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Bromination of 3,4-dihydro-2H-thiopyran derivatives leads to bromo-substituted 3,4-dihydro-2H-thiopyrans or 4H-thiopyrans, depending on the reaction conditions and the structure of the starting heterocycles.

The reaction of 2-chloro-N-(3-oxoalkenyl)acetamides with 1,3-benzothiazole-2(3H)-thione, 1,3-benzoxazole-2(3H)-thione, and 1-methyl-1,3-dihydro-2H-benzimidazole-2-thione led to the formation of 2-(heteroarylsulfanyl)-N-(3-oxoalkenyl)acetamides. By the action of a base, these compounds were converted into pyridin-2(1H)-ones containing a divalent sulfur atom in position C-3 bonded to a heterocyclic ring. Bromination, nitration, alkylation of 3-(1,3-benzothiazol-2-ylsulfanyl)pyridin-2(1H)-ones have been studied. The action of zinc in acetic acid transformed these compounds into 3-sulfanylpyridin-2(1H)-ones.

A number of previously undescribed derivatives of 2-amino-5-(2-aryl-2-oxoethyl)thiazol-4(5H)-one containing electron-donating substituents in the aromatic ring were synthesized by the reaction of (E)-4-aryl-4-oxobut-2-enoic acids with thiourea. Reduction of the reaction products with NaBH4 yielded diastereomeric alcohols, whereas bromination in AcOH was accompanied by elimination of HBr and the formation of (Z)-2-amino-5-(2-aryl-2-oxoethylidene)thiazol-4(5H)-ones.

Reactivity of 2-methyl-6-phenylbenzo[c][1,7]naphthyridine in alkylation, oxidation, and electrophilic substitution reactions has been studied. The reaction of 2-methyl-6-phenylbenzo[c][1,7]naphthyridines with POCl3 yielded the previously unknown 4-chloro-2-methyl-6-phenylbenzo[c][1,7]naphthyridine. Its dehalogenation and substitution of halogen by nitrogen and sulfur nucleophiles were studied.

A convenient method for the synthesis of methyl 8-oxo-3H,8H-2a,5a,7-triazaacenaphthylene-2-carboxylate by iodination of 7-allyl-4-methoxypyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester followed by elimination of hydrogen iodide has been developed. The use of 4-methoxypyrrolo[2,3-d]pyrimidine-6-carboxylic acid as the starting compound led to the formation of iodomethylpyrimido[5',4':4,5]-pyrrolo[2,1-c][1,4]oxazine, a promising precursor for the synthesis of a new tricyclic system based on pyrrolo[2,3-d]pyrimidine.

This study was focused on the oxidation reactions of 4,7- and 6,7-dihydroazolo[1,5-а]pyrimidines with bromine and mechanisms for such reactions were proposed. The effects of ethoxyphenyl substituent and azole ring on the reaction kinetics were demonstrated. The structures of the main products and intermediates of bromination and oxidation reactions were confirmed by 1H NMR spectroscopy, GCMS analysis, and X-ray structural analysis. It was established that the noticeable tuberculostatic activity of azolo[1,5-а]pyrimidines became considerably weaker in the case of their brominated analogs.

A sequence of microwave-assisted Suzuki cross-coupling reaction and bromination with N-bromosuccinimide was used for the synthesis of 3,3'-(5,5'-{5-[5-(9-ethyl-9H-carbazol-3-yl)-3-hexylthiophen-2-yl]pyrimidine-4,6-diyl}bis(thiophene-5,2-diyl))bis(9-ethyl-9H-carbazole). The obtained compound was characterized with regard to its optical properties, as well as possible applications in sensors for nitroaromatic compounds in acetonitrile solutions and in vapor phase.

Methods have been developed for the synthesis of anthra[2,3-b]thiophene-3(2)-carboxylic acids and their derivatives through modifications of 4,11-dibutoxy-3-methylanthra[2,3-b]thiophene-5,10-dione. A scheme involving methyl group transformations was proposed for the preparation of dibutoxyanthra[2,3-b]thiophene-3-carboxylic acid, including reactions of radical halogenation, hydrolysis, and oxidation of a 3-formyl derivative. 4,11-Dihydroxy-3-methylanthra[2,3-b]thiophene-2-carboxylic acid was synthesized from the appropriate carbonitrile, obtained by Rosenmund–von Braun reaction from 2-bromo-4,11-dibutoxy-3-methylanthra[2,3-b]-thiophene-5,10-dione.

3- and 8-Iodoimidazo[1,2-a]pyridines were synthesized from imidazo[1,2-a]pyridine under different substitution conditions. The molecular electrostatic potential calculations were performed to investigate the chemoselectivity of the substitution reaction. The molecular structures of the target compounds were characterized by single crystal X-ray diffraction analysis.

Bromination and iodination of 4-methallyl-5-methallylamino-1,2,4-triazole-3-thione lead to the annulation of five- and six-membered thiazaheterocycles, respectively. The usage of halogen excess does not give the product of 5-methallylamino group cyclization – the product of the bromine addition was isolated.

3,3-Bis(azidomethyl)oxetane and 3-azidomethyl-3-methyloxetane were obtained by bromination of pentaerythritol and metriol with a mixture of hydrobromic, acetic, and sulfuric acids, followed by cyclization in the presence of a phase-transfer catalyst TBAB, with the formation of oxetane ring and replacement of bromide substituents with azide ions. The copolymerization reaction of 3,3-bis-(azidomethyl)oxetane and 3-azidomethyl-3-methyloxetane was performed in the presence of a catalytic system prepared from triisobutylaluminum and water. The methods of small-angle and wide-angle X-ray diffraction analysis were used to determine the amorphous-crystalline and domain structures of the synthesized copolymers. We also present data about conformational and relaxation transitions in these statistical copolymers.

Reactions of α,ω-dibromoalkanes with pyrazole and 3,5-dimethylpyrazole in superbasic medium of dimethyl sulfoxide – potassium hydroxide were used for the synthesis of bidentate ligands: bis(pyrazol-1-yl)alkanes and bis(3,5-dimethylpyrazol-1-yl)alkanes linked by alkyl chains containing between four and twelve methylene groups. Oxidative iodination of the obtained compounds with I2–HIO3–H2SO4 system in acetic acid provided diiodo derivatives: bis(4-iodopyrazol-1-yl)alkanes and bis(4-iodo-3,5-dimethylpyrazol-1-yl)alkanes. The obtained diiodo derivatives of pyrazole were further converted to mono- and dipyrazolium salts by alkylation of nitrogen atom at position 2 of the pyrazole rings with iodomethane, as well as with methyl triflate. These products are of interest as precursors to mesoionic N-heterocyclic carbene complexes. The cytotoxicity of the obtained compounds was studied against THP-1 monocytic leukemia cells.

5-Bromo-5-fluoro- and 5-chloro-5-fluoro-6-hydroxy-5,6-dihydrouracils were obtained in high yields by oxidative halogenation of 5-fluorouracil. Nitration of 5-fluorouracil gave 5-fluoro-6-hydroxy-5-nitro-5,6-dihydrouracil. Theoretical calculations in B3LYP/6-311+G(d,p) // B3LYP/6-311G(d,p) + IEFPCM approximation and GIAO simulation of 13C NMR spectra and spin-spin coupling constants agree with the structure of the compounds obtained, which manifest an equatorial orientation of the fluorine atom and an axial orientation of the hydroxy group at position 6 of the dihydrouracil ring. The principal possibility of oxidative iodination of 5-halouracils was studied in B3LYP/CEP-121G approximation. It was found that reversible elimination of iodine by a nucleophilic agent to give the original compounds is the main transformation pathway of the intermediate in this process.

A new process for the synthesis of anticancer drug lenalidomide was developed, using platinum group metal-free and efficient reduction of nitro group with the iron powder and ammonium chloride. It was found that the bromination of the key raw material, methyl 2-methyl-3-nitrobenzoate, could be carried out in chlorine-free solvent methyl acetate without forming significant amounts of hazardous by-products. We also have compared the known synthetic methods for cyclization of methyl 2-(bromomethyl)-3-nitrobenzoate and 3-aminopiperidinedione to form lenalidomide nitro precursor.

A series of new 4,4-dialkyl- and 4,4-diaryl-4H-indeno[1,2-b]thiophenes and their 2-bromo derivatives were synthesized and characterized. An economical one-pot method for the preparation of the key starting material 2-(2-thienyl)benzoic acid and improved procedures for the synthesis of indeno[1,2-b]thiophen-4-one and 4,4-dialkyl-4H-indeno[1,2-b]thiophenes have been developed. The described methods were shown to be efficient for the preparation of the title compounds on a multigram scale.

N-Protected (S)-2-(diazoacetyl)pyrrolidines can be considered as a group of the N-protected (S)-proline derivatives. They can be conveniently prepared from the corresponding acyl chloride or mixed anhydride via Arndt–Eistert reaction.1 In recent years, the N-protected (S)-2-(diazoacetyl)-pyrrolidines have been widely explored as easily available, chiral building blocks bearing the reactive diazo function and have found numerous applications for the multistep synthesis of more complicated heterocycles including some natural products and their analogs. Some of them are reported to display biological activities, e.g., antifungal,2 α4β2 nicotinic acetylcholine receptor-binding,3 , 4 oxygen free radical scavenging,5 and selective antihistamine.6 Three types of key reactions performed with N-protected (S)-2-(diazoacetyl)pyrrolidines are a) halogenation via treatment with HX agents and N2 elimination, b) catalytic decomposition and generation of reactive ketenes via the Wolff rearrangement of the intermediate α-oxo carbenes, and c) (3+2) cycloaddition reactions of the diazo 1,3-dipole with C=S dipolarophiles. In this article, mainly the papers from the period after 2001 are reviewed.

A practical, robust and scalable synthesis of 6-bromo-4-chlorothieno[2,3-d]pyrimidine starting from cheap bulk chemicals has been developed. The method involves four synthetic steps: Gewald reaction, pyrimidone formation, bromination, and chlorination. The process relies on standard laboratory equipment, allowing to obtain the product in an overall yield of 49% without using chromatography for purification of the product and intermediates.

We have synthesized a series of 3-halo-substituted pyrimidobenzimidazolones and studied the alkylation reaction of the obtained derivatives.

Our investigation of electrochemical chlorination and bromination of pyrazoles decorated with electron-withdrawing and electron-donating groups showed that the product yield and composition depended on the substitution at the N-1 atom. We have shown for the first time the significant differences in halogenation reactivity patterns of N-unsubstituted and N-alkylpyrazoles.

A convenient method of accessing imidazole 2-halo derivatives is proposed, comprising O-acylation of imidazole N-oxide fluoroborate complexes with tosyl halogenides which further undergo cine-substitution of 3-tosyl group with a halogen anion. In conjunction with a previously proposed method of synthesizing N-oxides of 2-unsubstituted 1-arylimidazoles this method enables one to substantially expand the range of accessible compounds.

The ethyl ester of 7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxylic acid reaction with bromine in anhydrous acetic acid producing a mixture of the 9-bromo-substituted product and 6-ethoxycarbonyl-5,7-dihydroxy-2,3-dihydro-1H-pyrido[3,2,1-ij]quinolinium tribromide in a 1:1 ratio. It has been established experimentally that the diuretic activity of 9-bromo-7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxanilides increases substantially in comparison with their non-brominated analogs.

An effective method for the conversion of 1-acetyl-4-phenyl-2-pyrrolidone into 1-acetyl-4-phenyl-3-pyrrolin-2-one by bromination–dehydrobromination with N-bromosuccinimide, catalyzed by azo-bisisobutyronitrile or by UV irradiation is developed. The method was extended to the 1-acetyl-4-phenyl-3-pyrrolin-2-one structural analogs. An employment of an excess of N-bromosuccinimide under given reaction conditions leads to the bromination of 1-acetyl-4-phenyl-3-pyrrolin-2-one and its structural analogs at position 5.

Pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidines were formed on halogenation of 5-allyl-6-thioxopyrazolo[3,4-d]-pyrimidin-4-one, whereas 5-ethylsulfanyl-2-halomethyl[1,3]oxazolo[3,2-c]pyrazolo[4,3-e]pyrimidinium tri-halogenides were formed from 5-allyl-6-ethylsulfanyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one.

In this review, the issues concerning the effectiveness of catalysis by carbenes and their transition metal complexes in a range of organic reactions are discussed as one of the developing areas in contemporary organic chemistry. Among the transformations catalyzed by carbenes, our attention was directed to the transesterification and benzoin condensation reactions that are potentially important for practical application. In the case of transformations catalyzed by the metal carbene complexes, we focussed on the reduction of multiple bonds and the reductive dehalogenation of haloaromatic compounds that are important for organic synthesis and utilization of environmental toxicants.

Treatment of ethyl 7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxylate with bromine in aqueous acetic acid solution gave not only the expected ethyl 2-bromo-1,3-dioxo-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylate, but also an admixture of its 9-bromo-substituted isomer. The structural features of the major and minor reaction products are discussed.

A simple method has been proposed and used for the preparation of 1-allyl-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-di-hydroquinoline-3-carboxylic acid arylalkylamides. Similar to alkylamides of this acid, the arylalkylamides obtained are halogenated with cyclization by one equivalent of molecular bromine to give the corresponding 2-bromomethyl-7,8-dimethoxy-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]quinoline-4-carbox-amides. However, the reaction proceeds quite differently when using an excess of bromine. After the usual initial oxazole ring closure, the excess bromine brominates the aromatic ring of the amide fragment. The results of testing for the analgesic activity of these products are presented.

It has been shown experimentally that upon the reaction of 1-hexyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid 4-pyridylmethylidene hydrazide with molecular bromine in glacial acetic acid not only the azomethine carbon atom is brominated, but also the position 6 of the quinolone ring.