SYNTHESIS OF NEW SEPARATING AGENTS 

FOR NUCLEAR MATERIALS 

by 

JAEWOOK NAM, B.S. 

A DISSERTATION 

IN 

CHEMISTRY 

Submitted to the Graduate Faculty 

of Texas Tech University in 

Partial Fulfillment of 

the Requirements for 

the Degree of 

DOCTOR OF PHILOSOPHY 

Approved 

Accepted 

August, 1998 
ACKNOWLEDGMENTS 

First, I wish to express my deepest appreciation to Dr. Richard A. Bartsch, my 

supervising professor, for his guidance, encouragement, and professional advice 

throughout my graduate program at Texas Tech University. I would also like to thank to 

my doctoral committee members, Dr. David M. Bimey, Dr. Allan D. Headley, and Dr. 

John N. Marx, for their encouragement and advice. I wish to express my thanks to past 

and present members of the Bartsch Research Group, for their advice and friendship. 

Secondly, I am pleased to acknowledge support by the Nuclear Materials 

Technology Division of Los Alamos National Laboratory for the research on bifunctional 

anion-exchange resins for plutonium(rV) sorption and by the Chemistry Division of 

Argonne National Laboratory for the research on new cyclic polyether compounds for 

cesium ion extraction. 

Finally, I would like to give special thanks to my wife Seulhee for her love and 

support. Without her understanding and devotion, my study would not have been 

completed. I also wish to express special thanks to my aunt and uncle, Dr. Hee Sook 

Kim Chong and Dr. Key Ray Chong, for their love and support. I could not finish my 

acknowledgment without an expression of gratitude to my mother for her love and 

support. 
TABLE OF CONTENTS 

ACKNOWLEDGMENTS ii 

ABSTRACT xiv 

LIST OF TABLES xv 

LISTOFnOURES xvii 

LIST OF SCHEMES xviii 

CHAPTER 

1. INTRODUCTION 1 

1.1. Background for Nuclear Waste Management 1 

1.2. Plutonium Separation by Ion-Exchange Resins 3 

1.3. Cesium Separation by Cyclic Polyether Extractants 4 

1.4. Statement of Research Goals 6 

1.5. References 8 

2. SYNTHESIS OF POLYMER-BOUND SEPARATING 

AGENTS 10 

2.1. Results and Discussion 10 

2.1.1. Synthesis of Bifunctional Anion-Exchange Resins 10 

2.1.1.1. Trimethylammonium-Containing Bifunctional 

Anion-Exchange Resins 13 

2.1.1.2. Pyridinium-Containing Bifunctional 

Anion-Exchange Resins 16 

2.1.1.3. Trimethylphosphonium-Containing Bifunctional 

Anion-Exchange Resins 21 

2.1.1.4. N-Methylpicolinium-Containing Bifunctional 

Anion-Exchange Resins 23 

iii 
2.1.2. Evaluation of Bifunctional Anion-Exchange Resins 25 

2.1.3. Synthesis of Water-Soluble Poly(vinylpyridines) 30 

2.1.3.1. Hydroxyethyl-Substituted Water-Soluble 

Polymers 31 

2.1.3.2. 3-(Trimethylammonio)propyl-Substituted 

Water-Soluble Polymers 33 

2.2. Chapter Summary 35 

2.3. Experimental Procedures 36 

2.3.1. Sources of Reagents 36 

2.3.2. Purification of Reagents 36 

2.3.3. General 36 

2.3.4. General Procedure for the Synthesis of 

(co-Bromoalkyl)trimethylammonium 

Bromides 8-13 37 

2.3.4.1. (3-Bromopropyl)trimethylammonium Bromide (8) 37 

2.3.4.2. (4-Bromobutyl)trimethylammonium Bromide (9) 38 

2.3.4.3. (5-Bromopentyl)trimethylammonium Bromide (10) 38 

2.3.4.4. (6-Bromohexyl)trimethylammonium Bromide (11) 38 

2.3.4.5. (7-Bromoheptyl)trimethylammonium Bromide (12) 38 

2.3.4.6. (8-Bromooctyl)trimethylammonium Bromide (13) 39 

2.3.5. Preparation of [2-(2'-Bromoethoxy)ethyl]-

trimethylammonium Bromide (21) 39 

2.3.6. General Procedure for the Synthesis of 

Poly[N-(co-Trimethylammonioalkyl) 4-Vinylpyridinium 

Dibromides] 14-19 40 

2.3.6.1. Poly[N-(2-Trimethylammonioethyl) 

4-Vinylpyridinium Dibromide] (14) 40 

iv 
2.3.6.2. Poly[N-(3-Trimethylammoniopropyl) 

4-Vinylpyridinium Dibromide] (15) 40 

2.3.6.3. Poly[N-(4-Trimethylammoniobutyl) 

4-Vinylpyridinium Dibromide] (16) 40 

2.3.6.4. Poly[N-(5-Trimethylammoniopentyl) 

4-Vinylpyridinium Dibromide] (17) 41 

2.3.6.5. Poly[N-(6-Trimethylammoniohexyl) 

4-Vinylpyridinium Dibromide] (18) 41 

2.3.6.6. Poly[N-(8-Trimethylammoniooctyl) 

4-Vinylpyridinium Dibromide] (19) 41 

2.3.7- Preparation of Poly[2-(N-2'-Trimethylammonioethoxy)ethyl 

4-Vinylpyridinium Dibromide] (22) 41 

2.3.8. Preparation of N-(2-Bromoethyl)pyridinium 

Bromide (23) 42 

2.3.9. General Procedure for the Synthesis of 

N-(o>Bromoalkyl)pyridinium Bromides 25-28 42 

2.3.9.1. N-(3-Bromopropyl)pyridinium Bromide (25) 43 

2.3.9.2. N-(4-Bromobutyl)pyridinium Bromide (26) 43 

2.3.9.3. N-(5-Bromopentyl)pyridinium Bromide (27) 44 

2.3.9.4. N-(6-Bromohexyl)pyridinium Bromide (28) 44 

2.3.10. Preparation of N-[2-(2'-Bromoethoxy)ethyl]pyridinium 

Bromide (29) 44 

2.3.11. General Procedure for the Synthesis of 

Poly[N-co-(N'-Pyridinio)alkyl 4-Vinylpyridinium 

Dibromides] 30-34 45 

2.3.11.1. Poly[N-2-(N'-Pyridinio)ethyl 4-Vinylpyridinium 

Dibromide] (30) 45 

2.3.11.2. Poly[N-3-(N'-Pyridinio)propyl 4-Vinylpyridinium 

Dibromide] (31) 46 
2.3.11.3. Poly[N-4-(^N'-Pyridinio)butyl 4-Vinylpyridinium 

Dibromide] (32) 46 

2.3.11.4. Poly[N-5-(N'-Pyridinio)pentyl 4-Vinylpyridinium 

Dibromide] (33) 46 

2.3.11.5. Poly[N-6-(N'-Pyridinio)hexyl 4-Vinylpyridinium 

Dibromide] (34) 46 

2.3.12. General Procedure for the Synthesis of 

(O-Bromoalkyltrimethylphosphonium 

Bromides 35-39 47 

2.3.12.1. (2-Bromoethyl)trimethylphosphonium 

Bromide (35) 47 

2.3.12.2. (3-Bromopropyl)trimethylphosphonium 

Bromide (36) 47 

2.3.12.3. (4-Bromobutyl)trimethylphosphonium 

Bromide (37) 47 

2.3.12.4. (5-Bromopentyl)trimethylphosphonium 

Bromide (38) 48 

2.3.12.5. (6-Bromohexyl)trimethylphosphonium 

Bromide (39) 48 

2.3.13. General Procedure for the Synthesis of 

Poly[N-(co-Trimethylphosphonioalkyl) 

4-Vinylpyridinium Dibromides] 40-43 48 

2.3.13.1. Poly[N-(^2-Trimethylphosphonioethyl) 

4-Vinylpyridinium Dibromide] (40) 49 

2.3.13.2. Poly[N-(3-Trimethylphosphoniopropyl) 

4-Vinylpyridinium Dibromide] (41) 49 

2.3.13.3. Poiy[N-(4-Trimethylphosphoniobutyl) 

4-Vinylpyridinium Dibromide] (42) 49 

2.3.13.4. Poly[N-(5-Trimethylphosphoniopentyl) 

4-Vinylpyridinium Dibromide] (43) 49 

VI 
2.3.14. General Procedure for the Synthesis of 

Poly[N-(Picolyl) 4-Vinylpyridinium 

Chlorides] 47-49 50 

2.3.14.1. Poly[N-(2-Picolyl) 4-Vinylpyridinium 

Chloride] (47) 50 

2.3.14.2. Poly[N-(3-Picolyl) 4-Vinylpyridinium 

Chloride] (48) 50 

2.3.14.3. Poly[N-(4-Picolyl) 4-Vinylpyridinium 

Chloride] (49) 51 

2.3.15. Preparation of Poly(N-Methyl 4-Vinylpyridinium 

Iodide) (50) 51 

2.3.16. General Procedure for the Synthesis of 

Poly[N-(N'-Methylpicolinio) 4-Vinylpyridinium 

Diiodides] 51-53 52 

2.3.16.1. Poly[N-(2-N'-Methylpicolinio) 

4-Vinylpyridinium Diiodide] (51) 52 

2.3.16.2. Poly[N-(3-N'-Methylpicolinio) 

4-Vinylpyridinium Diiodide] (52) 52 

2.3.16.3. Poly[N-(4-N'-Methylpicolinio) 

4-Vinylpyridinium Diiodide] (53) 53 

2.3.17. Preparation of Partially Substituted 

Poly[N-(2'-Hydroxy)ethyl 4-Vinylpyridine] 55 53 

2.3.18. Preparation of Partially Substituted 

Poly[N-(2'-Hydroxy)ethyl 2-Vinylpyridine] 59 54 

2.3.19. Preparation of Partially Substituted 

Poly[N-(3-Trimethylammonio)propyl 

4-Vinylpyridinium Dibromide] 63 54 

2.3.20. Preparation of Partially Substituted 

Poly[N-(3-Trimethylammonio)propyl 

2-Vinylpyridinium Dibromide] 65 55 

2.4. References 56 

Vll 
3. SYNTHESIS OF CYCLIC POLYETHER EXTRACT ANTS 58 

3.1. Results and Discussion 58 

3.1.1. Synthesis of Carbon Atom-Linked Side Arm Cyclic 

Polyethers 58 

3.1.1.1. Preparation of Bis(l-hydroxyalkyl)-

Substituted Crown Ethers 59 

3.1.1.2. Preparation of Bis(2-hydroxyalkyl)-

Substituted Crown Ethers 63 

3.1.1.2.1. By Isomerization 64 

3.1.1.2.2. By Oxymercuration-Demercuration 66 

3.1.1.2.3. By Hydroboration-Oxidation 70 

3.1.2. Synthesis of Oxygen Atom-Linked Side Arm Cyclic 

Polyethers 71 

3.1.2.1. Elaboration of the Side Arm in a Catechol 

Derivative and Subsequent Cyclization 72 

3.1.2.2. Cyclization of a Protected Catechol and 

Subsequent Deprotection and Elaboration 

of the Side Arm 74 

3.1.2.3. Modification of Dibenzo-18-crown-6 and 

Subsequent Elaboration of the Side Arms 76 

3.1.2.3.1. Synthesis of Dihydroxy-Substituted 

Dibenzo-18-crown-6 76 

3.1.2.3.2. Synthesis of Di[(2-hydroxy)alkoxybenzo]-

18-crown-6 Involving Alkylation of 

Di(hydroxybenzo)-l 8-crown-6 79 

3.1.2.3.2.1. Reaction with Epoxides 80 

3.1.2.3.2.2. Reaction with Cyclic Sulfate Ester 83 

3.1.2.3.2.3. Reaction with Benzyl Bromide 87 

Vlll 
3.1.2.3.3. Synthesis of Di[(2-hydroxyalkoxy)benzo]-

18-crown-6 Involving a Grignard Reaction 88 

3.1.2.3.3.1. Grignard Reaction of an Acid Chloride 

Followed by Reduction 88 

3.1.2.3.3.2. Grignard Reaction of an Aldehyde 91 

3.2. Chapter Summary 95 

3.3. Experimental Procedures 96 

3.3.1. Sources of Reagents 96 

3.3.2. Purification of Reagents 96 

3.3.3. General 97 

3.3.4. General Procedure for the Synthesis of 

Dibenzo-18-crown-6 Diketones 66-69 97 

3.3.4.1. 4,4'(5')-Di[(butanoyl)benzo]-18-crown-6 (66) 98 

3.3.4.2. 4,4'(5')-Di[(hexanoyl)benzo]-l8-crown-6 (67) 98 

3.3.4.3. 4,4'(5')-Di[(decanoyl)benzo]-l8-crown-6 (68) 98 

3.3.4.4. 4,4'(5')-Di[(2-ethylhexanoyl)benzo]-18-crown-6 

(69) 99 

3.3.5. General Procedure for the Synthesis of 

Dibenzo-18-crown-6 Diols 70-72 99 

3.3.5.1. 4,4'(5')-Di[(l-hydroxybutyl)benzo]-18-crown-6 

(70) 99 

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) 100 

3.3.6. Preparation of 4,4'(5')-Di[(2-ethyl-l-hydroxyhexyl)benzo]-

18-crown-6(73) 100 
3.3.7. Preparation of 4,4'(5')-Di[(2-ethyl-l-

(2-hydroxyethoxy)hexyl)benzo]-l 8-crown-6 (74) 101 

3.3.8. Preparation of 4,4'(5>Di[(2-ethyl-l-(5-hydroxy3-oxapentoxy)hexyl)benzo]-18-crown-6 (75) 102 

3.3.9. Preparation of 4,4'(5')-Di[(2-ethylhexanoyl)benzo]-

21-crown-7(77) 102 

3.3.10. Preparation of 4,4'(5')-Di[(2-ethyl-1-hydroxyhexyl)benzo]-

21-crown-7(78) 103 

3.3.11. Preparation of 4,4'(5')-Di[(2-ethyl-l-(5-hydroxy3-oxapentoxy)hexyl)benzo]-21-crown-7 (79) 104 

3.3.12. Attempted Synthesis of 4,4'(5')-Di[(2-ethyl-2-

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

Di[(2-ethyl-l-hydroxyhexyl)benzo]-18-crown-6 (73) 

By Isomerization 105 

3.3.12.1. Isomerization with Sulfuric Acid 105 

3.3.12.2. Isomerization with Hydrochloric Acid 106 

3.3.13. Attempted Synthesis of Alkene-Substituted 

Dibenzo-18-crown-6 83 from Dibenzo-18-crown-6 

Diol 73 Giving a Mixture of Six Isomers 83-88 101 

3.3.14. Preparation of 4,4'(5')-Di[(l-decenyl)benzo]-

l 8-crown-6 (90) 107 

3.3.15. Attempted Synthesis of 4,4'(5')-Di[(2-ethyl-2-

hydroxyhexyl)benzo]-18-crown-6 (82) from the 

Mixture of Six Alkene-Substituted Isomers 83-88 

Giving a Mixture of Three Isomers 73, 82 and 89 108 

3.3.16. Attempted Synthesis of 4,4'(5')-Di[(2-hydroxydecyl)benzo]-

18-crown-6 (91) from 4,4'(5')-Di[(l-decenyl)benzo]-

18-crown-6 (90) Giving a Mixture of the Three Isomers 

72, 91 and 92 109 

3.3.16.1. By Hydroboration-Oxidation 109 

3.3.16.2. By Oxymercuration-Demercuration 110 
3.3.17. Preparation of l-(2'-Hydroxy)hexoxy-3,4-

methylenedioxybenzene (93) Ill 

3.3.17.1. With Cesium Carbonate Ill 

3.3.17.2. With Sodium Hydroxide Ill 

3.3.18. Preparation of 3,4-Dihydroxy-l-

(2'-hydroxy)hexoxybenzene (94) 112 

3.3.19. Attempted Synthesis of 4,4'(5')-

Di[(2-hydroxyhexoxy)benzo]-18-crown-6 (95) from 

3,4-Dihydroxy-1 -(2'-hydroxy)hexoxybenzene (94) 113 

3.3.20. Attempted Synthesis of 1-Benzyloxy-3,4-

methylenedioxybenzene (96) from Sesamol 114 

3.3.20.1. Method A 114 

3.3.20.2. Method B 115 

3.3.21. Attempted Synthesis of l-Benzyloxy-3,4-

dihydroxybenzene (97) from l-Benzyloxy-3,4-

methylenedioxybenzene (96) 115 

3.3.22. Preparation of 4,4'(5')-Di(nitrobenzo)-18-crown-6 

(98) 116 

3.3.23. Preparation of 4,4'(5')-Di(aminobenzo)-18-crown-6 

(99) 117 

3.3.24. Preparation of 4,4'(5')-Di(hydroxybenzo)-18-crown-6 (101) 

from 4,4'(5')-Di(aminobenzo)-18-crown-6 (99) 117 

3.3.24.1. 4,4'(5')-Di[(diazonium tetrafluoroborato)benzo]-

18-crown-6(100) 117 

3.3.24.2. 4,4'(5')-Di(hydroxybenzo)-18-crown-6 (101) 118 

3.3.25. Preparation of 4,4'(5')-Di(acetylbenzo)-

18-crown-6(102) 119 

3.3.26. Preparation of 4,4'(5')-Di(acetatobenzo)-

18-crown-6 (103) 119 

XI 
3.3.27. Preparation of 4,4'(5')-Di(hydroxybenzo)-

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

18-crown-6(103) 120 

3.3.28. Preparation of l-(2'-Hydroxyoctoxy)-3,4-

methylenedioxybenzene (104) 121 

3.3.28.1. With Cesium Carbonate 121 

3.3.28.2. With Sodium Hydroxide 122 

3.3.29. Attempted Synthesis of 4,4'(5')-

Di[(2-hydroxy)octoxybenzo]-18-crown-6 (105) 

from 4,4'(5>Di(hydroxybenzo)-18-crown-6 (101) 122 

3.3.30. Preparation of 4-Octyl-2,2-dioxo-1,3,2-

dioxathiolane (107) 123 

3.3.30.1. 4-Octyl-2-oxo-l,3,2-dioxathiolane (106) 123 

3.3.30.2. 4-Octyl-2.2-dioxo-l,3,2-dioxathiolane (107) 124 

3.3.31. Attempted Synthesis of l-(2'-Hydroxydecyloxy)-3,4-

methylenedioxybenzene (108) from Sesamol Giving a 

Mixture of Two Isomers 108 and 109 124 

3.3.31.1.1 -(2'-Hydroxydecyloxy)-3,4-

methylenedioxybenzene (108) 125 

3.3.31.2. l-[l'-(Hydroxymethyl)nonyloxy]-3,4-

methylenedioxybenzene (109) 125 

3.3.32. Preparation of 4,4'(5')-Di[(2-hydroxydecyloxy)benzo]-

18-crown-6(110) 126 

3.3.33. Preparation of (2-Hydroxydecyloxy)benzene (112) 127 

3.3.34. Preparation of 4,4'(5')-Di(benzyloxybenzo)-

18-crown-6(115) 127 

3.3.35. Preparation of (3,4-Methylenedioxy)phenoxyacetic Acid 

(118) 128 

Xll 
3.3.36. Attempted Synthesis of 

1 -(3',4'-Methylenedioxy)phenoxy-2-decanone (118) 

from (3,4-Methylenedioxy)phenoxyacetic Acid (119) 

Giving the Ester 120 129 

3.3.37. Preparation of (3.4-Methylenedioxy)phenoxyacetaldehyde 

Diethyl Acetal (123) 130 

3.3.38. Attempted Synthesis of 

(3,4-Methylenedioxy)phenoxyacetaldehyde (124) 

from (3,4-Methylenedioxy)phenoxyacetaldehyde 

Diethyl Acetal (123) 131 

3.3.39. Attempted Synthesis of 

(3,4-Methylenedioxy)phenoxyacetaldehyde (124) 

from (3,4-Methylenedioxy)phenoxyacetaldehyde 

Diethyl Acetal (123) Giving the 

Benzofuran Derivative 125 131 

3.4. References 133 

Xlll 
ABSTRACT 

Synthetic methods for the preparation of complexing agents for the separation of 

radionuclide materials are described in this dissertation. Several series of new 

bifunctional anion-exchange resins were prepared by reaction of ReillexTM 402 po]y(4-

vinylpyridine) resin with alkylating agents CL>-Br(CH2)nQ^ in Q"^ = trimethylammonio. 

trimethylphosphonio, and pyridinium groups. By variation of the number of methylene 

groups in the spacer, the distance between the two anion-exchange sites was 

systematically varied. The structural variations in these bifunctional anion-exchange 

resins were made to investigate their Pu(IV) sorption behavior from nitric acid media. 

Partial substitution of linear poly(vinylpyridine) with hydrophilic groups provided 

new water-soluble polymers which have potential for use in metal separation using 

ultrafiltration membranes. 

For the cesium extraction from acidic nitrate media, several series of macrocyclic 

polyether compounds which have oxygenated, aliphatic side arms were prepared. 

Acylation of dibenzo-18-crown-6 (or dibenzo-21-crown-7) and subsequent reduction 

provided new carbon atom-linked side armed cyclic polyether extractants. Several 

approaches to the synthesis of oxygen atom-linked side armed cyclic polyether 

extractants were explored with the model compound Sesamol. Although results of the 

model studies were promising, all attempts to extend the methods to the preparation of 

oxygen atom-linked side armed crown ethers were unsuccessful. 

XIV 
LIST OF TABLES 

1.1. Components of High-Level Nuclear Waste. 

- » - ) 

-s 

2.1. Preparation of N-(a)-Bromoalkyl)pyridinium Bromides 25-28 

from Varying Amounts of the 1 ,Ci>-Dibromoalkanes 19 

Measured K<i (mL/g) Values for Pu(IV) Sorption from 

Nitric Acid by ReillexTM HPQ and TrimethylammoniumContaining Bifunctional Anion-Exchange Resins 26 

2.3. Measured Kd (mUg) Values for Pu(IV) Sorption 

from Nitric Acid by Trimethylpyridinium-Containing 

Bifunctional Anion-Exchange Resins 27 

2.4. Measured IQ (mL/g) Values for Pu(IV) Sorption 

from Nitric Acid by Trimethylphosphonium-Containing 

Bifunctional Anion-Exchange Resins 28 

2.5. Measured K^ (mL/g) Values for Pu(rV) Sorption 

from Nitric Acid by Picolinium- and N-MethylpicoliniumContaining Bifunctional Anion-Exchange Resins 29 

2.6. Synthesis of Partially Substituted Poly(4-vinylpyridines) 54-58 

and Their Water Solubilities 32 

2.7. Synthesis of Partially Substituted Poly(2-vinylpyridines) 59 and 60 

and Their Water Solubilities 33 

2.8. Synthesis of Partially Substituted Poly(4-vinylpyridines) 61-63 

and Their Water Solubilities 34 

2.9. Synthesis of Partially Substituted Poly(2-vinylpyridines) 64 and 65 

and Their Water Solubilities 35 

3.1. Attempted Synthesis of Crown Ether Diol 82 by 

Oxymercuration-Demercuration 68 

3.2. Reactions of Sesamol with Epoxides 80 

3.3. Attempted Reactions of Di(hydroxybenzo)-18-crown-6 (101) 

with Epoxides 82 

XV 
3.4. Reactions of Sesamol with Cyclic Sulfate Ester 107 84 

3.5. Attempted Synthesis of (3,4-Methylenedioxy)phenoxyacetaldehyde 

(124) 94 

XVI 
LIST OF FIGURES 

1.1. Structure of Targeted New Bifunctional Anion-Exchange 

Resins 6 

1.2. Structure of a Targeted New Cyclic Polyether Extractant 7 

2.1. Structure of ReillexTM HPQ Resin 11 

2.2. Structures of the New Types of Anion-Exchange Resins 12 

2.3. Schematic Diagram of an Ultrafiltration Process with 

Macromolecular Complexes for the Separation of Metal Ions 31 

3.1. Possible Reaction Pathways upon Treatment of a Crown Ether 

Alcohol with Acid 64 

3.2. Pathways to the Alkene Isomers 83-88 67 

3.3. Proposed Mechanism for the Formation of Benzofuran Derivative 

125 93 

XVll 
LIST OF SCHEMES 

2.1. Synthesis of (co-Bromoalkyl)trimethylammonium Bromides 8-13 14 

2.2. Synthesis of Tetraalkylammonium-Containing Bifunctional 

Anion-Exchange Resins 14-19 15 

2.3. Synthesis of [2-(2'-Bromoethoxy)ethyl]trimethylammonium 

Bromide (21) 16 

2.4. Synthesis of Anion-Exchange Resin 22 16 

2.5. Synthesis of N-(2-Bromoethyl)pyridinium Bromide (23) 17 

2.6. Reaction of 1,2-Dibromoethane with Pyridine in Benzene 17 

2.7. Preparation of N-(CL)-Bromoalkyl)pyridinium Bromides 25-28 18 

2.8. Synthesis of N-[2-(2'-Bromoethoxy)ethyl]pyridinium 

Bromide (29) 20 

2.9. Synthesis of Pyridinium-Containing Bifunctional 

Anion-Exchange Resins 30-34 21 

2.10. Synthesis of (o>Bromoalkyl)trimethylphosphonium 

Bromides 35-39 22 

2.11. Synthesis of Trimethylphosphonium-Containing Bifunctional 

Anion-Exchange Resins 40-43 22 

2.12. Synthesis of Picolyl Substituted Poly(4-vinylpyridines) 47-49 23 

2.13. Synthesis of Poly(N-Methyl 4-Vinylpyridinium Iodide) (50) 24 

2.14. Synthesis of N-Methylpicolinium-Containing Bifunctional 

Anion-Exchange Resins 51-53 25 

3.1. Synthesis of Dibenzo-18-crown-6 Diketones 66-69 59 

3.2. Synthesis of Dibenzo-18-crown-6 Diols 70-73 60 

3.3. Synthesis of Dibenzo-18-crown-6 Diols 74 and 75 61 

xvni 
3.4. Synthesis of Di[(2-ethyl-l-hydroxyhexyl)benzo]-21-crown-7 (78) 62 

3.5. Synthesis of 4,4'(5')-Di[(2-ethyl-l-(5-hydroxy-3-oxapentoxy)-

hexyl)benzo]-21-crown-7 (79) 63 

3.6. Attempted Synthesis of 4,4'(5')-Di[(2-ethyl-2-hydroxyhexyl)benzo]-

18-crown-6(82) 65 

3.7. Dehydration of Crown Ether Diol 73 66 

3.8. Synthesis of 4,4'(5')-Di[(l-decenyl)benzo]-18-crown-6 (90) 69 

3.9. Attempted Synthesis of 4,4'(5')-Di[(2-hydroxydecyl)benzo]-

18-crown-6 (91) by Oxymercuration-Demercuration 70 

3.10. Attempted Synthesis of 4,4'(5')-Di[(2-hydroxydecyl)benzo]-

18-crown-6 (91) by Hydroboration-Oxidation 71 

3.11. Synthesis of the Protected Catechol Derivative 93 72 

3.12. Synthesis of Catechol Derivative 94 73 

3.13. Attempted Synthesis of 4,4'(5')-Di[(2-hydroxyhexoxy)benzo]-

18-crown-6(95) 74 

3.14. Attempted Synthesis of the Catechol Derivative 97 75 

3.15. Synthesis of 4,4'(5')-Di(hydroxybenzo)-18-crown-6 (101) 77 

3.16. Attempted Synthesis of 4,4'(5')-Di(hydroxybenzo)-

18-crown-6(101) 77 

3.17. Alternative Synthesis of 4,4'(5')-Di(hydroxybenzo)-

18-crown-6(101) 79 

3.18. Synthesis of Cyclic Sulfate Ester 107 83 

3.19. Synthesis of 4,4'(5')-Di[(2-hydroxydecyloxy)benzo]-

18-crown-6(110) 85 

3.20. Synthesis of 2-Hydroxydecyloxybenzene (112) 85 

3.21. Synthesis of 1 -(2'-Hydroxydecyloxy)-3,4-methylenedioxybenzene 

(108) 86 

xix 
3.22. Attempted Synthesis of Crown Ether Diol 110 87 

3.23. Synthesis of Di(benzyloxybenzo)-18-crown-6 (115) 88 

3.24. Strategy for Crown Ether Diol Synthesis Involving a 

Grignard Reaction of an Acid Chloride 89 

3.25. Synthesis of (3,4-Methylenedioxy)phenoxyacetic Acid (118) 90 

3.26. Attempted Synthesis of l-(3',4'-Methylenedioxy)phenoxy-2-

decanone (119) 90 

3.27. Strategy for Crown Ether Diol Synthesis Involving a 

Grignard Reaction of an Aldehyde 91 

3.28. Synthesis of (3,4-Methylenedioxy)phenoxyacetaldehyde 

Diethyl Acetal (123) 92 

3.29. Attempted Synthesis of (3,4-Methylenedioxy)phenoxyacetaldehyde 

(124) 93 

3.30. Attempted Synthesis of (3,4-Methylenedioxy)phenoxyacetaldehyde 

(124) 95 

XX 
CHAPTER 1 

INTRODUCTION 

1.1. Background for Nuclear Waste Management 

Since the U.S. Army Corps of Engineers built the first plutonium reactors and 

processing facilities in 1943 as part of the Manhattan Project, nuclear wastes have been 

accumulating from nuclear power production, national defense activities, and nuclear 

medicine over five decades. Any activity that uses radioactive materials inevitably 

generates nuclear wastes as by-products of their operation. Also, the management of 

nuclear wastes has received much more attention than other types of wastes due to their 

special handling and higher radiotoxicity. 

Currently, a number of facilities within the U. S. Department of Energy (DOE) 

have been involved in the management of nuclear waste. Across the DOE complex, 

underground stroage tanks have been used to capture, process, and store hazardous 

nuclear wastes. The majority of these wastes are stored at five DOE sites: the Hanford 

site in Richland, Washington; the Femald site in Femald, Ohio; the Idaho National 

Engineering Laboratory (INEL) near Idaho Falls, Idaho; the Oak Ridge Reservation in 

Oak Ridge, Tennessee; and the Savannah River site in Savannah River, South Carolina. 

The nuclear waste can be broadly divided into two categories, low-level waste 

(LLW) and high-level waste (HLW). A low-level waste generally has small amounts of 

radioactive material in large volumes of materials. The low-level waste will be 

converted to grout and disposed in shallow land burial sites at controlled locations. A 

high-level waste, on the other hand, has large quantities of radioactive material 
concentrated in a small mass. The radioactive materials found in high-level nuclear 

137, waste are transuranic elements and fission products, primarily Sr and Cs, as shown in 

Table 1.1. This high-level waste will be vitrified into borosilicate glass and removed to a 

deep geologic repository. 

Table 1.1. Components of High-Level Nuclear Waste. 

Element Half-life 

Specific Activity 

(Curies/gram) 

Fission Products 

137 Cs 

129i 

85 Kr 

144 Pr 

no Ag 

90 Sr 

99, Tc 

30 years 

5,900,000 years 

11 years 

17 minutes 

24 seconds 

29 years 

213,000 years 

87 

0.00017 

390 

75,500,000 

4,300,000,000 

140 

0.017 

Transuranics 

243 Am 

242 Cm 

239 Pu 

7,380 years 

163 days 

24,110 years 

0.2 

3,300 

0.6 
The nuclear waste stored in underground storage tank at several DOEs sites 

usually contains large amounts of a low-level radioactive fraction and non-radioactive 

elements mixed with lesser amounts of a high-level radioactive fraction. Therefore, 

pretreatment of high-level waste is performed to minimize the volume of high-level uaste 

because of the high cost of virtrification and geologic disposal. Minimization of the 

high-level waste can be achieved by separating the high-level fractions from the other 

materials and recycling as many of the useful components as possible. A number of 

chemical methods can be utilized for the separation of high-level waste: (1) solvent 

extraction; (2) ion-exchange chromatography; (3) precipitation; (4) dissolution; (5) 

solvent leaching; (6) filtration and membrane processes; and (7) combustion and 

degradation processes." 

1.2. Plutonium Separation bv Ion-Exchange Resins 

Ion-exchange processes have been used for the recovery and purification of 

plutonium from various waste forms. Both cation-exchange and anion-exchange 

systems are employed for the plutonium separation. The cation-exchange process has 

been found to be more useful for the concentration of large volumes of dilute solutions 

when moderate decontamination and low waste losses are desired. The anion-exchange 

process, on the other hand, is easily adapted to concentrated acid and salt solutions and 

allows higher decontamination.^ 

The anion-exchange process is rendered attractive for the recovery and 

purification of plutonium by two factors and a high degree of purification is expected. 

First, plutonium readily forms an anionic hexanitrate complex, Pu(N03)6*^, in nitric acid.^ 
Second, the anionic Pu(IV) nitrate complex is very strongly sorbed on a strong-base 

anion-exchange resins.^ 

An earlier study^ at Los Alamos National Laboratory indicated that macroporous 

LewatitTM MP-500-FK resin showed a dramatic improvement in anion-exchange process 

efficiency compared with the gel-type DowexTM 1 X 4 resin. Also, polyvinylpyridine 

anion-exchange resins were reported to be more resistant to radiation than the 

conventional polystyrene resins.^ In addition, these polyvinylpyridine resins have 

greater stability against attack by nitric acid.^ The basicity of nitrogen in the pyridine 

ring makes polyvinylpyridine highly resistant to electrophilic aromatic substitution. This 

chemical resistance is important factor in many nuclear industry processes. Another 

study revealed that Reillex^^ HPQ anion-exchange resin, which was a copolymer of 1 -

methyl-4-vinylpyridine and divinylbenzene, showed improved sorption kinetics and 

greater stability.^ 

1.3. Cesium Separation bv Cvclic Polyether Extractants 

Solvent extraction is one of the major areas of applications of cyclic polyether 

compounds and an efficient method for the separation of metal ions from an aqueous 

phase into an organic phase.^ Crown ethers and their analogs can serve as extractants 

due to their ability to transfer metal ions between two different liquid phases.'^ 

During the last two decades, much effort has been made toward the development 

of improved solvent extraction systems of Cs for its recovery from nuclear waste 

streams. The removal of this radionuclide, which is a major biological hazard and heat 

producer in waste, would simplify the handling and final disposal of nuclear waste. 

4 
1 1*7 

Also, the recovered Cs can be used for disinfestation and preservation of various 

agricultural products or sterilization of medical supplies.'' 

Due to the low charge density of cesium ion, the energy associated with bond 

formation between large cesium cation and the functional groups of organic extractants is 

insufficient to completely dehydrate such a large cation.'' To compensate, macrocyclic 

polyether compounds are selected as extractants. The energetics of cesium ion 

extraction by cyclic polyether extractants is favorable because littie or no change in the 

conformational energy of the extractant molecule is involved. 

Another problem of cesium extraction from acidic media is the difficulty of 

solubilizing the mineral-acid anions (NOs", CI", SO4 ') in a nonpolar organic phase. A 

number of approaches were made to enhance the transfer such anions into organic phases. 

First, mixed solvent extraction systems'^"*^ with crown ether extractants and organicphase-soluble carboxylic, phosphoric, and sulfonic acid as liquid cation exchangers were 

employed. Second, crown ethers with attached proton-ionizable groups were used as 

extractant in the cesium extraction from acidic media.'^ Although these approaches 

sometimes permit satisfactory cesium ion extraction, they often fail to provide complete 

recovery. 

In another study,'^'^ it was reported that the extraction and recovery of strontium 

from strongly acidic waste streams could be effected by the use of certain cyclic 

polyether extractants in various oxygenated, aliphatic organic phases. 
1.4. Statement of Research Goals 

The separation of radionuclide material from nuclear waste by various synthetic 

separating agents has been studied extensively since the 1940's. The investigations of 

these separating agents have focused mainly upon achieving high stability and high 

selectivity for certain radionuclide materials. 

The first portion of this dissertation deals with the synthesis of new polymerbound separating agents. This includes the syntheses of novel, bifunctional anionexchange resins and of water-soluble polymers. New bifunctional anion-exchange resins 

(Figure 1.1) are designed and synthesized for determination of the influence of variation 

in their structures upon the efficiency and selectivity of plutonium separation from nitric 

acid media. Structural variation within the bifunctional anion-exchange resins will 

include: (1) the identity of the second anion-exchange group; (2) the length of the spacer 

between two anion-exchange sites; and (3) the rigidity of the anion-exchange resin. 

4CH2CH^ 

Figure 1.1. Structure of Targeted New Bifunctional Anion-Exchange Resins. 
Water-solubility of linear polyvinylpyridines will be achieved by introducing a minimum 

level of hydrophilic groups into the polymer. 

The second portion of this dissertation will involve the synthesis of cyclic 

polyether extractants for further investigation of the influence of structural variation upon 

the efficiency and selectivity of cesium ion extraction from acidic nitrate media. 

Structural variation within the cyclic polyethers includes: (i) the identity of pivot atom; 

(ii) the crown ether ring size; and (iii) the length and branching of the side arms. For 

example, preparation of new cyclic polyether extractant shown in Figure 1.2 is proposed 

for study of its efficiency and selectivity in cesium ion extraction. 

HO 

I 

C6H13CHCH2O— 

^O 

^O ^ OH 

,0 0^^rs.^^OCH2CHC6Hi3 

O 

0^0 

Figure 1.2. Stmcture of a Targeted New Cyclic Polyether Extractant. 
1.5. References 

1. G. D. Russ, Jr., Nuclear Waste Disposal: Closing the Circle. Atomic Industrial 

Forum, Inc.. Maryland, 1984. p 11. 

2. J. T. Bell and L. H. Bell, Chemical Pretreatment of Nuclear Waste for Disposal 

Plenum, New York. 1994, p 1. 

3. J. L. Ryan. Chemistry of Plutonium in Anion Exchange Applications. U.S. 

Atomic Energy Commission Report TID-7607. 1961. pp 2-20. 

4. J. L. Ryan and E. J. Wheelwright. Ind. Eng. Chem., 1959, 57. 60. 

5. J. P. Faris and R. F. Buchanan. Some Application of Anion ExchangeSpectrographic Procedures in a Nitric Acid Medium. U. S. Atomic Energ> 

Commission Report TID-7606, 1960, pp 185-194. 

6. S. F. Marsh, Improved Recover, and Purification of Plutonium at Los Alamos 

Using Macroporous Anion Exchange Resin, Los Alamos National Laboratory 

Report LA-10906. May 1987. 

7. S. F. Marsh and K. K. S. Pillay, Effects of Ionizing Radiation on Modem Ion 

Exchange Materials. Los Alamos National Laboratory Report LA-12655-MS, 

October 1993. 

8. S. F. Marsh, Evaluation of a New, Macroporous Polyvinylpyridine Resin for 

Processing Plutonium Using Nitrate Anion Exchange. Los Alamos National 

Laboratory Report LA-11490, April 1989. 

9. H. Nakamura, M. Takagi. and K. Ueno. Anal. Chem., 1980, 52. 1668. 

10. Y. hioue, K. Wada, Y. Liu. M. Ouchi. A. Tai, and T. Hakshi. J. Org. Chem., 

1989, 54, 5268. 

11. W. W. Schulz and L. A. Bray, Sep. Sci. Technol. 1987. 22. 191. 

12. W. F. Kinard and W. J. McDowell, J. Inorg. Nucl Chem.. 1981. 43, 2947. 

13. W. J. McDowell, G. N. Case, and D. W. Aldrup. Sep. Sci. Technol, 1983, 75, 

1483. 

14. W. F. Kinard, W. J. McDowell, and R. R. Shoun, Sep. Sci Technol, 1980, 75, 

1013. 

15. W. J. McDowell. G. N. Case, J. A. McDonough, and R. A. Bartsch, Anal Chem., 

1992.6^.3013. 

8 
16. J. Strzelbicki and R. A. Bartsch, Anal Chem., 1981, 53, 1894. 

17. E. P. Horwitz, M. L. Dietz, and D. E. Fisher, Solvent Extr Ion Exch., 1991. 9. 1 

18. E. P. Horwitz, M. L. Dietz, and D. E. Fisher, Solvent Extr. Ion Exch., 1990, 8, 

557. 

19. E. P. Horwitz, M. L. Dietz, and D. E. Fisher, Solvent Extr. Ion Exch., 1990, 8. 

199. 
CHAPTER 2 

SYNTHESIS OF POLYMER-BOUND 

SEPARATING AGENTS 

2.1. Results and Discussion 

Separation of metal ions with polymer-bound complexing agents can be applied 

in various field of chemistry. Synthetic ion-exchange resins are useful organic 

compounds for the separation of heavy metals' and are rendered insoluble in all solvents 

by presence of 2-12% divinylbenzene as a crosslinking agent in the polymer-forming 

mixture. Crosslinking influences not only the solubility, but also the chemical, thermal, 

and mechanical stability of the polymer. An anion-exchange resin, one type of ionexchange resin, is a polymer that has positively charged sites, such as ammonium or 

phosphonium groups, as integral parts of the polymer matrix and an equivalent number of 

replaceable anions, such as chloride, sulfate, or hydroxide ions. To a lesser extent, 

water-soluble polymeric reagents with strong complexing properties have been 

synthesized and used to separate metal ions in a homogeneous phase. 

In this chapter, the synthesis of a variety of the new bifunctional anion-exchange 

resins will be described. The synthesis of water-soluble, anion-exchange polymers will 

be also described. 

2.1.1. Synthesis of Bifunctional Anion-Exchange Resins 

Since an anion-exchange process is most frequently used to recover plutonium 

from a wide range of impure nuclear materials, a variety of anion-exchange resins have 

10 
been evaluated. Research conducted at Los Alamos National Laboratory"^ reported that 

resin porosity and bead size were the two properties that most influence plutonium 

sorption kinetics. Replacement of the traditional polystyrene gel resin with the 

macroporous resin resulted in a dramatic improvement in process efficiency. Also, 

polyvinylpyridine anion-exchange resins have been reported to have greatly increased 

stability to chemical and radiolytic degradation.^ Recently, the macroporous anionexchange resin Reillex^"^ HPQ was reported to exhibit Pu(IV) sorption kinetics 

comparable or superior to that of conventional polystyrene resin. This resin also had 

greater stability to chemical and radiolytic degradation. Reillex HPQ is an anionexchange resin based on a partially methylated copolymer of 4-vinylpyridine and 

divinylbenzene as shown in Figure 2.1. 

f CHsCHim eCH2CH-)n eCHsCH^p eCH2CH^ 

Q 

-e CHCHr^ 

TM Figure 2.1. Structure of Reillex'"' HPQ Resin. 

Although the anion-exchange process with Reillex HPQ resin was improved, 

its Pu(IV) sorption kinetics were still slow compared to the related solvent extraction 

system. This slower exchange process might be due to the need of the mono-anionic 

Pu(rV) nitrate complex to locate a second site where it can absorb another nitrate anion. 

11 
Therefore, it was postulated that even better sorption of the anionic Pu(rV) nitrate 

complex might be obtained by introducing more ionic groups into the repeat unit in the 

anion-exchange resin. On the basis of this proposal, the synthesis of a variety of new 

types of anion-exchange resins, which have two ion-exchange sites per repeat unit, was 

envisioned. 

In this dissertation research, the syntheses of new types of bifunctional anionexchange resins (Figure 2.2) are explored. These resins consist of poly(4-vinylpyridine) 

resin that is modified by attaching a second anion-exchange group to the pyridine 

nitrogen of the base resin via an alkylene spacer. The second anion-exchange site 

includes trimethylammonium, pyridinium, trimethylphosphonium, and N-methylpicolinium groups. The new bifunctional anion-exchange resins have been evaluated at 

Los Alamos National Laboratory to determine the effect of structural variation of the 

anion-exchange resins upon the sorption of the anionic Pu(rV) nitrate complex.^ 

-fCH,—CH-b 

N^ 2X-

(CH2)^Y 

CH,—CH2XI 

CH2-

/ \ 

NI 

CH3 

•CH2—CH4J^ 

2XI 

CH2-

CHi 

-CH2—CH2XN 

I 

CH2 ' N-CH3 

X = CI, Br, I 

Y= — N^CH3)3, —P*(CH3)3, —N J 

Figure 2.2. Structures of the New Types of Anion-Exchange Resins. 

12 
For the synthesis of new types of anion-exchange resins, Reillex 402 polymer, 

a commercially available poly(4-vinylpyridine) crosslinked with 2% of 1,4-divinylbenzene was used. This approach has the advantage that the polymer backbone is 

already formed. A potential route for the synthesis of such anion-exchange resins is the 

preparation of appropriate ammonium, phosphonium, or pyridinium salts for use as 

alkylating agents followed by their coupling with poly(4-vinylpyridine). 

2.1.1.1. Trimethylammonium-Containing Bifunctional 

Anion-Exchange Resins 

Two-step processes accomplished the synthesis of trimethylammoniumcontaining bifunctional anion-exchange resins. The first step was the preparation of (cobromoalkyl)trimethylammonium bromides^'^ for use as the alkylating agents and the 

second step was the coupling reaction of Reillex 402 polymer with the (co-bromoalkyl)trimethylammonium bromides. 

A series of (co-bromoalkyl)trimethylammonium bromides was prepared as shown 

in Scheme 2.1. (co-Bromoalkyl)trimethylammonium bromides 8-13 were obtained from 

the commercially available 1 ,a>dibromoalkanes 1-6, respectively, by reaction with 

trimethylamine in benzene. Trimethylamine gas was bubbled into the solution for 4 

hours and then the reaction mixture was stirred overnight at room temperature. The 

quaternary ammonium bromides 8 and 10 were only slightly contaminated with the 

corresponding di-substituted products. The (7-bromoheptyl)trimethylammonium 

bromide (12) and (8-bromooctyl)-trimethylammonium bromide (13) were contaminated 

with 55% and 69% of di-substituted products, respectively, as determined by 'H NM R 

13 
spectroscopy. These mixtures of mono- and di-substituted products were used without 

purification, since the undesired di-substituted product should not affect the coupling 

reaction of poly(4-vinylpyridine) with the (co-bromoalkyl)trimethylammonium bromide. 

The reactant (2-bromoethyl)trimethylammonium bromide (7) was commercially 

available. 

Br(CH2)mBr 

N(CH3)3 

PhH,rt 

bubbling for 4 h 

then, stirring overnight 

Br(CH2)mNtCH3)3 Br" 

(CH3)3N'(CH2)niNtCH3)3 2 Br' 

1 

2 

3 

4 

5 

6 

in 

3 

4 

5 

6 

7 

8 

Yield of Monosubstitution Product 

8 

9 

10 

11 

12 

13 

76% 

83% 

83% 

85% 

37% 

29% 

Scheme 2.1. Synthesis of (co-Bromoalkyl)trimethylammonium Bromides 8-13. 

A new type of anion-exchange resin was prepared as shown in Scheme 2.2. 

TM Anion-exchange resins 14-19 were obtained from the reaction of Reillex 402 polymer 

with the appropriate (a>-bromoalkyl)trimethylammonium bromides 7-13, respectively, in 

11 ethanol at reflux. In earlier work from Bartsch's group, Jong Seung Kim found that 

swelling of this poly(4-vinylpyridine) was much greater in ethanol than in DMF. 

Therefore, ethanol was used as a solvent for the coupling reaction. Coupling yields for 

14 
the anion-exchange resins 14-19 were calculated from the percent of bromine in the 

elemental analysis data and confirmed by the CHN analyses data. 

iCH2CHin 

o 

N 

+.. + Br(CH2)niNTCH3)3 Br 

7 

8 

9 

10 

11 

13 

EtOH 

reflux. 

m 

2 

3 

4 

5 

6 

8 

lOd 

—t'-' _ 1 1 ;n 

2Bf 

•> - r 

(CH2)niNtCH3). 

Coupling vield 

14 59% 

15 91% 

16 87% 

17 99% 

18 100% 

19 38% 

Scheme 2.2. Synthesis of Tetraalkylammonium-Containing Bifunctional AnionExchange Resins 14-19. 

To probe the effect of replacing the central methylene group in the spacer of 

anion-exchange resin 17 with an oxygen atom, the preparation of anion-exchange resin 

22 was envisioned. The presence of an oxygen atom in the spacer should enhance the 

flexibility of the spacer in the anion-exchange resin. First, [2-(2'-bromoethoxy)ethyl]-

trimethylammonium bromide (21) was prepared in 80% yield from the commercially 

available bis(2-bromoethyl)ether (20) by reaction with trimethylamine in benzene 

(Scheme 2.3). The obtained [2-(2'-bromoethoxy)ethyl]trimethylammonium bromide 

15 
BrCH2CH20CH2CH2Br 

20 

N(CH3)3 

PhH,rt 

bubbling for 4 h 

then, stirring ovemight 

BiCH2CH20CH2CH2N'(CH3)3 Br' 

21 (80%) 

Scheme 2.3. Synthesis of [2-(2'-Bromoethoxy)ethyl]trimethylammonium 

Bromide (21) 

(21) was a 100% mono-substituted product. The subsequent coupling reaction of 

.TM Reillex 402 poly(4-vinylpyridine) with alkylating agent 21 produced anion-exchange 

resin 22 with a 68% coupling yield (Scheme 2.4). 

•CH2CHin 

+ BrCH2CH20CH2CH2N (CH3)3 Br 

EtOH 

reflux, 10 d 

21 

CH2CH ^ 

}s-yj 2Br' 

CH2CH20CH2CH2Nr'(CH3)3 

22 (68% Coupling yield) 

Scheme 2.4. Synthesis of Anion-Exchange Resin 22. 

2.1.1.2. Pvridinium-Containing Bifunctional 

Anion-Exchange Resins 

To investigate the effect of changing the second anion-exchange site, the 

synthesis of pyridinium-containing bifunctional anion-exchange resins was envisioned. 

N-(co-Bromoalkyl)pyridinium bromides are the requisite alkylating agent for the coupling 

16 
.TM 12.13 reaction with Reillex 402 poly(4-vinylpyridine). Several methods for the 

preparation of N-(co-bromoalkyl)pyridinium bromides were examined to optimize the 

reaction conditions. N-(2-Bromoethyl)pyridinium bromide (23) was obtained in 25% 

yield from pyridine by reaction with 1,2-dibromoethane in acetone under reflux for 15 

hours (Scheme 2.5), while the reaction of pyridine with 5.0 equivalents of 1,2-dibromoO 

N 

+ BrCH2CH2Br 

acetone 

reflux, 15 h 

© Br" 

CH2CH2Br 

23 (25%) 

Scheme 2.5. Synthesis of A^-(2-Bromoethyl)pyridinium Bromide (23). 

ethane in benzene under reflux for 6 hours produced mostly the bis-pyridinium salt 24 as 

the major product (Scheme 2.6). 

O 

N 

+ BrCH2CH2Br 

PhH 

reflux, 6 h 

Q"-CH2CH2— 

2 Br" 

24 

-~0> 

Scheme 2.6. Reaction of 1,2-Dibromoethane with Pyridine in Benzene. 

17 
N-(co-Bromoalkyl)pyridinium bromides 25-28 were obtained from the reaction of 

pyridine with l,(o-dibromoalkanes 1-4, respectively, in benzene, as shown in Scheme 2.7. 

In contrast to the synthesis of N-(2-bromoethyl)pyridinium bromide (23), these reactions 

in benzene gave better yields and selectivity for the mono-substituted products 

+ Br(CH2)mBr 

PhH 

reflux, 6 h 

d 

N-, Br-

(CH2)mBr 

©"-

-(CH2)rir^NQ^ 

^ 

2 Br" 

1 

2 

3 

4 

m 

3 

4 

5 

6 

25 

26 

27 

28 

Yield of Monosubstitution Product 

94% 

99% 

83% 

82% 

Scheme 2.7. Preparation of N-(co-Bromoalkyl)pyridinium Bromides 25-28. 

than those conducted in acetone. Several attempts to optimize the reaction conditions 

were performed, as shown in Table 2.1. Use of a large excess of 1 ,co-dibromoalkane (10 

equivalents) was found to improve both the yield and selectivity. 

18 
Table 2.1. Preparation of N-(co-Bromoalkyl)pyridinium Bromides 25-28 from V arying 

Amounts of the l.co-Dibromoalkanes. 

C)] + Br(CH2)inBr 

PhH 

reflux, 6 h 

Q 

N : Br-

(CH2)mBr 

^N^_<CH:)-N;P ) 

2 Br 

Molar equivalents of Ratio of mono- to 

Dibromoalkane l,co-dibromoalkane Yield (%) di-substitution product 

Br(CH2)3Br 

Br(CH2)4Br 

Br(CH2)5Br 

2.5 

5.0 

2.5 

5.0 

10.0 

2.5 

Br(CH2)6Br 

5.0 

10.0 

2.5 

10.0 

49 

94 

32 

86 

99 

48 

74 

91 

44 

90 

100:0 

100:0 

29:71 

71:29 

100:0 

40:60 

65:35 

88:12 

29:71 

88:12 

19 
N-[2-(2'-Bromoethoxy)ethyl]pyridinium bromide (29) was obtained from the 

reaction of pyridine with bis(2-bromoethyl)ether (20) in acetone under reflux for 15 hours 

(Scheme 2.8) with a ratio of mono- to di-substitution products of 96:4 as determined b\ 

H NMR spectroscopy. 

O 

N 

-I- BrCH2CH20CH2CH2Br 

acetone 

reflux, 15 h 

d N ; Br' 

CH2CH20CH2CH2Br 

20 29 (46%) 

Scheme 2.8. Synthesis of N-[2-(2'-Bromoethoxy)ethyl]pyridinium 

Bromide (29). 

The pyridinium-containing bifunctional anion-exchange resins 30-34 were 

TM synthesized from the reaction of Reillex 402 poly(4-vinylpyridine) with N-(cobromoalkyOpyridinium bromides 23 and 25-28, respectively, in ethanol at reflux for 10 

days, as shown in Scheme 2.9. The coupling yields were calculated from the combustion 

analysis data by the same method as that described previously for anion-exchange resins 

14-19. 

20 
CH2CH-)n- -f CH2CH^ 

N Q 

^NC^ Br 

(CH2)mBr 

EtOH 

reflux, 10 d 

Q 

N + 

2 Br' 

(CH2) . . / -<\C o 

23 

25 

26 

27 

28 

in 

2 

3 

4 

5 

6 

Coupling vield 

30 67% 

31 79% 

32 86% 

33 78% 

34 88% 

Scheme 2.9. Synthesis of Pyridinium-Containing Bifunctional Anion-Exchange 

Resins 30-34. 

2.1.1.3. Trimethvlphosphonium-Containing Bifunctional 

Anion-Exchange Resins 

To explore the effect of replacing the nitrogen atom with a phosphorus atom at the 

center of the second anion-exchange group, the synthesis of trimethylphosphoniumcontaining bifunctional anion-exchange resins was performed. 

The co-bromoalkyltrimethylphosphonium bromides 35-39 were obtained from the 

reaction''* of trimethylphosphine with 1 ,co-dibromoalkanes 23 and 1-4. respectively, in 

toluene, as shown in Scheme 2.10. Trimethylphosphonium bromides 35-38 were 

obtained as pure mono-substituted products and compound 39 was obtained as a mixture 

of mono- and di-substituted products with a ratio of 76:24 as determined by 'H NMR 

.TM spectroscopy. Subsequent coupling reactions of Reillex 402 poly(4-vinylpyridine) 

21 
P(CH3)3 + Br(CH2)mBr 

toluene 

rt,4d 

Br(CH2)mPtCH3)3 Br" 

<f. (CH3)3PlCH2)niP (CH3)3 2 Br 

23 

1 

2 

3 

4 

m 

2 

3 

4 

5 

6 

35 

36 

37 

38 

39 

Yield of Monosubstitution Product 

47% 

89% 

89% 

77% 

51% 

Scheme 2.10. Synthesis of (co-Bromoalkyl)trimethylphosphonium Bromides 35-

39. 

with the co-(bromoalkyl)trimethylphosphonium bromides 35-38 in ethanol produced 

trimethylphosphonium-containing bifunctional anion-exchange resins 40-43, 

respectively, as shown in Scheme 2.11. 

•fCH2CH^ •fCH2CH^ 

r j l + Br(CH2)mP'(CH3)3 Br 

N 

36 

37 

38 

39 

EtOH 

reflux, 10 d 

m 

2 

3 

4 

5 

40 

41 

42 

43 

2 Br 

N ; 

(CH2)n,PtCH3)3 

Coupling vield 

11% 

58% 

52% 

45% 

Scheme 2.11 Synthesis of Trimethylphosphonium-Containing Bifunctional 

Anion-Exchange Resins 40-43. 

22 
2.1.1.4. N-Methvlpicolinium-Containing Bifunctional 

Anion-Exchange Resins 

To probe the effect of more rigidly defined geometries in the bifunctional anionexchange resin, an N-methylpicolinium group was incorporated into the host poly(4-

vinylpyridine) resin. The synthesis of N-methylpicolinium-containing bifunctional 

anion-exchange resins was a two-step process. However, the synthetic sequence was 

different from that of the bifunctional anion-exchange resins discussed previously. First, 

a picolyl group was attached to the poly(4-vinylpyridine) resin and subsequently the 

second pyridine nitrogen was methylated to provide the second anion-exchange site. 

The picolyl-substituted poly(4-vinylpyridines) were synthesized as shown in 

Scheme 2.12. The coupling reaction of Reillex 402 poly(4-vinylpyridine) and 2-

picolyl chloride hydrochloride with K2CO3 in ethanol under reflux for 10 days produced 

poly[N-(2-picolyl)-4-vinylpyridinium chloride] (47). The reactions of poly(4-vinyl-

-eCH2CH^ 

N N 

•HCl 

K2CO3 

EtOH 

reflux, 10 d 

•fCH2CH^ 

0 CI 

N ; 

CH2 ^ 

N 

44 (ortho) 

45 (meta) 

46 (para) 

Coupling vield 

47 66% 

48 60% 

49 93% 

Scheme 2.12. Synthesis of Picolyl Substituted Poly(4-vinylpyridines) 47-49. 

23 
pyridine) with 3- and 4-picolyl chloride hydrochloride were performed under the same 

conditions. The bifunctional anion-exchange resins were synthesized by methylation of 

the picolyl-substituted poly(4-vinylpyridines). As a model reaction. poly(N-methyl 4-

vinylpyridinium iodide) (50) was synthesized from ReillexTM 402 poly(4-vinylpyridine) 

by the reaction with CH3I in ethanol as shown in Scheme 2.13. The reaction of picoK 1 

substituted poly(4-vinylpyridines) 47-49 with iodomethane in ethanol produced 

•fCH2CHin- —eCH2CH^ 

CH3I 

EtOH 

reflux, 2 d 

CH3 

50 (99% Coupling yield) 

Scheme 2.13. Synthesis of Poly(N-Methyl 4-Vinylpyridinium Iodide) (50). 

N-methylpicolinium-containing bifunctional anion-exchange resins 51-53, respectively, 

as shown in Scheme 2.14. A very low level of chloride ion in these bifunctional anionexchange resins 51-53 was found by elemental analysis. Also, the level of iodide ion 

was higher than that for the 1(X)% substituted N-methylpicolinium-containing 

bifunctional anion-exchange resins 51-53. Therefore, it appears that chloride ion was 

replaced with iodide ion during the reaction. The coupling yields for the anion-exchange 

resins 51-53 were calculated from the combustion analysis data with the assumption that 

all chloride ions in both reactant and product were replaced with iodide ions. 

24 
CH2CH^ 

CH3I 

EtOH 

reflux, 3 d 

^CH2CH^ 

0 21 

N + 

CH t). 

N^ 

I 

CHi 

47 {ortho) 

48 {meta) 

49 ipara) 

51 

52 

53 

Coupling vield 

40% 

71% 

85% 

Scheme 2.14. Synthesis of N-Methylpicolinium-Containing Bifunctional AnionExchange Resins 51-53. 

2.1.2. Evaluation of Bifunctional Anion-Exchange Resins 

The new bifunctional resins were evaluated for the separation of Pu(IV) from 

nitric acid at Los Alamos National Laboratory.^'^ Each bifunctional anion-exchange 

resin was evaluated by measuring the distribution coefficients (Kj values) of Pu(rV) from 

1, 3, 5, 7, and 9 M nitric acid. The Pu(IV) distribution coefficients were calculated by 

procedures developed at Los Alamos National Laboratory.'^ To obtain information 

about the sorption kinetics, IQ values for dynamic contact periods of 30 minutes, 2 hours, 

and 6 hours were measured. Initial contact solutions contained 3 g/L of plutonium. 

25 
The Pu(IV) sorption behavior of the trimethylammonium-containing bifunctional 

anion-exchange resins is shown in Table 2.2. The Kd values for these bifunctional 

anion-exchange resins surpass those observed for ReillexTM HPQ resin. 

Table 2.2. Measured Kd (mL/g) Values for Pu(IV) Sorption from Nitric Acid by 

ReillexTM HPQ and Trimethylammonium-Containing Bifunctional AnionExchange Resins.^ 

HN03 

(M) 

1 

3 

5 

7 

9 

Contact 

Time (h) 

0.5 

2 

6 

0.5 

2 

6 

0.5 

2 

6 

0.5 

2 

6 

0.5 

2 

6 

ReillexTM 

HPQ 

6.7 

7.1 

6.8 

69 

97 

100 

230 

410 

370 

490 

850 

680 

380 

1,200 

1,500 

2 

1.3 

1.4 

1.3 

30 

30 

29 

390 

410 

400 

2,100 

2,700 

2,300 

2,900 

4,000 

3,100 

Kd Value of n 

3 

2.5 

1.5 

1.7 

37 

39 

38 

540 

570 

570 

3,000 

4,000 

3,300 

3,200 

3,300 

3,800 

1 for -(CH2)n4 

1.2 

1.5 

1.4 

40 

41 

41 

600 

650 

660 

3,500 

3,500 

3,700 

3,900 

2,000 

2,700 

• Spacer 

5 

1.7 

1.1 

1.3 

61 

63 

60 

690 

910 

1,000 

3,500 

4,300 

3,800 

3,600 

3,300 

3,200 

6 

1.6 

1.7 

1.3 

73 

79 

81 

770 

990 

1,000 

2,100 

2,600 

2,400 

2,100 

3,800 

4,200 

26 
The Pu(IV) sorption behavior of the trimethylpyridinium-containing bifunctional anionexchange resins is shown in Table 2.3. 

Table 2.3. Measured Kd (mL/g) Values for Pu(rV) Sorption from Nitric Acid by 

Trimethylpyridinium-Containing Bifunctional Anion-Exchange Resins. 

HNO3 Contact Kd Value of n for -(CHi),,- Spacer 

(M) Time (h) 2 3 4 5~~ 

~ 1 05 To 09 Ts 2T 

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 

39 

57 

63 

170 

560 

710 

380 

2,400 

4,100 

850 

1,000 

1,000 

1.: 

1. 

52 

54 

56 

790 

790 

820 

5,100 

4,700 

5,600 

5,900 

9,400 

9,600 

O 1 

o -) 

1.5 2.1 2.1 

122 120 

92 140 160 

100 150 160 

1,400 1,300 

1,000 1,700 1,900 

1,400 2,000 2,100 

5,700 4.500 

4,700 8,800 6,800 

11,000 11,000 13,000 

7,000 6,600 

6,200 13,000 9,000 

7,700 13,000 11,000 

27 
The Pu(rV) sorption behavior of the trimethylphosphonium-containing bifunctional 

anion-exchange resins is shown in Table 2.3. 

Table 2.4. Measured Kd (mL/g) Values for Pu(rV) Sorption from Nitric Acid b\ 

Trimethylphosphonium-Containing Bifunctional Anion-Exchange Resins. 

HN03 

(M) 

1 

3 

5 

7 

9 

Contact 

Time (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 

44 

67 

72 

230 

650 

830 

800 

2,900 

3,700 

1,300 

3,700 

5,500 

Kd Value of n 

3 

07 

07 

0 7 

37 

43 

43 

450 

570 

680 

2,200 

3,300 

3,900 

3.100 

5,300 

7.700 

for -(CH2)n- Spacer 

4 

0.6 

0 7 

0.6 

48 

53 

77 

720 

840 

1,000 

3,100 

3.700 

6,600 

5,500 

6,100 

9,600 

5 

1.1 

0 9 

1.0 

78 

83 

57 

1.100 

1.200 

1,400 

5,800 

5,400 

8,300 

6,800 

9,500 

12,000 

28 
The Pu(rV) sorption behavior of the picolinium- and methylated picolinium-containing 

bifunctional anion-exchange resins is shown in Table 2.5. 

Table 2.5. Measured Kd (mL/g) Values for Pu(rV) Sorption from Nitric Acid b\ 

Picolinium- and N-Methylpicolinium-Containing Bifunctional AnionExchange Resins.'^ 

HN03 

(M) 

1 

3 

5 

7 

9 

Contact 

Time (h) 

0.5 

2 

6 

0.5 

2 

6 

0.5 

2 

6 

0 5 

2 

6 

0.5 

2 

6 

3-picolyl 

1.9 

1.5 

1.6 

61 

72 

74 

660 

950 

1,000 

3,100 

4,300 

5,300 

4,300 

7.700 

8,700 

Kd Value 

4-picolyl 

1.2 

1.3 

1.2 

51 

60 

60 

580 

750 

890 

3,800 

4,400 

4,800 

4,900 

5,600 

7,500 

Methylated 

3-picolyl 

1.2 

1.2 

1.7 

-

62 

64 

720 

820 

859 

3,800 

5.900 

6,900 

7,800 

7,700 

9.100 

Methylated 

4-picolyl 

-

-

-

-

-

45 

640 

780 

790 

4,000 

5,400 

6,400 

8,000 

8,500 

12,000 

29 
It was found that the new bifunctional anion-exchange resins exhibited better 

plutonium distribution coefficient values and sorption kinetics compared to ReillexTM 

HPQ resin. Among those bifunctional anion-exchange resins, resins with five-carbon 

spacers showed the best performance. The Kd values for Pu(rV) were higher in 5-9 M 

nitric acid and lower in 1-3 M nitric acid since plutonium easily forms the dianionic 

species, Pu(N03)6'", in 7 M nitric acid. This phenomenon makes it possible to perform 

the sorption-stripping process by changing the nitric acid concentration. 

2.1.3. Synthesis of Water-Soluble Poly(vinylpyridines) 

The combination of a macromolecular metal ion complexing agent with 

ultrafiltration is an attractive concept for the selective removal of metal ions from 

aqueous solutions. Ultrafiltration is a separation method for a homogeneous phase and 

has become a standard procedure for the separation of biomolecules. In ultrafiltration, 

the different chemical components are separated exclusively according to their molecular 

dimensions.'^ Metal ions can be separated from aqueous solutions by use of a watersoluble chelating polymer which selectively binds the desired metal ion species or groups 

in an ultrafiltration process, as shown in Figure 2.3. For this process, the 

macromolecular compounds should have water-solubility and high binding capacity for 

the metal ions. Poly(vinylpyridine) resin was reported to exhibit metal ion complexation 

between metal ions and the pyridine groups in the polymer. ' However, Reilline 

4200 and 2200 polymers, commercially available linear poly(4-vinylpyridine) and 

poly(2-vinylpyridine), are insoluble in water. 

30 
Solid Polymer METAL-CONTAINING EFFLUENT 

J 4 1 

POLYMER 

SOLUTION ULTRAFILTRATION 

Loaded and 

Concentrated 

Polymer 

REACTOR METAL-FREE EFFLUENT 

Figure 2.3. Schematic Diagram of an Ultrafiltration Process with 

Macromolecular Complexes for the Separation of Metal Ions. 

In this dissertation research, the synthesis of water-soluble poly(vinylpyridines) 

by the partial quatemization will be explored. A minimum level of quatemization is 

required to maximize the ability for chelation of metal ions by the pyridine units in the 

polymer. 

2.1.3.1. Hydroxvethvl-Substituted Water-Soluble Polymers 

The synthesis of partially substituted poly(4-vinylpyridines) and their waterTV/f 

solubilities are shown in Table 2.2. Reaction of Reilline 4200 polymer with varying 

molar equivalents of 2-bromoethanol in methanol was performed. Solubility of the 

partially substituted poly(4-vinylpyridine) in water was evaluated both with heating and 

without heating. Based upon the solubility tests, 20% substituted poly(4-vinylpyridine) 

55 was selected as the desired product. Even though the polymers 57 and 58 were 

soluble in hot water, they appeared to form supersaturated solutions upon being allowed 

to cool to room temperature. 

31 
Table 2.6. Synthesis of Partially Substituted Poly(4-vinylpyridines) 54-58 and 

Their Water Solubilities. 

fCH2CH ^ 

( ^ j + BrCH2CH20H 

MeOH 

reflux, 1 d 

CH2CH^x eCH2CH^ 

Q 

N 

Q 

N Br 

CH2CH2OH 

Partially substituted Water solubility 

poly(4-vinylpyridine) 

54 

55 

56 

57 

58 

^ Not determined. 

X 

0.65 

080 

085 

0.90 

0.95 

y 

035 

0.20 

015 

010 

0.05 

Without heating 

ND'^ 

Yes 

No 

No 

ND' 

With heating 

Yes 

ND' 

Yes 

Yes 

No 

The synthesis of partially substituted poly(2-vinylpyridines) was performed by 

using the same procedure as that given previously for the partially substituted poly(4-

vinylpyridines) compounds 54-58. The solubility test results are shown in Table 2.3. 

The 15% substituted poly(2-vinylpyridine) 59 was selected as the desired product. 

32 
Table 2.7. Synthesis of Partially Substituted Poly(2-vinylpyridines) 59 and 60 and 

Their Water Solubilkies. 

4CH2CH^ 

r ^ \ + BrCH2CH20H 

MeOH 

reflux, 1 d 

CH2CH^ 

Partially substituted 

poly(2-vinylpyridine) 

Water solubility 

Without heating With heating 

59 

60 

085 

0.90 

015 

OlO 

Yes 

No 

ND" 

Yes 

Not determined. 

2.1.3.2. 3-(Trimethvlammonio)propvl-Substituted 

Water-Soluble Polymers 

To investigate the effect of combining an anion-exchange process with a watersoluble polymer, the synthesis of partially 3-(trimethylammonio)propyl-substituted 

poly(vinylpyridine) was envisioned. 

The partially substituted poly(4-vinylpyridine) was synthesized from the reaction 

of ReillineTM 4200 polymer with (3-bromopropyl)trimethylammonium bromide in 

methanol, as shown in Table 2.4. Solubility tests for these water-soluble polymers were 

conducted in water and in aqueous NaN03 solution at room temperature to check their 

feasibility as potential metal ion separating agents from nuclear waste. Poly(4-

vinylpyridine) 63 with 30% substitution was selected as the desired product. 

33 
Table 2.8. Synthesis of Partially Substituted Poly(4-vinylpyridines) 61-63 and Their 

Water Solubilities. 

CHsCHin -eCH2CH^ 

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

MeOH 

reflux, 1 d 

-eCH2CH^ 

Q 

N 2 Br 

(CH2)3NYCH3)3 

Partially substituted 

poly(4-vinylpyridine) 

Water solubility 

Without NaNO. With NaN03 

61 

62 

63 

0.90 

0.80 

0.70 

OlO 

0.20 

O30 

Yes 

Yes 

Yes 

No 

No 

Yes 

The reaction of Reilline 2200 polymer with (3-bromopropyl)trimethylammonium bromide in methanol was performed as shown in Table 2.5. The synthesis 

and solubility testing followed the same procedures as those for the water-soluble 

polymers 61-63. Poly(2-vinylpyridine) 65 with 30% substitution was selected as the 

desired product. 

34 
Table 2.9. Synthesis of Partially Substituted Poly(2-vinylpyridines) 64 and 65 and Their 

Water Solubilities. 

CHjCH ^ 

N + 

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

f CH2CH^x ^ CH2CH 

MeOH 

reflux, 1 d 

N^(CH2)3NtCH3)3 

2 Br' 

Partially substituted 

poly(2-vinylpyridine) 

Water solubility 

Without NaN03 With NaNO? 

64 

65 

O80 

0.70 

0.20 

0.30 

Yes 

Yes 

No 

Yes 

2.2. Chapter Summary 

The synthesis of several series of new bifunctional anion-exchange resins was 

accomplished by modification of commercially available ReillexTM 402 poly(4-vinylpyridine) resin. Structural variations in these bifunctional anion-exchange resins were 

accomplished by changing the identity of the second anion-exchange group, the length of 

the spacer between two anion-exchange sites, and the rigidity of the anion-exchange 

resin. Investigations of the sorption behavior of these new bifunctional anion-exchange 

resins for Pu(IV) from nitric acid were performed at Los Alamos National Laboratory. 

A series of water-soluble polymers was synthesized by the partial substitution of 

commercially available, linear poly(4-vinylpyridine) (ReillineTM 4200) and poly(2-

vinylpyridine) (ReillineTM 2200) with hydrophilic groups which included 2-hydroxyethyl 

35 
and 3-(trimethylammonio)propyl groups. These polymeric reagents have potential for 

metal ion separation from a homogeneous aqueous phase. 

2.3. Experimental Procedures 

2.3.1. Sources of Reagents 

Commercially available reagents were used as received unless otherwise 

specified. Reillex'^^ 402 polymer, a 2% crosslinked copolymer of 4-vinylpyridine and 

1,4-divinylbenzene, was obtained from the Aldrich Chemical Co. and used without 

further purification. Reilline^^ 4200 polymer, a 60% methanol solution of linear poly(4-

vinylpyridine), and ReillineTM 2200 polymer, a 65% methanol solution of linear poly(2-

vinylpyridine), were obtained from the Reilly Industries, Inc. and used without further 

purification. 

2.3.2. Purification of Reagents 

Dry solvents were prepared as follows: benzene was stored over activated 4 A 

molecular sieves; acetone was distilled. 

2.3.3. General 

Melting points were obtained with a Mel-Temp (capillary tube) melting point 

apparatus. Infrared (IR) spectra were recorded with a Perkin-Elmer 1600 Series FT-IR 

on NaCl plates (film deposited from solution) or as KBr pellets and are reported in 

wavenumbers (cm'). Proton nuclear magnetic resonance ('H NMR) spectra were 

recorded with an IBM AF-200 spectrometer with the chemical shifts (6) reported 

36 
downfield from the internal standard tetramethylsilane (TMS, present at ca. 0.05% in 

CDCI3). Splitting patterns in the 'H NMR spectra are identified as: s, singlet; d, doublet: 

t, triplet; q, quartet; p, pentet; br s, broad singlet; dd, doublet of doublet; and m, multiplet. 

Elemental analyses were performed by Desert Analytics Laboratory of Tucson, 

Arizona. For the synthesized anion-exchange resins, the percent substitution was 

calculated from the percent of chloride, bromide, or iodide counter ion(s) and confirmed 

by the CHN analysis results. 

2.3.4. General Procedure for the Synthesis of 

(co-Bromoalkyl)trimethylammonium Bromides 8-13 

Into a 100-mL, three-necked, round-bottomed flask equipped with CaCb drying 

tube and a magnetic stirrer were added the appropriate 1 ,co-dibromoalkane (2.(X) g) and 

dry benzene (30 mL). Into the reaction mixture was bubbled rapidly (about 4 

bubbles/second) anhydrous trimethylamine for 4 hours (8 hours for 10.00 g) with stirring 

at room temperature. After the completion of the addition, the reaction mixture was 

allowed to stir ovemight at room temperature. The precipitated solid was filtered and 

washed with cold benzene (10 mL) to give the product. Sometimes, the desired monosalt product was contaminated with the bis-salt product. The ratio of mono-salt to bissalt was determined by comparison of the integrated areas for the -N"^(CH3)3 absorptions 

from the mono- and bis-salt in the 'H NMR spectrum. 

2.3.4.1. (3-BromopropyI)trimethyIammonium Bromide (8) was obtained in 

76% yield as a white solid with mp 204-206 °C (lit.^ mp 205 °C dec). IR (deposit from 

37 
MeOH solution on a NaCl plate): 1479 (C-H bending in -CHj-N^) cm"'. 'H NMR 

(CDCl3:DMSO-d6 (lOl)): 5 2.41-2.43 (m, 2H); 3.36 (s, 9H, mono-salt); 3.43 (s. 18H. 

bis-salt); 3.55 (t, 7= 6.2 Hz, 2H); 3.73-3.81 (m, 2H). Mono-salt:Bis-salt = 96:4. 

2.3.4.2. (4-Bromobutyl)trimethylammonium Bromide (9) was obtained in 83% 

yield as a white solid with mp 134-136 °C (ht.'° mp 131-134 °C). IR (deposit from 

MeOH solution on a NaCl plate): 1482 (C-H bending in -CH2-N'^) cm"'. 'H NMR 

(CDCl3:DMSO-d6 (10:1)): 6 1.96-2.01 (m, 4H); 3.36 (s, 9H, mono-salt); 3.53 (t, 7 = 6.0 

Hz, 2H); 3.65-3.74 (m, 2H). Mono-salt:Bis-sak = 100:0. 

2.3.4.3. (5-Bromopentyl)trimethylammonium Bromide (10) was obtained in 

83% yield as a white solid with mp 141-142 "C (ht.'^ mp 141-142 °C). IR (deposit from 

MeOH solution on a NaCl plate): 1484 (C-H bending in -CH2-N^) cm"'. 'H NMR 

(CDCl3:DMSO-d6 (10:1)): 6 1.56-1.59 (m, 2H); 1.84-2.00 (m, 4H); 3.36 (s, 9H, monosalt); 3.39 (s, 18H, bis-salt); 3.47 (t, 7 = 6.5 Hz, 2H); 3.59-3.67 (m, 2H). Mono-salt:Bissalt = 94:6. 

2.3.4.4. (6-Bromohexyl)trimethylammonium Bromide (11) was obtained in 

85% yield as a white solid with mp 109-110 °C (lit.'° mp 107-109 °C). IR (deposit from 

MeOH solution on a NaCl plate): 1480 (C-H bending in -CH2-N^) cm'. 'H NMR 

(CDCl3:DMSO-d6 (10:1)): 6 1.46-1.51 (m, 4H); 1.82-1.90 (m, 4H); 3.34 (s, 9H, monosalt); 3.44 (t, 7 = 6.6 Hz, 2H); 3.55-3.63 (m, 2H). Mono-salt:Bis-salt = 100:0. 

2.3.4.5. (7-Bromoheptyl)trimethylammonium Bromide (12) was obtained in 

37% yield as a white solid with mp 240 °C (dec). IR (deposit from MeOH solution on a 

NaCl plate): 1483 (C-H bending in -CH2-N"') cm"'. 'H NMR (DMSO-d6): 6 1.13-1.49 

38 
(m, 6H); 1.52-1.89 (m, 4H); 3.06 (s, 9H, mono-salt); 3.08 (s, 18H, bis-salt); 3.30-3.38 (m. 

2H); 3.54 (t, 7 = 6.7 Hz, 2H). Mono-salt:Bis-salt = 45:55. 

2.3.4.6. (8-Bromooctyl)trimethylammonium Bromide (13) was obtained in 

29% yield as a white solid with mp 210 °C (dec). IR (deposit from MeOH solution on a 

NaCl plate): 1482 (C-H bending in -CH2-N^) cm"'. 'H NMR (DMSO-d6): 6 1.13-1.47 

(m, lOH); 1.57-1.76 (m, 2H); 3.05 (s, 9H, mono-salt); 3.06 (s, 18H, bis-salt); 3.26-3.35 

(m, 2H); 3.54 (t, 7 = 6.6 Hz, 2H). Mono-salt:Bis-sak = 31:69. 

2.3.5. Preparation of 

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

Bromide (21) 

Into a 100-mL, three-necked, round-bottomed flask equipped with CaCl2 drying 

tube and a magnetic stirrer were added bis(2-bromoethyl)ether (2.00 g, 8.62 mmol) and 

dry benzene (30 mL). Into the reaction mixture was bubbled rapidly (about 4 

bubbles/second) anhydrous trimethylamine for 2 hours with stirring at room temperature. 

After the completion of the addition, the reaction mixture was allowed to stir ovemight at 

room temperature. The precipitated solid was filtered and washed with cold benzene (10 

mL) to give 2.01 g (80%) of the product as a white solid with mp 105-107 °C. IR 

(deposit from MeOH solution on a NaCl plate): 1479 (C-H bending in -CH2-N^); 1289 

and 1117 (C-0) cm'. 'H NMR (CDCl3:DMSO-d6 (10:1)): 6 3.35 (s, 9H); 3.55-3.60 (m, 

2H); 3.79-3.97 (m, 6H). Anal. Cacld. for C7Hi7Br2NO: C, 28.89; H, 5.89. Found: C, 

29.28; H, 5.83. 

39 
2.3.6. General Procedure for the Synthesis of 

Poly[N-(co-Trimethylammonioalkyl) 4-Vinylpyridinium 

Dibromides] 14-19 

Into a 1000-mL, one-necked, round-bottomed flask were added Reillex^^ 402 

poly(4-vinylpyridine) (5.00 g, 47.6 mmol), an appropriate (co-bromoalkyl)trimethylammonium bromide (8-13) (47.6 mmol), and absolute ethanol (380 mL). The reaction 

mixture was refluxed for 10 days under nitrogen. After cooling to room temperature, the 

reaction mixture was filtered and the solid was washed on the funnel with ethanol (3 X 20 

mL) and water (2 X 20 mL). The solid was dried with benzene in a Dean-Stark 

apparatus to give the desired product. 

2.3.6.1. Poly[N-(2-Trimethylammonioethyl) 4-Vinylpyridinium Dibromide] 

(14) was obtained in 60% yield by weight as a white solid with mp > 300 °C. IR (KBr): 

1637 (C=N); 1478 (C-H bending in -CH2-N"') cm"'. Elemental analysis calculated for 

(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-Vinylpyridinium Dibromide] 

(15) was obtained in 77% yield by weight as a white solid with mp > 300 °C. IR (KBr): 

1638 (C=N); 1475 (C-H bending in -CH2-N'') cm'. Elemental analysis calculated for 

(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-Vinylpyridinium Dibromide] 

(16) was obtained in 81 % yield by weight as a white solid with mp > 300 °C. IR (KBr): 

1638 (C=N); 1474 (C-H bending in -CH2-N"') cm"'. Elemental analysis calculated for 

40 
(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-Vinylpyridinium Dibromide] 

(17) was obtained in 69% yield by weight as a white solid with mp > 300 °C. IR (KBr): 

1638 (C=N); 1474 (C-H bending in -CH2-N^) cm"'. Elemental analysis calculated for 

(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-Vinylpyridinium Dibromide] 

(18) was obtained in 67% yield by weight as a white solid with mp > 300 °C. IR (KBr): 

1638 (C=N); 1474 (C-H bending in -CH2-N^) cm"'. Elemental analysis calculated for 

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-Vinylpyridinium Dibromide] 

(19) was obtained in 47% yield by weight as a white solid with mp > 3(X) °C. IR (KBr): 

1637 (C=N); 1474 (C-H bending in -CH2-N'') cm'. Elemental analysis calculated for 

(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. Preparation of 

Poly[2-(N-2'-Trimethylammonioethoxy)ethyl 

4-Vinylpyridinium Dibromide] (22) 

Into a 1000-mL, one-necked, round-bottomed flask were added Reillex^^ 402 

poly(4-vinylpyridine) (7.00 g, 66.6 mmol), [2-(2'-bromoethoxy)ethyl]trimethylammonium bromide (21) (19.38 g, 66.6 mmol), and absolute ethanol (530 mL). The 

41 
reaction mixture was refluxed for 10 days under nitrogen. After cooling to room 

temperature, the reaction mixture was filtered and the solid was washed on the funnel 

with ethanol (3 X 50 mL) and water (2 X 50 mL). The solid was dried with benzene in a 

Dean-Stark apparatus to give 19.31 g (73%) of the product as a white solid with mp > 

300 °C. IR (KBr): 1639 (C=N); 1474 (C-H bending in -CH2-N^) cm"'. Elemental 

analysis calculated for (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. Preparation of 

N-(2-Bromoethyl)pyridinium Bromide (23) 

Into a 1000-mL, three-necked, round-bottomed flask were added pyridine (16.00 

g, 20.0 mmol), 1,2-dibromoethane (187.86 g, l.(X) mol), and dry acetone (500 mL) 

under nitrogen. The reaction mixture was refluxed for 15 hours. The precipitated solid 

was filtered and washed with cold acetone (50 mL) to give 13.51 g (25%) of the product 

as a solid with mp 125-130 °C (lit.'^ mp 111 °C). IR (deposit from MeOH solution on a 

NaCl plate): 1632 (C=N); 1487 (C-H bending in -CH2-N^) cm"'. 'H NMR (DMSO-de): 

54.14 (t, 7= 5.9 Hz, 2H); 5.06-5.12 (m, 2H); 8.25 (t, 7= 7.1 Hz, 2H); 8.70 (t, 7= 7.8 

Hz, IH); 9.17 (d, 7 = 5.8 Hz, 2H). 

2.3.9. General Procedure for the Synthesis of 

N-(o>-Bromoalkyl)pyridinium Bromide 25-28 

Into a 100-mL, three-necked, round-bottomed flask were added pyridine (1.60 g, 

20.0 mmol) and dry benzene (10 mL) under nitrogen. A solution of the 1 ,o>-dibromoalkane (10.0 equivalent, 5.0 equivalent for 1,3-dibromopropane) in 10 mL of dry benzene 

42 
was added. The reaction mixture was refluxed for 6 hours and then stirred ovemight at 

room temperature under nitrogen. The precipitated solid was filtered, washed with cold 

benzene (10 mL), and dried over phosphorous pentoxide to give the product. 

Sometimes, the desired mono-salt product was contaminated with the bis-salt product. 

The -CH2-N^ absorptions for the mono- and bis-salt overlapped in the 'H NMR spectrum 

and could not be utilized directiy to determine the level of bis-salt contamination in the 

mono-salt. Integration of the absorption for -CH2-Br in the mono-salt and the 

absorption for -CH2-N"^ from the mono-salt and bis-salt allowed the mono-salt:bis-salt 

ratio to be calculated from; 

mono-salt integration of -CH2-Br 

bis-salt [(integration of -CH2-N"*') - (integration of -CH2-Br)] 

2.3.9.1. N-(3-Bromopropyl)pyridinium Bromide (25) was obtained in 94% 

yield as a solid with mp 133-136 °C (lit.'° mp 136 °C). IR (deposit from MeOH solution 

on a NaCl plate): 1635 (C=N); 1488 (C-H bending in -CHz-N^) cm"'. 'H NMR (DMSOd6): 5 2.49-2.56 (p, 2H); 3.59 (t, 7 = 6.6 Hz, 2H); 4.77 (t, 7 = 7.1 Hz, 2H); 8.19 (t, 7 = 6.8 

Hz, 2H); 8.63 (t, 7= 7.8 Hz, IH); 9.08-9.29 (m, 2H). Mono-sak:Bis-sak = 100:0. 

2.3.9.2. N-(4-Bromobutyl)pyridinium Bromide (26) was obtained in 99% yield 

as a gum-like solid. IR (deposit from MeOH solution on a NaCl plate): 1634 (C=N); 

1488 (C-H bending in -CH2-N-') cm"'. 'H NMR (DMSO-de): 5 1.78-2.10 (m, 4H); 3.58 

(t, 7 = 6.5 Hz, 2H); 4.69 (t, 7 = 7.1 Hz, 2H); 8.20 (t, 7=7.1 Hz, 2H); 8.64 (t, 7 = 7.8 Hz, 

IH); 9.15 (d, 7= 5.2 Hz, 2H). Mono-salt:Bis-salt = 100:0 

43 
2.3.9.3. N-(5-Bromopentyl)pyridinium Bromide (27) was obtained in 83% yield 

as a gum-like solid from a larger-scale mn with 3.96 g (50.0 mmol) of pyridine. IR 

(deposit from MeOH solution on a NaCl plate): 1633 (C=N); 1487 (C-H bending in 

-CH2-N^) cm"'. ' H NMR (DMSO-de): 5 1.80-2.46 (m, 6H); 3.96 (t. 7= 6.6 Hz, 2H, 

-CH2-Br); 4.99-5.48 (m, 2H, -CH2-N^); 8.67 (t, 7= 6.9 Hz, 2H); 9.12 (t, 7 = 7.7 Hz, IH): 

9.80 (t, 7= 6.7 Hz, 2H). Mono-sak:Bis-sah = 88:12. 

2.3.9.4. N-(6-Bromohexyl)pyridinium Bromide (28) was obtained in 82% yield 

as a solid with mp 128-133 °C (lit.'^ mp 127-128 °C) from a larger-scale run with 3.96 g 

(50.0 mmol) of pyridine. IR (deposit from MeOH solution on a NaCl plate): 1632 

(C=N); 1485 (C-H bending in -CH2-N'') cm"'. 'H NMR (DMSO-de): 5 1.30-1.43 (m, 

4H); 1.76-1.97 (m, 4H); 3.53 (t, 7 = 6.6 Hz, 2H, -CH2-Br); 4.54-4.80 (m, 2H, -CH2-N^): 

8.20 (t, 7 = 6.5 Hz, 2H); 8.64 (t, 7 = 7.5 Hz, IH); 9.22 (t, 7 = 7.3 Hz, 2H). Monosalt:Bis-sak = 88:12. 

2.3.10. Preparation of 

N-[2-(2'-Bromoethoxy)ethyl]pyridinium 

Bromide (29) 

Into a lOO-mL, three-necked, round-bottomed flask were added pyridine (0.79 g, 

10.0 mol), bis(2-bromoethyl)ether (11.60 g, 50.0 mmol), and dry acetone (25 mL) under 

nitrogen. The reaction mixture was refluxed for 15 hours. The solvent was evaporated 

in vacuo to give 1.49 g (46%) of product as a yellow, viscous liquid. The desired monosalt product was contaminated with the bis-salt product. The -CH2-N^ absorptions for 

the mono- and bis-salt overiapped in the 'H NMR spectmm and could not be utilized 

directiy to determine the level of bis-salt contamination in the mono-salt. Integration of 

44 
the absorption for -CH2-Br in the mono-salt and the absorption for -CH2-N^ from the 

mono-salt and bis-salt allowed the mono-salt:bis-salt ratio to be calculated from: 

mono-salt integration of -CH2-Br 

bis-salt [(integration of -CH2-N"^) - (integration of -CH2-Br)] 

IR (deposk from MeOH solution on a NaCl plate): 1634 (C=N); 1487 (C-H bending in 

-CH2-N^) cm"'. ' H NMR (DMSO-de): 5 3.53-3.59 (m, 2H); 3.77 (t, 7 = 5.4 Hz, 2H, 

-CH2-Br); 3.98-4.03 (m, 2H); 4.91-4.96 (m, 2H, -CH2-N^); 8.18-8.27 (m, 2H); 8.65-8.69 

(m, IH); 9.12-9.20 (m, 2H). Mono-salt:Bis-sak = 94:6. 

2.3.11. General Procedure for the Synthesis of 

Poly[N-(0-(N'-Pyridinio)alkyl 4-Vinylpyridinium 

Dibromides] 30-34 

Into a 1000-mL, one-necked, round-bottomed flask were added Reillex^^ 402 

poly(4-vinylpyridine) (5.00 g, 47.6 mmol), the appropriate N-(o>bromoalkyl)pyridinium 

bromide 15-19 (47.6 mmol), and absolute ethanol (380 mL). The reaction was refluxed 

for 10 days under nitrogen. After cooling to room temperature, the reaction mixture was 

filtered and the solid was washed on the funnel with ethanol (3 X 20 mL) and water (2 X 

20 mL). The solid was dried with benzene in a Dean-Stark apparatus to give the 

polymeric product. 

2.3.11.1. Poly[N-2-(N'-Pyridinio)ethyl 4-Vinylpyridinium Dibromide] (30) 

was obtained in 55% yield by weight as a pale brown solid with mp > 300 °C. IR (KBr): 

1636 (C=N); 1458 (C-H bending in -CH2-N'^) cm"'. Elemental analysis calculated for 

45 
(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)propyl 4-Vinylpyridinium Dibromide] (31) 

was obtained in 76% yield by weight as a white solid with mp > 300 °C. IR (KBr): 1637 

(C=N); 1458 (C-H bending in -CH2-N"^) cm"'. Elemental analysis calculated for 

(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)butyl 4-Vinylpyridinium Dibromide] (32) 

was obtained in 60% yield by weight as a pale brown solid with mp > 300 °C. IR (KBr): 

1637 (C=N); 1458 (C-H bending in -CH2-N"') cm"'. Elemental analysis calculated for 

(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)pentyl 4-Vinylpyridinium Dibromide] (33) 

was obtained in 61% yield by weight as a pale brown solid with mp > 300 °C. IR (KBr): 

1637 (C=N); 1453 (C-H bending in -CH2-N'') cm"'. Elemental analysis calculated for 

(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)hexyl 4-Vinylpyridinium Dibromide] (34) 

was obtained in 60% yield by weight as a pale brown solid with mp > 300 °C. IR (KBr): 

1637 (C=N); 1458 (C-H bending in -CH2-N^) cm"'. Elemental analysis calculated for 

(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, 7.00 

46 
2.3.12. General Procedure for the Synthesis of 

co-Bromoalkyltrimethylphosphonium Bromides 35-39 

Into a 250-niL, three-necked, round-bottomed flask were added trimethylphosphine (60 nti:., of a 1.0 M solution in toluene, 60.0 mmol) and the appropriate 1 .codibromoalkane (1.67 equivalent) under nitrogen. The reaction mixture was stirred for 4 

days at room temperature. The precipitated solid was filtered and washed with cold 

benzene (10 mL) to give the product. Sometimes, the desired mono-salt product was 

contaminated with the bis-salt product. The ratio of mono-salt to bis-salt was 

determined by the comparison of the integrated areas for the -P^(CH3)3 absorptions from 

the mono- and bis-salt in the 'H NMR spectmm. 

2.3.12.1. (2-Bromoethyl)trimethylphosphonium Bromide (35) was obtained in 

47% yield as a white solid with mp 250-255 °C. IR (deposit from MeOH solution on a 

NaCl plate): 1427 (C-H bending in -CH2-P^); 1293 and 975 (C-H bending in CHB-P^) 

cm"'. ' H NMR (DMS0-d6): 5 1.93 (d, 7= 15.2 Hz, 9H); 2.88-3.03 (m, 2H); 3.73-3.86 

(m, 2H). Anal. Cacld. For C5H,3Br2P: C, 22.75; H, 4.89. Found: C, 22.99; H, 4.89. 

2.3.12.2. (3-Bromopropyl)trimethylphosphonium Bromide (36) was obtained 

in 89% yield as a white solid with mp 173-175 °C (lit." mp 164 "C). IR (deposit from 

MeOH solution on a NaCl plate): 1440 (C-H bending in -CH2-P^); 1298, 1001 and 981 

(C-H bending in CH3-P^) cm"'. 'H NMR (DMS0-d6): 5 1.88 (d. 7= 14.9 Hz. 9H); 2.05-

2.12 (m, 2H); 2.27-2.34 (m, 2H); 3.62 (t, 7 = 6.2 Hz. 2H). Mono-salt:Bis-sak = 100:0. 

2.3.12.3. (4-Bromobutyl)trimethylphosphonium Bromide (37) was obtained in 

89% yield as a white solid with mp 135-139 °C (lit." mp 132 °C). IR (deposit from 

MeOH solution on a NaCl plate): 1433 (C-H bending in -CH2-P^); 1300 and 971 (C-H 

47 
bending in CH3-P"') cm"'. 'H NMR (DMSO-d6): 5 1.57-1.70 (m. 2H); 1.87 (d,7= 14.9 

Hz, 9H); 1.83-1.99 (m, 2H); 2.20-2.35 (m, 2H); 3.59 (t, 7= 6.5 Hz, 2H). Mono-salt:Bissak= 100:0. 

2.3.12.4. (5-Bromopentyl)trimethylphosphonium Bromide (38) was obtained 

in 77% yield as a white solid with mp 126-128 °C (lit.'^ mp 386 "C). IR (deposit from 

MeOH solution on a NaCl plate): 1426 (C-H bending in -CH2-P^); 1301 and 986 (C-H 

bending in CH3-P^) cm"'. 'H NMR (CDC13): 5 1.63-1.67 (m, 4H); 1.91-1.97 (m, 2H); 

2.23 (d, 7 = 14.3 Hz, 9H); 2.48-2.73 (m, 2H); 3.46 (t, 7 = 6.4 Hz, 2H). Mono-salt:Bissak = 100:0. 

2.3.12.5. (6-Bromohexyl)trimethylphosphonium Bromide (39) was obtained in 

51 % yield as a white solid with mp 260 °C (dec.) (ht.^^ mp 190 °C). IR (deposit from 

MeOH solution on a NaCl plate): 1423 (C-H bending in -CH2-P''); 1304 and 971 (C-H 

bending in CHB-P"") cm"'. 'H NMR (DMSO-de): 5 1.48-1.64 (m. 4H); 1.86 (d, 7= 14.9 

Hz, 9H, mono-salt); 1.83 (d, 7= 14.8 Hz, 18H, bis-salt); 2.14-2.26 (m, 6H); 3.55 (t, 7 = 

6.6 Hz, 2H). Mono-salt:Bis-salt = 76:24. 

2.3.13. General Procedure for the Synthesis of 

Poly[N-(co-Trimethylphosphonioalkyl) 4-Vinylpyridinium 

Dibromides] 40-43 

Into a 1000-mL, one-necked, round-bottomed flask were added Reillex^^ 402 

poly(4-vinylpyridine) (5.00 g, 47.6 mmol), the appropriate (O-bromoalkyltrimethylphosphonium bromide 35-38 (47.6 mmol), and absolute ethanol (380 mL). The reaction 

mixture was refluxed for 10 days under nitrogen. After cooling to room temperature, the 

48 
reaction mixture was filtered and the solid was washed on the funnel with ethanol (3 X 20 

mL) and water (2 X 20 mL). The solid was dried with benzene in a Dean-Stark 

apparatus to give the desired product. The percent substitution for the poly(N-cotrimethylphosphonioalkyl 4-vinylpyridinium dibromide) was calculated from the percent 

of bromine as determined by combustion analyses. 

2.3.13.1. Poly[N-(2-Trimethylphosphonioethyl) 4-VinyIpyridinium 

Dibromide] (40) was obtained in 51% yield by weight as a pale yellow solid with mp > 

300 °C. IR (KBr): 1637 (C=N); 1474 (C-H bending in -CH2-N'') cm'. Elemental 

analysis calculated for (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-Vinylpyridinium 

Dibromide] (41) was obtained in 77% yield by weight as a white solid with mp > 3(X) °C. 

IR (KBr): 1637 (C=N); 1474 (C-H bending in -CH2-N^) cm"'. Elemental analysis 

calculated for (Ci3H22Br2NP)o.75(C7H7N)o.25: Br, 38.22; C, 44.04; H, 5.87; N, 4.47; P, 

7.41 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-Vinylpyridinium 

Dibromide] (42) was obtained in 74% yield by weight as a white solid with mp > 3(X) °C. 

IR (KBr): 1638 (C=N); 1474 (C-H bending in -CH2-N^) cm"'. Elemental analysis 

calculated for Ci4H24Br2NP: Br, 40.24; C, 42.34; H, 6.09; N, 3.53; P, 7.80 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-Vinylpyridinium 

Dibromide] (43) was obtained in 71 % yield by weight as a white solid with mp > 300 

49 
°C. IR (KBr): 1638 (C=N); 1466 (C-H bending in -CHz-N^) cm"'. Elemental analysis 

calculated for (C,5H26Br2NP)o.82(C7H7N)o.,8: Br, 36.80; C, 45.74; H, 6.39: N. 3.93; P. 

7.13 Found: Br, 36.47; C, 46.89; H, 6.85; N, 4.44; P, 5.35. 

2.3.14. General Procedure for the Synthesis of 

Poly[N-(Picolyl) 4-Vinylpyridinium 

Chlorides] 47-49 

Into a lOOO-mL, one-necked, round-bottomed flask were added Reillex^^ 402 

poly(4-vinylpyridine) (10.00 g, 95.1 mmol), the appropriate co-picolyl chloride 

hydrochloride (95.1 mmol), anhydrous potassium carbonate (50.1 mmol), and absolute 

ethanol (650 mL). The reaction was refluxed for 10 days under nitrogen. After cooling 

to room temperature, the reaction mixture was filtered and the solid was washed on the 

funnel with ethanol (3 X 20 mL) and water (2 X 20 mL). The solid was dried with 

benzene in a Dean-Stark apparatus to give the polymeric product. The percent 

substitution for the poly[N-(co-picolyl) 4-vinylpyridinium chloride] was calculated from 

the percent of chlorine as determined by combustion analyses. 

2.3.14.1. Poly[N-(2-Picolyl) 4-Vinylpyridinium Chloride] (47) was obtained in 

79% yield by weight as a red-brown solid with mp > 300 °C. IR (KBr): 1637 (C=N); 

1474 (C-H bending in -CH2-N^) cm"'. Elemental analysis calculated for 

(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-Vinylpyridinium Chloride] (48) was obtained in 

68% yield by weight as a tan solid with mp > 300 °C. IR (KBr): 1637 (C=N); 1458 (C-H 

50 
bending in -CH2-N"') cm"'. Elemental analysis calculated for 

(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-Vinylpyridinium Chloride] (49) was obtained in 

79% yield by weight as a red-brown solid with mp > 300 °C. IR (KBr): 1637 (C=N); 

1458 (C-H bending in -CH2-N^) cm"'. Elemental analysis calculated for 

(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. Preparation of 

Poly(N-Methyl 4-Vinylpyridinium Iodide) (50) 

Into a 500-mL, one-necked, round-bottomed flask were added Reillex^^ 402 

poly(4-vinylpyridine) (2.00 g, 19.0 mmol), methyl iodide (2.70 g, 19.0 mmol), and 

absolute ethanol (150 mL). The reaction was refluxed for 2 days under nitrogen. After 

cooling to room temperature, the reaction mixture was filtered and the solid was washed 

on the funnel with ethanol (3 X 20 mL) and water (2 X 20 mL). The solid was dried 

with benzene in a Dean-Stark apparatus to give 4.21 g (90%) of the product as a yellow 

solid with mp > 300 °C. IR (KBr): 1637 (C=N); 1458 (C-H bending in CH3-N^) cm"'. 

Elemental analysis calculated for (C8H,oIN)o.99(C7H7N)o.oi: I, 51.14; C, 39.07; H, 4.09; N, 

5.70 Found: I, 5074; C, 39.34; H, 4.35; N, 5.58. 

51 
2.3.16. General Procedure for the Synthesis of 

Poly[N-(N'-Methylpicolinio) 4-Vinylpyridinium 

Diiodide] 51-53 

Into a lOOO-mL, one-necked, round-bottomed flask were added the appropriate 

poly[N-(o>-picolyl) 4-vinylpyridinium chloride] 47-49 (7.00 g, 30.1 mmol), methyl iodide 

(9.45 g, 66.6 mmol), and absolute ethanol (530 mL). The reaction mixture was refluxed 

for 3 days under nitrogen. After cooling to room temperature, the reaction mixture was 

filtered and the solid was washed on the funnel with ethanol (3 X 20 mL). The solid was 

dried with benzene in a Dean-Stark apparatus to give the desired product. The percent 

substitution for the poly[N-(co-N'-methylpicolinio) 4-vinylpyridinium diiodide] was 

calculated from the percent of iodine as determined by combustion analyses. 

Note: If one assumes that the weight of the partially substituted poly[N-(copicolyl) 4-vinylpyridinium chloride] is the weight of the unsubstituted ReillexTM 402 

poly(4-vinylpyridine), then reaction with 1.0 equivalent of methyl iodide based on the 

unsubstituted Reillex''"'^ 402 poly(4-vinylpyridine) would guarantee an excess of methyl 

iodide. 

2.3.16.1. Poly[N-(2-N'-Methylpicolinio) 4-Vinylpyridinium Diiodide] (51) was 

obtained in 56% yield by weight as a dark red solid with mp > 300 °C. IR (KBr): 1637 

(C=N); 1458 (C-H bending in -CH2-N^) cm"'. Elemental analysis calculated for 

(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-Vinylpyridinium Diiodide] (52) was 

obtained in 91% yield by weight as a yellow solid with mp > 300 °C. IR (KBr): 

52 
1634 (C=N): 1469 (C-H bending in -CH2-N") cm"'. Elemental analysis calculated for 

(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-Vinylpyridinium Diiodide] (53) was 

obtained in 96% yield by weight as a yellow solid with mp > 300 °C. IR (KBr): 1637 

(C=N); 1458 (C-H bending in -CHi-N^) cm"'. Elemental analysis calculated for 

(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. Preparation of Partially Substituted 

Poly[N-(2'-Hydroxy)ethyl 4-Vinylpyridine] 55 

Into a 100-mL, one-necked, round-bottomed flask were added ReillineTM 42(X) 

polymer (5.00 g, of a 60% MeOH solution, 28.5 mmol), 2-bromoethanol (0.71 g, 5.71 

equivalent, 0.20 equivalent), and methanol (25 mL). The reaction mixture was refluxed 

for 1 day. The product was isolated by precipitation with Et^O (50 mL). The solvent 

was decanted from the precipitated solid and the precipitated solid was dried in vacuo to 

give 0.64 g (17%) of the product as a yellow solid with mp > 3(X) °C. IR (deposit from 

MeOH solution on a NaCl plate): 1640 (C=N); 1454 (C-H bending in -CH2-N^) cm"'. 

Note: The precipitated solid was very sticky. Therefore, filtration could not be 

conducted. 

53 
2.3.18. Preparation of Partially Substituted 

Poly[N-(2'-Hydroxy)ethyl 2-Vinylpyridine] 59 

Into a lOO-mL, one-necked, round-bottomed flask were added ReillinTM 2200 

polymer (5.00 g, of a 65% MeOH solution, 30.9 mmol), 2-bromoethanol (0.58 g, 4.64 

mmol, 0.15 equivalent), and methanol (25 mL). The reaction mixture was refluxed for 1 

days. The product was isolated by precipitation with Et20 (50 mL). The solvent was 

decanted from the precipitated solid and the precipitated solid was dried in vacuo to give 

0.74 g (19%) of the product as a yellow solid with mp > 300 °C. IR (deposit from 

MeOH solution on a NaCl plate): 1641 (C=N); 1454 (C-H bending in -CH2-N"') cm"'. 

Note: The precipitated solid was very sticky. Therefore, filtration could not be 

conducted. 

2.3.19. Preparation of Partially Substituted 

Poly[N-(3-Trimethylammonio)propyl 

4-Vinylpyridinium Dibromide] 63 

Into a 100-mL, one-necked, round-bottomed flask were added ReillineTM 4200 

polymer (5.00 g, of a 60% MeOH solution, 28.5 mmol), 3-bromopropyltrimethylammonium bromide (2.23 g, 8.55 mmol, 0.30 equivalent), and methanol (25 mL). The 

reaction mixture was refluxed for 1 day. The product was isolated by precipitation with 

Et20 (100 mL). The solvent was decanted from the precipitated solid and the 

precipitated solid was dried in vacuo to give 2.75 g (53%) of the product as a solid with 

mp > 300 °C. IR (deposit from MeOH solution on a NaCl plate): 1637 (C=N); 1474 (C-H 

bending in -CH2-N"^) cm"'. 

54 
Note: The precipitated solid was very sticky. Therefore, filtration could not be 

conducted. 

2.3.20. Preparation of Partially Substituted 

Poly[N-(3-Trimethylammonio)propyl 

2-Vinylpyridinium Dibromide] 65 

Into a 100-mL, one-necked, round-bottomed flask were added Reilline^^ 2200 

polymer (5.00 g, of a 65% MeOH solution, 30.9 mmol), 3-bromopropyltrimethylammonium bromide (2.42 g, 9.27 mmol, 0.30 equivalent), and methanol (25 mL). The 

reaction mixture was refluxed for 1 day. The product was isolated by precipitation with 

Et20 (100 mL). The solvent was decanted from the precipitated solid and the 

precipitated solid was dried in vacuo to give 1.84 g (32%) of the product as a solid with 

mp > 300 °C. IR (deposit from MeOH solution on a NaCl plate): 1637 (C=N); 1474 (CH bending in -CH2-N^) cm"'. 

Note: The precipitated solid was very sticky. Therefore, filtration could not be 

conducted. 

55 
2.4. References 

1. A. K. De, Separation of Heavy Metals, Pergamon, Oxford, 1961, Part II. 

2. F. Helfferich, Ion Exchange, McGraw-Hill, New York, 1962, p 10. 

3. R. Kunin, Ion Exchange Resins, Wiley, New York, 1958, p 73. 

4. S. F. Marsh, Improved Recovery and Purification of Plutonium at Los Alamos 

Using Macroporous Anion Exchange Resin, Los Alamos National Laboratory 

Report LA-10906, May 1987. 

5. S. F. Marsh and T. D. Gallegos, The Infiuence of Plutonium Concentration and 

Solution Flow Rate on the Effective Capacity of Macroporous Anion Exchange 

Resin, Los Alamos National Laboratory Report LA-10990, July 1987. 

6. T. E. Gangwer, M. Goldstein, and K. K. S. Pillay, Radiation Effects on Ion 

Exchange Materials, Brookhaven National Laboratory Report BNL-50781, 1977, 

p. 88. 

7. S. F. Marsh, Evaluation of a New, Macroporous Polyvinylpyridine Resin for 

Processing Plutonium Using Nitrate Anion Exchange, Los Alamos National 

Laboratory Report LA-11490, April 1989. 

8. S. F. Marsh, G. D. Jarvinen, J. S. Kim, J. Nam, and R. A. Bartsch, React. Fund. 

Polymers, 1997, 35, 75. 

9. A. P. Gray, D. C. Schlieper, E. E. Spinner, and C. J. Cavallito, 7. Am. Chem. Soc, 

1955, 77, 3648. 

10. J. Bielavsky, J. Vachek, and F. Omst, Coll. Czech. Chem. Commun., 1972, 37, 

1044. 

11. J. S. Kim, unpublished results. 

12. A. N. Kost, M. A. Yurovskaya, A. S. Vyazgin, and A. 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, and D. N. 

Kramer, 7 Med Chem., 1985, 28,\\\. 

14. E. Renaud, R. B. Russell, S. Fortier, S. J. Brown, and M. C. Baird, 7. Organomet. 

Chem.,1991, 419, AQi3. 

15. S. F. Marsh, G. D. Jarvinen, R. A. Bartsch, J. Nam, and M. E. Barr, 7. Radioanal 

Nucl Chem., in press. 

56 
16. S. F. Marsh, Z. V. Svitra, and S. 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. Los Alamos 

National Laboratory report LA-12654 rev., August 1994. 

17. H. Strathmann and K. Kock, Recent Developments in Separation Sciences. CRC 

Press, Inc., Florida, 1978, Vol. TV, Chapter 3. 

18. H. Nishide and E. Tsuchida, Makromol Chem., 1976, 777, 2295. 

19. A. Sugii, N, Ogawa, Y. linuma, and H. Yamamura, Talanta, 1981, 28, 551. 

20. Y. T. Bao and C. G. Pitt, 7. Polym. ScL Part A: Polym. Chem., 1990, 28, 741. 

21. P. Thanei-Wyss and P. G. Waser, Helv. Chim. Acta, 1983, 66, 2198. 

22. H. Schmidbaur and H. P. Scherm, Chem. Ber., 1977, II0. 1576. 

23. H. Schmidbaur and H. P. Scherm, Z. Naturforsch. B: Anorg. Chem. Org. Chem., 

1919,34b, 1347-

57 
CHAPTER 3 

SYNTHESIS OF CYCLIC POLYETHER EXTRACTANTS 

3.1. Results and Discussions 

Separation of metal ions with macrocyclic polyethers using various methods 

continues to receive a great deal of attention due to their applications in many chemical 

and biological systems. For example, the extraction of cesium ions from acidic nitrate 

media with macrocyclic polyethers is an important process for the removal and recovery 

of radioactive cesium from nuclear waste streams.' 

In this chapter, the synthesis of a variety of new macrocyclic polyethers which are 

potential complexing agents for cesium ion will be described. The attempted synthesis 

of other macrocyclic polyethers will be also described. 

3.1.1. Synthesis of Carbon Atom-Linked 

Side Arm Cyclic Polyethers 

Solvent extraction processes for the removal and recovery of radioactive cesium 

ions from acidic, high activity nuclear waste with a series of macrocyclic polyethers have 

been reported."^""^ Recently, it was reported that the extraction of cesium ion from acidic 

nitrate solution by macrocyclic polyethers can be enhanced by the use of the oxygenated. 

aliphatic solvents (e.g., alcohols and ketones) which are able to dissolve sufficient 

amounts of water.^ In these oxygenated solvents, a higher concentration of water 

facilitated both cation and anion solvation and resulted in the more efficient cesium ion 

extraction. Although aromatic macrocyclic polyethers yield higher levels of cesium ion 

extraction than do aliphatic macrocyclic polyethers, they usually have limited solubilities 

58 
in oxygenated, aliphatic solvents.^ In another report by Bartsch et al.,^ several crown 

ether alcohols with a hydroxy or hydroxyalkyl group attached to the polyether ring served 

as bifunctional ligands for simultaneous anion solvation and cation complexation. 

In this dissertation research, the synthesis of new macrocyclic polyethers into 

which the oxygenated, aliphatic side arms are incorporated is an important objective. 

Such compounds with systematic structural variation are to be examined at Argonne 

National Laboratory for cesium ion extraction from acidic nitrate media. 

3.1.1.1. Preparation of Bis(l-hydroxyalkyl)-

Substituted Crown Ethers 

For the synthesis of the crown ether diols, corresponding crown ether diketones 

were needed as synthetic precursors. A series of crown ether diketones were prepared as 

shown in Scheme 3.1. The dibenzo-18-crown-6 diketones 66-69 were obtained 

O 7 RCO2H 

^ ^"^^yi^^^^^ Eaton's reagent 

O O 

O 

->-

50 oC, 4-6 h 

66 

67 

68 

69 

79% 

55% 

49% 

92% 

R Yield 

C3H7 

C5H11 

C9H19 

CHC4H9 

C2H5 

Scheme 3.1. Synthesis of Dibenzo-18-crown-6 Diketones 66-69. 

59 
from commercially available dibenzo-18-crown-6 by diacylation^'^ with the appropriate 

carboxylic acid and Eaton's reagent (prepared from methanesulfonic acid and 

phosphorous pentoxide).^ 

The series of crown ether diols 70-73 was prepared in high yields from the 

dibenzo-18-crown-6 diketones 66-69, respectively, by reduction''-^ with NaBH4 in EtOHCH2CI2 as shown in Scheme 3.2. Since the crown ether diketones 66-68 were neariy 

insoluble in EtOH at room temperature, CH2CI2 was used as a co-solvent for the 

reduction reactions to provide better solubility of the reactant. For the preparation of 

crown ether diol 73, EtOH was the only solvent. 

»• RC 

EtOH-CH2Cl2 "^^-"^^O 

rt,4h 

O > OH 

O 

O 

R Yield 

66 C3H7 70 Quantitative 

67 C5H1, 71 90% 

68 C9H,9 72 80% 

69 CHC4H9 73 87% 

C2H5 

Scheme 3.2. Synthesis of Dibenzo-18-crown-6 Diols 70-73. 

To determine the effect upon cesium ion extraction of the presence of one or more 

ethyleneoxy units between the aromatic ring and the hydroxyl group in compound 73, the 

synthesis of new crown ether diols was accomplished as shown in Scheme 3.3. New 

60 
dibenzo-18-crown-6 diols 74 and 75 were obtained in high yields from the precursor diol 

73 by the reaction with a catalytic amount of sulfuric acid and an excess of the 

appropriate ethylene glycol in CH2CI2. 

HO 

I 

C4H9CHCH 

C2H5 

OH 

O^^^^^CHCHC4H9 

C2H5 

HO O OH 

cat. H2SO4 

CH2CI2 

rt, 15 h 

73 

HO O O 

I 

C4H9CHCH 

C2H5 

O O OH 

I 

C HC HC 4H9 

C2H5 

74 

75 

n 

0 

1 

Yield 

83% 

76% 

Scheme 3.3. Synthesis of Dibenzo-18-crown-6 Diols 74 and 75. 

To investigate the effect of the size of the polyether ring on cesium ion extraction, 

the synthesis of dibenzo-21 -crown-7 derivatives was performed. Dibenzo-21 -crown-7 

diol 78 was prepared by the method developed by Bradshaw et alJ'^ as shown in 

Scheme 3.4. First, dibenzo-21-crown-7 diketone 77 was obtained from dibenzo-21-

crown-7 (76) by reaction with 2-ethylhexanoic acid and Eaton's reagent. Subsequent 

61 
reduction of dibenzo-21-crown-7 diketone 77 with NaBYU in EtOH gave di[(2-ethyl-l 

hydroxyhexyl)benzo]-21-crown-7 (78) in quantitative yield. 

a° 

o 

^^f" ^ 

o o 

C4H9CHCO2H 

C2H5 

Eaton's reagent 

y^^/ " 30-35 OC. 4-6 h 

76 77 (83%) 

NaBH4 

EtOH 

rt, 24h 

HO 

I 

C4H9CHCH 

C2H5 

O OH 

u o 

78 (Quantitative yield) 

Scheme 3.4. Synthesis of Di[(2-ethyl-l-hydroxyhexyl)benzo]-21-crown-7 (78). 

A dibenzo-21-crown-7 diol 79 was prepared by same method as was utilized for 

the synthesis of the dibenzo-18-crown-6 diol 75 as shown in Scheme 3.5. Reaction of 

the dibenzo-21-crown-7 diol 78 with an excess of diethylene glycol and a catalytic 

amount of sulfuric acid in CH2CI2 gave 4,4'(5')-di[(2-ethyl-l-(5-hydroxy-3-oxapentoxy)-

hexyl)-benzo]-21-crown-7 (79) in high yield. 

62 
HO 

C4H9CHCHC2H5 

OH 

CHCHC4H9 HO O 

C H. 

OH 

cat. H2SO4 

CH2CI2 

rt, 15 h 

78 

/^A/—\ 

O O OH 

I 

CHCHC4H9 

I 

C2H5 

79 (84%) 

Scheme 3.5. Synthesis of 4,4•(5')-Di[(2-ethyl-l-(5-hydroxy-3-oxapentoxy)-

hexyl)benzo]-21-crown-7 (79). 

3.1.1.2. Synthesis of Bis(2-hydroxyalkyl)-

Substituted Crown Ethers 

Since cesium ion extraction was to take place from acidic nitrate media, the 

stability of polyether extractants to acidic conditions has to be taken into account along 

with their extraction ability for cesium ion. Treatment of bis( 1 -hydroxyalkyl)-

substituted crown ethers with aqueous nitric acid could lead to several pathways as 

shown in Figure 3.1. The hydroxyl group on the side arm of the crown ether can react 

with acid to generate an oxonium ion, which can then dissociate to produce a benzylic 

63 
H® -H^O 

73 80 

81 

elimination 

rearrangement 

combination 

Figure 3.1. Possible Reaction Pathways upon Treatment of a Crown Ether 

Alcohol with Acid. 

carbocation and water. This benzylic carbocation is a potential intermediate for a variety 

of reactions, including elimination to form an alkene, rearrangement to form a more 

stable carbocation, or combination with nucleophiles. The stability of the polyether 

extractants could be enhanced if formation of the benzylic carbocation were prevented. 

Therefore, movement of the hydroxyl group from the first to the second carbon atom in 

the side arm was envisioned. To this end, the synthesis of bis(2-hydroxyalkyl)-

substituted crown ethers was attempted. 

3.1.1.2.1. By Isomerization 

For the preparation of bis(2-hydroxyalkyl)-substituted crown ethers, the reaction 

of bis(l-hydroxyalkyl)-substituted crown ethers with hydrochloric acid or sulfuric acid 

64 
was conducted as shown in Scheme 3.6. With 5% hydrochloric acid, the reaction gave 

the unreacted starting material 73. Reaction with concentrated HCl yielded the 

unreacted starting material 73 with a small amount of elimination product 83. Reaction 

with sulfuric acid (5% or concentrated) gave a mixture of elimination products 83-88. 

instead of the desired product 82. 

OH 

HO 

'O O^^^^^CHCHCH, Aci d HO 

. f^^V - u.^^^uHY"^"" ^ Acid "V ^^- ^ 

C4H9CHCH-|-^ II 1^ II CaH. X ^ C4H<,CCH2-[- ^ 

CH2CI 2 

rt 

73 

^ O ^ OH 

O 0,^^;f>^^CH2CC4H^ 

82 

, 0 0^^^fSs.CH=CC4H^ 

C4H^=CH-|-: 11^ J ^ C,H5 

C,H 2"5 

83 

+ C3H7CH=CCH 

C2H5 - ^ y 

84 

.CH2C^IHCH3 

CH3CH=CC:H.^^ OA J ^^"^ 

85 

C4H9C=CH 

C2H5 OC. X^ -' 

K6 

C4H9C=CH 

C2H5 

O 

o o 

o o 

87 

.CH2C=CHCH3 

I 

C4H, 

+ C3H7CH=CCH: 

C2H5 

^tr^^y^O 0.^^^;;v^CH2C=CHCH3 

!~r: II 

o 

88 

o ^ 

C4Hy 

Scheme 3.6. Attempted Synthesis of 4,4'(5*)-Di[(2-ethyl-2-

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

65 
3.1.1.2.2. By Oxymercuration-Demercuration 

For the synthesis of bis(2-hydroxyalkyl)-substituted crown ethers, a bis-alkenesubstituted crown ether was prepared as a precursor for an oxymercuration-demercuration 

process (Scheme 3.7). The dehydration of bis( 1 -hydroxyalkyl)-substituted crown ether 

73 with p-toluenesulfonic acid'^ yielded a mixture of six alkene isomers 83-88 with a 

ratio of 1-alkene to 2-alkene side groups = 83:17 as determined from the H NMR 

spectrum of the mixture. Alkene isomers 84 and 85 resulted from the rearrangement of 

the benzylic carbocation as shown in Figure 3.2. 

ro OH 

HO ^-j^v^O 0^rs...^CHCHC4H, 

C4H9CHCH-P |T T Ij C2H5 

C2H5 ^^"^ 0 o-"^* ^ 

73 

^?\.^ 0 0...^^v^CH=CC4Hy 

83 

85 

^^^ 0 0.^^s^CH2C=CHCH3 

C4H9C=CH4- I JL J C4Hy * 

87 

TsOH 

phH 

reflux, 30 min. 

^J^V^O 0^^;^^^CH2C=CHC3H7 

84 

^J?^ 0 O.^^^CH2C=CHC,H7 

K6 

^?\^ 0 0^^v,^^CH2C=CHCH3 

C3H7CH=CCH2-+ I X^ J C4H, 

C2H5 ^^-^ 0 0^^^= ^ 

88 

Scheme 3.7. Dehydration of Crown Ether Diol 73. 

66 
OHH 

C-C-CH2C3H7 

H CH2CH3 

H+ 

73 

-H2O 

(a)H 

® ^ 1 

CMZ-CH^CtH 

I I 2C3H7 -H+ 

H CH2CH3 

1,2-Hydride Shift 

(via a) 

0 (b)H 

CH2-C^HC3H7 -H+ 

;CHCH3 (c)(^ 

H (via b) 

-H+ 

(via c) 

C H—C C4 H9 

C2H5 

CH.C=CHC^H7 

"I 

C2HS 

CH2C=CHCH3 

C4H9 

Figure 3.2. Pathways to the Alkene Isomers 83-88. 

The synthesis of bis(2-hydroxyalkyl)-substituted crown ether 82 was attempted by 

oxymercuration-demercuration as shown in Table 3.1. Oxymercuration of the bisalkene-substituted crown ether mixture 83-88 with mercury(n) acetate" (or mercury(II) 

trifluoroacetate'^) in H2O-THF followed by demercuration with NaOH-NaBH4 gave a 

mixture of crown ether diols 73, 82 and 89. It is envisioned that bis-alkene-substituted 

crown ethers 84 and 85 gave a single product, crown ether diol 82, as expected for a 

Markovnikov addition. On the other hand, addition to the double bond in crown ether 83 

might give the two isomers 73 and 82 due to the possible competition of benzylic and 

tertiary carbocations. Also, bis-alkene-substituted crown ethers 86-88 would give a 

mixture of crown ether diols 82 and 89. 

67 
Table 3.1. Attempted Synthesis of Crown Ether Diol 82 by OxymercurationDemercuration. 

Bis-alkene-substituted 

Crown Ether Mixture 

83-88 

l)Hg(0Ac)2 

H2O-THF 

rt, 1 d 

2) NaOH-NaBH4 

C4H9CHCH 

C2H5 

O 

o o 

o o 

o 

OH 

I 

CHCHC4H 

I 4n4 

73 

HO 

C4H9CCH2 

C2H5 

O 

o o 

O Q 

O 

OH 

I 

CH2CC4H9 

C2H5 

HO 

I 

C4H9CHCH 

C2H5 

O 

o o 

o o 

o 

OH 

I 

CH.CCjHu 

"I 

82 89 

Ratio of side groups^ 

Mercury reagent Yield, % (1-alcohol :2-alcohol) 

Hg(OAc): 33 65:35 

Hg(OCOCF3)2 63 64:36 

Determined from the H NMR spectrum of the product mixture. 

To prevent the possible competition of benzylic and tertiary carbocations in the 

addition of water to the double bond, the synthesis of an alkene-substituted crown ether 

with unbranched side arms was performed as shown in Scheme 3.8. The dehydration 

of 4,4'(5')-di[(l-hydroxydecyl)benzo]-18-crown-6 (72) with p-toluenesulfuric acid 

produced 4,4'(5')-di[(l-decenyl)benzo]-18-crown-6 (90). 

10 

68 
^ O ^ OH ^ O 

H(j) ^v^^ O 0^^:^..CHCH2C«Hn TsOH ,^^"-^* ^ d^^^^CH=CHC,H 

C«H.^H2CH^^ ,X J 7; ^ C«H.^H=CH^^ ^Xj 

L^O^ reflux, 2 h C^O ^ 

72 90 (59%) 

Scheme 3.8. Synthesis of 4,4'(5*)-Di[(l-decenyl)benzo]-18-crown-6 (90). 

The synthesis of 4,4'(5')-di[(2-hydroxydecyl)benzo]-18-crown-6 (91) from the 

alkene substituted crown ether 90 by oxymercuration-demercuration with mercury(II) 

trifluoroacetate was attempted as shown in Scheme 3.9. However, the reaction gave a 

mixture of the isomeric 1- and 2-hydroxyalkyl-substituted crown ethers 72, 91 and 92. 

From the results discussed above, oxymercuration-demecuration of alkenesubstituted crown ethers was judged to be unable to produce the desired bis(2-

hydroxyalkyl)-substituted crown ether selectively. 

69 
^ o ^ 

C8H,7CH=CH-^ 11 

p o 

o 

90 

CH=CHCgH 17 

l)Hg(OCOCF3)2 

H2O-THF 

rt. 1 d 

2) NaOH-NaHH4 

HO 

I 

CSHITCHZCH 

o 

o 

72 

OH 

CHCH2C8H17 HO 

+ CsHnCHCHj 

o o 

o o 

o 

91 

OH 

I 

CHiCHCjfHp 

+ CgHnCHzCH 

O 

o o 

o o 

o 

92 

OH 

I 

CH2CHCgHi7 

(28%, l-alcohol:2-alcohol = 45:55) 

Scheme 3.9. Attempted Synthesis of 4,4'(5')-Di[(2-hydroxydecyl)benzo]-18-

crown-6 (91) by Oxymercuration-Demercuration. 

3.1.1.2.3. By Hydroboration-Oxidation 

Since the oxymercuration-demercuration process of the crown ether alkenes gave 

a mixture of two crown ether diol isomers, another synthesis of bis[2-hydroxyalkyl] 

13 substituted crown ether by hydroboration-oxidation was attempted as shown in Scheme 

3.10. Hydroboration of 4,4'(5')-di[(l-decenyl)benzo]-18-crown-6 (90) with sodium 

borohydride and boron trifluoride etherate and subsequent oxidation with hydrogen 

peroxide gave a mixture of crown ether diols 72, 91 and 92. Hydroboration-oxidation 

gave an even lower proportion of the desired crown ether diol 91 than did 

oxymercuration-demercuration. 

70 
CO 

C8H,7CH=CH-P II 

o o 

o 

90 

CH=CHC8H S"!? 

l)NaBH4,THF 

BF30Et2, OoC, 20 min 

then, rt, lOh 

2) OH-. H2O2, OoC 

then, rt, 3 h 

HO 

I 

CgHi7CH2CH ^ Y° 

r^°^ 

^*'*-''^^ I 

72 

OH 

I 

CHCH2CgH|7 HO 

+ CRHHCHCH Z 

o 

o o 

o o 

o 

91 

OH 

I 

CH^CHCgHfHO 

+ C8H,7CH2CH 

O O 

O O 

o 

92 

OH 

I 

.CH2CHCjjHi7 

(28%, 1-alcohol. 2-alcohol = 66:34) 

Scheme 3.10. Attempted Synthesis of 4,4'(5')-Di[(2-hydroxydecyl)benzo]-18-

crown-6 (91) by Hydroboration-Oxidation. 

3.1.2. Synthesis of Oxygen Atom-Linked 

Side Arm Cyclic Polyethers 

In addition to the attempted synthesis of bis(2-hydroxyalkyl)-substituted dibenzo18-crown-6 compounds, the preparation of oxygen atom linked side arm cyclic 

polyethers in which the side arms are joined to the benzene rings of the dibenzo-18-

crown-6 through an oxygen atom was attempted. A benzylic carbocation could not be 

formed from such diols under acidic conditions. Three strategies for the preparation of 

an "O-linked" side arm dibenzo-18-crown-6 were explored: (i) elaboration of the side 

71 
arm in a catechol derivative and subsequent cyclization to form a disubstituted dibenzo18-crown-6; (ii) cyclization of a protected catechol derivative to form a disubstituted 

dibenzo-18-crown-6 and subsequent deprotection and elaboration of the side arm: and 

(iii) modification of commercially available dibenzo-18-crown-6 to form a disubstituted 

dibenzo-18-crown-6 and subsequent elaboration of the side arms. 

3.1.2.1. Elaboration of the Side Arm in a Catechol 

Derivative and Subsequent Cyclization 

For use in the preparation of an "O-linked" side arm dibenzo-18-crown-6 

compound, the catechol derivative 94 was synthesized in two steps from the 

commercially available Sesamol. The protected catechol derivative 93 was obtained 

from the reaction of Sesamol with cesium carbonate and 1,2-epoxyhexane in acetonitrile 

as shown in Scheme 3.11. Reaction of Sesamol with sodium hydroxide and 1,2-

epoxyhexane in r-butanol at reflux for 3 days gave same 93 in a lower yield of 45%. 

OH 

Sesamol 

1)CS2C03 

CH3CN 

reflux, 3 h 

2) 

O 

Z_A-—-•C4H9 

reflux, 60 h 

OH 

I 

OCH2CHC4H9 

93 (78%) 

Scheme 3.11. Synthesis of the Protected Catechol Derivative 93. 

72 
Attempts to use sodium hydride or potassium hydride as the base in tetrahydrofuran did 

not give the desired product. 

Subsequently, the protecting group was removed by the reaction of the protected 

catechol derivative 93 with boron trichloride in dichloromethane"^ to give a catechol 

derivative 94 as shown in Scheme 3.12. Attempted deprotection with Dowex-50W-X8 

ion exchange resin in water (or THF-water) at 70°C for 24 hours gave only the recovered 

reactant. 

OH OH 

I I 

OCH2CHC4H9 Bci HO.,^^?s..,^OCH2CHC4H9 

CH2CI2 HOX' J 

rt, 1 h 

93 94 (50%) 

Scheme 3.12. Synthesis of Catechol Derivative 94. 

The synthesis of 4,4'(5')-di[(2-hydroxyhexoxy)benzo]-18-crown-6 (95) by the 2+2 

type of cyclization developed by Pedersen'^ for the preparation of dibenzo-18-crown-6 

was attempted as shown in Scheme 3.13. The reaction of the catechol derivative 94 with 

sodium hydroxide and bis(2-chloroethyl) ether in w-butanol gave only very small 

amounts of the desired disubstituted dibenzo-18-crown-6 95 contaminated with 

unidentified impurities. Several attempts to purify the cmde product by column 

chromatogarphy or recrystallization did not give the pure compound 95. 

73 
94 

OH 

I 

OCH2CHC4H9 

CI 

NaOH 

O CI Ai-BuOH 

reflux, 16 h 

^ 

HO 

C4H9CHCH2O 

O 

O OH 

I 

0..^^^s^OCH2CHC4H9 

O O' 

O, 

95 

Scheme 3.13. Attempted Synthesis of 4,4'(5')-Di[(2-hydroxyhexoxy)benzo]-18-

crown-6 (95). 

3.1.2.2. Cyclization of a Protected Catechol and 

Subsequent Deprotection and Elaboration of the Side Arm 

The assumption that the functionalized side arm in the catechol derivative 94 was 

detrimental to the cyclization reaction led to the another synthetic approach which 

includes cyclization and subsequent elaboration of the side arm. The benzyl group was 

chosen as a protecting group since it should be unaffected by the basic conditions to be 

used in the cyclization to form the dibenzo-18-crown-6 compound. 

The synthesis of the benzyl group protected catechol 97 was attempted as shown 

in Scheme 3.14. The synthesis of the benzyl-protected Sesamol 96 was attempted by 

two different methods. The reaction of Sesamol with sodium hydroxide and benzyl 

74 
OH 

Sesamol 

BnCl, NaOH 

dioxane, lOOoC, 1 d 

or 

BnCl, NaOH 

C6H5CH2N"(C2H5)3 Cr 

CH2CI2-H2O. rt, 1 d 

OCH.Ph 

96 

BCI3. CH2CI2 

rt, 30 min 

) ( 

OCHzPh 

97 

Scheme 3.14. Attempted Synthesis of the Catechol Derivative 97. 

16 chloride in dioxane was performed. The H NMR spectra indicated that product 96 

obtained from column chromatography was contaminated with an unidentified impurity, 

which was not indicated by thin layer chromatographic analysis. Another synthesis 

using a phase transfer-catalyzed reaction was attempted. Sesamol was reacted with 

sodium hydroxide and benzyl chloride in the presence of a phase transfer catalyst and 

gave the same result as the first method. Despite the presence of the impurity in 

compound 96, deprotection of methylene group was attempted. It was thought that the 

impurity might be separable after the deprotection of compound 96. The reaction of the 

75 
impure benzylated Sesamol 96 with boron trichloride in dichloromethane did not give the 

desired product 97, but an unidentified mixture of products. 

3.1.2.3. Modification of Dibenzo-18-crown-6 and 

Subsequent Elaboration of the Side Arms 

3.1.2.3.1. Synthesis of Dihydroxy-Substituted 

Dibenzo-18-crown-6 

For the synthesis of di(hydroxybenzo)-18-crown-6, two methods were explored. 

The first preparative sequence for the dihydroxy substituted dibenzo-18-crown-6 is 

shown in Scheme 3.15. Reaction of dibenzo-18-crown-6 with nitric acid in acetic acid 

and chloroform at room temperature'^ gave a di(nitrobenzo)-18-crown-6 (98). 

Subsequent hydrogenation with 10% Pd-C in dimethylformamide at room temperature'^ 

provided di(aminobenzo)-18-crown-6 (99). The di(hydroxybenzo)-18-crown-6 (101) 

was obtained by two-step processes.'^ The reaction of di(aminobenzo)-l8-crown-6 (99) 

with NaN02 in aqueous fluoroboric acid gave a bis-diazonium tetrafluoroborate 100. 

Subsequent reaction with trifluoroacetic acid and potassium carbonate produced 

di(hydroxybenzo)-18-crown-6 (101). Another attempt for the preparation of dihydroxysubstituted dibenzo-18-crown-6 was performed as shown in Scheme 3.16. The reaction 

of di(aminobenzo)-18-crown-6 (99) with NaN02 in aqueous sulfuric acid at 0 °C to form 

the bis-diazonium sulfate in situ followed by refluxing'^ gave an unidentified mixture of 

products. 

76 
O' 

^O 

o, 

O' 

HN0 3 

O' 

o 

ACOH-CH3C1 

rt, 24h 

- ^ O9N 

O 

o 

o, 

O' 

.NO. 

O, 

98 (79%) 

H2, Pd-C 

DMF 

rt, 24h 

H9NO 

^O 

o 

o 

o. 

99 (99%) 

l)NaN02. HBF4 

NH2 H2O, OOC, 30 min 

2) K2CO3 

CF3CO2H 

reflux, 24 h 

HO- -

O 

,0 O 

^O 

o 

101 (40%) 

Scheme 3.15. Synthesis of 4,4'(5')-Di(hydroxybenzo)-18-crown-6 (101). 

H2N--

o o 

Q O 

O 

99 

l)NaN02, H2SO4 

NH2 H2O, 0 OC 

2) H2SO4, H2O 

reflux, 5 min 

^ H0- -

O 

O O 

O 0 

O 

101 

OH 

Scheme 3.16. Attempted Synthesis of 4,4'(5')-Di(hydroxybenzo)-18-crown-6 

(101). 

77 
An alternative synthetic route to di(hydroxybenzo)-18-crown-6 was developed 

(Scheme 3.17) due to the low yield for the last step in the method shown in Scheme 3.15. 

In this new synthetic sequence, di(acetylbenzo)-18-crown-6 (102) was obtained from the 

reaction of dibenzo-18-crown-6 with acetic acid and Eaton's reagent at 50°C. Several 

attempts for the preparation of di(acetatobenzo)-18-crown-6 (103) by a Baeyer-Villiger 

reaction were performed. An attempt with w-CPBA-TsOH^^ gave an unidentified 

mixture of products and the starting material remained unreacted from the attempt with 

H202-CF3CH20H.^' Other attempts with w-CPBA" or m-CPBA-CF3C02H-- gave low 

yields. Reaction of crown ether diketone 102 with m-chloroperoxybenzoic acid in 

dichloromethane in the presence of Na2HP04^'^ gave the crown ether diester 103 in high 

yield. Hydrolysis^'* of the crown ether diester 103 with sodium hydroxide in methanoldichloromethane yielded di(hydroxybenzo)-18-crown-6 (101) in high yield. 

78 
CH3C02H 

Eaton's reagent 

50 OC, 6 h 

102 (64%) 

m-CPBA 

Na2HP04 

CH2CI2 

rt, 2d 

O 

II •^ CH3CO— 

o o 

0.^^\^0CCH 3 NaOH 

Me0H-CH2Cl2 

rt, 24h 

103 (78%) 

101 (83%) 

Scheme 3.17. Alternative Synthesis of of 4,4'(5')-Di(hydroxybenzo)-18-crown-6 

(101). 

3.1.2.3.2. Synthesis of Di[(2-hydroxy)alkoxybenzo]-18-crown-6 

Involving Alkylation of Di(hydroxybenzo)-18-crown-6 

For the synthesis of "O-linked" side arm crown ethers, side arm elaboration 

reactions of di(hydroxybenzo)-l 8-crown-6 were performed. Analogous reactions of 

Sesamol as a model study were perfomed in advance of the reaction with 

di(hydroxybenzo)-18-crown-6. 

79 
3.1.2.3.2.1. Reaction with Epoxides. Reactions of Sesamol with 1,2-

epoxyhexane or 1,2-epoxyoctane using different base-solvent combinations were 

performed as shown in Table 3.2. The reactions provided the desired products in 39-

81 % yields. The cesium carbonate-acetonitrile combination at reflux for 3 days gave the 

best results. An analogous reaction with potassium carbonate in acetonitrile was 

Table 3.2. Reactions of Sesamol with Epoxides. 

OH 

O 

R 

C4H9 

C6H13 

93 

104 

OH 

I 

OCH2CHR 

R Base (equiv.) Solvent Temp. Time, d Yield, % 

C4H9 

C4H9 

C4H9 

C4H9 

CeHn 

CeHn 

CeHn 

CeHn 

C6H13 

CS2CO3 (2.5) 

K2CO3 (2.5) 

CS2CO3 (2.5) 

CS2CO3 (2.5) 

CS2CO3 (2.5) 

CS2CO3 (2.5) 

Li2C03 (2.5) 

NaOH (2.0) 

NaOH (2.0) 

CH3CN 

CH3CN 

DMF 

DMF 

CH3CN 

DMF 

DMF 

?-BuOH 

/-BuOH 

reflux 

reflux 

80°C 

115°C 

reflux 

80°C 

reflux 

reflux 

reflux 

3 

3 

3 

3 

3 

3 

3 

3 

7 

78 

a 

62 

62 

81 

51 

58 

39 

40 

The reaction was incomplete. 

80 
incomplete after refluxing for 3 days. Reactions with hydride base (NaH or KH) in 

acetonitrile or dimethylformamide did not give the desired product. 

Reactions of di(hydroxybenzo)-18-crown-6 (101) with 1,2-epoxyhexane or 1.2-

epoxyoctane using different base-solvent combinations were attempted as shown in Table 

3.3. None of the reactions produced the desired products 95 and 105, respectively. 

Reactions using carbonate bases (CS2CO3, K2CO3, or Li2C03) in acetonitrile or 

dimethylformamide gave a very low mass balance, with the isolated products being only 

about 1/10 of the starting material by weight. These inorganic bases were replaced by 

the organic bases of l,8-diazabicyclo[5,4,0]undec-7-ene (DBU) and proton sponge, since 

complexation of deprotonated di(hydroxybenzo)-18-crown-6 with metal cations could 

conceivably deactivate the nucleophile. However, reactions with DBU or proton sponge 

gave only the unreacted starting material. Also, model reactions of Sesamol with 

organic bases (DBU, proton sponge, or triethylamine) produced only the unreacted 

starting material. Reaction with sodium hydroxide as the base gave small amounts of the 

desired product 105 that was contaminated with the unidentified impurity. However, the 

obtained product 105 was still contaminated with this unidentified impurity even after 

several attempts of purification by column chromatography and recrystallization. 

Analysis of the 'H NMR spectra of the products from these reactions indicated that the 

dibenzo-18-crown-6 dialkoxide which was initially formed from the reaction of 

di(hydroxybenzo)-18-crown-6 with the epoxide reacted further with more epoxide to give 

elongated side arms. 

81 
Table 3.3. Attempted Reactions of Di(hydroxybenzo)-18-crown-6 (101) with Epoxides. 

o 

Horr° o 

O 0 

o 

OH 

O 

^ RCHCH2O 

o 

o o 

o o 

o 

OH 

I 

OCH.CHR 

101 

R 

C4H9 

CeHn 

95 

105 

Epoxide (equiv.) Base (equiv.) Solvent Temp. Time, d 

,2-epoxyhexane (2.0) CS2CO3 (5.0) 

,2-epoxyhexane (2.0) K2CO3 (5.0) 

,2-epoxyhexane (2.2) CS2CO3 (5.0) 

,2-epoxyoctane (2.2) CS2CO3 (5.0) 

,2-epoxyoctane (5.0) CS2CO3 (5.0) 

,2-epoxyoctane (2.2) CS2CO3 (5.0) 

,2-epoxyoctane (2.0) Li2C03 (5.0) 

,2-epoxyoctane (2.0) NaOH (4.0) 

,2-epoxyoctane (2.0) NaOH (4.0) 

,2-epoxyoctane (2.0) DBU (4.0) 

CH3CN 

CH3CN 

DMF 

CH3CN 

CH3CN 

DMF 

DMF 

/-BuOH 

r-BuOH 

CH^CN 

,2-epoxyoctane (2.0) Proton sponge (4.0) CH3CN 

reflux 

reflux 

115°C 

reflux 

reflux 

80 °C 

reflux 

reflux 

reflux 

reflux 

reflux 

7 

3 

3 

3 

3 

3 

3 

7 

3 

82 
3.1.2.3.2.2. Reaction with Cvclic Sulfate Ester. To circumvent the formation of 

multi-addition products postulated in the reaction of di(hydroxybenzo)-18-crown-6 with 

epoxides, the synthesis of di[(2-hydroxyalkoxy)benzo]-18-crown-6 by the reaction of 

di(hydroxybenzo)-18-crown-6 with a cyclic sulfate ester was envisioned. The cyclic 

sulfate ester 107 was prepared by reaction of 1,2-decanediol with thionyl chloride and 

triethylamine in dichloromethane at 0 °C and subsequent oxidation of cyclic sulfite ester 

106 with sodium periodate in the presence of ruthenium(ni) chloride hydrate in CCUCH3CN-H2O at 0 °C^^ as shown Scheme 3.18. 

OHOH ?\ 0 0 

I I SOCl2,Et3N ^S^ RuCl3-H20, NaI04 ^S ^ 

CH3(CH2)7CHCH2 • O p • O O 

CH2CI2 ^ ' CCI4-CH3CN-H2O ^ ) f 

OOC, 15 min ^^"'^ OoC, Ih ^^^^^ 

106 107 (95% overall) 

Scheme 3.18. Synthesis of Cyclic Sulfate Ester 107. 

Elaboration of the side arm by reaction of an aryloxide with the cyclic sulfate 

ester was investigated using an adaptation of a literature method.'^"^^ The subsequent 

reaction was to be hydrolysis of the sulfate group. Model reactions with Sesamol were 

performed as shown in Table 3.4. Under all of the conditions employed, the reactions 

produced the desired product 108 together with its structural isomer 109. Variations of 

base-solvent combination and reaction temperature did not appreciably affect the ratio of 

the desired product 108 to its structural isomer 109. 

83 
Table 3.4. Reactions of Sesamol with Cyclic Sulfate Ester 107. 

o 

< 

o 

OH 

Sesamol 

DBase 

CgHn 

3) H2SO4, H2O 

THF 

rt, 1 h 

OH 

O^^^^^^OCHzCHCgHn 

<oXT 

108 

O 

< 

O 

,OCHC8H,7 

CHoOH 

109 

Yield' of 108:109 

Base (equiv.) Solvent Temp. Time, d 108 + 109, % Ratio 

CS2CO3 (2.5) CH3CN 

CS2CO3 (2.5) 

DBU (2.5) 

DMF 

CS2CO3 (2.5) CH3CN 

CH3CN 

CS2CO3(1.0) CH3CN 

CS2CO3 (2.5) CH3CN 

reflux 

80 °C 

50 °C 

50 °C 

50 °C 

50 °C 2 

69 (56) 

62 (48) 

49(44) 

45 (39) 

75(47) 

77 (46) 

-4:1 

-6:1 

-5:1 

-6:1 

-4:1 

-4:1 

The yields of 108 and 109 are combined. The isolated yield of 108 is shown in the parenthesis. 

Reaction of di(hydroxybenzo)-18-crown-6 with cyclic sulfate ester 107 and 

cesium carbonate in acetonitrile was attempted as shown in Scheme 3.19. From this 

reaction, 4,4'(5')-di[(2-hydroxydecyloxy)benzo]-18-crown-6 (110) was obtained in 21% 

yield by recrystallization from methanol. Another attempt using 1,8-diazabicyclo-

[5,4,0]undec-7-ene (DBU) as the base gave the compound 110 in 17% yield by column 

chromatography. However, the obtained product from the reaction with DBU was still 

contaminated with small amounts of impurity. 

84 
HO 

p O' 

OH 

l)Cs2C03 

CH3CN 

reflux, 3 h 

0"^0 

CsH 17 

reflux, 1 d 

3)H2S04, H2O 

THF 

rt, 1 h 

HO 

C8H,7CHCH20 

^ 

o o 

O 

O 

OH 

I 

OCH.CHC^Hl101 110(21%) 

Scheme 3.19. Synthesis of 4,4'(5')-Di[(2-hydroxydecyloxy)benzo]-18-crown-6 

(110). 

In an attempt to increase the reactivity of the aryloxide nucleophile, reaction of 

the isolated potassium phenoxide compounds with the cyclic sulfate ester was attempted. 

As a model study, potassium phenoxide (111) was prepared and reacted with cyclic 

sulfate ester 107 followed by hydrolysis to give (2-hydroxydecyloxy)benzene (112) in 

45% yield as shown in Scheme 3.20. Another model reaction was performed with 

OH KOH 

MeOH 

rt 

O'K^ 

111 

o^^o 

CgH 17 CH3CN 

rt,2h 

then, reflux, 5 min 

2) IN HCl 

reflux, 3 h 

OH 

a

OCHjCHCgHp 

112 (45% overall) 

Scheme 3.20. Synthesis of 2-Hydroxydecyloxybenzene (112). 

85 
Sesamol as shown in Scheme 3.21. Potassium 3,4-methylenedioxy-phenoxide (113) was 

prepared using same method as the preparation of potassium phenoxide (111). Reaction 

of 113 with the cyclic sulfate ester 107 followed by hydrolysis of the sulfate group gave 

l-(2'-hydroxydecyloxy)-3,4-methylenedioxybenzene (108) in 68% yield. The reaction 

o 

< 

OH KOH O 

C 

Sesamol 

MeOH 

n 

< 

113 

OK* 

1) o<>.-^o 

O^^O 

CgHn 

CH3CN 

rt, 2h 

then, reflux, 5 min 

2) IN HCl 

reflux, 3 h 

O 

< 

O 

OH 

OCH.CHCsHn 

108 (68% overall) 

Scheme 3.21. Synthesis of 1 -(2'-Hydroxydecyloxy)-3,4-niethylenedioxybenzene 

(108). 

was then attempted with the di-potassium salt of di(hydroxybenzo)-18-crown-6 114 as 

shown in Scheme 3.22. Although the same method was employed as in the model 

reactions, the obtained product 110 was still contaminated with unidentified impurities 

after attempted purification. 

86 
KOH 

MeOH 

rt 

OK^ 

101 114 

CH3CN ^ ^ 

rt,2h 

then, reflux, 5 min 

2) IN HCl 

reflux, 3 h 

HO ^ ^ 

C8H,7CHCH20-h 

110 (30%) 

OH 

1 

.OCH2CHC8H,7 

1 

Scheme 3.22. Attempted Synthesis of Crown Ether Diol 110. 

Although reaction of di(hydroxybenzo)-18-crown-6 with the cyclic sulfate ester produced 

the desired product in 21% yield, the method does not seem promising since it gives a 

complex mixture of products which includes a small amount of the desired product and 

significant amounts of unidentified impurities. 

3.1.2.3.2.3. Reaction with Benzyl Bromide. Since the reaction of 

di(hydroxybenzo)-18-crown-6 with epoxides and cyclic sulfate ester often produced a 

complex mixture of products, it seemed worthwhile to ascertain that the alkylation of 

di(hydroxybenzo)-18-crown-6 was achievable. Benzylation of di(hydroxybenzo)-18-

crown-6 was attempted as shown in Scheme 3.23. Reaction of di(hydroxybenzo)-18-

crown-6 (101) with cesium carbonate and benzyl bromide in acetonitrile gave 

87 
di(benzyloxybenzo)-18-crown-6 (115) in 80% yield. Thus reaction with an active 

alkylating agent did indeed give the desired product of di-alkylation. 

1)CS2C03 

\ ^ I CH3CN ( o 

a

O OY=:^O H reflux. 3 h ff^V' ^ °Y^> ^ 

O 0"^^====:^ 2)PhCH2Br ^^"'^^Jk ^ Q'^ ^ 

OCH^Ph 

O^ reflux, 1 d O 

101 115 (80%) 

Scheme 3.23. Synthesis of Di(benzyloxybenzo)-18-crown-6 (115). 

3.1.2.3.3. Synthesis of Di[(2-hydroxyalkoxy)benzo]-18-crown-6 

Involving a Grignard Reaction 

While the synthesis of di[(2-hydroxyalkoxy)benzo]-18-crown-6 described above 

was accomplished by alkylation of di(hydroxybenzo)-18-crown-6, another synthetic route 

to di[(2-hydroxyalkoxy)benzo]-18-crown-6 involving a Grignard reaction as a key step 

was explored. 

3.1.2.3.3.1. Grignard Reaction of an Acid Chloride Followed by Reduction. For 

the synthesis of di[(2-hydroxyalkoxy)benzo]-18-crown-6, a four step synthesis starting 

from di(hydroxybenzo)-18-crown-6 (101) was proposed (Scheme 3.24). The hydroxy 

groups of di(hydroxybenzo)-18-crown-6 (101) was to be converted into oxyacetic acid 

side arms. Then, crown ether dicarboxylic acid 116 was to be converted to crown ether 

diketone via a Grignard reaction of the acid chloride derivative 117. Subsequent 

reduction would provide crown ether diol. 

88 
HO 

O 

o o 

o o 

o 

OH O 

II HOCCH.O 

O 

O O 

O O 

O 

O 

II 

OCH-,COH 

101 116 

O 

II 

RCCH--0 

O 

O O 

o o 

O 

o 

II 

OCH.CR 

o 

C1CCH20 

.0 o^ 

o o 

o 

II 

OCHoCCl 

117 

HO 

I 

RCHCH2O 

O 

O O 

O O 

O 

OH 

I 

OCH2CHR 

Scheme 3.24. Strategy for Crown Ether Diol Synthesis Involving a Grignard 

Reaction of an Acid Chloride. 

To probe the viability of this synthetic strategy, a model reaction with Sesamol 

was performed. Reaction of Sesamol with bromoacetic acid and sodium hydride in 

tetrahydrofuran produced (3,4-methylenedioxy)phenoxyacetic acid (118) in 57% yield as 

shown in Scheme 3.25. With carboxylic acid derivative 118 in hand, the synthesis of 1 -

(3',4'-methylenedioxy)phenoxy-2-decanone (119) was attempted as shown in Scheme 

3.26. Reaction of carboxylic acid 118 with oxalyl chloride in benzene followed by a 

89 
< 

Sesamol 

l)NaH 

THF 

rt, 2h 

2) BrCH2C02H 

rt, ovemight 

3) H3O+ 

OCH2CO2H 

118 (57%) 

Scheme 3.25. Synthesis of (3,4-Methylenedioxy)phenoxyacetic acid (118). 

Grignard reaction ' with octylmagnesium bromide in the presence of iron(ni) 

acetylacetonate in tetrahydrofuran gave the desired product 119 (as identified by 

appropriate peaks in the ' H NMR spectmm of the product) together with the unexpected 

ester product 120. Isolation of the desired product 119 could not be achieved and only a 

o 

< 

o 

OCH2CO2H 

118 

1)(C0C1)2 

benzene 

reflux, 2 h 

2)C8Hi7MgBr 

3% Fe(acac)3 

THF 

rt, 40 min 

O 

< 

o 

OCH2CC8 II H 17 o 

< 

o 

o 

OCH2COC8 11 H 17 

119 120 

Scheme 3.26. Attempted Synthesis of l-(3',4'-Methylenedioxy)phenoxy-2-

decanone (119). 

very small amount of ester product 120 was isolated in 4% yield by recrystallization. 

The detailed mechanism for the formation of the unexpected ester product 120 was 

unclear. Removal of oxygen by a nitrogen sweep of the reaction did not suppress 

formation of the ester product. 

90 
3.1.2.3.3.2. Grignard Reaction of an Aldehyde. Secondary alcohols can be 

generated by Grignard reactions of aldehydes. Incorporation of an aldehyde group into 

the side arm of crown ether diol 101 would make it possible to synthesize di[(2-

hydroxyalkoxy)benzo]-18-crown-6 as shown in Scheme 3.27 Di(hydroxybenzo)-18-

crown-6 (101) is treated to convert to crown ether 121 followed by deprotection of 

diethyl acetal group to give crown ether dialdehyde 122. A subsequent Grignard 

reaction of this product 122 would produce the desired crown ether diol. 

(ElO)2CHCH20+ 

.OCH2CH(OEl); 

HO 

RCHCH2O 

101 

o o C o ^ 

OH 

I 

OCH2CHR 

121 

HCCH2O-I- II 

O O 

O 

II 

OCH,CH 

122 

Scheme 3.27. Strategy for Crown Ether Diol Synthesis Involving a Grignard 

Reaction of an Adehyde. 

A model reaction with Sesamol was used to investigate the feasibility of this 

synthetic strategy. For incorporation of the aldehyde group into the side arm, 

commercially available bromoacetaldehyde diethyl acetal was chosen. The reaction of 

Sesamol with cesium carbonate and bromoacetaldehyde diethyl acetal in acetonitrile gave 

91 
(3,4-methylenedioxy)phenoxyacetaldehyde diethyl acetal (123) in high yield as shown in 

Scheme 3.28. 

1)CS2C03 

CH3CN 

reflux, 3 h 

2) BrCH2CH(OEt)2 

reflux, 1 d 

0 ^ 

0 ^ 0 0CH2CH(0Et) 

Sesamol 123 (93%) 

Scheme 3.28. Synthesis of (3,4-Methylenedioxy)phenoxyacetaldehyde Diethyl 

Acetal (123). 

For the (3,4-methylenedioxy)phenoxyacetaldehyde (124) to be used for in a 

Grignard reaction, deprotection of the diethyl acetal group was needed. Reaction of the 

protected aldehyde 123 with boron trifluoride etherate and sodium iodide in acetonitrile 30 

gave an unexpected benzofuran derivative 125 in 50% yield (Scheme 3.29). 

92 
o 

< 

o 

OCH2CH(Oa)2 

123 

^ 

BF3.(OEt)2 

Nal 

CH3CN 

reflux, 2 h 

O 

II OCH.CH 

124 

125 (50%) 

Scheme 3.29. Attempted Synthesis of (3,4-Methylenedioxy)-

phenoxyacetaldehyde (124). 

A possible mechanism for the formation of benzofuran derivative 125 is presented 

in Figure 3.3. Initial Lewis acid complexation with the carbonyl oxygen and subsequent 

o 

0^,^^\^°^"2CIHI BF3(OEt)2 

O 

< 1 1 

124 

0 

rO 

z-^- ^l l 

t^OCHz—CH O 

< 

Co. 

O e 

H O-BF3 

iX)^ -H ® 

125 

H ® O^ ^H 

© 0 

Cp-BF3 

H 

Figure 3.3. Proposed Mechanism for the Formation of Benzofuran Derivative 

125. 

93 
attack of 7C-bond in benzene to carbonyl carbon atom would form a five membered ring. 

The abstraction of proton and the release of the positive charge on oxygen atom in furan 

would give the aromaticity back to molecule with the formation of benzene. Then, 

dehydration would produce the benzofuran derivative 125. 

Other attempts to deprotect the diethyl acetal group in (3,4-methylenedioxy)-

phenoxyacetaldehyde diethyl acetal (123) with 50% aqueous trifluoroacetic acid in 

chloroform ' or ferric chloride hexahydrate^^ were conducted as shown in Table 3.5. 

Table 3.5. Attempted Synthesis of (3,4-methylenedioxy)phenoxyacetaldehyde (124). 

OCH2CH(OEt)2 50% CF3CO2H O 

123 

or 

FeCl3-6H20 

124 

O 

II 

OCH2CH 

<Xi^ 

125 

Reagent Solvent Temp. Time Products 

CF3CO2H CHCI3 

CF3CO2H CHCI3 

CF3CO2H CHCI3 

CF3CO2H CHCI3 

FeCl36H20 CH2CI2 

0°C 

rt 

50 °C 

50 °C 

rt 

1.5 h 

ovemight 

2h 

ovemight 

1 h 

Unreacted 123 

Unreacted 123 

124 and unreac 

124 and 125 

124,125 and u 

From attempted deprotection with trifluoroacetic acid at 0 °C or room 

temperature, the unreacted starting material 123 was recovered. Raising the reaction 

temperature to 50 °C for 2 hours produced only an 18% conversion to the aldehyde 124. 

94 
hicreasing the reaction time at 50 °C gave significant amounts of the benzofuran 

derivative 125 together with the desired aldehyde 124. Attempted deprotection of (3.4-

methylenedioxy)phenoxyacetaldehyde diethyl acetal (123) with ferric chloride 

hexahydrate in dichloromethane^^ gave a mixture of unreacted 123, the desired aldehyde 

124, and the benzofuan derivative 125. 

Treatment of (3,4-methylenedioxy)phenoxyacetaldehyde diethyl acetal (123) with 

hydrochloric acid in tetrahydrofuran^^ did not produce the desired product 124 as shown 

in Scheme 3.30. An unidentified mixture of products was obtained. 

O 

0^^^;;^\^OCH2CH(OEt)2 2N HCl 0^.^^\^OCH2CH 

<XJ -^—X— <„XJ 

rt,24h 

123 124 

Scheme 3.30. Attempted Synthesis of (3,4-Methylenedioxy)-

phenoxyacetaldehyde (124). 

3.2. Chapter Summary 

Several series of bis(l-hydroxyalkyl)-substituted crown ethers were prepared by 

acylation of dibenzo-18-crown 6 or dibenzo-21 -crown-7 followed by reduction. Further 

elaboration on the hydroxyl functional group of the bis(l-hydroxyalkyl)-substituted 

crown ethers was also accomplished. 

The synthesis of bis(2-hydroxyalkyl)-substituted crown ethers was attempted by 

three different methods. Attempted isomerization of the hydroxyl group gave an 

elimination product. Other attempts for the synthesis of bis(2-hydroxyalkyl)-substituted 

95 
crown ethers by oxymercuration-demercuration or hydroboration-reduction of crown 

ether alkenes gave mixtures of two isomeric crown ether diols. 

Attempted 2+2 reactions of Sesamol and bis(2-chloroethyl) ether and base did not 

form the desired substituted dibenzo-18-crown-6 compound. 

Although reactions of Sesamol with base and an epoxide gave efficient coupling, 

this reaction could not be extended to di(hydroxybenzo)-18-crown-6. Secondly, the 

feasibility of a potential synthesis of di[(hydroxyalkoxy)benzo]-18-crown-6 compounds 

by a method which was tested by reaction sequence involves a Grignard reaction of a 

carbonyl functional group was found to be unsuccessful for the model compound 

Sesamol. 

3.3. Experimental Procedures 

3.3.1. Sources of Reagents 

Commercially available reagents were used as received unless otherwise 

specified. Sesamol from Aldrich was dried by benzene azeotropic distillation with a 

Dean-Stark apparatus. 

3.3.2. Purification of Reagents 

Dry solvents were prepared as follows: tetrahydrofuran (THF) was freshly 

distilled from sodium metal ribbon or chunks and benzophenone ketyl; CH3CN was 

distilled from CaH2; N,N-dimethylformamide (DMF) was distilled from MgS04 under 

reduced pressure; r-BuOH was distilled from CaH2; n-BuOH was distilled from CaH2. 

96 
Dibenzo-18-crown-6 from Jassen Chimica was purified by column 

chromatography on alumina with ethyl acetate-hexanes (1:3) as eluent followed by 

recrystallization from hexanes-CH2Cl2. 

3.3.3. General 

The instrumentation used in this portion of research was same as that described in 

the Experimental Procedure section of Chapter 2. 

Thin layer chromatography (TLC) was conducted with either Alumina GF or 

Silica Gel GF Uniplates from Analtech. Column chromatography was performed with 

80-200 mesh alumina from Fisher Scientific or 60-200 mesh silica gel from EM Sciences. 

3.3.4. General Procedure for the Synthesis of 

Dibenzo-18-crown-6 Diketones 66-69 

Into a 250-mL, three-necked, round-bottomed flask fitted with a thermometer 

were added dibenzo-18-crown-6 (lO.CX) g, 42.0 mmol, 1.0 equivalent), the appropriate 

carboxylic acid (2.0 equivalents), and Eaton's reagent^ (76.00 g) under nitrogen. The 

reaction mixture was stirred magnetically for 4-6 hours at 50 °C under nitrogen. During 

this time, the reaction mixture turned cherry red. The reaction mixture was poured into a 

mixture of 150 g of ice and 150 mL of water and stirred ovemight with a mechanical 

stirrer at room temperature. The reaction mixture was separated by filtration. The 

filtered solid was dissolved in 150 mL of CH2CI2 and washed veiy vigorously with 5% 

NaOH solution (3 X 100 mL) and water (3 X 100 mL). The CH2CI2 layer was dried over 

MgS04 and evaporated in vacuo. Column chromatography on alumina with CH2CI2 as 

eluent gave the product. 

97 
Notes: 1. For the condensation of 10.0 mmol of carboxylic acid, 9.(X) g of Eaton's 

reagent was used. 

2. In the acylation with 2-ethylhexanoic acid, sometimes the solid was 

very sticky after pouring the reaction mixture into the water and then stirring ovemight. 

In this case, the aqueous solution was decanted from the solid. 

3.3.4.1. 4,4'(5')-Di[(butanoyl)benzo]-18-crown-6 (66) was obtained in 79% 

yield as a light yellow solid with mp 162-165 °C (lit.^ mp 149-159 and 174-182 ''C). IR 

(deposit from CH2CI2 solution on a NaCl plate): 1673 (C=0); 1267 and 1139 (C-O) cm '. 

^H NMR (CDCI3): 5 0.99 (t, J = 7.4 Hz, 6H); 1.65-1.80 (m, 4H); 2.88 (t, J = 7.3 Hz, 4H); 

4.00-4.25 (m, 16H); 6.85 (d, J = 8.3 Hz, 2H); 7.50-7.59 (m, 4H). Anal. Calcd. for 

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) was obtained in 55% 

yield as a light yellow solid with mp 125-128 °C (lit.^ mp 144-147 °C). IR (deposit from 

CH2CI2 solution on a NaCl plate): 1673 (C=0); 1271 and 1141 (C-O) cm"'. 'H NMR 

(CDCI3): 6 0.90 (t, y = 6.8 Hz, 6H); 1.30-1.75 (m, 12H); 2.89 (t, J = 1.4 Hz, 4H); 4.00-

4.25 (m, 16H); 6.85 (d, 7= 8.3 Hz, 2H); 7.50-7.58 (m, 4H). Anal. Calcd. for 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) was obtained in 49% 

yield as a light yellow solid with mp 121 -124 °C (lit.^ mp 117-129 °C). IR (deposit from 

CH2CI2 solution on a NaCl plate): 1668 (C=0); 1270 and 1141 (C-O) cm'. 'H NMR 

(CDCI3): 60.80 (t, 7 = 6.4 Hz, 6H); 1.03-1.42 (m, 24H); 1.50-1.76 (m, 4H); 2.82 (t, 7 = 

7.4 Hz, 4H); 3.95-4.16 (m, 16H); 6.78 (d, 7= 8.3 Hz, 2H); 7.44-7.50 (m, 4H). 

98 
3.3.4.4. 4,4'(5')-Di[(2-ethylhexanoyl)benzo]-18-crown-6 (69) was obtained in 

92% yield as a light yellow solid with mp 89-91 °C. IR (deposit from CH2CI2 solution 

on a NaCl plate): 1668 (C=0); 1265 and 1139 (C-O) cm'. 'HNM R (CDCI3): 60.81-

1.79 (m, 28H); 3.19-3.40 (m, 2H); 4.01-4.24 (m, 16H); 6.86 (d, 7 = 8.3 Hz, 2H); 7.52-

7.59 (m, 4H). Anal. Calcd. for C36H52O8: C, 70.56; H, 8.55. Found: C, 70.63; H, 8.52. 

3.3.5. General Procedure for the Synthesis of 

Dibenzo-18-crown-6 Diols 70-72 

Into a 500-mL, one-necked, round-bottomed flask were added 10.(X) g of the 

appropriate dibenzo-18-crown-6 diketone (66, 67, or 68) (1.0 equivalent), NaBH4 (5.2 

equivalents), absolute ethanol (150 mL), and dichloromethane (1(X) mL) under nitrogen. 

The reaction mixture was stirred for 4 hours at room temperature under nitrogen and then 

poured into 100 mL of water. The reaction mixture was neutralized with 6 N HCl 

solution to pH = 7 in an ice bath. The mixture was extracted with CH2CI2 (3 X 1(X) mL), 

dried over MgS04, and evaporated in vacuo to give the product. 

3.3.5.1. 4,4'(5')-Di[(l-hydroxybutyl)benzo]-18-crown-6 (70) was obtained after 

column chromatography on alumina with EtOAc as eluent to remove a small amount of 

less polar impurity, then with EtOAc-MeOH (10:1) as eluent in quantitative yield as a 

white solid with mp 145-152 °C (lit.^ mp 135-147 °C). IR (deposit from CH2CI2 solution 

on a NaCl plate): 3374 (O-H); 1264 and 1137 (C-O) cm"'. 'H NMR (CDCI3): 5 0.92 (t, 7 

= 7.2 Hz, 6H); 1.24-1.80 (m, 8H); 2.01 (s, 2H); 4.01-4.20 (m, 16H); 4.59 (t, 7= 5.8 Hz, 

2H);6.86(d,7=11.9Hz,6H). 

99 
3.3.5.2. 4,4'(5')-Di[(l-hydroxyhexyl)benzo]-18-crown-6 (71) was obtained after 

recrystallization from CH2Cl2-hexanes in 90% yield as a light yellow solid with mp 127-

132 °C (lit.^ mp 135-145 °C). IR (deposit from CH2CI2 solution on a NaCl plate): 3382 

(O-H); 1263 and 1139 (C-O) cm"'. 'H NMR (CDCI3): 8 0.85 (t, 7= 6.4 Hz, 6H); 1.08-

1.89 (m, 16H); 1.93 (s, 2H); 3.99-4.19 (m, 16H); 4.56 (t, 7= 6.6 Hz, 2H); 6.84 (d, 7 = 

12.1 Hz, 6H). 

3.3.5.3. 4,4'(5')-Di[(l-hydroxydecyl)benzo]-18-crown-6 (72) was obtained after 

column chromatography on alumina with EtOAc as eluent to remove a small amount of 

less polar impurity, then with EtOAc-MeOH (20:1) as eluent in 80% yield as a white 

solid with mp 134-137 °C (lit.^ mp 120-122 and 145-148 °C). IR (deposit from CH2CI2 

solution on a NaCl plate): 3374 (O-H); 1266 and 1141 (C-O) cm"'. 'H NMR (CDCI3): 6 

0.87 (t, 7= 6.4 Hz, 6H); 1.06-1.82 (m, 32H); 1.85 (d, 7= 2.8 Hz, 2H); 4.00-4.20 (m, 

16H); 4.54-4.60 (m, 2H); 6.85 (d, 7 = 12.0 Hz, 6H). 

3.3.6. Preparation of 4,4'(5')-

Di[(2-ethyl-l-hydroxyhexyl)benzo]-18-crown-6 (73) 

Into a 500-mL, one-necked, round-bottomed flask were added 4,4'(5')-Di[(2"-

ethylhexanoyl)benzo]-18-crown-6 (69) (6.00 g, 9.79 mmol), NaBH4 (1.94 g, 51.4 mmol), 

and absolute ethanol (150 mL) under nitrogen. The reaction mixture was stirred for 24 

hours at room temperature under nitrogen and then poured into 120 mL of water. The 

mixture was neutralized with 6 N HCl solution to pH = 7 in an ice bath. The mixture 

was extracted with CH2CI2 (3 X 100 mL), dried over MgS04, and evaporated in vacuo. 

Column chromatography on alumina with CH2CI2 as eluent to remove the unconsumed 

100 
reactant, then with EtOAc as eluent gave 5.24 g (87%) of the product as a white solid 

with mp 130-136 °C. IR (deposit from CH2CI2 solution on a NaCl plate): 3392 (O-H): 

1261 and 1139 (C-O) cm"'. 'H NMR (CDCI3): 80.78-1.65 (m. 30H); 1.72 (s. 2H): 4.00-

4.17 (m, 16H); 4.43-4.60 (m,2H); 6.84 (d, 7 = 9.1 Hz. 6H). Anal. Calcd. for C36H56O8: 

C, 70.10: H, 9.15. Found: C, 70.46; H, 9.09. 

3.3.7. Preparation of 

4,4'(5')-Di[(2-ethyl-1 -(2-hydroxyethoxy)hexyl)benzo]-

18-crown-6(74) 

Into a 10(X)-mL, one-necked, round-bottomed flask were added 4,4'(5')-

di[(2-ethyl-l-hydroxyhexyl)benzo]-18-crown-6 (73) (5.23 g, 8.48 mmol), ethylene glycol 

(10.55 g. 0.17 mol), and CH2CI2 (425 mL) under nitrogen. Concentrated H2SO4 (26 

drops) was added and the reaction mixture was stirred for 15 hours at room temperature 

under nitrogen. The reaction mixture was washed with water (3 X 1(X) mL), dried over 

MgS04, and evaporated in vacuo. Column chromatography on alumina with EtOAc as 

eluent to remove a small amount of less polar impurity, then with EtOAc-MeOH (20:1) 

as eluent gave 4.98 g (83%) of the product as a yellow, viscous liquid. IR (deposit from 

CH2CI2 solution on a NaCl plate): 3384 (O-H); 1261 and 1138 (C-O) cm"'. 'H NMR 

(CDCI3): 80.73-1.53 (m, 30H); 3.29-3.38 (m, 4H); 3.62-3.70 (m. 4H); 4.03-4.17 (m, 

20H); 6.76-6.82 (m, 6H). Anal. Calcd. for C40H64O10: C, 68.15; H, 9.15. Found: C, 

68.41; H, 9.18. 

Note: The ethylene glycol was dried with a benzene azeotrope in a Dean-Stark 

apparatus. 

101 
3.3.8. Preparation of 

4,4X5')-Di[(2-ethyl-l-(5-hydroxy3-oxapentoxy)hexyl)benzo]-18-crown-6 (75) 

Into a 100-mL, one-necked, round-bottomed flask were added 4,4'(5')-

di[(2-ethyl-l-hydroxyhexyl)benzo]-18-crown-6 (73) (0.48 g, 0.78 mmol), diethylene 

glycol (1.66 g, 15.6 mmol), and CH2CI2 (40 mL) under nitrogen. Concentrated H2SO4 (3 

drops) was added and the reaction mixture was stirred for 15 hours at room temperature 

under nitrogen. The reaction mixture was washed with water (3 X 20 mL), dried over 

MgS04, and evaporated in vacuo. Column chromatography on alumina with EtOAc as 

eluent to remove a small amount of less polar impurity, then with EtOAc-MeOH (20:1) 

as eluent gave 0.47 g (76%) of the product as a yellow, viscous liquid. IR (deposit from 

CH2CI2 solution on a NaCl plate): 3420 (O-H); 1261 and 1137 (C-O) cm"'. 'H NMR 

(CDCI3): 8 0.65-1.71 (m, 30H); 2.52 (br s, 2H); 3.34-4.29 (m, 34H); 6.71-6.81 (m, 6H). 

Anal. Calcd. for C44H72O12: C, 66.64; H, 9.15. Found: C, 66.72; H, 9.29. 

Note: The diethylene glycol was dried with a benzene azeotrope in a Dean-Stark 

apparatus. 

3.3.9. Preparation of 

4,4'(5')-Di[(2-ethylhexanoyl)benzo]-21-crown-7 (77) 

Into a 250-mL, three-necked, round-bottomed flask fitted with a thermometer 

were added dibenzo-21-crown-7 (76) (12.00 g, 27.7 mmol), 2-ethylhexanoic acid (9.41 g, 

65.3 mmol), and Eaton's reagent^ (60.00 g) under nitrogen. The reaction mixture was 

stirred magnetically for 4-6 hours at 30-35 °C under nitrogen. During this time, the 

reaction mixture turned cherry red. The reaction mixture was poured into a mixture of 

102 
120 g of ice and 120 mL of water and stirred ovemight at room temperature with a 

mechanical stirrer. The reaction mixture was separated by filtration. The filtered solid 

was dissolved in 150 mL of CH2CI2 and washed very vigorously with 5% NaOH solution 

(3 X 100 mL) and water (3 X 100 mL). The CH2CI2 layer was dried over MgS04 and 

evaporated in vacuo. Column chromatography on alumina with CH2CI2 as eluent gave 

16.11 g (83%) of the product as a white solid with mp 63-65 °C. IR (deposit from 

CH2CI2 solution on a NaCl plate): 1670 (C=0); 1266 and 1136 (C-O) cm"'. 'H NMR 

(CDCI3): 8 0.81-0.89 (m, 12H); 1.17-1.83 (m, 16H); 3.26-3.33 (m, 2H); 3.89-4.27 (m, 

20H); 6.88 (d, 7=8.1 Hz, 2H); 7.53-7.62 (m, 4H). Anal. Calcd. for C38H56O9: C, 69.49; 

H, 8.59. Found: C, 69.30; H, 8.52. 

Notes: 1. Dibenzo-21-crown-7 was prepared by a literature method."^ 

2. Sometimes the solid was very sticky after pouring the reaction mixture 

into the water and then stirring ovemight. In this case, the aqueous solution was 

decanted from the solid. 

3.3.10. Preparation of 4,4'(5')-

Di[(2-ethyl-1 -hydroxyhexyl)benzo]-21 -crown-7 (78) 

Into a 250-mL, one-necked, round-bottomed flask were added 4,4'(5')-di[(2-

ethylhexanoyl)benzo]-21-crown-7 (77) (4.60 g, 7.00 mmol), NaBH4 (1.38 g, 36.58 

mmol), and absolute ethanol (125 mL) under nitrogen. The reaction mixture was stirred 

for 24 hours at room temperature under nitrogen and then poured into 100 mL of water. 

The mixture was neutralized with 6 N HCl solution to pH = 7 in an ice bath. The 

mixture was extracted with CH2CI2 (3 X 100 mL), dried over MgS04, and evaporated in 

103 
vacuo. Column chromatography on silica gel with Et20 gave the product in quantitative 

yield as a colorless, viscous liquid. IR (deposit from CH2CI2 solution on a NaCl plate): 

3449 (O-H); 1264 and 1139 (C-O) cm"'. 'H NMR (CDCI3): 8 0.70-1.63 (m, 30H); 1.77 

(s, 2H); 3.80-4.23 (m, 20H); 4.45-4.62 (m, 2H); 6.83-6.91 (m, 6H). Anal. Calcd. for 

C38H60O9: C, 69.06; H, 9.15. Found: C, 69.05; H, 8.88. 

3.3.11. Preparation of 

4,4'(5')-Di[(2-ethyl-l-(5-hydroxy3-oxapentoxy)hexyl)benzo]-21 -crown-7 (79) 

Into a 1000-mL, one-necked, round-bottomed flask were added 4,4'(5')-

di[(2-ethyl-l-hydroxyhexyl)benzo]-21-crown-7 (78) (5.03 g, 7.16 mmol), diethylene 

glycol (15.92 g, 0.15 mol), and CH2CI2 (380 mL) under nitrogen. Concentrated H2SO4 

(23 drops) was added and the reaction mixture was stirred for 15 hours at room 

temperature under nitrogen. The reaction mixture was washed with water (3 X 100 mL), 

dried over MgS04, and evaporated in vacuo. Column chromatography on alumina with 

EtOAc as eluent to remove a small amount of less polar impurity, then with EtOAcMeOH (20:1) as eluent gave 5.33 g (84%) of the product as a yellow viscous liquid. IR 

(deposit from CH2CI2 solution on a NaCl plate): 3454 (O-H); 1262 and 1135 (C-O) cm"'. 

'H NMR (CDCI3): 8 0.64-1.72 (m, 30H); 2.50 (br s, 2H); 3.25-4.31 (m, 38H); 6.73-6.87 

(m, 6H). Anal. Calcd. for C46H760,3: C, 66.00; H, 9.15. Found: C, 65.88; H, 9.09. 

Note: The diethylene glycol was dried with a benzene azeotrope in a Dean-Stark 

apparatus. 

104 
3.3.12. Attempted Synthesis of 

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

18-crown-6 (82) from 4,4'(5')-Di[(2-ethyl-lhydroxyhexyl)benzo]-18-crown-6 (73) 

by Isomerization 

3.3.12.1. Isomerization with Sulfuric Acid 

Into a lOO-mL, one-necked, round-bottomed flask were added 4,4'(5')-di[(2-ethyll-hydroxyhexyl)benzo]-18-crown-6 (73) (0.10 g, 0.16 mmol) and CH2CI2 (20 mL). 

Concentrated H2SO4 (0.50 mL) was added and the reaction mixture was stirred for 6 

hours at room temperature. The reaction mixture was neutralized with 5% aqueous 

Na2C03 and washed with water (20 mL). The CH2CI2 layer was dried over anhydrous 

Na2S04 and evaporated in vacuo. Column chromatography on alumina with Et20 as 

eluent to remove the less polar impurity, then with EtOAc as eluent gave 0.09 g of a 

mixture of six isomers of alkene substituted products 83-88. The ratio of the 1 -alkene 

side group to the 2-alkene side group in the mixture was determined from integration of 

the vinylic proton absorptions in the 'H NMR spectrum of the mixture. IR (deposit from 

CH2CI2 solution on a NaCl plate): 1603 (C=C); 1260 and 1139 (C-O) cm"'. 'H NMR 

(CDCI3): 8 0.84-2.25 (m, 28H); 3.21 (d, 7 = 4.1 Hz, 2H, benzylic protons of 2-alkene side 

group); 3.30 (d, 7 = 2.2 Hz, 2H, benzylic protons of of 2-alkene side group); 4.02-4.16 

(m, 16H); 5.14-5.39 (m, 2H, vinylic protons of 2-alkene side group); 6.15 (s, 2H, vinylic 

protons of 1-alkene side group); 6.67-6.83 (m, 6H). The ratio of l-alkene:2-alkene side 

groups = 73:27. 

Note: Another attempt with 5% H2SO4 gave a mixture of the six alkene 

substituted products 83-88 with a ratio of of l-alkene:2-alkene side groups = 3:1. 

105 
3.3.12.2. Isomerization with Hydrochloric Acid 

Into a 100-mL, one-necked, round-bottomed flask were added 4,4'(5')-di[(2-ethyll-hydroxyhexyl)benzo]-18-crown-6 (73) (0.10 g, 0.16 mmol) and CH2CI2 (20 mL). HCl 

(5%, 0.50 mL) was added and the reaction mixture was stirred for 6 hours at room 

temperature. The reaction mixture was neutralized with 5% aqueous Na2C03 and 

washed with water (20 nti:.). The CH2CI2 layer was dried over anhydrous Na2S04 and 

evaporated in vacuo to give the unreacted starting material. 

Note: Another attempt with concentrated HCl gave the unreacted starting material 

73 and a small amount of elimination product 83 with ratio of 73:83 = 85:15 on the basis 

of the H NMR spectrum. The ratio of the starting material 73 to the alkene substituted 

product 83 was determined by the comparison of the integration areas for the benzylic 

proton absorption from 73 and the vinylic proton absorption from 83. 

3.3.13. Attempted Synthesis of Alkene-Substituted 

Dibenzo-18-crown-6 83 from 

Dibenzo-18-crown-6 Diol 73 

Giving a Mixture of Six Isomers 83-88 

Into a 250-mL, one-necked, round-bottomed flask were added 4,4'(5')-di[(2-ethyll-hydroxyhexyl)benzo]-18-crown-6 (73) (1.00 g, 1.62 mmol), p-toluenesulfonic acid 

(0.10 g, 0.53 mmol), and dry benzene (1(X) mL). A Dean-Stark apparatus was attached 

to the reaction flask to remove water during the reaction. The reaction mixture was 

refluxed for 30 minutes under nitrogen. The solvent was evaporated in vacuo and the 

residue was dissolved in 100 mL of CH2CI2. The CH2CI2 layer was washed with water 

(3 X 20 mL), dried over MgS04, and evaporated in vacuo. Column chromatography on 

alumina with CH2Cl2-EtOAc (40:1) as eluent gave a mixture of six isomers 83-88 as a 

106 
white solid. The ratio of the 1-alkene side group to the 2-alkene side group in the 

mixture was determined by the comparison of the integration areas for the vinylic proton 

absorptions in the mixture of six isomers of alkene substituted products 83-88. The ratio 

of 1-alkene:2-alkene side groups = 83:17. 

3.3.14. Preparation of 

4,4'(5')-Di[(l-decenyl)benzo]-18-crown-6(90) 

Into a 500-mL, one-necked, round-bottomed flask were 4,4'(5')-di[(lhydroxydecyl)benzo]-18-crown-6 (72) (4.50 g, 6.69 mmol), p-toluenesulfonic acid (0.45 

g, 2.37 mmol), and dry benzene (300 mL). A Dean-Stark apparatus was attached to the 

reaction flask to remove water during the reaction. The reaction mixture was refluxed 

for 2 hours under nitrogen. The solvent was evaporated in vacuo and the residue was 

dissolved in 300 mL of CH2CI2. The CH2CI2 layer was washed with water (3 X 50 mL), 

dried over MgS04, and evaporated in vacuo. Column chromatography on alumina with 

EtOAc-hexanes (1:2) as eluent gave 2.50 g (59%) of the product as a white solid with mp 

130-131 °C. IR (deposit from CH2CI2 solution on a NaCl plate): 1600 (C=C); 1266 and 

1139 (C-O) cm"'. 'H NMR (CDCI3): 80.88 (t, 7= 6.4 Hz, 6H); 1.08-1.59 (m, 24H); 

2.06-2.29 (q, 4H); 3.92-4.31 (m, 16H); 5.97-6.19 (m, 2H); 6.28 (d, 7= 15.8 Hz, 2H); 

6.77-6.90 (m, 6H). Anal. Calcd. for C40H60O6: C, 75.43; H, 9.50. Found: C, 75.37; H, 

9.59. 

107 
3.3.15. Attempted Synthesis of 

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

18-crown-6 (82) from the Mixture of Six AlkeneSubstituted Isomers 83-88 Giving a Mixture 

of Three Isomers 73, 82 and 89 

Mercury(n) acetate (0.98 g, 3.06 mmol) was dissolved in 3 mL of water in a 

50-mL, one-necked, round-bottomed flask. After a clear solution was obtained, 3 mL 

of THF was added to precipitate a yellow solid. To this reaction mixture was added the 

alkene-substituted dibenzo-18-crown-6 mixture (0.89 g, 1.53 mmol) with vigorous 

stirring. After stirring for 1 day at room temperature, 3.0 N NaOH solution (5 mL) was 

added followed by addition of 0.5 N NaBILi in 3.0 N NaOH solution (5 mL). The water 

layer was saturated with NaCl and K2CO3. The organic layer was separated and the 

water layer was washed with THF (10 mL). The combined organic layers were dried 

over MgS04, and evaporated in vacuo. Column chromatography on alumina with 

EtOAc as eluent to remove the unreacted starting material and with EtOAc-MeOH (20:1) 

as eluent and then recrystallization from CH2Cl2-hexanes gave 0.31 g (33%) of a mixture 

of three isomers 73, 82 and 89. The ratio of the 1 -alcohol side group to the 2-alcohol 

side group in the mixture was determined by the comparison of the integration areas for 

the benzylic proton absorptions in the 'H NMR spectrum of the mixture. IR (deposit 

from CH2CI2 solution on a NaCl plate): 3404 (O-H); 1267 and 1140 (C-O) cm"'. 'H 

NMR (CDCI3): 8 0.75-2.21 (m, 32H); 2.65 (s, 4H, benzylic protons of 2-alcohol side 

group); 3.88-4.29 (m, 16H); 4.46-4.57 (m, 2H, benzylic protons of 1-alcohol side group): 

6.69-6.91 (m, 6H). The ratio of 1-alcohol:2-alcohol side groups = 65:35. 

108 
Note: Another attempt with mercury(n) trifluoroacetate gave 0.35 g (63%) of a 

mixture of three isomers 73, 82 and 89 with a ratio of 1-alcohol:2-alcohol side groups = 

64:36. 

3.3.16. Attempted Synthesis of 

4,4'(5')-Di[(2-hydroxydecyl)benzo]-18-crown-6(91) 

from 4,4'(5')-Di[(l-decenyl)benzo]-18-crown-6 (90) 

Giving a Mixture of the Three Isomers 72. 91 and 92 

3.3.16.1. By Hydroboration-Oxidation 

Into a 100-mL, one-necked, round-bottomed flask were added NaBH4 (0.12 g, 

3.14 mmol) and dry THF (10 mL). A solution of 4,4*(5')-di[(l-decenyl)benzo]-18-

crown-6 (90) (0.90 g, 1.41 mmol) in 20 mL of dry THF was added into the reaction 

mixture. Boron trifluoride etherate (0.45 g, 3.14 mmol) was added dropwise into the 

reaction mixture during a period of 20 minutes at 0 °C under nitrogen. The reaction 

mixture was stirred for 10 hours at room temperature under nitrogen. To the reaction 

mixture were added dropwise 6 N aqueous NaOH solution (2.5 mL) and 30% aqueous 

H2O2 solution (3 mL) at 0 °C. The reaction mixture was stirred for an additional 3 hours 

at room temperature. To the reaction mixture were added CH2CI2 (20 mL) and water (10 

mL) and the mixture was shaken. The organic layer was separated, washed with 5% 

aqueous NaHC03 solution (3 X 20 mL), dried over MgS04, and evaporated in vacuo to 

give 0.92 g (97%) of the mixture of three isomers 72, 91 and 92. The ratio of the 1-

alcohol side group to the 2-alcohol side group in the mixture was determined by the 

comparison of the integration areas for the -CH-OH absorptions in the 'H NMR 

spectrum of the mixture. IR (deposit from CH2CI2 solution on a NaCl plate): 3404 (OH); 1267 and 1140 (C-O) cm'. 'H NMR (CDCI3): 80.73-2.83 (m, 40H); 3.61-3.85 (m, 

109 
2H, -CH-OH of 2-alcohol side group); 4.02-4.17 (m, 16H); 4.56 (t, 7 = 6.6 Hz. 2H. -CHOH of 1-alcohol side group): 6.70-6.88 (m, 6H). The ratio of 1-alcohol:2-alcohol side 

groups = 66:34. 

Note: Attempts to separate isomers 72, 91 and 92 by recrystallization with 

different solvents (EtOH, acetone, EtOAc, and CH2Cl2-hexanes) were unsuccessful. 

3.3.16.2. By Oxymercuration-Demercuration 

Mercury(II) trifluoroacetate (0.67 g, 1.58 mmol) was dissolved in 2 mL of water 

in a 50-mL, one-necked, round-bottomed flask. After a clear solution was obtained. 2 

mL of THF was added to precipitate the yellow solid. To this reaction mixture was 

added 4,4'(5')-di[(l-decenyl)benzo]-18-crown-6 (90) (0.50 g, 0.79 mmol) with vigorous 

stirring. After stirring for 1 day at room temperature, 3.0 N NaOH solution (5 mL) was 

added followed by addition of 0.5 N NaBHi in 3.0 N NaOH solution (5 mL). The water 

layer was saturated with NaCl and K2CO3. The organic layer wiis separated and the 

water layer was washed with THF (10 mL). The combined organic layers were dried 

over MgS04, and evaporated in vacuo. Column chromatography on alumina with 

EtOAc as eluent to remove the unreacted starting material and then with EtOAc-MeOH 

(20:1) as eluent gave 0.15 g (28%) of a mixture of the three isomers 72, 91 and 92. The 

ratio of the 1-alcohol side group to the 2-alcohol side group in the mixture was 

determined by the comparison of the integration areas for the -CH-OH absorptions in the 

'H NMR spectrum of the mixture. The ratio of l-alcohol:2-alcohol side groups = 45:55. 

110 
3.3.17. Preparation of l-(2'-Hydroxy)hexoxy3,4-methylenedioxybenzene (93) 

3.3.17.1. With Cesium Carbonate 

Into a 250-mL, three-necked, round-bottomed flask were added Sesamol (1.00 g. 

7.24 mmol), CS2CO3 (5.90 g, 18.1 mmol), and dry CH3CN (50 mL) under nitrogen. The 

reaction mixture was refluxed for 3 hours and then a solution of 1,2-epoxyhexane (0.73 g. 

7.24 mmol) in 25 mL of CH3CN was added over 2 hours. The reaction mixture was 

refluxed for 60 hours under nitrogen. The reaction mixture was filtered and the filtered 

solids were washed with CH2CI2. The combined filtrate and washings were evaporated 

in vacuo and the residue was dissolved in 50 mL of CH2CI2. The CH2CI2 layer was 

washed with water (25 mL), dried over MgS04, and evaporated in vacuo. Column 

chromatography on alumina with EtOAc-hexanes (1:10) as eluent to remove a small 

amount of less polar impurity, then with EtOAc-hexanes (1:5) as eluent gave 1.35 g 

(78%) of l-(2'-hydroxy)hexoxy-3,4-methylenedioxybenzene (93) as a yellowish, viscous 

liquid. IR (deposit from CH2CI2 solution on a NaCl plate): 3448 (O-H); 1186 and 1038 

(C-O) cm"'. ' H NMR (CDCI3): 8 0.92 (t, 7 = 7.0 Hz, 3H); 1.25-1.60 (m, 6H); 2.42 (d, 7 

= 3.5 Hz, IH); 3.70-3.78 (m, IH); 3.86-3.98 (m, 2H); 5.91 (s, 2H); 6.32 (dd, 7= 2.5 and 

8.4 Hz, IH); 6.50 (d, 7 = 2.4 Hz, IH); 6.69 (d, 7= 8.4 Hz, IH). Anal. Calcd. for 

C13H18O4: C, 65.53; H, 7.61. Found: C, 65.66; H, 7.71. 

3.3.17.2. With Sodium Hydroxide 

Into a 250-mL, three-necked, round-bottomed flask were added Sesamol (1.00 g, 

7.24 mmol), NaOH (0.58 g, 14.5 mmol), and r-BuOH (50 mL) under nitrogen. The 

111 
reaction mixmre was refluxed for 2 hours and then 1,2-epoxyhexane (0.73 g, 7.24 mmol) 

was added slowly into the reaction mixture under nitrogen. The reaction mixture was 

refluxed for 3 days. The reaction mixture was cooled to room temperamre and the tBuOH was evaporated in vacuo. The residue was dissolved in 50 mL of CH2CI2. The 

CH2CI2 layer was washed with water (2 X 25 mL) and the combined aqueous layers were 

extracted with CH2CI2 (2 X 25 mL). The combined CH2CI2 layers were evaporated in 

vacuo. Column chromatography on alumina with EtOAc-hexanes (1:10) as eluent to 

remove a small amount of less polar impurity, then with EtOAc-hexanes (1:5) as eluent 

gave 0.78 g (45%) of l-(2'-hydroxy)hexoxy-3,4-methylenedioxybenzene (93) as a 

yellowish, viscous liquid. 

3.3.18. Preparation of 3,4-Dihydroxyl-(2'-hydroxy)hexoxybenzene (94) 

Into a solution of l-(2'-hydroxy)hexoxy-3,4-methylenedioxybenzene (1.10 g, 4.62 

mmol) in 100 mL of CH2CI2 was added boron trichloride (1.08 g, 9.24 mmol) under 

nitrogen. The reaction mixture was stirred for 1 hour at room temperature under 

nitrogen. MeOH (20 mL) was added to destroy the excess of boron trichloride and the 

solvent was evaporated in vacuo. The residue was dissolved in 1 N aqueous HCl 

solution (50 mL) and the aqueous layer was extracted with CH2CI2 (7 X 1(X) mL). The 

combined CH2CI2 layers were evaporated in vacuo. Short column chromatography on 

silica gel with EtOAc-CH2Cl2 (1:5) as eluent to remove the more polar impurity and then 

recrystallization from CH2CI2 gave 0.53 g (50%) of 3,4-dihydroxy-l-(2'-hydroxy)-

hexoxybenzene (94) as a white solid with mp 73-76 °C. IR (deposit from CH2CI2 

solution on a NaCl plate): 3265 (O-H); 1165 (C-O) cm"'. 'H NMR (CDCbiDMSO-d^ 

112 
(10:1)): 8 0.92 (t, 7 = 7.0 Hz, 3H); 1.29-1.53 (m, 6H); 3.26 (br s, IH): 3.70-3.88 (m, 3H): 

6.29 (dd, 7 = 2.8 and 8.6 Hz, IH); 6.51 (d, 7 = 2.8 Hz, IH); 6.74 (d, 7 = 8.6 Hz, IH); 7.58 

(br s, 2H). Anal. Calcd. forCi2Hi804: C, 63.70; H, 8.02. Found: C, 63.41; H, 8.18. 

Note: Et20 may be substituted for CH2CI2 as the extracting solvent due to the low 

solubility of the product in CH2CI2. 

3.3.19. Attempted Synthesis of 

4,4'(5')-Di[(2-hydroxyhexoxy)benzo]-18-crown-6 (95) 

from 3,4-Dihydroxy-l-(2'-hydroxy)hexoxybenzene (94) 

Into a 100-mL, three-necked, round-bottomed flask equipped with a reflux 

condenser and a thermometer were added 3,4-dihydroxy-l-(2'-hydroxy)hexoxybenzene 

(94) (1.00 g, 4.42 mmol) and «-butanol (15 mL). Into the reaction mixture were added 

NaOH pellets (0.18 g, 4.49 mmol). The reaction mixture was heated to reflux and a 

solution of bis(2-chloroethyl)ether (0.33 g, 2.28 mmol) in 5 mL of n-butanol was added 

over 2 hours. After the reaction mixture was refluxed for an additional hour, it was 

cooled to 90 °C and NaOH pellets (0.18 g, 4.49 mmol) were added. The reaction 

mixture was refluxed for 30 minutes and a solution of bis(2-chloroethyl) ether (0.33 g, 

2.28 mmol) in 5 mL of n-butanol was added over a period of 2 hours. The reaction 

mixture was refluxed for 16 hours and cooled to room temperature, then acidified by the 

addition of concentrated HCl (1 drop). The solvent was evaporated in vacuo and the 

residue was dissolved in 200 mL of CH2CI2. The CH2CI2 layer was washed with water 

(3 X 50 mL), dried over MgS04, and evaporated in vacuo. Column chromatography on 

silica gel with EtOAc as eluent to remove the less polar impurities and then with EtOAcMeOH (10:1) as eluent and recrystallization from Et20 twice gave a white solid. IR 

113 
(deposit from CH2CI2 solution on a NaCl plate): 3380 (O-H); 1223, 1128. and 1060 (C0)cm"'. 'HNMR(CDCl3):80.92(t,7=6.9Hz,6H); 1.22-1.56 (m, 12H);2.31 (brs. 

2H); 3.71-4.13 (m, 22H); 6.39 (dd, 7 = 2.7and 8.7 Hz, 2H); 6.51 (d, 7= 2.4 Hz. 2H): 6.80 

(d, 7 = 8.7 Hz, 2H). 

Note: Column chromatography gave an impure product because there were many 

side products from the reaction mixture by TLC analysis. Recrystallization attempts 

gave a small amount of the product and the yield of the product was not determined. 

The obtained product was contaminated with a small amount of impurity that was not 

identified. 

3.3.20. Attempted Synthesis of 

1 -Benzyloxy-3,4-methylenedioxybenzene (96) 

from Sesamol 

3.3.20.1. Method A 

Into a 100-mL, three-necked, round-bottomed flask were added Sesamol (1.30 g, 

9.41 mmol), NaOH (0.38 g, 9.41 mmol), and dioxane (20 mL). Into the reaction mixture 

was added benzyl chloride (1.19 g, 9.41 mmol). The reaction mixture was stirred for 24 

hours at 1(X) °C under nitrogen. After cooling to room temperature, the reaction mixture 

was poured into 1(X) mL of H2O and the aqueous layer was extracted with CH2CI2 (3 X 

1(K) mL). The CH2CI2 layer was washed with 5 % aqueous NaOH solution (1(X) mL), 

dried over MgS04, and evaporated in vacuo. Column chromatography on silica gel with 

CH2Cl2-hexanes (1:5) as eluent gave 1.81 g of a yellow, viscous liquid. 

Note: The reaction gave a product that was contaminated with some impurities. 

The unidentified impurities were not separable by column chromatography. 

114 
3.3.20.2. Method R 

Into a 250-mL, one-necked, round-bottomed flask were added Sesamol (1.00 g. 

7.24 mmol), NaOH (0.43 g, 10.9 mmol), benzyl chloride (1.83 g, 14.5 mmol), and 

benzyltriethylammonium chloride (1.65 g, 7.24 mmol). Into the reaction mixture were 

added CH2CI2 (40 mL) and H2O (40 mL). The reaction mixture was stirred for 24 hours 

at room temperature. The CH2CI2 layer was separated and the aqueous layer was 

extracted with CH2CI2 (2 X 50 nti^). The combined CH2CI2 layer was washed with 2 N 

aqueous NaOH solution (100 mL) and brine (100 mL), dried over MgS04, and 

evaporated in vacuo. Column chromatography on silica gel with CH2Cl2-hexanes (1:5) 

as eluent gave 0.10 g of a yellow, viscous liquid. 

Note: The reaction performed under phase transfer catalyst gave the same result 

as Method A. The obtained product was contaminated with unidentified impurities. 

3.3.21. Attempted Synthesis of 

l-Benzyloxy-3,4-dihydroxybenzene (97) from 

1 -Benzyloxy-3,4-methylenedioxybenzene (96) 

Into a solution of l-benzyloxy-3,4-methylenedioxybenzene (96) (1.00 g, 4.38 

mmol) in 1(X) mL of CH2CI2 was added boron trichloride (1.03 g, 8.76 mmol) under 

nitrogen. The reaction mixture was stirred for 30 minutes at room temperature under 

nitrogen. MeOH (20 mL) was added over 10 minutes to destroy the excess of boron 

trichloride and then the solvent was evaporated in vacuo. The residue was dissolved in 1 

N aqueous HCl (100 mL) and the aqueous layer was extracted with CH2CI2 (3 X 100 

mL). The CH2CI2 layer was evaporated in vacuo. Column chromatography on silica gel 

with EtOAc-hexanes (1:10) as eluent gave a product. 

115 
Note: The starting material was contaminated with unidentified impurities and 

was used without further purification. The reaction gave 0.02 g of a less polar and 0.04 

g of a more polar product. Both products were found to be not the desired product by 'H 

NMR and IR spectroscopic analysis. 

3.3.22. Preparation of 

4,4'(5')-Di(nitrobenzo)-18-crown-6(98) 

Into a 10(X)-mL, three-necked, round-bottomed flask equipped with a mechanical 

stirrer and an additional funnel were added dibenzo-18-crown-6 (15.00 g, 41.6 mmol) 

and CHCI3 (325 mL). Into the reaction mixture was added glacial acetic acid (284 mL) 

with stirring at room temperature. A solution of 102 mL of 68% HNO3 and 33 mL of 

glacial acetic acid was added dropwise with an additional funnel while cooling the 

reaction mixture in an ice-water bath with the temperature around 10 °C. After the 

addition was completed, the reaction mixture was stirred for 24 hours at room 

temperature. The reaction mixture was washed with water (100 mL) and the organic 

layer was washed with a saturated aqueous Na2C03 (3 X 100 mL). The organic layer 

was dried over MgS04, and then recrystallization from CHCI3 to give 14.73 g (79%) of a 

product as a yellow solid with mp 209-213 °C (lit.'^ mp 199-201 and 245-248 °C for the 

4,4'- and 4,5'-isomers, respectively). IR (deposit from MeOH solution on a NaCl plate): 

1516 and 1338 (N=0); 1228 and 1130 (C-O) cm"'. 'H NMR (DMSO-d6): 8 3.70-4.39 

(m, 16H); 7.16 (d, 7= 9.0 Hz, 2H); 7.72 (d, 7= 2.6 Hz, 2H); 7.90 (dd, 7= 2.6 and 8.9 Hz, 

2H). 

116 
Note: After drying over MgS04, the product precipitated from the CHCI3 solution 

while standing for 1 day at room temperature. Sometimes, the CHCI3 solution was 

placed in a refrigerator to increase the yield. 

3.3.23. Preparation of 

4,4'(5')-Di(aminobenzo)-18-crown-6(99) 

A mixture of 4,4'(5')-di(nitrobenzo)-18-crown-6 (98) (10.00 g, 22.2 mmol) and 

10% Pd on carbon (2.00 g) in 200 mL of DMF was subjected to 60 psi of hydrogen 

pressure for 24 hours at room temperature. The catalyst was filtered with Celite and 

washed with CH2CI2 several times. The solvent was removed from the combined filtrate 

and washings by distillation under vacuum to give 8.56 g (99%) of a product as a red 

solid with mp 182-184 °C (lit.'"^ mp 176.5-177.5 and 197-198 °C for the 4,4'- and 4,5'-

isomers, respectively). IR (deposit from MeOH solution on a NaCl plate): 3329 (N-H); 

1230 and 1123 (C-O) cm"'. 'H NMR (DMSO-dg): 8 3.76-3.94 (m, 16H); 4.68 (s, 4 NH); 

6.05 (dd, 7 = 2.3 and 8.4 Hz, 2H); 6.24 (d, 7 = 2.3 Hz, 2H), 6.62 (d, 7 = 8.4 Hz, 2H). 

3.3.24. Preparation of 

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

from 4,4'(5')-Di(aminobenzo)-18-crown-6 (99) 

3.3.24.1. 4,4'(5')-Di[(diazonium tetrafluoroborato)benzo]-18-crown-6 (100). 

Into a 100-mL, one-necked, round-bottomed flask were added 4,4'(5')-di(aminobenzo)-

18-crown-6 (99) (1.00 g, 2.56 mmol) and H2O (20 mL). Into the suspension was added 

48% fluoroboric acid (12.60 mL). The suspension was stirred in an ice-salt bath. A 

solution of NaN02 (0.36 g) in 2 mL of H2O was added and the mixture was stirred for 30 

117 
minutes in the ice-salt bath. The solid was filtered and washed with Et20 (100 mL) to 

give 1.28 g of a brown solid in a quantitative yield. IR (deposit from MeOH solution on 

a NaCl plate): 2248 (N^N); 1240 and 1126 (C-O) cm"'. 'H NMR (DMSO-d6): 8 3.72-

4.61 (m, 16H); 7.51 (d, 7 = 9.2 Hz, 2H); 8.18 (d, 7= 2.4 Hz, 2H): 8.44 (dd, 7= 2.3 and 

9.1Hz,2H). 

Note: The 4,4'(5')-Di[(diazonium tetrafluoroborato)benzo]-18-crown-6 was used 

for the next step without purification. 

3.3.24.2. 4,4'(5')-Di(hydroxybenzo)-18-crown-6 (101). K2CO3 (0.36 g, 2.60 

mmol) was added cautiously to 15 mL of CF3CO2H in a 100-mL, three-necked, roundbottomd flask at 0 °C. Then, 4,4'(5')-di[(diazonium tetrafluoroborato)benzo]-18-crown-6 

(100) (1.28 g, 2.60 mmol) was added. The reaction mixture was refluxed for 24 hours 

and poured into 50 mL of water. The resulting mixture was placed in a refrigerator 

ovemight and the precipitated solid was filtered. Short column chromatography on silica 

gel with MeOH as eluent and then recrystallization from MeOH-H20 twice using 

activated carbon gave 0.40 g (40%) of a product as a light yellow solid with mp 217-220 

°C (lit.^'^ mp 190-194 and 215.5-216.5 °C for the 4,4'- and 4,5'-isomers, respectively). IR 

(deposit from MeOH solution on a NaCl plate): 3194 (O-H); 1222 and 1126 (C-O) cm"'. 

'H NMR (DMSO-d6): 8 3.68-4.19 (m, 16H); 6.25 (dd, 7 = 2.4 and 8.6 Hz, 2H); 6.40 (d, 7 

= 2.4 Hz, 2H); 6.73 (d, 7 = 8.6 Hz, 2H); 8.98 (s, 2H). 

118 
3.3.25. Preparation of 

4,4'(5')-Di(acetylbenzo)-18-crown-6(102) 

Into a 500-mL, three-necked, round-bottomed flask equipped with a thermometer 

were added dibenzo-18-crown-6 (26.00 g, 72.1 mmol), glacial acetic acid (8.66 g, 144.3 

mmol), and Eaton's reagent (188.00 g) under nitrogen. The reaction mixture was stirred 

magnetically for 6 hours at 50 °C under nitrogen. During this time, the reaction mixture 

turned cherry red. The reaction mixture was poured into a mixture of 250 g of ice and 

250 mL of water and the resulting mixture was stirred ovemight at room temperature. 

The solid was filtered and the filtered solid was dissolved in 500 mL of CH2CI2. The 

CH2CI2 layer was washed with 5% aqueous NaOH solution (3 X 150 mL) and brine (150 

mL). The CH2CI2 layer was dried over MgS04, and evaporated in vacuo. Column 

chromatography on alumina with CH2Cl2-EtOAc (3:1) as eluent and then recrystallization 

from CH2Cl2-hexanes gave 20.66 g (64%) of the product as a light yellow solid with mp 

202-206 °C (lit.^ mp 200-208 °C). IR (deposit from CH2CI2 solution on a NaCl plate): 

1668 (C=0); 1273 and 1132 (C-O) cm"'. 'H NMR (CDCI3): 8 2.55 (s, 6H); 3.95-4.34 

(m, 16H); 6.86 (d, 7 = 8.3 Hz, 2H); 7.49-7.58 (m, 4H). 

3.3.26. Preparation of 

4,4'(5')-Di(acetatobenzo)-18-crown-6(103) 

Into a 100-mL, one-necked, round-bottomed flask were added 4,4'(5')-

di(acetylbenzo)-18-crown-6 (102) (0.30 g, 0.67 mmol) and CH2CI2 (20 mL) under 

nitrogen. After the 102 had dissolved, purified m-chloroperbenzoic acid (m-CPBA) 

(0.58 g, 3.35 mmol) and Na2HP04 (0.25 g) were added. The reaction mixture was 

stirred for 2 days at room temperature under nitrogen. The reaction mixture was filtered 

119 
and the filtered solids were washed with CH2CI2. The combined filtrate and washings 

were washed with saturated aqueous NaHC03 (3 X 20 mL), 5 % aqueous Na2S203 (20 

mL), and brine (20 mL). Then, the CH2CI2 layer was dried over MgS04, and evaporated 

in vacuo. Recrystallization from CH2Cl2-hexanes gave 0.25 g (78%) of the product as a 

light yellow solid with mp 183-186°C. IR (deposit from CH2CI2 solution on a NaCl 

plate): 1758 (C=0); 1210 and 1136 (C-O) cm"'. 'H NMR (CDCI3): 8 2.27 (s, 6H); 3.92-

4.28 (m, 16H); 6.59-6.65 (m, 4H); 6.83-6.87 (m, 2H). Anal. Calcd. for C24H28O10 X 0.2 

H2O: C, 60.04; H, 5.96. Found: C, 59.76; H, 5.96. 

Note: The m-chloroperbenzoic acid (m-CPBA) was purified by a literature 

method.^'' A solution of m-CPBA in Et20 was washed with pH 7.5 buffer solution 

several times and the Et20 layer was evaporated in vacuo. The purified m-CPBA was 

dried under vacuum. 

3.3.27- Preparation of 

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

from 4,4'(5')-Di(acetatobenzo)-18-crown-6 (103) 

Into a 500-mL, one-necked, round-bottomed flask were added 4,4'(5')-

di(acetatobenzo)-18-crown-6 (103) (2.00 g, 4.20 mmol), MeOH (150 mL), and CH2CI2 

(1(X) mL) under nitrogen. A solution of NaOH (0.62 g, 15.4 mmol) in 10 mL of MeOH 

was added. The reaction mixture was stirred for 24 hours at room temperature under 

nitrogen. The reaction mixture was neutralized with concentrated HCl and the solvent 

was evaporated in vacuo. Recrystallization of the residue from MeOH-H20 gave 1.37 g 

(83%) of a product as a light brown solid with mp 217-220 °C (lit.'"' mp 190-194 and 

215.5-216.5 °C for the 4,4'- and 4,5'-isomers, respectively). IR (deposit from MeOH 

120 
solution on a NaCl plate): 3195 (O-H); 1225 and 1124 (C-O) cm"'. 'H NMR (DMSOde): 8 3.58-4.22 (m, 16H); 6.23 (dd, 7 = 2.5 and 8.6 Hz, 2H); 6.38 (d, 7 = 2.4 Hz, 2H); 

6.71 (d, 7 = 8.6 Hz, 2H); 8.97 (s, 2H). Anal. Calcd. for C20H24O8 X 0.8 H2O: C, 59.05; 

H, 6.34. Found: C, 58.72; H, 5.97. 

Note: Prior to submission for elemental analysis, the 4,4'(5')-di(hydroxybenzo)-

18-crown-6 was dried over P2O5 under vacuum with heating by refluxing toluene in a 

drying pistol. 

3.3.28. Preparation of l-(2'-Hydroxyoctoxy)-

3,4-methylenedioxybenzene (104) 

3.3.28.1. With Cesium Carbonate 

Into a 250-mL, three-necked, round-bottomed flask were added Sesamol (0.60 g, 

4.34 mmol), CS2CO3 (3.54 g, 10.9 mmol), and CH3CN (50 mL) under nitrogen. The 

reaction mixture was refluxed for 3 hours and then a solution of 1,2-epoxyoctane (0.56 g, 

4.34 mmol) in 25 mL of CH3CN was added over 2 hours. The reaction mixture was 

refluxed for 3 days under nitrogen, cooled to room temperature, and filtered. The 

filtered solid was washed with CH2CI2. The combined filtrate and washings were 

evaporated in vacuo and the residue was dissolved in 50 mL of CH2CI2. The CH2CI2 

layer was washed with water (25 mL), dried over MgS04, and evaporated in vacuo. 

Column chromatography on alumina with EtOAc-hexanes (1:10) as eluent gave 0.94 g 

(81 %) of a yellow solid with mp 37-40 °C. IR (deposit from CH2CI2 solution on a NaCl 

plate): 3424 (O-H); 1187 and 1039 (C-O) cm"'. 'H NMR (CDCI3): 8 0.89 (t, 7 = 6.5 Hz, 

3H); 1.16-1.69 (m, lOH); 2.36 (d, 7 = 3.4Hz, IH); 3.68-4.07 (m, 3H); 5.91 (s, 2H); 6.32 

121 
(dd, 7 = 2.5 and 8.4 Hz, IH); 6.50 (d, 7 = 2.5 Hz, IH); 6.70 (d, 7 = 8.5 Hz. IH). Anal. 

Calcd. for C15H22O4: C, 67 65; H, 8.33. Found: C, 67.62; H, 8.39. 

3.3.28.2. With Sodium Hvdroxide 

Into a 250-mL, three-necked, round-bottomed flask were added Sesamol (1.00 g, 

7.24 nunol), NaOH (0.58 g, 14.5 mmol), and r-BuOH (50 mL) under nitrogen. The 

reaction mixture was refluxed for 2 hours and then 1,2-epoxyoctane (0.93 g, 7.24 mmol) 

was added dropwise. The reaction mixture was refluxed for 3 days under nitrogen, 

cooled to room temperature, and evaporated in vacuo. The residue was dissolved in 50 

mL of CH2CI2. The CH2CI2 layer was washed with water (2 X 25 mL) and the combined 

aqueous layers were extracted with CH2CI2 (2 X 25 mL). The combined CH2CI2 layers 

were dried over MgS04, and evaporated in vacuo. Column chromatography on alumina 

with EtOAc-hexanes (1:5) as eluent gave 0.71 g (37%) of a light yellow solid. 

3.3.29. Attempted Synthesis of 4,4'(5')-

Di[(2-hydroxy)octoxybenzo]-18-crown-6 (105) 

from 4,4'(5')-Di(hyroxybenzo)-18-crown-6 (101) 

Into a 250-mL, three-necked, round-bottomed flask were added 4,4'(5')-

di(hydroxybenzo)-18-crown-6 (101) (0.20 g, 0.51 mmol), NaOH (0.08 g, 2.04 mmol), 

and r-BuOH (50 mL) under nitrogen. The reaction mixture was refluxed for 2 hours and 

then 1,2-epoxyoctane (0.13 g, 1.02 mmol) was added dropwise. The reaction mixture 

was refluxed for 3 days under nitrogen, cooled to room temperature, and evaporated in 

vacuo. The residue was dissolved in 50 mL of CH2CI2. The CH2CI2 layer was washed 

with water (2 X 25 mL) and the combined aqueous layers were extracted with CH2CI2 (2 

122 
X 25 mL). The combined CH2CI2 layers were dried over MgS04, and evaporated in 

vacuo. Column chromatography on silica gel with MeOH-CH2Cl2 (1:10) as eluent to 

remove the less polar impurities and then recrystallization from EtOAc-hexanes gave 

0.04 g (12%) of a product as yellow solid. 'H NMR (CDCI3): 8 0.89 (t, 7 = 6.3 Hz, 6H): 

1.09-1.74 (m, 20H); 2.38 (br s, 2H); 3.68-4.28 (m, 22H); 6.38 (dd, 7= 2.7 and 8.7 Hz, 

2H); 6.50 (d, 7 = 2.7 Hz, 2H); 6.77 (d, 7 = 8.7 Hz, 2H). 

Note: The product obtained by recrystallization was contaminated with a small 

amount of unidentified impurities. Therefore, its melting point was not measured. 

3.3.30. Preparation of 

4-Octyl-2,2-dioxo-l,3,2-dioxathiolane (107) 

3.3.30.1. 4-Octyl-2-oxo-l,3,2-dioxathiolane (106). To 1,2-decanediol (2.00 g, 

11.5 mmol) dissolved in 50 mL of CH2CI2 in a 250-mL, one-necked, round-bottomed 

flask under nitrogen, Et3N (4.65 g, 45.9 mmol) was added. The reaction mixture was 

cooled to 0 °C in an ice bath and thionyl chloride (2.05 g, 17.2 mmol) was added. The 

reaction mixture was stirred for 15 minutes in the ice bath then the reaction was quenched 

by the addition of water (1(X) mL). The organic layer was separated and the aqueous 

layer was extracted with CH2CI2 (3 X 50 mL). The combined CH2CI2 layers were dried 

over MgS04 and evaporated in vacuo. The residue was dried under vacuum to give a 

yellow, viscous liquid. 

Note: The obtained decane 1,2-cyclic sulfite was used in the next step without 

further purification. 

123 
3.3.30.2. 4-Octyl-2,2-dioxo-l,3,2-dioxathiolane (107). To 4-octyl-2-oxo-1,3,2 

dioxathiolane (106) dissolved in 60 mL of CCI4-CH3CN (1:1) in a 250-mL, one-necked, 

round-bottomed flask cooled to 0 °C in an ice bath were added NaI04 (4.91 g. 22.96 

mmol), H2O (50 mL), and RuCh x H2O (0.02 g, 0.11 mmol, 1 mol %). The reaction 

mixture was stirred for 1 hour at 0 °C and Et20 (50 mL) was added. The organic layer 

was separated and the aqueous layer was extracted with Et20 (3 X 100 mL). The 

combined organic layers were washed with brine (50 mL), dried over MgS04, and 

evaporated in vacuo. Column chromatography on silica gel with CH2Cl2-hexanes (3:1) 

as eluent gave 2.58 g (95%) of a product as a pale yellow, viscous liquid. IR (deposit 

from CH2CI2 solution on a NaCl plate): 1385 and 1208 (S=0) cm"'. 'H NMR (CDCI3): 8 

0.88 (t, 7= 6.5 Hz, 3H); 1.09-2.10 (m, 14H); 4.34 (t, 7= 8.5 Hz, IH); 4.69-4.76 (m, IH); 

4.92-5.05 (m, IH). Anal. Calcd. for C,oH2o04S: C, 50.82; H, 8.53. Found: C, 51.12; H, 

8.50. 

3.3.31. Attempted Synthesis of 

l-(2'-Hydroxydecyloxy)-3,4-methylenedioxybenzene 

(108) from Sesamol Giving a Mixture of 

Two Isomers 108 and 109 

Into a 250-mL, three-necked, round-bottomed flask were added Sesamol (0.36 g, 

2.62 mmol), CS2CO3 (2.13 g, 6.55 mmol), and CH3CN (50 mL) under nitrogen. The 

reaction mixture was refluxed for 3 hours and then a solution of 4-octyl-2,2-dioxo-1,3,2-

dioxathiolane (107) (0.62 g, 2.62 mmol) in 25 mL of CH3CN was added over 2 hours. 

The reaction mixture was refluxed for 1 day under nitrogen, cooled to room temperature, 

and filtered. The filtered solid was washed with CH2CI2. The combined filtrate and 

124 
washings were evaporated in vacuo and the residue was dried under vacuum for 1 hour. 

The crude sulfate was suspended in 50 mL of THF and 10 mL of 20 % aqueous H2SO4 

solution was added to the stirred suspension. The reaction mixture was stirred for 1 hour 

at room temperature, 50 mL of samrated aqueous Na2C03 was added, and stirring was 

continued for additional 20 minutes at room temperature. The organic layer was 

separated and the aqueous layer was extracted with CH2CI2 (3 X 100 mL). The 

combined organic layers were dried over MgS04 and evaporated in vacuo. Column 

chromatography on silica gel with EtOAc-hexanes (1:5) as eluent gave the product. 

3.3.31.1.1-(2'-Hydroxydecyloxy)-3,4-methylenedioxybenzene (108) was 

obtained 56% yield as a white solid with mp 52-55 °C. IR (deposit from CH2CI2 solution 

on a NaCl plate): 3420 (O-H); 1194 and 1035 (C-O) cm"'. 'H NMR (CDCI3): 8 0.88 (t, 7 

= 6.4 Hz, 3H); 1.07-1.69 (m, 14H); 2.35 (d, 7= 3.6 Hz, IH); 3.70-4.07 (m, 3H); 5.91 (s, 

2H); 6.32 (dd, 7= 2.6 and 8.5 Hz, IH); 6.50 (d, 7 = 2.5 Hz, IH); 6.70 (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-methylenedioxybenzene (109) 

was isolated in 13% yield as a yellow, viscous liquid. IR (deposit from CH2CI2 solution 

on a NaCl plate): 3421 (O-H); 1182 and 1040 (C-O) cm"'. 'H NMR (CDCI3): 8 0.87 (t, 7 

= 6.4Hz, 3H); 1.03-1.81 (m, 14H); 2.17 (brs, IH); 3.58-3.87 (m, 2H); 4.08-4.27 (m, 

IH); 5.91 (s, 2H); 6.38 (dd, 7 = 2.5 and 8.5 Hz, IH); 6.53 (d, 7 = 2.4 Hz, IH); 6.69 (d, 7 = 

8.4 Hz, IH). Anal. Calcd. for C17H26O4: C, 69.36; H, 8.90. Found: C, 69.71; H, 9.23. 

125 
3.3.32. Preparation of 4,4'(5')-

Di[(2-hydroxydecyloxy)benzo]-18-crown-6 (110) 

Into a 250-mL, three-necked, round-bottomed flask were added 4.4'(5')-

di(hydroxybenzo)-18-crown-6 (101) (0.31 g, 0.79 mmol), CS2CO3 (1.29 g, 3.95 mmol). 

and CH3CN (50 mL) under nitrogen. The reaction mixture was refluxed for 3 hours and 

then a solution of 4-octyl-2,2-dioxo-l,3,2-dioxathiolane (107) (0.41 g, 1.74 mmol) m 25 

mL of CH3CN was added over 2 hours. The reaction mixture was refluxed for 1 day 

under nitrogen, cooled to room temperature, and filtered. The filtered solids were 

washed with CH2CI2. The combined filtrate and washings were evaporated in vacuo and 

the residue was dried under vacuum for 1 hour. The cmde sulfate ester was suspended in 

50 mL of THF and 10 mL of 20 % aqueous H2SO4 solution was added. The reaction 

mixmre was stirred for 1 hour at room temperature, 50 mL of saturated aqueous Na2C03 

was added, and stirring was continued for additional 20 minutes at room temperature. 

The organic layer was separated and the aqueous layer was extracted with CH2CI2 (3 X 

1(X) mL). The combined organic layers were dried over MgS04 and evaporated in 

vacuo. Column chromatography on silica gel with CH2Cl2-MeOH (40:1) as eluent and 

then recrystallization from MeOH gave 0.12 g (21%) of a white solid with mp 128-131 

°C. IR (deposit from CH2CI2 solution on a NaCl plate): 3384 (O-H); 1226 and 1138 (CO) cm"'. 'H NMR (CDCI3): 8 0.88 (t, 7 = 6.4 Hz, 6H); 1.10-1.72 (m, 28H); 2.27 (d, 7 = 

3.2 Hz, 2H); 3.71-4.27 (m, 22H); 6.39 (dd, 7 = 2.7 and 8.7 Hz, 2H); 6.51 (d, 7 = 2.7 Hz, 

2H); 6.80 (d, 7 = 8.6 Hz, 2H). Anal. Calcd. for C40H64O10: C, 68.15; H, 9.15. Found: C. 

67.89; H, 9.10. 

126 
3.3.33. Preparation of (2-Hydroxydecyloxy)benzene (112) 

Into a 100-mL, three-necked, round-bottomed flask were added potassium 

phenoxide (111) (0.21 g, 1.59 mmol) and CH3CN (10 mL) under nitrogen. A solution of 

4-octyl-2,2-dioxo-l,3,2-dioxathiolane (107) (0.38 g, 1.59 mmol) in 10 mL of CH3CN was 

added with stirring under nitrogen. The reaction mixture was stirred for 2 hours at room 

temperature and then refluxed for 5 minutes under nitrogen. The solvent was evaporated 

in vacuo and the residue was dried under vacuum for 2 hours. To this crude sulfate ester 

was added 10 mL of 1 N aqueous HCl solution. The reaction mixture was refluxed for 3 

hours and then extracted with CH2CI2 (3 X 50 mL). The combined CH2CI2 layers were 

dried over MgS04 and evaporated in vacuo. Recrystallization from hexanes gave 0.18 g 

(45%) of a white solid with mp 63-65 °C. IR (deposit from CH2CI2 solution on a NaCl 

plate): 3417 (O-H); 1097 and 1076 (C-O) cm"'. 'H NMR (CDCI3): 8 0.88 (t, 7 = 6.4 Hz, 

3H); 1.10-1.71 (m, 14H); 2.34 (s, IH); 3.81-4.12 (m, 3H); 6.89-6.96 (m, 3H), 7.25-7.33 

(m, 2H). Anal. Calcd. for C16H26O2: C, 76.75; H, 10.47. Found: C, 76.47; H, 10.54. 

Note: Potassium phenoxide was prepared by a literature method.^^ 

3.3.34. Preparation of 

4,4'(5')-Di(benzyloxybenzo)-18-crown-6 (115) 

Into a 250-mL, three-necked, round-bottomed flask were added 4,4'(5')-

di(hydroxybenzo)-18-crown-6 (101) (0.17 g, 0.43 mmol), CS2CO3 (0.70 g, 2.15 mmol), 

and CH3CN (50 mL) under nitrogen. The reaction mixture was refluxed for 3 hours and 

then a solution of benzyl bromide (0.16 g, 0.95 mmol) in 25 mL of CH3CN was added 

over 2 hours. The reaction mixture was refluxed for 1 day under nitrogen, cooled to 

127 
as 

room temperature, and filtered. The filtered solids were washed with CH2CI2. The 

combined filtrate and washings were evaporated in vacuo and the residue was dissolved 

in 50 mL of CH2CI2. The CH2CI2 layer was washed with water (25 mL), dried over 

MgS04, and evaporated in vacuo. Column chromatography on silica gel with CH2CI2 

eluent to remove a small amount of less polar impurity, then with CH2Cl2-MeOH (100:1) 

as eluent gave 0.20 g (80%) of 4,4'(5')-di[benzyloxybenzo]-18-crown-6 (115) as a white 

solid with mp 144-146 ''C. IR (deposit from CH2CI2 solution on a NaCl plate): 1228, 

1140, and 1028 (C-O) cm'. 'H NMR (CDCI3): 8 3.90-4.22 (m, 16H); 4.99 (s, 4H); 6.46 

(dd, 7 = 2.6 Hz, 2H); 6.57 (d, 7 = 2.8 Hz, 2H); 6.81 (d, 7 = 8.7 Hz, 2H); 7.29-7.44 (m, 

lOH). Anal. Calcd. For C34H36O8: C, 71.31; H, 6.34. Found: C, 71.13; H, 6.27. 

3.3.35. Preparation of 

(3,4-Methylenedioxy)phenoxyacetic Acid (118) 

Into a 250-mL, three-necked, round-bottomed flask were added Sesamol (3.00 g, 

21.72 mmol), NaH (2.61 g, 108.60 mmol, 95% dry), and dry THF (50 mL) under 

nitrogen. The reaction mixture was stirred for 2 hours at room temperature under 

nitrogen. A solution of bromoacetic acid (4.53 g, 32.58 mmol) in 20 mL of dry THF was 

added over 3 hours under nitrogen. The reaction mixture was stirred ovemight at room 

temperature under nitrogen. Water was added carefully to destroy the excess NaH. The 

THF was evaporated in vacuo and the remaining aqueous layer was extracted with 

EtOAc (3 X 20 mL) to remove the unreacted starting material and the organic impurities. 

Then, the aqueous layer was acidified with 6 N HCl to pH = 1. The acidified aqueous 

layer was extracted with CH2CI2 (3 X 50 mL). The combined CH2CI2 layers were dried 

128 
over MgS04 and evaporated in vacuo. Recrystallization from EtOH gave 2.42 g (57 %) 

of a product as a light yellow solid with mp 160-165 °C. IR (deposit from CH2CI2 on a 

NaCl plate): 3400 (O-H); 1733 (C=0); 1185 and 1032 (C-O) cm'. 'H NMR (CDCI3): 8 

4.51 (s, 2H); 5.92 (s, 2H); 6.32 (dd, 7= 2.6 and 8.5 Hz, IH); 6.54 (d, 7= 2.5 Hz, IH); 

6.69 (d, 7= 8.5 Hz, IH). Anal. Calcd. for CgHgOs: C, 55.11; H, 4.11. Found: C, 55.22; 

H, 4.20. 

3.3.36. Attempted Synthesis of 

l-(3',4'-Methylenedioxy)phenoxy-2-decanone (119) 

from (3,4-Methylenedioxy)phenoxyacetic Acid (118) 

Giving the Ester 120 

Into a 100-mL, three-necked, round-bottomed flask were added (3,4-

methylenedioxy)phenoxyacetic acid (118) (0.30 g, 1.53 mmol) and dry benzene (30 mL). 

Oxalyl chloride (1.17 g, 9.18 mmol) was added under nitrogen and the reaction mixture 

was refluxed for 2 hours. The benzene was evaporated in vacuo and the residue was 

dried under vacuum for 2 hours. Fe(acac)3 (0.02 g, 0.05 mmol) and dry THF (50 mL) 

were added to the crude (3,4-methylenedioxy)phenoxyacetic acid chloride under 

nitrogen. Then, a solution of CgHnMgBr (1.53 mmol) in THF was added dropwise with 

stirring over 30 minutes at room temperature under nitrogen. After completion of 

addition, the reaction mixture was stirred for additional 10 minutes under nitrogen and 

then 10% aqueous HCl solution (20 mL) was added to quench the reaction. The reaction 

mixture was extracted with CH2CI2 (3 X 50 mL) and the combined CH2CI2 layers were 

washed with saturated NaHC03 (50 mL) and water (50 mL), dried over MgS04, and 

evaporated in vacuo. Column chromatography on silica gel with EtOAc-hexanes (1:3) 

129 
as eluent and then recrystallization from hexanes gave 0.02 g (4%) of ester 120 as a white 

solid. IR (deposit from CH2CI2 solution on a NaCl plate): 1763 (C=0): 1181 and 1040 

(C-O)cm"'. 'HNMR(CDCl3):8 0.88(t,7=6.4Hz, 3H): 1.09-1.80(m. 12H): 4.19 (i, 7 

= 6.7 Hz, 2H); 4.55 (s, 2H); 5.92 (s, 2H); 6.31 (dd,7= 2.6 and 8.5 Hz, IH); 6.54 (d. 7 = 

2.6 Hz, IH); 6.70 (d, 7 = 8.5 Hz IH). 

3.3.37. Preparation of 

(3,4-Methylenedioxy)phenoxyacetaldehyde 

Diethyl Acetal (123) 

Into a 250-mL, three-necked, round-bottomed flask were added Sesamol (2.00 g. 

14.5 mmol), CS2CO3 (11.79 g, 36.2 mmol), and dry CH3CN (50 mL) under nitrogen. 

The reaction mixmre was refluxed for 3 hours and then a solution of bromoacetaldehyde 

diethyl acetal (3.14 g, 15.93 mmol) in 25 mL of dry CH3CN was added over 2 hours. 

The reaction mixmre was refluxed for 1 day under nitrogen, cooled to room temperature, 

and filtered. The filtered solid was washed with CH2CI2 several times. The combined 

filtrate and washings were evaporated in vacuo and the residue was dissolved in 50 mL of 

CH2CI2. The CH2CI2 layer was washed with water (25 mL), dried over MgS04, and 

evaporated in vacuo. Column chromatography on silica gel with EtOAc-hexanes (1:10) 

as eluent gave 3.42 g (93%) of a light yellow viscous liquid. IR (deposit from CH2CI2 on 

aNaClplate): 1243 and 1132 (C-O) cm"'. 'H NMR (CDCI3): 8 1.24 (t,7= 7.0 Hz, 6H); 

3.54-3.83 (m, 4H); 3.93 (d, 7 = 5.2 Hz, 2H); 4.80 (t, 7 = 5.2 Hz, IH); 5.90 (s, 2H); 6.33 

(dd, 7= 2.6 and 8.5 Hz, IH); 6.52 (d, 7 = 2.5 Hz, IH); 6.69 (d, 7= 8.5 Hz, IH). Anal. 

Calcd. for CnHigOs X 0.1 H2O: C, 60.97; H, 7.16. Found: C, 60.76; H, 7.30. 

130 
3.3.38. Attempted Synthesis of 

(3,4-Methylenedioxy)phenoxyacetaldehyde (124) 

from (3,4-Methylenedioxy)phenoxyacetaldehyde 

Diethyl Acetal (123) 

To a solution of (3,4-methylenedioxy)phenoxyacetaldehyde diethyl acetal (0.55 g. 

2.16 mmol) in 10 mL of CHCI3 was added 50% aqueous CF3CO2H (5 mL) and the 

reaction nuxmre was refluxed for 2 hours. The reaction mixture was extracted with 

CH2CI2 (3 X 50 mL). The combined organic layers were washed with brine (25 mL). 

dried over MgS04, and evaporated in vacuo to give an aldehyde product 124 together 

with unreacted starting material 123. The ratio of 123 to 124 was determined by 

comparison of the integration areas for the -CH2- of the methylenedioxy group for 123 

and 124. ' H NMR (CDCI3) for 124: 8 4.49 (d, 7 = 0.8 Hz, 2H); 5.93 (s. 2H): 6.27 (dd, 7 

= 2.6 and 8.5 Hz, IH); 6.52 (d, 7 = 2.5 Hz, IH); 6.70 (d, 7= 8.4 Hz, IH). The ratio of 

123:124 = 82:18. 

3.3.39. Attempted Synthesis of 

(3,4-Methylenedioxy)phenoxyacetaldehyde (124) 

from (3,4-Methylenedioxy)phenoxyacetaldehyde 

Diethyl Acetal (123) Giving 

the Benzofuran Derivative 125 

Into l(X)-mL, three-necked, round-bottomed were added (3,4-methylenedioxy)phenoxyacetaldehyde diethyl acetal (1.00 g, 3.93 mmol), sodium iodide (0.88 g, 

5.90 mmol), and dry CH3CN (30 mL). Boron trifluoride etherate (0.84 g, 5.90 mmol) 

was added and the reaction mixture was refluxed for 2 hours under nitrogen. The 

reaction mixture was cooled to room temperature and saturated aqueous NaHC03 was 

added to quench the reaction. The reaction mixture was extracted with CH2CI2 (3 X 50 

131 
mL) and the combined organic layers were washed with 10 % aqueous Na2S203 (25 mL) 

and brine (25 mL). The organic layer was dried over MgS04 and evaporated in vacuo. 

Column chromatography on silica gel with EtOAc-hexanes (1:20) as eluent gave 0.32 g 

(50%) of a white solid with mp 70-71 °C. IR (deposit from CH2CI2 on a NaCl plate): 

1121 and 1026 (C-O) cm"'. 'H NMR (CDCI3): 8 5.98 (s, 2H); 6.64 (dd. 7 = 0.8 and 2.1 

Hz, IH); 6.95 (s. IH); 6.99 (s. IH); 7.52 (d, 7 = 2.1 Hz, IH). Anal. Calcd. for C9H6O3: 

C, 66.67; H, 3.73. Found: C, 66.82: H, 3.96. 

132 
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134