Synthesis and antimicrobial activity of new 1,2,4-triazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole,thiopyrane, thiazolidinone,and azepine derivatives

4-oxo-4-phenylbutanehydrazide 3 was reacted with aryl or alkyl isothiocyanates to give the corresponding N-substituted-2-(4-oxo-4-phenylbutanoyl) hydrazine-1-carbothioamide 4a-c . Cyclization of thiosemicarbazides 4a-c with sodium hydroxide led to the formation of 3-(4-sub-5-thioxo-1,2,4-triazol-3-yl)-propanone 5a-c . Desulfurization of thiosemicarbazides 4a-c by mercuric oxide afforded 3-(5-(sub-amino)-1,3,4-oxadiazol-2-yl)-propanone 6a-c . The reaction of 4a-c with phosphorus oxychloride gave 3-(5-(sub-amino)-1,3,4-thiadiazol-2-yl)-propanone 7a-c . Treatment of 4a-c with ethyl-bromoacetate or α-bromopropionic acid gave N′-(3-sub-thiazolidin-2-ylidene)-butanehydrazide 8a-c and (N′-(3-sub-oxothiazolidin-2-ylidene)-butanehydrazide 9a-c . Chlorination of oxothiazolidine-hydrazide 9a-c by phosphorus oxychloride afforded N-(3-sub-4-oxothiazolidine)-butane-hydrazonoyl-chloride 10a-c . The reaction of 10a-c with mercaptoacetyl-chloride yielded 2-((4-benzoyl-thiopyrane) hydrazono)-3-sub-thiazolidinone 11a-c . Also, reacted of 10a-c with hydrazine hydrate afforded N″-(3-sub-oxothiazolidine)-butane-hydrazon-hydrazide 12a-c . The 3-sub-2-((pyridazine) hydrazono) thiazolidinone 13a-c was obtained by cyclization of 12a-c via refluxing in DMF. The reaction and cyclized of 9a-c with chloroacetyl-chloride in ethanolic KOH afforded 1-((3-sub-4-oxothiazolidine) amino)-azepine-dione 14a-c . The chemical structures of the new compounds have been confirmed by diverse spectroscopy analyses such as IR, NMR, MS, and elemental analysis. The synthesized compounds were tested for their antimicrobial activity and these compounds were considered (Pyridazin-hydrazono-thiazolidinone 13a-c , oxothiazolidin-azepinedione 14a-c , N-thiazolidin-hydrazon-hydrazide 12a-c , and thiopyran-hydrazono-thiazolidinone 11a-c ) the most effective as antimicrobial activity.     

Synthesis,characterization, and biological activities of some novel thienylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines and related heterocycles

3-Cyano-5-ethoxycarbonyl-6-methyl-4-(2′-thienyl)-pyridine-2(1H)-thione ( 1 ) is synthesized and reacted with chloroacetamide or chloroacetonitrile to give 3-amino-5-ethoxycarbonyl-6-methyl-4(2′-thienyl)-thieno[2,3-b]pyridine-2-carboxamide 3a or its 2-carbonitrile analog 3b , respectively. Cyclocondensation of 3a with triethylorthoformate produced the corresponding pyridothienopyrimidineone 4 , which on heating with phosphorus oxychloride gave 4-chloropyrimidine derivative 5 . Compound 5 was used as key intermediate for synthesizing compounds 6 , 9 , 10 , 11 , and 12 upon treatment with some nucleophilic reagents such as thiourea, 5-phenyl-s-triazole-3(1H)-thione, piperidine, morpholine, or hydrazine hydrate, respectively. Reaction of pyridothienopyrimidinethione 6 with N-(4-tolyl)-2-chloroacetamide or ethyl bromoacetate afforded the corresponding S-substituted methylsulfanylpyrimidines 7 or 8 . The condensation of 3b with triethylorthoformate gave azomethine derivative 13 , which was reacted with hydrazine hydrate to give ethyl 3-amino-3,4-dihydro-4-imino-7-methyl-9-(2′-thienyl)pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-8-carboxylate ( 14 ). Compounds 12 and 14 were used as precursors for synthesizing other new thienylpyridothienopyrimidines as well as isomeric thienyl-s-triazolopyridothieno- pyrimidines. All synthesized compounds were characterized by elemental and spectral analyses such as IR, ¹H NMR, and ¹³C NMR. In addition, majority of synthesized compounds were tested for their antifungal activity against five strains of fungi. Moreover, compounds 3a , 5 , 6 , 8 , and 22 were screened for their anticancer activity against HEPG-2 and MCF-7 cell lines.     

A new domino reaction based on [4+2]-cycloadditions of pyrido[1,2-a]pyrazines with azadienophiles

The reaction of pyrido[1,2-a]pyrazines 1 with nitroso compounds 2 provides pyridyl substituted 1,2,4-triazinones 4 via a domino reaction which involves a cycloaddition and a ring transformation reaction. The intermediate and regioselective formed oxadiazines 4′ were trapped by complexation yielding the (CO)₄Mo-complex 5. Derivatives of diazene such as N-phenyltriazolindione 6a , phthalazinedione 6b or esters of azodicarboxylic acid 6c-6f reacted with 1 to give different derivatives of 1,2,4-triazine 7a-f . The use of oxygen gave oxadiazinones 8 .     

The 1,3-Dipolar Cycloadditions of Nitrile Oxides and Nitrile Imines to Alkyl Dicyanoacetates

The readily available alkyl dicyanoacetates 1 reacted with the 1,3-dipolar reagents arenecarbonitrile oxides 2 ′ and arenecarbonitrile imines 5 ′ to afford 1,2,4-oxadiazol and 1,2,4-triazol derivatives. The arenecarbonitrile oxides 2 ′ with electron-donating groups on the arene ring gave products 3a – d resulting from addition on both CN groups of 1 , and those with electron-withdrawing groups provided mono-adducts 4a – e (Scheme 1). Arylnitrile imines 5 ′ reacted with 1 to offer both bis- and mono-addition products (Scheme 2); the bis-adducts 8a , b possess an ester structure, whereas the mono-adducts 6a – d present a ketene-hemiacetal structure.     

Synthesis of New Fused and Spiro Heterocyclic Systems from 3,5‐Pyrazolidinediones

4‐Bromo‐1‐phenyl‐3,5‐pyrazolidinedione 2 reacted with different nucleophilic reagents to give the corresponding 4‐substituted derivatives 3–8 . The cyclized compounds 9–11 were achieved on refluxing compounds 3 , 4 or 6_a in glacial acetic acid or diphenyl ether. 4,4‐Dibromo‐1‐phenyl‐3,5‐pyrazolidinedione 12 reacted with the proper bidentates to give the corresponding spiro 3,5‐pyrazolidinediones 13–15 , respectively. The 4‐aralkylidine derivatives 16_a‐c , were subjected to Mannich reaction to give Mannich bases 17_a‐c‐22_a‐c , respectively. 4‐(p‐Methylphenylaminomethylidine)‐1‐phenyl‐3,5‐pyrazolidinedione 23 or 4‐(p‐methylphenylazo)‐1‐phenyl‐3,5‐pyrazolidinedione 29 were prepared and reacted with active nitriles, cyclic ketones and N,S‐acetals to give pyrano[2,3‐c]pyrazole, pyrazolo[4′,3′:5,6]pyrano[2,3‐c]pyrazole, spiropyrazole‐4,3′‐pyrazole and spiropyrazole‐4,3′‐[1,2,4]triazolane derivatives 24–34 , respectively.     

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 thiazolium betaines and the ring expansion reaction via 1,4-dipolar cycloaddition

The 1,4-dipolar cycloaddition of 3-phenyl-7-[N-pheny(carbamoyl)]-5,6-dihydroimidazo[2,1-b]thia-zolium betaine (7d) with a series of aliphatic alkylating agents such as ethyl bromoacetate, α-chloroacetone, and ethyl 4-chloroacetoacetate gave a variety of new ring-expanded cycloadducts 10a-c instead of ring transformation compounds 9 . This result was derived from the difference of reactivity between N- and S-alkylations of thiazolium betaines 7a,d. The advantage of our method is to prepare the triheterocyclic compounds 10a-c of complicated structure using reactive thiazolium betaine 7d in a one-pot without isolation of intermediates. Treatment of N-bridged thiazolo compounds 1a-c with benzoyl isothiocyanate led to new thiazolium betaines 2a-c , which were reacted with methyl iodide to afford the S-alkylated quarternary ammonium salts 3a-c. Synthesis of new 2-iminothiazolinium betaines 5a,b also was carried out.     

Alkyl heterocycles in heterocyclic synthesis (II): Novel synthesis of isoquinoline,thiazolopyridine, and thieno[2,3‐b]pyridine derivatives

Treating 5‐(4‐phenylcarboxamido)‐3‐cyano‐4‐methylpyridin‐2(1H)thione ( 3 ) with elemental sulfur yielded thienopyridine 4 . Compound 4 reacts with acrylonitrile to give isoquinoline 7 . Compound 7 was also, prepared from 3 and methylenemalononitrile. Reaction of 3 with dimethylacetylene dicarboxylate (DMAD) gave the pyridothiazole 9 . Also, 3 reacted with N,N‐dimethylchloroacetamide ( 10 ) to afford compound 11 which further reacted with the reagents 12 , 13 and 14 providing the thieno[2,3‐b]pyridine derivatives 15 , 16 and 17 respectively.     

Reactions of 2-hydroxybenzonitrile with isocyanates

Triethylamine catalyzes the reaction of 2-hydroxybenzonitrile ( 1 ) with aryl isocyanates to form the corresponding carbamates 2a-c , as well as the cyclization of the latter compounds to either 4[N-(N-arylcarbamoyl)-imino]-3-aryl-2H-1,3-benzoxazin-2-ones 4a-c , or 4-arylamino-2H-1,3-benzoxazin-2-ones 7a-c , depending on the reaction temperature. Under analogous conditions, the carbamates obtained from 1 and 2-chloroethyl isocyanate, 3-chloropropyl isocyanate and ethyl isocyanatoacetate undergo a double cyclization yielding imidazo- and pyrimido[1,2-c|1,3]benzoxazinones 13a,b,17 . Upon heating in phenyl ether, compounds 7a-c , rearrange to 2-(2-hydroxyphenyl)-4(3H)-quinazolinones 10a-c .     

Synthesis of Pyrimidines,Thienopyrimidines, and Pyrazolopyrimidines

5-Ethoxycarbonyl-4-methyl-2-phenylpyrimidin-6(1H)-thione ( 3 ), which was prepared from the reaction of ethyl g -aminocrotonate 1 with benzoyl isothiocyanate ( 2 ) in refluxing acetone, was reacted with a series of halopgenated reagents to give S-alkyl derivatives 4a-g . Upon treatment of compounds 4a-c with sodium ethoxide were cyclized into thienopyrimidine 10a-c . Pyrimidinethione 3 was reacted with hydrazine hydrate to give hydroxypyrazolopyrimidine derivative 6 . The later compound was obtained by heating compound 4a with hydrazine hydrate under neat conditions, but when the reaction was carried using hydrazine hydrate in ethanol, the corresponding carbohydrazide 5 was produced.     

Synthesis of Fused Azoles and N-Heteroaryl Derivatives Based on Pyrano[2,3-c]Pyrazole

. Condensation of 3 with different reagents gave 3-substituted-1,2,4-triazolo[1,5-c]pyrimidine and tirazolo[3,4-c]pyrimidine derivatives 4, 5, 8a,b, 9a,b, 11, 12a-c,14,15 respectively. Interaction of 1 with formic acid afforded N-formyl derivative 17. The formation of 16 took place in trifluoroacetic acid.     

Synthesis and analgesic activity of some new pyrazoles and triazoles bearing a 6,8-dibromo-2-methylquinazoline moiety

2-(6,8-Dibromo-2-methylquinazolin-4-yloxy)-acetohydrazide (4) was prepared by the reaction of 6,8-dibromo-2-methylbenzo-[d][1,3]oxazin-4-one with formamide to afford quinazolinone 2, followed by alkylation with ethyl chloroacetate to give the ester 3. Treatment of ester 3 with hydrazine hydrate and benzaldehyde afforded 4 and styryl quinazoline 5. The hydrazide was reacted with triethyl orthoformate, acetylacetone and ethyl acetoacetate and benzaldehyde derivatives to afford the corresponding pyrazoles 6, 7, 9 and hydrazone derivatives 10a-c. Cyclization of hydrazones 10a-c with thioglycolic acid afforded the thiazole derivatives 11a-c. Reaction of the hydrazide with isothiocyanate derivatives afforded hydrazinecarbothioamide derivatives 12a-c, which cyclized to triazole-3-thiols and thiadiazoles 13a-c and 14a-c, respectively. Fusion of the hydrazide with phthalimide afforded the annelated compound 1,2,4-triazolo[3,4-a]isoindol-5-one (15). The newly synthesized compounds were characterized by their spectral (IR, 1H-, 13C-NMR) data. Selected compounds were screened for analgesic activity.     

Synthesis and structure of dihydro-1,2,4-triazin-6(1H) ones

Reactions of the iminoesters 3a-c with hydrazine or 1,2-dimethylhydrazine gave 4,5-dihydro- 4a-c or 2,5-dihydro-1,2,4-triazin-6(1H) ones 7a-c , respectively. When methylhydrazine was employed, 1-methyl-4, 5-dihydro- 5a-c and 2-methyl-2,5-dihydro-1,2,4-triazin-6(1H) ones 6a-c were obtained. Compounds 6a-c exist as zwitterions in the solid state and in polar aprotic solvents.     

Synthesis and Biological Evaluation of Some Heterocyclic Compounds from Salicylic Acid Hydrazide

Different heterocyclic compounds were prepared starting from 2‐hydroxy benzohydrazide; for example, cyclization of hydrazide hydrazone 3 derived from 2‐hydroxybenzohydrazide 2 with acetic anhydride or concentrated sulfuric acid gave 1,3,4‐oxadiazole derivatives 4 – 5 . On the other hand, direct cyclization of 2‐hydroxy benzohydrazide 2 with one carbon cyclizing agent gave a new derivative of 1,3,4‐oxadiazole 7 , 8 , 9 , 10 , 11 . Heating of hydrazide hydrazone 3 with thioglycolic acid in pyridine gave thiazolidinone 12 . When 2‐hydroxy benzohydrazide 2 reacted with aliphatic carboxylic acids such as formic acid or acetic acid, it gave the corresponding N‐formyl or N‐acetyl derivatives 6 . Subsequent cyclization of 6 using phosphorous pentasulphide in pyridine gave 1,3,4‐thiadiazoles 13 . Cyclization of 2‐hydroxy benzohydrazide with ethyl acetoacetate gives pyrazolone derivative 14 . Finally, when an ethanolic solution of acid hydrazide 2 was treated with ammonium thiocyanate in 35% HCl, it gave the thiosemicarbazide 15 . Subsequent treatment of 15 with concentrated sulfuric acid or 10% sodium hydroxide gave 5‐amino‐1,3,4‐thiadiazole 16 and 1,2,4‐triazole 17 , respectively. The structures of all newly isolated compounds were confirmed using ¹H NMR, IR spectra, and elemental analyses. The antimicrobial activities for all isolated compounds were examined against different microorganisms.     

Syntheses of substituted-oxazolo-1,3,4-thiadiazoles, 1,3,4-oxadiazoles,and 1,2,4-triazoles

Starting from readily available methyl 5-methyloxazole-4-carboxylate ( 1 ) and 4-methyl-5-oxazolylcar-boxylic acid hydrazide ( 11 ) the title compounds were prepared. The reaction of compound 1 with hydrazine hydrate afforded the corresponding hydrazide 2 . The reaction of compound 2 with formic acid yielded 1-formyl-2-(5-methyloxazole-4-carboxyl)hydrazine ( 3 ). Refluxing of the latter with phosphorus pentasulfide in xylene gave compound 5 in 62% yield. The reaction of compound 3 with phosphorus pentoxide afforded compound 4 . Starting from hydrazide 11 , compounds 13 and 14 were prepared similarly. Reaction of compound 2 with substituted isothiocyanate yielded compound 9 which was cyclized in basic medium to 4-alkyl-5-(5-methyl-4-oxazolyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione ( 10 ). The isomer 19 was prepared similarly. Methylation and subsequent oxidation of compound 19 gave compound 21 . Reaction of the acid 7 with thiosemicarbazide in the presence of phosphorus oxychloride gave 2-amino-5-(5-methyl-4-oxazolyl)1,3,4-thiadiazole ( 8 ). 2-Amino-5-(4-methyl-5-oxazolyl)-1,3,4-thiadiazole ( 17 ) was prepared from acyl chloride 15 by the usual method.     

Furopyridines. XXIV. Nitration,chlorination, acetoxylation and cyanation of 2,3-dihydrofuro[2,3-b]-, -[3,2-b]-, -[2,3-c]- and -[3,2-c]pyridine N-Oxides

Nitration of 2,3-dihydrofuro[3,2-b]- N-oxide 3b and -[2,3-c]pyridine N-oxide 3c afforded the nitropyridine compounds 4b, 5b and 6 from 3b and 4c, 5c, 5′c and 7 from 3c , while -[2,3-b]- N-oxide 3a and -[3,2-c]pyridine N-oxide 3d did not give the nitro compound. Chlorination of 3b and 3c with phosphorus oxychloride yielded mainly the chloropyridine derivatives 15b, 15′b from 3b and 15c and 15′c from 3c , whereas 3a and 3d gave pyridine derivatives formed through fission of the 1–2 ether bond of the furo-pyridines 13a , 14 and 13d . Acetoxylation of 3b and 3c gave 3-acetoxy derivatives 18b and 18c and the parent compound 1b and 1c . Acetoxylation of 3a yielded compounds formed through fission of the 1–2 bond 16 and 17 and 3d gave furopyridones 19 and 19 ′. Cyanation of 3b and 3c yielded mainly the cyanopyridine compounds 20b, 20c and 20′c . Cyanation of 3a and 3d gave the cyanopyridine compounds 20a , 20d and 20′d accompanying formation of the pyridine derivatives 21a, 21d and 21′d .     

Synthesis and Characterization of New Heterocyclic Compounds Containing Thienylbenzo[h]Quinoline Moiety

In this paper the reaction of 2‐(2′‐thienylmethylene)‐3,4‐dihydronaphthalen‐2(1H)‐one ( 1 ) with cyanothioacetamide gave a mixture of 3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2(1H)‐thione ( 2 ) and the related disulfide 3 . Compound 2 was reacted with some halo compounds namely; ethyl chloroacetate, chloroacetamide, chloro(N‐(p‐chlorophenyl))acetamide, N¹‐chloroacetylsulfanilamide, and 2‐chloromethyl‐1H‐benzimidazole to produce a series of 2‐(substituted)methylthio‐3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)benzo[h]quinolines 4a , 4b , 4c , 4d , 4e and 11 . Upon heating the latter compounds with sodium ethoxide, they underwent intramolecular Thorpe–Zeigler cyclization to furnish the corresponding 2‐(substituted)‐3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]thieno[2,3‐b]quinolines 5a , 5b , 5c , 5d , 5e and 12 . (3‐Cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2‐ylthio)acethydrazide ( 8 ) and the related isomer, 3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)thieno[2,3‐b]benzo[h]quinoline‐2‐carbohydrazide ( 9 ), were also synthesized. Most of the aforementioned compounds were used as key intermediates for synthesizing other benzo[h]quinolines, benzo[h]thieno[2,3‐b]quinolines as well as benzo[h]pyrimido[4′,5′:4,5] thieno[2,3‐b]quinolines. The structure of all synthesized compounds was confirmed by spectroscopic measurements and analytical analyses.     

Synthesis of nitrogen‐containing heterocycles 9. Preparation and carbon‐carbon bond cleavage of spiro[cycloalkane[1′,2′,4′]‐triazolo[1′,5′‐a][1′,3′,5′]triazine] derivatives and related compounds

Diaminomethylenehydrazones of cyclic ketones 1–5 reacted with ethyl N‐cyanoimidate (I) at room temperature or with bis(methylthio)methylenecyanamide (II) under brief heating to give directly the corresponding spiro[cycloalkane[1′,2′,4′]triazolo[1′,5′,‐a][1′,3′‐5′]triazine] derivatives 7–12 in moderate to high yields. Ring‐opening reaction of the spiro[cycloalkanetriazolotriazine] derivatives occurred at the cycloalkane moiety upon heating in solution to give 2‐alkyl‐5‐amino[1,2,4]triazolotriazines 13–16. Diaminomethylenehydrazones 17–19, of hindered acyclic ketones, gave 2‐methyl‐7‐methylthio[1,2,4]‐triazolo[1,5‐a][1,3,5]triazines 21–23 by the reaction with II as the main products with apparent loss of 2‐methylpropane from the potential precursor, 2‐tert‐butyl‐2‐methyl‐7‐methylthio[1,2,4]triazolo[1,5‐a]‐[1,3,5]triazines 20, in good yields. In general, bis(methylthio)methylenecyanamide II was found to be a favorable reagent to the one‐step synthesis of the spiro[cycloalkanetriazolotriazine] derivatives from the diaminomethylenehydrazones. The spectral data and structural assignments of the fused triazine products are discussed.     

CHLOROSULFONATION OF SOME CRISSCROSS CYCLOADDUCTS FROM ISOCYANATES AND DIARYL AZINES

Abstract

Reaction of chlorosulfonyl isocyanate (1) with arylaldehyde azines (7) gave the 2:1 crisscross adducts (8);attempts to prepare a disulphonamide of 8a gave only a mixture of the monosulfamide 9 and the diureide 10. The latter with trichloromethanesulfenyl chloride afforded the derivative 12a. and with chlorosulfonic acid hydrazinodicarbonamide (11). The azine 7a with benzoyl isocyanate (2) gave the expected crisscross adduct 13. With thiobenzoyl isocyanate (3) however, both 7a and 7d gave the 1: 1 adducts (14). whereas 7c gave a different 2: 1 adduct (15). Treatment of 14a with 1 gave the ureide 16. With both methyl isocyanate (4) and phenyl isocyanate (S), 7a gave the expected crisscross adducts (17a and b), and 7c with 5 similarly gave 17c. When 7a was treated with 1 followed by aqueous potassium iodide, the diureide (10) was formed; concentrated nitric acid converted 10 into the triazolenone (18). Treatment of 18 with chlorosulfonic acid-thionyl chloride gave the sulfonyl chloride (19) which was characterised as the sulfonamides (20 a-d).

Diarylsulfamoyl azines (21 a-f) with 1 and potassium iodide, gave the diureides 22 a-f. 4-Methoxy-3-sulfamoylbenzaldehydeazines (23 a-c) reacted with 3 to give the 1: I adducts 24 a-c, while 4-chlorosulfonylphenyl isocyanate (6) with benzaldehyde azine (7a) gave the bis-chlorosulfonyl adduct (25a). characterised as the diethylsulfonamide 25b. Attempted chlorosulfonation of the tetraphenyl cycloadduct 17b did not give the tetrasulfonyl chloride (although the reaction was successful with the more reactive rnethoxy adduct 17c); the tetrasulfonyl chloride (26a) was converted into 3 sulfonamides (26 b-d). The unsymmetrically-substituted diaryl azines (27) reacted with 1 and potassium iodide to yield the diureides 28 a-f. Analogous cycloadditions of 1 with several keto azines were unsuccessful. Selected compounds will be screened for medicinal and pesticidal activity; compounds 9,10 and 12a showed fungicidal activity against barley powdery mildew.     

Synthesis and Molluscicidal Activity of Phosphorus-Containing Heterocyclic Compounds Derived from 5,6-Bis (4-bromophenyl)-3-hydrazino-1,2,4-triazine

Novel N¹-(phosphoryl moiety)-N²-(1,2,4-triazin-3-yl)hydrazines 4, 6, 8, 9 and 12, iminophosphorane 3, iminophosphane 5, 1,2,4-triazinyldiazaphospholine 7, 1,2,4,3-triazaphospholinotriazines 2, 10, 11, and 1,2,4-triazino[3,2-c][1,2,4,5] triazaphosphine 13 have been obtained via treatment 5,6-bis(4-bromophenyl)-3-hydrazino-1,2,4-triazine (1) with various polyfunctional phosphorus reagents by stirring at room temperature or refluxing for long time in tetrahydrofuran. Structures of these compounds have been deduced upon the basis of elemental and spectral data. Molluscicidal activity of the prepared compounds against Biomphalaria Alexandrina snails (the intermediate host of Schistosoma mansoni) showed considerable activities.