Studies in the imidazole series

The reaction of 2-mercaptobenzimidazole and 5, 6-dimethyl-2-mercaptobenzimidazole with -halogenoketones has given a series of 2--oxoalkylthio- and 2--oxoaralkylthiobenzimidazoles—intermediate products for the synthesis of thiazolo[3,2-a]benzimidazoles. The compounds obtained exhibit the phenomenon of ring-chain tautomerism.For part XXXV, see [6].     

Cyclocondensation of n-(prop-2-yn-1-yl)- and n-(penta-2,4-diyn-1-yl)- <Emphasis Type="Italic">o</Emphasis>-phenylenediamines with phenyl isothiocyanate and carbon disulfide

The cyclocondensation of N-(prop-2-yn-1-yl)-o-phenylenediamines with phenyl isothiocyanate leads to the formation of 1-(prop-2-yn-1-yl)-1,3-dihydro-2H-benzimidazole-2-thiones irrespective of the substituent nature at the triple bond. Reactions of both mono- and diacetylenic derivatives of o-phenylenediamine with carbon disulfide in the presence of KOH proceed with the formation of two heterocyclic nuclei simultaneously. From N-(prop-2-yn-1-yl)-o-phenylenediamines containing an aryl substituent at the triple bond, and N-(penta-2,4-diyn-1-yl)-o-phenylenediamines 2-methylidene-2,3-dihydro[1,3]thiazolo[3,2-a]benzimidazoles are formed. The latter are readily isomerized under the action of base giving thiazolo[3,2-a]benzimidazoles. The cyclocondensation of N-(alk-2-yn-1-yl)-o-phenylenediamines with CS₂ leads to [1,3]thiazino[3,2-a]benzimidazoles.     

Molecular modeling and cyclization reactions of 2-(4-oxothiazolidine-2-ylidene) acetonitrile

Diazotization of 2-(4-oxothiazolidine-2-ylidene) acetonitrile 1 with aryl diazonium chloride derivatives afforded 4-thiazolidinones 2a, b, whereas 3a, b derivatives produced through reaction of arylcarbonohydrazonoyl dicyanide with thioglycolic acid. Cyclization of 2a with aromatic aldehydes and malononitrile gave the expected substituted thiazolo [3,2-a] pyridines 4a, b. The reaction of 1 with anthraldehyde (1:1 molar ratio) gave the expected 4,5-dihydro-4-oxothiazole derivatives 5 which condensed with other mole p-chlorobenzaldehyde and gave the corresponding bisarylidine derivative 6. Thiazolo [3,2-a] pyridine enaminonitrile derivative 7 produced through addition of malononitrile to bisarylidine 6. Also, compound 7 reacted with other mole of malononitrile and furnished thiazolo [3,2-a] pyridine 12, furthermore, compound 7 refluxed with phenyl hydrazine, thiourea, and formic acid, to form the corresponding thiazolo [3,2-a] pyridines 13, 15 and 17, respectively. Also, compound 1 reacted with phNCS in presence of KOH and afforded 19. The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. Also, valuable information is obtained from calculation of the molecular parameters including electronegativity, net dipole moment of the compounds, total energy, electronic energy, binding energy, electrophilicity index, HOMO and LUMO energy.     

Studies of imidazo[1,2-a]benzimidazole derivatives. 21. Synthesis of haloketones in the imidazo[1,2-a] benzimidazole series

Methods for the synthesis of imidazo[1,2-a]benzimidazole haloketone derivatives have been investigated. It has been found that -bromoketone derivatives of this heterocycle can be prepared either by bromination of 3-acylimidazo[1,2-a]benz-imidazoles with bromine in glacial acetic acid or by acylation of 3-unsubstituted imidazo[1,2-a]benzimidazoles with haloanhydride derivatives of -bromoalkanoic acids. Treatment of imidazo[1,2-a]benzimidazoles with 3-chloropropionyl chloride results in the formation of imidazo[1,2-a]benzimidazolyl-3-propionyl chloride and bis(imidazo[1,2-a]benzimidazolyl)propan-3-one derivatives as side products. Reaction of 2-phenylimidazo[1,2-a]benzimidazoles with 3-bromopropionic acid in polyphosphoric acid gives benzocyclohepten[5,6:4,5]imidazo[1,2-a]benzimidazole derivatives.For Communication 20, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 339–345, March, 1986.     

Investigations in the imidazole series LXIII. Synthesis of imidazo[1,2-a]imidazole derivatives from 2-aminoimidazoles

A number of imidazo[1,2-a]imidazole derivatives were synthesized by the reaction of 1-methyl-2-aminoimidazole with-bromoketones. The intermediate 1-methyl-3-acylmethyl-2-iminoimidazolines were isolated, and the conditions for their cyclization to imidazo-[l,2-a]imidazole derivatives were studied.See [1] for communication LXII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1692–1694, December, 1971     

Research on imidazo[1,2-a] benzimidazole derivatives

2-Acyl-substituted 3-methyl(phenyl)-9-methylimidazo[1,2-a]benzimidazoles were synthesized by three methods: by the reaction of -halo ketones with 3-benzoyl-2-imino-1-methylbenzimi-dazoline, by reaction of acetic anhydride or acetyl bromide with 1-methyl-2-phenacylaminobenzimidazole, and by acylation of 3-substituted imidazo[1,2-a]benzimidazoles. Some of the properties of the resulting 2-acyl-substituted compounds were studied.See [1] for communication XIV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 111–115, January, 1977.     

Pyrimidinthiones (Part I): Utility of 2-Thioxopyrimidin-6-(1H)ones as Ring Transformer in the Synthesis of Fused Bi- and Tri-Cyclic Heterocyclic Compounds and Their Potential Biological Activities

The pyrimidinethiones have wide biological and pharmaceutical activities, that have attracted considerable interest in recent years especially as antiviral inhibiting production of hepatitis B virus (HBV), and in vitro insulin-mimetic. Activity of the complexes of pyrimidinone derivatives evaluated from 50% inhibitory concentration promoted us to study the transformation of the 2-thioxopyrimidin-6(1H) ones to fused bi- and tri-cyclic heterocyclic compounds having the pyrimidine moieties and screening their biological activity.

The reactivity of 2-mercapto-4-aryl-5-cyanopyrimidin-6(1H)ones (1) towards alkylation by different mono and bifunctional halo-organic compounds has been investigated to give S-monoalkylated products 2, 7 and 9; S- and N-dialkylated products 3, 13 and 14. Treatment of 1 and/or 2 with hydrazine hydrate as a nitrogen nucleophile have been investigated to give 4, treatment of 4 with CS₂ and sodium nitrite in the presence of acetic acid (0°C) produced 1,2,4-triazolopyrimidin-5(1H)one derivatives (5)and tetrazolo[1,5-a]pyrimidin-5(1H)ones (6), respectively. Also cyclization of 7 and 9 gave [1,3]thiazolo[3,2-a]pyrimidin-5(1H)one and [1,3]thiazolo[3,2-a]pyrimidin-3,5-dione derivatives 8 and 10 respectively, treatment of 10 with aromatic aldehyde produces 11 which reacted with guanidine HCl to give pyrimido[4,5-d]thiazolo[3,2-a]pyrimidin-6(1H)one derivative 12. Reaction of 14 with o-phenylenediamine was investigated and gave [1,4]quinoxalino[2,3-b][1,3]thiazolo[3,2-a]pyrimidin-9(1H)one derivative 15.     

Mesoionic compounds with a bridge nitrogen atom. 20. Thiazoloquinoxalinium oxide salts

It was established that the protonation and alkylation of mesoionic thiazolo[3,2-a]quinoxalinium 1-oxides does not take places at the oxide oxygen atom but rather at the nitrogen atom in the 5-position. The -electron structures of the compounds obtained were studied by the Pariser-Parr-Pople (PPP) method.See [1] for Communication 19.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 842–845, June, 1990.     

Derivatives of 2-mercapto-6-methyluracil

The reaction of the sodium salt of 2-mercapto-6-methyluracil with , -dibromoalkanes Br(CH₂)Br (n=1,4,5,6) has given the corresponding , -bis(4-hydroxy-6-methyl-2-pyrimidinylthio) alkanes. The reaction of the same salt with 1,2-dibromoethane gave 7-methyl-5-oxo-2,3,4,5-tetrahydrothiazolo[3,2-a]pyrimidine and 5-methyl-7-oxo-2,3,4,7-tetrahydrothiazolo[3,2-a]pyrimidine, and its reaction with 1,3-dibromopropane led to 8-methyl-6-oxo-3,4,5,6-tetrahydro-2H-pyrimidino[2,1-b]-1,3-thiazine.     

Investigations in the imidazole series

Cyclization of 2--oxoalkylthio- and 2--oxoaralkylthiobenzimidazoles and the reaction of 2-mercaptobenzimidazoles with -halogenoketones in the absence of bases has given a number of derivatives of thiazolo[3, 2-a]benzimidazole, cyclopentenothiazolo[3, 2-a]benzimidazole, and tetrahydrobenzothiazolo[3, 2-a]benzimidazole.For part XXXVI, see [6].     

An efficient synthesis of novel pyridothieno-fused thiazolo[3,2-a]pyrimidinones via Pictet–Spengler reaction

An efficient method for the synthesis of novel pyrido[3',2':4',5']thieno[3',2':2,3]pyrido [4,5:d][1,3]thiazolo[3,2-a]pyrimidine-4-one derivatives (5) has been developed using a Pictet-Spengler reaction between 2-(3-aminothieno[2,3-b]pyridin-2-yl)thiazolo[3,2-a] pyrimidin-5-one (3), which could be obtained from the condensation of 7-(chloromethyl)-5H-thiazolo[3,2-a]pyrimidin-5-one (1) with 3-cyanopyridine-2-thione (2) via Thorpe-Ziegler isomerization, and aromatic aldehydes under NH₂SO₃H as catalysis in good yields.     

Condensed imidazo-1,2,4-azines. 21. Synthesis of 2-arylfuro(pyrrolo-, thieno-)[2,3-e]-1,2,4-triazino[2,3-a]benzimidazoles by cyclization of 2-aroyl-1,2,4-triazino[2,3-a]benzimidazol-4H-3-ones

2-[(-Ethyl-, arylimino)phenethyl]-1,2,4-triazino[2,3-a]benzimidazoles were obtained by reaction of 2-aroylmethyl-1,2,4-triazino[2,3-a]benzimidazol-4H-3-ones with ethyl(aryl)amines or urea. By the action of phosphorus oxychloride, these benzimidazoles cyclize into substituted pyrrolo[2,3-e]-1,2,4-triazino[2,3-a]benzimidazoles, heating of which in polyphosphoric acid leads to the formation of furo[2,3-e]-1,2,4-triazino[2,3-a]benzimidazoles, while by the action of P₄S₁₀, they are transformed into thieno[2,3-e]-1,2,4-triazino[2,3-a]benzimidazoles.For Communication 20, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1109–1113, August, 1989.     

Iodocyclization of 2-[allyl(methallyl)sulfanyl]-6-(trifluoromethyl)pyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

Iodination of 2-[allyl(methallyl)sulfanyl]-6-(trifluoromethyl)pyrimidin-4(3H)-ones was accompanied by cyclization to 2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium triiodides. 3-(Iodomethyl)-3-methyl- 7-oxo-5-(trifluoromethyl)-2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium triiodide was reduced with sodium iodide to 3,3-dimethyl-7-oxo-5-(trifluoromethyl)-2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium iodide.     

Synthesis of biologically important novel fluorinated spiro heterocycles under microwaves catalyzed by montmorillonite KSF

The arylidienes of fluorinated spiro thiazolidines (5) containing α,β-unsaturated function have been used as component of Micheal addition with equimolar amount of 2-aminopyridine (6a) to give novel fluorinated spiro [indole-3,2′-pyrido[1,2-a]thiazolo[5,4-e]pyrimidines] (7) in a single step under microwaves in presence of montmorillonite KSF as solid support. The new improved synthetic method for fluorinated spiro [indole-3,2′-thiazolo[4,5-d]pyrimidines] (8) has also been developed involving the reaction of (5) with thiourea under monomode microwave reactor. Comparison with conventional synthesis and multimode microwave oven indicated the enhanced yield with faster reactions under monomode microwave reactor. Structure-activity relationships between the chemical structures and the antimycobacterial, antifungal activity of the evaluated compounds are also discussed.     

Alkylation of 2-(hydroxyimino)-5<Emphasis Type="Italic">H</Emphasis>-[1,3]thiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]-pyrimidin-3(2<Emphasis Type="Italic">H</Emphasis>)-ones

Alkylation products were obtained from ethyl 2-(hydroxyimino)-7-methyl-3-oxo-5-aryl-2,3- dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-6-carboxylates at the treatment with alkyl halides, dimethyl sulfate, and diazomethane. Diazomethane alkylated the initial substrate at the oxygen atom of the carbonyl group of the thiazolidine fragment, the other reagents, at the oxygen atom of the hydroxyimino group.     

Regioselectivity and stereoselectivity of electrophilic quaternization of substituted 2-allyl(2-cyclohexen-1-yl)thionicotinic acids to thiazolo[3,2-a]pyridinium salts

The electrophilic quaternization of substituted 2-allyl(2-cyclohexen-1-yl)-thionicotinic acids proceeds regioselectively and stereoselectively as a trans process with the formation of salts of 4a,10a-cis-4,4a-trans-1,2,3,4,4a,10a-hexahydrobenzothiazolo-[3,2-a]pyridinium acids. Trihalides of thiazolo[3,2-a]-pyridinium acids exist in equilibrium with their betaine form. The formation of betaines and reactions that proceed with a change in the anionic part of thiazolo[3,2-a]pyridinium salts have virtually no effect on the conformation of the heterocyclic cation.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 256–263, February, 1990.     

Cyclocondensation of 3-amino-2-iminonaphtho[1,2-d]thiazole with oxalic acid derivatives

Refluxing 3-amino-2-iminonaphtho[1,2-d]thiazole ( 1 ) with diethyl oxalate ( 2a ) in a 2:1 molar ratio in dry pyridine provided 2,2′-binaphtho[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazole ( 3 ). On the other hand, when 1 was treated with excess amount of 2a in dimethylformamide, it afforded ethyl naphtho[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazole-2-carboxylate ( 4a ) on heating and ethyl N-(2-iminonaphtho[1,2-d]thiazol-3-yl)oxamate ( 5 ) by stirring at room temperature. Cyclization of 5 upon fusion led to the formation of 3-hydroxy-2H-naphtho-[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazin-2-one ( 6 ). Compound 6 could also be prepared directly from 1 by refluxing either with 2a neatly, in glacial acetic acid or with oxalic acid ( 2b ) in the same medium. The acid form of 4a might be obtained from 1 and 2b on heating in dimethylformamide, but it was decarboxylated to naphtho-[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazole ( 4b ) during the reaction.     

An efficient synthesis of new thiazolopyrimidinones under microwave irradiation

7‐Chloromethyl‐6‐nitro‐5H‐thiazolo[3,2‐a]pyrimidin‐5‐one ( 2 ) is obtained by cyclocondensation of 2‐aminothiazole with ethyl 4‐chloroacetoacetate. This product was shown to react with various nitronate or malonate anions under microwave irradiation to give potentially bioactive 6‐nitro‐5H‐thiazolo[3,2‐a]pyrimidin‐5‐ones. Extension to other anions centered on S atom allows for the generalization this synthetic procedure.     

Research on imidazo[1,2-a] benzimidazole derivatives

,-Unsaturated ketones of the imidazo[1,2-a]benztmidazole series were synthesized from 3-formyl- and 3-acetyl-substituted imidazo[1,2-a]benzimidazoles by crotonic condensation in the presence of alkaline catalysts. The ,-unsaturated ketones can also be obtained by direct acylation of 3-unsubstituted imidazo[1,2-a]benzimidazoles with the chlorides of unsaturated acids. The properties and pharmacological activity of the ketones obtained were studied.See [1] for communication XIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1660–1665, December, 1976.