4-Methyl-1,2,5-oxadiazole-3-carbonitrile in the synthesis of 1,2,5-oxadiazolyl-1,2,4-oxadiazoles

4-Methyl-1,2,5-oxadiazole-3-carbonitrile reacts with hydroxylamine to form 4-methyl-1,2,5-oxadiazole-3-carboxamidoxime, which turned out to be the useful starting compound in the synthesis of 3-(1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazoles.     

Exploratory chemistry of 3-aroylformamido-4-aryl-1,2,5-thiadiazoles

Apart from the previous report, the reaction of 3-(4-nitrobenzoylformamido)-4-(4-nitrophenyl)-1,2,5-thiadiazole ( 2a ) with m-chloroperbenzoic acid in chloroform at room temperature did not proceed, whereas at reflux temperature the same reaction gave 4-nitrobenzoic acid ( 5 ) (86%) and a minute amount of a mixture of 4-nitrobenzoylformamide ( 6 ) and 3-amino-4-(4-nitrophenyl)-1,2,5-thiadiazole ( 7a ). On the other hand the same reaction in a mixture of ethanol and chloroform (1:4) at room temperature gave 3-ethoxycarbamoyl-4-(4-nitrophenyl)-1,2,5-thiadiazole ( 8a ) (24%) as an isolable product. When 3-aroylformamido-4-aryl-1,2,5-thiadiazoles 2 in tetrahydrofuran were treated with various alkoxides in the corresponding alcohols at room temperature, 3-amino-4-aryl- 7 , 3-alkoxycarbamoyl-4-aryl- 8 , and 3-aryl-4-(aryl)(hydroxy)acetamido-1,2,5-thiadiazoles 9 were isolated. The ratios of which were dependent on the kind of bases and the solvent employed. Selected compounds 2 were allowed to react with phosphorus pentasulfide in the presence of pyridine at reflux to give 3-aryl-4-arylacetarnido-1,2,5-thiadiazoles 17 (55–64%), which were also produced by the reaction of 2 with either Lawesson's reagent or hydrogen sulfide gas in the presence of pyridine at reflux.     

Synthesis of 3-methyl-4-(5-R-1H-1,2,4-triazol-3-yl)-1,2,5-oxadiazoles

A number of 3-methyl-4-(5-R-1H-1,2,4-triazol-3-yl)-1,2,5-oxadiazoles were obtained in high yields by thermal dehydration of acylated 4-methyl-1,2,5-oxadiazole-3-carboxamide hydrazones.     

Synthesis of 3-(6-R-Benzothiazol-2-yl)-4-methyl-1,2,5-oxadiazoles

The nitrosation of N-aryl-3-oxobutanethioamides afforded 1-(6-R-benzothiasol-2-yl)-1-hydroxyimino-2-propanones that at oximation with hydroxylamine were converted into 1-(6-R-benzothiazol-2-yl)-1,2-dihydroxyiminopropanes. The latter were dehydrated by heating with succinic anhydride at 140°C yielding therewith 3-(6-R-benzothiazol-2-yl)-4-methyl-1,2,5-oxadiazoles.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005, pp. 759–761.Original Russian Text Copyright © 2005 by Britsun, Borisevich, Samoilenko, Lozinskii.     

Vinyl derivatives of heterocyclic systems and their polymers: 3-vinyl-1,2,5-thiadiazole

3-Vinyl-1,2,5-thiadiazole is prepared by different methods: by one-pot reaction from 1,2,5-thiadiazole, by cyclization of 3,4-diamino-1-butene, and by the Wittig procedure either from 1,2,5-thiadiazolylimethylenetriphenyl-phosphorane or from 3-formyl-1,2,5-thiadiazole. Some physical and chemical properties are described.     

1,2,5-Trimethyl-4-aminopiperidine and 3, 6-dimethyl-4-phenyl-2-aminopyridine

1,2,5-Trimethylpiperid-4-one is used to prepare 1, 2, 5-trimethyl-4-aminopiperidine, which is then converted to 1, 2, 5-trimethyl-4-(diethylaminoacetylamino)piperidine. Amination of 2, 5-dimethyl-4-phenylpyridine is effected, and 3, 6-dimethyl-4-phenyl-2-aminopyridine is thereby obtained.     

Some Reactions of 3,6-Bis(4-amino-1,2,5-oxadiazol-3-yl)-1,4,2,5-dioxadiazine

Diazotization and nitration of 3,6-bis(4-amino-1,2,5-oxadiazol-3-yl)-1,4,2,5-dioxadiazine gave, respectively, 3,6-bis(4-azido-1,2,5-oxadiazol-3-yl)-1,4,2,5-dioxadiazine and 3,6-bis(4-nitroamino-1,2,5-oxadi-azol-3-yl)-1,4,2,5-dioxadiazine. The latter reacted with nitrogenous bases to form the corresponding salts.     

The chemistry of 1,2,5-thiadiazoles V. Synthesis of 3,4-diamino-1,2,5-thiadiazole and [1,2,5] thiadiazolo[3,4-b]pyrazines

The o-diamine, 3,4-diamino-1,2,5-thiadiazole ( 2 ), was synthesized from 3,4-dichloro-1,2,5-thiadiazole ( 3 ) hy three methods. Aqueous glyoxal cyclized 2 into [1,2,5]thiadiazolo[3,4–6]-pyrazine ( 14 ). 3,4-Dichloro-1,2,5-thiadiazole 1,1-dioxide ( 18 ) reaeted with 2 to give 1,3-dihydro-bis[1,2,5]thiadiazolo[3,4-b:3′,4′-e]pyrazine 2,2-dioxide ( 19 ). The reaction of 2 with selenium oxyehloride led to [1,2,5]selenadiazolo[3,4-c] [1,2,5]thiadiazole ( 12 ). Ring closure of 2,3-diaminoquinoxaline ( 4 ) with thionyl chloride or selenium oxychloride gave [1,2,5]thiadiazolo-[3,4-b]quinoxaline ( 21 ) and [1,2,5]selenadiazolo[3,4-b]quinoxaline ( 22 ), respectively. Sulfurous acid reduced 21 to the 4,9-dihydro derivative 23 , which was reoxidized to 21 with chloranil. Aqueous hase hydrolyzed 21 to 4 via the hydrated intermediate 24 . Aqueous glyoxal cyclized 4 to the covalent hydrate of pyrazino[2,3-b]quinoxaline ( 26 ), 27 , which was dehydrated to 26 . Compound 26 underwent rapid addition of two alcohols in a process analogous to covalent hydration.     

Reactivity of 3,5-bis-(4-amino-1,2,5-oxadiazol-3-yl)-1,2,4-triazole

Alkylation of 3,5-bis(4-amino-1,2,5-oxadiazol-3-yl)-1,2,4-triazole with haloalkanes afforded N-CH₂R derivatives, and nitration furnished the corresponding bis-N-nitramine isolated as a trisodium salt. Treatment of the latter with CH₃I resulted in denitration. Diazotization and oxidation of 3,5-bis(4-amino-1,2,5-oxadiazol-3-yl)-1,2,4- triazole, its N-methyl and N-carboxy derivatives gave rise to the corresponding azido and nitro derivatives. Salts of 3,5-bis(4-amino-1,2,5-oxadiazol-3-yl)-1,2,4-triazol-5-acetic acid with nitrogen-containing bases were synthesized. It was established that the character of reaction products of 3,5-bis(4-amino-1,2,5-oxadiazol-3-yl)-1,2,4-triazole with formaldehyde depended on the acid-base properties of the medium.__________Translated from Zhurnal Organicheskoi Khirmii, Vol. 41, No. 2, 2005, pp. 270–276.Original Russian Text Copyright © 2005 by Sergievskii, Romanova, Mel’nikova, Tselinskii.     

Synthesis and Reactivity of Azidoximes: III. 1-Azido(4-amino-1,2,5-oxadiazol-3-yl)aldoxime in the Cycloaddition Reaction

By 1,3-dipolar addition of 1-azido(4-amino-1,2,5-oxadiazol-3-yl)aldoxime to propargyl alcohol and phenylacetylene bicyclic 4-amino-1,2,5-oxadiazol-3-yl(4-R-1,2,3-triazol-1-yl)ketoximes were obtained which in reaction with acetic anhydride afforded the corresponding O-acyl derivatives. Diazotization of 4-amino-1,2,5-oxadiazol-3-yl(4-R-1,2,3-triazol-1-yl)ketoximes furnished 4-azido derivatives. The treatment of 4-amino-1,2,5-oxadiazol-3-yl(4-hydroxymethyl-1,2,3-triazol-1-yl)ketoxime with SOCl₂ resulted in 4-amino-1,2,5-oxadiazol-3-yl(4-chloromethyl-1,2,3-triazol-1-yl)ketoxime, whose chlorine atom was readily replaced by azide ion affording 4-amino-1,2,5-oxadiazol-3-yl(4-azidomethyl-1,2,3-triazol-1-yl)ketoxime.     

Novel intramolecular cyclization of 2-(buta-1,3-dienyl)-3-methylpyrazines and 3-(buta-1,3-dienyl)-4-methyl-1,2,5-oxadiazoles into 5H-cycloheptapyrazines and 4H-cyclohepta-1,2,5-oxadiazoles

2-(Buta-1,3-dienyl)-3-methylpyrazines (5) and 3-(buta-1,3-dienyl)-4-methyl-1,2,5-oxadiazoles (10) were synthesized starting from base-induced reaction of 2,3-dimethylpyrazine or 3,4-dimethyl-1,2,5-oxadiazole with α,β-unsaturated carbonyls. The thus obtained heteroaromatics bearing a butadienyl moiety and a methyl at the adjacent position underwent intramolecular cyclization by the action of LDA to give the corresponding heteroaromatics fused with a seven-membered ring [7 (8)] and [11 (12)] in moderate to high yields.     

5,6,7,8-Tetrahydro-4H-1,2,5-oxadiazocin-6-one durch Ringerweiterung nach Addition eines 3-Isoxazolidinons mit 3-Amino-2H-azirinen

5,6,7,8-Tetrahydro-4H-1,2,5-oxadiazocin-6-ones, Ring Enlargement Products from a 3-Isoxazolidinone and 3-Amino-2H-azirines 3-Dimethylamino-2H-azirines 1 and 4,4-dimethyl-3-isoxazolidinone ( 7 ) undergo already at room temperature a ring enlargement reaction to yield 5,6,7,8-tetrahydro-4H-1,2,5-oxadiazocines of type 8 . The structure of 8a has been confirmed by X-ray crystallography. The conformation of the eight-membered ring with a trans-amide group is of particular interest (Fig. 1 and 2).     

Inhibitors of platelet aggregation. 4. [1,2,5]Thiadiazolo[3,4-c]acridines, 7,8,9,10-Tetrahydro[1,2,5] thiadiazolo[3,4-c]acridities,and 8,9-Dihydro-7H-cyclopenta[b][1,2,5] thiadiazolo[3,4-H]quinolines

The condensation of 4-amino-2,1,3-benzothiadiazole (IV) with diphenyliodonium-2-earboxylate gave N-(2,1,3-benzothiadiazoI-4-yl)anthranilic acid (V) (28%), which was cyclized with phosphorus oxychloride to 6-chloro[1,2,5]thiadiazolo[3,4-c]acridine (VI) (84%). Treatment of VI with 3-(dimethylamino)-1-propanethiol hydrochloride in phenol afforded 6-[ [3-(dimethylamino)-propyl]thio] [1,2,5]thiadiazolo[3,4-c]acridine (VII) (65%). The reaction of IV with a mixture of methyl and ethyl 2-oxocyclohexanecarboxylate gave the adduct, which was ring closed in Dowtherm to 7,9,10,1 1-tetrahydro[1,2,5] thiadiazolo[3,4-c]acridin-6(8H)one (VIII) (70%). Chlorination of VIII with phosphorus oxychloride gave 6-chloro-7,8,9,10-tetrahydro[1,2,5]thiadiazolo[3,4-c]acridine (IX) (84%), which was condensed with 3-(dimethylamino)-1-propanethiol hydrochloride in phenol yielding 6-[ [3-(dimethylamino)propyl]thio]-7,8,9,10-tetrahydrof 1,2,5]-thiadiazolo[3,4-c]acridine (X) (27%). 6-[ [3(1)imethylamino)propyl]thio]-8,9-dihydro-7H-cyclopenta[b] [1,2,5]thiadiazolo[3,4-h]quinoline (XIII) (25%) was prepared similarly from IV and a mixture of methyl and ethyl 2-oxocyclopentanecarboxylate via 7,8,9,10-tetrahydro-6H-cyclopenta[b][1,2,5]thiadiazolo[3,4-h]quinolin-6-one (XI) (85%) and 6-chloro-8,9-dihydro-7H-cyclopenta[b][1,2,5]thiadiazolof3,4-h]quinoline (XII) (56%). The effects of compounds VII-XIII as inhibitors of platelet aggregation are discussed.     

Synthesis of unsymmetrical 4-oxo-2-vinyl-4H-chromene-3-carbonitrile dyes via Knoevenagel reaction

New 4-oxo-2-vinyl-4H-chromene-3-carbonitrile derivatives have been synthesized by the Knoevenagel reaction of 2-methyl-4-oxo-4H-chromene-3-carbonitrile with aromatic and heteroaromatic aldehydes. Spectral properties of the obtained compounds have been studied.     

1,2,5-Trimethyl-4-(p-hydroxyaryl)-δ3-tetrahydropyridines and their spatial structure

The condensation of 1,2,5-trimethylpiperidine-4-one with phenol and isomeric cresols yields 1,2,5-trimethyl-4-(p-hydroxyphenyl)- and (p-hydroxytolyl)-³-tetrahydropyridines, the structure and conformation of which have been studied by proton NMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1367–1370, October, 1986.     

4-Alkyl(aryl)-3-amino-1,2,5-thiadiazole 1,1-dioxides

Two methods have been developed for the synthesis of 3-amino-1,2,5-thiadiazole 1,1-dioxides; one leads to 4-alkyl derivatives, the other to 4-aryl analogs.     

Reaction of 2-methyl-3-ethoxycarbonyl-4-hydroxythiophene with hydrazines

2-Methyl-3-ethoxycarbonyl-4-(N,N-dimethylhydrazino)thiophene (II) and 2-methyl-3-ethoxy-carbonyl-4-(N-phenylhydrazino)thiophene (III) are formed by the action of substituted hydrazines — N,N-dimethylhydrazine and phenylhydrazine — on 2-methyl-3-ethoxycarbonyl-4-hydroxythiophene (I). At the same time, the thiophene ring of hydroxythiophene I undergoes hydrazinolysis under the influence of hydrazine hydrate to form 3-mercaptomethyl-4-ethoxycarbonyl-5-methylpyrazole (IV). Structure IV was proved by IR, UV, and PMR spectroscopy and by hydrogenolysis of IV to the known 3,5-dimethyl-4-ethoxycarbonylpyrazole (V).Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 759–761, June, 1971.     

1,2,5-Trimethyl-4-allyl(propargyl)-4-aryl(hetaryl)aminopiperidines

Individual geometrical isomers of some 1,2,5-trimethyl-4-allyl-4-aryl(hetaryl)aminopiperidines were isolated, and their structures were established. 1,2,5-Trimethyl-4-propargyl-4-aryl(aralkyl)aminopiperidines were obtained from 1,2,5-trimethyl-4-aryliminopiperidines and propargylmagnesium bromide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 942–946, July, 1991.     

Reactions of isomeric 6-methyl-2-methylthio-4cyanomethoxypyrimidine and 6-methyl-2methylthio-3-cyanomethylpyrimidinone-4 with n-nucleophiles

It was found that 6-methyl-2-methylthio-4-cyanomethoxypyrimidine (O-isomer) reacted via the cyano group with ammonia and hydroxylamine to give an amldine and an amidoxime respectively. The O-isomer did not react with either primary or secondary amines under similar conditions, but nucleophilic substitution at position 2 of the O-isomer was effected by converting the 2-methylthio group into a 2-methylsu fonyl. 6-Methyl-2methylthio-3-cyanomethylpyrimidinone-4 (N₃-isomer) formed imidazo[1, 2-a]pyrirnidinones-5 with ammonia and primary amines, 2-amino-6-methyl-3-cyanomethylpyrirrtidinones-4 with secondary amines and either an amidoxime or an imidazo[1, 2-a]pyrimidinone-5 with hydroxylamine, depending on the reaction temperature.Vilnius University. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 703-707, May, 1996. Original article submitted November 3, 1995.     

Preparation of 1,2,5-thiadiazole-3-carboxaldehydes

1,2,5-Thiadiazole-3-carboxaldehydes 1a-c were prepared by the acid-catalyzed decomposition of 3-azido-methyl-1,2,5-thiadiazoles 2a-c in 68-83% yields, respectively. Pyrolysis of 2a and 2b afforded the imidazoles 4a and 4b in low yields. NBS -bromination of 1a and 1b gave the corresponding carboxylic acids 10a and 10b via acid bromides 9. Azides 2a and 2b gave the s-triazines 8a and 8b on treatment with NBS.