bluuebunny/crossref_metadata_2025 huggingface dataset:
Directed ortho‐lithiation of chloroquinolines. Application to synthesis of 2,3‐disubstituted quinolines
Authors: Marsais F. , Godard A. , Queguiner G.
Published: March 2009

2‐, 3‐ and 4‐Chloroquinolines were selectively lithiated at low temperature by lithium diisopropylamide at the more acidic C‐3, C‐4 and C‐3 positions respectively. Reaction of 2‐chloro‐3‐lithioquinoline with electrophiles led to various 2,3‐disubsthuted quinolines. The versatility of this functionalization methodology is enhanced by the C‐2 halogen reactivity towards oxygen or nitrogen nucleophiles. So, a great variety of 2,3‐di‐substituted quinolines were synthesized, such as 2‐chloro, 2‐alkoxy, 2‐aminoquinolines or 2‐quinolones bearing an hydroxy, carbonyl (aldehyde, ketone or carboxylic acid), iodo, trimethylsilyl or boronic acid moiety at the C‐3. Some of the resulting 2,3‐disubstituted synthons were annelated to tetracyclic polyaromatics, which possess the xanthone or indole structure. This could be achieved via further functionalization of the quinoline ring either by SNAr2 or heteroaromatic cross‐coupling reactions, after the first directed‐lithiation step.
Synthesis and DNA‐binding study of A thiazole‐containing analog of netropsin
Authors: Plouvier Bertrand , Houssin Raymond , Bailly Christian , Hénichart Jean‐Pierre
Published: March 2009

In order to study the influence of the nature of the heterocyclic rings of Netropsin (Nt) on the binding to specific nucleotide sequences in the minor groove of DNA, a thiazole‐containing analogue (Thia‐Nt) was designed. Optimized syntheses of the key compound 2‐aminothiazole‐4‐carboxylic acid and Thia‐Nt were reported together with the results of a preliminary study of Thia‐Nt‐DNA binding.
Preparation, proton and carbon‐13 structure determination, and fungicidal activity of chlorinated 1‐arylamino‐1H‐pyrrole‐2,5‐diones
Authors: Yaroslavskym Carmela , Bracha Peretz , Glaser Robert
Published: March 2009

1‐(2′,4′‐dichloro)phenylamino‐1H‐pyrrole‐2,5‐dione and 1‐(2′,4′,6′‐trichloro)phenylamino‐1H‐pyrrole‐2,5‐dione were prepared via direct chlorination of 2‐phenyl‐3‐oxo‐6‐hydroxy‐2H‐pyridazine. Both pmr and mass spectroscopy clearly showed that dichloro substitution occurred in the aromatic moiety and not in the vinylic region of the molecule. The former method showed that pyridiazine‐ to pyrrole‐ring isomerization had occurred already at the level of dichlorination. The identical 2′,4′‐dichlorophenyl and 2′,4′,6′‐trichlorophenylpyr‐rolediones were also prepared by reaction of maleic anhydride with the appropriate arylhydrazine. Similar 2′,4‐dichlorophenyl and 2′,4′,6′‐trichlorophenyl analogues were prepared using dichloromaleic anhydride. Cmr spectroscopic techniques were used for pyridazine‐/pyrrole‐ring stereochemical assignment of products derived from dichloromaleic anhydride. 1‐(2′,4′‐dichloro)phenylamino‐1H‐pyrrole‐2,5‐dione and the trichloro‐phenyl analogue were shown to exhibit fungicidal activity in both in‐vivo and in‐vitro assays.
Some acylations of 3‐phenyl and 3‐mesityl‐4,5‐dihydroisoxazoles
Authors: Corsaro Antonino , Chiacchio Ugo , Perrini Giancarlo , Caramella Pierluigi , Albini Franca Marinone
Published: March 2009

A study on the acetylation and benzoylation of title compounds by quenching the corresponding 4‐carbanions with acyl chlorides or esters is reported. The obtained ketones are formed as minor regioisomeric adducts in the cycloadditions of benzo and mesitonitrile oxide to methyl and phenyl vinyl ketone. The quenching with methyl chloroformate was also examined as a possible convenient route to 4‐methoxycarbonyl‐3‐aryl‐4,5‐dihydroisoxazoles.
Photochemical methoxy/hydroxymethyl rearrangement in 3‐methoxy‐N‐substituted‐4‐pyriclones
Authors: Stiplošek Z. , Šindler‐Kulyk M. , Jakopĉić K. , Meić Z. , Vikić‐Topić D.
Published: March 2009

N‐Substituted 3‐methoxy‐4‐pyridones Ia‐e rearrange to the corresponding N‐substituted 3‐hydroxymethyl‐4‐pyridones IIa‐e when irradiated at 254 or 300 nm in benzene or toluene solution.
Dimerization of pyrazolyl‐5‐hydroxypyrrolidinones to tetrazocines
Authors: Brinkmeyer Raymond S. , Terando Norman H.
Published: March 2009

The dimerization of the hydroxypyrrolidinones 5 and 9 yield the tetrazocines 8 and 11. In addition, in the case of compound 9, the ring‐fused hexaazacyclododecane 12 was isolated. X‐ray diffraction analysis of compound 11 verified the dimeric structure of these products.
Synthesis and identification of 4‐methyl‐N‐(4H‐1,2,4‐triazol‐4‐yl)‐2‐benzothiazolamine, an impurity in the synthesis of tricyclazole
Authors: Dreikorn Barry A. , Unger Paul
Published: March 2009

The synthesis of 4‐methyl‐N‐(4H‐1,2,4‐triazol‐4‐yl)‐2‐benzothiazolamine, 4, a by‐product in the synthesis of tricyclazole, 1, by oxidative cyclization of the corresponding thiourea, 12, with thionyl chloride, is described.
Studies on naphthyridines. Part 2. Synthesis of 4‐substituted and 6‐substituted 1,6‐naphthyridin‐5(6H)‐ones
Authors: Balogh Mária , Hermecz István , Simon Kálmán , Pusztay Levente
Published: March 2009

Ethyl 4‐substituted 2‐methyl‐5‐oxo‐5,6‐dihydro‐1,6‐naphthyridine‐3‐carboxylates 3a‐h were synthetized in a one‐step reaction from diethyl 2,6‐diraethylpyridine‐3,5‐dicarboxylates 1a‐h by aminomethinylation with 1,3,5‐triazine (2). The 6‐substitued derivatives 6a‐z,aa‐ff could be obtained from diethyl 2‐[2‐(dimethylamino)‐vinyl]‐6‐methylpyridine‐3,5‐dicarboxylate (4) either directly or via the isolated intermediate 2‐[2‐(arylamino)‐vinyl]pyridine compounds 5a‐i.
Pyridazines. L. Syntheses and reactions of phenyl(3‐pyridazinyl)methane derivatives
Authors: Heinisch Gottfried , Huber Thierry
Published: March 2009

A convenient approach to phenyl (3‐pyridazinyl) ketone (6) and phenyl(3‐pyridazinyl)methanol (7) is proposed. Reactions of the related diarylmethyl chloride 8 with various N‐ and S‐nucleophiles were found to afford the expected amines 9a‐c, 10a‐c and thioethers 11a,b in satisfactory yields.
Some stable derivatives of 7,8‐dihydropurines
Authors: Pendergast William , Hall William R.
Published: March 2009

The synthesis of a number of 7,8‐dihydropurines is described. The unusual stability of these molecules is due to the presence of an electron withdrawing substituent in the 6‐position.
Research on heterocyclic compounds. XXIII. Phenyl derivatives of fused imidazole systems
Authors: Abignente E. , De Caprariis P. , Fattorusso E. , Mayol L.
Published: March 2009

The reaction of various heteroarylamines with ethyl 2‐benzoyl‐2‐bromoacetate was used to obtain some imidazo[1,2‐a]pyridines, imidazo[1,2‐a]pyrimidines, imidazo[2,1‐b]thiazoles and imidazo[2,1‐b]benzothiazoles characterized by the presence of a phenyl moiety on the imidazole ring. In the case of thiazole and benzothiazole derivatives, unexpected by‐products were isolated and their structures elucidated.
Synthesis of 3‐benzoyl‐4,7‐dihydro‐7‐oxopyrrolo[3,2‐b]pyridine‐6‐carboxylic acid derivatives as potential antimicrobial agents
Authors: Abdalla Ghassan M. , Sowell J. Walter
Published: March 2009

A series of twelve newly synthesized derivations of 3‐benzoyl‐4,7‐dihydro‐7‐oxopyrrolo[3,2‐b]pyridine‐6‐carboxylic acid from 2‐methyl‐3‐benzoyl‐4‐aminopyrrole is reported.
Oxidative halogenation of substituted pyrroles with cu(II). Part I. Bromination of some 3‐acetylpyrroles
Authors: Petruso S. , Caronna S. , Sprio V.
Published: March 2009

3‐Acetylpyrroles are brominated with copper(II) bromide. The reaction afforded almost quantitatively only nuclear monobromination. Evidence for the structures of final compounds was by mass spectrometry, 1H‐nuclear magnetic resonance, ir, and elemental analysis.
Synthesis and absorption spectra of 2‐substituted 5,8‐dimethoxy‐4H‐1‐benzothiopyran‐4‐one 1,1‐dioxides
Authors: Watanabe Shigeru , Nakazumi Hiroyuki , Akagi Nobuo , Maeda Katsumi , Kitao Teijiro
Published: March 2009

2,3‐Dibromo‐5,8‐dimethoxy‐4H‐1‐benzothiopyran‐4‐one (thiochromone) 1,1‐dioxide which was a starting material to prepare sulfone analogues of 1,4‐naphthoquinone dyes was easily prepared from 5,8‐dimethoxythiochroman‐4‐one by oxidation and bromination. The reactions of 2,3‐dibromo‐5,8‐dimethoxythiochromone 1,1‐dioxide 4 with aliphatic and aromatic amines in ethanol below 20° gave 2‐substituted derivatives 12a‐e and at higher reaction temperature the amination gave 2‐arylamino derivatives 13c‐e debrominated at C‐3. The visible absorption spectra of these derivatives were investigated by the PPP MO method.
Bromination of sydnones. III. Bromination of 3‐(2‐substituted‐phenyl)sydnones and subsequent side chain modification
Authors: Turnbull Kenneth , Blackburn Thomas L. , Esterline Daniel T.
Published: March 2009

Bromination of the sydnone ring of several ortho‐substituted N‐arylsydnones is reported. Subsequent side‐chain modification generally can be achieved without concomitant removal of the 4‐bromo protective group.
Oxidative halogenation of substituted pyrroles with cu(II). Part II. Bromination of some ethyl 3‐pyrrolecarboxylates and corresponding acids
Authors: Petruso S. , Caronna S. , Sferlazzo M. , Sprio V.
Published: March 2009

Ethyl 3‐pyrrolecarboxylates and their corresponding acids are brominated with copper(II) bromide. The reaction afforded at 0°, with high‐yield nuclear monobromination.
1,3‐Dipolar cycloaddition reactions of vinylcephalosporins with diazoalkanes
Authors: Pitlik János , Gunda Tamás E. , Miskolczi István
Published: March 2009

The vinylcephalosporin (1) undergoes a regio‐ and stereoselective 1,3‐dipolar cycloaddition with diazomethane to give novel cephalosporins, a 3‐pyrazolinocephem (4) and a double adduct (5). The vinylcephalosporin sulphoxide (2) gives only the pyrazolinocephem (7). In the reaction with diphenyldiazomethane upon heating the initially formed pyrazolines decompose and cyclopropylcephalosporin (9) formation takes place. The determination of the structures and stereochemistry of these compounds is also described.
An unusual HgCl rearrangement in electron impact mass spectrometry of some halomercurioalkyl derivatives
Authors: Ghezzo Elena , Sturaro Alberto , Traldi Pietro , Bravo Pierfrancesco , Viani Fiorenza
Published: March 2009

The electron impact mass spectrometric behaviour of three 2‐methyl‐2‐chloromercuriomethyl‐2,6‐dihydro‐5H‐pyrano[3,2‐c]quinolin‐5‐ones have been studied in detail with the aid of metastable ion data. The primary loss of C4H7, necessarily involving an unusual HgCl rearrangement, is discussed and justified by the formation of a thermodinamically stable Hg‐containing cyclic structure.
Pyridazines. LI. On the Reactivity of Pyridazine‐carbaldehydes towards Selected Active‐Hydrogen Compounds
Authors: Dostal Wolfgang , Heinisch Gottfried , Holzer Wolfgang , Perhauc Ingrid , Zheng Changtu
Published: March 2009

Reactions of 3‐pyridazinecarbaldehyde and 4‐pyridazinecarbaldehyde with various active methylene carbanions were studied. The products obtained in Knoevenagel reactions, Wittig‐Horner‐Emmons reactions, and Hantzsch‐type reactions are presented.
Polycondensed heterocycles. IV. synthesis of 1,4‐dioxo‐2,3,3a,4‐tetrahydro‐1H‐pyrrolo[2,1‐c][1,4]benzothiazine
Authors: Nacci V. , Campiani G. , Garofalo A.
Published: March 2009

A method for the synthesis of the title compound 3 consisted of an intramolecular cyclization in a stannic chloride catalyzed Friedel‐Crafts reaction of N‐(2‐methylthiophenyl)‐5‐oxoproline chloride 10, prepared by chlorination of the corresponding acid 9 obtained by hydrolysis of its ethyl ester 8. Condensation of 2‐methylthioaniline 4 with diethyl bromomalonate 5 afforded diethyl 2‐methylthioanilinomalonate 6 which gave 8 either directly by reaction with ethyl acrylate or by alkylation with ethyl β‐bromopropionate or ethyl acrylate and cyclization of resulting triethyl 2‐(2‐methylthio)anilino‐2‐carboxyglutarate 7. This method was not convenient because of the poor yield of 3 (14%).

On the other hand, cyclization of N‐(2‐mercaptophenyl)‐5‐oxoproline 14 with DCC and DMAP provided 3 in 45% yield. Oxidation with m‐CPBA of the esters 11 and 8, demethylation via the Pummerer rearrangement of the respective sulphoxides 12 and 17 with TFAA and oxidation with iodine of resulting N‐(2‐mercap‐tophenyl)‐5‐oxoproline esters 13 and 18 gave the corresponding disulphides 16 and 19. Hydrolysis of these latter compounds and reduction of the resulting bis[2‐[2‐(hydroxycarbonyl)‐5‐oxo‐1‐pyrrolidinyl]phenyl] disulphide 15 with sodium dithionite afforded the required 14. Deprotection of t‐butyl ester 13 with TFA at 55° to obtain 14 led to 3 in 42% yield. Finally the Pummerer rearrangement of N‐(2‐methylsulphinylphenyl)‐5‐oxo‐proline 20 yielded the mixture of 14 and 15.
Synthesis of methyl‐substituted lariat ethers containing a 13‐crown‐4 ring
Authors: Wakita Ryuhei , Yonetani Masayuki , Nakatsuji Yohji , Okahara Mitsuo
Published: March 2009

Convenient synthetic procedures for preparing two kinds of methyl‐substituted lariat ethers containing a 13‐crown‐4 ring, 1 and 2, are described. Compounds 1a‐1c were obtained from the reaction of 2‐bromomethyl‐2‐methyl‐13‐crown‐4 (5) with the appropriate alkoxide. Compound 5 was prepared without the need for prior protection of the bromomethyl group. For the synthesis of compounds 2a‐2c, which possess an electron‐donating group on the central carbon of the trimethyl moiety of the 13‐crown‐4 ring, the substituents were introduced before cyclization.
1,3‐Dipolar cycloaddition reactions of 1,3,4‐oxadiazin‐6‐ones with nitrile oxides
Authors: Argyropoulos N. G. , Corobili E. , Terzis A. , Mentzafos D.
Published: March 2009

2,5‐Diaryl‐1,3,4‐oxadiazin‐6‐ones 1 gave with nitrile oxides 2 1,2,4‐oxadiazole derivatives 4. When mesitonitrile oxide 2a was used, bis‐adducts 3 were also formed. The cycloadditions showed a remarkable site selectivity towards one carbon nitrogen double bond. The structure of both adducts was fully characterized by X‐ray analysis.
Tautomerism in some quinaldyl sulfones
Authors: Douglass James E. , Gebhart Myron A.
Published: March 2009

A series of quinaldyl sulfones was synthesized and their tautomeric composition was determined by 1H nmr.
Some transformations of 3‐amino‐4‐alkoxycarbonyl‐6‐hydroxy‐2H‐1‐benzopyran‐2‐ones. The synthesis of [1] benzopyrano[3,4‐d]‐[1,3]oxazine and [1] benzopyrano[3,4‐d]pyrimidine derivatives
Authors: Fajgelj Simona , Stanovnik Branko , Tišler Miha
Published: March 2009

Acylation of 4‐alkoxycarbonyl‐3‐amino‐6‐hydroxy‐2H‐1‐benzopyran‐2‐one derivatives 3 and 4 gave under mild conditions the O‐substituted derivatives 5–10, N,O‐disubstituted derivative 11 and N,N‐disubstituted derivative 12. The compound 4 was transformed with benzoyl chloride under more drastic conditions into 13, a derivative of a new heterocyclic system 2‐benzopyrano[3,4‐d][1,3]oxazine. The derivatives of 1‐benzopyrano‐[3,4‐d]pyrimidine 19 and 20 were prepared either from 3 and 4 through the corresponding N‐heteroarylformamidines 14 and 15 and N‐heteroarylformamide oximes 17 and 18 or by cyclization of thiourea derivative 20.
Synthesis,1H,13C‐NMR and mass spectral study of aryloxyquinuclidinium salts
Authors: Cosme A. , Arias M. S. , Gálvez E. , Ruano C. , Ruano C.
Published: March 2009

A series of3‐aryl‐3‐hydroxy‐N‐(4′‐aryloxobutyl)quinuclidinium salts have been synthesized. The1H nmr,13C nmr and mass spectra of these compounds are described and discussed.
Electron impact mass spectrometry and collisional spectroscopy in the structural characterization of 4‐benzylidene and 4‐phenylethylidene‐2‐phenyl‐5(4H)‐oxazolones
Authors: Curcuruto O. , Traldi P. , Cativiela C. , De Villegas M. D. Diaz , Garcia J. I. , Mayoral J. A. , Ajò D.
Published: March 2009

The mass spectrometric behaviour of four isomeric oxazolones is rationalized by means of metastable ion studies and bond order calculations via semiempirical methods. The data allow the identification of a possible intermediate structure of molecular species that accounts easily for the observed primary decomposition pathways.
8‐Bromo‐6‐alkylamino‐2‐trifluoromethyl‐9H‐purines with in vitro activity against influenza a virus
Authors: Kelley James L. , Linn James A. , Tisdale Margaret
Published: March 2009

Several derivatives of 8‐bromo‐6‐dimethylamino‐2‐trifluoromethyl‐9H‐purine (1) were synthesized for structure‐activity relationship studies of anti‐influenza A virus activity. The 8‐bromopurines were prepared by reaction of the anion of the 6‐alkylamino‐2‐trifluoromethylpurines with N‐bromosuccinimide. Several compounds had anti‐influenza activity comparable to ribavirin, but no in vivo activity was observed.
On triazoles XXIII [1]. The reaction of 5‐amino‐1,2,4‐triazoles with thiacyclohexane β‐oxo esters [2]
Authors: Reiter József , Esses‐Reiter Klára
Published: March 2009

Six novel isomeric ring systems, namely the thiopyrano[4,3‐d]‐1,2,4‐triazolo[1,5‐a]pyrimidine, the thiopyrano[3,4‐e]‐1,2,4‐triazolo[1,5‐a]pyrimidine, the thiopyrano[3,4‐d]‐1,2,4‐triazolo[1,5‐a]pyrimidine, the thiopyrano[4,3‐e]‐1,2,4‐triazolo[1,5‐a]pyrimidine, the thiopyrano[3,2‐d]‐1,2,4‐triazolo[1,5‐a]pyrimidine and the thiopyrano[2,3‐e]‐1,2,4‐triazolo[1,5‐a]pyrimidine were synthesised. Spectroscopical evidence was given for the structure of compounds obtained.
Homolytic alkylations of substituted pyridazines [1]
Authors: Samaritoni Jack G. , Babbitt George
Published: March 2009

The unsymmetrically substituted pyridazines 1 (X  Ph, CH3) have been found to undergo homolytic heteroaromatic alkylation in moderate to good yields with high regioselectivity. The site of substitution was established by conversion to 5 and measurement of the pyridazine proton coupling constant. In addition, homolytic alkylations of 1 (X  CH3) afforded the N‐alkylated products 6 and 7.
Products from furans. XV. Synthesis of novel tyramine derivatives via 6‐hydroxy‐2H‐pyran‐3(6H)‐ones
Authors: Georgiadis Minas P. , Apostolopoulos Costas D. , Haroutounian Serkos A.
Published: March 2009

Furan chemistry was utilized for the synthesis of several novel tyramine derivatives. Thus 2H‐pyran‐3(6H)‐ones were used as keystone intermediates for the preparation of novel α,β‐disubstituted tyramine derivatives. Furthermore by the same approach tyramine was derivatized with a molecule of GABA.
13C NMR investigation of tautomeric and acid‐base equilibria of pyrazolone T and three analogs
Authors: Bell Sandra J. , Mazzola Eugene P. , Dinovi Michael J. , Reynolds William F. , Nielsen Kathy W.
Published: March 2009

Pyrazolone T and three derivatives have been characterized by 13C and, in part, 15N nmr at several pH values. The 13C chemical shifts have been assigned at, or near, the equivalence points and pKa values of these four compounds. Closely situatued quaternary carbon signals were assigned by means of a heteronuclear chemical shift correlation (FLOCK) experiment which is sensitive to, and was optimized for, 3‐bond C‐H couplings. The 13C chemical shift data indicate the existence of both tautomeric and acid‐base equilibria and demonstrate that the four congeners exist in surprisingly different forms at certain common pH values.
Synthesis and NMR spectroscopy (1H 13C) of 1‐(2′‐benzothiazolyl)‐3(5),4‐polymethylenepyrazoles and related compounds
Authors: Elguero J. , Martinez A. , Singh S. P. , Kumar D.
Published: March 2009

A series of 3(5),4‐trimethylene and 3(5),4‐tetramethylenepyrazoles (tetrahydroindazoles) have been prepared from 2‐acylcyclanones using two methods: direct reaction with a substituted hydrazine and through an NH‐pyrazole followed by nucleophilic substitution. The results mainly concern the 2‐benzothiazolyl substituent, but 2,4‐dinitrophenyl derivatives were also studied for comparison. The orientation of the reactions (isomer ratio), the deshielding in 1H nmr of the 5‐methyl and 5‐methylene signals when a benzothiazolyl residue is at position 1, and the ring strain effect on heterocyclic carbons chemical shifts, are discussed.
Synthesis of brain‐targeted 5‐iodo‐, 5‐vinyl‐ and (E)‐5‐(2‐iodovinyl)‐2′‐deoxyuridines coupled to a dihydropyridine ⇌ pyridinium salt redox chemical delivery system
Authors: Kumar Rakesh , Ji Gueijun , Wiebe Leonard I. , Knaus Edward E.
Published: March 2009

5‐Iodo‐3′‐O‐(1‐methyl‐1,4‐dihydropyridyl‐3‐carbonyl)‐2′‐deoxyuridine (15a), 5‐vinyl‐3′‐O‐(1‐methyl‐1,4‐di‐hydropyridyl‐3‐carbonyl)‐2′‐deoxyuridine (15b) and (E)‐5‐(2‐iodovinyl)‐3′‐O‐(1‐methyl‐1,4‐dihydropyridyl‐3‐carbonyl)‐2′‐deoxyuridine (15c) were synthesized for future evaluation as lipophilic brain‐selective antiviral agents for the treatment of herpes simplex encephalitis. Quaternization of the 3′‐O‐(3‐pyridylcarbonyl) compounds 10–11 using iodomethane afforded the corresponding 1‐methylpyridinium salts 12–13 which were reduced with sodium dithionite to yield the corresponding 3′‐O‐(1‐methyl‐1,4‐dihydropyridyl‐3‐carbonyl) compounds 14–15.
Intramolecular photoreactions of 4‐(ω‐alkenyloxy)‐6‐methyl‐2‐pyrones
Authors: Shimo Tetsuro , Yasuda Mitsuo , Tajima Jun , Somekawa Kenichi
Published: March 2009

Photoirradiations of 4‐(ω‐alkenyloxy)‐2‐pyrones 1 gave site‐ and regio‐specific intramolecular [2 + 2]‐cycloadducts 2 being oxatricyclic lactones, and/or Dewar‐type valence‐isomer derivatives 4. The reaction path depended upon the alkenyl chain length. Namely the two or three carbon chain gave rise to intramolecular [2 + 2]‐cycloaddition, while the four carbon chain caused both valence‐isomerization and cycloaddition. Hydrolysis of the cycloadducts 2 gave oxabicycloalkanecarboxylic acids 7.
Substituent interaction with ring sulfur in some heterocyclic compounds
Authors: Mckinnon David M. , Abouzeid A. A.
Published: March 2009

The infrared carbonyl absorptions of 7‐acetyl‐1,2‐benzisothiazoles are similar to 7‐acetylbenzo[b]thiophenes, but are lower by approximately 15 cm−1 than the corresponding benzo[b]furans. The reasons for this are discussed.
Photochemical synthesis of 2‐substituted benzothiazoles
Authors: Muthusamy Sengoden , Paramasivam Rangasamy , Ramakrishnan Vayalakkavoor T.
Published: March 2009

The photochemical reaction of 1‐indolethiocarbanilides 1, di‐ and tri‐substituted thioureas 3–5 and 4,4‐di‐methyl‐2,6‐dioxothiocyclohexanecarboxanilides 9 affording the respective benzothiazoles are described.
The convergent syntheses of pyrazinyl and quinoxalinyl phenylmethanones from 2‐lithio pyrazines and quinoxalines
Authors: Ward John S. , Merritt Leander
Published: March 2009

Pyrazines and quinoxalines bearing 2‐substituents that direct ortho metalation reacted with lithium 2,2,6,6‐tetramethylpiperidide to produce 2‐substituted‐3‐lithiopyrazines and quinoxalines. These lithio reagents reacted with N‐methoxy‐N‐methylbenzamide to give good to moderate yields of 3‐substituted pyrazinyl or quinoxalinylphenylmethanones. The 3‐methylthio substituents of some ketone products were oxidized to methylsulfonyl groups that were susceptible to nucleophilic displacement.
A convenient synthesis of 5,14‐methano‐16‐oxo‐1,5,6‐benzoxadiazonino[3,4‐b]quinoxalines utilizing a 1,3‐dipolar cycloaddition reaction and an intramolecular alcoholysis
Authors: Kurasawa Yoshihisa , Kim Ho Sik , Katoh Ritsuko , Kawano Tae , Takada Atsushi , Okamoto Yoshihisa
Published: March 2009

The reaction of the hydrazones 5a‐c with 2‐chloroacrylonitrile produced the 1,2‐diazepino[3,4‐b]quinoxaline hydrochlorides 6a‐c, which were transformed into the 5,6,7,13‐tetrahydro‐5,14‐methano‐16‐oxo‐1,5,6‐benzoxadiazonino[3,4‐b]quinoxalines 7a‐c, respectively. The oxidation of 7a‐c with diethyl azodicarboxylate afforded the 7,13‐dihydro‐5,14‐methano‐16‐oxo‐1,5,6‐benzoxadiazonino[3,4‐b]quinoxalines 8a‐c, respectively. Compounds 7a‐c and 8a‐c were also obtained by a one‐pot synthesis from 5a‐c and 6a‐c, respectively.
Ozonolysis of 5‐bromo‐ and 5‐ethoxy‐2‐phenyloxazoles. The products and the reaction mechanism
Authors: Kashima Choji , Arao Hideki
Published: March 2009

The ozonolysis of 2‐phenyloxazoles having the good leaving group as an anion at C‐5 position gave mainly N‐benzoylisocyanate (2) with the formation of carbon dioxide.
A simple synthesis of 2(3H)‐benzoxazolones using phenyl chloroformate
Authors: Maleski Robert J. , Osborne C. Edward , Cline Sharon M.
Published: March 2009

2(3H)‐Benzoxazolones 3 can be prepared directly from the corresponding 2‐aminophenols and phenyl chloroformate. The intermediate 2‐hydroxy phenylcarbamates 2 are formed easily in aqueous alcohol solvent and these are converted rapidly to product, without their isolation, using one equivalent of sodium hydroxide. The synthesis accommodates a wide variety of substituents, including the easily hydrolyzed ethyl ester.
A facile and novel synthesis of 5‐phenylimidazo[4,5‐c][1,8]naphthyridin‐4(5H)‐ones
Authors: Kuroda Takeshi , Suzuki Fumio
Published: March 2009

A convenient and regioselective synthesis of a new heterocycle, 5‐phenyl‐1H or 3H‐imidazo[4,5‐c][1,8]‐naphthyridin‐4(5H)‐one 1‐a or 1‐b, is described. Methyl 2‐anilinonicotinate 15 was transformed into the valuable intermediate, N‐phenyl‐3‐azaisatoic anhydride 4 using trichloromethyl chloroformate (TCF). Treatment of 4 with the anion of ethyl nitroacetate gave 4‐hydroxy‐3‐nitro‐1‐phenyl‐1,8‐naphthyridin‐4(5H)‐one 3. Compound 3 was chlorinated, aminated, reduced, and cyclized to afford 5‐phenylimidazo[4,5‐c][1,8]naphthyridin‐4(5H)‐one 1. Regioselective substitution at the 1 or 3‐position in the imidazole moiety of 1 was achieved by minor changes of the above scheme.
Total assignment of the 1H and 13C NMR spectra of benzo[f][1]benzothieno[2,3‐c]quinoline by inverse‐detected two‐dimensional NMR techniques
Authors: Shockcor John P. , Crouch Ronald C. , Martin Gary E. , Cherif Abdallah , Luo Jiann‐Kuan , Castle Raymond N.
Published: March 2009

The proton and carbon nmr spectra of benzo[f][1]benzothieno[2,3‐c]quinoline have been totally assigned using a combination of 2D nmr methods including concerted use of HMQC (heteronuclear multiple quantum correlation) and HMBC (heteronuclear multiple bond correlation) experiments.
An unusual reaction at C‐3 of 4‐methoxy‐6‐methyl‐2‐pyrone
Authors: Moreno‐Mañas M. , Pleixats R.
Published: March 2009

Triacetic acid lactone methyl ether, 4, can be lithiated at C‐3 under kinetically controlled conditions. Further reaction with (E)‐2‐methyl‐3‐(4‐nitrophenyl)propenal results in an unusual condensation at C‐3.
Synthesis and NMR study of 9′‐substituted spiroindolinonaphthoxazine derivatives
Authors: Kakishita Tomonari , Matsumoto Kiyoichi , Kiyotsukuri Tsuyoshi , Matsumura Kenji , Hosoda Masahiro
Published: March 2009

A photochromic spiroindolinonaphthoxazine derivative, 1,3,3‐trimethyl‐9′‐hydroxy‐spiro[indoline‐2,3′(3H)‐ naphtho[2,1‐b][1,4]oxazine] 3 was synthesized by condensation of 1,2,3,3‐tetramethylindolenium iodide 1 and l‐nitroso‐2,7‐dihydroxynaphthalene 2. Further, two new derivatives, 5 and 7, were prepared in good yields by the reactions of 3 with the hexafluoropropene trimer 4 and 4‐[perfluoro(2‐isopropyl‐1,3‐dimethyl‐1‐butenyl)‐oxybenzoyl chloride 6, respectively. Their unique structural features and property are discussed based on 1H‐, 13C‐ and 19F nmr spectral data.
C‐2 Arylamino substituted purineara‐carbocyclic nucleosides as potential anti‐cytomegalovirus agents
Authors: Koga Masakazu , Schneller Stewart W.
Published: March 2009

There are reports in the literature that placement of an arylamino side chain at the C‐2 position of purine nucleosides produces compounds capable of inhibiting DNA polymerase. To evaluate the potential of this class of compounds as antiviral agents that act by inhibiting viral DNA polymerase,ara‐carbocyclic purine nucleosides possessing a 4‐(l‐butyl)phenylamino and a 3,5‐dichlorophenylamino substituent at C‐2 were chosen as the prototype structures and have been prepared from 2,4,6‐trichloropyrimidine in 6 steps. For the antiviral analysis, human cytomegalovirus served as the principal virus since it expresses a virally specific DNA polymerase. None of the compounds showed activity towards this virus, but they were found to display some toxicity towards one or more cell lines.
Synthesis of fluoro and trifluoromethyl derivatives of 2‐phenylquinolin‐4‐ol
Authors: Janda Lubomir , Nguyen Johnny , Patterson Steven E. , Strekowski Lucjan
Published: March 2009

A tert‐butoxide base‐mediated cyclization of fluoro‐ and trifluoromethyl‐substituted Schiff bases 12‐19 produces 4‐tert‐butoxyquinolines 23‐30 which are hydrolyzed to quinolin‐4‐ols 31‐38.
Synthesis of trans‐thienyl‐3‐ethoxycarbonyl‐2,3‐dihydro[1,5]benzothiazepin‐4(5H)‐ones
Authors: Letois Bertrand , Lancelot Jean Charles , Saturnino Carmela , Robba Max , De Caprariis Paolo
Published: March 2009

A series of trans‐thienyl‐3‐ethoxycarbonyl‐2,3‐dihydro[1,5]benzothiazepin‐4(5H)‐ones 6‐8 was synthesized from thienylmethylidenemalonates 3a‐3c and 2‐aminobenzenethiol 3d in the presence of triethylamine hydrochloride at 160°. The [1,5]benzothiazepines 6‐8 were alkylated using 2‐dimethylaminochloroethane, 3‐dimethylaminochloropropane and 3‐(N‐piperidino)chloropropane in order to obtain the corresponding 5‐aminoalkylbenzothiazepinones 9‐14.
Pyrimidine derivatives. IX. Synthesis of bromosubstituted 5‐nitro‐2,4(1H,3H)‐pyrimidinedione derivatives
Authors: Kinoshita Toshio , Watanabe Yukihiro , Nakao Setsuko , Furukawa Sunao
Published: March 2009

The following 5‐nitro‐2,4(1H,3H)‐pyrimidinediones possessing bromo substituted side chains at the 1‐ and 6‐positions were prepared by bromination of 3,6‐dimethyl‐1‐(ω‐hydroxyalkyl)‐5‐nitro‐2,4(1H,3H)‐pyrimidinediones 4a and 4b and its nitrates 2a and 2b. The three of mono‐bromo derivatives are: 1‐(ω‐acetoxyalkyl and ω‐hydroxyalkyl)‐6‐bromomethyl‐3‐methyl. 6a, 6b, 7a and 7b and 1‐(ω‐bromoalkyl)‐3,6‐dimethyl‐2,4(1H,3H)‐ pyrimidinediones 8a and 8b. The one type dibromo derivatives are: 1‐(ω‐bromoalkyl)‐6‐bromomethyl‐3‐methyl‐2,4(1H,3H)‐pyrimidinediones 5a and 5b.
A new diene, 2‐methoxy‐1,3‐pentadiene‐5‐ol. Synthesis and intramolecular diels‐alder reactions
Authors: Jørgensen Tine , Nielsen Helle Chris , Malhotra Nageshwar , Becher Jan , Begtrup Mikael
Published: March 2009

Reactions of the diene 1‐benzyloxy‐2‐methoxy‐1,3‐pentadiene‐5‐ol in intramolecular Diels‐Alder reactions using maleic anhydride or fumaric acid ethyl ester is described. The new reactive diene is prepared starting from 3‐methoxypyridine. The structure of the diene was elucidated by a NOE nmr experiment.
Nitroimidazoles X. Syntheses of substituted 2‐(1‐methyl‐5‐nitro‐2‐imidazolyl)quinolines
Authors: Shafiee A. , Parang K. , Khazan M. , Ghasemian F.
Published: March 2009

Reduction of substituted‐2‐nitrobenzaldehyde (1) afforded substituted‐2‐aminobenzaldehyde (2). Reaction of compound 2 with 2‐acetyl‐1‐methyl‐5‐nitroimidazole (3) under basic conditions afforded substituted 2‐(1‐methyl‐5‐nitro‐2‐imidazolyl)quinolines 4. Reaction of compound 4 (R = X) with hydrogen peroxide in acetic acid afforded compound 5 which was transformed to compound 6 with phosphorus oxychloride.
Synthesis of 4,5‐dihydro‐1H,3H‐thieno[3,4‐c]thiophene and 4,5‐dihydro‐1H,3H‐thieno[3,4‐c]furan
Authors: Ripoll Jean‐Louis , Vallée Yannick , Khalid Mohamed , Hakiki Abdelhak
Published: March 2009

4,5‐Dihydro‐1H,3H‐thieno[3,4‐c]thiophene and 4,5‐dihydro‐1H,3H‐thieno[3,4‐c]furan were synthesized by retro Diels‐Alder reactions under flash vacuum thermolysis conditions.
The HMQC‐NOESY experiment without decoupling during acquisition for detection of nOe between pseudo‐equivalent protons
Authors: Castle Lyle W. , Johnston Milton D. , Camoutsis Charalampos L. , Castle Raymond N.
Published: March 2009

The pseudo‐symmetric structure of benzo[f]phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline causes overlap of the resonances corresponding to H1 and H15 and also those of H11 and H12. We report here the observation of nOe between these pseudo‐equivalent protons using the HMQC‐NOESY experiment acquired without decoupling during acquisition.
Structural study of 3‐methyl‐2,4‐diphenyl‐3‐azabicyclo[3.3.1]nonan‐9β‐ol
Authors: Iriepa I. , Gil‐Alberdi B. , Galvez E. , Torres R. , Gomez‐Sal P. , Bellanato J.
Published: March 2009

The infrared spectra in several media and the crystal structure of 3‐methyl‐2,4‐diphenyl‐3‐azabicyclo[3.3.1]‐nonan‐9β‐ol (I) (Scheme I) have been determined, in order to complete the structural study described for the title compound from the 1H and 13C nmr data [1]. The bicyclic system adopts a flattened chair‐chair conformation in which the cyclohexane ring is more flattened. The methyl and phenyl groups are in equatorial positions and the OH group in an axial position with respect to the piperidine ring.
A short and general synthesis of 1,3‐dihydro‐6‐heteroaryl‐5‐perfluoroalkyl‐2H‐imidazo[4,5‐b]pyridin‐2‐ones
Authors: Kuo Gee‐Hong , Bacon Edward R. , Singh Baldev , Eissenstat Michael A. , Lesher George Y.
Published: March 2009

Trifluoro or pentafluoroacylation of heteroaryl‐enamines 2a,b gave the corresponding perfluoroacylated heteroaryl‐enamines 3a‐c. Heating the latter compounds with diethyl iminomalonate gave 2‐amino‐3‐pyridinecarboxylates 4a‐c. Hydrolysis to the free acids 5a‐c, and reaction with diphenylphosphoryl azide afforded the desired 1,3‐dihydro‐6‐heteroaryl‐5‐perfluoroalkyl‐2H‐imidazo[4,5‐b]pyridin‐2‐ones 6a‐c.
In situ vinylindole synthesis. Diels‐alder reactions with maleimides to give tetrahydrocarbazoles
Authors: Noland Wayland E. , Walhstrom Mary J. , Konkel Michael J. , Brigham Mark E. , Trowbridge Annette G. , Konkel Lisa M. C. , Gourneau Ronald P. , Scholten Cheryl A. , Lee Nina H. , Condoluci John J. , Gac Todd S. , Pour Mehrdad Mostafaei , Radford Peter M.
Published: March 2009

Tetrahydrocarbazoles have been prepared in one‐flask syntheses from indoles, ketones or aldehydes, and maleimides, with acid catalysis. The reactions involve a condensation of the indole with the ketone or aldehyde, followed by an in situ trapping of the vinylindole in a Diels‐Alder addition with a maleimide. Isomerization of the double bond into the indole nucleus gave the tetrahydrocarbazoles which were isolated (6, 9, and 10). Variation of the indole, carbonyl compound, and maleimide has been explored. The predominant stereochemistry of the tetrahydro ring in the products is all‐cis, although a second stereoisomer has been isolated. Two regioisomers were generated from all unsymmetrical 2‐alkanones, except 2‐butanone, which gave the single isomer 9a. Aromatization of tetrahydrocarbazoles 6 to carbazoles 7 was accomplished with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone.
Cyclocondensation of α‐hydroxyimino‐β‐alkyl/arylimino‐β‐methylthioketones with hydrazine hydrate: Synthesis of 3(5)‐aryl‐5(3)‐alkyl/arylamino‐4‐nitroso (or amino) pyrazoles
Authors: Chakrasali R. T. , Srinivasa Rao Ch. , Ila H. , Junjappa H.
Published: March 2009

The title pyrazoles were synthesized through cyclocondensation of hydroxyiminoimine derivatives 1a‐j with hydrazine hydrate.
Naphth[1,2‐d]oxazole intermediates in the preparation of 3‐hydroxy‐4‐(1‐alkyl‐3‐methyl‐5‐hydroxy‐4‐pyrazolyl)‐azo‐1‐naphthalenesulfonamide dyes
Authors: Katritzky Alan R. , Rachwal Bogumila , Rachwal Stanislaw , Macomber David , Smith Terrance P.
Published: March 2009

Acylation of 4‐amino‐3‐hydroxy‐1‐naphthalenesulfonic acid (3) with benzoyl chloride in pyridine gave pyridinium 3‐hydroxy‐4‐(N‐benzoylamino)‐1‐naphthalenesulfonate (12) which was converted by thionyl chloride followed by diethylamine into N,N‐diethyl‐2‐phenylnaphth[1,2‐d]oxazole‐5‐sulfonamide (14). The naphthoxazole moiety was hydrolyzed with potassium hydroxide and the resulting N,N‐diethyl‐4‐amino‐3‐hydroxy‐1‐naphthalenesulfonamide (11) coupled with 1‐alkyl‐3‐methyl‐5‐pyrazolones. The 2‐phenylnaphth[1,2‐d]oxazole intermediates and various by‐products were investigated.
Flavonoids. 43 [1,2]. Deprotonation‐initiated aryl migration with sulfur dioxide extrusion: A route to 2,3‐dihydro‐2,3‐diaryl‐3‐hydroxy‐4H‐1‐benzopyran‐4‐ones
Authors: Patonay Tamás , Hegedüs László , Patonay‐Péli Erzsébet
Published: March 2009

Treatment of trans‐2,3‐dihydro‐2‐aryl‐3‐nosyloxy‐4H‐1‐benzopyran‐4‐ones with various bases afforded 2,3‐dihydro‐r‐2‐aryl‐t‐3‐hydroxy‐c‐(4‐nitrophenyi)‐4H‐1‐benzopyran‐4‐ones in a deprotonation‐initiated aryl migration followed by sulfur dioxide extrusion. In the presence of hydroxide and methoxide ions a secondary ring cleavage has also been observed. However, the reaction of trans‐2,3‐dihydro‐2‐aryl‐3‐nosyloxy‐4H‐1‐benzopyran‐4‐ones with cyanide ions gave 2,3‐dihydro‐r‐2‐aryl‐t‐4‐cyano‐c‐3,c4‐epoxy‐4H‐1‐benzopyrans in a carbonyl attack of cyanide followed by an internal substitution reaction.
Cyclocondensation reaction of 1,2‐diamino‐4‐methylbenzene and p‐substituted acetophenones
Authors: Insuasty Braulio , Abonia Rodrigo , Quiroga Jairo , Meier Herbert
Published: March 2009

1,2‐Diamino‐4‐methylbenzene 1 reacts in the presence of sulphuric acid with 4‐substituted acetophenones 2a‐e yielding 2,4‐diaryl‐2,3‐dihydro‐2,8‐dimethyl‐1H‐1,5‐benzodiazepines 3a‐e and as minor component 2,4‐diaryl‐2,3‐dihydro‐2,7‐dimethyl‐1H‐1,5‐benzodiazepines 4a‐e. The ratio 3:4 is in the range of 7:3. The structure determination of the regioisomers was performed by NOE measurements.
Reactions of 6‐thiotheophylline with alkylating agents and epichlorohydrin: Isolation of S‐alkylated 6‐thiotheophylline and 7‐(2,3‐thioepoxypropyl)theophylline
Authors: Hayashi Hiroaki , Suzuki Fumio , Yasuzawa Toru , Ueno Hideo
Published: March 2009

Alkylation of 6‐thiotheophylline (1) under the aprotic basic condition affords S‐alkylated 6‐thiotheophylline (3) together with an N7 ‐alkylated product 4. There is a tendency that the more reactive the alkylating agents are, the higher the yields of S‐alkylated products are. On the other hand, treatment of 6‐thiotheophylline (1) with epichlorohydrin afforded an unexpected product, 7‐(2,3‐thioepoxypropyl)theophylline (6), neither an S‐alkylated compound 3g nor an N7 ‐alkylated compound 4g. The chemical structure was determined by nmr spectroscopic analysis.
Synthesis of perhydropyrazino[1,2‐d][1,4]diazepine, a new heterocyclic compound
Authors: Gubert S. , Braojos C. , Anglada L. , Bolós J. , Sacristán A. , Ortiz J. A.
Published: March 2009

A novel heterocycle, perhydropyrazino[1,2‐d][1,4]diazepine, is prepared in good yield by an efficient method starting from facile available compounds.
Alkali metal mediated conversion of arene oxides and arene imines into aromatic hydrocarbons
Authors: Elmalak Omar , Rabinovitz Mordecai , Blum Jochanan
Published: March 2009

K‐Region oxides and imines of phenanthrene, chrysene benz[a]anthracene, and dibenz[a,h]anthracene react in tetrahydrofuran with lithium and sodium to give the parent hydrocarbons. In the presence of excessive metal, the latter are converted into dianions from which the parent compounds can be regenerated upon quenching with oxygen. Metalate derivatives of the oxides and imines are proposed to be the corresponding reaction intermediates in the deoxygenation and deamination processes.
Condensed as‐triazines. Synthesis of 7‐aryl‐8H‐[1,4]thiazino[2,3‐e]‐1,2,4‐triazin‐3(2H)‐one
Authors: Lee Kuan‐Han , Huang Bor‐Ruey , Chen Yeh‐Long , Wei Dau‐Chang , Tzeng Cherng‐Chyi
Published: March 2009

Ring closure of 6‐amino‐3‐oxo‐as‐triazine‐5‐thione with α‐haloketones provides the thiazino[2,3‐e]‐1,2,4‐triazines which dehydrate via an unusual pathway to give 7‐aryl‐8H[1,4]thiazino[2,3‐e]‐1,2,4‐triazin‐3(2H)‐ones.
The diels‐alder reaction of 5‐aminopyrazole‐4‐carbonitrile with dmad: Synthesis and structural determination of dimethyl 2‐(p‐toluenesulfonylamino)‐3‐cyano‐4‐imino‐1,4‐dihydropyridine‐5,6‐dicarboxylate
Authors: Tominaga Yoshinori , Castle Raymond N. , Kent Dalley N.
Published: March 2009

The Diels‐Alder reaction of 5‐amino‐1‐(p‐toluenesulfonyl)pyrazole‐4‐carbonitrile with dimethyl acetylenedi‐carboxylate was carried out in the presence of potassium carbonate in dimethyl sulfoxide. The reaction gave dimethyl 2‐(p‐toluenesulfonylamino)‐3‐cyano‐4‐imino‐1,4‐dihydropyridine‐5,6‐dicarboxylate. The product was formed by transformation of the original Diels‐Alder adduct followed by rearrangement of the p‐toluenesul‐fonylamino group into the 2‐position of the pyridine ring. The structure of the product was irrefutably established by X‐ray crystallography. This reaction is the first example of a pyrazole ring serving as the diene in a [4 + 2] cycloaddition reaction.
The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 13. Dibenzo‐[f,h]phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline
Authors: Luo Jiann‐Kuan , Castle Raymond N.
Published: March 2009

The synthesis of a previously unknown polycyclic heterocyclic ring system, dibenzo[f,h]phenanthro‐[9′,10′:4,5]thieno[2,3‐c]quinoline (4), was accomplished via photocyclization of the appropriate amide followed by chlorination. Substitution of the chlorine atom with hydrazine followed by removal of the hydrazine moiety with 10% copper sulfate solution afforded the parent ring system 4. The unequivocal assignment of its highly congested 1H and 13C spectra was accomplished by utilizing two‐dimensional nmr methods.
Synthesis of monoalkenylated crown ethers and C‐pivot cryptands
Authors: Yi Guoliang , Bradshaw Jerald S. , Krakowiak Krzysztof E. , Huang Mingxian , Lee Milton L.
Published: March 2009

The synthesis of two N‐(2‐allyloxy)ethyl‐substituted diaza‐crowns and two C‐pivot (allyloxy)methyl‐substi‐tuted cryptands is described. Controlled etherization of N,N‐bis(2‐hydroxyethyl)‐4,13‐diaza‐18‐crown‐6 with allyl bromide and sodium hydride gave N‐(2‐allyloxy)ethyl‐N‐(2‐hydroxyethyl)‐4,13‐diaza‐18‐crown‐6 in a good yield. This macrocycle was reacted with sodium hydride and tetrahydrofurfuryl chloride or 3,3‐dimeth‐ylbutyl tosylate to give expected N‐(2‐allyloxy)ethyl‐N'‐tetrahydrofurfuryloxy)ethyl‐[or (3,3‐dimethylbutoxy)‐ethyl]‐substituted products 3 or 4. 6,13‐Dimethylenyl‐14‐crown‐4 (9) and 9,19‐dimethylenyl‐20‐crown‐6 (10) were treated with mercuric acetate, followed by sodium borohydride in strong base to give macrocyclic diols 11 and 12, respectively. These diols were reacted with sodium hydride and the ditosylate derivative of allyloxymethyl‐substituted triethyleneglycol 13 to produce the C‐pivot (allyloxy)methyl‐substituted macrotri‐cycles 6 and 7.
A highly selective hydrogen‐deuterium exchange in indolium heptamethine cyanines
Authors: Lipowska Malgorzata , Patterson Steven E. , Patonay Gabor , Strekowski Lucjan
Published: March 2009

Chemical shift assignments in 1H nmr spectra of four tricarbocyanines have been made. Studies by 1H nmr have shown a rapid acid‐catalyzed proton exchange at positions 1′,7′ and a much slower exchange at positions 3′,5′ of the heptamethine chain. Base catalysis results in a slow exchange at positions 1′,7′ only.
Efficient synthesis of azetidine through N‐trityl‐ or N‐dimethoxytritylazetidines starting from 3‐amino‐l‐propanol or 3‐halopropylamine hydrohalides
Authors: Huszthy Peter , Bradshaw Jerald S. , Krakowiak Krzysztof E. , Wang Tingmin , Dalley N. Kent
Published: March 2009

Efficient synthetic routes for the preparation of azetidine starting from commercially available 3‐amino‐l‐propanol or 3‐halopropylamine hydrohalides are reported. First, the appropriate N‐trityl‐ or N‐dimethoxy‐trityl protected tosyloxy‐ or halopropylamines were prepared. These precursors were then cyclized into the N‐trityl‐ or N‐dimethoxytritylazetidines. The N‐protecting groups were removed in the presence of perchloric acid giving the hydrogen perchlorate salt of azetidine. The latter compound was transformed into its free base using a strong base under anhydrous conditions. The relatively expensive 4,4′‐dimethoxytrityl chloride and less expensive trityl chloride used in these synthetic procedures were recycled in good yields. Azetidine hydrogenperchlorate can be used to prepare N‐substituted azetidines without the need to isolate the free azetidine.
Synthesis and antiviral evaluation of β‐L‐Xylo‐fuanosyl nucleosides of the five naturally occurring nucleic acid bases
Authors: Gosselin Gilles , Bergogne Marie‐Christine , Imbach Jean‐Louis
Published: March 2009

The β‐L‐xylo‐furanosyl analogues of the naturally occurring nucleosides have been synthesized and their antiviral properties examined. All these compounds were hitherto unknown and they were stereospecifically prepared by glycosylation of pyrimidine and purine aglycons with a suitably peracyl‐L‐xylo‐furanose (specially synthesized from L‐xylose for our present purpose), followed by removal of the protecting groups. All the prepared compounds were tested for their activity against a variety of DNA and RNA viruses (including HIV), but they did not show significant antiviral activity.
Synthesis of 1‐(N‐arylaminomethyl)‐3‐methyl‐1,8‐dihydrocycloheptapyrazol‐8‐ones
Authors: Piao Ming‐Zhu , Wang Dao‐Lin , Lu Du‐Ren , Imafuku Kimiaki
Published: March 2009

Reactions of 3‐methyl‐1,8‐dihydrocycloheptapyrazol‐8‐one (2) with arylamines in the presence of formaldehyde gave 1‐(N‐arylaminomethyl)‐3‐methyl‐1,8‐dihydrocycloheptapyrazol‐8‐ones 5a‐l in good yields. 1,3,5‐Tris(phenyl‐ and 4‐methoxyphenyl)hexahydro‐1,3,5‐triazines or bis(3‐nitroanilino)methane, which were condensation products of arylamines and formaldehyde, also reacted with compound 2 to afford 5a,c,j, respectively.
Synthesis of 2‐carbamoylmethyl‐6‐β‐D‐ribofuranosylpyridine with the aid of a Pd(0)‐catalyzed reaction
Authors: De Vos Eric , Esmans Eddy L. , Alderweireldt Frank C. , Balzarini Jan , De Clercq Erik
Published: March 2009

D‐Allo/D‐altro‐2‐(2,4:3,5‐di‐O‐benzylidenepentitol‐l‐yl)‐6‐ethoxycarbonylmethylpyridine was synthesized from 2‐bromo‐6‐(2,4:3,5‐di‐O‐benzylidenepentitol‐1‐yl)pyridine or 2‐(2,4:3,5‐di‐O‐benzylidenepentitol‐1‐yl)‐6‐iodopyridine by means of a tetrakis(triphenylphosphine)palladium(O)‐catalyzed reaction with Reformatsky's reagent. Subsequent ammonolysis and mesylation of the D‐altro‐ethoxycarbonylmethyl compound gave D‐altro‐2‐carbamoylmethyl‐6‐(1‐O‐mesyl‐2,4:3,5‐di‐O‐benzylidenepentitol‐l‐yl)pyridine which was cyclized to 2‐carbamoylmethyl‐6‐β‐D‐ribofuranosylpyridine.
Synthesis and conformational properties of 2′‐deoxy‐2′‐methylthio‐pyrimidine and ‐purine nucleosides: Potential antisense applications
Authors: Fraser Allister , Wheeler Patrick , Dan Cook P. , Sanghvi Yogesh S.
Published: March 2009

A convenient and shorter synthesis of 2′‐deoxy‐2′‐methylthiouridine analogs 5, −5‐methyluridine 6, ‐cyti‐dine 15, −5‐methylcytidine 16, ‐adenosine 27 and ‐guanosine 34 was accomplished. Successful conversion of ribonucleosides (5‐methyl U, U, A, G) into the corresponding 2′‐substituted nucleosides involves nucleophilic displacement (SN2) of an appropriate leaving group at the 2′‐position by methanethiol, a soft nucleophile. Reaction between 2,2′‐anhydrouridine and methanethiol in the presence of N1,N1,N3,N3‐tetramethylguani‐dine in N,N‐dimethylformamide gave 5, in 75% yield. Preparation of 6 by a similar route was described. Acylated 5 and 6 were transformed into their triazole derivatives, which on ammonolysis furnished 15 and 16, respectively in good yield. Similarly, tetraisopropyldisiloxanyl (TIPS) protected 2′‐O‐aratriflates‐ of‐adenosine and ‐guanosine reacted with methanethiol in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene at ‐ 25°, followed by deblocking of the TIPS protecting group furnished 27 and 34, respectively. The confor‐mational flexibility (N/S equilibrium) of the sugar moiety in nucleosides 5, 15, 27 and 34 was studied utilizing nmr spectroscopy, suggesting that the 2′‐methylthio group influenced the sugar conformation to adopt a rigid S‐pucker in all cases. The extra stiffness of the sugar moiety in these analogs is believed to be due to the electronegativity of the substituent and the steric bulk. The usefulness of these nucleosides to prepare uniformly modified 2′‐deoxy‐2′‐methylthio oligonucleotides for antisense therapeutics is proposed.