Showing papers in "Journal of Heterocyclic Chemistry in 1990"
TL;DR: In this article, the substitution of protonated heteroaromatic bases by nucleophilic carbon-centered radicals has been developed as one of the most general reactions in the heterocyclic series; its great interest results from the fact that it reproduces most of the numerous aspects of the Friedel-Crafts aromatic substitution, but with opposite reactivity and selectivity.
Abstract: The substitution of protonated heteroaromatic bases by nucleophilic carbon-centered radicals has been developed as one of the most general reactions in the heterocyclic series; its great interest results from the fact that it reproduces most of the numerous aspects of the Friedel-Crafts aromatic substitution, but with opposite reactivity and selectivity. The most recent developments, concerning the generation of free radicals by iodine and hydrogen abstraction and decarboxylation of carboxylic acids are particularly discussed. Some processes of high synthetic value were designed on the basis of the kinetic and thermodynamic features of all the elementary steps involved in complex but selective chain processes. New general procedures for the monosubstitution in the homolytic alkylation and acylation are reported and discussed.
186 citations
175 citations
TL;DR: In this article, the Suzuki Pd(0)-catalyzed coupling between arylboronic acids and bromides or iodides in weakly alkaline medium was evaluated.
Abstract: Several Pd-catalyzed coupling reactions have been evaluated for the synthesis of 5-substituted uracils. A convenient reaction, further developed by us, is the Suzuki Pd(0)-catalyzed coupling between arylboronic acids and aryl bromides or iodides in weakly alkaline medium. However, all attempts to use 5-bromo- or 5-iodouracil as the aryl halide failed. On the other hand, couplings between 2,4-di-t-butoxy-5-bromopyrimidine and various arylboronic acids were successful. In cases when the arylboronic acids were not available, it was better to reverse the coupling functionalities and use 2,4-di-t-butoxy-5-pyrimidineboronic acid and arylbromides. A large number of 5-aryluracils were prepared in this way. They were obtained in almost quantitative yields by dealkylation of the 5-aryl-2,4-di-t-butoxypyrimidines. However, a great drawback of these procedures is the highly allergenic properties of 2,4-dichloro-5-bromopyrimidine, which is an intermediate in the synthesis of 2,4-di-t-butoxy-5-bromopyrimidine and 2,4-di-t-butoxy-5-pyrimidineboronic acid. In order to avoid this intermediate the coupling between 5-bromo-2,4-ditrimethylsilyloxypyrimidine and arylboronic acids were attempted but failed. Also attemptes to prepare 2,4-di-trimethylsilyloxy-5-pyrimidineboronic acid failed due to migration of a silyl group to the 5-position upon halogen-metal exchange. We therefore turned to the use of tin derivatives instead of boronic acids in the coupling reaction, which can be carried out under neutral conditions. Thus 5-(1-methyl-2-pyrrolyl)uracil, which could not be prepared from 2-bromo-1-methylpyrrole and 2,4-di-t-butoxy-5-pyrimidineboronic acid was obtained through the Pd(0)-catalyzed coupling of 1-methyl-2-trimethylstannylpyrrole and 2,4-di-t-butoxy-5-bromopyrimidine followed by dealkylation. However, the great advantage with the tin derivatives was that 5-bromo-2,4-ditrimethylsilyloxypyrimidine could be used in the coupling with aryltin derivatives giving 5-aryluracils in reasonable yields. We also tried to use unprotected 5-halouracils in the coupling reactions. We were unsuccessful with the 5-bromo derivative. However, with 5-iodouracil coupling was achieved in some cases.
121 citations
TL;DR: The cyclization of 5-amino-3-methylthiopyrazole-4-carbonitriles or 4-carboxamides 3a-j, which were prepared by the reaction of ketene dithioacetals with formamide or carbon disulfide, was described in this article.
Abstract: The cyclization of 5-amino-3-methylthiopyrazole-4-carbonitriles or 4-carboxamides 3a-j, which were prepared by the reaction of ketene dithioacetals 1a,b [1a: bis(methylthiomethylenemalononitrile; 1b: bis(methylthio)methylenecyanoacetamide] with hydrazines (hydrazine hydrate, phenylhydrazine, p-chlorophenylhydrazine, p-nitrophenylhydrazine), with formamide or carbon disulfide proceeded to give the corresponding 4-amino- or 4-hydroxy-3-methylthiopyrazolo[3,4-d]pyrimidines 6a-h in good yields. 3-Aminopyrazolo[3,4-d]pyrimidine derivatives 6i-1 were also obtained by the application of the cyclization reaction of 3,5-diaminopyrazoles with formamide.
92 citations
TL;DR: In this paper, the reactions between 3-benzoyl-2-isothiocyanato-4,5,6,7-tetrahydrobenzo[b]thiophene and hydrazine or primary amines have been studied.
Abstract: The reactions between 3-benzoyl-2-isothiocyanato-4,5,6,7-tetrahydrobenzo[b]thiophene and hydrazine or primary amines have been studied. The products obtained were identified as derivatives of 4-phenyl-2-thioxo-2,3,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidine. Their easy reduction with sodium borohydride provided a useful method for the synthesis of 3-substituted-4-phenyl-2-thioxo-1,2,3,4,5,6,7,8-octahydrobenzo[4,5]thieno[2,3-d]pyrimidines. Both kind of compounds were evaluated as potential analgesic, anti-inflammatory and anti-arthritic agents.
83 citations
63 citations
TL;DR: In this article, an aromatic aldehyde and bis(3-ethyl-4-methyl-2-pyrrolyl)-methane were obtained from acetonitrile in the presence of a catalytic amount of trichloroacetic acid, followed by p-chloranil oxidation.
Abstract: The title compounds were prepared from an aromatic aldehyde and bis(3-ethyl-4-methyl-2-pyrrolyl)-methane in acetonitrile in the presence of catalytic amount of trichloroacetic acid, followed by p-chloranil oxidation. The reaction conditions employed here are milder than those previously reported, allowing efficient preparation of porphyrins with acid-labile groups such as cyclic acetals, for which the previous method provided no direct synthetic access. Using the new method, aromatic aldehydes with acid-labile groups, as well as sterically hindered aldehydes, gave the corresponding porphyrins in satisfactory yields (50–90%). This method therefore can be widely utilized for synthesis of 5,15-diaryloctaalkylporphyrins.
59 citations
TL;DR: In this article, a one-pot synthetic approach to the novel 3a,4,5,6-tetrahydro[1,2,4]oxadiazolo[4, 5-a][1,5]benzodiazepine system is described.
Abstract: An one-pot synthetic approach to the novel 3a,4,5,6-tetrahydro[1,2,4]oxadiazolo[4,5-a][1,5]benzodiazepine system, by 1,3-dipolar cycloaddition of benzonitriloxides to 1,5-benzodiazepine derivatives, is described. The structure and stereochemistry of the obtained adducts have been assigned by means of spectroscopic measurements.
58 citations
TL;DR: Polarized ethylenes having both electron-donating (an amino or a methylthio group) and electron-accepting (cyano, carbamoyl, methyl ester) groups on the adjacent two olefinic carbon atoms were prepared by the condensation of S-alkylthioamidinium salts or methyl dithiocarboxylates with the corresponding active methylene compounds in good yields.
Abstract: Polarized ethylenes having both electron-donating (an amino or a methylthio group) and electron-accepting (cyano, carbamoyl, methyl ester) groups on the adjacent two olefinic carbon atoms were prepared by the condensation of S-alkylthioamidinium salts or methyl dithiocarboxylates with the corresponding active methylene compounds in good yields. These polarized ethylenes were alternatively synthesized by the reaction of thioamides or methyl dithiocarboxylates with tetracyanoethylene oxide in good yields. Reactions of these polarized ethylenes with hydrazine or guanidine derivatives occurred smoothly to give the corresponding pyrazole and pyrimidine derivatives in good yields. The synthesis of 5-aza[2.2.3]cyclazine derivatives using polarized ethylenes is also described.
57 citations
TL;DR: The pyrazolo[3,4-d]pyrimidin-3-one congeners of guanosine, adenosine and inosine is described in this paper.
Abstract: Synthesis of the pyrazolo[3,4-d]pyrimidin-3-one congeners of guanosine, adenosine and inosine is described. Glycosylation of 3-methoxy-6-methylthio-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (13) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose (16) in the presence of boron trifluoride etherate gave 3-methoxy-6-methylthio-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4(5H)-one (17) which, after successive treatments with 3-chloroperoxybenzoic acid and methanolic ammonia, afforded 6-amino-3-methoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)one (18). The guanosine analog, 6-amino-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione (21), was made by sodium iodide-chlorotrimethylsilane treatment of 6-amino-3-methoxy-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4(5H)one (19), followed by sugar deprotection. Treatment of the adenine analog, 4-amino-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one (11), according to the high temperature glycosylation procedure yielded a mixture of N-1 and N-2 ribosyl-attached isomers. Deprotection of the individual isomers afforded 4-amino-3-hydroxy-1-βribofuranosylpyrazolo-[3,4-d]pyrimidine (26) and 4-amino-2-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-3(7H)-one (27). The structures of 26 and 27 were established by single crystal X-ray diffraction analysis. The inosine analog, 1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione (28), was synthesized enzymatically by direct ribosylation of 1H-pyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione (8) with ribose-1-phosphate in the presence of purine nucleoside phosphorylase, and also by deamination of 26 with adenosine deaminase.
54 citations
TL;DR: In this paper, a 12% overall yield from 4,4′-dimethyl-2,2′-bipyridine (3) via a 5-step reaction sequence involving the intermediate 4, 4′-R2-2.2.
Abstract: 4,4′-Divinyl-2,2′-bipyridine (2) was prepared in 12% overall yield from 4,4′-dimethyl-2,2′-bipyridine (3) via a 5 step reaction sequence involving the intermediate 4,4′-R2-2,2′-bipyridines: R = COOH, 4; CO2CH3, 5; CH2OH, 6; CHO, 7. The newly synthesized compounds 2, 6 and 7 were characterized by melting point, infrared, 1H nmr, mass spectrometry and elemental analysis.
TL;DR: In this paper, the relative esters of 4-substituted 2-amino-, 2-methyl- or 2-phenyl-5-pyrimidine carboxylic acids were obtained in moderate yields by reaction of the above dinucleophiles with ethyl 2,2-diformylacetate.
Abstract: Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with N-C-N dinucleophiles such as guanidine, acetamidine or benzamidine afforded in high yields the relative esters of 4-substituted 2-amino-, 2-methyl- or 2-phenyl-5-pyrimidinecarboxylic acids, respectively. These esters were hydrolyzed to the corresponding carboxylic acids, which were converted by heating to 4-substituted 2-pyrimidinamines, 2-methyl or 2-phenylpyrimidines, respectively, generally in excellent yields. The 4-unsubstituted ethyl 2-amino-, 2-methyl- and 2-phenyl-5-pyrimidinecarboxylates were obtained in moderate yields by reaction of the above dinucleophiles with ethyl 2,2-diformylacetate. These esters were hydrolyzed and the corresponding acids (with the exception of the 2-methyl derivative) were decarboxylated to give 2-pyrimidinamine and 2-phenylpyrimidine in satisfactory yields.
TL;DR: Synthesis of several bis(4-arylthiosemicarbazido- 1, bis(2-arylamino-1,3,4thiadiazol-5-yl)- 5 and bis( 4-aryl-1.2,4-triazolin-3-thione-5yl)- 2 pentanes is described.
Abstract: Synthesis of several bis(4-arylthiosemicarbazido- 1, bis(2-arylamino-1,3,4-thiadiazol-5-yl)- 5 and bis(4-aryl-1,2,4-triazolin-3-thione-5-yl)- 2 pentanes is described. Sulphides 3 and sulphones 4 are also prepared from 2 by alkylation and subsequent oxidation with hydrogen peroxide respectively.
TL;DR: In the presence of copper(I) chloride, the palladium catalyzed oxidation of methyl 2-ethenylbenzoates (2-ETHB) and 2-Ebenzamides has been studied.
Abstract: In the presence of copper(I) chloride, the palladium catalyzed oxidation of methyl 2-ethenylbenzoates and 2-ethenylbenzamides have been studied. This reaction was used to form isocoumarins and 1-isoquinolinones.
TL;DR: In this paper, 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 treatement with chromic anhydride, yielded the corresponding tetrahydro derivatives, IV.
Abstract: 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 treatement 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, 1 H NMR, MS and X-ray spectroscopy.
TL;DR: In this article, the synthesis of the title compounds 3 upon cyclodehydration with thionyl chloride of the corresponding bis-aroylhydrazides 2 is described and their spectral properties are examined.
Abstract: The synthesis of the title compounds 3 upon cyclodehydration with thionyl chloride of the corresponding bis-aroylhydrazides 2 is described and their spectral properties are examined.
TL;DR: In this article, a practical method for the preparation of 2-chloro-4,6-di(heteroaryl)pyrimidines and their 5-methyl homologues from readily available 2chloropyrimidine and 2chloro -5-methylpyrimidine, respectively, is described.
Abstract: A practical method for the preparation of 2-chloro-4,6-di(heteroaryl)pyrimidines and their 5-methyl homologues from readily available 2-chloropyrimidine and 2-chloro-5-methylpyrimidine, respectively, is described. The method is based on the addition reactions of heteroaryllithium reagents with chloropyrimidines followed by dehydrogenation of the resultant substituted dihydropyrimidines. The use of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone as the dehydrogenation agent gives the best results. Side reactions in the addition step are discussed.
TL;DR: In this paper, the reaction of ethyl 4,4,4 trifluoroacetoacetate with methylhydrazine produced not only the previously reported 5-hydroxy-3-(trifluoromethyl)pyrazole 1 but also its unknown isomer the 3-hydrox-5-(trifioromethemyl) pyrazole 4.
Abstract: Reaction of ethyl 4,4,4-trifluoroacetoacetate with methylhydrazine produced not only the previously reported 5-hydroxy-3-(trifluoromethyl)pyrazole 1 but also its unknown isomer the 3-hydroxy-5-(trifluoromethyl)pyrazole 4 The structure assignements are etablished based on 13 C NMR spectra Compound 1 was converted to 5-chloro-3-(trifluoromethyl)pyrazolecarboxylic acid 3 in two steps
TL;DR: In this article, 3,6-Dichloropyridazine was ortho-lithiated by lithium 2,2,6,6tetramethylpiperidide.
Abstract: 3,6-Dichloropyridazine was ortho-lithiated by lithium 2,2,6,6-tetramethylpiperidide. The resulting lithio compound was reacted with carbonyl derivatives iodine and trimethylchlorosilane. An azaxanthone was synthesised. An unusual regioselectivity for the lithiation of 2,4-dichloropyrimidine was studied.
TL;DR: In this article, the two structural isomers, 4 and 5, of 1-substituted-4-iminomethyl-1,2,3-triazoles are interconvertible when heated in dimethyl sulfoxide at 80°.
Abstract: The two structural isomers, 4 and 5, of 1-substituted-4-iminomethyl-1,2,3-triazoles are interconvertible when heated in dimethyl sulfoxide at 80°. The equilibrium position depends on the electronic properties of the R-substituent, favoring 5 for R = alkyl, benzyl and anisyl, and 4 for p-chlorophenyl and p-nitrophenyl. An interesting application is the synthesis of 1-alkyl-1,2,3-triazole-4-carbaldehydes from 1-phenyl-1,2,3-triazole-4-carbaldehyde by Scheme I. The hydrazones 4ij and the oxime 4k do not rearrange due to an unfavorable Z-configuration around the C N bond, whereas the acyloximino derivative 4m is converted into the nitrile 11. The structures of the products have been fully characterized by 13C nmr spectroscopy and the mechanistic details of the rearrangement are discussed.
TL;DR: In this article, three synthetic entries of functionalized 6-fluoro-7-substituted indole derivatives were developed in connection with the preparation of 7-fluororo-8-substantituted-1,3,4,9-tetrahydropyrano[3, 4-b]indole-1-acetic acid derivatives.
Abstract: Three practical synthetic entries of functionalized 6-fluoro-7-substituted indole derivatives were developed in connection with the preparation of 7-fluoro-8-substituted-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid derivatives 11. The first route, which permits group modification about position 8 of the pyranoindole skeleton, employs 2-bromo-3-fluoroaniline (18) as a key intermediate, the preparation of which was achieved by either a novel ortho metalation of 15 or via the intermediacy of 22. The second route utilizes 32 to append a terminally functionalized three carbon side chain onto the indole template and in addition leads to 43 from 40. The third route to the 7-fluoro-8-substituted-pyranoindole skeleton complements route two in that the synthetic pathway exploits 32 in a nucleophilic fashion to construct a terminally functionalized two carbon appendage onto the indole nucleus.
TL;DR: In this article, the diazotisation of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile and ethyl-2-amide-4.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23
Abstract: 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.
TL;DR: In this paper, an efficient synthesis of 2-n-dodecylthio-4-phenylthiomethyl-1,3,4-thiadiazole-5-thione is described.
Abstract: Facile synthesis of 2-n-dodecylthio-4-phenylthiomethyl-1,3,4-thiadiazole-5-thione 6, starting from 2,5-dimercapthothiadiazole via 2-n-dodecylthio-1,3,4-thiadiazole-5-thione 2, 2-n-dodecylthio-4-hydroxymethyl-1,3,4-thiadiazole-5-thione 4 and 2-n-dodecylthio-4-chloromethyl-1,3,4-thiadiazole-5-thione 5 is described.
TL;DR: In this paper, 2,4-disubstituted thiosemicarbazides were allowed to react with α-bromoacetophenone to give the anticipated 2,3-dihydro-6H-1,3, 4thiadiazines.
Abstract: 2,4-Disubstituted thiosemicarbazides were allowed to react with α-bromoacetophenone to give the anticipated 2,3-dihydro-6H-1,3,4-thiadiazines, whereas with β-propiophenone and γ-butyrophenone to afford the unexpected 2,3-dihydro-1,3,4-thiadiazole. The reaction mechanism was also discussed.
TL;DR: In this article, the structure of the 4-Thiocarbamoyl-5-aminoisoxazole (4,3d) compound was definitively assigned by X-ray analysis.
Abstract: 4-Thiocarbamoyl-5-aminoisoxazole 4 was used as a convenient starting material for preparing both isoxazolo[5,4-d]pyrimidine-4(5H)thiones 5 and 4-aminoisothiazolo[4,3-d]isoxazole 6. The structure of the latter compound was definitively assigned by X-ray analysis.
TL;DR: In this article, a stereo-specific cycloaddition of 2,3-disubstituted oxiranes to heterocumulenes, including carbodiimides, isocyanates and carbon dioxide, is catalytically promoted by dialkyltin diiodide-hexamethylphosphoric triamide (HMPA) system, producing various five-membered heterocycles.
Abstract: Stereospecific cycloaddition of 2,3-disubstituted oxiranes to heterocumulenes, including carbodiimides, isocyanates and carbon dioxide, is catalytically promoted by dialkyltin diiodide-hexamethylphosphoric triamide (HMPA) system, producing various five-membered heterocycles, where the configuration of the carbons in the oxirane ring is retained. In particular, the addition of isocyanates to oxiranes gave stereo-specifically two types of products, dioxolan-2-imines and oxazolidin-2-ones independently, while the rearrangement of the former to the latter product has been already proposed.
TL;DR: The reaction of pyridinium or isoquinolinium N-ylides with methoxy-substituted ethylenes gave the corresponding indolizine and pyrrolo[2,1-a]isoquinoline derivatives bearing acetyl, aroyl, cyano, ester group at the 1-position in one step as mentioned in this paper.
Abstract: The reaction of pyridinium or isoquinolinium N-ylides with methoxy-substituted ethylenes gave the corresponding indolizine and pyrrolo[2,1-a]isoquinoline derivatives bearing acetyl, aroyl, cyano, ester group at the 1-position in one step. Pyrazolo[1,5-a]pyridine, pyrazolo[1,5-a]quinoline, and pyrazolo[5,1-a]isoquinolines were also synthesized in good yields from the corresponding aromatic N-imines and methoxyethylene derivatives.
TL;DR: In this paper, it was shown that the primary reaction products between dehydroacetic acid and p-chlorophenylhydrazine or 4-phenylthiazol-2-yl hydrazine are 4-acetylacetyl-5-hydroxypyrazoles.
Abstract: It has been established that the primary reactions products between dehydroacetic acid and p-chlorophenylhydrazine or 4-phenylthiazol-2-ylhydrazine are 4-acetylacetyl-5-hydroxypyrazoles. These compounds react with the above hydrazines to yield 4-(pyrazol-5′-yl)-2-pyrazolin-5-ones which exist in solution as 5-hydroxypyrazoles.