Synthesis of Polyfunctionally Substituted Fused Pyrimidine Derivatives as Antimicrobial Agents

A variety of pyrimidine derivatives 2—4 and annulated pyrimidine derivatives 5—17 have been synthesized via a sequence of heterocyclization reaction of readily available 6-naphthyl-4-oxo-2-thioxo-1,2,3,4-tetrahydroprimi-     

Synthesis of Several Polyfunctionally Substituted Fused Pyrimidines Incorporating Quinone Compounds

The synthesis of several new polyfunctionally substituted fused pyrimidines via reaction of 2‐amino 1,4‐naphthoquinone 2 with different reagents is described.     

Synthesis of Polyfunctionally Substituted Pyrazolonaphthyridine,Pentaazanaphthalene, and Heptaazaphenanthrene Derivatives

6-aminopyrazolo[3,4-b]pyridine-5-carbonitrile (2) was used as a precursor for the synthesis of a variety of pyrazolo[3,4-b][1,8]naphthyridines (3, 4) and pentaazacyclopenta[b]naphthalenes (5–10, 13, 14) via the initial addition to either the cyano or amino group followed by cyclization. Also, a series of heptaazadicyclopenta[a,g]naphthalenes (15–17) and heptaazacyclopenta[b]phenanthrenes (18, 19) were obtained via the interaction of 4-(dibenzothiophen-2-yl)-1,5-dihydro-5-imino-3-methyl-1-phenyl-1,2,6,8,9-pentaazacyclopenta[b]naphthalen-6-ylamine (14) with different reagents. The structures of the synthesized compounds were established by elemental and spectral analyses.     

Studies on Fused Azoles: Synthesis of Several Polyfunctionally Substituted Fused Azoles

The synthesis of several new polyfunctionally substituted fused pyrazoles via reaction of 5‐amino‐3‐methylthio‐1H‐pyrazole‐4‐carboxylate ( 2 ) with different reagents is described.     

Synthesis of Novel Polyfunctionally Substituted Thieno[2,3‐c]pyridazines

4‐Cyano‐5,6‐dimethylpyridazin‐3‐(2H)‐thione 3b was used as a key intermediate for the synthesis of novel polysubstituted thieno[2,3‐c]pyridazines.     

Synthesis and Evaluation of Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(5-pentadecyl-1,3,4-thiadiazol-2-yl)acetamide

Reaction of 5-pentadecyl-1,3,4-thiadiazol-2-amine 2 with ethyl cyanoacetate gave 2-cyano-N-(5-pentadecyl-1,3,4-thiadiazol-2-yl)acetamide 3, which was used to synthesize different heterocyclic derivatives with coumarin, pyrazole, thiazole, pyridine, pyrimidine, and thiophene rings. Propoxylation of these compounds by using 5 mol of propylene oxide produced nonionic surface active agents. Antimicrobial and surface activities were evaluated.     

Heterocyclic Synthesis with Enamines: Convenient Syntheses of Polyfunctionally Substituted Pyrazole,Pyridine, Pyrimidine and Pyrazolo[3,4-d]pyrimrdine Derivatives

Facile syntheses of pyrazole, pyridine, pyrimidine and pyrazolo[3,4-d]pyrimidine derivatives have been achieved by the reaction of β-enamino nitrile 2a with hydrazines, phenyl isothiocyanate, thiourea and active methylene reagents. The β-enamino ketone 2e with the same reagents affords 3,5-dimethyl heterocyclic ring systems.     

Reactions of Heteroaryl Substituted Propenones

Summary. Thienyl- and furylpropenones reacted with malonates, cyanoacetates, and malononitrile giving addition products which could be cyclized to heteroaryl substituted dihydropyranes, cyclohexanols, and piperidones. Heteroaryl substituted cyclopropyl ketones were prepared by reactions with Me₃SO⁺ I⁺, and by reaction with Lewis acids they were transformed into substituted dihydrobenzo[b]furanone or -thiophenone, or -hydroxy ketones. Cycloadditions with thiophene derivatives allowed the synthesis of substituted benzo[b]thiophene derivatives, but with poor yields. Structures and stereochemistry were established mainly by means of NMR spectroscopy.     

Enaminone as Building Blocks in Organic Chemistry: A Novel Route to Polyfunctionally 2‐Substituted 5,6,7,8‐Tetrahydronaphthalenes and Their Antiviral Evaluation

The enaminone 2 reacts with different reagents to afford anilino, aroylpyridine, 1,3,5‐tri‐tetrahydronaphthoyl‐benzene, pyridine, 2,3,6‐trisubstituted pyridines, pyrazole, pyrido[1,2‐a]benzimidazole, and hydrazone derivatives 4 , 6 , 8 , 9 , 11 , 13 , 15 , 17 , 20 , and 21 . The antiviral evaluation of some selected new products showed promising antiviral activity against human adenovirus 7 and human rotavirus Wa strain.     

A Facile Synthesis of Substituted Benzodiazepines Using Solid Support

An easy and convenient synthetic procedure for the preparation of benzodiazepines by coupling microwaves with the solvent technique have been elaborated.     

A Novel One-Pot Synthesis of Polyfunctionally Substituted Thiopyrano(2,3- b )pyridine and Pyrido(2,3- b )pyridine Derivatives under Solid-Liquid Phase-Transfer Catalysis

Ketoketene thioacetals or cyanoketene thioacetals which were formed by treatment of a variety of active methylenes containing f -keto or f -cyano group with CS 2 or with PhNCS were allowed to react with 2-aminoprop-1-ene-1,1,3-tricarbonitrile under PTC conditions to afford thiopyrano(2,3- b )pyridine 3a-12a or pyrido(2,3- b )pyridine 3b-12b derivatives.     

Studies with Polyfunctionally Substituted Heteroaromatics: The Reaction of Heterocyclic Enaminonitriles with α‐β‐Unsaturated Nitriles

5‐Amino‐4‐cyano‐3‐phenylpyrazole ( 1 ) reacts with cinnamonitriles ( 2 ) to yield the pyrazolo[1,5‐a]pyrimidines ( 3 ). Also, 5‐amino‐4‐cyano‐1‐phenylpyrazole ( 4 ) reacts with cinnamonitriles ( 2 ) to yield the pyrazolo[3,4‐b]pyridine derivatives ( 5 ). In contrast to this reaction, enaminothiophene ( 6 ) reacts with cinnamonitriles ( 2 ) to yield compound ( 7 ) not ( 8 ). The enaminopyrane ( 9 ) reacts with cinnamonitriles ( 2 ) to yield ( 10 ). Finally we have attempted to add cinnamonitriles ( 2 ) to thiopyrane ( 13 ); only rearrangement and aromatization product ( 14 ) was isolated.     

Synthesis and Antimicrobial Activity of Polyfunctionally Substituted Heterocyclic Compounds Derived from 5‐Cinnamoylamino‐2‐Cyanomethyl‐1,3,4‐Thiadiazole

Cinnamoyl isothiocyanate 1 was reacted with 2‐cyanoethanoic acid hydrazide 2 to afford 1‐cyanoacetyl‐4‐substituted thiosemicarbazide 3, which on treatment with a mixture of glacial acetic acid and acetic anhydride gave the desired 5‐cinnamoylamino‐2‐cyanomethyl‐1,3,4‐thiadiazole 4 . Compound 4 was subjected to react with aromatic aldehydes, phenylisothiocyanate, carbon disulphide, and arylidene malononitrile to give coumarin 5 , thiazolidines 8 , 9, and 1,3,4‐thiadiazolo[3,2‐a]pyridine 13 derivatives. The structures of all synthesized compounds were ascertained by spectral and analytical data. Antimicrobial activity of some of prepared compounds was investigated, and compounds 7, 8 were found to exhibit the highest strength.     

Reaction of 3-Benzoyl-2,3-dibromopropionic Acid with Substituted ortho-Phenylenediamines

3-Benzoyl-2,3-dibromopropionic acid reacts with 4-substituted o-phenylenediamines to give 3-aryl-2-carboxymethylene-1,2-dihydroquinoxalines.     

Reactions of 3,4-Dichloro-N-R-maleimides with Substituted 2-Thiouracils

Reactions of 3,4-dichloro-N-R-maleimides with substituted thiouracils at 40°C gave a 1:1 mixture of isomers of pyrrolothiazolopyrimidinetriones. Under conditions of thermodynamic control (100°C, 5 h) only pyrrolo[3',4':4,5]thiazolo[3,2-a]pyrimidine-4,6,8-triones were formed, hydrolysis of which followed by decarboxylation gave 5-oxo-5H-thiazolo[3,2-a]pyrimidine-2-carboxamide. The structure of N²-phenyl-6-methyl-5-oxo-5H-thiazolo[3,2-a]pyrimidine-2-carboxamide was confirmed by X-ray crystallography. Analogous cyclization of 3,4-dichloro-N-R-maleimides with 2-thioxoquinazol-4-one also gave a mixture of two isomers which were successfully separated by fractional crystallization.     

Bromination of Substituted 5H-Imidazo[1,2-b]-1,2,4-triazepin-4-ones and -thiones

The reactions of substituted 5H-imidazo[1,2-b]-1,2,4-triazepin-4-ones and -thiones with bromine and N-bromosuccinimide have been studied. Derivatives of 3- and 8-bromo-, 3,8-dibromoimidazo[1,2-b]-1,2,4-triazepine and 5H-2-bromomethyl-3-methyl-7,8-diphenylimidazo[1,2-b]-1,2,4-triazepin-4-one are formed, depending on the degree of substitution, the nature of the brominating agent, and the reaction conditions.     

Substituted pyridines

2, 5-Dimethylpiperidol-4, 1, 2, 5-trimethylpiperidol-4, and the gamma isomer of 1, 2, 5-trimethyl-4-phenylpiperidol-4 are dehydrated by various methods. The secondary piperidols mentioned are used to synthesize 5-methyl-2-formylpyridine and 5-methyl-4-phenyl-2-formylpyridine.     

Derivatives of sym-Triazines. 6. Some Special Features of the Addition of Substituted Acetylenes to Triazine Monoazides

The special features of the interaction of 2-azido-4-R-6-R'-sym-triazines with some acetylenic compounds have been investigated. A series of new derivatives of sym-triazine linked at position 2 with a 1,2,3-triazole ring has been synthesized.     

Substituted pyridines

5-Methyl-4-phenyl-2-styryipyridine has been oxidized to 5-methyl-4-phenylpyridinie-2-carboxylic acid. The decarboxylation of this acid has given 3-methyl-4-phenylpyrldine. To prove the structure of -(5-methyl-4-phenyl-2-pyridyl)acetophenone, it has been converted into 2, 5-dimethyl-4-phenylpyridine. The reaction of benzyl chloride with the lithium derivative of 2, 5-dimethyl-4-phenylpyridine has been studied. 3,7-Dimethyl-2-azafluorene has been obtained from 2,5-dimethyl-4-p-tolylpyridine.     

Substituted pyridines

2-Benzyl-3,6-dimethyl-4-phenylpyridine has been obtained from 2,5-dimethyl-4-phenyl-pyridine by the Ladenburg—Chichibabin reaction. The compounds formed in its oxidation have been studied.Translated from Khimiya Geterotsiklicheskikh Soedinii, Vol. 6, No. 6, pp. 779–781, June, 1970.