A. M. Mahmoud

One pot synthesis of novel thiazolo[3,2-b][1,2,4]triazoles: A useful synthetic application of the acidified acetic acid method

Thiazolo[3,2-b][1,2,4]triazoles and some of its analogues were firstly synthesized starting from 3-benzyl-1,2,4-triazole-5-thiol (13). 3-Benzyl-1,2,4-triazole-5-thiol (13) was synthesized and reacted with aromatic ketones using the acidified acetic acid method (AcOH/H+) to give directly the cyclized 5-aryl-2-benzyl-1,3-thiazolo[3,2-b][1,2,4]triazoles (15a-f) rather the thioketones 14. The isomeric 2-benzyl[2,3-c]-1,2,4-triazoles 16 could not be obtained using this method. The reaction of 1-phenylacetyl-3-thiosemicarbazide (17) with phenyl bromomethyl ketones in refluxing ethanol afforded the 2-(phenylacetyl-hydrazino)-4-phenylthiazole (18) which, cyclized into 16a upon refluxing in POCl3. The tricyclic system 20a–d was successfully prepared in one pot reaction using the acidified acetic acid in high reaction yield and short reaction time. Formation of both 15a–l and or 16a–c was assigned by the molecular minimization energy (MME) calculations which indicated that the formation of 15 is more favorable than the isomeric compounds 16. Examination of the biological activity against the selected bacteria and fungi revealed that the title compounds possess significant growth promoting effect.

A convenient one-pot synthesis of 2-benzimidazolyl-thioacetophenones and thiazolo[3,2-a]benzimidazoles

Abstract 2-Mercaptobenzimidazole ( 1 ) reacts with aromatic ketones 2a-d in acidified acetic acid giving 2-benzimidazolylthioacetophenones 3a-d . Which on cyclization yield thiazolo[3,2-a]-benzimidazoles 4a-d . Acetylation of 3a,d gave the N-acetyl derivatives 5a,d . Cyclization of 3a-d or 5d in acetic anhydride or acetic anhydride / pyridine mixture afforded 6a-d . While reaction of 1 with aliphatic or alicyclic ketones gave directly 2,3-disubstituted thiazolo[3,2-a]benzimidazoles 7a-f and 8a-d respectively.

Synthesis and Studies of Triazolothiadiazines. An Approach Toward New Biologically Active Heterocyclic Compounds

The first synthesis of the 1,2,4-triazolo[5,1-b][1,3,5] thiadiazine and some of its analogues, possessing a thiadiazino-s-triazole bicyclic ring system was performed starting from 2-benzyltriazole-5-thiol. The title compounds 6a–g were synthesized via double Mannich reaction in one step in high yields. The route employed the nucleophilic addition of two moles of CH 2 O onto the NH and SH groups of the triazole ring followed by cyclocondensation with elimination of two H 2 O molecules to form the thiadiazine derivatives. Examination of the biological activity against the selected fungi and bacteria is the main goal of this article. The tested compounds against fungi revealed that the title compounds were active against most strains of fungi, while the tested compounds were inactive against Gram +Ve and Gram –Ve bacteria. All new synthesized compounds were confirmed using the spectral analyses and the direction of the cyclization was confirmed using the molecular mechanics calculations.

Studies on the Synthesis and Cyclization Reactions of2-(5-Amino-3-arylpyrazol-1-yl)-3-methylquinoxalines

A series of2-(5-amino-3-arylpyrazol-1-yl)-3-methylquinoxalines (2a–d)has been synthesized by the condensation of2-hydrazino-3-methylquinoxaline (1) with substitutedbenzoylacetonitriles and converted into the corresponding3,4-diaryl-1-(3-methylquinoxalin-2-yl)-4,8-dihydro-1H -pyrazolo[3,4-e ][1,4]thiazepin-7(6H )-ones(7a–d) and2-(3-aryl-4,5,6,7-tetrahydro-5-alkyl/aryl-1H -pyrazolo[3,4-d ]pyrimidin-1-yl)-3-methylquinoxalines(8a–e).

A Convenient One-Pot Synthesis of Pyrazolo[3,4-d]pyrimidines and s-Triazolo[3,4-b][1,3,5]thiadiazines

Abstract The reaction of 5-amino-3-aryl-1-phenylpyrazoles (1a-d) with formaldehyde and secondary amines in boiling ethanol gave the corresponding 4-alkylaminomethyl derivatives (2a-f) and bis-(4-pyrazolyl)methane (4a,b) as byproduct. Such reaction with primary aliphatic and aro matic amines at room temperature afforded 1,3,5-trisubstituted (5a-h) and 1,3.5,7-tetrasubstituted tetrahydropyrazolo[3,4-d]pyrimidines (8a-k) respectively in good yield. Similarily, the Mannich reaction of 5-mercapto-3-phenyl-1,2,4-triazole (9) with secondary amines, in boiling ethanol, and primary aromatic amines, at room temperature, gave 2 -substituted aminomethyl derivatives (10a-c) and (14a-g) respectively,while with primary aliphatic amines, p-toluidine and p-anisidine,at room temperature,and with other primary aromatic amines, in boiling ethanol, afforded the cyclized products 12,4-triazolo[3,4-b]thiadiazines (13a-e); (15f,g) and (15a-e), respectively.

Synthesis and reactions of new 4-chloro-2-methylpyrimidino[4′,5′:4,5]thiazolo[3,2-a]-benzimidazoles

Summary4-Chloro-2-methylpyrimidino[4′,5′:4,5]thiazolo[3,2-a]benzimidazole (3) was prepared by chlorination of2 which could also be converted directly to 2-methylpyrimidino[4′,5′:4,5]-thiazolo[3,2-a]benzimidazol-4-thiol (4). Nucleophilic substitution of3 with alcohols, phenols, primary amines, secondary amines, sodium azide, and mercaptoacetic acid gave the corresponding derivatives. The thiol derivative4 was reacted with alkyl/aralkyl halides, phenacyl bromide derivatives, bromoacetone, chloroanilides, bromomalonic ester, and ethyl bromoacetate to afford compounds of potential pharmacological interest.Zusammenfassung4-Chlor-2-methylpyrimidino[4′,5′:4,5]thiazolo[3,2-a]benzimidazol (3) wurde durch Chlorierung von2, welches auch direkt zu 2-Methylpyrimidino[4′,5′:5,4]thiazolo[3,2-a]-benzimidazol-4-thiol (4) umgesetzt werden kann, hergestellt. Nucleophile Substitution von3 mit Alkoholen, Phenolen, primären Aminen, sekundären Aminen, Natriumazid und Mercaptoessigsäure ergab die entsprechenden Derivate. Das Thiolderivat4 wurde mit Alkyl/Alkarylhalogeniden, Phenacylbromidderivaten, Bromaceton, Chloraniliden, Brommalonsäureester und Bromessigsäureethylester zu potentiell pharmakologisch interessanten Verbindungen umgesetzt.