Alaa A. Hassan

Synthesis of novel pyrazole derivatives and evaluation of their antidepressant and anticonvulsant activities

Substituted carboxylic acid hydrazides 1a-d reacted with ethenetetracarbonitril 2 in dimethyl formamide with the formation of diacylhydrazines 4a-d and 5-amino-1-substituted pyrazole-3,3,4-tricarbonitriles 5a-d. On the other hand, 1a-d reacted with diethyl (E)-2,3-dicyanobutenedioate 3 to give oxadiazole derivatives 10a-d and pyrazolone derivatives 11a-d, respectively. The prepared compounds 4a-d, 5a-d and 11a-d were evaluated each for antidepressant activity using tail suspension behavioral despair test and anticonvulsant activity against PTZ induced seizures in mice. Compounds 4a and 4b induced markedly antidepressant activity compared to imipramine, and their activities as antidepressant nearly equal twice the activity of imipramine at 10 mg kg(-1) dose level. On the other hand, compounds 11b, 11a and 11d exhibited remarkable protective effect against clonic seizures induced by i.p. injection of PTZ at a dose level of 20 mg kg(-1). The results of anticonvulsant activity are nearly close to phenobarbital sodium at a dose level of 30 mg kg(-1) and more potent than phenytoin sodium at a dose level of 30 mg kg(-1).

REACTION OF DIIMINES AND BENZYNE

Abstract The reaction between benzyne and the Schiff bases 1a,b and 15a,b leads to the 1,4-bis(2‵-substituted acridin-10-yl)benzene 4a,b , the N-phenylarylamines 10a,b and the 10-(4‵-formylphenyl)-substituted acridines 11a,b (from 1a,b ) and the 2-substituted acridine-10-carboxyaldehyde 18a,b (from 15a,b ). Cyclohexyl (4-cyclohexyliminomethylbenzylidine)amine 1c reacts with benzyne by an ene-reaction to give cyclohexenyl[(4-cyclohexyliminomethylphenyl)benzylidine]amine 14 .

A novel synthesis of heterocycles from thiocarbohydrazides

SummaryThe reaction of thiocarbohydrazides1a and thiocarbazones1b with tetracyanoethylene (TCNE) afforded the thiazol, thiadiazole, thiazine, and thiadiazepine derivatives4–7. 2-Dicyanomethyleneindane-1,3-dione (CNIND) reacted with1a,b to give aminoindenopyrazolopyridazinone (12) and phenyl-1,2,3,4-tetraazacyclopentafluorene (13). The indazole and oxathiadiazole derivatives17 and19 were formed during the reaction of1b with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDO). 6,7-Dichloro-5-phenylpyrazolophthalazinol (21) was obtained from the reaction of1b with 2,3,5,6-tetrachloro-1,4-benzoquinone (CHL-p). The oxidative cyclization of thiodicarbazones2a–d with the above acceptors afforded the thiadiazole and thiadiazine derivatives8 and10.ZusammenfassungDie Reaktion der Thiocarbohydrazide1a und der Thiocarbazone1b mit Tetracyanoethylen (TCNE) ergab die Thiazol-, Thiadiazol-, Thiazin- und Thiadiazepinderivate4–7. 2-Dicyanomethylenindan-1,3-dion (CNIND) liefert mit1a,b Aminoindenopyrazolopyridazinon (12) und Phenyl-1,2,3,4-tetraazacyclopentafluoren (13). Die Indazol- und Oxathiadiazolderivate17 und19 wurden durch Reaktion von1b mit 1,3-Dichlor-5,6-dicyano-1,4-benzochinon (DDQ) gebildet. 6,7-Dichlor-5-phenylpyrazolophthalazinol (21) wurde aus1b und 2,3,5,6-Tetrachlor-1,4-benzochinon (CHL-p) erhalten. Die oxidative Cyclisierung der Thiodicarbazone2a–d mit den obengenannten Akzeptoren ergab die Thiadiazol- und Thiadiazinderivate8 und10.

Novel heterocyclics from 3-substituted-5H-1,2,4-triazino-[5,6-b]indoles and π-acceptors

Abstract The reaction of 1,2,4-triazino[5,6-b]indole-3-thione 1 with tetracyanoethylene (TCNE) afforded the disulfide 6 the tricyanovinylation product 8 and thiazolotriazinoindole 11. 3-Aryl-5H-1,2,4-triazino[5,6-b] indoles 2a,b reacted with TCNE to give pentacyanopropene 12 and 3-aminotriazinoindole derivatives 14a,b. 3-Hydrazino-5H-1,2,4-triazino[5,6-b]indole 3 reacted with TCNE, dicyanomethyleneindane-1,3-dione (CNIND)and 2,3-dicyano-1,4-naphthoquinone (DCNQ)to form triazolotriazinoindoles 17 and the triazepinotriazinoindoles 16,24 and 26. The reaction of 3, with chlorinated quinones gave the quinazolinetriones 21–23.

Chemical interactions between 2-mercaptobenzazoles and π-acceptors

Summary2-Mercaptobenzazoles (1a–c) interact with several π-acceptors such as tetracyanoethylene (TCNE) 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 2,3,5,6-tetrachloro-1,4-benzoquinone (CHL) dicyanomethyleneindane-1,3-dione (CNIND), 2,3-dicyano-1,4-naphthoquinone (DCNQ), 9-dicyanomethylene-2,4,7-trinitrofluorene (DTF), and 2,3-dichloro-1,4-naphthoquinone (DCHNQ)via the formation of charge-transfer (CT) complexes to yield various heterocyclic compounds.ZusammenfassungDie 2-Mercaptobenzazole1a–c reagieren mit verschiedenen π-Akzeptoren wie Tetracyanoethylen (TCNE), 2,3-Dichlor-5,6-dicyano-1,4-benzochinon (DDQ), 2,3,5,6-Tetrachlor-1,4-benzochinon (CHL), Dicyanomethylenindan-1,3-dion (CNIND), 2,3-Dicyano-1,4-naphthochinon (DCNQ), 9-Dicyanomethylen-2,4,7-trinitrofluoren (DTF) und 2,3-Dichlor-1,4-naphthochinon (DCHNQ) unter Ausbildung von charge transfer — Komplexen (CT) zu heterocyclischen Verbindungen.

CHEMICAL INTERACTIONS BETWEEN TETRACYANOETHYLENE AND S-METHYLDITHIOCARBAZATE AS WELL AS AZOMETHINE DERIVATIVES

Abstract The charge-transfer (CT) complexes of Schiff bases 2a-e derived from S-methyldithiocarbazate and tetracyanoethylene (TCNE) have been studied spectrophotometrically. S-methyldithiocarbazate 1 reacted with TCNE to yield 3-amino-4,5-dicyano-6-S-methyl-pyridazine 12 and 4,5-diamino-1,8-di-S-meth-ylpyridazino[4,5-d]pyridazine 13 via CT-complexes, whereas 2a-e reacted with TCNE to afford 3-aryl-4-amino-5-cyano-6-S-methylpyridazines 22 and 3-aryl-5-S-methyl-1,2,4-thiadizaoles 16.

SYNTHESIS OF PYRIDAZINE AND 1,3-THIAZINE DERIVATIVES VIA CT-COMPLEXATION BETWEEN THIOSEMICARBAZIDES AND TETRACYANOETHYLENE

Abstract Intermolecular charge transfer (CT) complexes of aromatic aldehyde thiosemicarbazones with some π-acceptors such as 7,7,8,8-tetracyanoquinodimethane, 2-(dicyanomethylene)indane-1,3-dione and 9-dicyanomethylene-2,4,7-trinitrofluorene have been studied spectrophotometrically. Aromatic aldehyde thiosemicarbazones, and thiosemicarbazide reacted with tetracyanoethylene via CT-complex formation to give 1,3-thiazine and pyridazine derivatives.

New reaction of ethenetetracarbonitrile with N-arylisoindolines

N-Arylisoindolines 1a - i react with ethenetetracarbonitrile 2 in aerated benzene by formation of (3-(2-aryl-3-dicyanomethylene- 2,3-dihydro-1H-isoindol-1-ylidene)-2-aryl-2,3-dihydro-1H-isoindol-1-ylidene)propanedinitriles 8a- i (20 - 36%), N-aryl-3-dicyano- methylene-isoindol-2-ones 9a - i (15 - 21%) and N-arylphthalimides 10a- i (4- 9%) as well as 1,1,2,2-tetracyanoethane 11 (35 - 55%). The structure of 8d has been unambiguously confirmed by a single crystal X-ray structure analysis. A rationale for the formation of products 8 - 11 is presented. q 2003 Elsevier Science Ltd. All rights reserved.

Synthesis and antibacterial activity of 4-aryl-2-(1-substituted ethylidene)thiazoles.

(E)‐4‐Aryl‐2‐[2‐(1‐substituted ethylidene)hydrazinyl]thiazoles and (Z)‐3‐substituted‐4‐aryl‐2‐[(E)‐(1‐phenylethylidene)hydrazono]‐2,3‐dihydrothiazoles were synthesized by the reaction of (substituted ethylidene)hydrazinecarbothioamides with ω‐bromoacetophenones. The characterization of this new class of compounds was performed using different spectroscopic tools. The structure of (Z)‐3‐benzyl‐4‐(4‐bromophenyl)‐2‐[(E)‐(1‐phenylethylidene)hydrazono]‐2,3‐dihydrothiazole 6e was unambiguously confirmed by single‐crystal X‐ray crystallography. Compounds 5a–e, 5i, 6e, 6g, and 6i were screened for their in vitro antibacterial activity against different strains of microorganisms; most of the tested compounds exhibited promising antibacterial activity against some organisms compared to ciprofloxacin and sulbactam penicillin. Compounds 5e, 5i, 6e, 6g, and 6i exhibited several‐fold significant antibacterial activity against the Gram‐positive bacteria Staphylococcus aureus, better than ciprofloxacin, with minimum inhibitory concentration values ranging from 0.05 to 0.4 µg/mL. The rest of the tested compounds gave significant antibacterial activities against different Gram‐negative bacterial strains.

Formation of 5-alkylidenepyrazol-4(1 H )-ones and 3-amino-6-aryl-5-cyanopyridazine-4-carboxylates from arenealdehyde thiosemicarbazones and unsaturated 1,2-diesters

The reaction of arenealdehyde 4-phenylthiosemicarbazones 1a–f with dimethyl ethynedicarboxylate (6) gave methyl [3-aryl-4-oxo-1-(phenylthiocarbamoyl)-4,5-dihydro-1H-pyrazol-5-ylidene]ethanoates 10a–f in 73-79% yield, while, by reaction with diethyl (E)-2,3-dicyanobutenedioate (7), compounds 1a–f are transformed into ethyl [3-aryl-4-oxo-1-(phenylthiocarbamoyl)-4,5-dihydro-1H-pyrazol-5-ylidene]cyanoacetates 15a–f (54-61%) and ethyl 3-amino-6-aryl-5-cyanopyridazine-4-carboxylates 24a–f (22-26%). Rationales for these transformations are presented.