow n ether s were prepare db y acylatio n o f

dibenzo-18-crow n 6 o r

dibenzo-2 1 -crown- 7 followe db y reduction . Furthe r elaboratio n o n th e hydroxy l functiona l grou p of

th e bis(l-hydroxyalkyl)-substitute d crow n ether s wa s als o accomplished . Th e synthesi s o f

bis(2-hydroxyalkyl)-substitute d crow n ether s wa s attempte db y thre e differen t

methods . Attempte disomerizatio n o f th e hydroxy l grou p gav e a n eliminatio n product . Othe r attempt s fo

r th e synthesi s of

bis(2-hydroxyalkyl)-substitute d 9 5crow n ether s b y oxymercuration-demercuratio n or hydroboration-reductio n o f crow n ethe r alkene s gav e mixture s of tw o isomeri c crow n ethe r diols . Attempte d2+ 2 reaction s o f Sesamo l an dbis(2-chloroethyl ) ethe r an dbas e di dno t for mth e desire dsubstitute ddibenzo-18-crown- 6 compound . Althoug h reaction s of

Sesamo l wit

h bas e an da

n epoxid e gav e efficient

coupling , thi s reactio n coul dno t

b e extende dt o di(hydroxybenzo)-18-crown-6 . Secondly , th e feasibility o f

apotentia l synthesi s of

di[(hydroxyalkoxy)benzo]-18-crown- 6 compound s b y ametho dwhic h wa s teste db y reactio n sequenc e involve s aGrignar dreactio n o f a carbony l functional grou p wa s foun dt o b e unsuccessfu l fo r th e mode l compoun d Sesamol . 3.3. Experimental Procedure s 3.3.1 . Source s o

f Reagent s Commerciall y availabl e reagent s were use da s receive dunles s otherwis e specified . Sesamo l fro mAldric h wa s drie db y benzen e azeotropi c distillatio n wit h a Dean-Star k apparatus . 3.3.2 . Purificatio n o f Reagent s Dry solvent s wer e prepare da s follows : tetrahydrofura n (THF ) wa s freshl y distille dfro msodiu mmetal ribbon o r chunk s an dbenzophenon e ketyl ; CH3C N wa s distille dfro mCaH2 ; N,N-dimethylformamid e (DMF ) wa s distille dfromMgS0 4 unde r reduce dpressure ; r-BuO H wa s distille dfro mCaH2 ; n-BuO H wa s distille dfromCaH2 . 9 6Dibenzo-18-crown- 6 fro mJasse n Chimic awa s purifie db y column chromatograph y on alumin awit h ethy l acetate-hexane s (1:3 ) a s eluen t followe dby recrystallizatio n fro mhexanes-CH2Cl2 . 3.3.3 . General Th e instrumentatio n use di n thi s portio n o

f researc h wa s same a s tha t describe di

n th e Experimenta l Procedur e sectio n of Chapter 2 . Thi n laye r

chromatograph y (TLC ) wa s conducte dwit h eithe r Alumin aG F or Silic aGe l G F Uniplate s fromAnaltech . Colum n chromatograph y wa s performe dwit h 80-20 0 mes h alumin afromFishe r Scientifi c o r

60-20 0 mes h silic agel fro mE M Sciences . 3.3.4 . General Procedure fo r th e Synthesi s o

f Dibenzo-18-crown- 6 Diketone s 66-6 9 Int o a250-mL , three-necked , round-bottome dflask fittedwit h athermomete r were adde ddibenzo-18-crown- 6 (lO.CX ) g , 42. 0 mmol , 1.0 equivalent) , th e appropriat e carboxyli c aci d(2. 0 equivalents) , an dEaton' s reagent ^ (76.0 0 g ) unde r

nitrogen . Th e reactio n mixtur e wa s stirre dmagneticall y fo r 4- 6 hour s a

t 5 0 °C unde r nitrogen . Durin g thi s time , th e reactio n mixtur e turne dcherr y red . Th e reactio n mixtur e wa s poure dint o a mixtur e o f

15 0 g o f ic e an d15 0 m

L of water an dstirre dovemigh t

wit h amechanical stirre r a t roo mtemperature . Th e reactio n mixture wa s separate db y filtration . Th e filtere dsoli dwa s dissolve di n 15 0 m L o f CH2CI 2 an dwashe dvei y vigorousl y wit h 5 % NaO H solutio n ( 3 X 10 0 mL ) an dwate r ( 3 X 100 mL) . Th e CH2CI 2 layer wa s drie dove r MgS0 4 an devaporate din vacuo. Column chromatograph y on alumin awit h CH2CI 2 a s eluen t gav e th e product . 9 7Notes : 1 . Fo r th e condensatio n o f

10. 0 mmo l o

f carboxyli c acid , 9.(X

) g o f Eaton' s reagen t wa s used . 2 . I n th e acylatio n wit

h 2-ethylhexanoi c acid , sometime s th e soli dwa s ver y stick y afte r pourin g th e reactio n mixture int o th e water an dthe n stirrin g ovemight . I n thi s case , th e aqueou s solutio n wa s decante dfromth e solid . 3.3.4.1 . 4,4'(5')-Di[(butanoyl)benzo]-18-crown- 6 (66 ) wa s obtaine di n 79 % yiel da s aligh t

yello w soli dwit

h m p 162-16 5 ° C (lit. ^ m

p 149-15 9 an d174-18 2 ''C) . I R (deposi t fro mCH2CI

2 solutio n on aNaC l plate) : 167 3 (C=0) ; 126 7 an d113 9 (C-O ) cm' . ^ H NM R(CDCI3) : 5 0.9 9 (t , J = 7. 4 Hz , 6H) ; 1.65-1.8 0 (m , 4H) ; 2.8 8 (t , J = 7. 3 Hz , 4H) ; 4.00-4.2 5 (m , 16H) ; 6.8 5 (d , J = 8. 3 Hz , 2H) ; 7.50-7.5 9 (m , 4H) . Anal . Calcd . fo r C28H36O8 ; C , 67.18 ; H , 7.25 . Found : C , 66.82 ; H , 7.28 . 3.3.4.2 . 4,4'(5')-Di[(hexanoyI)benzo]-18-crown- 6 (67 ) wa s obtaine di n 55 % yiel da s aligh t

yello w soli dwit

h m p 125-12 8 °C

(lit. ^ m p 144-14 7 °C) . I

R(deposi t

fro m CH2CI 2 solutio n on aNaC l plate) : 167 3 (C=0) ; 127 1 an d114 1 (C-O ) cm"' . ' H NM R (CDCI3) : 6 0.9 0 (t , y = 6. 8 Hz , 6H) ; 1.30-1.7 5 (m , 12H) ; 2.8 9 (t , J = 1.4 Hz , 4H) ; 4.00

- 4.2 5 (m , 16H) ; 6.8 5 (d , 7 = 8. 3 Hz , 2H) ; 7.50-7.5 8 (m , 4H) . Anal . Calcd . fo r C32H44O8 : C , 69.04 ; H , 7.97 . Found : C , 69.23 ; H , 8.01 . 3.3.4.3 . 4,4'(5')-Di[(decanoyl)benzo]-18-crown- 6 (68 ) wa s obtaine di n 49 % yiel da s aligh t

yello w soli dwit

h m p 12 1 -12 4 ° C (lit. ^ m

p 117-12 9 °C) . I

R(deposi t

fro m CH2CI 2 solutio n o n aNaC l plate) : 166 8 (C=0) ; 127 0 an d 114 1 (C-O ) cm' . ' H NM R (CDCI3) : 60.8 0 (t , 7 = 6. 4 Hz , 6H) ; 1.03-1.4 2 (m , 24H) ; 1.50-1.7 6 (m , 4H) ; 2.8 2 (t , 7 = 7. 4 Hz , 4H) ; 3.95-4.1 6 (m , 16H) ; 6.7 8 (d , 7 = 8. 3 Hz , 2H) ; 7.44-7.5 0 (m , 4H) . 9 83.3.4.4 . 4,4'(5')-Di[(2-ethylhexanoyl)benzo]-18-crown- 6 (69 ) wa s obtaine di n 92 % yiel da s aligh t

yello w soli dwit

h m p 89-9 1 °C . I

R(deposi t

fromCH2CI

2 solutio n on aNaC l plate) : 166 8 (C=0) ; 126 5 an d113 9 (C-O ) cm' . 'HNM R(CDCI3) : 60.81

- 1.7 9 (m , 28H) ; 3.19-3.4 0 (m , 2H) ; 4.01-4.2 4 (m , 16H) ; 6.8 6 (d , 7 = 8. 3 Hz , 2H) ; 7.52

- 7.5 9 (m , 4H) . Anal . Calcd . for C36H52O8 : C , 70.56 ; H , 8.55 . Found : C , 70.63 ; H , 8.52 . 3.3.5 . General Procedur e fo r th e Synthesi s o

f Dibenzo-18-crown- 6 Diol s 70-7 2 Int o a500-mL , one-necked , round-bottome dflask wer e adde d10.(X

) g of th e appropriat e dibenzo-18-crown- 6 diketon e (66 , 67 , o r 68 ) (1. 0 equivalent) , NaBH 4 (5. 2 equivalents) , absolut e ethano l (15 0 mL) , an ddichloromethan e (1(X ) mL ) unde r

nitrogen . Th e reactio n mixtur e wa s stirre dfo r 4 hour s a t roo mtemperatur e unde r

nitroge n an dthen poure dint o 10 0 m L o

f water . Th e reactio n mixture wa s neutralize dwit h 6 N HC l solutio n t o p H = 7 i

n a n ic e bath . Th e mixtur e wa s extracte dwit h CH2CI 2 ( 3 X 1(X

) mL) , drie dove r MgS04 , an devaporate din vacuo t o giv e th e product . 3.3.5.1 . 4,4'(5')-Di[(l-hydroxybutyl)benzo]-18-crown- 6 (70 ) wa s obtaine dafte r column chromatograph y o n alumin awit h EtOA c a s eluen t

t o remov e asmal l amoun t o f les s polar impurity , the n wit

h EtOAc-MeO H (10:1 ) a s eluen t i n quantitativ e yiel da s a whit e soli dwit

h mp 145-15 2 °C

(lit. ^ m p 135-14 7 °C) . I

R(deposi t

fro mCH2CI 2 solutio n o n aNaC l plate) : 337 4 (O-H) ; 126 4 an d113 7 (C-O ) cm"' . ' H NM R(CDCI3) : 5 0.9 2 (t , 7

= 7. 2 Hz , 6H) ; 1.24-1.8 0 (m , 8H) ; 2.0 1 (s , 2H) ; 4.01-4.2 0 (m , 16H) ; 4.5 9 (t , 7 = 5. 8 Hz , 2H);6.86(d,7=11.9Hz,6H) .

9 93.3.5.2 . 4,4'(5')-Di[(l-hydroxyhexyl)benzo]-18-crown- 6 (71 ) wa s obtaine dafte r recrystallizatio n fromCH2Cl2-hexane s i n 90 % yiel d a s alight

yello w soli dwit

h m p 127

- 13 2 ° C (lit. ^ mp 135-14 5 °C) . I R(deposi t

fromCH2CI

2 solutio n on aNaC l plate) : 338 2 (O-H) ; 126 3 an d113 9 (C-O ) cm"' . ' H NM R(CDCI3) : 8 0.8 5 (t , 7 = 6. 4 Hz , 6H) ; 1.08

- 1.8 9 (m , 16H) ; 1.9 3 (s , 2H) ; 3.99-4.1 9 (m , 16H) ; 4.5 6 (t , 7 = 6. 6 Hz , 2H) ; 6.8 4 (d , 7 = 12. 1 Hz , 6H) . 3.3.5.3 . 4,4'(5')-Di[(l-hydroxydecyl)benzo]-18-crown- 6 (72 ) wa s obtaine dafte r colum n chromatograph y on alumin awit h EtOA c a s eluen t

t o remov e asmal l amount o f les s polar impurity , the n wit

h EtOAc-MeO H (20:1 ) a s eluen t i n 80 % yiel da s awhite soli dwit h mp 134-13 7 ° C (lit. ^ m

p 120-12 2 an d145-14 8 °C) . I R(deposi t

fro mCH2CI 2 solutio n o n aNaC l plate) : 337 4 (O-H) ; 126 6 an d114 1 (C-O ) cm"' . ' H NM R(CDCI3) : 6 0.8 7 (t , 7 = 6. 4 Hz , 6H) ; 1.06-1.8 2 (m , 32H) ; 1.85 (d , 7 = 2. 8 Hz , 2H) ; 4.00-4.2 0 (m , 16H) ; 4.54-4.6 0 (m , 2H) ; 6.8 5 (d , 7 = 12. 0 Hz , 6H) . 3.3.6 . Preparatio n of

4,4'(5')

- Di[(2-ethyl-l-hydroxyhexyl)benzo]-18-crown- 6 (73 ) Int o a500-mL , one-necked , round-bottome d flask were adde d4,4'(5')-Di[(2"

- ethylhexanoyl)benzo]-18-crown- 6 (69 ) (6.0 0 g , 9.7 9 mmol) , NaBH 4 (1.9 4 g , 51. 4 mmol) , an dabsolut e ethano l (15 0 mL ) unde r nitrogen . Th e reactio n mixtur e wa s stirre dfor 2 4 hour s a t roo mtemperatur e unde r

nitroge n an d the n poure dint o 120 mL o f water . Th e mixtur e wa s neutralize dwit h 6 N HC l solutio n t o p H = 7 i n a n ic e bath . Th e mixtur e wa s extracte dwit

h CH2CI 2 ( 3 X 100 mL) , drie dove r MgS04 , an devaporate din vacuo. Colum n chromatograph y on alumin awit h CH2CI 2 a s eluen t

to remov e th e unconsume d 100reactant , the n wit h EtOA c a s eluen t

gav e 5.24 g (87% ) of

th e produc t

a s awhite soli d wit h mp 130-13 6 °C. I

R(deposi t

fromCH2CI

2 solutio n o

n aNaC l plate) : 339 2 (O-H) : 126 1 an d113 9 (C-O ) cm"' . ' H NM R(CDCI3) : 80.78-1.6 5 (m . 30H) ; 1.7 2 (s . 2H) : 4.00

- 4.1 7 (m , 16H) ; 4.43-4.6 0 (m,2H) ; 6.8 4 (d , 7 = 9. 1 Hz . 6H) . Anal . Calcd . fo r C36H56O8 : C , 70.10 : H , 9.15 . Found : C , 70.46 ; H , 9.09 . 3.3.7 . Preparatio n of 4,4'(5')-Di[(2-ethyl- 1 -(2-hydroxyethoxy)hexyl)benzo]

-

18-crown-6(74 ) Int o a10(X)-mL , one-necked , round-bottome dflask were adde d4,4'(5')

- di[(2-ethyl-l-hydroxyhexyl)benzo]-18-crown- 6 (73 ) (5.2 3 g , 8.4 8 mmol) , ethylen e glyco l (10.5 5 g . 0.1 7 mol) , an dCH2CI 2 (42 5 mL ) unde r

nitrogen . Concentrate dH2SO 4 (2 6 drops ) wa s adde dan dth e reactio n mixtur e wa s stirre d fo r 1 5 hour s a

t roo mtemperatur e unde r nitrogen . Th e reactio n mixtur e wa s washe dwit h water ( 3 X 1(X ) mL) , drie dover MgS04 , an devaporate din vacuo. Colum n chromatograph y on alumin awit h EtOA c a s eluen t t o remov e asmal l amoun t o f les s pola r impurity , the n wit

h EtOAc-MeO H (20:1 ) a s eluen t gav e 4.9 8 g (83% ) o f

th e produc t

a s ayellow , viscou s liquid . I R(deposi t

fro m CH2CI 2 solutio n on aNaC l plate) : 338 4 (O-H) ; 126 1 an d113 8 (C-O ) cm"' . ' H NM R (CDCI3) : 80.73-1.5 3 (m , 30H) ; 3.29-3.3 8 (m , 4H) ; 3.62-3.7 0 (m . 4H) ; 4.03-4.1 7 (m , 20H) ; 6.76-6.8 2 (m , 6H) . Anal . Calcd . for C40H64O10

: C , 68.15 ; H , 9.15 . Found : C , 68.41 ; H , 9.18 . Note : Th e ethylen e glyco l wa s drie dwit h abenzen e azeotrop e i

n aDean-Star

k apparatus . 10 13.3.8 . Preparatio n o f 4,4X5')-Di[(2-ethyl-l-(5-hydroxy

3-oxapentoxy)hexyl)benzo]-18-crown- 6 (75 ) Int o a100-mL , one-necked , round-bottome dflask were adde d4,4'(5')

- di[(2-ethyl-l-hydroxyhexyl)benzo]-18-crown- 6 (73 ) (0.4 8 g , 0.7 8 mmol) , diethylen e glyco l (1.6 6 g , 15. 6 mmol) , an dCH2CI 2 (4 0 mL ) under

nitrogen . Concentrate dH2SO 4 ( 3 drops ) wa s adde dan dth e reactio n mixture wa s stirre dfo r 1 5 hour s a

t roo mtemperatur e unde r nitrogen . Th e reactio n mixtur e wa s washe dwit h water ( 3 X 2 0 mL) , drie dover MgS04 , an devaporate din vacuo. Colum n chromatograph y on alumin awit h EtOA c a s eluen t t o remov e asmal l amoun t of les s pola r impurity , the n wit

h EtOAc-MeO H (20:1 ) a s eluen t gav e 0.4 7 g (76% ) o f

th e produc t

a s ayellow , viscou s liquid . I R(deposi t

fro m CH2CI 2 solutio n o n aNaC l plate) : 342 0 (O-H) ; 126 1 an d113 7 (C-O ) cm"' . ' H NMR (CDCI3) : 8 0.65-1.7 1 (m , 30H) ; 2.5 2 (b r s , 2H) ; 3.34-4.2 9 (m , 34H) ; 6.71-6.8 1 (m , 6H) . Anal . Calcd . for

C44H72O12: C , 66.64 ; H , 9.15 . Found : C , 66.72 ; H , 9.29 . Note : Th e diethylen e glyco l wa s drie dwit h abenzen e azeotrop e i

n aDean-Star

k apparatus . 3.3.9 . Preparatio n o f 4,4'(5')-Di[(2-ethylhexanoyl)benzo]-21-crown- 7 (77 ) Int o a250-mL , three-necked , round-bottome dflask fitte dwit h athermomete r wer e adde ddibenzo-21-crown- 7 (76 ) (12.0 0 g , 27. 7 mmol) , 2-ethylhexanoi c aci d(9.4 1 g , 65. 3 mmol) , an dEaton' s reagent ^ (60.0 0 g ) unde r

nitrogen . Th e reactio n mixtur e wa s stirre dmagneticall y for

4- 6 hour s a

t 30-3 5 ° C unde r

nitrogen . Durin g thi s time , th e reactio n mixtur e turne dcherry red . Th e reactio n mixtur e wa s poure dint o amixtur e of 10212 0 g of

ic e an d120 mL o

f wate r an dstirre dovemigh t

a t roo mtemperatur e wit

h a mechanica l stirrer . Th e reactio n mixtur e wa s separate db y filtration. Th e filteredsoli d wa s dissolve din 15 0 m

L of CH2CI 2 an dwashe d ver

y vigorousl y wit

h 5 % NaO H solutio n ( 3 X 10 0 mL ) an dwate r

( 3 X 10 0 mL) . Th e CH2CI 2 layer wa s drie dove r

MgS04 and evaporate din vacuo. Column chromatograph y o n alumin awit

h CH2CI 2 a s eluen t

gav e 16.1 1 g (83% ) o f

th e produc t

a s awhite soli dwit

h m p 63-6 5 °C . I

R(deposi t

fro m CH2CI 2 solutio n on aNaC l plate) : 167 0 (C=0) ; 126 6 an d 113 6 (C-O ) cm"' . ' H NM R (CDCI3) : 8 0.81-0.8 9 (m , 12H) ; 1.17-1.8 3 (m , 16H) ; 3.26-3.3 3 (m , 2H) ; 3.89-4.2 7 (m , 20H) ; 6.8 8 (d , 7=8. 1 Hz , 2H) ; 7.53-7.6 2 (m , 4H) . Anal . Calcd . fo r C38H56O9 : C , 69.49 ; H , 8.59 . Found : C , 69.30 ; H , 8.52 . Notes : 1 . Dibenzo-21-crown- 7 wa s prepare db y aliteratur e method." ^ 2 . Sometime s th e soli dwa s ver y stick y afte r pourin g th e reactio n mixture int o th e wate r

an dthe n stirrin g ovemight . I n thi s case , th e aqueou s solutio n wa s decante dfro mth e solid . 3.3.10 . Preparatio n o f 4,4'(5')

- Di[(2-ethyl- 1 -hydroxyhexyl)benzo]-2 1 -crown- 7 (78 ) Int o a250-mL , one-necked , round-bottome d flask wer e adde d4,4'(5')-di[(2

- ethylhexanoyl)benzo]-21-crown- 7 (77 ) (4.6 0 g , 7.0 0 mmol) , NaBH 4 (1.3 8 g , 36.5 8 mmol) , an dabsolut e ethano l (12 5 mL ) unde r nitrogen . Th e reactio n mixtur e wa s stirre d fo r 2 4 hour s a

t roo mtemperatur e unde r

nitroge n an dthen poure dint o 100 m L o f water . Th e mixtur e wa s neutralize dwit h 6 N HC l solutio n t o p H = 7 i n a n ic e bath . Th e mixtur e wa s extracte dwit h CH2CI 2 ( 3 X 100 mL) , drie dove r MgS04 , an devaporate din 10 3vacuo. Column chromatograph y on silic agel wit h Et2 0 gav e th e produc t

i n quantitativ e yiel da s acolorless , viscou s liquid . IR(deposi t fromCH2CI

2 solutio n on aNaC l plate) : 344 9 (O-H) ; 126 4 an d113 9 (C-O ) cm"' . ' H NM R(CDCI3) : 8 0.70-1.6 3 (m , 30H) ; 1.7 7 (s , 2H) ; 3.80-4.2 3 (m , 20H) ; 4.45-4.6 2 (m , 2H) ; 6.83-6.9 1 (m , 6H) . Anal . Calcd . fo r C38H60O9 : C , 69.06 ; H , 9.15 . Found : C , 69.05 ; H , 8.88 . 3.3.11 . Preparatio n o

f 4,4'(5')-Di[(2-ethyl-l-(5-hydroxy

3-oxapentoxy)hexyl)benzo]-2 1 -crown- 7 (79 ) Int o a1000-mL , one-necked , round-bottome d flask were adde d4,4'(5')

- di[(2-ethyl-l-hydroxyhexyl)benzo]-21-crown- 7 (78 ) (5.0 3 g , 7.1 6 mmol) , diethylen e glyco l (15.9 2 g , 0.1 5 mol) , an dCH2CI 2 (38 0 mL ) unde r

nitrogen . Concentrate dH2SO 4 (2 3 drops ) wa s adde dan dth e reactio n mixtur e wa s stirre dfo r 1 5 hour s a

t roo m temperatur e unde r

nitrogen . Th e reactio n mixture wa s washe d wit h water ( 3 X 100 mL) , drie dove r MgS04 , an devaporate din vacuo. Colum n chromatograph y on alumin awit h EtOA c a s eluen t

t o remov e asmal l amoun t o f les s pola r impurity , the n wit

h EtOAc

MeO H (20:1 ) a s eluen t

gav e 5.3 3 g (84% ) of

th e produc t

a s ayello w viscou s liquid . I R (deposi t fro mCH2CI

2 solutio n on aNaC l plate) : 345 4 (O-H) ; 126 2 an d113 5 (C-O ) cm"' .

' H NM R(CDCI3) : 8 0.64-1.7 2 (m , 30H) ; 2.5 0 (b r s , 2H) ; 3.25-4.3 1 (m , 38H) ; 6.73-6.8 7 (m , 6H) . Anal . Calcd . for C46H760,3 : C , 66.00 ; H , 9.15 . Found : C , 65.88 ; H , 9.09 . Note : Th e diethylen e glyco l wa s drie dwit h abenzen e azeotrop e i

n aDean-Star

k apparatus .

10 43.3.12 . Attempte dSynthesi s o f 4,4'(5')-Di[(2-ethyl-2-hydroxyhexyl)benzo]

- 18-crown- 6 (82 ) from4,4'(5')-Di[(2-ethyl-l

hydroxyhexyl)benzo]-18-crown- 6 (73 )

b y Isomerizatio n 3.3.12.1 . Isomerizatio n wit h Sulfuri c Aci d Int o alOO-mL , one-necked , round-bottome d flask were adde d4,4'(5')-di[(2-ethyl

l-hydroxyhexyl)benzo]-18-crown- 6 (73 ) (0.1 0 g , 0.1 6 mmol ) an dCH2CI 2 (2 0 mL) . Concentrate dH2SO

4 (0.5 0 mL ) wa s adde dan dth e reactio n mixtur e wa s stirre dfo r 6 hour s a t roo mtemperature . Th e reactio n mixtur e wa s neutralize dwit h 5 % aqueou s Na2C0 3 an dwashe dwit

h water (2 0 mL) . Th e CH2CI

2 layer wa s drie dove r

anhydrou s Na2S0 4 an devaporate din vacuo. Column chromatograph y o n alumin awit

h Et2 0 a s eluen t t o remov e th e les s pola

r impurity , the n wit

h EtOA c a s eluen t

gav e 0.0 9 g of

a mixtur e of

si x isomer s o f

alken e substitute d product s 83-88 . Th e rati o of th e 1 -alken e sid e grou p t o th e 2-alken e sid e grou p i n th e mixture wa s determine dfromintegratio n of th e vinyli c proto n absorption s i n th e ' H NM Rspectru mof th e mixture . I

R(deposi t

fro m CH2CI 2 solutio n o n aNaC l plate) : 160 3 (C=C) ; 126 0 an d113 9 (C-O ) cm"' . ' H NM R (CDCI3) : 8 0.84-2.2 5 (m , 28H) ; 3.2 1 (d , 7 = 4. 1 Hz , 2H , benzyli c proton s o f 2-alken e sid e group) ; 3.3 0 (d , 7 = 2. 2 Hz , 2H , benzyli c proton s of o f 2-alken e sid e group) ; 4.02-4.1 6 (m , 16H) ; 5.14-5.3 9 (m , 2H , vinyli c proton s of 2-alken e sid e group) ; 6.1 5 (s , 2H , vinyli c proton s o f

1-alkene sid e group) ; 6.67-6.8 3 (m , 6H) . Th e rati o of l-alkene:2-alken e sid e group s = 73:27 . Note : Anothe r

attemp t wit h 5 % H2SO

4 gav e amixtur e of

th e si x alken e substitute dproduct s 83-8 8 wit h arati o of

of l-alkene:2-alken e sid e group s = 3:1 . 1053.3.12.2 . Isomerizatio n wit h Hydrochlori c Aci d Int o a100-mL , one-necked , round-bottome dflask wer e adde d4,4'(5')-di[(2-ethyl

l-hydroxyhexyl)benzo]-18-crown- 6 (73 ) (0.1 0 g , 0.1 6 mmol ) and CH2CI 2 (2 0 mL) . HC l (5% , 0.5 0 mL ) wa s adde dan dth e reactio n mixture wa s stirre dfo r 6 hour s a t roo m temperature . Th e reactio n mixtur e wa s neutralize d wit h 5 % aqueou s Na2C0 3 and washe dwit

h wate r (2 0 nti:.) . Th e CH2CI

2 layer wa s drie dover

anhydrou s Na2S04 and evaporate din vacuo t o giv e th e unreacte d startin g material . Note : Anothe r

attemp t wit h concentrate d HC l gav e th e unreacte dstartin g material 7 3 an dasmal l amoun t

of eliminatio n produc t

8 3 wit h rati o of 73:8 3 = 85:1 5 o

n th e basi s of th e H NM Rspectrum . Th e rati o of th e startin g material 7 3 t o th e alken e substitute d produc t 8 3 wa s determine db y th e compariso n o f th e integratio n area s fo

r th e benzyli c proto n absorptio n from7 3 an dth e vinyli c proto n absorptio n from83 .

3.3.13 . Attempte dSynthesi s of Alkene-Substitute d Dibenzo-18-crown- 6 8 3 fro m Dibenzo-18-crown- 6 Dio l 7 3 Givin g aMixtur e of

Si x Isomer s 83-8 8 Int o a250-mL , one-necked , round-bottome dflask were adde d4,4'(5')-di[(2-ethyl

l-hydroxyhexyl)benzo]-18-crown- 6 (73 ) (1.0 0 g , 1.6 2 mmol) , p-toluenesulfoni c aci d (0.1 0 g , 0.5 3 mmol) , an ddr y benzen e (1(X

) mL) . A Dean-Star

k apparatu s wa s attache d t o th e reactio n flask

t o remov e wate r

durin g th e reaction . Th e reactio n mixtur e wa s refluxe dfor

3 0 minute s unde r

nitrogen . Th e solven t

wa s evaporate din vacuo an dth e residu e wa s dissolve di

n 10 0 mL of

CH2CI2 . Th e CH2CI

2 layer wa s washe dwit

h water ( 3 X 2 0 mL) , drie dove r

MgS04 , an devaporate din vacuo. Column chromatograph y on alumin awit

h CH2Cl2-EtOAc (40:1 ) a s eluen t gav e amixtur e o

f si x isomer s 83-8 8 a s a 10 6whit e solid . Th e rati o of th e 1-alken

e sid e grou p t o th e 2-alken e sid e grou p i n th e mixtur e wa s determine db y th e compariso n of th e integratio n area s fo

r th e vinyli c proto n absorption s in th e mixtur e of si x isomer s of

alken e substitute dproduct s 83-88 . Th e rati o o f 1-alkene:2-alken e sid e group s = 83:17 . 3.3.14 . Preparatio n o

f 4,4'(5')-Di[(l-decenyl)benzo]-18-crown-6(90 ) Int o a500-mL , one-necked , round-bottome d flask were 4,4'(5')-di[(l

hydroxydecyl)benzo]-18-crown- 6 (72 ) (4.5 0 g , 6.6 9 mmol) , p-toluenesulfoni c aci d(0.4 5 g , 2.3 7 mmol) , an ddr

y benzen e (30 0 mL) . A Dean-Star k apparatu s wa s attache dt o th e reactio n flask

t o remov e wate r

durin g th e reaction . Th e reactio n mixtur e wa s refluxe d fo r 2 hour s unde r

nitrogen . Th e solven t

wa s evaporate din vacuo an dth e residu e wa s dissolve din 30 0 mL o f

CH2CI2 . Th e CH2CI

2 layer wa s washe d wit

h wate r ( 3 X 5 0 mL) , drie dove r MgS04 , an devaporate din vacuo. Colum n chromatograph y on alumin awit h EtOAc-hexane s (1:2 ) a s eluen t gav e 2.5 0 g (59% ) o

f th e produc t

a s awhite soli dwit

h m p 130-13 1 °C . IR(deposi t

fromCH2CI

2 solutio n o

n aNaC l plate) : 160 0 (C=C) ; 126 6 and 113 9 (C-O ) cm"' . ' H NM R(CDCI3) : 80.8 8 (t , 7 = 6. 4 Hz , 6H) ; 1.08-1.5 9 (m , 24H) ; 2.06-2.2 9 (q , 4H) ; 3.92-4.3 1 (m , 16H) ; 5.97-6.1 9 (m , 2H) ; 6.2 8 (d , 7 = 15. 8 Hz , 2H) ; 6.77-6.9 0 (m , 6H) . Anal . Calcd . for C40H60O6 : C , 75.43 ; H , 9.50 . Found : C , 75.37 ; H , 9.59 .

10 73.3.15 . Attempte dSynthesi s o f 4,4'(5')-Di[(2-ethyl-2-hydroxyhexyl)benzo]

- 18-crown- 6 (82 ) fromth e Mixtur e o f Si x Alkene

Substitute dIsomer s 83-8 8 Givin g aMixtur e of Thre e Isomer s 73 , 8 2 an d8 9 Mercury(n ) acetat e (0.9 8 g , 3.0 6 mmol ) wa s dissolve d i n 3 m L of water i n a 50-mL , one-necked , round-bottome dflask. Afte r aclea r solutio n wa s obtained , 3 m L o f TH F wa s adde dt o precipitat e ayello w solid . T o thi s reactio n mixtur e wa s adde dth e alkene-substitute ddibenzo-18-crown- 6 mixture (0.8 9 g , 1.5 3 mmol ) wit h vigorou s stirring . Afte

r stirrin g fo

r 1 da y a t roo mtemperature , 3. 0 N NaO H solutio n ( 5 mL ) wa s adde dfollowe db y additio n of 0. 5 N NaBIL

i i n 3. 0 N NaO H solutio n ( 5 mL) . Th e water laye r wa s saturate dwit

h NaC l an dK2CO3 . Th e organi c layer wa s separate dan dth e wate r laye r wa s washe dwit

h TH F (1 0 mL) . Th e combine d organi c layer s were drie d ove r MgS04 , an devaporate din vacuo. Colum n chromatograph y o n alumin awit h EtOA c a s eluen t

t o remov e th e unreacte dstartin g material an dwit h EtOAc-MeO H (20:1 ) a s eluen t an dthe n recrystallizatio n fro mCH2Cl2-hexane s gav e 0.3 1 g (33% ) of amixture of thre e isomer s 73 , 8 2 an d89 . Th e rati o o f th e 1 -alcoho l sid e grou p t o th e 2-alcoho l sid e grou p i

n th e mixtur e wa s determine db y th e compariso n of th e integratio n area s fo

r th e benzyli c proto n absorption s i n th e ' H NM Rspectru mo f th e mixture . I

R(deposi t fro mCH2CI

2 solutio n o n aNaC l plate) : 340 4 (O-H) ; 1267 an d114 0 (C-O ) cm"' . ' H NM R(CDCI3) : 8 0.75-2.2 1 (m , 32H) ; 2.6 5 (s , 4H , benzyli c proton s of 2-alcoho l sid e group) ; 3.88-4.2 9 (m , 16H) ; 4.46-4.5 7 (m , 2H , benzyli c proton s of 1-alcoho l sid e group) : 6.69-6.9 1 (m , 6H) . Th e rati o o f 1-alcohol:2-alcoho l sid e group s = 65:35 .

10 8Note : Anothe r attemp t wit h mercury(n ) trifluoroacetat e gav e 0.3 5 g (63% ) o f a mixtur e o f

thre e isomer s 73 , 8 2 an d8 9 wit h arati o o f 1-alcohol:2-alcoho l sid e group s = 64:36 . 3.3.16 . Attempte dSynthesi s o f 4,4'(5')-Di[(2-hydroxydecyl)benzo]-18-crown-6(91 ) from4,4'(5')-Di[(l-decenyl)benzo]-18-crown- 6 (90 ) Givin g aMixtur e of

th e Thre e Isomer s 72 . 9 1 an d9 2 3.3.16.1 . B y Hydroboration-Oxidatio n Int o a100-mL , one-necked , round-bottome dflask were adde dNaBH

4 (0.1 2 g , 3.1 4 mmol ) an ddr

y TH F (1 0 mL) . A solutio n o f 4,4*(5')-di[(l-decenyl)benzo]-18

- crown- 6 (90 ) (0.9 0 g , 1.4 1 mmol ) i n 2 0 mL o

f dr y TH F wa s adde dint o th e reactio n mixture . Boro n trifluorid e etherat e (0.4 5 g , 3.1 4 mmol ) wa s adde ddropwis e int o th e reactio n mixtur e durin g aperio dof 2 0 minute s a

t 0 ° C unde r

nitrogen . Th e reactio n mixtur e wa s stirre dfor

1 0 hour s a

t roo mtemperatur e unde r

nitrogen . T o th e reactio n mixtur e wer e adde ddropwis e 6 N aqueou s NaO H solutio n (2. 5 mL ) an d30 % aqueou s H2O 2 solutio n ( 3 mL ) a

t 0 °C . Th e reactio n mixture wa s stirre dfo r a n additional 3 hour s a t roo mtemperature . T o th e reactio n mixtur e wer e adde dCH2CI

2 (2 0 mL ) an dwater

(1 0 mL ) an dth e mixtur e wa s shaken . Th e organi c layer wa s separated , washe dwit h 5 % aqueou s NaHC0 3 solutio n ( 3 X 2 0 mL) , drie dove r MgS04 , andevaporate din vacuo t o giv e 0.9 2 g (97% ) of

th e mixtur e of

thre e isomer s 72 , 9 1 an d92 . Th e rati o o f th e 1

- alcoho l sid e grou p t o th e 2-alcoho l sid e grou p i n th e mixtur e wa s determine db y th e compariso n of

th e integratio n area s for

th e -CH-O H absorption s i n th e ' H NM R spectru mo f

th e mixture . I

R(deposi t

fromCH2CI

2 solutio n on aNaC l plate) : 340 4 (O

H) ; 126 7 an d114 0 (C-O ) cm' . ' H NM R(CDCI3) : 80.73-2.8 3 (m , 40H) ; 3.61-3.8 5 (m , 1092H , -CH-O H o f 2-alcoho l sid e group) ; 4.02-4.1 7 (m , 16H) ; 4.5 6 (t , 7 = 6. 6 Hz . 2H . -CH

O H o f 1-alcoho l sid e group) : 6.70-6.8 8 (m , 6H) . Th e rati o of 1-alcohol:2-alcoho l sid e group s = 66:34 . Note : Attempt s t o separat e isomer s 72 , 9 1 an d9 2 b y recrystallizatio n wit h different solvent s (EtOH , acetone , EtOAc , an dCH2Cl2-hexanes ) were unsuccessful . 3.3.16.2 . B y Oxymercuration-Demercuratio n Mercury(II ) trifluoroacetat e (0.6 7 g , 1.5 8 mmol ) wa s dissolve di n 2 m L of water i n a50-mL , one-necked , round-bottome dflask. Afte r aclea r solutio n wa s obtained . 2 mL o f TH F wa s adde dt o precipitat e th e yello w solid . T o thi s reactio n mixtur e wa s adde d4,4'(5')-di[(l-decenyl)benzo]-18-crown- 6 (90 ) (0.5 0 g , 0.7 9 mmol ) wit h vigorou s stirring . Afte

r stirrin g fo

r 1 da y a t roo mtemperature , 3. 0 N NaO H solutio n ( 5 mL ) wa s adde dfollowe db y additio n o f 0. 5 N NaBH i i

n 3. 0 N NaO H solutio n ( 5 mL) . Th e water laye r wa s saturate dwit

h NaC l an dK2CO3 . Th e organi c layer wii s separate dandth e wate r laye r wa s washe dwit

h TH F (1 0 mL) . Th e combine d organi c layer s were drie d ove r MgS04 , an devaporate din vacuo. Colum n chromatograph y on alumin awit h EtOA c a s eluen t

t o remov e th e unreacte dstartin g material an dthen wit h EtOAc-MeO H (20:1 ) a s eluen t

gav e 0.1 5 g (28% ) o

f amixtur e o

f th e thre e isomer s 72 , 9 1 an d92 . Th e rati o o f th e 1-alcoho l sid e grou p t o th e 2-alcoho l sid e group i n th e mixtur e wa s determine db y th e compariso n of th e integratio n area s fo

r th e -CH-O H absorption s i n th e

' H NM Rspectru mo f

th e mixture . Th e rati o o f l-alcohol:2-alcoho l sid e group s = 45:55 .

11 03.3.17 . Preparatio n o f l-(2'-Hydroxy)hexoxy

3,4-methylenedioxybenzen e (93 ) 3.3.17.1 . With Cesiu mCarbonat e Int o a250-mL , three-necked , round-bottome dflask were adde dSesamo l (1.0 0 g . 7.2 4 mmol) , CS2CO

3 (5.9 0 g , 18. 1 mmol) , an ddr y CH3C N (5 0 mL ) unde r

nitrogen . Th e reactio n mixtur e wa s refluxe dfo r 3 hour s an d the n asolutio n o f 1,2-epoxyhexan e (0.7 3 g . 7.2 4 mmol ) in 2 5 mL o f

CH3C N wa s adde dover

2 hours . Th e reactio n mixtur e wa s refluxe dfor

6 0 hour s unde r

nitrogen . Th e reactio n mixture wa s filteredan dth e filtere d solid s wer e washe dwit

h CH2CI2 . Th e combine d filtrate an d washing s were evaporate d in vacuo an dth e residu e wa s dissolve di n 5 0 m L of CH2CI2 . Th e CH2CI

2 layer wa s washe dwit

h wate r (2 5 mL) , drie dove r

MgS04 , an d evaporate din vacuo. Colum n chromatograph y on alumin awit h EtOAc-hexane s (1:10 ) a s eluen t t o remov e asmal l amoun t o f les s polar

impurity , the n wit

h EtOAc-hexane s (1:5 ) a s eluen t gav e 1.3 5 g (78% ) o f l-(2'-hydroxy)hexoxy-3,4-methylenedioxybenzen e (93 ) a s ayellowish , viscou s liquid . IR(deposi t

fromCH2CI

2 solutio n on aNaC l plate) : 344 8 (O-H) ; 118 6 and103 8 (C-O ) cm"' . ' H NM R(CDCI3) : 8 0.9 2 (t , 7 = 7. 0 Hz , 3H) ; 1.25-1.6 0 (m , 6H) ; 2.4 2 (d , 7

= 3. 5 Hz , IH) ; 3.70-3.7 8 (m , IH) ; 3.86-3.9 8 (m , 2H) ; 5.9 1 (s , 2H) ; 6.3 2 (dd , 7 = 2. 5 an d 8. 4 Hz , IH) ; 6.5 0 (d , 7 = 2. 4 Hz , IH) ; 6.6 9 (d , 7 = 8. 4 Hz , IH) . Anal . Calcd . fo r C13H18O4 : C , 65.53 ; H , 7.61 . Found : C , 65.66 ; H , 7.71 . 3.3.17.2 . With Sodiu mHydroxid e Int o a250-mL , three-necked , round-bottome dflask wer e adde dSesamo l (1.0 0 g , 7.2 4 mmol) , NaO H (0.5 8 g , 14. 5 mmol) , an dr-BuO H (5 0 mL ) unde r nitrogen . Th e 11 1reactio n mixmr e wa s refluxe dfo r 2 hour s an d the n 1,2-epoxyhexan e (0.7 3 g , 7.2 4 mmol ) wa s adde dslowl y int o th e reactio n mixtur e unde r nitrogen . Th e reactio n mixtur e wa s refluxe dfor

3 days . Th e reactio n mixtur e wa s coole dt o roo mtemperamr e an dth e tBuO H wa s evaporate din vacuo. Th e residu e wa s dissolve d i n 5 0 m L of CH2CI2 . Th e CH2CI 2 laye r wa s washe dwit

h water ( 2 X 2 5 mL ) an dth e combine daqueou s layer s wer e extracte dwit

h CH2CI 2 ( 2 X 2 5 mL) . Th e combine dCH2CI 2 layer s were evaporate din vacuo. Column chromatograph y on alumin awit h EtOAc-hexane s (1:10 ) a s eluen t to remov e asmal l amoun t

of les s pola r impurity , then wit

h EtOAc-hexane s (1:5 ) a s eluent gav e 0.7 8 g (45% ) of

l-(2'-hydroxy)hexoxy-3,4-methylenedioxybenzen e (93 ) a s a yellowish , viscou s liquid . 3.3.18 . Preparatio n of 3,4-Dihydroxy

l-(2'-hydroxy)hexoxybenzen e (94 ) Int o asolutio n of

l-(2'-hydroxy)hexoxy-3,4-methylenedioxybenzen e (1.1 0 g , 4.6 2 mmol ) in 10 0 mL o f

CH2CI 2 wa s adde dboro n trichlorid e (1.0 8 g , 9.2 4 mmol ) unde r nitrogen . Th e reactio n mixtur e wa s stirre d for 1 hour a t roo mtemperatur e unde r nitrogen . MeO H (2 0 mL ) wa s adde dt o destro y th e exces s of boro n trichlorid e an dth e solven t wa s evaporate din vacuo. Th e residu e wa s dissolve di n 1 N aqueou s HC l solutio n (5 0 mL ) an dth e aqueou s layer wa s extracte dwit

h CH2CI 2 ( 7 X 1(X

) mL) . Th e combine dCH2CI

2 layer s wer e evaporate din vacuo. Shor t column chromatograph y o n silic age l wit

h EtOAc-CH2Cl 2 (1:5 ) a s eluen t t o remov e th e more pola

r impurit y an dthen recrystallizatio n fromCH2CI 2 gav e 0.5 3 g (50% ) of

3,4-dihydroxy-l-(2'-hydroxy)

- hexoxybenzen e (94 ) a s awhit e soli dwit h m p 73-7 6 °C. I

R(deposi t

fromCH2CI

2 solutio n o n aNaC l plate) : 326 5 (O-H) ; 116 5 (C-O ) cm"' . ' H NM R(CDCbiDMSO-d ^ 11 2(10:1)) : 8 0.9 2 (t , 7 = 7. 0 Hz , 3H) ; 1.29-1.5 3 (m , 6H) ; 3.2 6 (b r s , IH) : 3.70-3.8 8 (m , 3H) : 6.2 9 (dd , 7 = 2. 8 an d8. 6 Hz , IH) ; 6.5 1 (d , 7 = 2. 8 Hz , IH) ; 6.7 4 (d , 7 = 8. 6 Hz , IH) ; 7.5 8 (b r s , 2H) . Anal . Calcd . forCi2Hi804 : C , 63.70 ; H , 8.02 . Found : C , 63.41 ; H , 8.18 . Note : Et2 0 ma

y b e substitute dfo

r CH2CI 2 a s th e extractin g solven t du e to th e low solubility of

th e produc t

i n CH2CI2 . 3.3.19 . Attempte dSynthesi s o f 4,4'(5')-Di[(2-hydroxyhexoxy)benzo]-18-crown- 6 (95 ) fro m3,4-Dihydroxy-l-(2'-hydroxy)hexoxybenzen e (94 ) Int o a100-mL , three-necked , round-bottome dflask equippe dwit

h areflux condense r an dathermomete r

were adde d3,4-dihydroxy-l-(2'-hydroxy)hexoxybenzen e (94 ) (1.0 0 g , 4.4 2 mmol ) an d«-butano l (1 5 mL) . Int o th e reactio n mixtur e were adde d NaO H pellet s (0.1 8 g , 4.4 9 mmol) . Th e reactio n mixture wa s heate dt o reflu x an da solutio n o f

bis(2-chloroethyl)ethe r

(0.3 3 g , 2.2 8 mmol ) i

n 5 m L of n-butano l wa s adde d ove r 2 hours . After

th e reactio n mixtur e wa s refluxe dfo r a n additional hour , it

wa s coole dt o 9 0 ° C an dNaO H pellet s (0.1 8 g , 4.4 9 mmol ) were added . Th e reactio n mixtur e wa s refluxe dfo

r 3 0 minute s an dasolutio n of bis(2-chloroethyl ) ethe r

(0.3 3 g , 2.2 8 mmol ) in 5 m L o f

n-butano l wa s adde dove r aperio d of

2 hours . Th e reactio n mixtur e wa s refluxe dfor

1 6 hour s an dcoole dt o roo mtemperature , the n acidifie db y th e additio n o f

concentrate dHC l ( 1 drop) . Th e solven t wa s evaporate din vacuo an dth e residu e wa s dissolve di

n 20 0 mL o f

CH2CI2 . Th e CH2CI

2 layer wa s washe dwit

h water ( 3 X 5 0 mL) , drie dove r

MgS04 , an devaporate din vacuo. Column chromatograph y o n silic age l wit

h EtOA c a s eluen t

t o remov e th e les s pola

r impuritie s an dthe n wit

h EtOAc

MeO H (10:1 ) a s eluen t

an drecrystallizatio n fromEt2 0 twic e gav e awhit e solid . IR

11 3(deposi t

fro mCH2CI

2 solutio n on aNaC l plate) : 338 0 (O-H) ; 1223 , 1128 . an d106 0 (C

0)cm"' . 'HNMR(CDCl3):80.92(t,7=6.9Hz,6H) ; 1.22-1.5 6 (m , 12H);2.3 1 (brs . 2H) ; 3.71-4.1 3 (m , 22H) ; 6.3 9 (dd , 7 = 2.7an d8. 7 Hz , 2H) ; 6.5 1 (d , 7 = 2. 4 Hz . 2H) : 6.8 0 (d , 7 = 8. 7 Hz , 2H) . Note : Column chromatograph y gav e a n impure produc t

becaus e ther e wer

e man y sid e product s fro mth e reactio n mixtur e by TL C analysis . Recrystallizatio n attempt s gav e asmal l amoun t

o f th e produc t

an dth e yiel do

f th e produc t

wa s no t determined . Th e obtaine dproduc t

wa s contaminate dwit

h asmal l amount

of impurit y tha t wa s no t identified . 3.3.20 . Attempte dSynthesi s o f 1 -Benzyloxy-3,4-methylenedioxybenzen e (96 )

fromSesamo l 3.3.20.1 . Metho dA Int o a100-mL , three-necked , round-bottome dflask wer e adde dSesamo l (1.3 0 g , 9.4 1 mmol) , NaO H (0.3 8 g , 9.4 1 mmol) , an ddioxan e (2 0 mL) . Int o th e reactio n mixture wa s adde dbenzy l chlorid e (1.1 9 g , 9.4 1 mmol) . Th e reactio n mixtur e wa s stirre dfo r 24 hour s a t 1(X ) ° C unde r

nitrogen . Afte

r coolin g to roo mtemperature , th e reactio n mixture wa s poure dint o 1(X

) m L of H2 O an dth e aqueou s layer

wa s extracte dwit

h CH2CI 2 ( 3 X 1(K ) mL) . Th e CH2CI

2 laye r wa s washe dwit

h 5 % aqueou s NaO H solutio n (1(X ) mL) , drie dove r

MgS04 , an devaporate din vacuo. Colum n chromatograph y on silic age l wit h CH2Cl2-hexane s (1:5 ) a s eluen t gav e 1.8 1 g of

ayellow , viscou s liquid . Note : Th e reactio n gav e aproduc t that wa s contaminate dwit

h som e impurities . Th e unidentifie dimpuritie s wer e no t separabl e b y column chromatography . 11 43.3.20.2 . Metho dR

Int o a250-mL , one-necked , round-bottome dflask were adde dSesamo l (1.0 0 g . 7.2 4 mmol) , NaO H (0.4 3 g , 10. 9 mmol) , benzy l chlorid e (1.8 3 g , 14. 5 mmol) , an d benzyltriethylammoniu mchlorid e (1.6 5 g , 7.2 4 mmol) . Int o th e reactio n mixtur e wer e adde dCH2CI

2 (4 0 mL ) an dH2

O (4 0 mL) . Th e reactio n mixtur e wa s stirre dfo r 24 hour s a t roo mtemperature . Th e CH2CI 2 layer wa s separate dan dth e aqueou s laye r wa s extracte dwit

h CH2CI 2 ( 2 X 5 0 nti^) . Th e combine dCH2CI 2 layer wa s washe dwit

h 2 N aqueou s NaO H solutio n (10 0 mL ) an dbrin e (10 0 mL) , drie dove r MgS04 , an d evaporate din vacuo. Column chromatograph y on silic age l wit h CH2Cl2-hexane s (1:5 ) a s eluen t gav e 0.1 0 g o f

ayellow , viscou s liquid . Note : Th e reactio n performe dunde r phas e transfer

catalys t gav e th e same resul t a s Metho dA . Th e obtaine dproduc t wa s contaminate dwit

h unidentifie dimpurities . 3.3.21 . Attempte dSynthesi s o f l-Benzyloxy-3,4-dihydroxybenzen e (97 ) fro m 1 -Benzyloxy-3,4-methylenedioxybenzen e (96 ) Int o asolutio n o f

l-benzyloxy-3,4-methylenedioxybenzen e (96 ) (1.0 0 g , 4.3 8 mmol ) i n 1(X ) mL o f CH2CI 2 wa s adde dboro n trichlorid e (1.0 3 g , 8.7 6 mmol ) under nitrogen . Th e reactio n mixtur e wa s stirre dfor 3 0 minute s a

t roo mtemperatur e unde r nitrogen . MeO H (2 0 mL ) wa s adde dove r 1 0 minute s t o destro y th e exces s of boro n trichlorid e an dthe n th e solven t wa s evaporate din vacuo. Th e residu e wa s dissolve di n 1 N aqueou s HC l (10 0 mL ) an dth e aqueou s laye r wa s extracte d wit

h CH2CI 2 ( 3 X 100 mL) . Th e CH2CI

2 laye r wa s evaporate din vacuo. Column chromatograph y on silic agel wit h EtOAc-hexane s (1:10 ) a s eluen t gav e aproduct . 11 5Note : Th e startin g material wa s contaminate dwit h unidentifie dimpuritie s and wa s use dwithou t

further purification . Th e reactio n gav e 0.0 2 g o f ales s pola

r an d0.0 4 g of amor e polar

product . Bot

h product s were foun dto b e no t th e desire dproduc t

b y ' H NM Ran dIRspectroscopi c analysis . 3.3.22 . Preparatio n o

f 4,4'(5')-Di(nitrobenzo)-18-crown-6(98 ) Int o a10(X)-mL , three-necked , round-bottome dflask equippe dwit

h amechanical stirre r an da n additiona l funnel were adde ddibenzo-18-crown- 6 (15.0 0 g , 41. 6 mmol ) an dCHCI 3 (32 5 mL) . Int o th e reactio n mixtur e wa s adde dglacial aceti c aci d(28 4 mL ) wit h stirrin g a

t roo mtemperature . A solutio n o f 10 2 m L of 68 % HNO 3 an d3 3 m

L o f glacia l aceti c aci dwa s adde ddropwis e wit h a n additional funnel whil e coolin g th e reactio n mixtur e i

n a n ice-wate r

bat h wit h th e temperatur e aroun d1 0 °C . Afte r th e additio n wa s completed , th e reactio n mixtur e wa s stirre dfo r 2 4 hour s a

t roo m temperature . Th e reactio n mixtur e wa s washe dwit h water (10 0 mL ) an dth e organi c laye r wa s washe dwit

h asaturate daqueou s Na2C0 3 ( 3 X 100 mL) . Th e organi c layer wa s drie dove r

MgS04 , an dthe n recrystallizatio n fromCHCI 3 t o giv e 14.7 3 g (79% ) o f a produc t a s ayello w soli dwit

h m p 209-21 3 ° C (lit.' ^ m

p 199-20 1 an d245-24 8 ° C fo r th e 4,4'

- an d4,5'-isomers , respectively) . I R(deposi t

fro mMeO H solutio n on aNaC l plate) : 151 6 an d133 8 (N=0) ; 122 8 an d113 0 (C-O ) cm"' . ' H NM R(DMSO-d6) : 8 3.70-4.3 9 (m , 16H) ; 7.1 6 (d , 7 = 9. 0 Hz , 2H) ; 7.7 2 (d , 7 = 2. 6 Hz , 2H) ; 7.9 0 (dd , 7 = 2. 6 an d8. 9 Hz , 2H) .

11 6Note : Afte r dryin g ove r

MgS04 , th e produc t

precipitate d fromth e CHCI 3 solutio n whil e standin g for

1 da y a t roo mtemperature . Sometimes , th e CHCI 3 solutio n wa s place di n arefrigerato r

t o increas e th e yield .

3.3.23 . Preparatio n o

f 4,4'(5')-Di(aminobenzo)-18-crown-6(99 ) A mixtur e of

4,4'(5')-di(nitrobenzo)-18-crown- 6 (98 ) (10.0 0 g , 22. 2 mmol ) an d 10 % P do n carbo n (2.0 0 g ) in 20 0 m L of DM F wa s subjecte dt o 6 0 ps i of hydroge n pressur e for

2 4 hour s a

t roo mtemperature . Th e catalys t wa s filtere dwit

h Celit e an d washe dwit

h CH2CI 2 several times . Th e solven t wa s remove dfromth e combine dfiltrate an dwashing s b y distillatio n unde r vacuu mt o giv e 8.5 6 g (99% ) of aproduc t a s are d soli dwit h mp 182-18 4 ° C (lit.'" ^ m p 176.5-177. 5 an d197-19 8 °C fo r th e 4,4'

- an d4,5'

- isomers , respectively) . I R(deposi t

fromMeO H solutio n on aNaC l plate) : 332 9 (N-H) ; 123 0 an d112 3 (C-O ) cm"' . ' H NM R(DMSO-dg) : 8 3.76-3.9 4 (m , 16H) ; 4.6 8 (s , 4 NH) ; 6.0 5 (dd , 7 = 2. 3 an d8. 4 Hz , 2H) ; 6.24 (d , 7 = 2. 3 Hz , 2H) , 6.6 2 (d , 7 = 8. 4 Hz , 2H) . 3.3.24 . Preparatio n o

f 4,4'(5')-Di(hydroxybenzo)-18-crown-6(101 ) from4,4'(5')-Di(aminobenzo)-18-crown- 6 (99 ) 3.3.24.1 . 4,4'(5')-Di[(diazoniu m tetrafluoroborato)benzo]-18-crown- 6 (100) . Int o a100-mL , one-necked , round-bottome dflask wer e adde d4,4'(5')-di(aminobenzo)

- 18-crown- 6 (99 ) (1.0 0 g , 2.5 6 mmol ) an dH2 O (2 0 mL) . Int o th e suspensio n wa s adde d 48 % fluoroboric aci d(12.6 0 mL) . Th e suspensio n wa s stirre d i n a n ice-sal t bath . A solutio n o f

NaN0 2 (0.3 6 g ) i

n 2 mL o f H2 O wa s adde d an dth e mixtur e wa s stirre dfo r 3 0 11 7minute s i

n th e ice-sal t

bath . Th e soli dwa s filteredan dwashe d wit h Et2 0 (10 0 mL ) to giv e 1.2 8 g of

abrow n soli di

n aquantitativ e yield . I

R(deposi t

fromMeO H solutio n o

n aNaC l plate) : 224 8 (N^N) ; 124 0 an d112 6 (C-O ) cm"' . ' H NM R(DMSO-d6) : 8 3.72

- 4.6 1 (m , 16H) ; 7.5 1 (d , 7 = 9. 2 Hz , 2H) ; 8.1 8 (d , 7 = 2. 4 Hz , 2H) : 8.44 (dd , 7 = 2. 3 an d 9.1Hz,2H) . Note : Th e 4,4'(5')-Di[(diazoniu mtetrafluoroborato)benzo]-18-crown- 6 wa s use d for th e nex t ste p withou t

purification . 3.3.24.2 . 4,4'(5')-Di(hydroxybenzo)-18-crown- 6 (101) . K2CO3 (0.3 6 g , 2.6 0 mmol ) wa s adde dcautiousl y t o 1 5 m L of CF3CO2 H i n a100-mL , three-necked , round

bottom dflask

a t 0 °C. Then , 4,4'(5')-di[(diazoniu mtetrafluoroborato)benzo]-18-crown- 6 (100 ) (1.2 8 g , 2.6 0 mmol ) wa s added . Th e reactio n mixture wa s refluxe dfo r 2 4 hour s an dpoure dint o 5 0 mL of water . Th e resultin g mixture wa s place di n arefrigerato r ovemigh t an dth e precipitate dsoli dwa s filtered . Shor t colum n chromatograph y o

n silic a ge l wit h MeO H a s eluen t

an dthe n recrystallizatio n fro mMeOH-H2 0 twic e usin g activate dcarbo n gav e 0.4 0 g (40% ) of aproduc t a s alight yello w soli dwit

h m p 217-22 0

° C (lit.^' ^ mp 190-19 4 an d215.5-216. 5 ° C fo r th e 4,4'

- an d4,5'-isomers , respectively) . I R (deposi t fromMeO H solutio n o

n aNaC l plate) : 319 4 (O-H) ; 122 2 an d112 6 (C-O ) cm"' .

' H NM R(DMSO-d6) : 8 3.68-4.1 9 (m , 16H) ; 6.2 5 (dd , 7 = 2. 4 an d8. 6 Hz , 2H) ; 6.4 0 (d , 7

= 2. 4 Hz , 2H) ; 6.7 3 (d , 7 = 8. 6 Hz , 2H) ; 8.9 8 (s , 2H) .

11 83.3.25 . Preparatio n o f 4,4'(5')-Di(acetylbenzo)-18-crown-6(102 ) Int o a500-mL , three-necked , round-bottome dflask equippe dwit

h athermomete r wer e adde ddibenzo-18-crown- 6 (26.0 0 g , 72. 1 mmol) , glacial aceti c aci d(8.6 6 g , 144. 3 mmol) , an dEaton' s reagen t (188.0 0 g ) unde r

nitrogen . Th e reactio n mixtur e wa s stirre d magneticall y for

6 hour s a t 5 0 ° C unde r

nitrogen . Durin g thi s time , th e reactio n mixture turne dcherry red . Th e reactio n mixture wa s poure dint o amixtur e of 25 0 g o f ic e and 25 0 m L o f

wate r an dth e resultin g mixtur e wa s stirre dovemigh t a t roo mtemperature . Th e soli dwa s filteredan dth e filtere dsoli dwa s dissolve di n 50 0 m L of CH2CI2 . Th e CH2CI 2 laye r wa s washe dwit

h 5 % aqueou s NaO H solutio n ( 3 X 15 0 mL ) an dbrin e (15 0 mL) . Th e CH2CI

2 laye r wa s drie dover

MgS04 , an devaporate din vacuo. Colum n chromatograph y o n alumin awit h CH2Cl2-EtOA

c (3:1 ) a s eluen t

an dthe n recrystallizatio n fro mCH2Cl2-hexane s gav e 20.6 6 g (64% ) o f th e produc t

a s aligh t yello w soli dwit

h m p 202-20 6 ° C (lit. ^ m

p 200-20 8 °C). I

R(deposi t

fro mCH2CI 2 solutio n o

n aNaC l plate) : 166 8 (C=0) ; 127 3 an d113 2 (C-O ) cm"' . ' H NM R(CDCI3) : 8 2.5 5 (s , 6H) ; 3.95-4.3 4 (m , 16H) ; 6.8 6 (d , 7 = 8. 3 Hz , 2H) ; 7.49-7.5 8 (m , 4H) . 3.3.26 . Preparatio n of 4,4'(5')-Di(acetatobenzo)-18-crown-6(103 ) Int o a100-mL , one-necked , round-bottome d flask wer e adde d4,4'(5')

- di(acetylbenzo)-18-crown- 6 (102 ) (0.3 0 g , 0.6 7 mmol ) an dCH2CI 2 (2 0 mL ) unde r nitrogen . Afte

r th e 10 2 ha ddissolved , purifie dm-chloroperbenzoi c aci d(m-CPBA ) (0.5 8 g , 3.3 5 mmol ) an dNa2HP0 4 (0.2 5 g ) wer e added . Th e reactio n mixtur e wa s stirre dfor 2 day s a t roo mtemperatur e unde r

nitrogen . Th e reactio n mixtur e wa s filtered 11 9an dth e filteredsolid s wer e washe dwit h CH2CI2 . Th e combine dfiltrate an dwashing s wer e washe dwit

h saturate daqueou s NaHC0 3 ( 3 X 2 0 mL) , 5 % aqueou s Na2S20 3 (2 0 mL) , an dbrin e (2 0 mL) . Then , th e CH2CI 2 layer wa s drie dove r

MgS04 , an devaporate d in vacuo. Recrystallizatio n fromCH2Cl2-hexane s gav e 0.2 5 g (78% ) o f th e produc t

a s a ligh t yello w soli dwit

h m p 183-186°C . I

R(deposi t fromCH2CI

2 solutio n o

n aNaC l plate) : 175 8 (C=0) ; 121 0 an d113 6 (C-O ) cm"' . ' H NM R(CDCI3) : 8 2.2 7 (s , 6H) ; 3.92

- 4.2 8 (m , 16H) ; 6.59-6.6 5 (m , 4H) ; 6.83-6.8 7 (m , 2H) . Anal . Calcd . fo r C24H28O1 0 X 0. 2 H2O : C , 60.04 ; H , 5.96 . Found : C , 59.76 ; H , 5.96 . Note : Th e m-chloroperbenzoi c aci d(m-CPBA ) wa s purifie db y aliteratur e method.^' ' A solutio n of

m-CPB A i

n Et2 0 wa s washe dwit

h p H 7. 5 buffe

r solutio n several time s an dth e Et2 0 laye r wa s evaporate din vacuo. Th e purifie dm-CPB A wa s drie dunde r

vacuum . 3.3.27

- Preparatio n o f 4,4'(5')-Di(hydroxybenzo)-18-crown- 6 (101 ) from4,4'(5')-Di(acetatobenzo)-18-crown- 6 (103 ) Int o a500-mL , one-necked , round-bottome dflask were adde d4,4'(5')

- di(acetatobenzo)-18-crown- 6 (103 ) (2.0 0 g , 4.2 0 mmol) , MeO H (15 0 mL) , an dCH2CI 2 (1(X ) mL ) unde r

nitrogen . A solutio n of

NaO H (0.6 2 g , 15. 4 mmol ) i n 1 0 m L o f MeO H wa s added . Th e reactio n mixtur e wa s stirre dfor 2 4 hour s a

t roo mtemperatur e under nitrogen . Th e reactio n mixtur e wa s neutralize dwit h concentrate dHC l an dth e solven t wa s evaporate din vacuo. Recrystallizatio n of th e residu e fromMeOH-H2 0 gav e 1.3 7 g (83% ) of aproduc t a s aligh t brow n soli dwit

h m p 217-22 0 °C

(lit.'" ' m p 190-19 4 an d 215.5-216. 5 ° C for

th e 4,4'

- an d4,5'-isomers , respectively) . I R(deposi t

fromMeO H 120solutio n o n aNaC l plate) : 319 5 (O-H) ; 122 5 an d112 4 (C-O ) cm"' . ' H NM R(DMSO

de): 8 3.58-4.2 2 (m , 16H) ; 6.2 3 (dd , 7 = 2. 5 an d8. 6 Hz , 2H) ; 6.3 8 (d , 7 = 2. 4 Hz , 2H) ; 6.7 1 (d , 7 = 8. 6 Hz , 2H) ; 8.9 7 (s , 2H) . Anal . Calcd . fo r C20H24O 8 X 0. 8 H2O : C , 59.05 ; H , 6.34 . Found : C , 58.72 ; H, 5.97 . Note : Prio r

t o submissio n fo

r elemental analysis , th e 4,4'(5')-di(hydroxybenzo)

- 18-crown- 6 wa s drie dove r P2O 5 unde r vacuu mwit

h heatin g b y refluxin g toluen e i n a dryin g pistol . 3.3.28 . Preparatio n of l-(2'-Hydroxyoctoxy)

- 3,4-methylenedioxybenzen e (104 ) 3.3.28.1 . Wit

h Cesiu mCarbonat e Int o a250-mL , three-necked , round-bottome dflask were adde dSesamo l (0.6 0 g , 4.3 4 mmol) , CS2CO

3 (3.5 4 g , 10. 9 mmol) , an dCH3C N (5 0 mL ) unde r

nitrogen . Th e reactio n mixtur e wa s refluxe dfo r 3 hour s an dthe n asolutio n o f 1,2-epoxyoctan e (0.5 6 g , 4.3 4 mmol ) in 2 5 mL o f

CH3C N wa s adde dove r

2 hours . Th e reactio n mixtur e wa s refluxe dfor

3 day s unde r

nitrogen , coole dt o roo mtemperature , an dfiltered . Th e filtere dsoli dwa s washe dwit h CH2CI2 . Th e combine dfiltrate an dwashing s were evaporate din vacuo an dth e residu e wa s dissolve di n 5 0 m L o f CH2CI2 . Th e CH2CI

2 laye r wa s washe dwit

h wate r (2 5 mL) , drie dove r

MgS04 , an d evaporate din vacuo. Column chromatograph y on alumin awit h EtOAc-hexane s (1:10 ) a s eluen t gav e 0.9 4 g (8 1 % ) o f ayello w soli dwit

h m p 37-4 0 °C . I

R(deposi t

fro mCH2CI 2 solutio n o

n aNaC l plate) : 342 4 (O-H) ; 118 7 an d103 9 (C-O ) cm"' . ' H NM R(CDCI3) : 8 0.8 9 (t , 7 = 6. 5 Hz , 3H) ; 1.16-1.6 9 (m , lOH) ; 2.3 6 (d , 7 = 3.4Hz , IH) ; 3.68-4.0 7 (m , 3H) ; 5.9 1 (s , 2H) ; 6.3 2 12 1(dd , 7 = 2. 5 an d8. 4 Hz , IH) ; 6.5 0 (d , 7 = 2. 5 Hz , IH) ; 6.7 0 (d , 7 = 8. 5 Hz . IH) . Anal .

Calcd . for C15H22O4 : C , 6 7 65 ; H , 8.33 . Found : C , 67.62 ; H , 8.39 . 3.3.28.2 . With Sodiu mHvdroxid e Int o a250-mL , three-necked , round-bottome dflask were adde dSesamo l (1.0 0 g , 7.2 4 nunol) , NaO H (0.5 8 g , 14. 5 mmol) , an d r-BuO H (5 0 mL ) unde r nitrogen . Th e reactio n mixtur e wa s refluxe dfo r 2 hour s an dthen 1,2-epoxyoctan e (0.9 3 g , 7.2 4 mmol ) wa s adde ddropwise . Th e reactio n mixtur e wa s refluxe dfo r 3 day s unde r

nitrogen , coole dt o roo mtemperature , an devaporate din vacuo. Th e residu e wa s dissolve di n 5 0 mL o f CH2CI2 . Th e CH2CI

2 layer wa s washe dwit

h water ( 2 X 2 5 mL ) an dth e combine d aqueou s layer s wer e extracte dwit h CH2CI 2 ( 2 X 2 5 mL) . Th e combine dCH2CI 2 layer s wer e drie dove r

MgS04 , an devaporate din vacuo. Colum n chromatograph y o

n alumin a wit h EtOAc-hexane s (1:5 ) a s eluen t gav e 0.7 1 g (37% ) o

f aligh t yello w solid . 3.3.29 . Attempte dSynthesi s o f 4,4'(5')

- Di[(2-hydroxy)octoxybenzo]-18-crown- 6 (105 ) from4,4'(5')-Di(hyroxybenzo)-18-crown- 6 (101 ) Int o a250-mL , three-necked , round-bottome dflask were adde d4,4'(5')

- di(hydroxybenzo)-18-crown- 6 (101 ) (0.2 0 g , 0.5 1 mmol) , NaO H (0.0 8 g , 2.0 4 mmol) , an dr-BuO H (5 0 mL ) unde r nitrogen . Th e reactio n mixtur e wa s refluxe dfo r 2 hour s and the n 1,2-epoxyoctan e (0.1 3 g , 1.0 2 mmol ) wa s adde d dropwise . Th e reactio n mixtur e wa s refluxe dfor

3 day s unde r

nitrogen , coole dto roo mtemperature , an devaporate din vacuo. Th e residu e wa s dissolve di n 5 0 m L of CH2CI2 . Th e CH2CI

2 layer wa s washe d wit h wate r ( 2 X 2 5 mL ) an dth e combine daqueou s layer s wer e extracte dwit h CH2CI 2 ( 2 122X 2 5 mL) . Th e combine dCH2CI 2 layer s were drie dove r

MgS04 , an devaporate din vacuo. Colum n chromatograph y on silic age l wit h MeOH-CH2Cl 2 (1:10 ) a s eluen t to remov e th e les s polar

impuritie s an dthe n recrystallizatio n fromEtOAc-hexane s gav e 0.0 4 g (12% ) of

aproduc t a s yello w solid . ' H NM R(CDCI3) : 8 0.8 9 (t , 7 = 6. 3 Hz , 6H) : 1.09-1.7 4 (m , 20H) ; 2.3 8 (b r s , 2H) ; 3.68-4.2 8 (m , 22H) ; 6.3 8 (dd , 7 = 2. 7 an d8. 7 Hz , 2H) ; 6.5 0 (d , 7 = 2. 7 Hz , 2H) ; 6.7 7 (d , 7 = 8. 7 Hz , 2H) . Note : Th e produc t

obtaine db y recrystallizatio n wa s contaminate dwit h asmal l amoun t o f unidentifie dimpurities . Therefore , it s meltin g poin t wa s no t measured . 3.3.30 . Preparatio n o

f 4-Octyl-2,2-dioxo-l,3,2-dioxathiolan e (107 ) 3.3.30.1 . 4-Octyl-2-oxo-l,3,2-dioxathiolan e (106) . T o 1,2-decanedio l (2.0 0 g , 11. 5 mmol ) dissolve di

n 5 0 m L of CH2CI 2 i n a250-mL , one-necked , round-bottome d flask unde r nitrogen , Et3 N (4.6 5 g , 45. 9 mmol ) wa s added . Th e reactio n mixtur e wa s coole dt o 0 ° C i

n a n ic e bat h an dthiony l chlorid e (2.0 5 g , 17. 2 mmol ) wa s added . Th e reactio n mixtur e wa s stirre dfo r 1 5 minute s i

n th e ic e bat

h the n th e reactio n wa s quenche d b y th e additio n o f

wate r (1(X ) mL) . Th e organi c layer wa s separate dan dth e aqueou s laye r wa s extracte dwit

h CH2CI 2 ( 3 X 5 0 mL) . Th e combine dCH2CI 2 layer s were drie d ove r MgS0 4 an devaporate din vacuo. Th e residu e wa s drie dunde r vacuu mt o giv e a yellow , viscou s liquid . Note : Th e obtaine ddecan e 1,2-cycli c sulfite wa s use d i n th e nex t ste p withou t further purification .

12 33.3.30.2 . 4-Octyl-2,2-dioxo-l,3,2-dioxathiolan e (107) . T o 4-octyl-2-oxo-1,3, 2

dioxathiolan e (106 ) dissolve di n 6 0 m L of CCI4-CH3C

N (1:1 ) i n a250-mL , one-necked , round-bottome dflask

coole dt o 0 ° C i

n a n ic e bat h were adde d NaI0 4 (4.9 1 g . 22.9 6 mmol) , H2

O (5 0 mL) , an dRuC h x H2 O (0.0 2 g , 0.1 1 mmol , 1 mo l %) . Th e reactio n mixtur e wa s stirre dfor

1 hour a t 0 ° C an dEt2 0 (5 0 mL ) wa s added . Th e organi c layer wa s separate dan dth e aqueou s laye r wa s extracte dwit

h Et2 0 ( 3 X 100 mL) . Th e combine dorgani c layer s were washe dwit h brin e (5 0 mL) , drie dove r MgS04 , and evaporate din vacuo. Column chromatograph y o n silic agel wit

h CH2Cl2-hexane s (3:1 ) a s eluen t gav e 2.5 8 g (95% ) of

aproduc t a s apal e yellow , viscou s liquid . I R(deposi t fro mCH2CI

2 solutio n o n aNaC l plate) : 138 5 an d120 8 (S=0 ) cm"' . ' H NM R(CDCI3) : 8 0.8 8 (t , 7 = 6. 5 Hz , 3H) ; 1.09-2.1 0 (m , 14H) ; 4.3 4 (t , 7 = 8. 5 Hz , IH) ; 4.69-4.7 6 (m , IH) ; 4.92-5.0 5 (m , IH) . Anal . Calcd . fo r C,oH2o04S : C , 50.82 ; H , 8.53 . Found : C , 51.12 ; H , 8.50 . 3.3.31 . Attempte dSynthesi s of

l-(2'-Hydroxydecyloxy)-3,4-methylenedioxybenzen e (108 ) fromSesamo l Givin g aMixtur e of Tw o Isomer s 10 8 an d10 9 Int o a250-mL , three-necked , round-bottome dflask were adde dSesamo l (0.3 6 g , 2.6 2 mmol) , CS2CO

3 (2.1 3 g , 6.5 5 mmol) , an dCH3C N (5 0 mL ) unde r

nitrogen . Th e reactio n mixtur e wa s refluxe dfo r 3 hour s an dthe n asolutio n o f 4-octyl-2,2-dioxo-1,3,2

- dioxathiolan e (107 ) (0.6 2 g , 2.6 2 mmol ) i n 2 5 mL o

f CH3C N wa s adde dove r

2 hours . Th e reactio n mixtur e wa s refluxe dfo r 1 da y unde r nitrogen , coole dt o roo mtemperature , an dfiltered . Th e filteredsoli dwa s washe dwit h CH2CI2 . Th e combine dfiltrate and 12 4washing s wer e evaporate din vacuo an dth e residu e wa s drie dunde r vacuu mfo

r 1 hour . Th e crud e sulfate wa s suspende di n 5 0 m L of TH F an d1 0 m

L o f 2 0 % aqueou s H2SO

4 solutio n wa s adde dt o th e stirre dsuspension . Th e reactio n mixtur e wa s stirre dfo r 1 hour a t roo mtemperature , 5 0 mL of samrate daqueou s Na2C0 3 wa s added , an dstirrin g wa s continue dfor

additiona l 2 0 minute s a

t roo mtemperature . Th e organi c layer wa s separate dan dth e aqueou s laye r wa s extracte dwit

h CH2CI 2 ( 3 X 100 mL) . Th e combine dorgani c layer s were drie dove r MgS0 4 an devaporate din vacuo. Colum n chromatograph y o n silic age l wit h EtOAc-hexane s (1:5 ) a s eluen t gav e th e product . 3.3.31.1. 1-(2'-Hydroxydecyloxy)-3,4-methylenedioxybenzen e (108 ) wa s obtaine d56 % yiel da s awhit e soli dwit h m p 52-5 5 °C . I

R(deposi t

fromCH2CI

2 solutio n o n aNaC l plate) : 342 0 (O-H) ; 1194 an d103 5 (C-O ) cm"' . ' H NM R(CDCI3) : 8 0.8 8 (t , 7

= 6. 4 Hz , 3H) ; 1.07-1.6 9 (m , 14H) ; 2.3 5 (d , 7 = 3. 6 Hz , IH) ; 3.70-4.0 7 (m , 3H) ; 5.9 1 (s , 2H) ; 6.3 2 (dd , 7 = 2. 6 an d8. 5 Hz , IH) ; 6.5 0 (d , 7 = 2. 5 Hz , IH) ; 6.7 0 (d , 7 = 8. 4 Hz , IH) . Anal . Calcd . for

C17H26O4 : C , 69.36 ; H , 8.90 . Found : C , 69.15 ; H , 8.94 . 3.3.31.2 . l-[l'-(Hydroxymethyl)nonyloxy]-3,4-methylenedioxybenzen e (109 ) wa s isolate din 13 % yiel da s ayellow , viscou s liquid . I R(deposi t

fro mCH2CI 2 solutio n o n aNaC l plate) : 342 1 (O-H) ; 118 2 an d104 0 (C-O ) cm"' . ' H NM R(CDCI3) : 8 0.8 7 (t , 7

= 6.4Hz , 3H) ; 1.03-1.8 1 (m , 14H) ; 2.1 7 (brs , IH) ; 3.58-3.8 7 (m , 2H) ; 4.08-4.2 7 (m , IH) ; 5.9 1 (s , 2H) ; 6.3 8 (dd , 7 = 2. 5 an d8. 5 Hz , IH) ; 6.5 3 (d , 7 = 2. 4 Hz , IH) ; 6.6 9 (d , 7 = 8. 4 Hz , IH) . Anal . Calcd . fo r C17H26O4 : C , 69.36 ; H , 8.90 . Found : C , 69.71 ; H , 9.23 .

1253.3.32 . Preparatio n o f 4,4'(5')

- Di[(2-hydroxydecyloxy)benzo]-18-crown- 6 (110 ) Int o a250-mL , three-necked , round-bottome dflask were adde d4.4'(5')

- di(hydroxybenzo)-18-crown- 6 (101 ) (0.3 1 g , 0.7 9 mmol) , CS2CO 3 (1.2 9 g , 3.9 5 mmol) . an dCH3CN (5 0 mL ) unde r nitrogen . Th e reactio n mixture wa s refluxe dfo r 3 hour s and the n asolutio n o f

4-octyl-2,2-dioxo-l,3,2-dioxathiolan e (107 ) (0.4 1 g , 1.7 4 mmol ) m2 5 m L of CH3C N wa s adde dover

2 hours . Th e reactio n mixture wa s refluxe dfo r 1 da y unde r nitrogen , coole dt o roo mtemperature , an dfiltered. Th e filteredsolid s were washe dwit

h CH2CI2 . Th e combine dfiltrate an dwashing s were evaporate din vacuo an d th e residu e wa s drie dunde r vacuu mfo

r 1 hour . Th e cmd e sulfat e este r wa s suspende di

n 5 0 m L o f TH F an d1 0 m

L of 2 0 % aqueou s H2SO

4 solutio n wa s added . Th e reactio n mixmr e wa s stirre dfor

1 hou r a t roo mtemperature , 5 0 m

L o f saturate daqueou s Na2C0 3 wa s added , an dstirrin g wa s continue dfo r additional 2 0 minute s a

t roo mtemperature . Th e organi c laye r

wa s separate dan dth e aqueou s layer wa s extracte dwit

h CH2CI 2 ( 3 X 1(X ) mL) . Th e combine dorgani c layer s were drie dover MgS0 4 an devaporate din vacuo. Column chromatograph y o n silic age l wit h CH2Cl2-MeOH (40:1 ) a s eluen t and the n recrystallizatio n fro mMeO H gav e 0.1 2 g (21% ) o f awhite soli dwit

h m p 128-13 1 °C . I R(deposi t

fromCH2CI

2 solutio n on aNaC l plate) : 338 4 (O-H) ; 122 6 an d113 8 (C

O ) cm"' . ' H NM R(CDCI3) : 8 0.8 8 (t , 7 = 6. 4 Hz , 6H) ; 1.10-1.7 2 (m , 28H) ; 2.2 7 (d , 7 = 3. 2 Hz , 2H) ; 3.71-4.2 7 (m , 22H) ; 6.3 9 (dd , 7 = 2. 7 an d 8. 7 Hz , 2H) ; 6.5 1 (d , 7 = 2. 7 Hz , 2H) ; 6.8 0 (d , 7 = 8. 6 Hz , 2H) . Anal . Calcd . for C40H64O10: C , 68.15 ; H , 9.15 . Found : C . 67.89 ; H , 9.10 .

12 63.3.33 . Preparatio n o f (2-Hydroxydecyloxy)benzen e (112 ) Int o a100-mL , three-necked , round-bottome dflask were adde dpotassiu m phenoxid e (111 ) (0.2 1 g , 1.5 9 mmol ) an dCH3C N (1 0 mL ) unde r

nitrogen . A solutio n o

f 4-octyl-2,2-dioxo-l,3,2-dioxathiolan e (107 ) (0.3 8 g , 1.5 9 mmol ) i n 1 0 m L o f CH3C N wa s adde dwit h stirrin g unde r

nitrogen . Th e reactio n mixture wa s stirre dfo r 2 hour s a t roo m temperatur e an dthe n refluxe dfo r 5 minute s under

nitrogen . Th e solven t

wa s evaporate d in vacuo an dth e residu e wa s drie dunde r vacuu mfo

r 2 hours . T o thi s crud e sulfat e este r wa s adde d1 0 m L o f

1 N aqueou s HC l solution . Th e reactio n mixtur e wa s refluxe dfo r 3 hour s an dthe n extracte dwit h CH2CI 2 ( 3 X 5 0 mL) . Th e combine dCH2CI 2 layer s wer

e drie dove r MgS0 4 an devaporate din vacuo. Recrystallizatio n fro mhexane s gav e 0.1 8 g (45% ) of awhit e soli dwit

h m p 63-6 5 °C . I

R(deposi t fro mCH2CI 2 solutio n o

n aNaC l plate) : 341 7 (O-H) ; 109 7 an d107 6 (C-O ) cm"' . ' H NM R(CDCI3) : 8 0.8 8 (t , 7 = 6. 4 Hz , 3H) ; 1.10-1.7 1 (m , 14H) ; 2.3 4 (s , IH) ; 3.81-4.1 2 (m , 3H) ; 6.89-6.9 6 (m , 3H) , 7.25-7.3 3 (m , 2H) . Anal . Calcd . for C16H26O2 : C , 76.75 ; H , 10.47 . Found : C , 76.47 ; H , 10.54 . Note : Potassiu mphenoxid e wa s prepare d b y aliteratur e method.^^

3.3.34 . Preparatio n o

f 4,4'(5')-Di(benzyloxybenzo)-18-crown- 6 (115 ) Int o a250-mL , three-necked , round-bottome dflask were adde d4,4'(5')

- di(hydroxybenzo)-18-crown- 6 (101 ) (0.1 7 g , 0.4 3 mmol) , CS2CO 3 (0.7 0 g , 2.1 5 mmol) , an dCH3CN (5 0 mL ) unde r nitrogen . Th e reactio n mixtur e wa s refluxe dfo r 3 hour s an d the n asolutio n o f

benzy l bromid e (0.1 6 g , 0.9 5 mmol ) i n 2 5 mL o f

CH3C N wa s adde d ove r 2 hours . Th e reactio n mixtur e wa s refluxe dfo r 1 da y unde r nitrogen , coole dt o 12 7as

roo mtemperature , an dfiltered. Th e filteredsolid s wer e washe dwit

h CH2CI2 . Th e combine dfiltrat e an dwashing s were evaporate din vacuo an dth e residu e wa s dissolve d i n 5 0 m L o f

CH2CI2 . Th e CH2CI

2 layer wa s washe dwit

h water (2 5 mL) , drie dover MgS04 , an devaporate din vacuo. Colum n chromatograph y o

n silic agel wit

h CH2CI 2 eluen t t o remov e asmal l amoun t o f les s pola r impurity , the n wit

h CH2Cl2-MeOH (100:1 ) a s eluen t gav e 0.2 0 g (80% ) of

4,4'(5')-di[benzyloxybenzo]-18-crown- 6 (115 ) a s awhit e soli dwit h mp 144-14 6 ''C . I

R(deposi t fro mCH2CI 2 solutio n o

n aNaC l plate) : 1228 , 1140 , an d102 8 (C-O ) cm' . ' H NM R(CDCI3) : 8 3.90-4.2 2 (m , 16H) ; 4.9 9 (s , 4H) ; 6.4 6 (dd , 7 = 2. 6 Hz , 2H) ; 6.5 7 (d , 7 = 2. 8 Hz , 2H) ; 6.8 1 (d , 7 = 8. 7 Hz , 2H) ; 7.29-7.4 4 (m , lOH) . Anal . Calcd . Fo r

C34H36O8 : C , 71.31 ; H , 6.34 . Found : C , 71.13 ; H , 6.27 . 3.3.35 . Preparatio n o

f (3,4-Methylenedioxy)phenoxyaceti c Aci d(118 ) Int o a250-mL , three-necked , round-bottome dflask were adde dSesamo l (3.0 0 g , 21.7 2 mmol) , NaH (2.6 1 g , 108.6 0 mmol , 95 % dry) , an ddr y TH F (5 0 mL ) under nitrogen . Th e reactio n mixtur e wa s stirre dfo r 2 hour s a t roo mtemperatur e under nitrogen . A solutio n o f

bromoaceti c aci d (4.5 3 g , 32.5 8 mmol ) i n 2 0 m L o f dr y TH F wa s adde dove r

3 hour s unde r

nitrogen . Th e reactio n mixtur e wa s stirre dovemigh t a t roo m temperatur e unde r

nitrogen . Wate r

wa s adde dcarefull y t o destro y th e exces s NaH . Th e TH F wa s evaporate din vacuo an dth e remainin g aqueou s layer wa s extracte dwit

h EtOA c ( 3 X 2 0 mL ) t o remov e th e unreacte dstartin g material an dth e organi c impurities . Then , th e aqueou s laye r

wa s acidifie dwit

h 6 N HC l t o p H = 1 . Th e acidifie daqueou s laye r wa s extracte dwit

h CH2CI 2 ( 3 X 5 0 mL) . Th e combine dCH2CI 2 layer s were drie d 12 8ove r

MgS0 4 an devaporate din vacuo. Recrystallizatio n fro mEtO H gav e 2.4 2 g (5 7 % ) of aproduc t a s aligh t yello w soli dwit

h m p 160-16 5 °C. I

R(deposi t

fro mCH2CI 2 o n a NaC l plate) : 340 0 (O-H) ; 173 3 (C=0) ; 118 5 an d103 2 (C-O ) cm' . ' H NM R(CDCI3) : 8 4.5 1 (s , 2H) ; 5.9 2 (s , 2H) ; 6.3 2 (dd , 7 = 2. 6 an d 8. 5 Hz , IH) ; 6.5 4 (d , 7 = 2. 5 Hz , IH) ; 6.6 9 (d , 7 = 8. 5 Hz , IH) . Anal . Calcd . fo r CgHgOs : C , 55.11 ; H , 4.11 . Found : C , 55.22 ; H , 4.20 . 3.3.36 . Attempte dSynthesi s of

l-(3',4'-Methylenedioxy)phenoxy-2-decanon e (119 ) from(3,4-Methylenedioxy)phenoxyaceti c Aci d(118 )

Givin g th e Ester

12 0 Int o a100-mL , three-necked , round-bottome dflask were adde d(3,4

- methylenedioxy)phenoxyaceti c aci d(118 ) (0.3 0 g , 1.5 3 mmol ) an ddr y benzen e (3 0 mL) . Oxaly l chlorid e (1.1 7 g , 9.1 8 mmol ) wa s adde dunde r nitroge n an dth e reactio n mixture wa s refluxe dfor

2 hours . Th e benzen e wa s evaporate din vacuo an dth e residu e wa s drie dunde r

vacuu mfo

r 2 hours . Fe(acac) 3 (0.0 2 g , 0.0 5 mmol ) an ddr y TH F (5 0 mL ) were adde dt o th e crud e (3,4-methylenedioxy)phenoxyaceti c aci dchlorid e unde r nitrogen . Then , asolutio n of CgHnMgB r

(1.5 3 mmol ) i

n TH F wa s adde ddropwis e wit h stirrin g ove r

3 0 minute s a

t roo mtemperatur e unde r

nitrogen . Afte

r completio n o

f addition , th e reactio n mixtur e wa s stirre dfor additional 1 0 minute s unde r nitroge n and the n 10 % aqueou s HC l solutio n (2 0 mL ) wa s adde dt o quenc h th e reaction . Th e reactio n mixtur e wa s extracte dwit h CH2CI 2 ( 3 X 5 0 mL ) an dth e combine dCH2CI 2 layer s were washe dwit

h saturate dNaHC0 3 (5 0 mL ) an dwate r (5 0 mL) , drie dove r

MgS04 , an d evaporate din vacuo. Column chromatograph y on silic agel wit h EtOAc-hexane s (1:3 ) 129a s eluen t

an dthe n recrystallizatio n fromhexane s gav e 0.0 2 g (4% ) o f este r 12 0 a s awhit

e solid . IR(deposi t

fromCH2CI

2 solutio n o

n aNaC l plate) : 176 3 (C=0) : 118 1 an d1040 (C-O)cm"' . 'HNMR(CDCl3): 8 0.88(t,7=6.4Hz , 3H) : 1.09-1.80(m . 12H) : 4.1 9 (i , 7

= 6. 7 Hz , 2H) ; 4.5 5 (s , 2H) ; 5.9 2 (s , 2H) ; 6.3 1 (dd,7 = 2. 6 an d 8. 5 Hz , IH) ; 6.5 4 (d . 7 = 2. 6 Hz , IH) ; 6.7 0 (d , 7 = 8. 5 H z IH) . 3.3.37 . Preparatio n o

f (3,4-Methylenedioxy)phenoxyacetaldehyd e

Diethy l Aceta

l (123 ) Int o a250-mL , three-necked , round-bottome d flask were adde dSesamo l (2.0 0 g . 14. 5 mmol) , CS2CO

3 (11.7 9 g , 36. 2 mmol) , an ddr y CH3C N (5 0 mL ) unde r

nitrogen . Th e reactio n mixmr e wa s refluxe dfo r 3 hour s an dthen asolutio n o f bromoacetaldehyd e diethy l acetal (3.1 4 g , 15.9 3 mmol ) i n 2 5 m L of dr y CH3C N wa s adde dover

2 hours . Th e reactio n mixmr e wa s refluxe dfo r 1 da y unde r nitrogen , coole dt o roo mtemperature , an dfiltered. Th e filtere dsoli dwa s washe dwit h CH2CI 2 severa l times . Th e combine d filtrate an dwashing s wer e evaporate din vacuo an dth e residu e wa s dissolve di n 5 0 m L o f CH2CI2 . Th e CH2CI

2 laye r wa s washe dwit

h water (2 5 mL) , drie dove r

MgS04 , an d evaporate din vacuo. Column chromatograph y on silic agel wit h EtOAc-hexane s (1:10 ) a s eluen t gav e 3.4 2 g (93% ) of

aligh t yello w viscou s liquid . I R(deposi t

fromCH2CI

2 o n aNaClplate) : 124 3 an d113 2 (C-O ) cm"' . ' H NM R(CDCI3) : 8 1.2 4 (t,7 = 7. 0 Hz , 6H) ; 3.54-3.8 3 (m , 4H) ; 3.9 3 (d , 7 = 5. 2 Hz , 2H) ; 4.8 0 (t , 7 = 5. 2 Hz , IH) ; 5.9 0 (s , 2H) ; 6.3 3 (dd , 7 = 2. 6 an d8. 5 Hz , IH) ; 6.5 2 (d , 7 = 2. 5 Hz , IH) ; 6.6 9 (d , 7 = 8. 5 Hz , IH) . Anal . Calcd . for CnHigO s X 0. 1 H2O : C , 60.97 ; H , 7.16 . Found : C , 60.76 ; H , 7.30 . 13 03.3.38 . Attempte dSynthesi s o f (3,4-Methylenedioxy)phenoxyacetaldehyd e ( 124 ) from(3,4-Methylenedioxy)phenoxyacetaldehyd e

Diethy l Aceta

l (123 ) T o asolutio n of

(3,4-methylenedioxy)phenoxyacetaldehyd e diethy l aceta l (0.5 5 g . 2.1 6 mmol ) in 1 0 m

L of CHCI 3 wa s adde d50 % aqueou s CF3CO2 H ( 5 mL ) andth e reactio n nuxmr e wa s refluxe dfo r 2 hours . Th e reactio n mixture wa s extracte dwit h CH2CI 2 ( 3 X 5 0 mL) . Th e combine dorgani c layer s wer e washe dwit

h brin e (2 5 mL) . drie dove r MgS04 , an devaporate din vacuo t o giv e a n aldehyd e produc t

12 4 togethe r wit h unreacte dstartin g material 123 . Th e rati o o f 12 3 t o 12 4 wa s determine db y compariso n of

th e integratio n area s fo

r th e -CH2

- o

f th e methylenediox y grou p fo r 12 3 an d124 . ' H NM R(CDCI3 ) fo r 124 : 8 4.4 9 (d , 7 = 0. 8 Hz , 2H) ; 5.9 3 (s . 2H) : 6.27 (dd , 7

= 2. 6 an d8. 5 Hz , IH) ; 6.5 2 (d , 7 = 2. 5 Hz , IH) ; 6.7 0 (d , 7 = 8. 4 Hz , IH) . Th e rati o o f 123:12 4 = 82:18 . 3.3.39 . Attempte dSynthesi s o f (3,4-Methylenedioxy)phenoxyacetaldehyd e ( 124 ) from(3,4-Methylenedioxy)phenoxyacetaldehyd e Diethy l Aceta

l (123 ) Givin g th e Benzofura

n Derivativ e 125 Int o l(X)-mL , three-necked , round-bottome dwere adde d (3,4-methylene

dioxy)phenoxyacetaldehyd e diethy l acetal (1.0 0 g , 3.9 3 mmol) , sodiu miodid e (0.8 8 g , 5.9 0 mmol) , an ddr

y CH3C N (3 0 mL) . Boro n trifluorid e etherat e (0.8 4 g , 5.9 0 mmol ) wa s adde dan dth e reactio n mixtur e wa s refluxe dfo r 2 hour s unde r

nitrogen . Th e reactio n mixtur e wa s coole dt o roo mtemperatur e an dsaturate d aqueou s NaHC0 3 wa s adde dt o quenc h th e reaction . Th e reactio n mixtur e wa s extracte dwit h CH2CI 2 ( 3 X 5 0 13 1mL ) an dth e combine dorgani c layer s were washe dwit h 1 0 % aqueou s Na2S20 3 (2 5 mL ) an dbrin e (2 5 mL) . Th e organi c laye r wa s drie dover

MgS0 4 an devaporate din vacuo. Column chromatograph y on silic agel wit h EtOAc-hexane s (1:20 ) a s eluen t gav e 0.3 2 g (50% ) o f awhit e soli dwit

h m p 70-7 1 °C. I

R(deposi t fro mCH2CI 2 o n aNaC l plate) : 112 1 an d102 6 (C-O ) cm"' . ' H NMR(CDCI3) : 8 5.9 8 (s , 2H) ; 6.6 4 (dd . 7 = 0. 8 and2. 1 Hz , IH) ; 6.9 5 (s . IH) ; 6.9 9 (s . IH) ; 7.5 2 (d , 7 = 2. 1 Hz , IH) . Anal . Calcd . fo r C9H6O3 : C , 66.67 ; H , 3.73 . Found : C , 66.82 : H , 3.96 .

13 23.4 . Reference s

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20 . H . Suginom e an dS . Yamada , 7 Org Chem., 1985 , 50, 2489 . 21 . M . Matsumot o an dH . Kobayashi , Heterocycles, 1986 , 24, 2443 . 22 . J . J . Sosnowski , E . B . Danaher , an dR . K . Murray , Jr. , 7 Org Chem.. 1985 , 50. 2759 . 23 . S . S . C . Koc h an dA . R . Chamberiin , Synth. Commun.. 1989 . 19, 829 . 24 . S.-I . Nakatsuka , K . Ueda , O . Asano , an dT . Goto , Heterocycles, 1987 , 26. 65 . 25 . B . M . Ki man dK . B . Sharpless , Tetrahedron Lett., 1989 , 30, 655 . 26 . D . A . Tomali aan dJ . C . Falk , 7 Heterocycl Chem.. 1972 , 9 , 891 . 27 . M . S . Berridge , M . P . Franceschini , E . Rosenfeld , an dT . J . Tewson , 7 . Org. Chem., 1990, 55, 1211 . 28 . C . Cardellicchio , V . Fiandanese , G . Marchese , andL . Ronzini , Tetrahedron Lett., 1987 , 28, 2053 . 29 . V . Fiandanese , G . Marchese , V . Martina , an dL . Ronzini , Tetrahedron Lett.. 1984 . 25, 4805 . 30 . A . K . Mandal , P . Y . Shrotri , an dA . D . Ghogare , Synthesis, 1986 , 221 . 31 . R . A . Ellison , E . R . Lukenbach , an dC.-W . Chiu , Tetrahedron Lett., 1975 , 499 . 32 . S . E . Sen , S . L . Roach , J . K . Boggs , G . J . Ewing , an dJ . Magrath , 7 Org. Chem., 1997 , 62, 6684 . 33 . R . Chinchilla , C . Najera , an dP . Sanchez-Agullo , Tetrahedron: Asymmetry 1994 , 5 , 1393 . 34 . P . Hamley , A . B . Holmes , D . R . Marshall , an dJ . M . MacKinnon , 7 . Chem. Soc. Perkin Trans. 1, 1991, 1793 .

13 4