Bromination of 2-acetylthiophene and its derivatives

A new method has been developed for the bromination of thiophene and its derivatives. The method consists in the action of N-bromosuccinimide in acetic anhydride and glacial acetic acid on the thiophene derivatives. In the bromination of 2-acetylthiophene and its derivatives, the bromine replaces the hydrogen atom in the 5 position of the thiophene ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 185–187, February, 1973.     

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.     

The bromination of 2-amino- and 2-acetylamino-4-(2-furyl)-thiazoles

The bromination of 2-amino-and 2-acetylamino-4-(2-furyl)thiazoles has been studied, and it has been shown that bromination takes place first in the furan ring and then, with an excess of bromine, also in the thiazole ring in position 5.     

Heterocyclization of 2-(Propargylsulfanyl)-1,3-thiazole Derivatives by the Action of Halogens

Reactions of 2-(propargylsulfanyl)-5-methyl-1,3,4-thiadiazole, N-[5-(propargylsulfanyl)-1,3,4-thiadiazol- 2-yl]benzamide, 2-(propargylsulfanyl)-1,3-benzothiazole, and 2-(propargylsulfanyl)-4,5-dihydro-1,3- thiazole with iodine involved annulation of the unsaturated substituent with formation of fused thiazole ring. 2(5)-(Propargylsulfanyl)-1,3,4-thiadiazole derivatives reacted with bromine to give mixtures of heterocyclization products and bromine adducts to the triple bond. The bromination of 2-(propargylsulfanyl)-4,5-dihydro- 1,3-thiazole afforded only the bromine addition product to the triple bond.     

Bromination of 4-substituted thiazolylhydrazones

4-Phenyl- and 4-methylthiazolylhydrazones were brominated in chloroform and acetic acid. The use of 1.5 equivalents of bromine led to the exclusive formation of the 5-halo derivatives. Effects of substituents on the thiazole ring and of the hydrazone fragment aromatic ring on the course of the reaction were discovered.Urals State Technical University-UPI, 620002 Yekaterinburg. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 991–995, July, 1995. Original article submitted March 1, 1995.     

Bromination of 4-(2-thienyl)thiazoles and 2-(2-thienyl)quinoline

Depending on the substituent, the bromination of 4-(2-thienyl)thiazoles and 2-(2-thienyl)quinoline takes place in the 5 position of the thiophene or thiazole ring. When an amino group is present in the 2 position of the thiazole ring, bromination takes place in the 5 position of the thiazole ring. When excess brominating agent is present, a second bromine atom enters the 5 position of the free ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 35–38, January, 1982.     

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.     

Halogenation of 2-Unsubstituted and 2-Methylimidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridine Derivatives

Halogenation of 2-unsubstituted and 2-methylimidazo[4,5-b]pyridines and their N-methyl derivatives with bromine and chlorine in acetic acid takes different pathways, depending on the acetic acid concentration. The bromination in 50% aqueous acetic acid gives only 6-bromoimidazo[4,5-b]pyridines; bromination and chlorination of 2-unsubstituted imidazo[4,5-b]pyridines in glacial acetic acid leads to 5,6-dibromo(dichloro)imidazo[4,5-b]pyridin-2-ones, and bromination of 2-methylimidazo[4,5-b]pyridines in glacial acetic acid involves both the pyridine ring and the 2-methyl group to afford the corresponding 6-bromo-2-tribromomethylimidazo[4,5-b]pyridines.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 3, 2005, pp. 457–461.Original Russian Text Copyright © 2005 by Yutilov, Lopatinskaya, Smolyar, Gres’ko.     

Bromination of 1-(4-nitrophenyl)-2-formylpyrrole

Depending on the amount of bromine, the bromination of 1-(4-nitrophenyl)-2-formylpyrrole with bromine in chloroform without a catalyst gives 5-bromo and 4,5-dibromo derivatives. 4-Bromo-1-(4-nitrophenyl)-2-formylpyrrole is formed in the presence of excess AlC1₃, while a mixture of 3,4- and 4,5-dibromo derivatives with preponderance of the latter is formed with excess bromine. The results are compared with the literature data on the bromination of 2-formylpyrrole, 2-formylfuran, and 2-formylthiophene and are interpreted with allowance for the electronacceptor effect of the p-nitrophenyl substituent attached to the nitrogen atom of the pyrrole ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 662–665, May, 1982.     

Kinetics of the bromination of tetraazaporphin

The kinetics of the bromination of tetraazaporphin by bromine in glacial acetic acid were studied. It is suggested that bromination takes place through the formation of a molecular complex between porphyrin and bromine. Possible reaction schemes are proposed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 619–624, May, 1992.     

Bromination of N,N'-Substituted Malonodiamides

Aiming at preparation of biologically active compounds a bromination of N,N'-substituted malonodiamides in a glacial acetic acid was carried out. The use of one equiv of bromine provided monobromo derivatives, with two equiv of bromine dibromo-substituted products were obtained. Among the N,N'-dibenzylamides of alkylmalonic acids only the methyl homolog underwent bromination. The structure of compounds was proved by IR and ¹H NMR spectroscopy. The effect of the compounds synthesized on the central nervous system was investigated.     

Synthesis of 2-carbethoxy-3-methyl-4-hydroxybenzofuran derivatives

A number of 2-.carbethoxy-3-methylbenzofuran derivatives were synthesized. A 5,5-gem-dibromo derivative was obtained in the bromination of 2-carbethoxy-3-methyl-4-oxo-4, 5,6,7,tetrahydrobenzofuran. Dehydrobromination of this, dibromo derivative gave 2-carbethoxy-3-methyl-4-hydroxy-5-bromobenzofuran. Depending on the structure of the starting compound and the brominating agent, the bromine in the bromination of 2-carbethoxy-3-methyl-4-hydroxy- and 4-acetoxybenzofurans with bromine and N-bromosuccinimide is incorporated either in the methyl group or in 5 and 7 positions of the benzofuran ring. The nitration of 2-carbethoxy-3-methyl-4-hydroxybenzofuran and its bromo derivative leads to 5-nitro- and 5,7-dinitrobenzofuran derivatives. The structures of the synthesized benzofuran derivatives were established by means of the PMR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 27–29, January, 1980.     

Synthesis of isomeric bromo(diethoxyphosphorylmethyl)furans

Series of the previously unknown bromo(diethoxyphosphorylmethyl)furans including four of six possible regioisomers is synthesized. The target products were obtained by bromination of the corresponding (diethoxyphosphorylmethyl)furans or by a four-step synthesis including bromination of isomeric methyl-furancarboxylates, reduction of the products formed to the corresponding alcohols, substitution of hydroxy group with halogen and phosphorylation by the Michaelis-Becker reaction. It was established for the first fime that in the course of bromination of alkyl carboxylates and phosphonates of the furan series under the typical conditions of electrophilic reaction (Br₂ + 10% molar of AlCl₃, chloroform) the substituent enters not only into the heteroring, but also into the side chain. In the case of 5-methyl-2-(diethoxyphosphorylmethyl)furan only the last reaction pathway is observed. It is shown that bromo(chloromethyl)furans react with sodium diethyl phosphite not only according to the Michaelis-Becker scheme leading to phosphonates, but also by the pathway of debromination of the furan ring. The last unexpected reaction may acquire a practical use for removing a substituent protecting the α-position of the furan ring under mild conditions.     

Bromination and nitration of 2 (3) - ph enyl-5(6)-hydroxybenzofurans

It was established that substituents primarily are incorporated in the benzene ring in the bromination and nitration of 2(3)-phenyl-5(6)-hydroxybenzofurans. The acetoxy derivatives of the same benzofurans are brominated and nitrated only in the free position of the furan ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 311–315, March, 1976.     

Synthesis and some transformations of 2-(2-furyl)naphtho[1,2-<Emphasis Type="Italic">d</Emphasis>]oxazole

By condensation of 1-amino-2-hydroxynaphthalene with furoyl chloride in 1-methyl-2-pyrrolidone 2-(2-furyl)naphtho[1,2-d]oxazole was synthesized and brought into electrophylic substitution reactions: nitration, bromination, sulfonation, formylation, and acylation. The substituent commonly was introduced into the position 5 of the furan ring, but at the nitration and bromination electrophilic attack was directed both at the furan ring and the naphthalene fragment.     

Synthesis and some transformations of 5-(N-tosylaminomethyl)furfuryl alcohols

Preparative methods were developed for the synthesis of 5-(N-tosylaminomethyl)furfuryl alcohols, and their behavior during the action of acidic catalysts was studied. It was established that the furan ring of these compounds is stable in the presence of orthophosphoric acid in glacial acetic acid and that their hydroxyl and N-tosylaminomethyl groups are involved in the transformations.     

N-Bromosuccinimide assisted oxidation of 5-aminopyrazoles: formation of bis diazenylderivatives

Treatment of 5-amino-4-cyanopyrazoles with N-bromosuccinimide, in DMF at rt gave azo dyes resulting from dimerization through the amino groups and further oxidation.With bromine water the dimer was also formed but, bromination occurred on the aryl ring, either at reflux or rt. Reduction of the azo group with zinc in acetic acid originated the corresponding pyrazoles.     

Antianexiety activity of pyridine derivatives synthesized from 2-chloro-6-hydrazino-isonicotinic acid hydrazide

A series of oxadiazole pyridine derivatives were synthesized by using 2-chloro-6-hydrazinoisonicotinic acid hydrazide as starting material. Treatment of the hydrazide with carbon disulfide to afford the oxadiazole derivative, which was treated with 5-methyl-2-furancarbaldehyde, formic acid, acetic acid/acetic anhydride, or phthalic anhydride to yield the corresponding pyridinodiazoles and on imide. Condensation of the hydrazide with p-fluorobenzaldehyde in ethanol or acetic acid in the presence of sodium acetate afforded hydrazone and oxadiazole derivatives, which were acetylated and cyclized with acetic anhydride to N-acetyloxadiazole derivatives. The hydrazone was treated with acetic acid in the presence of sodium acetate, or bromine water/sodium acetate to give on oxadiazole, while it was cyclized with chloroacetyl chloride in the presence of TEA to oxoazetidinaminoisonicotinamide. Finally, condensation of the hydrazide with acid anhydrides in refluxing glacial acetic acid afforded the corresponding bisimide derivatives. The pharmacological screening showed that many of these obtained compounds have good antianexiety activity comparable to diazepam^® as positive control.     

1,2,6-Phosphadiazine-1,3-dione derivatives

A number of new 1-aryloxy-5-methyl-1,2,3,6-tetrahydro-1,2,6-phosphadiazine-1,3-diones were obtained from arylphosphoric acid dichlorides through the corresponding diamidophosphoric acid esters. Conversion of the 1-phenoxy and 1-ethoxy derivatives to 6-methyl-4-hydroxypyrimidine under Vilsmeierformylation conditions was observed. These compounds were thionated to give the corresponding 1,3-dithiones; the 1-phenoxy derivative was subsequently methylated in the 6 position and animated to give the phosphorus-containing analog of 6-methyl-2-thiocytosine. The bromination of the 1-ethoxy compound and replacement of the bromine by a secondary amine residue were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 972–976, July, 1978.     

Chemistry of benzo[b]selenophene

The bromination of benzo[b]selenophene with an equimolecular amount of bromine and its acetylation with acetic anhydride in the presence of boron trichloride etherate proceed to form a mixture of isomeric 2- and 3-substituted derivatives; 2,3-dibromobenzo[b]selenophene is formed on bromination with two equivalents of bromine. Benzo[b]selenophene-2-carboxylic acid, its acid chloride and methyl ester, as well as 2-acetylbenzo[b]selenophene, were synthesized from the lithium derivative of benzo[b]selenophene.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 15–19, January, 1972.