Azza M. Abdel-Fattah

SYNTHESIS AND REACTIONS OF POLYNUCLEAR HETEROCYCLES WITH NEW RING SYSTEMS

Abstract Condensation of 5,6-dimethyl-2-hydrazino-3,4-dihydrothieno[2,3-d]pyrimidin-4-one (2) with aromatic aldehydes gave the arylhydrazones 3a-c which cyclized into thienotriazolopyrimidin-5- one 4a-c. Reactions of 2 with aliphatic acids afforded the thienotriazolopyrimidin-5-one 5a.b. Also, reaction of 2 with each of carbon disulfide and nitrous acid afforded 3-mercaptothienotriazolopyrimidin-5-one 7, and tetrazolothienopyrimidin-5-one 8, respectively, the latter compound 8 could be reduced to 2-aminothienopyrimidin-4-one 9. On the other hand, 2-hydrazino derivative 2 condensed with δ-haloketones yielded 3-substituted-thienopyrimidotriazin-6-one 10a.b with new ring system, and with β-diketones, β-ketoesters to form 2- (I-pyrazolyl) derivatives 13a-c, 14. The 2-pyrazolinone derivative 15 condensed with aromatic aldehydes to afford arylidene derivatives 16a-c. Also, reaction of 2 with ethyl cyanoacetate yielded 2-(pyrazolyl) derivatives 17.

NEW SYNTHESIS OF IMIDAZO[1,2-a]- AND PYRIMIDO[1,2-a]PYRIMIDINES

Abstract 6-Aryl-4-oxo-2- thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles (1) reacted with bromomalo-nonitrile(2) to give 3-amino-7-aryl-5-oxo-5H-thiazolo[3,2-a]pyrimidine-2,6-dicarbonitriles (3a-c). The latter compounds reacted with either formic acid, formamide or ammonium thiocyanate to yield the 7-aryl-9-oxo-4-substituted-thiazolo[3,2-a:4,5-d′]dipyrimidine-8-carbonitrile derivatives (4–6), respectively. Compounds (3a-c) could be converted into 7-aryl-3-amino-1-benzyl-5-oxo-5H-imidazo[1,2-a]pyrimidine-6-carbonitriles (8) and 4-amino-8-aryl-2,6-dioxo-3-substituted-1,2-dihydro-6H-pyrim-ido[1,2-a]pyrimidn-7-carbonitriles (9) by treatment in boiling ethanol with benzylamine and cyclic secondary amines, respectively.

Anti-Alzheimer and Anti-Cox-2 Activities of the Newly Synthesized 2,3′-Bipyridine Derivatives (I)

3-Amino-4-aryl-6-pyridin-3-ylthieno[2,3-b]pyridine-2-carbohydrazides 3a,b were used as the starting materials in the present study. Our targets here were represented by the synthesis of several 3-amino-N′-4-arylmethylenes 5a,b, N-formamides 8a,b, ethyl imidoformate 10b, N,N-dimethyl-N′-imidoformamides 12a,b, N-acetyl-N-acetamides 14a,b, 1,3,4-oxadiazole-2-thiol 16a,b, pyrazolothienopyridines 20a,b, 2-[(3,5-dimethyl-1H-pyrazol-1-yl)carbonyl]-4-aryl-6-pyridin-3-ylthieno[2,3-b]pyridin-3-amines 22a,b, 2-carbonyl-5-methyl-2,4-dihydro-3H-pyrazol-3-ones 24a,b, and 2-carbonyl-pyrazolidine-3,5-diones 26a,b. The newly synthesized heterocyclic compounds were tested as anti-Alzheimer and anti-COX-2 agents, and their structures were elucidated by considering the data of IR, 1H NMR, mass spectra, and elemental analyses. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Thieno[2,3-b]pyridine-2-carbohydrazide in Polyheterocyclic Synthesis: The Synthesis of Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine, Pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine, and Pyrazolyl, Oxadiazolylthieno[2,3-b]pyridine Derivatives

Pyrdine-2(1H)-thione 1 reacted with ethyl chloroacetate 2 to give 2-S-ethoxy-carbonylmethylpyridine derivative 3, which could be cyclized into thieno[2,3-b]-pyridine-2-carbohydrazide derivative 5 by boiling with hydrazine hydrate. The latter compound reacted with cinnamonitrile derivatives 6a, b, triethylorthoformate, formic acid, dimethylformamide-dimethylacetal, and diethyl carbonate to give the corresponding shiff base 7a, b and pyrido[3′,2′;-4,5]thieno[3,2-d]pyrimidine derivatives 10–13 in respective manner. On the other hand, compound 5 also reacted with carbondisulphide and phenyl isothiocyanate to afford the corresponding 2-(1,3,4-oxadiazolo-2-yl)thieno[2,3-b]pyridine derivatives 18 and 22. Finally, compound 5 reacted with some β-dicarbonyl compounds, such as ethyl acetoacetate, acetylacetone and ethyl β-arylazoacetoacetate, to yield the corresponding 2-(pyrazol-1-yl-carbonyl)thieno[2,3-b]pyridine derivatives 24, 25, and 27 respectively.

A FACILE SYNTHESIS OF ISOXAZOLO [5′,4′:4,5]THIAZOLO[3,2-a]THIENO PYRIMIDINES A NEW RING SYSTEM

Abstract In a one-pot synthesis 6,7-dimethyl-2-arylidine-5-H-thieno[2,3-d]pyrimidine-3,5-diones 2 were prepared via the reaction of a ternary mixture of 5,6-dimethyl-2-thioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-4-one (1), chloroacetic acid, and a proper aldehyde. Compound 2 reacted with hydroxylamine to afford 2,3-dihydro-7,8-dimethyl-3-substituted-9H-isoxazolo[5′,4′:4,5]thiazolo [3,2-a] thieno[2,3-d]pyrimidin-9-ones (4). Reaction of 1 with 3-chloropent-2,4-dione in ethanolic potassium hydroxide yielded the S-acetylacetone derivative 5d. The latter compound reacted with hydrazines and thiourea affording the 2-pyrazolthio and the 2-pyrimidinylthio derivatives 11 and 12, respectively. Compound 5d also underwent cyclization on boiling with acetic anhydride/pyridine solution to yield 2-acetyl-3,6,7-trimethyl-5H-thieno[2,3-d]thiazolo[3,2-a]pyrimidin-5-one (13). The 2-methylthioderivative 5a was converted into the corresponding 2-methyl sulphone derivative 9 on treatment with hydrogen peroxide.

2-CYANOETHANETHIOAMIDE IN HETEROCYCLIC SYNTHESIS: NOVEL SYNTHESIS OF THIENO[2,3-B]PYRIDINE, PYRAZOLO[3,4-B]PYRIDINE AND PYRIDOPYRAZOLO- 1,2,4-TRIAZINE DERIVATIVES

Abstract Several new synthesis of thieno[2.3-blpyridine, pyrazolo[3,4-b[pyridine and pyridopyrazolo-1,2,4-triazine derivatives via the reactions of pyridinethiones with halogenated compounds, hydrazine hydrate and active methylene compounds.

A NOVEL SYNTHESIS OF THIENO[2,3-b]PYRIDINE, PYRIDOTHIENOTRIAZINE AND PYRIDOTHIENOPYRIMIDINE DERIVATIVES

Abstract Pyridinethiones 1a,b prepared according to literature procedures1 were reacted with chloroacetamide (2), p-chlorophenacylbromide (8), α-chloroacetylacetone (11), ethylchloroacetate (15) to give 2-S-acetamidopyridines 3a,b, 2-S-aroylmethylpyridine 9[a]†, b, thieno[2,3-b]pyridines 3a,b and 2-S-ethoxycarbonylmethylpyridines 16a,b respectively. Cyclization reactions on 3a,b, 9b, and 16a,b to synthesize 4a,b, 10a,b and 17a,b respectively. Nitrous acid, acetic anhydride and formic acid had been used to build a new additional ring in 5a,b, 6a,b and 7a,b through their reactions with 4a,b. Hydrazidic acid derivatives 18a,b used as a synthons for the preparation of 2-pyrazoloylthieno[2,3-b]pyridines 21a,b, pyridothienopyrimidines 22a,b, and 2-hydrazonothieno[2,3-b]pyridines 21a-b, through their reactions with acetylacetone (20), formic acid and either aromatic aldehyde 23a,b or cinnamonitriles 24a,b respectively.

Pyridine-2(1H)-thione in Heterocyclic Synthesis: Synthesis of Some New Nicotinic Acid Ester, Thieno[2, 3-b]pyridine, Pyrido[3′, 2′: 4, 5]thieno [3, 2-d]pyrimidine, and Thiazolylpyrazolo[3, 4-b]pyridine Derivatives

Nicotinic acid esters 3a–c were prepared by the reaction of pyridine-2(1H)-thione derivative 1 with α-halo-reagents 2a–c. Compounds 3a–c underwent cyclization to the corresponding thieno[2, 3-b]pyridines 4a–c via boiling in ethanol/piperidine solution. Compounds 4a–c condensed with dimethylformamide-dimethylacetal (DMF-DMA) to afford 3-{[(N,N-dimethylamino)methylene]amino}thieno[2, 3-b]- pyridine derivatives 6a–c. Moreover, compounds 4a–c and 6a–c reacted with different reagents and afforded the pyrido[3′,2′:4, 5]thieno[3, 2-d]pyrimidine derivatives 10a–d, 11a–c, 12a,b, 14a,b, 17, and 19. In addition, pyrazolo[3, 4-b]pyridine derivative 20 (formed via the reaction of 1 with hydrazine hydrate) reacted with ethylisothiocyanate yielded the thiourea derivative 21. Compound 21 reacted with α-halocarbonyl compounds to give the 3-[(3H-thiazol-2-ylidene)amino]-1H-pyrazolo[3, 4-b]pyridine derivatives 23a–c, 25, and 27a,b.

Synthesis, Characterization, and Reactions of Pyridine-3-Carbonitrile Derivatives

2-Thioxopyridine-3-carbonitrile derivatives 6a-c reacted with several halogen containing reagents 7a-d to afford the corresponding thieno[2,3-b]pyridine derivatives 9a-l, respectively. Thieno[2,3-b]pyridines 9c, g,k used for the preparation of their corresponding carbohydrazide derivatives 10a-c which in turn, used as good synthons for the synthesis of N-phenylmethylenethieno[2,3-b]pyridine-2-carbohydrazides 13a–c, pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidinones 15a-c, 16a-c and 17 and 1,3,4-oxadiazole-2-thiols 20a-c and 21a-c via their reactions with benzaldehyde or benzylidenemalononitrile, triethylorthoformate and carbon disulfide followed by hydrazine hydrate respectively. Considering the data of IR, 1H NMR, mass spectra, and elemental analyses elucidated the chemical structures of the newly synthesized heterocyclic compounds.

Regioselective Synthesis and Reactions of a Polynuclear Heterocyclic Derived From Pyrido[2,3-d]pyrimidines With a New Ring System

2-thioxopyrido[2,3-d]pyrimidin-4-(1H)-ones 3 were synthesized by a reaction of α,β-unsaturated ketones with aminouracil. A series of pyrido[2,3-d]pyrimidine derivatives have been synthesized by a reaction of 3 with arylaldehydes, hydroxylamine hydrochloride, alkyl halides, arylazoketones, hydrazine hydrate, and thioureas to give a series of a new polynuclear heterocyclic ring added to parent compound 3 with a new ring system. 2-methylthio derivatives were converted to corresponding 2-methylsulphone derivatives 16 on treatment with hydrogen peroxide.