Fries reaction and dakin rearrangement in benzo-2,1,3-thiadiazoles

The Fries rearrangement of 4- and 5-acetoxybenzo-2,1,3-thiadiazoles has given 4-hydroxy-7-acetyl- and 5-hydroxy-4-acetylbenzo-2,1,3-thiadiazoles, which on oxidation afford mixtures of 5-chloro-4,7-dioxo- and 5,6-dichloro-4,7-dioxobenzo-2,1,3-thiadiazole and of 6-chloro-4,5-dioxo- and 6,7-dichloro-4,5-dioxobenzo-2,1,3-thiadiazole. Reaction of 6,7-dichloro-4,5-dioxobenzo-2,1,3-thiadizole with ortho-phenyl-enediamine gives 4,5-dichloro-2,1,3-thiadiazolo[4,5-a]phenazine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1683–1687, December, 1987.     

Investigations on 2, 1, 3-thia- and selenadiazoles

Nitration and nitrosation of 4-hydroxy-5-methyl-benzo-2, 1, 3-thiadiazole gives 4-hydroxy-5-methyl-7-nitro-and 4-hydroxy-5-methyl-7-nitrosobenzo-2, 1, 3-thiadiazoles. Oxidation of the latter, or of 4,7-diamino-5-methylbenzo-2,1,3-thiadiazole gives 5-methyl-4,7-dihydroxy-2, 1, 3-thiadiazole, forming derivatives with sodium bisulfite or hydroxylamine, and reduced by sodium dithionite to 5-methyl-4, 7-dihydroxybenzo-2, 1, 3-thiadiazole. The latter is also obtained by diazotizing 5-methyl-4-hydroxy-7-aminobenzo-2, 1, 3-thiadiazole, and decomposing the diazonium salt. Nitration of 4-ethoxybenzo-2, 1, 3-thiadiazole with sodium ethoxide gives 4-ethoxy-7-aminobenzo-2, 1, 3-thiadiazole, acetylated to 4-ethoxy-7-acetaminobenzo-2, 1, 3-thiadiazole.For Part XXXVII see [1].     

Conversion of 4-substituted benzo-2,1,3-thiadiazoles to 5-chloro-4,7-dioxobenzo-2,1,3-thiadiazole by action of hydrogen peroxide and hydrochloric acid

Under the influence of hydrogen peroxide and hydrochloric acid in acetonitrile 4-substituted benzo-2,1,3-thiadiazoles form 5-chloro-4,7-dioxobenzo-2,1,3-thiadiazole. 4-Alkoxy- and 4-[(alkoxycarbonyl)methoxy]benzo-2,1,3-thiadiazoles give, in addition, the corresponding 5,7-dichloro derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 114–117, January, 1988.     

Oxidation of halohydroxybenzo-2,1,3-thiadiazoles with nitric acid

4,5-Dioxobenzo-2,1,3-thiadiazole has been synthesized. Its structure was proven by conversion to the known 4,5-dioximinobenzo-2,1,3-thiadiazole and to 2,1,3-thiadiazolo[4,5-a]phenazine, and by reduction to 4,5-dihydroxybenzo-2,1,3-thiadiazole. Oxidation of 5,6-dichloro-4,7-dihydroxy- and 5,7-dichloro-4-hydroxy-benzo-2,1,3-thiadiazoles forms 5,6-dichloro-4,7-dihydroxybenzo-2,1,3-thiadiazole, of known structure, and 7-chloro-4,5-dioxobenzo-2,1,3-thiadiazole; the latter by reaction with ortho-phenylene diamine is converted to 4-chloro-2,1,3-thiadiazolo[4,5-a]phenazine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 850–852, June, 1987.     

Researches on 2,1,3-thia-and selenadiazole

Chlorination of benzo-2,1,3-thiadiazole (I) in the presence of iron and paraform gives only 4-chlorobenzo-2,1,3-thiazole. Chlorination of 5,6-dimethylbenzo-2,1,3-thiadiazole (II) under exactly the same conditions gives only 5,6-dimethyl-4,7-dichlorobenzo-2,1,2-thiadiazole. Similarly chloromethylation of II in the presence of paraform gives only 5,6-dimethly-4,7-di(chloromethyl)benzo-2,1,3-thiadiazole. Chlorination and chloromethylation of I proceed through the intermediate formation of monosubstituted compounds which change into disubstimted ones.It is known [2,3] that Chlorination of benzo-2,1,3-thiadiazole (I) and its 5,6-dimethyl derivative (II) with chlorine in the presence of iron gives mainly the 4,7-dichloro substitution products III and IV respectively.It was previously shown [4] that chloromethylation of I with dichlorodimethyl ether in the presence of anhydrous aluminum chloride also gives mainly 4,7-di(chloromethyl)benzo-2,1,3-thiadiazole (V). Bases and pseudo-bases (paraform, urotropine. dimethylformamide) have a retarding effect on chloromethylation. When the reaction is run in the presence of these latter the products comprise besides V, 4-chloromethyl-2,1,3-thiadiazole (VI), or else, if enough base is added, there is no reaction.For Part XLII see [1].     

Synthesis of 5-fluoro-2-methyl-3-(2-trifluoromethyl-1,3,4-thiadiazol-5-yl)-4(3H)-quinazolinone and related compounds with potential antiviral and anticancer activity

The synthesis of ten new substituted 1,3,4-thiadiazolyl-4(3H)-quinazolinones 8–11, 13, 17 , and 20–23 is reported. Compounds 8–11 were prepared by condensation of 5-fluoro-2-methyl-3,1-benzoxazin-4-one (3) and 5-substituted 2-amino-1,3,4-thiadiazoles 4–7. Compound 13 was obtained by condensation of 5-fluoro-2-methyl-3,1-benzoxazin-4-one (3) with DL-α-amino-?-caprolactam (12) . Compound 17 was synthesized by condensation of 6-bromo-2-methyl-3,1-benzoxazin-4-one (16) and 2-amino-5-t-butyl-1,3,4-thiadiazole (5) . Compounds 20–23 were obtained by condensation of 5-chloro-6,8-dibromo-2-methyl-3,1-benzoxazin-4-one (19) and 5-substituted 2-amino-1,3,4-thiadiazoles 4–7, respectively. The substituted 3,1-benzoxazin-4-ones 3, 16, and 19 were obtained in good yield by refluxing the appropriate anthranilic acid, 1,15 , and 18 with acetic anhydride (2) .     

Researches on 2, 1, 3-thia- and selenadiazole

4-Hydroxy-, 4-hydroxy-5-methyl-, 4-hydroxy-7-methylbenzo-2,1,3-thiadiazoles are polymorphous.4-Hydroxybenzo-2,1,3-thiadiazole (I), 4-hydroxy-5-methyl- and 4-hydroxy-7-methylbenzo-2, 1, 3-thiadiazoles (II and III) melt at 114–115°, 110–112°, 100–102° C, respectively, after recrystallization from water [2–4], but after recrystallization from petrol ether [5] they melt at 128–129°, 124–125°, and 119–120° C [5]. In this connection we recrystallized these phenols repeatedly from petrol ether after recrystallizing them from water, and their melting points rose as expected [5]. On the other hand, the compounds with melting points 128–129°, 124–125°, 119–120° C (ex petrol ether), after repeated crystallization from water melted at 114–115°, 110–112°, 100–102° C, respectively.For Part XXXVIII see [1].     

Oxidation and reduction of some derivatives of benzo-2,1,3-thiadiazole

In the reduction of 4-hydroxy-7-phenylazobenzo-2,1,3-thiadiazole and of 4-hydroxy-7-nitro-benzo-2,1, 3-thiadiazole with sodium hydrosulfite, 7-amino-4-hydroxybenzo-2,1,3-thiadiazole is obtained. The reduction of 4-hydroxybenzo-2,1,3-thiadiazole leads to 2,3-diaminophenol which forms 5-hydroxyquinoxaline with the bisulfite derivative of glyoxal. The oxidation of 4-hydroxy- and 4-aminobenzo-2,1,3-thiadiazoles with potassium dichromate in an acid medium has yielded 4,7-dioxo-4,7-dihydrobenzo-2,1,3-thiadiazole, which has been converted into 4,7-dihydroxybenzo-2,1,3-thiadiazole and 4,7-di(hydroxyimino)-4,7-dihydrobenzo-2,1,3-thiadiazole.Translated from Khimiya Geterotsikliches-kikh Soedinenii, No. 7, pp. 926–929, July, 1973.     

Synthesis and Chemical Behaviour of 4, 5-Dideoxy-4, 5-Epithio-2, 3-DI-0-Methanesulfonyl-L-Xylose Dimethyl Acetal

ABSTRACT

Selective substitution of the primary sulfonate group in 2, 3, 4, 5-tetra-0-methanesulfonyl-D-arabinose dimethyl acetal (1) gives 5-S-acetyl-2, 3, 4-tri-0-methanesulfonyl--5-thio-D-arabinose dimethyl acetal (2) which is further converted into the title compound (3). Reductive desul-furization of 3 afforded deoxy dimethyl acetal derivatives 5 and 6 in a low yield. Unsaturated monosaccharide derivative 7 was obtained as the only reaction product from 3 with triphenylphosphine. Catalytic hydrogenation of 7 gave dideoxy-sugar 6 in a satisfactory yield. Finally, epi-sulfide 3 with acetyl chloride afforded 4-chloro-4-deoxy derivative 4, which can be recycled into the starting 3.     

Synthesis and mass-spectrometric study of 2-amino- and 2-chloro-5-aryl-1,3,4-thiadiazoles

The cyclization of aldehyde thiosemicarbazones with ferric chloride yielded 2-amino-5-aryl-1,3,4-thiadiazoles, forming 2-chloro-5-aryl-1,3,4-thiadiazoles in the Sandmeyer reaction. The mass-spectrometric behavior of the 2-amino- and 2-chloro-5-aryl-1,3,4-thiadiazoles was studied; the typical routes of fragmentation characteristic of each group of compounds were found.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1416–1419, October, 1986.     

NMR study on the tautomeric equilibria between the hydrazone imine and diazenyl enamine forms in side chained quinoxalines: Solvent effects and temperature dependence

The reaction of 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydro-1,2,4-triazolo[4,3-a]quinoxaline 6 with 4-ethoxycarbonyl-1-methyl-1H-pyrazole-5-diazonium chloride or 4-cyano-1,3-dimethyl-1H-pyrazole-5-diazonium chloride gave 7-chloro-4-[α-(4-ethoxycarbonyl-1-methyl-1H-pyrazol-5-ylhydrazono)-ethoxycarbonylmethyl]-1,2,4-triazolo[4,3-a]quinoxaline 8a or 7-chloro-4-[α-(4-cyano-1,3-dimethyl-1H-pyrazol-5-ylhydrazono)ethoxycarbonylmethyl]-1,2,4-triazolo[4,3-a]quinoxaline 8b , respectively, while the reaction of 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydrotetrazolo[1,5-a]quinoxaline 7 with 4-ethoxycarbonyl-1-methyl-1H-pyrazole-5-diazonium chloride or 4-cyano-1,3-dimethyl-1H-pyrazole-5-diazomum chloride provided 7-chloro-4-[α-(4-ethoxycarbonyl-1-methyl-1H-pyrazol-5-ylhydrazono)ethoxycarbonylmethyl]tetrazolo[1,5-a]quinoxaline 9a or 7-chloro-4-[α-(4-cyano-1,3-dimethyl-1H-pyrazol-5-ylhydrazono)ethoxycarbonylmethyl]tetrazolo[1,5-a]quinoxaline 9b , respectively. Compounds 8a,b and 9a,b showed the tautomeric equilibria between the hydrazone imine C and diazenyl enamine D forms in dimethyl sulfoxide and/or trifluoroacetic acid, and the effects of solvent and temperature on the tautomer ratios of C to D were studied by the nmr measurements in a series of mixed trifluoroacetic acid/dimethyl sulfoxide media (compounds 8a,b and 9a,b ) and at various temperatures (compounds 8a,b ).     

1-芳酰基-4-取代吡唑甲酰基氨基硫脲和环化产物的合成及生物活性

利用1-苯基-3-甲基-5-氯-4-吡唑甲酰基异硫氰酸酯(Ⅰ)与芳酰肼(Ⅱ)的加成反应合成了系列新的酰胺基硫脲衍生物(Ⅲ),并将Ⅲ在酸性条件下进行环化反应得到2-取代吡唑甲酰基氨基-5-芳基-1,3,4-噻二唑(Ⅳ).生物活性测定结果表明部分化合物Ⅲ和Ⅳ具有较好的除草活性.     

Direct amination of 2-methyl-7-chloroceramidonine with ammonia or sodamide

Treatment of 2-methyl-7-chloroceramidonine with aqueous ammonia gives 2-methyl-6-amino-7-chloro-ceramidonine, while treatment with sodamide gives 2-methyl-7-chloro-8-aminoceramidonine.     

Investigations of 2,1,3-thia- and selenadiazoles

All three possible isomeric amines are obtained by the reaction of 4- or 5-methylbenzo-2,1,3-thiadiazoles with hydroxylamine sulfate in concentrated sulfuric acid. Under similar conditions, 5,6-dimethyl-4-aminobenzo-2,1,3-thiadiazole is obtained from 5,6-dimethylbenzo-2,1,3-thiadiazole.See [1] for communication LXIV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 601–602, May, 1971.     

Investigation of nitrogen- and sulfur-containing heterocycles

The reaction of 5-amino-4-chloro- and -4-methoxy-6~mercaptopyrimidines with 4-methoxy-, 4-amino-, and 2,4-diethoxyphenacyl chlorides has yielded 5-amino-4-chloro- and -4-methoxy-6-phenacylthiopyrimidines. The reaction of 2, 5-diamino-4-methyl-6-mercaptopyrimidine with 4-methoxyphenacyl chloride has yielded 2-amino-6-hydroxy-6-(4-methoxyphenyl)-4-methyl-5, 6-dihydropyrimido[4, 5-b]-1,4-thiazine, and that with 4-aminophenacyl chloride has yielded the corresponding 7H-pyrimido[4, 5-b]-1,4-thiazine.For part IV, see [1].     

Synthesis of the potent mutagen 3,5,8-trimethyl-3H-imidazo[4,5-f]quinoxalin-2-amine

The mutagenic title compound (5,8-DiMeIQx) was synthesized by two different routes: from 2-methyl-4,6-dinitroaniline; and from 4-chloro-2-methyl-6-nitroaniline. The latter and more convenient route involved 2,1,3-benzoselenadiazole intermediates.     

Researches on 2,1,3-thia- and selenadiazole XLV. Nitration of 4-hydroxy- and 4-ethoxybenzo-2,1,3-thiadiazoIe

Nitration of 4-hydroxybenzo-2,1,3-thiadiazole under conditions generally used for phenols, gave a high yield of 4-hydroxy-5-nitrobenzo-2,1,3-thiadiazole. The latter is readily reduced to 4-hydroxy-S-aminobenzo-2,1,3-thiadiazole which on treatment with orthoformic ester gives oxazolo [5,4-e]benzo-2,1,3-thiadiazole. 4-Ethoxybenzo-2,1,3-thiadiazole is nitrated under similar conditions, giving a high yield of a mixture of equal quantities of 4-ethoxy-S-nitro- and 4-ethoxy-7-nitrobenzo-2,1,3-thiadiazole.     

2-甲基-1,5-苯并硫氮杂的基态和激发态反应的研究 I: 2-甲基-1,5-苯并硫氮杂-4(5H)-酮的卤化和亲核取代反应

2-甲基-1,5-苯并硫氮杂-4(5H)-酮(1a)与不同的氯化试剂-五氯化磷、三氯氧磷和氯化砜在不同的条件下氯化,可分别生成:2-甲基-4-氯-1,5-苯并硫氮杂(2a)、2-氯-4-甲基-1,5-苯并硫氮杂(3a)、2-二氯甲基苯并噻唑(5)、2-三氯甲基苯并噻唑(6)和2-甲基-1,5-苯并硫氮杂-4(5H)-酮盐酸盐(4).2-甲基-4-氯-1,5-苯并硫氮杂与醇钠反应生成相应的2-甲基-4-烷氧基-1,5-苯并硫氮杂外,还可以分离到它的2,4-异构体,2-烷氧基-4-甲基-1,5-苯并硫氮杂.产物的结构均经元素分析、红外光谱、^1H和^1^3C核磁共振谱和质谱鉴定.     

Bromination of 2,1,3-benzothiadiazoles

The bromination of 2,1,3-benzothiadiazoles in 47% hydrobromic acid at elevated temperature has led to a general preparative method for the synthesis in high yield of otherwise difficulty accessible brominated 2,1,3-benzothiadiazoles. The typical addition reaction is apparently eliminated under these reaction conditions and substitution takes place exclusively. Bromination of 2,1,3-benzothiadiazole occurs successively at positions 4 and 7. 4-Substituted 2,1,3-benzothia-diazoles are selectively brominated at position 7. 5-Bromo- and 5-methyl-2,1,3-benzothiadiazole are brominated consecutively at positions 4 and 7.     

Regioselective preparation of vinyl chlorides from 2-methylcyclohexanone

Treatment of 2-methylcyclohexanone with PCl₅, in hexane at reflux gives predominantly 2-ch1oro-3-methylcyclohexene (3). ⁵On the other hand, treatment with catechyl phosphorus trichloride followed by alcoholic KOH gives predominantly the isomeric viny1 chloride, 1-chloro-2-methylcyclohexene (4).