bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactions of 4‐cyano‐ and 4‐methylimidazoles with isocyanates
Authors: Mitsuhashi Keiryo , Itho Ei‐Ichi , Kawahara Takeo , Tanaka Kiyoshi
Published: March 2009

4‐Cyano‐ and 4‐methylimidazoles reacted with methyl and aryl isocyanates to give exclusively 1‐(substituted carbamoyl)‐4‐cyano‐ and 4‐methylimidazoles, respectively. Refluxing of 1‐carbamoyl‐4‐methylimidazoles in nitrobenzene yielded 2‐carbamoyl‐4‐methylimidazoles through a known migration, whereas the 4‐cyano analogues could not be caused to migrate. On the other hand, the treatment of 4‐cyano‐1‐(methylcarbamoyl)imidazole with methyl isocyanate under the basic conditions resulted in the formation of 2‐methyl‐1‐(methylcarbamoylimino)‐2, 3‐dihydro‐1H‐imidazo[1, 5‐c]imidazol‐3‐one which must be formed via the migration of the carbamoyl group to another nitrogen followed by the intramolecular cyclization of the newly introduced carbamoyl group with its viccyano group.
Studies on the synthesis of heterocyclic compounds. Part X. One‐step route to 1,2‐dimethyl‐3‐R‐5‐salicyloylimino‐3‐pyrazolines
Authors: Plescia Salvatore , Daidone Giuseppe
Published: March 2009

This communication outlines the development of a direct synthetic route to 1,2‐dimethyl‐3‐R‐5‐salicyloyl‐imino‐3‐pyrazolines, starting from readily available 3(5)‐aminopyrazoles 1a, b, c and methyl salicylate. The structures of the new compounds 3a, b, c were determined on the basis of analytical and spectroscopic data as well as on the acid hydrolysis products.
Synthesis, structure elucidation and antibacterial activity of 6‐ethyl‐6,9‐dihydro‐9‐oxopyrazolo[3,4‐f]quinoline‐8‐carboxylic acid
Authors: Schwan Thomas J. , Freedman Raymond , Pollack Jay R.
Published: March 2009

The preparation, structure elucidation and antibacterial activity of 6‐ethyl‐6,9‐dihydro‐9‐oxopyrazolo‐[3,4‐f]quinoline‐8‐carboxylic acid are reported.
Synthesis of 5‐Aryl‐3‐(4‐pyridyl)‐1,2,4‐oxadiazoles
Authors: Braña Miguel F. , Castellano José M. , Yunta Maria J. R.
Published: March 2009

The title oxadiazoles were formed in the reaction of N‐(4‐pyridylmethyl)arylamides with nitrosyl chloride in low yields.
Reductive cleavage of ether and thioether bonds on 1,3‐benzodioxole and 1,3‐benzoxathiole derivatives
Authors: Melis Stefana , Sotgiu Francesca , Piras Pier Paolo , Plumitallo Antonio
Published: March 2009

The reaction of lithium and sodium diethylamide with 1,3‐benzodioxoles and 1,3‐benzoxathioles is here reported. 1,3‐Benzodioxoles exhibit selective cleavage of the ether bond with formation of alkoxyphenols; 1,3‐benzoxathioles when reacting with sodium diethylamide lead to 2‐alkoxybenzenethiols while with lithium diethylamide give 2‐alkoxybenzenethiols together with 2‐(alkylthio)phenols.
Synthesis of some 4‐substituted‐2‐(o‐halogenophenyl)‐1,2,3‐triazoles
Authors: Swartz David L. , Karash Angela R. , Berry Laura A. , Jaeger David L.
Published: March 2009

Mesoaldehyde 1,3‐dioxime was treated with either 2,4,6‐trichlorophenyl‐ (a), o‐fluorophenyl‐ (b), or o‐bromophenyl‐ (c) hydrazine to give the corresponding mesoaldehyde 1,3‐dioxime‐2‐halogenophenylhydrazones (1a,b,c). The latter were O‐acetylated with acetic anhydride, and cyclized to triazole 4‐oximes (3b, c) or triazole 4‐O‐acetyloximes (6a,b,c) with cesium carbonate, then converted to nitriles (7a,b,c) by refluxing with acetic anhydride followed by pyrolysis, or to aldehydes (4a,b,c) by hydrolysis. The nitriles (7a,b,c) were also converted to acids (9a,b,c), esters (10a,b,c), amides (8a,c), an alcohol (11a), and an amine (12a). In addition, tetrazoles of two types were prepared. The first (13d,e) were obtained from the acid chlorides by the action of 5‐aminotetrazole, whereas the second (14f) was produced from the respective nitrile by the action of ammonium azide.
Kinetic study on the acid hydrolysis of 1‐aryl‐2‐phenyl‐2‐imidazolines. Basicity‐rate of hydrolysis and structure relationships
Authors: Fernández Beatriz M. , Reverdito Ana M. , Perillo Isabel A. , Lamdan Samuel
Published: March 2009

Rate constants (kobs) of hydrolysis in sulfuric acid‐water mixtures at 100° for five 1‐aryl‐2‐phenyl‐2‐imidazolines were determined. The influence of substituents in the phenyl group at N‐1 upon the rate of hydrolysis was studied. When the imidazoline ring is considered to be a substituent of the benzene ring at N‐1, a good correlation with the Hammett equation is found.

In opposition to the behavior in alkaline media it was observed that reaction rates were enhanced by electron‐withdrawing phenyl substituents and reduced by electron‐releasing groups providing, similarly, a change in the mechanism of the reaction in the second case that was not observed in the first. Agreement with the Hammett equation allowed comparison between experimental and “calculated” rate constants which are fairly close. An equation relating the rate constants with the pKa values of the imidazolinium ions is given.
Reaction between ethyl ω‐chloroalkylimidates and hydrazides
Authors: Bonanomi Michele , Baiocchi Leandro
Published: March 2009

It is already known that ethyl ω‐chloroalkylimidate hydrochlorides and aroyl hydrazides gave, when reacted together in boiling ethanol, 2‐aryl‐5‐ω‐haloalkyl‐1,3,4‐oxadiazoles. It has now been found that the reaction follows a different course in the presence of triethylamine. In particular, 2‐aryl‐5,6,7,8‐tetrahydro‐1,2,4‐triazolo[5,1‐α]pyridines were obtained from ethyl δ‐chlorovalerimidate, whereas N‐aroylaminoimino‐pyrrolidines are the products obtained from ethyl γ‐chlorobutyrimidate. A similar case, in which the closure of the triazole ring to obtain a dihydropyrrolotriazole was found to be more difficult than the corresponding closure to a tetrahydrotriazolopyridine, is described. Also the reaction between the imidates and carbethoxy‐hydrazine, which gives piperidine and pyrrolidine derivatives, is reported.
Reaction of 1,1′‐iminobis‐2‐butanols with sulfuric acid
Authors: Hernestam Sven
Published: March 2009

Treatment of 1,1′‐iminobis‐2‐butanols with 70% w/w sulfuric acid gives cis‐ and trans‐2,6‐diethylmorpholines, 3‐ethyl‐4‐methylpyridine and unsaturated 3‐ethyl‐4‐methylpiperidines. Hydrogenation of the unsaturated 3‐ethyl‐4‐methylpiperidines gives cis‐ and trans‐3‐ethyl‐4‐methylpiperidines. With 50% w/w sulfuric acid cis‐ and trans‐2,6‐diethylmorpholines and a small amount of cis‐ and trans‐2‐ethyl‐7‐methyl‐hexahydro‐1,4‐oxazepines are obtained.
Deoxygenation of quinoxaline and phenazine N‐oxides by catalytic transfer reduction and by iodide in the presence of pyridine/sulfur trioxide complex
Authors: Demirdji S. H. , Haddadin M. J. , Issidorides C. H.
Published: March 2009

Quinoxaline and phenazine di‐N‐oxides are deoxygenated under mild conditions by catalytic transfer reduction or by treatment with sodium iodide in the presence of pyridine/sulfur trioxide complex.
Preparation of phenylquinoxaline from α,α‐diaminoketones and dimethyl‐O‐phenylenediamine
Authors: Saeed Ali A. H. , Ebraheem Ebraheem K.
Published: March 2009

Amination of α,α‐diaminoketones 1 by 4,5‐dimethyl‐o‐phenylenediamine gave 6,7‐dimethyl‐2‐phenylquinoxaline (II) in a high yield. The reaction may occur through formation of α‐ketoazomethine III. The α,α‐di‐aminoketones were obtained by condensation of phenylglyoxal and substituted anilines.
Pyridazines. XXVI. A novel synthesis of pyrano[2,3‐d]pyridazines
Authors: Heinisch Gottfried , Holzer Wolfgang , Nawwar Galal A. M.
Published: March 2009

A novel approach to the title ring system starting with conveniently available cinnamoylacetonitrile (1) is proposed. It involves the Japp‐Klingemann reaction of 1 followed by thermally induced cyclisation of hydrazones 2 and subsequent addition of the resulting pyridazine derivatives 3 to 2‐substituted cinnamonitriles 4a, 4b. The structures of the pyrano[2,3‐d]pyridazines 5a, 5b, thus obtained, were established on basis of spectroscopic data.
Synthesis of 3‐substituted‐4‐methyl‐5‐acetyl‐4‐thiazoline‐2‐thione
Authors: D'Amico John J. , Bollinger Frederic G. , Freeman John J.
Published: March 2009

The reaction of various potassium salts [RNHC(=S)SK, R = N(CH3)2, morpholino, piperidino, and hexahydro‐1‐(1H)‐azepinyl] with 3‐chloro‐2,4‐pentanedione in ethanol at 25–30° afforded the 1‐acetylacetonyl substitutedaminodithiocarbamates 1–4 [RNHC(=S)SCH(COCH3)2]. Under refluxing conditions, the same reactants gave the heterocyclic compounds 5–8. Possible mechanism and supporting ir, nmr and mass spectral data are discussed.
Synthesis of 3a,4,5,6,7a‐Hexahydro‐3a‐hydroxy‐3‐substitutedamino‐2‐benzothiazolinethiones and Related Compounds
Authors: D'Amico John J. , Bollinger Frederic G. , Freeman John J. , Dahl William E.
Published: March 2009

The reaction of various potassium or ammonium salts [RNHC(=S)SM, M = K or NH4; R = N(CH3)2, morpholino, pyrrolidino, piperidino, and hexahydro‐1‐(1H)‐acepinyl] with 2‐chlorocyclohexanone in alcohol at 25–30° afforded the title compounds 1 and 3–6. The treatment of these compounds with a catalytic amount of p‐toluenesulfonic acid in refluxing benzene furnished the dehydrated products 2 and 7–10. The reaction of potassium dithiocarbazate with 2‐chlorocyclohexanone or 3‐chloro‐3,4‐pentanedione in refluxing ethanol afforded 11, a six membered heterocycle and 12, a five membered heterocycle, respectively. Possible mechanisms and supporting nmr, ir, uv mass spectral data are discussed.
Mechanistic observations in the gewald syntheses of 2‐aminothiophenes
Authors: Peet Norton P. , Sunder Shyam , Barbuch Robert J. , Vinogradoff Anna P.
Published: March 2009

The Gewald syntheses were employed to prepare a series of 2‐amino‐3‐carboethoxythiophenes, and the syntheses of two of these, namely, the 3,4‐trimethylene (1f) and 3,4‐tetramethylene (1g) derivatives, were examined in detail. In two preparations of1f, octahydro‐6a‐(4‐morpholinyl)‐2‐thioxocyclopenta[b]pyrrole‐3‐carboxylic acid (7) was a co‐product. The structure of7was ascertained from its 300 MHz1H nmr and13C nmr spectra, and by its conversion to 1,4,5,6‐tetrahydro‐2‐mercaptocyclopenta[b]pyrrole‐3‐carboxylic acid ethyl ester (8). Isolation of7and other observations led to postulated mechanisms for three of the Gewald thiophene syntheses.
Heterocycles. Part VIII. Synthesis of new substituted benz[g]indazoles
Authors: El‐Rayyes N. R. , Al‐Jawhary A.
Published: March 2009

Aryl aldehydes I reacted with α‐tetralone to give the corresponding 2‐arylidene‐1‐tetralone II. Condensation of the latter chalcones with hydrazine, methylhydrazine and phenylhydrazine produced the corresponding benzo[g]indazoles III, V and VI respectively. Acetylation of the 2H‐benz[g]indazole derivatives III gave the corresponding 2‐acetylated compounds IV. The structure of all products was elucidated by chemical and spectroscopic methods.
An unexpected product from the cyclodesulfurization of 5‐[1‐(3‐methoxycarbonyl)thioureido]‐1‐(β‐D‐ribofuranosyl)imidazole‐4‐ carboxamide with dicyclohexylcarbodiimide
Authors: Chern Ji‐Wang , Groziak Michael P. , Townsend Leroy B.
Published: March 2009

The treatment of 5‐[1‐(3‐methoxycarbonyl)thioureido]‐1‐(β‐D‐ribofuranosyl)imidazole‐4‐carboxamide with N,N'‐dicyclohexylcarbodiimide in N,N‐dimethylformamide has afforded 4‐cyano‐5‐[1‐(3‐methoxycarbonyl)‐ureido]‐1‐(β‐D‐ribofuranosyl)imidazole.
Substituted γ‐Lactones. 35. Reduction of 4‐aroyl‐3‐hydroxy‐2(5H)‐furanones
Authors: Zimmer Hans , Manning M. J. , Ventura M. , Amer Adel , El Massry Abdel Monem
Published: March 2009

The reduction of 4‐aroyl‐3‐hydroxy‐2(5H)‐furanons 1a‐c was investigated using different reducing agents. Sodium borohydride reacts with type 1 compounds by loss of water to yield 4‐(arylmethylene)‐2,3(4H,5H)‐furandiones 2a‐c. Platinum or charcoal supported by pallodium chloride transforms 1a to 4‐benzyl‐3‐hydroxy‐2(5H)‐furanone (3). Compounds 2a and 2b react with o‐phenylenediamine to give 3‐(E‐(1′‐hydroxymethyl‐2′‐aryl)ethenyl]‐2‐quinoxalinones 4a and 4b. The lactone 3 under the same conditions splits out formaldehyde and forms 3‐(2′‐phenylethyl)‐2‐quinoxalinone (6). The structure assignments of the novel compounds are based on elemental analysis and nmr as well as ir spectroscopic data.
Synthesis of 8‐methylpyrido[2,3‐d:6,5‐d'x]dipyrimidine‐2,4,6(3H,10H,7H)‐triones and their use in the oxidation of alcohols
Authors: Moriyama Kenji , Nagamatsu Tomohisa , Yoneda Fumio
Published: March 2009

A new‐type pyridodipyrimide, 8‐methylpyrido[2,3‐d:6,5‐d']dipyrimidine‐2,4,6(3H,10H,7H)‐triones were prepared by the condensation of 6‐alkyl‐ or 6‐aryl‐amino‐2‐methylpyrimidin‐4(3H)‐ones with 2,4,6‐trichloropyrimidine‐5‐carbaldehyde or 3‐alkyl‐6‐chloro‐5‐formyluracils. The pyridodipyrimidines thus obtained oxidized alcohols under neutral conditions to yield the corresponding carbonyl compounds and a significant autorecycling in the oxidation was observed.
Studies on pyrrolidinones. A convenient synthesis of 2‐methyl‐5‐(5‐oxo‐1‐benzyl‐2‐pyrrolidinyl)‐1,3,4‐oxadiazole
Authors: Rigo Benoǐt , Couturier Daniel
Published: March 2009

2‐Methyl‐5‐(5‐oxo‐1‐benzyl‐2‐pyrrolidinyl)‐1,3,4‐oxadiazole is easily obtained by dehydration of N‐acetyl‐1‐benzylpyroglutamic acid hydrazide with a methanesulfonic acid/phosphoric anhydride mixture.
Furopyridines. III. A new synthesis of furo[3,2‐b]pyridine
Authors: Shiotani Shunsaku , Morita Hiroyuki
Published: March 2009

A convenient synthesis of furo[3,2‐b]pyridine and its 2‐ and 3‐methyl derivatives from ethyl 3‐hydroxypiconate (1) is described. The hydroxy ester1wasO‐alkylated with ethyl bromoacetate or ethyl 2‐bromopropionate to give the diester2aor2b. Cyclization of compound2aafforded ethyl 3‐hydroxyfuro[3,2‐b]pyridine‐2‐carboxylate (3) which in turn was hydrolyzed and decarboxylated to give furo[3,2‐b]pyridin‐3‐(2H)‐one (4a). Cyclization of2bgave the 2‐methyl derivative4b. Reduction of4aand4bwith sodium borohydride yielded the corresponding hydroxy derivative5aand5brespectively, which were dehydrated with phosphoric acid to give furo[3,2‐b]pyridine (6a) and its 2‐methyl derivative (6b). 2‐Acetylpyridin‐3‐ol (8) was converted to the ethoxycarbonylmethyl ether (9) byO‐alkylation with ethyl bromoacetate, which was cyclized to give 3‐methylfuro[3,2‐b]pyridine‐2‐carboxylic acid (10). Decarboxylation of10afforded 3‐methylfuro[3,2‐b]pyridine (11).
Studies on the constituents of bocconia cordata. III Structure elucidation of bocconine by means of nuclear magnetic resonance spectroscopic studies
Authors: Konda Yaeko , Harigaya Yoshihiro , Onda Masayuki
Published: March 2009

The nmr spectroscopic studies on methoxybocconine are described. The spectral data indicate bocconine to be 2,3,7,8‐bis(methylenedioxy)‐10‐methoxy‐5‐methylbenzo[c]phenanthridine.
New syntheses of per‐N‐alkyl‐substituted triaza‐ and tetraaza‐crovm compounds containing an allyloxymethyl substituent
Authors: Krakowiak Krzysztof E. , Bradshaw Jerald S. , Forsnes Evan V. , Izatt Reed M.
Published: March 2009

Seven new per‐N‐alkyl‐substituted triaza‐ and tetraaza‐crovm compounds have been prepared using commercially available or easily synthesized per‐N‐alkyl‐substituted oligoethylene and oligopropylene polyamines, tetraazapentaethylene and tetraazaheptaethylene glycols. Five of these new polyaza‐crowns have a pendant allyloxymethyl substituent.
Crossed bisadducts in the reaction of pyridine with two different nitrile oxides
Authors: Albini Franca Marinone , De Franco Rita , Bandiera Tiziano , Caramella Pierluigi , Corsaro Antonino , Perrini Giancarlo
Published: March 2009

Bisadducts of some aromatic nitrile oxides to pyridine are described. Crossed adducts are formed by exposure of pyridine to a couple of different nitrile oxides.
Synthesis of nitrogen‐containing heterocycles. 4. A facile route to new 1, 2, 4‐triazole derivatives
Authors: Miyamoto Yoshiko , Yamazaki Chiji
Published: March 2009

The reaction of amino‐N(4),N(4)‐dimethylaminornethylenehydrazones 1 of some aliphatic carbonyl compounds with ethyl ethoxymethylenecyanoacetate 2 gave directly symmetrical gem‐bis(3‐dimethylamino‐1, 2, 4‐triazol‐1‐yl)alkanes 4 and (3‐dimethylamino‐1, 2, 4‐triazol‐1‐yl)alkenes 5 at room temperature, with the former being major product. On the other hand, the reaction of amino‐N(4)‐methylaminomethylenehydrazone homologue 1 of aliphatic ketone with 2 gave ethyl 2‐alkyl‐5‐methylamino[1, 2, 4]triazolo[1, 5‐c]pyrimidine‐8‐carboxylate 7 as the only product with elimination of alkane.
Methyl 2‐benzoylamino‐3‐dimethylaminopropenoate in the synthesis of heterocyclic systems. An attempt to prepare benzoylamino substituted azolo‐ and azinopyrimidines with a bridgehead nitrogen atom
Authors: Stanovnik Branko , Van De Bovenkamp Henry , Svete Jurij , Hvala AleŠ , Simoni č Igor , Tišler Miha
Published: March 2009

Methyl 2‐benzoylamino‐3‐dimethylaminopropenoate (2) was introduced as a new reagent for the preparation of fused pyrimidinones 4 from heterocyclic α‐amino compounds in acetic acid. In this manner, derivatives of pyrido[1,2‐a]pyrimidine 4a,b,f, pyrimido[1,2‐b]pyridazine 4g, pyrimido[1,2‐c]pyrimidine 4j, pyrazino[1,2‐a]pyrimidine 4k, thiazolo[2,3‐b]pyrimidine 41, pyrazolo[1,5‐a]pyrimidine 4m, and 1,2,4‐triazolo‐[1,5‐a]pyrimidine 4n were prepared.
Synthesis and spectra of 12‐(o‐ and p‐R‐phenyl)‐9,9‐dimethyl‐7,8,9,10,11,12‐hexahydro and 8,9,10,11‐tetrahydrobenz[a]acridin‐11‐ones. Structure correction of 1,2,3,4,5,6‐hexahydro and 1,2,3,4‐tetrahydro‐2,2‐dimethyl‐5‐aryl‐6‐aza‐9,10‐benzophenanthren‐4‐ones. II
Authors: Martínez Roberto , Cortés Eduardo , Toscano R. Alfredo , Linzaga Irma
Published: March 2009

It has been reported that the reaction of β‐naphthylamine, dimedone and the appropriate aromatic aldehyde in ethanol gave 1,2,3,4,5,6‐hexahydro‐2,2‐dimethyl‐5‐aryl‐6‐aza‐9,10‐benzophenanthren‐4‐ones, III, which upon treatment with chromic anhydride, yielded the corresponding tetrahydro derivatives, IV. However, the attempted preparation of these compounds resulted instead of the formation of isomeric acridin‐11‐ones, V and VI. Structures were confirmed by ir, 1H nmr, ms and X‐ray spectroscopy.
Synthesis of 2‐N‐(benzo[b]thiophen‐2‐yl)benzo and heterofused‐1,2,3‐triazoles
Authors: Sabnis R. W. , Rangnekar D. W.
Published: March 2009

A novel efficient synthesis of 2‐N‐(benzo[b]thiophen‐2‐yl)benzo and heterofused‐1,2,3‐triazoles was achieved by the diazotisation of 2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carbonitrile and ethyl‐2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carboxylate and coupling with selected aromatic and heterocyclic amines followed by air oxidation in the presence of cupric acetate.
A convenient synthesis of pyridazine‐3,4‐dicarboxylic acid by a hetero diels‐alder reaction
Authors: Vors Jean‐Pierre
Published: March 2009

A convenient route to prepare unsubstituted pyridazine‐3,4‐dicarboxylic acid on a preparative scale is described. The synthesis involves a hetero Diels‐Alder reaction between a new 1,2‐diaza‐1,3‐diene and ethyl vinyl ether and oxidation of the intermediate 1,4,5,6‐tetrahydropyridazine as the key step.
Synthesis of 1‐aryl‐1,2,3‐triazole‐4,5‐dimethanol‐4,5‐bis(isopropylcarbamates) as potential antineoplastic agents
Authors: Lalezari I. , Gomez L. A. , Khorshidi M.
Published: March 2009

Starting with aryl azides, 1‐aryl‐1,2,3‐triazole‐4,5‐dimethanol‐4,5‐bis(isopropylcarbamates), a new class of potential antineoplastic agents, were synthesized. In vitro antileukemic and antitumor actmües of the compounds synthesized were also evaluated.
Syntheses of 6‐fluoro‐7‐piperazin‐1‐yl‐9‐cyclopropyl‐2,3,4,9‐tetrahydroisothiazolo[5,4‐b]quinoline‐3,4‐dione and 6‐fluoro‐7‐piperazin‐1‐yl‐9‐p‐fluorophenyl‐2,3,4,9‐tetrahydroisothiazolo[5,4‐b]quinoline‐3,4‐dione
Authors: Chu Daniel T. W.
Published: March 2009

The syntheses of 6‐fluoro‐7‐piperazin‐1‐yl‐9‐cyclopropyl (or 9‐p‐fluorophenyl)‐2,3,4,9‐tetrahydroisothiazolo[5,4‐b]quinoline‐3,4‐diones as well as novel synthesis of isothiazolo‐3(2H)‐one system are described. Key steps include the regiospecific displacement of a sulfinyl group and the amination of the resultant mercapto derivative followed by an intramolecular nucleophilic displacement cyclization reaction to generate the novel 2,3,4,9‐tetrahydroisothiazolo[5,4‐b]quinoline‐3,4‐dione nucleus.
One step synthesis of pyrimido[1,2‐a][1,8]naphthyridinones, pyrido[1,2‐a]pyrimidinones and 1,8‐naphthyridinones. Antihypertensive agents. V
Authors: Ferrarini Pier Luigi , Mori Claudio , Primofiore Giampaolo , Calzolari Lorella
Published: March 2009

The condensation of 2,6‐diaminopyridine and 2‐acetamido‐6‐aminopyridine with β‐keto esters in polyphosphophoric acid was studied. In this reaction some 1,8‐naphthyridinones, pyrido[1,2‐a]pyrimidinones and pyrimido[1,2‐a][1,8]naphthyridinones variously substituted were obtained.
Methyl 2‐benzoylamino‐3‐dimethylaminopropenoate in the synthesis of fused pyranones. The synthesis of derivatives of tetrahydro‐2H‐1‐benzopyran‐2‐one, isomeric 2H‐naphtho[1,2‐b]pyran‐2‐one and 3H‐naphtho[2,1‐b]pyran‐3‐one, pyrano[3,2‐c]benzopyran‐2,5‐dione, and 7H‐pyrano[2,3‐d]pyrimidin‐7‐one
Authors: Ornik Brina , Čadež Zvonko , Stanovnik Branko , Tišler Miha
Published: March 2009

Methyl 2‐benzoylamino‐3‐dimethylaminopropenoate (1) reacts with carbocyclic and heterocyclic 1,3‐diketones or potential 1,3‐diketones, such as 1,3‐cyclohexanediones 2–4, and 4‐hydroxy‐2H‐1‐benzopyran‐2‐one derivative 17, in acetic acid to afford the corresponding 3‐benzoylamino substituted 5‐oxo‐5,6,7,8‐tetrahydro‐2H‐1‐benzopyran‐2‐ones 5–7, and 2H,5H‐pyrano[3,2‐c][1]benzopyran‐2,5‐dione derivative 18. 1‐Naphthol (12) and 2‐naphthol (13) produce the isomeric 2H‐naphtho[1,2‐b]pyran‐2‐one (14) and 3H‐naphtho[2,1‐b]pyran‐3‐one (15) derivatives, respectively. Ethyl cyclopentanone‐2‐carboxylate (8) and ethyl cyclohexanone‐2‐carboxylate (9) do not react under these conditions, while in polyphosphoric acid the cyclization of the reagent 1 is taking place to give 4‐dimethylaminomethylene‐2‐phenyl‐5(4H)‐oxazolone (10). 4,6‐Dihydroxypyrimidine derivative 19 affords in acetic acid the noncyclized intermediate 20, which can be further transformed in polyphosphoric acid into 7H‐pyrano[2,3‐d]pyrimidin‐7‐one derivative 21.
Synthesis, anticancer and antimicrobiological activities of pyrrolo[2,3‐d]pyrimidines
Authors: Quijano M. Luisa , Nogueras Manuel , Sánchez Aldolfo , De Cienfuegos Gerardo Alvarez , Melgarejo Miguel
Published: March 2009

Reactions of 6‐amino‐3,4‐dihydro‐2‐methoxy‐4‐oxopyrimidine 1a and its 3‐methyl derivative 1b with chloroacetaldehyde and chloroacetyl chloride are discussed in this paper. Amongst others compounds, we have obtained, in low yield, the novel ring system oxazolo[3,2‐c]pyrrolo[3,2‐e]pyrimidine. The anticancer and antimicrobial activities of some of the obtained products are described.
New cyclobutyl analogs of adenosine and guanosine. Part 1. Synthesis of the 9‐[3,3‐bis(hydroxymethyl)cyclobutyl]purine nucleoside analogs
Authors: Boumchita Hassane , Legraverend Michel , Bisagni Emile , Huel Christiane
Published: March 2009

The synthesis of 1‐amino‐3,3‐bis(benzyloxymethyl)cyclobutane has been performed from 3,3‐bis(benzyloxymethyl)cyclobutanone, via the corresponding oxime which was reduced with lithium aluminum hydride. The amine thus obtained led to two new cyclobutyl analogs of adenosine and guanosine which were devoid of antiviral activity against HSV‐1, HCMV and HIV in cell culture.
Synthesis of 6‐quinoxalinyldihydropyrazolo[1,5‐a]pyrimidin‐7‐ones by a ring transformation. Tautomeric structure of dihydropyrazolo[1,5‐a]pyrimidin‐7‐ones in a solution
Authors: Kurasawa Yoshihisa , Kim Ho Sik , Takada Atsushi , Okamoto Yoshihisa
Published: March 2009

The reaction of 3‐(N,N‐dimethylcarbamoyl)furo[2,3‐b]quinoxaline hydrochloride 1 with the 5‐aminopyrazoles 6a‐e gave 6‐quinoxalinyldihydropyrazolo[1,5‐a]pyrimidin‐7‐ones 7a‐e, respectively. Compounds 7a‐e were found to predominate as the 4,7‐dihydro‐7‐oxo form in a solution based on the NOE data.
Polycyclic N‐hetero compounds. XXXVIII. Synthesis and evaluation of antidepressive activity of [1]benzothieno[2′,3′:4,5]furo[3,2‐d]primidines and their precursors
Authors: Sasaki Kenji , Tashima Yohsuke , Nakayama Taiji , Hirota Takashi
Published: March 2009

Synthesis of [1]benzothieno[2′,3′:4,5]furo[3,2‐d]pyrimidines is described. Antidepressive evaluation of these compounds and their precursors were screened by inhibitory action of reserpine‐induced hypothermia.
Reaction of 2‐dimethylaminomethylene‐1,3‐diones with dinucleophiles. X. synthesis of 5‐substituted ethyl or methyl 4‐isoxazolecarboxylates and methyl 4‐(2,2‐dimethyl‐1‐oxopropyl)‐5‐isoxazolecarboxylate
Authors: Schenone Pietro , Fossa Paola , Menozzi Giulia
Published: March 2009

Reaction of ethyl or methyl 2‐dimethylaminomethylene‐3‐oxoalkanoates with hydroxylamine hydrochloride in methanol solution afforded in high yields the relative esters of 5‐substituted 4‐isoxazolecarboxylic acids II. These esters were hydrolyzed generally with concentrated hydrochloric acid‐acetic acid mixtures to the corresponding carboxylic acids in satisfactory yields.

Ethyl or methyl esters II isomerized with sodium ethoxide or methoxide, respectively, to the corresponding esters or hemiesters of 2‐cyano‐3‐oxoalkanoic acids generally in excellent to satisfactory yields.

Reaction of methyl 5,5‐dimethyl‐3‐dimethylaminomethylene‐2,4‐dioxohexanoate with hydroxylamine hydrochloride afforded in moderate yield methyl 4‐(2,2‐dimethyl‐1‐oxopropyl)‐5‐isoxazolecarboxylate, which was converted by acid hydrolysis as above to 4‐t‐butyl‐4‐hydroxyfuro[3,4‐d]isoxazol‐6‐(4H)‐one.
Triphenodioxazine‐1,8‐dicarboxylic acid as an oxidation product of 3‐hydroxyanthranilic acid
Authors: Hick Larry A. , Manthey Michael K. , Truscott Roger J. W.
Published: March 2009

The oxidation of 3‐hydroxyanthranilic acid (30HA) 1 by aqueous buffered potassium ferricyanide produces a number of coloured compounds. These include cinnabarinic acid 2 (yellow), a p‐quinone dimer 3 (red) and 9‐carboxy‐2‐hydroxy‐3H‐phenoxazin‐3‐one 4 (brown). Also present by tlc is a bright pink compound. The structure of this compound has been demonstrated to be triphenodioxazine‐1,8‐dicarboxylic acid 5a.
Synthesis of novel acyclonucleosides. Reactions of 1‐(1‐bromo or 3‐bromo‐2‐oxopropyl)pyridazin‐6‐ones
Authors: Choi Sam‐Yong , Lee Sang‐Gyeong , Yoon Yong‐Jin
Published: March 2009

Reaction of 1‐(3‐bromo‐2‐oxopropyl)pyridazin‐6‐ones 1 and 2 with sodium azide at room temperature gave the corresponding 1‐(3‐azido‐2‐oxopropyl)pyridazin‐6‐ones 3 and 4, whereas reaction of 1‐(1‐bromo‐2‐oxo‐propyl)pyridazin‐6‐ones 5 and 6 with excess sodium azide afforded 4‐azido‐5‐chloropyridazin‐6‐one 7 and 4,5‐diazido‐3‐nitropyridazin‐6‐one 8 by dealkylation. Some 1‐(2‐hydroxypropyl)pyridazin‐6‐ones 9, 10, 11 were synthesized from the corresponding 1‐(2‐oxopropyl) derivatives 1, 2, 3. 4,5‐Dichloro‐1‐(2,3‐dihydroxypropyl)‐pyridazin‐6‐one 13 was also prepared from compound 9 via the corresponding 2,3‐epoxypropyl derivative 12. Treatment of compound 5 with thiourea gave 4,5‐dichloro‐1‐(2‐amino‐4‐methylthiazol‐5‐yl)pyridazin‐6‐one 14. Reaction of compounds 1 and 2 with thiourea at 20° afforded the corresponding 3‐formamidinylthio‐2‐oxo‐propyl derivatives 15 and 16, whereas treatment of compound 1 with thiourea at 45° gave 4,5‐dichloro‐1‐[(2‐aminothiazol‐5‐yl)methyl]pyridazin‐6‐one 17. Compound 17 was also prepared from compound 15 by refluxing in ethanol.
Photocyclization reactions. Part 1. Synthesis of dihydrobenzofuranols using photocyclization of 2‐alkoxybenzaldehydes, 2′‐alkoxyacetophenones, 2‐formylphenoxyacetic acids and 2‐acetylphenoxyacetic acids
Authors: Horaguchi Takaaki , Tsukada Chikara , Hasegawa Eietsu , Shimizu Takahachi , Suzuki Tsuneo , Tanemura Kiyoshi
Published: March 2009

Photocyclization reactions were carried out on 2‐alkoxybenzaldehydes 1a‐f, 2′‐alkoxyacetophenones 2a‐h, 2‐formylphenoxyacetic acids 1i‐l and 2‐acetylphenoxyacetic acids 2i‐m. Irradiation of 1a‐f and 2a‐h in acetonitrile gave the corresponding dihydrobenzofuranols 3, 5 and dihydroisobenzofuranols 4, 6. Using carboxylic acids 1i‐1, 2i‐m as starting materials, decarboxylation occurred immediately to give the corresponding ethers 1a‐d, 2a‐e. Further irradiation of the solution afforded dihydrobenzofuranols 3, 5 and dihydroisobenzofuranols 4, 6. Substituent effects on photocyclization and reaction pathways are discussed.
Synthesis of 7,8‐dihydro‐6H‐pyrazolo[3,4‐b]quinolin‐5‐ones and related derivatives
Authors: Gatta Franco , Pomponi Massimo , Marta Maurizio
Published: March 2009

This paper describes the synthesis of a new series of 4‐amino‐1‐(unsubstituted and chloro or fluoro substituted benzyl)‐7,8‐dihydro‐6H‐pyrazolo[3,4‐b]quinolin‐5‐ones 8 and the corresponding 7,8‐dihydro‐6H,9H‐pyrazolo[3,4‐b]quinoline‐4,5‐diones 13. The derivatives obtained by reaction of these compounds with sodium azide in concentrated sulfuric acid are also reported.
Synthesis of novel quino[2,3‐b][1,5]benzodiazepin‐12‐ones
Authors: Rao K. Rama , Bhanumathi N. , Sattur P. B.
Published: March 2009

The synthesis of potentially biologically biologically active quino[2,3‐b][1,5]benzodiazepin‐12‐ones has been reported for the first time by the reaction of 2‐chloroquinoline‐3‐carboxylic acids with o‐phenylenediamine.
Synthesis of novel c‐hetero‐fused thiophene derivatives
Authors: Rangnekar D. W. , Mavlankar S. V.
Published: March 2009

An efficient synthesis of novel 5‐(4‐nitrophenyl)‐2‐benzoxazol‐2‐yl‐c‐hetero‐fused thiophenes was achieved by the condensation of 5‐(4‐nitrophenyl)‐2‐benzoxazol‐2‐yl‐3,4‐dichlorothiophene with ethylene glycol, ethylenediamine, substituted thioamides and 2‐mercaptobenzimidazole using sodium carbonate in refluxing dimethyl formamide.
Furopyridines. XI. 13C NMR Spectra of 2‐ or 3‐Substituted Furo[2,3‐b]‐, Furo[3,2‐b]‐, Furo[2,3‐c]‐ and Furo[3,2‐c]pyridine
Authors: Shiotani Shunsaku , Morita Hiroyuki
Published: March 2009

The 13C nmr spectra of 2‐ or 3‐monosubstituted furo[2,3‐b]‐ 1a‐1j, furo[3,2‐b]‐ 2a‐2j, furo[2,3‐c]‐ 3a‐3j and furo[3,2‐c]pyridine derivatives 4a‐4j are reported. Effects by change in annelation and substituent effects on 13C chemical shifts and carbon‐proton coupling constants are discussed. The spectra of benzo[b]furan derivatives 5a‐5j having the corresponding substituent are also reported for comparison.
Antiinflammatory 1‐phenylpyrazole‐4‐heteroarylalkanoic acids
Authors: Goddard Carl J.
Published: March 2009

A series of antiinflammatory agents, based on the structural integration of fentiazac and lonazolac, was synthesized.
A regiospecific synthesis of 8‐Methoxy‐1,2,3,4,5,6‐hexahydro‐1,6‐methano‐3‐benzazocines
Authors: Mazzocchi P. H. , Kordoski E. W. , Harrison A. M.
Published: March 2009

A regiospecific synthesis of the 6‐methoxy‐1,2,3,4,5,6‐hexahydro‐1,6‐methano‐3‐benzazocine system is reported.
Synthesis and anticonvulsant activity of 3‐alkyl‐3,4‐dihydro‐2(1H)‐quinazolinones
Authors: Kornet Milton J.
Published: March 2009

Previously we reported the potent anticonvulsant activity of 3‐dimethylamino‐3,4‐dihydro‐2(1H)‐quinazolinone. In this report, a series of 3‐alkyl‐3,4‐dihydro‐2(1H)‐quinazolinones was synthesized in three steps from isatoic anhydrides or an anthranilic acid. Structure/activity investigations revealed optimal activity for the 3‐isopropyl and 3‐cyciohexyl analogs. These compounds were effective against seizures induced by maximal electroshock.
A novel non photochemical ring contraction of 4‐pyrones to cyclopent‐2‐enones
Authors: Jakopčic K. , Kojić J. , Orhanović Z. , Stiplošek Z. , Nagl A. , Hergold A.
Published: March 2009

Unlike comenic acid or most other 4‐pyrones, methyl or ethyl comenate reacts with aromatic amines under mild conditions in the sense of ring contraction to 3‐arylamino‐2,4‐dihydroxy‐2‐cyclopentenone‐4‐carboxylates. The structure of the new cyclopentenone derivatives were determined from their characteristic spectroscopic behaviour and was confirmed by X‐ray crystallographic studies of compound Vb.
N‐bis(methylthio)methylene derivatives. 5. New synthesis of 2‐aminoindolizine and related compounds via a formal [3 + 3] cycloaddition reaction using N‐bis(ethoxycarbonylmethylthio)methylenephenylsulfonamides
Authors: Tominaga Yoshinori , Ueda Hiroshi , Ogata Koichiro , Kohra Shinya
Published: March 2009

Reaction of pyridinium N‐ylide 5a with N‐bis(ethoxycarbonyl)methylthio)(p‐substituted‐phenyl)sulfon‐amides 2a,c in the presence of triethylamine as a base in ethanol gave diethyl 2‐(p‐substituted‐phenylsulfonyl)aminoindolizine‐1,3‐dicarboxylates 9a,b via a new formal [3 + 3] cycloaddition reaction. In a similar manner, 2‐sulfonylaminopyrrolo[2,1‐a]isoquinoline derivatives 11a‐e were also obtained by the reaction of 2a‐c and 4a,b with the corresponding isoquinoline N‐ylides 10a.b with good results.
1,3‐dipolar cycloaddition of nitrile oxides with 2‐phenyl‐4‐ethoxymethylene‐5(4H)‐oxazolone
Authors: Coutouli‐Argyropoulou E. , Thessalonikeos E.
Published: March 2009

2‐Phenyl‐4‐ethoxymethylene‐5(4H)‐oxazolone 1 reacts regioselectively with nitrile oxides to give cycloadducts 3. Reactions of the cycloadducts 3 with nucleophiles lead to 4‐aminoisoxazole derivatives.
Research on nitrogen containing heterocyclic compounds. XVIII. Synthesis of 9H‐pyrrolo[2,1‐c]‐s‐triazolo[4,3‐a][1,4]benzodiazepine, a novel tetracyclic ring of pharmaceutical interest
Authors: Stefancich Giorgio , Artico Marino , Silvestri Romano
Published: March 2009

Reaction of di‐4‐morpholinylphosphinic chloride on 5,10‐dihydro‐9H‐pyrrolo[2,1‐c][1,4]benzodiazepin‐11‐one 9 afforded 11‐(di‐4‐morpholinylphosphinyloxy)‐5H‐pyrrolo[2,1‐c][1,4]benzodiazepine 10. Displacement of di‐4‐morpholinylphosphinyloxy group of 10 by formylhydrazine with concomitant intramolecular cyclization led directly to 9H‐pyrrolo[2,1‐c]‐s‐triazolo[4,3‐a][1,4]benzodiazepine 7, a novel nitrogen heterocyclic ring of pharmaceutical interest. A new procedure for the synthesis of 9 is also described.
A synthesis of 3‐hydroxymethyl‐2‐(6‐methylheptanoyl)‐4‐butanolide (a‐factor)
Authors: Kinoshita Takamasa , Hirano Madoka
Published: March 2009

The A‐Factor was conveniently synthesized from 3‐furoic acid via the Birch reduction.
Configurational assignments of oximes derived from 5‐formyl and 5‐acyl‐1,2,4‐triazines
Authors: Rykowski Andrzej , Guzik Eliza , Makosza Mieczyslaw , Holzer Wolfgang
Published: March 2009

The configuration of (3‐substituted)‐1,2,4‐triazin‐5‐ylcarbaldoximes and (3‐substituted)alkyl‐1,2,4‐triazin‐5‐ylketoximes was determined by means of 1H‐nmr, 13C‐nmr, 15N‐nmr and homonuclear NOE‐difference spec‐troscopy. Oximes resulting from reaction of 1,2,4‐triazines with nitroalkanes were found to be either pure E‐isomers or E/Z‐mixtures with the amount of E‐isomer greatly predominating. Detailed 13C‐nmr data of the oximes investigated are presented.
Synthesis of 1,2,3,4‐tetraphenyl‐9,10,16,17, 23,24‐hexadodecyloxyphthalocyanine
Authors: Yang Jiang , Rogers Thomas C. , Van De Mark Michael R.
Published: March 2009

The unsymmetrical 1,2,3,4‐tetraphenyl‐9,10,16,17,23,24‐hexadodecyloxyphthalocyanine was synthesized utilizing steric hinderance of a tetraphenyl group to limit substitution.
The photolysis of 1‐(4,5‐dihydro‐1H‐imidazol‐2‐yl)benzotriazole
Authors: Döpp Dietrich , Orlewska Czeslawa , Saczewski Franciszek
Published: March 2009

1‐(4,5‐Dihydro‐1H‐imidazolo‐2‐yl)benzotriazole was photolyzed at 254 nm yielding 1,2‐dihydro‐4H‐imidazo‐[1,2‐a]benzimidazole.
Synthesis of 1,6‐dihydro‐5‐hydroxy‐6‐oxo‐3‐(trifluoromethyl)‐4‐pyridazinecarboxylates
Authors: Hegde Shridhar G. , Jones Claude R.
Published: March 2009

The reaction of 2‐(alkylamino)‐3‐(trifluoroacetyl)butenedioates 2a‐b with alkyl and aryl hydrazines in ether provides 1,6‐dihydro‐6‐oxo‐3‐(trifluoromethyl)‐4‐pyridazinecarboxylates as their alkylamine salts 3a‐g. The structures of these products are substantiated using 2D nmr and 15N nmr techniques.
Oxidations of 3,6‐diamino‐1,2,4,5‐tetrazine and 3,6‐bis(s,s‐dimethylsulfilimino)‐1,2,4,5‐tetrazine
Authors: Coburn M. D. , Hiskey M. A. , Lee K.‐Y. , Ott D. G. , Stinecipher M. M.
Published: March 2009

Oxidation of 3,6‐diamino‐1,2,4,5‐tetrazine (1) with most peracids gave 3,6‐diamino‐1,2,4,5‐tetrazine 1,4‐dioxide (3) as the major product; however, treatment of 1 with peroxytrifluoroacetic acid (PTFA) gave 3,6‐diamino‐1,2,4,5‐tetrazine 1‐oxide (4) as the major product along with a small amount of 3‐amino‐6‐nitro‐1,2,4,5‐tetrazine 2,4‐dioxide (5). Oxidation of 3,6‐bis(S,S‐dimethylsulfilimino)‐1,2,4,5‐tetrazine (6) with 3‐chloroperoxybenzoic acid (MCPBA) gave 3‐S,S‐(dimethylsulfilimino)‐6‐nitroso‐1,2,4,5‐tetrazine (7), which was oxidized further with dimethyldioxirane to 3‐(S,S‐dimethylsulfoximino)‐6‐nitro‐1,2,4,5‐tetrazine (8). All attempts to obtain 3,6‐dinitro‐1,2,4,5‐tetrazine (2) by further oxidation of 7 or 8 failed.
Ring opening reaction of 1,2‐diaryl‐3‐methyl‐1,4,5,6‐tetrahydropyrimidinium salts with metal hydride complexes
Authors: Maso MÓNica Dal , Orelli Liliana , Perillo Isabel A.
Published: March 2009

The reaction of a series of 1,2‐diaryl‐3‐methyl‐1,4,5,6‐tetrahydropyrimidinium iodides 1 with reducing agents acting by hydride ion transfer was studied. With excellent yields alkaline borohydrides readily reacted to form N'‐aryl‐N‐benzyl‐N‐methyltrimethylenediamines 3 by reductive cleavage of the intermediate hexahydropyrimidine 2. Ring opening is explained by the formation of a stabilized iminium ion, which also accounts for the cyclic aminal 2 hydrolysis observed in alcoholic solution after gradual addition of borohydride. Reactions with lithium aluminum hydride or with borane failed to render satisfactory results due to insolubility of the salt in solvents commonly employed. Comparisons are made with the behaviour of 1H‐4,5‐dihydroimidazolium salts which were studied in an earlier paper.
Synthesis of (‐)(s)‐2‐hydroxymethyl‐2,3‐dihydro‐1,4‐benzodioxine by enzyme‐catalyzed resolution in organic media
Authors: Mauleón David , Lobato Cinta , Carganico Germano
Published: March 2009

The chiral primary alcohol 2‐hydroxymethyl‐2,3‐dihydro‐1,4‐benzodioxine (1) has been resolved by enantioselective acetylation in vinyl acetate solution, using Pseudomonas sp. Amano PS lipase. Enantiomers (‐)‐S1 (99% ee) and (+)‐R‐1 (72% ee) were obtained in 45 and 65% yield, respectively.
Schmidt rearrangement of 1,2,3,5,10,10a‐hexahydropyrrolo[1,2‐b]‐isoquinoline‐3,10‐diones
Authors: Mérour Jean‐Yves , Cossais FranÇOise , Piroëlle Simone , Mazéas Daniel
Published: March 2009

The Schmidt rearrangement of 1,2,3,5,10,10a‐hexahydropyrrolo[1,2‐b]isoquinoline‐3,10‐diones has been studied. The structure of the lactams obtained has been determined by chemical reactivity and characterized by means of ir, 1H and 13C nmr spectroscopy.
Synthesis of thieno[3,2‐d]pyrimidine‐2,4‐diones cyclic and acyclic nucleosides as potential anti HIV agents
Authors: Jourdan Fabrice , Ladurée Daniel , Robba Max
Published: March 2009

Synthesis of cyclic and acyclic nucleosides was achieved by alkylation of 7‐methyl or arylthieno[3,2‐d]‐pyrimidine‐2,4‐diones following the Vorbrüggen and Niedballa's method [1]. After a possible deprotection, potential anti HIV agents were obtained.
Angular to linear rearrangement of an isoindolo[2,1‐a]quinazoline skeleton
Authors: Guillaumel Jean , Demerseman Pierre
Published: March 2009

Demethylation of the angular 3‐methoxyisoindolo[2,1‐a]quinazolin‐11(5H)‐one by pyridinium chloride led to the rearranged linear 8‐hydroxyisoindolo[1,2‐b]quinazolin‐12(10H)‐one.
Reactivity of 1‐(2‐nitrophenyl)‐5‐aminopyrazoles under basic conditions and synthesis of new 3‐, 7‐, and 8‐substituted pyrazolo[5,1‐c][1,2,4]benzotriazine 5‐oxides, as benzodiazepine receptor ligands
Authors: Costanzo Annarella , Guerrini Gabriella , Bruni Fabrizio , Selleri Silvia
Published: March 2009

The reaction of 1‐(2‐nitrophenyl)‐5‐aminopyrazoles under basic conditions has been reinvestigated and the structures of the obtained pyrazolo[5,1‐c][1,2,4]benzotriazine 5‐oxides confirmed by spectroscopic means. In particular the different aromatic nucleophilic attack on 8‐chloro derivatives 4a and 6a and 7‐nitro derivatives 11a and 12a was determined. From these latter compounds unexpected (phenyl‐ONN‐azoxy)pyrazoles were isolated.
A simple procedure for the synthesis of 3‐(substituted‐sulfanyl)‐4‐hydroxy‐6‐substituted‐pyran‐2‐ones
Authors: Para K. S. , Ellsworth E. L. , Prasad J. V. N. Vara
Published: March 2009

A series of 3‐(substituted sulfanyl)‐4‐hydroxy‐6‐substituted‐pyran‐2‐ones were synthesized for Human immunodeficiency virus‐1 protease inhibition. These compounds were synthesized in a simple and convergent fashion to allow us a rapid preparation of many structurally diversified analogues. Thus the condensation of trimethylsilyl enol ethers of corresponding ketones, with 2‐(S‐substituted)propane‐1,3‐dioates afforded the corresponding pyrones in 24–70% isolated yields.
The synthesis of biologically relevant 4(5)‐phosphono‐5(4)‐aminoimidazoles using a Pd‐catalyzed coupling reaction
Authors: Lin Jing , Thompson Charles M.
Published: March 2009

Regiochemically defined 1‐benzyl‐4‐phosphono‐5‐carboalkoxyimidazoles were synthesized from the corresponding 4‐bromoimidazoles using a tetrakis(triphenylphosphine)palladium(0)‐catalyzed coupling reaction with diethyl phosphite. The corresponding Michaelis‐Arbusov reaction failed to give a phospho‐nylated product. The carbomethoxy moiety was converted to an amino group using a Curtius rearrangement to afford 1‐benzyl‐4‐phosphono‐5‐amino‐imidazoles. Following deprotection and hydrolysis, phos‐phonic acid‐linked aminoimidazoles were accessed that resemble intermediates formed during purine biosynthesis.
Synthesis of 2,3‐dihydropyrazolo[5,1‐b]thiazoles via a tandem condensation sulfur‐extrusion reaction
Authors: Hanefeld Wolfgang , Schlitzer Martin
Published: March 2009

2,3‐Dihydropyrazolo[5,1‐b]thiazoles 3 are the first representatives of a heterocyclic system, which are conveniently prepared by heating 3‐aminorhodanines 1 with ethyl 2‐bromo‐3,3‐diethoxypropionate (2), via a tandem condensation‐sulfur extrusion reaction.
Chemoselective preparation of ketones by the grignard reaction of N‐acylpyrazoles
Authors: Kashima Choji , Kita Isanobu , Takahashi Katsumi , Hosomi Akira
Published: March 2009

N‐Acylpyrazoles afford chemoselectively the corresponding ketones in good yields by the use of equimolar amounts of Grignard reagent. In the case of an optically active N‐acylpyrazole, optical asymmetry was retained in comparable optical yield. Ketone formation by the Grignard reactions can be regarded as an important functionalization in a synthetic loop using pyrazoles as the auxiliary compound.
First synthesis of chiral 3‐vinylindoles as 4π‐components for diels‐alder reactions
Authors: Pindur Ulf , Lutz Gundula , Rogge Martina
Published: March 2009

The first syntheses of chiral 3‐ and 2‐vinylindoles bearing sulfoxide or (‐)‐menthyloxy functional groups at the β‐vinyl positions by way of procedures based on the Horner‐Wadsworth‐Emmons and Wittig reactions, respectively, are described. Some Diels‐Alder reactions demonstrating the 4π‐reactivity of these compounds are reported.
Synthesis and biological activities of tetrahydroquinazoline analogs of aminopterin and methotrexate
Authors: Gangjee Aleem , Zaveri Nurulain , Queener Sherry F. , Kisliuk Roy L.
Published: March 2009

(6R,6S)‐5,8‐Dideaza‐5,6,7,8‐tetrahydroaminopterin (1) and (6R,6S)‐5,8‐dideaza‐5,6,7,8‐tetrahydromethotrexate (2) were synthesized as potential inhibitors of dihydrofolate reductase (DHFR) and as antitumor agents. Cyclohexanone‐4‐carboxaldehyde dimethyl acetal, a key intermediate [10] was synthesized from cyclohexane‐1,4‐dione monoethylene ketal, which was converted via a Wittig reaction to its exocyclic 4‐methylene derivative which in turn, was converted to the 4‐aldehyde via a hydroboration‐oxidation sequence. Selective protection of the 4‐aldehyde as the dimethylacetal and cyclization with dicyandiamide afforded the 6‐dimethylacetal of 2,4‐diamino‐5,6,7,8‐tetrahydroquinazoline. Protection of the 2,4‐diamino moieties and selective deprotection of the 6‐aldehyde followed by reductive amination with p‐aminobenzoyl‐L‐glutamate afforded 2,4‐bisacetamido‐5,8‐dideaza‐5,6,7,8‐tetrahydroaminopterin (11). Deprotection of 11 afforded 1. Compound 2 was obtained from 11 via N10‐methylation and deprotection. The N10‐methyl analogue 2 was 2–10 fold more potent than 1 as an inhibitor of various DHFRs. In the in vitro preclinical screening program of the National Cancer Institute, compound 2 inhibited the growth of eighteen of the twenty nine tumor cell lines in culture at a GI50 > 1.0 × 10−8 M.
Synthesis and reactions of lithio derivatives of 1‐allenylbenzotriazole
Authors: Katritzky Alan R. , Verin Sergei V.
Published: March 2009

1‐(2‐Chloropropen‐2‐yl)benzotriazole (6) is converted by heating with sodium hydroxide or by lithium diisopropylamide at ‐78° into 1‐allenylbenzotriazole (1) in high yield. Allene 1 undergoes in situ lithiation at the α‐carbon and subsequent reactions with iodomethane or carbonyl compounds to produce 1‐(1‐substituted allenyl)benzotriazoles 9 and 2a‐c, respectively. Three equivalents of lithium diisopropylamide dilithiated 1 and afforded symmetrical 1‐(1,3‐disubstituted allenyl)benzotriazoles 11a,b upon reaction with ketones. The unsymmetrical 1‐(1,3‐disubstituted allenyl)benzotriazole 5 was obtained via a stepwise addition of benzophenone to the lithio derivative of 1 followed by a second lithiation and quenching with acetone. Monosubstituted allenes 2a and 8 were cyclized into the benzotriazolyl substituted dihydrofuran 3 and dihydropyrrole 4 respectively.
Synthesis of novel 1‐alkyl or 1‐aryl‐2‐(4‐substituted‐1‐piperazinyl)‐1‐H‐benzothieno[2,3‐d]imidazoles
Authors: Guerrera F. , Salerno L. , Sarvà M. C. , Siracusa M. A.
Published: March 2009

The synthesis of novel 1‐alkyl or 1‐aryl‐2‐(4‐substituted‐1‐piperazinyl)‐1‐H‐benzothieno[2,3‐d]imidazoles 7e‐x starting from 2‐nitro‐3‐bromobenzo[b]thiophene is described. These compounds were prepared as potential H1‐antihistaminic agents.
Chemical and electrochemical reduction of some pyrazolo[1,5‐a]pyrimidines
Authors: Bellec Christian , Lhommet GÉRard
Published: March 2009

Various pyrazolo[1,5‐a]pyrimidines 1 are prepared by two different ways. Their chemical reduction by sodium borohydride leads generally to 4,5,6,7‐tetrahydro compounds 3, while lithium aluminum hydride yields 4,7‐dihydro derivatives 2 at room temperature, and 3 in refluxing tetrahydrofuran. A complex mixture of oxidizable hydrodimers is obtained by electrochemical reduction. An electroreduction at a more negative potential also gives 4,7‐dihydro compounds 2. A new 4,5‐dihydropyrazolo[1,5‐a]pyrimidine has been obtained by condensation of 5‐amino‐3‐methyl‐1H‐pyrazole with acetophenone.
Photochromism of fulgides and stereoelectronic factors: Synthesis of (E)‐4(3)‐adamantyhdene‐(5)‐dicyanomethylene‐3(4)‐[1‐(2,5‐dimethylfuryl)ethylidene]tetrahydrofuran‐2‐one 4 and 4a and (E)‐4‐adamantylidene‐3‐[2,6‐dimethyl‐3,5‐bis(p‐diethyl‐aminostyryl)benzylidene]tetrahydrofuran‐2,5‐dione 10
Authors: Sun Zhiyuan , Hosmane Ramachandra S. , Tadros Maher , Guha Shekhar , Chen Wenpeng , Chen Jar‐Mo
Published: March 2009

In the search for fulgides with potential semiconductor laser compatibility, 4‐adamantylidene‐5‐dicyanomemylene‐3‐[1‐(2,5‐dimethyl‐3‐furyl)ethylidene]tetrahydrofuran‐2‐one (4), along with its regioisomer 4a, have been synthesized from the corresponding fulgide 6 containing a succinic anhydride ring by reaction with malononitrile in the presence of diethylamine. Upon irradiation with a uv light at λmax 350 run, a mixture of 4 and 4a revealed a considerably enhanced bathochromic shift to the visible region, λmax 605 nm as compared with the starting fulgide 6 which, upon analogous uv irradiation, absorbed at λmax 515 nm. In the search for semiconductor‐laser‐compatible fulgides with increased efficiency for the reverse bleaching reaction, another fulgide (E)–adamantylidene‐3‐[2,6‐dimethyl‐3,5‐bis(p‐diethylaminostyryl)‐benzylidene]tetrahydrofuran‐2,5‐dione (10) was synthesized in seven steps starting from 2‐bromo‐m‐xylene. However, 10 failed to undergo electrocyclic ring‐closure upon irradiation with a uv light at λmax 350 nm. The analogous fulgide 8, which contains an isopropylidene functionality in place of the adamantyl group of 10, was resynthesized for comparison, and showed two absorption maxima, one at 545 nm and the other at 620 nm. The missing physico‐chemical data for 8 have also been provided.