Heterocyclic analogs of pleiadiene. XVI. Nitration of perimidine and its 1- and 2-methyl derivatives

Perimidine and 2-methylperimidine are nitrated by 1 mole of nitric acid in acetic acid to give a mixture of 4(9)- and 6(7)-mononitro derivatives. Renitration gives a mixture of 6,9- and 6,7-dinitroperimidines. Depending on the conditions, 6,7,9-trinitroperimidines and 4,6,7,9-tetranitroperimidines are formed when a large excess of nitric acid is present. 1-Methylperimidine is nitrated by 1 mole of nitric acid to give a mixture of 4-, 6-, and 7-mononitro derivatives.     

Nitration of 2- and 4-[2-(2-furyl)vinyl]thiazole derivatives

Nitration of 4-methyl-2-[2-(nitro-2-furyl)vinyl]thiazole with a mixture of concentrated nitric and sulfuric acids leads to 4-methyl-5-nitro-2-[2-(3,5-dinitro-2-furyl)vinyl]thiazole. Under the same conditions 2-methyl- and 2-acetamido-4-[1-R-2-(5-nitro-2-furyl)vinyl]thiazoles (R=CH₃, Cl) are nitrated in the 3 position of the furan ring, 2-amino-4-[1-chloro-2-(5-nitro-2-furyl)vinyl]thiazole is nitrated in the 5 position of the thiazole ring and 2-acetamido-5-nitro-4-[2-(2-furyl)vinyl]thiazole undergoes profound changes. Under the influence of a mixture of of nitric acid and acetic anhydride the latter compound is converted quantitatively to the 5-nitro derivative (with respect to the furan ring), whereas 4-[2-(5-nitro-2-furyl)vinyl]thiazole derivatives do not undergo reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 314–317, March, 1977.     

Nitro derivatives of 3-hydroxyquinoline

The nitration of 3-hydroxyquinoline with concentrated nitric acid in sulfuric acid at ?30 to +30°C gives 5-nitro-3-hydroxyquinoline (85–92%) and 7-nitro-3-hydroxyquinoline (7–12%). 4-Nitro-3-hydroxyquinoline is formed in 70% yield by nitration in acetic acid. 4,5-Dinitro-3-hydroxyquinoline is formed by further nitration of 4- and 5-nitro-3-hydroxyquinolines.     

Reaction of 2-acetamido-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one with dimethylamine and formaldehyde. Formation of two isomeric mannich bases

2-Acetamido-3, 7-dihydropyrrolo[2, 3-d)pyrimidin-4-one reacts with dimethylamine and formaldehyde in glacial acetic acid to afford the two isomeric Mannich products, 2-acetamido-3, 7-dihydro-5-dimethylamino-methylpyrrolo[2, 3-d]pyrimidin-4-one, and 2-acetamido-3, 7-dihydro-6-dimethylaminomethylpyrrolo[2, 3-d]-pyrimidin-4-one, in a ratio of 3:1, respectively.     

Synthesis and reactions of halo-, nitro-, and arylazo-substituted 3-aminotropolones. Formation of 8H-cyclohept[d]oxazol-8-one derivatives

3-Acetamidotropolone ( 1a ) reacted with bromine and fuming nitric acid to afford respectively 3-acetamido-7-bromo- ( 1b ) and -5,7-dibromotropolone ( 1c ) and 3-acetamido-5-nitrotropolone ( 1d ). Azo-coupling reaction of 1a gave 3-acetamido-5-(4-methylphenylazo)tropolone ( 1f ). Bromination of 1d and 1f gave 7-bromo-substituted compounds 1e and 1g , respectively. The compounds 1b-g were hydrolyzed to afford 3-aminotropolones 4b-g , which reacted with triethyl orthoformate to give the corresponding 8H-cyclohept[d]oxazol-8-ones 5b-g . Heating of 3-acetamidotropolones 1a-d with polyphosphoric acid gave 2-methyl-8H-cyclohept[d]oxazol-8-ones 6a-d .     

Amino acids in the synthesis of heterocyclic compounds. Transformations of thiazolones into imidazole derivatives

5(4H)-Thiazolone derivative 4 , obtained from N-dithiocarbobenzoxyglycine ( 1 ) and N,N-dimethyl-N′-heteroarylformamidines 3 in acetic anhydride, was rearranged with sodium methoxide in methanol followed by acidification with acetic acid into imidazole-4-carboxylic acid derivatives 5, 6 and 7 . These were further converted with methyl iodide into methylthio derivatives 8 , with hydrogen peroxide into the corresponding disulphide 9 , with hydrazine and amines into hydrazide 10 and amides 11 . In the reactions of 4a and 6a with amines in the presence of dichloromethane symetrically disubstituted methanes 14–18 were formed.     

Synthetic Studies on Sialoglycoconjugates 14: Synthesis of Ganglioside GM3 Analogs Containing The Carbon 7 And 8 Sialic Acids

ABSTRACT

Ganglioside GM₃ analogs, containing 5-acetamido-3, 5-dideoxy-L-arabino-heptulosonic acid and 5-acetamido-3, 5-dideoxy-D-galacto-octulosonic acid have been synthesiyed. Glycosylation of 2-(trimethylsilyl)ethyl 0-(6-0-benzoyl-ß-D-galactopyranosyl)-(l→4)-2, 6-di-0-benzoyl-ß-D-glucopyranoside (5), with methyl (methyl 5-acetamido-4, 7-di-0-acetyl-3, 5-dideoxy-2-thio-ß-L-arabino-2-heptulo-pyranosid)onate (2) or with methyl (methyl 5-acetamido-4, 7, 8-tri-0-acetyl-3, 5-dideoxy-2-thio-α-D-galacto-2-octulopyranosid)onate (4), which were respectively prepared from the corresponding 2-S-acetyl derivatives (1 and 3) by selective 2-S-deacetylation and subsequent S-methylation, using dimethyl(methylthio)sulfonium triflate as a glycosyl promoter, gave 2-(trimethylsilyl)ethyl 0-(methyl 5-acet-amido-4, 7-di-0-acetyl-3, 5-dideoxy-ß-L-arabino-2-heptulopyranosyl-onate)-(2→3)-0-(6-0-benzoyl-ß-D-galactopyranosyl)-(1→4)-2, 6-di-0-benzoyl-ß-D-glucopyranoside (6) and 2-(trimethylsilyl)ethyl (0)-(methyl 5-acetamido-4, 7, 8-tri-0-acetyl-3, 5-dideoxy-α-D-galacto-2-octulopyranosylonate)-(2→3)-0-(6-0-benzoyl-ß-D-galactopyranosyl)-(l-4)-2, 6-di-0-benzoyl-ß-D-glucopyranoside (10), respectively. Compounds 6 and 10 were converted, via 0-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the corresponding trichloroacetimidates 9 and 13, respectively.

Glycosylation of (2S, 3R, 4E)-2-azido-3-0-benzoyl-4-octadecen1, 3-duik (14) with 9 or 13 affored the ß-glcosides (15 and 18), which were converted, via selective reduction of the azide group, coupling with octadecanoic acid, 0-deacylation, and deesterification, into the title compounds, respectively.     

Formation of 4,7-dioxo-5-acetamido-4,7-dihydrobenzofurazan from 4-oxo-5-hydroximino-4,5,6,7-tetrahydrobenzofurazan and -furoxan and investigation of its reaction with amines

The reaction of 4-oxo-5-hydroximino-4,5,6,7-tetrahydrobenzofurazan and 4-oxo-5-hydroximino-4,5,6,7-tetrahydrobenzofuroxan with acetic anhydride in the presence of an acid gives 4,7-diacetoxy-5-acetamidobenzofurazan and 2,3-diacetoximino-5-acetamido-1,4-benzoquinone, respectively, which were used to obtain 4,7-dioxo-5-acetamido-4,7-dihydrobenzofurazan. The synthesized quinone reacts with amines to give the corresponding aminoquinones; when 4,7-dioxo-5-acetamido-6-anilino-4,7-dihydrobenzofurazan is heated, it is readily converted to 5-phenyl-6-methyl-4,8-dioxo-1H-imidazo[4,5-f]benzofurazan.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 532–536, April, 1993.     

A rapid method for simultaneous estimation of 5-hydroxy-3-indole acetic acid (5HIAA) and 5-hydroxytryptamine (5HT) in rat brain

The authors describe a method to separate 5-hydroxy-3-indole acetic acid (5HIAA) from 5-hydroxyindole derivatives by means of a batch procedure using Dowex 50 WX 12 resins. These compounds were assayed by the Maickel and Miller procedure, and 5-hydroxytryptamine (5HT) was then calculated as the difference between total 5-hydroxyindoles and 5HIAA. This procedure allows a rapid assay of 5HT and 5HIAA in about 60 mg of rat cerebral tissue, but it may not be used when large amounts of 5-hydroxytryptophan are present.     

Studies on the reactivity of new types of tetracyclic‐1,5‐benzoxazepines: Part V

The syntheses of tetracyclic 1,5‐benzoxazepines 3a‐e from heterocyclic (3‐chloroaldehydes 1a‐e and 2‐aminophenol are reported herein (Scheme I). Attempted lithium aluminium hydride (LiAlH₄) reduction of the imine double bond in 3a‐e failed to furnish the corresponding saturated compounds 5a‐e. Attempted catalytic hydrogenation of 3a‐e in the presence of acetic acid and acetic anhydride gave surprisingly only the acetoxy derivatives 6a‐e in high yields (Scheme II). Base catalysed hydrolysis of acetoxy derivatives 6a‐e furnished, as expected, the corresponding phenolic derivatives 7a‐e , in moderate yields. Attempted cyclofunctionalization of 3a‐e either with mercaptoacetic acid or its methyl ester to obtain the new penta‐cyclic heterocycles 4a‐e was, however, not successful.     

Synthesis of 4-deoxy-4-nitrosialic acid

The synthesis of 4-deoxy-4-nitrosialic acid (3,4,5-trideoxy-4-nitro-D-glycero-beta-D-galacto-non-2-ulopyranosonic acid, 5), was completed in seven steps starting from D-arabinose. Coupling of the 6-carbon fragment, 2-acetamido-1,2-dideoxy-1-nitro-D-mannitol (6) with ethyl alpha-(bromomethyl)acrylate afforded a 2 : 1 mixture of ethyl 5-acetamido-2,3,4,5-tetradeoxy-2-methylene-4-nitro-D-glycero-D-galacto-nononate (9a-S) and ethyl 5-acetamido-2,3,4,5-tetradeoxy-2-methylene-4-nitro-D-glycero-D-talo-nononate (9a-R). This mixture of enones was subjected to ozonolysis, and following reduction of the ozonide, the resultant products cyclised to the pyranosides. The target compound, ethyl 4-deoxy-4-nitrosialate (11a) was isolated by fractional crystallisation. Hydrolysis of the ethyl ester proved problematic; thus, the synthesis was modified by using tert-butyl alpha-(bromomethyl)acrylate. Following ozonolysis of the corresponding tert-butyl enoate esters and diastereomer separation, the tert-butyl ester of 4-nitrosialic acid (11b) could be deprotected under acidic conditions to afford . The target compound is a useful intermediate for synthesis of a variety of C-4 substituted sialic acid derivatives, and it is synthesised by a modular route.     

Nitration of 2,3′-bithienyl

The nitration of 2,3′-bithienyl ( 1 ) with fuming nitric acid in acetic anhydride at 0° gives a mixture of 3-nitro- ( 2 ), 2′ -nitro- ( 3 ) and 5-nitro-2,3′-bithienyl ( 4 ) with relative percentages of 38.7%, 34.8% and 26.5%. When the nitration of 1 was carried out with fuming nitric acid in acetic acid at 20°, the same compounds 2, 3 and 4 were obtained, but with different relative percentages: 20.4%, 36.5% and 43.1% respectively. The results of the mononitration of 1 are compared with those obtained in other electrophilic substitutions and with the theoretical predictions. The further nitrations of 2, 3 and 4 with nitric acid in acetic anhydride at room temperature lead to the formation of five dinitro-2,3′-bithienyl isomers. Compound 2 gives a mixture of 2′,3-dinitro- ( 5 ) and 3,5′-dinitro-2,3′-bithienyl ( 6 ); compound 3 gives a mixture of 5 , 2′,5-dinitro- ( 7 ) and 2′,4-dinitro-2,3′-bithienyl ( 8 ); compound 4 gives 7 and 5,5′-dinitro-2,3′-bithienyl ( 9 ). The possible reasons of the formation of the various dinitro-2,3′-bithienyl isomers are discussed.     

Oxidation-Reduction Conversions of Derivatives of 1,4-Dihydropyridine and 4H-pyran on Interaction of Alicyclic 1,5-Diketones wth 4-Aminoazobenzene

The interaction of 2,2'-methylenedicyclohexanone and 2,2'-methylenedicyclopentanone with 4-aminoazobenzene in acetic acid leads to reduction of the azo group of 1,4-dihydropyridine and 4H-pyran derivatives formed as intermediates. The reduction products were isolated as the corresponding pyridinium salts.     

1,3-benzoxathioles. Electrophilic aromatic substitution

Some electrophilic substitution reactions on 1,3-benzoxathiole derivatives are described. Bromination and acylation reactions take place in position 5, i.e., para to the oxygen atom. 1,3-Benzoxathiole nitration yields a mixture of the corresponding sulfoxide and of the 6-nitro derivative when performed with 33% nitric acid, while, using a mixture of 40% nitric acid and acetic acid or acetyl nitrate, the 6-nitroderivative is obtained together with large amounts of gummy products. 2,2-Dimethyl-1,3-benzoxathiole nitration with 33% nitric acid yields disulfide XI, while with 33% nitric acid and acetic acid or with acetyl nitrate a mixture of disulfide XI and XII is obtained. The structure of the products have been determined by spectroscopic methods.     

Synthesis of o-nitrosoacylbenzenes from o-nitrobenzyl alcohols and their derivatives

Nitration of substituted benzyl alcohols, as well as ethers and esters derived therefrom, with nitric acid in acetic anhydride was studied. The corresponding o-nitrobenzyl alcohols and their derivatives formed as the primary products are capable of being converted into o-nitrosoacylbenzenes by the action of acids.     

Purines. XIV. Synthesis and properties of 8-nitroxanthine and its N-methyl derivatives

Xanthine ( 1 ) and its N-methyl derivatives 2–16 have been nitrated to the corresponding 8-nitro derivatives 17–32 under different reaction conditions. Nitration in glacial acetic acid with nitric acid works well with the N-7 unsubstituted and some of the 9-methylxanthines, respectively, whereas the 7-methylxanthine derivatives react best with nitronium tetrafluoroborate in sulfolane or glacial acetic acid. The 8-nitro group can be displaced nucleophilically to form 8-chloro-, 33, 34 , 8-ethoxy-, 35,36 , and uric acid derivatives 37–40 , respectively. The newly synthesized 8-nitroxanthines have been characterized by elemental analyses, pK-determinations and uv and ¹H-nmr spectra.     

Synthesis of aldehydes and nitriles in the 5-hydroxyindole series

A preparative method for the synthesis of previously inaccessible 3-formyl-5-hydroxyindole derivatives by Vilsmeier formylation of 5-acetoxyindoles is proposed. 5-Hydroxyindole-3-carboxylic acid nitriles and their 4-dimethylamino-methyl derivatives were obtained from 3-formyl-5-hydroxyindoles through their oximes.     

A facile synthesis of novel pyrazolo[5′,1′:3, 4]-[1, 2, 4]triazino[6, 5-f][1, 3, 4]thiadiazepines

The reaction of the 3-substituted 4-aminopyrazolo[5, 1-c][1, 2, 4]triazines 1a-d with thiosemicarbazide hydrochloride in acetic acid gave new pyrazolo[5′,1′:3, 4][1, 2, 4]triazino[6, 5-f][1, 3, 4]thiadiazepines 3, 4 and 6 , which were converted into the 5-oxo derivatives 5 and 7 by hydrolysis in hydrochloric acid/acetic acid.     

Reductive acetylation of nitrocarboxylic acids of the thiophene and furan series or their esters

The corresponding 4-acetylamino-2-thiophenecarboxylic acids or their esters were produced by the action of reduced iron on solutions of 4-nitro-2-thiophenecarboxylic acid, its derivatives, or their esters in a mixture of acetic acid and acetic anhydride. Esters of 5-acetylamino-2-thiophenecarboxylic or 5-acetylamino-2-furancarboxylic acids are formed from esters of 5-nitro-2-thiophenecarboxylic or 5-nitro-2-furancarboxylic acids. Free 5-nitro-2-thiophenecarboxylic and 5-nitro-2-furancarboxylic acids are entirely decomposed under the conditions of reductive acetylation by iron. The ester of 5-acetylamino-3-thiophenecarboxylic acid was obtained from the methyl ester of 5-nitro-3-thiophenecarboxylic acid.     

Conversions of methyl esters of (6-methyl-2-methylthio-4-pyrimidinyloxy)- and (3,4-dihydro-6-methyl-2-methylthio-4-oxo-3-pyrimidinyl)acetic acids

A study has been made of nucleophilic reactions (hydrolysis, hydrazinolysis, ammonolysis, reduction) and electrophilic reactions (bromination, nitration) of isomeric methyl esters of (6-methyl-2-methylthio-4-pyrimidinyloxy) acetic acid and (3,4-dihydro-6-methyl-2-methylthio-4-oxo-3-pyrimidinyl)acetic acid. Carboxyl-group derivatives and also derivatives with substituents in position 5 of the pyrimidine ring have been synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1655–1659, December 1992.