Part 1: Synthesis of Polyfused Heterocyclic Systems Derived From 3-Phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6,8-dione

3-Phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6,8-dione ( 1 ) was condensed with o -aminothiophenol, 2-amino-ethanol or cystamine to afford compounds 2-4 respectively. Treatment of compound 1 with dimethylthiomethylenemalononitrile yielded the corresponding pyrano[3,2- f ][1,2,4]triazolo[3,4- b ]-[1,3,4]thiadiazepine derivative 5 . 7-[5-Amino-1,3-dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6,8-dione ( 6 ) was obtained by treating compound 1 with CS 2 and chloroacetonitrile. Thiation of compound 1 gave the corresponding thioanalog 7 , which in turn was condensed with malononitrile to give 3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6-one-8-ylidenemalononitrile ( 8 ). On treating compound 8 with benzaldehyde or p -nitrobenzaldehyde, pyrano[1,2,4]triazolo[1,3,4]thiadiazepin derivatives 9a , b , respectively, were obtained. Compound 8 was treated with CS 2 and methyl iodid to give the corresponding dithiomethylmethylene derivative 10 which was subjected to react with aniline to give pyrido[1,2,4]triazolo[1,3,4]thiadiazepine derivative 11 . Compound 8 was treated with 3-aminopyridine, o -aminothiophenol, or o -phenylenediamene to yield compounds 12 and 13a , b respectively. Finally, tertiary amines or activated phenols were condensed with compound 8 to yield compounds 14 and 15a , b respectively.     

Efficient Routes for the Synthesis of Novel Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines)

Bis(triazolo[3,4‐b]thiadiazine) 4 in which the fused system is linked directly to the benzene core can be synthesized in 75% yield by, firstly, preparation of bis(s‐triazole) 2 followed by reaction with phenacyl bromide 3 in refluxing EtOH/DMF mixture containing piperidine. Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) 8 and 11 in which the triazolothiadiazines are linked to benzene core via alkyl or ether linkage were synthesized in 70 and 72% yields, respectively, starting from dicarboxylic acids 5 and 9 upon treatment with two moles of thiocarbohydrazide 6 to give the corresponding bis(4‐amino‐5‐mercapto‐s‐triazolo‐3‐y1) derivatives 7 and 10 and subsequent reaction with two equivalents of phenacyl bromide. Bis(6‐phenyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines) 15a , 15b , 15c , 15d , 15e , 15f , which are linked to arene cores via sulfanylmethylene spacers, were prepared by the reaction of 4‐amino‐4H‐1,2,4‐triazole‐3,5‐dithiol 12 with the appropriate bis(bromomethyl)benzenes 13a , 13b , 13c , 13d , 13e , 13f to give bis(4‐amino‐5‐mercapto‐4H‐3‐sulfanylmethyl)arenes 14a , 14b , 14c , 14d , 14e , 14f and subsequent reaction with phenacyl bromide. Compounds 15a , 15b , 15c , 15d , 15e , 15f were alternatively obtained in 60–70% yields by twofold substitution of 13a , 13b , 13c , 13d , 13e , 13f with two equivalents of 6‐phenyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine‐3‐thiol 16 in refluxing EtOH/DMF mixture containing KOH. Bis(triazolothiadiazine) 22 attached to the benzene core through the thiadiazine ring via an amine linkage was prepared in 70% yield starting from p‐phenylenediamine 19 by, firstly, acylation with chloroacetyl chloride 18 followed by bis‐alkylation with 1,2,4‐triazole 20 and subsequent intramolecular ring closure upon treatment with phosphorus oxychloride.     

Synthesis and antimicrobial evaluation of some 1,2,4‐triazole, 1,3,4‐oxa(thia)diazole,and 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivatives

3‐Methyl‐2‐benzofurancarboxylic acid hydrazide ( 2 ) reacts with carbon disulfide and pota‐ ssium hydroxide to give the corresponding potassium carbodithioate salt 3 . Treatment of the latter salt with hydrochloric acid, hydrazine hydrate, and with phen‐ acyl bromide afforded the corresponding 1,3,4‐oxadia‐ zole‐5‐thione 4 , 4‐amino‐1,2,4‐triazole‐5‐thione 5 , and thiazolidine‐2‐thione 9 derivatives, respectively. The reaction of either 1,3,4‐oxadiazole‐5‐thione 4 or 4‐amino‐1,2,4‐triazole‐5‐thione 5 with phenacyl bromide resulted in the formation of 1,2,4‐triazolo[3, 4‐b]‐1,3,4‐thiadiazine derivative 8 . Treatment of compounds 3 or 4 with hydrazonoyl halides 10a–d furn‐ ished the same 1,3,4‐thiadiazol‐2‐ylidene derivatives 11a–d . The 7‐arylhydrazono‐1,2,4‐triazolo[3,4‐ b ]‐1, 3,4‐thiadiazine derivatives 12a–d were obtained either by treatment of 4‐amino‐1,2,4‐triazole‐5‐thione 5 with hydrazonoyl halides 10a–d or by coupling of the 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivative 8 with diazonium salts. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:621–627, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20162     

Bis(α‐bromo ketones): Versatile Precursors for Novel Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) and Bis(as‐triazino[3,4‐b][1,3,4]thiadiazines)

A synthesis of bis(α‐bromo ketones) 5a‐c and 6b,c was accomplished by the reaction of bis(acetophenones) 3a‐c and 4b,c with N‐bromosuccinimide in the presence of p‐toluenesulfonic acid (p‐TsOH). Treatment of 5a‐c and 6b,c with each of 4‐amino‐3‐mercapto‐1,2,4‐triazoles 9a,b and 4‐amino‐6‐phenyl‐3‐mercapto‐1,2,4‐triazin‐5(4H)‐ones 13 in refluxing ethanol afforded the novel bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) 10a‐d and 11a‐c as well as bis(as‐triazino[3,4‐b][1,3,4]thiadiazines) 14a‐c and 15 , respectively, in good yields. Compounds 11b and 11c underwent NaBH₄ reduction in methanol to give the target 1,ω‐bis{4‐(6,7‐dihydro‐3‐substituted‐5H‐1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)phenoxy}butanes 12a and 12b in 42 and 46% yields, respectively.     

Synthesis,Characterization, and Antimicrobial Evaluation of the Novel Triazolotriazolopyridines and Pyridotriazolotriazines

The starting compound 2‐hydrazinyl‐7‐(4‐methoxyphenyl)‐5‐oxo‐3,5‐dihydro[1,2,4]triazolo[1,5‐a ]pyridine‐6,8‐dicarbonitrile ( 5 ) was efficiently synthesized from 1,6‐diamino‐4‐(4‐methoxyphenyl)‐2‐oxo‐1,2‐dihydropyridine‐3,5‐dicarbonitrile ( 1 ). A novel series of polynuclear [1,2,4]triazolo[4′,3′:2,3][1,2,4]triazolo[1,5‐a ]pyridines 6 , 7 , 8 , 9 , 10 and pyrido[1′,2′:2,3][1,2,4]triazolo[5,1‐c ][1,2,4]triazines 11 , 12 , 13 , 14 , 15 have been synthesized. Structures of the newly synthesized products have been deduced on the basis of elemental analysis and spectral data. The synthesized compounds were screened for their antimicrobial activity.     

A Facile Synthesis of Aryl‐Substituted Hydrazono‐Pyrazolyl[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin Derivatives

Some inimitable and therapeutic coumarin‐substituted fused[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadizole derivatives were synthesized by the cyclocondensation reaction of 2‐oxo‐2H‐chromene‐3‐carboxylic acid ( 1 ) and 4‐amino‐5‐hydrazinyl‐4H‐[1,2,4]‐triazole‐3‐thiol ( 2 ) by using phosphorous oxychloride as a cyclizing agent. This cyclized intermediate 3‐(3‐hydrazino‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐chromen‐2‐one ( 3 ) later condensation with various ethyl 2‐(2‐arylhydrazono)‐3‐oxobutanoates ( 4 ) in NaOAc/MeOH under reflux conditions afforded the corresponding new series of aryl‐substituted hydrazono‐pyrazolyl‐[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin derivatives ( 5 ) in good to excellent yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, IR, ¹H NMR and mass spectroscopic studies.     

Synthesis,Acidity Constants and Tautomeric Structure of 7‐Arylhydrazono[1,2,4]Triazolo[3,4‐b][1,3,4]thiadiazines in Ground and Excited States

7‐Arylhydrazono[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines 4 were synthesized from the reactions of 4‐amino‐5‐phenyl‐4H‐[1,2,4]triazole‐3‐thiol 2 and 2‐(2‐naphthyl)‐2‐oxoethanehydrazonoyl bromides 1 and their acid dissociation constants pK and pK*, in the ground and excited states, respectively, were determined. Both pK and pK* constants were correlated by Hammett equation. The pK and the spectral data presented indicate that the title compounds exist predominantly in the hydrazone tautomeric form.     

Synthesis of Some New Fused and Polyfused [1,2,4]Triazolo-[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazepines

7-[1,3-Dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-6,8-dione and 7-[5-oxo-1,3-dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]-thiadiazepine-6,8-diones were obtained by treating 3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazepine-6,8-diones with CS₂ and chloroacetyl chloride, respectively. Treatment of the above compounds with mercaptoacetic acid gave 1,2-dibromoethane or the corresponding spiro polyfused heterocycles. Some other triazolothiadiazepine derivatives including spiro polyfused compounds were also synthesized. __________ Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1256–1264, August, 2005.     

Synthesis of Coumarin Substituted Triazolothiadiazine Derivatives via Ring Transformation Reaction

A novel ring transformation reaction for the synthesis of 3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones has been described. Reaction of 3‐(2‐bromoacetyl)coumarins ( 1 ) with 5‐aryl‐1,3,4‐oxadiazole‐2‐thiol ( 2 ) gave ketones ( 4a–h ). The in situ formed ketones ( 4a–h ) were reacted with hydrazine hydrate to give 3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones ( 3a–h ) and not 5 or 6 . The compounds ( 3a–h ) can also be prepared by the reaction of 3‐(2‐bromoacetyl)coumarins ( 1 ) with 5‐aryl‐1,3,4‐oxadiazole‐2‐thiol ( 2 ) in anhydrous ethanol to give corresponding 3‐(2‐(5‐aryl‐1,3,4‐oxadiazol‐2‐ylthio)acetyl)‐2H‐chromen‐2‐ones ( 4a–h ). These on reaction with hydrazine hydrate in acetic acid gave corresponding 3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones ( 3a–h ).     

Synthesis under microwave irradiation of [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazoles and other diazoles bearing indole moieties and their antimicrobial evaluation

Microwave-assisted synthesis of some novel compounds, namely, 3-(2-methyl-1H-indol-3-yl)-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a,b was accomplished via bromination of 2-methyl-3-[4-(arylideneamino)-5-mercapto-4H-[1,2,4]triazol-3-yl]-1H-indoles 3a,b. Also, new [1,3,4]thiadiazoles 12a,b, [1,2,4]triazoles 15a,b and [1,3,4]oxadiazoles 19a,b, with indole moieties, were prepared by cyclization of 1-[(2-methyl-1H-indole)-3-carbonyl]thiosemicarbazides 8a,b under microwave irradiation using different reaction conditions. Moreover, reaction of acid hydrazide 7 with ethyl 2-(N-phenylhydrazono)-3-oxobutanoate (20) gave the respective phenylhydrazonopyrazole derivative 21 under the reaction conditions employed. The structures of the synthesized compounds were assigned based on elemental analyses and spectral data (IR, (1)H-NMR, (13)C-NMR, MS). The antifungal and antibacterial activities of the new products were also evaluated.     

Heterocyclic synthesis containing bridgehead nitrogen atom: Synthesis of 3‐[(2H)‐2‐oxobenzo[b]pyran‐3‐yl]‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazine and thiazole derivatives

The reaction of 2H‐2‐oxobenzo[b]pyran‐3‐hydrazide ( 2 ) with carbon disulfide in basic DMF afforded potassium thiocarbamate 3 , which readily underwent heterocyclization upon its reaction with hydrazine and/or phenacyl bromide to yield 1,2,4‐tiazole ( 4 ) and thiazole 7 derivatives, respectively. Condensation of 4 with substituted phenacyl bromide and/or chloranil gave 1,2,4‐triazole[3,4‐b]thiadiazine ( 5a,b ) and 3,10‐bis‐[2H‐2‐oxobenzo[b]pyran‐3‐yl]‐6,13‐dichloro‐bis‐1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazino[5′,6′‐b:5′,6′‐e]cyclohexa‐1,4‐diene ( 6 ), respectively. Cyclization of thiosemicarbazide 10 by refluxing it in sodium hydroxide and/or phosphoryl chloride afforded triazole 13 and thiadiazole 15 derivatives, respectively. Also, 10 reacted with phenacyl bromide in the presence of anhydrous sodium acetate to give the oxothiazolidine derivative 17 . The structure of the synthesized compounds were confirmed by elemental analyses, IR, ¹H NMR, and mass spectra. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:114–120, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10109     

Synthesis of 6‐(5‐Methylisoxazol‐3yl)‐3‐alkyl Sulfanyl‐[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadiazoles

A new series of isoxazole substituted fused triazolo‐thiadiazoles have been synthesized by the cyclocondensation of 5‐methylisoxazole‐3‐craboxylic acid and 4‐amino 1,2‐4‐triazole‐ 3,5‐dithiol using phosphorous oxychloride. The cyclised intermediate 6‐(5‐methylisoxazol‐3‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole‐3‐thiol later on S‐alkylated with different alkyl halides in ethanol to give the title products in good to excellent yields.     

Synthesis of new derivatives of 3‐aryl‐1,5‐dimethyl‐1H‐[1,2,4]triazolo[4′,3′:1,2]pyrimido[4,5‐e][1,3,4]oxadiazines as potential antiproliferative agents

Starting from pyrimido[4,5‐e][1,3,4]oxadiazines ( 3a , 3b , 3c ) , a synthetic pathway to [1,2,4]triazolo[4′,3′:1,2]pyrimido[4,5‐e][1,3,4]oxadiazines ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i ) is described. The reaction of pyrimido[4,5‐e][1,3,4]oxadiazines ( 3a , 3b , 3c ) with hydrazine hydrate afforded the corresponding hydrazino derivatives ( 4a , 4b , 4c ) . Further treatment of these compounds with different orthoesters in acetic acid gave the corresponding [1,2,4]triazolo[4′,3′:1,2]pyrimido[4,5‐e][1,3,4]oxadiazines ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i ) . Compound ( 3a ) and ( 5b ) , as examples, were tested on different cancer cell lines including HeLa, MCF‐7, and HepG2. Malignant cells were cultured in DMEM medium and incubated with different concentrations of the titled compounds. Cell viability was quantitated by MTT assay. J. Heterocyclic Chem., (2010).     

Enaminones as building blocks for the synthesis of substituted pyrazoles with antitumor and antimicrobial activities

Novel N-arylpyrazole-containing enaminones 2a,b were synthesized as key intermediates. Reactions of 2a,b with active methylene compounds in acetic acid in the presence of ammonium acetate afforded substituted pyridine derivatives 5a-d. Enaminones 2a,b also reacted with aliphatic amines such as hydrazine hydrate and hydroxylamine hydrochloride to give bipyrazoles 8a,b and pyrazolylisoxazoles 9a,b, respectively. On the other hand, treatment of 2a,b with a heterocyclic amine and its diazonium salt yielded the respective [1,2,4]triazolo[4,3-a]pyrimidines 12a,b and pyrazolylcarbonyl[1,2,4]triazolo-[3,4-c][1,2,4]triazines 14a,b. Moreover, 2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one (17) was prepared via reaction of enaminone 2a with aminothiouracil (15). Cyclocondensation of 17 with the appropriate hydrazonoyl chlorides 18a-c gave the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-ones 21a-c. The cytotoxic effects of compounds 2b, 14a and 17 against human breast cell line (MCF-7) and liver carcinoma cell line (HEPG2) were screened and in both lines they showed inhibition effects comparable to those of 5-fluorouracil, used as a standard. The antimicrobial activity of some products chosen as representative examples was also evaluated.     

Synthesis of New Pyrimido[4,5‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine Derivatives via S/N Smiles Rearrangement

Several new pyrimido[4,5‐e ][1,2,4]triazolo[3,4‐b ][1,3,4]thiadiazine derivatives ( 5a , 5b , 5c , 5d , 5e , 5f , 5g ) were synthesized through the condensation reaction of 5‐bromo‐4,6‐dichloropyrimidine ( 1 ) and 4‐amino‐5‐methyl‐4H‐1,2,4‐triazole‐3‐thiol ( 2 ). The single crystal X‐ray data of one of the derivatives confirmed the occurrence of the S/N type Smiles rearrangement during the course of the reaction.     

Synthesis and isomerization of thienotriazolopyrimidine and thienotetrazolopyrimidine derivatives with potential anti‐inflammatory activity

Several derivatives containing the thieno[2,3‐d]pyrimidine system were prepared starting from 2‐amino‐4,5‐dihydronaphtho[2,1‐b]thiophene‐1‐carbonitrile ( 1 ). In particular, the synthesis and structure characterization of 8,9‐dihydronaphtho‐ [1′,2′:4,5]thieno[3,2‐e][1,2,4]triazolo[4,3‐c]pyrimidine derivatives 13–16 and their isomerization to 8,9‐dihydronaphtho[1′,2′:4,5]thieno[3,2‐e][1,2,4]‐triazolo[1,5‐c]pyrimidine derivatives 17–20 under different suitable reaction conditions were reported and verified with X‐ray analysis. Moreover, compounds 13, 14 and 22 were tested as potential anti‐inflammatory agents and derivative 14 showed potent activity in carrageenan test. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:226–234, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20114     

C5‐Alkyl‐1,3,4‐Oxadiazol‐2‐ones Undergo Dealkylation upon Nitrogen Insertion to Form 2H‐1,2,4‐Triazol‐3‐ones: Synthesis of 1,2,4‐Triazol‐3‐one Hybrids with Triazolothiadiazoles and Triazolothiadiazines

The present study emphasizes on the dealklylation of 3‐aryl‐5‐alkyl‐2‐oxo‐Δ⁴‐1,3,4‐oxadiazoles when reacted with formamide resulting in the formation of 2‐aryl‐2H‐1,2,4‐triazol‐3(4H )‐ones as major product. Subsequent reactions of 2‐aryl‐2H‐1,2,4‐triazol‐3(4H )‐one gave triazolo[3,4‐b ][1,3,4]thiadiazoles and triazolo[3,4‐b ][1,3,4]thiadiazines derivatives incorporated with 1,2,4‐triazol‐3‐one.     

New access to pyrazole,oxa(thia)diazole and oxadiazine derivatives

1,4‐Disubstituted thiosemicarbazides 1b–f reacted with ethenetetracarbonitrile ( 5 ) in di‐ methylformamide with formation of 2‐substituted 5‐phenyl‐1,3,4‐thiadiazoles 2a–f and 2‐substituted 5‐phenyl‐1,3,4‐oxadiazoles 4a–f . Upon addition of 5 to 1c–e in chlorobenzene, 3‐amino‐2‐benzoyl‐4,5,5‐tri‐ cyano‐2,5‐dihydro‐1H‐pyrazole‐1‐[N‐(4‐tricyanovi‐nyl)phenyl]carbothioamide ( 12 ), 5‐benzylamino‐, and 5‐allylamino‐4‐benzoyl‐2,3‐dihydro‐[1,3,4]thiadiazol‐ 2,2‐dicarbonitrile ( 13a,b ) and 5‐amino‐1‐benzoylpyrazole‐3,4‐dicarbonitrile ( 14 ) as well as 2‐phenyl‐ 4H‐[1,3,4]‐oxadiazine‐5,6‐dicarbonitrile ( 15 ) were formed. Rationales for the role of the solvent and the conversions observed are presented. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:12–19, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20071     

Synthesis and antimicrobial activity of some new pyrazole, fused pyrazolo[3,4-d]-pyrimidine and pyrazolo[4,3-e][1,2,4]-triazolo[1,5-c]pyrimidine derivatives

Hydrazonyl bromides 2a,b reacted with active methylene compounds (dibenzoylmethane, acetylacetone, ethyl acetoacetate, phenacyl cyanide, acetoacetanilide, ethyl cyanoacetate, cyanoacetamide and malononitrile) to afford the corresponding 1,3,4,5- tetrasubstituted pyrazole derivatives 5-12a,b. Reaction of 12a,b with formamide, formic acid and triethyl orthoformate give the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4- d]pyrimidin-4(3H)one and 5-ethoxymethylene-aminopyrazole-4-carbo-nitrile derivatives 13-15a,b, respectively. Compounds 15 a,b reacted with benzhydrazide and hydrazine hydrate to afford pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine and [4-iminopyrazolo- [3,4-d]pyrimidin-5-yl]amine derivatives 16 a,b and 17 a,b. Reactions of compounds 17 a,b with triethyl orthoformate and carbon disulfide give the corresponding pyrazolo[4,3-e]- [1,2,4]triazolo[1,5-c]pyrimidine derivatives 18a,b and 19 a,b, respectively.     

Synthesis of Triazoles,Oxadiazoles and Condensed Heterocyclic Compounds Containing Cinchopheny and Studies on Biological Activity of Representative Compounds

Compounds 2‐arylamino‐5‐cinchophenyl‐1,3,4‐oxadiazoline ( 7 ) and 3‐thio‐4‐amino‐5‐cinchophenyl‐1,2,4‐triazole ( 3 ) have been synthesized utilizing cinchophen as the starting material. The compound 3‐cinchopheny‐s‐triazolo[3,4‐b]‐1,2,3,4‐thiatriazole ( 4 ) was prepared from compound 3 . Condensation of 3 with aromatic acid in the presence of POCl₃ gave 10 new 6‐aryl‐3‐cinchopheny‐1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles ( 5 ). Some of the representative compounds were screened for antibacterial activity. The structures of these new compounds have been confirmed by means of elemental analysis, IR, ¹H NMR and MS.