Introduction of substituents into the benzene nucleus op indole

It has been shown that in the nitration of 1-acetyl-6-nitroindoline with nitric acid (d 1.52) in acetic anhydride, the second nitro group enters position 5 of the indoline ring. In the nitration of 5- and 6-acetylaminoindolines, the nitro group enters positions 6 and 5 of the indoline ring, respectively.For part VIII, see [1].     

Unusual Acetylation of 2-Methyl-1-phenylsulfonylindole

Acetylation of 2-methyl-1-phenylsulfonylindole with an excess of aluminium chloride and acetic anhydride afforded exclusively 6-acetyl-3-chloro-2-methylindole and 6-acetyl-3-chloro-2-methyl-1-phenylsulfonylindole.     

4-乙酰基-1,3-二氟苯硝化反应机理研究

以4-氨基-1,3-二氟苯、乙酸酐和浓硝酸等为原料,合成了4-乙酰基-5-硝基-1,3-二氟苯,并且采用FTIR和1H NMR对产物进行了表征.采用量子化学方法,探讨了在酸催化条件下4-乙酰基-1,3-二氟苯硝化反应过程中的微观机理,在密度泛函理论的B3LYP/6-311G**水平下搜索得到反应路径,并对各中间体、过渡态和产物进行几何优化、振动频率分析和标准热力学函数计算;反应路径经过IRC验证.在MP2/6-311G**水平上对所有中间体、过渡态和产物进行更精确的能量计算.     

Synthesis of 3-arylamino-4(3H)quinazolinone derivatives from 1-acetyl- or 1-ethoxycarbonylmethylene-2-arylhydrazines

By reacting 1-acetyl- or 1-ethoxycarbonylehloromethylene-2-arylhydrazines ( 2a-c ) with anthranilic acids (1a-b) the corresponding C-acetyl- or C-ethoxyearbonylcarbohydrazonamide derivatives (3a-d) were obtained. Ring closure of the carbohydrazonamides with acetic anhydride afforded 2-carboethoxy- or 2-acetyl-3-arylamino-4(3H)quinazolinones ( 4a-d ). The ester derivatives undergo basic hydrolysis with decarboxylation to 3-arylamino-4(3H)quinazolinones ( 5a-b ).     

Indolizine derivatives. VII. indolizines via cyclizations of 2-(2-Pyridyl)methylene-1,3-diketones and −1,3-Keto esters

The reaction of 3-(2-pyridyl)methylene-2,4-pentanedione with acetic anhydride gives at 60° 1-(1-acetoxy-3-methyl-2-indolizinyl)ethanone ( 3a ) or, in the presence of 2,4-pentanedione, 3-(2-acetyl-3-methyl-7-indolizinyI)-2,4-pentanedione ( 7a ) in good yield. In refluxing acetic anhydride, 1-(3-methyl-2-indolizinyl)ethanone ( 4a ) is the main product. In refluxing dimethyl sulfoxide the cycloaddition product, 3-[2-acetyl-3-(2-pyridyl)-l-indolizinyl)]-2,4-pentanedione ( 6 ), is obtained. Ethyl 2-(2-pyridyl)methylene-3-oxobutanoate and ethyl 2-(2-pyridyl)methylene-3-oxo-3-phenylpropanoate behave analogously. The stereochemistry of the keto esters has a marked influence on the course of cyclization. The mechanisms are discussed.     

Tetrahydropyridines and furans from the reaction of 4-t-butylpyridine 1-oxide with t-butyl and 1-adamantyl mercaptan

The reaction of 4-t-butylpyridine 1-oxide (1) with t-butyl or 1-adamantyl mercaptan in acetic anhydride yielded the expected 2- and 3-alkylthio-4-t-butylpyridines and 1-acetyl-2,6-bis-(alkylthio)-3-acetoxy-4-t-butyl- and the unexpected 1-acetyl-2-acetoxy-3,6-bis(alkylthio-4-t-butyl-1,2,3,6-tetrahydropyridines. The addition of t-butyl mercaptan to a solution of 1 in acetic anhydride containing triethylamine produced the expected 1-acetyl-2-t-dmtylthio-3-acetoxy-4-t-butyl-6-hydroxy-1,2,3,4-tetrahydropyridine ( 6a ) and the unexpected 1-acetyl-2,6-bis(hydroxy)-3-t-butylthio-4-t-butyl-1,2,3,6-tetrahydropyridine. Mild alkaline hydrolysis of 6a yielded predominantly 2-[(acetamido) (t-butylthio)methyl]-3-t-butyl-5-hydroxy-2,5-dihydrofuran. The latter was converted by very mild acidic reagents to the corresponding furan and with 2,4-dinitrophenylhydrazine and sulfuric acid furnished 3-t-butylfurfural 2,4-dinitrophenyl-hydrazone.     

Synthesis and reactions ofβ-substituted furans

3-Bromofuran has been obtained in good yield by the reaction of 4, 5-dibromo-3, 6-endoxohexahydrophthalic anhydride with quinoline at 210–220° C. It has been shown that the reaction of 3-bromofuran with acetic anhydride in the presence of perchloric acid forms 2-acetyl-3-bromofuran.     

N2′-acetyl-6-diacetoxymethylpterin

Treatment of folic acid with bromine in 48% hydrobromic acid gives the hydrobromide salt of 6-formylpterin ( 1 ), and acetylation of 1 with recovered acetic anhydride leads to N^2′-acetyl-6-diacetoxymethylpterin ( 3 ).     

Fluoroazoles. III. Synthesis and 1H and 1–9F nmr spectra of 3-, 4-, and 5-fluoro-1-methylpyrazole

The three monofluoro derivatives of N-methylpyrazole have been synthesized. 3-Fluoro-1-methylpyrazole and 4-fIuoro-1-methylpyrazole were prepared from the appropriate amines by diazotization and photochemical irradiation of the diazonium salts in tetrafluoroboric acid. 5-Fluoro-1-methylpyrazole was obtained from 1-acetyl-3-fluoropyrazole and methyl fluorosulfonate, and also by direct methylation of 3(5) fluoropyrazole with dimethyl sulfate. The ^1–9F chemical shifts of these N-methylated fluoroazoles cover a great range (ca. 50 ppm) and show a good correlation with the chemical shifts of H₃, H₄, and H₅ protons of 1-methylpyrazole. An unexpected long-range coupling ⁵J (F-CH₃) is observed in 3-fluoro-1-methylpyrazole.     

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.     

Carbon-13 spectra of some tetrahydropyridines. The structure of the tetrahydropyridines from 3,5-lutidine 1-oxide and mercaptans in acetic anhydride

The reaction of 3,5-lutidine 1-oxide ( 1 ) with t-butyl mereaptan in acetic anhydride, with or without triethylamine, was reinvestigated. There was obtained 2-t-butylthio-3,.5-lutidine as the major product, a small quantity of 3-(t-bulylthio)methyl-5-picoline, 1-acetyl-2,3-diacetoxy-3,5-dirnethyl-6-t-butylthio-1,2,3,6-tetrahydropyridine (which represents a structure revision) and l-acetyl-2,6-dihydroxy-3-t-butylthio-3,5-dimethyl-1,2,3,6-tetrahydropyridine. A similar reaction of 1 with 1-adamantyl mercaptan furnished 2-(l-adamantylthio)-3,5-lutidine and 1-acetyl-2,3-diacetoxy-3,5-dimethyl-6-(1-adamantylthio)-1,2,3,6-tetrahydropyridine. The structures of these new tetrahydropyridines were established primarily by carbon-13 nmr spectra.     

Synthesis of 4H-1,3,4-oxadiazino[5,6-b]quinoxalines from 2-substituted quinoxaline 4-oxides

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 8 with acetic anhydride resulted in the intramolecular cyclization to give 8-chloro-2,4-dimethyl-4H-1,3,4-oxadiazino[5,6-b]quinoxaline 7a , while the reaction of compound 8 with acetic anhydride/pyridine or acetic anhydride/acetic acid afforded 3-(2,2-diacetyl-1-memymydrazmo)-7-chloro-2-oxo-1,2-dihydroquinoxaline 9 , effecting no intramolecular cyclization. The reaction of 2-(2-acetyl-1-methylhydrazino)-6-chloroquinoxaline 4-oxide 10a or 6-chloro-2-(1-methyl-2-trifluoroacetylhydrazino)quinoxaline 4-oxide 10b with phosphoryl chloride provided compound 7a or 8-chloro-4-memyl-2-trifluoromethyl-4H-1,3,4-oxadiazino[5,6-b]quinoxaline 7b , respectively. The reaction of compound 7b with phosphorus pentasulfide gave 7-chloro-3-(1-methyl-2-trifluoroacetylhydrazino)-2-thioxo-1,2-dihydroquinoxaline 11 , whose dehydration with sulfuric acid in acetic acid afforded 8-chloro-4-methyl-2-trifluoromemyl-4H-1,3,4-thiadiazino[5,6-b]quinoxaline 12 .     

Zur direkten Nitrierung des Benzimidazolons und der Reduktion einiger dieser Nitrierungsprodukte

Different methods of direct nitration led to mono-, di-, tri- and tetranitrobenzimidazolone. Nitration of benzimidazolone with conc. HNO₃ in glacial acetic acid and acetic anhydride at 30° gives 5-nitrobenzimidazolone, at 70° dinitrobenzimidazolone. Nitration with fuming HNO₃ at 60° gives pure trinitrobenzimidazolone. The tetranitrobenzimidazolone is received by nitration with acetyl nitrate at 70°. Reduction of mono- and dinitrobenzimidazolone to the corresponding amines is best carried out with hyrazine and Raney nickel.     

Base catalyzed acylative decarboxylation. Part III. Acylation of homophthalic acid

Homophthalic acid (I) reacts with acetic anhydride in the presence of base to form the expected product, o-carboxyphenylacetone (III). Besides III, three other new products were formed, namely, 3-methyl-4-carboxyisocoumarin (II), 4-acetyl-3-methylisocoumarin (IV) and 8-acetyl-7-methylnaphtho[1,2-c]isocoumarin. A mechanism for the formation of these compounds is presented. The presence of 3-methyl-4-carboxyisocoumarin (II) supports an earlier suggestion (1) that acylation can occur prior to and without decarboxylation, which has been a point of concern in this reaction.     

Nitration of trans-2-styrylthiophene

The nitration of trans-2-styrylthiophene in carbon tetrachloride, nitroethane and acetic anhydride has been investigated. The nitration products were: β-nitro-2-styrylthiophene as the main product with 3-nitro-2-styrylthiophene and the 5-nitro isomer in smaller amounts. They were identified by the chromato-graphic and spectroscopic (uv and nmr) comparison with the reference compounds. The isomer percentages, determined by glc, were unchanged under different nitration conditions (time, temperature and molar ratio), but were dependent on the solvent used.     

Tetrahydropyridinediols and related aldehydes from the reactions of pyridine N-oxide with mercaptans

A new series of tetrahydropyridines was isolated when 1-adamantyl or t-butyl mercaptan was added last to a solution of pyridine N-oxide and triethylamine in acetic anhydride. Under these conditions, the predominant tetrahydropyridines proved to be 1-acetyl-2-alkylthio-3-acetoxy-6-hydroxy-1,2,3,6-tetrahydropyridines. These carbinolamides were isomerized in part during silica gel column chromatography to trans-4-acetoxy-5-alkylthio-5-acetamido-2-pentenals.     

Synthesis of 3-(3-Acetyl-5-aryl-2,3-dihydro-1,3,4-oxadiazol-2-yl)chromones

A method is proposed for the synthesis of 3-(3-acetyl-5-aryl-2,3-dihydro-1,3,4-oxadiazol-2-yl)chromones which consists of the conversion of 3-formylchromones to aroylhydrazones and their subsequent heterocyclization using acetic anhydride.     

Investigation of some nitrogen compounds of 2,2′-dithienyl

The dithienyl analog (I) of cinchophen was obtained by condensation of isatin with 5-acetyl-2,2-dithienyl in alkaline media. The nitration of I with cupric nitrate in acetic anhydride gave 5-(4-carboxy-2-quinolyl)-5-nitro and 5-(4-carboxy-2-quinolyl)-3- nitro-2,2-dithienyls, the structures of which were established by alternative synthesis.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 770–772, June, 1972.     

Pyridazines. IV. The synthesis and some reactions of acetylpyridazines

Two 3-acetylpyridazines have been prepared. N-Oxidation of 3-acetylpyridazine ( 6 ) gave only 3-acetylpyridazine 1-oxide ( 7 ). During the N-oxidation of 3-acetyl-6-methoxypyridazine ( 10 ), three primary products, namely, 3-acetyl-6-methoxypyridazine 1-oxide ( 12 ), 3-acetyl-6-methoxy-pyridazine 2-oxide ( 13 ), 3-acetylpyridazin-6-one ( 14 ) and an artifact, 3-methoxypyridazine 1-oxide ( 15 ) were obtained. Furthermore, it has been shown that 3-methoxypyridazine 1-oxide ( 15 ) can be obtained in quantitative yield by treatment of 3-acetyl-6-methoxypyridazine 2-oxide ( 13 ) with dilute sodium hydroxide solution at room temperature. This represents a novel deacylation reaction. Nitration of 3-acetylpyridazine 1-oxide, ( 7 ) gave 3,4-bis(3′-pyridazinoyl)furoxan 1′,1′-dioxide ( 19 ) rather than a simple nitration product. 3-Acetyl-pyridazine ( 6 ) and 3-acetyl-6-methoxypyridazine ( 10 ) also gave furoxans ( 22 and 23 ) upon nitration.     

On formation of thiohydantoins from amino acids under acylation conditions

Reactions of glycine, alanine, and phenylalanine with acetic anhydride and ammonium thiocyanate give the 1-acetyl-2-thiohydantoins 2a-c. These results appear to contradict prior literature reports pertaining to this reaction.