Investigation of imidazo[1,2-a]benzimidazole derivatives

Esters of 1-alkyl- and 1-aralkyl-2-iminobenzimidazoline-3-acetic acids are converted to esters of 2,9-dimethylimidazo[1,2,-a]benzimidazole-3-carboxylic acid on heating with acetic anhydride. The brief action of acetic anhydride on the free iminobenzimidazolineacetic acids gives 2-oxo-2,3-dihydroimidazo[1,2-a]benzimidazoles, which are converted to 2,9-substituted 3-acetylimidazo[1,2-a]benzimidazoles on prolonged heating with acetic anhydride.See [1] for communication V.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 111–114, January, 1973.     

Role of Epoxides in the Oxidation of Allyl Alcohol,Allyl Formate,and Allyl Acetate in Acetic Acid

The formation of epoxy derivatives as intermediate products in the oxidation of allyl alcohol, allylformate, allyl acetate in acetic acid was proved. Intermediate epoxy compounds undergo further trans-formations: They react with acetic acid to give glycerol esters or are converted into polyethers of glyceroland its esters. The rate constants for transformations of 2,3-epoxypropanol, 2,3-epoxypropyl formate, and 2,3-epoxypropyl acetate along these pathways were measured. Higher selectivity of glycerol ester formation from allyl formate was substantiated.     

Reaction of 2-(2-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-indol-3-ylidene)acetic acid esters with benzene-1,2-diamine and 2-aminobenzenethiol

2-(2-Oxo-2,3-dihydro-1H-indol-3-ylidene)acetic acid esters reacted with benzene-1,2-diamine or 2-aminobenzenethiol to give (2-oxo-2,3-dihydro-1H-indol-3-yl)-substituted 3,4-dihydroquinoxalin-2(1H)-ones or 2H-1,4-benzothiazin-3(4H)-ones.     

Synthesis of methyl esters of 5-amino-4-(substituted amino)-2-methylthio-7H-pyrrolo[2,3d]-pyrimidine-6-carboxylic acids

The optimum route for the synthesis of methyl esters of N-[(4-substituted amino)-5-cyano-2-methylthiopyrimidin-6-yl]amino acids (which are starting materials for preparing the methyl esters of the corresponding 5-amino-4-(substituted amino)pyrrolo[2,3-d]pyrimidine-6-carboxylic acids) is via subsequent reactions of 4,6-dichloro-2-methylthiopyrimidine-5-carbonitrile with amines and methyl glycinate. In some examples, the reaction of methyl N-(4-chloro-2-methylthio-6-pyrimidinyl)aminoacetate with amines occurs to give the corresponding acid amides. The previously unknown synthesized derivatives of pyrimidin-6-yl amino acids and 4,5-diaminopyrrolo[2,3-d]pyrimidine- 6-carboxylic acids possess fungicidal properties.Vilnius University, Vilnius 2006, Lithuania. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No 7, pp. 955–961, July, 2000.     

Synthesis of 2,3-substituted thienylboronic acids and esters

A noncryogenic protocol for the synthesis of 2-substituted 3-thienylboronic acids and esters as well as 3-substituted 2-thienylboronic acids and esters has been developed. Electrophiles were introduced regiospecifically in the 2-position of 2,3-dibromothiophene and in the 3-position of 2-bromo-3-iodothiophene by halogen-magnesium exchange followed by quenching with electrophiles. Palladium-catalyzed borylation of the 2,3-substituted halothiophenes with pinacolborane and P(t-Bu)3 as ligand for Pd produced 9 and 10. The borylation protocol was tolerated by a range of functional groups; however, strongly electron-withdrawing substituents decreased the stability of the thienylboronic acids and esters.     

1,3,4,6-Tetracarbonyl Compounds: VI. Synthesis of 2-Substituted 6-Aryl-3,4-dihydroxy-6-oxo-2,4-hexadienoic Acid Esters and Amides

The Knoevenagel reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with ethyl cyanoacetate or malonodinitrile yields 2-substituted 6-aryl-3,4-dihydroxy-6-oxo-2,4-hexadienoic acid esters or amides which exhibit biological activity. The structure of the products is discussed, taking into account the structure of known 3,4-dihydroxy-6-oxo-2,4-hexadienoic acid esters and 1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones.     

Stereodivergent synthesis of cyclic γ-aminobutyric acid – GABA analogues

A novel synthetic route towards two series of enantiomerically pure cyclic analogues of 2,3-cis- and 2,3-trans-γ-aminobutyric acid (GABA) was developed. The route is based on the elongation and stereodivergent manipulation of a readily accessible enantiomerically pure γ-substituted α-aminolactone. The five-step route towards the 2,3-cis-substituted GABA analogues was achieved via straightforward carbon chain extension of the lactone using a non-classical Wittig reaction followed by chemoselective reduction and a protecting group switch. The five-step route towards the 2,3-trans-substituted GABA analogues employed elongation of the same aminolactone using a Horner-Wadsworth-Emmons reaction and highly stereoselective intramolecular oxa-Michael addition as the key synthetic manipulations. Altogether this chemistry has allowed the stereodivergent preparation of a novel class of GABA analogues in two diastereomeric series.     

Synthesis of 2-Substituted 5-(1,2,3-Selenadiazol-4-yl)furan-3-carboxylic Acids Esters

Russian Journal of General Chemistry - A series of semicarbazones have been obtained from 2-substituted 5-acetylfurancarboxylic acid esters. When oxidized with selenium dioxide in acetic acid,...     

Chemistry of thienopyridines. VIII. Substitution products derived from thieno[2,3-b] pyridine 7-oxide

Thieno[2,3-b]pyridine (I) was concerted to the N-oxide (II, 53%) by means of hydrogen peroxide and acetic acid. Nitration of II in sulfuric acid gave 4-nitrothieno[2,3-b]pyridine 7-oxide (III, 50%), while nitration in acetic acid formed the isomeric 5-nitrothieno[2,3-b]pyridine 7-oxide (IV, 54%). Compounds III and IV were reduced to the corresponding 4- and 5-aminothieno[2,3-b]pyridines, respectively. Treatment of III with acetyl chloride gave 4-chlorothieno-[2,3-b]pyridine 7-oxide (XI, 81%), convertible in two steps to 4-(N-substituted amino)thieno-[2,3-b]pyridines (especially of the 4-dialkylaminoalkylamino type) for screening as potential antimalarial drugs. 4-Aminothieno[2,3-b]pyridine reacted with aromatic aldehydes to give Schiff's bases and other products. Mechanisms for some of the reactions are suggested. NMR spectral data are reported for various 4-substituted thieno[2,3-b]pyridine compounds.     

Quinoline synthesis: scope and regiochemistry of photocyclisation of substituted benzylidenecyclopentanone O-alkyl and O-acetyloximes

Irradiation of substituted 2-benzylidenecyclopentanone O-alkyl and O-acetyloximes in methanol provides a convenient synthesis of alkyl, alkoxy, hydroxy, acetoxy, amino, dimethylamino and benzo substituted annulated quinolines. para-Substituents yield 6-substituted-2,3-dihydro-1H-cyclopenta[b]quinolines with 8-substituted products being obtained from ortho-substituted starting materials. Reactions of meta-substituted precursors are highly regioselective, with alkyl substituents leading to 5-substituted 2,3-dihydro-1H-cyclopenta[b]quinolines and more strongly electron-donating substituents generally resulting in 7-substituted products. 2-Furylmethylene and 2-thienylmethylene analogues yield annulated furo- and thieno-[2,3e]pyridines respectively. Sequential E- to Z-benzylidene group isomerisation and six pi-electron cyclisation steps result in formation of a short-lived dihydroquinoline intermediate which spontaneously aromatises by elimination of an alcohol or acetic acid. For 2-benzylidenecyclopentanone O-allyloxime, singlet excited states are involved in both steps.     

New approach to the synthesis of 2,3-substituted γ-aminobutyric acids and their derivatives

A new approach to the synthesis of 2,3-substituted γ-aminobutyric acids is proposed. This method consists of the selective catalytic reduction of substituted 3-cyanopropanoic acid esters, which are generated in high yield in the reaction of disubstituted cyclopropenes with sodium cyanide in the corresponding alcohol.     

Diastereotopic derivatives of chiral alkoxyisoindolinones

A method for synthesis of 2,3-substituted 3-hydroxyisoindolin-1-one acyl derivatives, modified reactivators of tumor suppressor protein p53, was developed; these compounds were synthesized and characterized. It was shown that diastereomeric esters of Boc-N-protected amino acids, unlike esters with a free amino group, can be preparatively isolated by flash chromatography using achiral media.     

Formation of imidazolidine derivatives from dimethyl (2,2-dimethylhydrazino)succinate in reactions with allyl and phenyl isothiocyanates

The reaction of (2,2-dimethylhydrazino)succinic acid ester with allyl and phenyl isothiocyanates leads to esters of 1-substituted (3-dimethylamino-5-oxo-2-thioxo-4-imidazolidinyl)acetic acids, which in protic solvents undergo a slight degree of elimination of dimethylamine to give esters of 1-substituted (5-oxo-2-thioxoimidazolidin-4-ylidene)acetic acids. The structure of methyl (1-allyl-5-oxo-2-thioxoimidazolidin-4-ylidene)acetate was proved by x-ray diffraction analysis.Communication 3 from the series Derivatives of hydrazino carboxylic acids, See [1] for communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1219–1223, September, 1987.     

Thermal rearrangement of indolyl oxime esters to pyridoindoles

Acyl oximes derived from a variety of indolylalkanones underwent a ring closure sequence during FVP to afford 9H-pyrido[2,3-b]indoles. Unlike UV light promoted reactions of oxime esters, the mechanism is almost certainly not mediated by iminyl radicals but probably involves tautomerism, elimination of acetic acid, and a final electrocyclic ring closure.     

Synthesis and Antimicrobial Evaluation of Halogen-Containing Arylidene Thiazolo Triazinediones

A series of 7-substituted arylidene-1,3-thiazolo[2,3-c]-1,2,4-triazine-4,6-diones were synthesized in an one-pot multicomponent reaction of 6-arylmethyl-3-mercapto-1,2,4-triazin-5-ones with substituted benzaldehydes and monochloroacetic acid in the presence of acetic anhydride, acetic acid, and sodium acetate. The structures of the new compounds were supported by IR, ¹H NMR, MS, and analytical data. All the new compounds were tested for their antibacterial and antifungal activity. Arylidene thiazolo triazinediones with 1,3-benzodioxolo substituent at seventh and p-chlorophenyl or 2,4-dichlorophenyl substituents at third displayed good antibacterial and antifungal activity. And also compound bearing 2,3,5-trimethoxyphenyl substituent at seventh and 2,4-dichlorophenyl substituent at third displayed good activity.     

Dynamic Kinetic Resolution of 2,3-Dihydrobenzo[b]furans: Chemoenzymatic Synthesis of Analgesic Agent BRL 37959

An efficient asymmetric synthesis of (S)-2,3-dihydrobenzo[b]furan-3-carboxylic acid (8?a) and (S)-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylic acid (8?b) was established. Key to the success was the highly stereoselective enzymatic kinetic resolution of the corresponding methyl or ethyl esters that was further developed into a dynamic process. As a reliable and fast tool for analysing the enantiomeric excess, HPLC coupled with a CD detector was utilized. The route was completed by a Friedel-Crafts acylation of ethyl (S)-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylate (7?c) followed by saponification leading to (S)-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylic acid (2), an analgesic agent.     

Synthesis of α,β-unsaturated butenolides from allenic acids

The electrophile-initiated cyclisation of allenic acids and esters provides a general route for the synthesis of β-substituted α,β-unsaturated butenolides.     

New convenient synthesis of 2,3-diaminothieno[2,3-d]pyrimidin-4(3H)-one derivates from substituted alkyl 2-(1H-tetrazol-1-yl)thiophene-3-carboxylates

4,5-Disubstituted and 4-substituted alkyl 2-amino-thiophene-3-carboxylates react with triethyl orthoformate and sodium azide in acetic acid to yield new 2-(1H-tetrazol-1-yl)-4-R¹-5-R²-thiophene derivates. It was established that the reaction of these tetrazoles with hydrazine generates the insufficiently studied 2,3-diaminothieno[2,3-d]pyrimidin-4(3H)-one system. It is significant that the reaction mentioned above is the unique tetrazole ring cleavage under the action of hydrazine.     

Synthesis in the 2-mercaptobenzothiazole series V. Thiazolidino[2, 3-b]-benzothiazolines

Reaction of 2-mercaptobenzothiazoles substituted at position 6 by chlorine, dimethylsulfamido, benzamido, and nitro groups, with chlorobromoalkanes, is used to synthesize the corresponding 6-substituted 2-(-chloroalkylmercapto)benzothiazoles. Oxidation of these compounds with hydrogen peroxide in acetic acid converts them to sulfoxides and sulfones, while heating in nitrobenzene cyclizes them to 6 substituted 2,3-dihydrothiazolo[2,3-b]benzothiazolium chlorides. The latter and previously obtained quaternary salts are converted by sodium borohydride into derivatives of a new tricyclic system, thiazolidino[2,3-b]benzothiazoline.For Part IV see [1].     

Esterification of 1,2,5-oxadiazolylacetic acids with polynitro alcohols

Reactions of 4-substituted (1,2,5-oxadiazol-3-yl)acetic acids with 2,2,2-trinitro- and 2-fluoro-2,2-dinitroethanols afford the corresponding esters that can be useful as components of gas generating compositions.