V. Ya. Sosnovskikh

Regioselective synthesis of 2- and 5-trifluoromethyl-or 2- and 5-difluoromethylpyrazolo[1,5-c]pyrimidines based on 7,7,7-trifluoro-or 7,7-difluoro-2,4,6-trioxoheptanoic and 6-trifluoromethyl-or 6-difluoromethylcomanic acids

Abstract6-Tri- and 6-difluoromethylcomanic acids and their ethyl esters reacted with aminoguanidine, predominantly giving 5-RF-pyrazolo[1,5-c]pyrimidines, whereas the reaction of the openchain synthetic equivalents, i.e., ethyl 7,7,7-trifluoro- and 7,7-difluoro-2,4,6-trioxoheptanoates, with this polynucleophile allowed us to obtain regioselectively 2-RF-pyrazolo[1,5-c]pyrimidines.

Reactions of 2-Mono- and 2,6-Disubstituted 4-Pyrones with Phenylhydrazine as General Method for the Synthesis of 3-(N-Phenylpyrazolyl)Indoles

Phenylhydrazine reacted regioselectively with 6-substituted 4-pyrone-2-carboxylic acids (or esters) in protic and aprotic solvents, leading to phenylhydrazones of 3-(3-R-1-phenylpyrazol-5-yl)- or 3-(5-R-1-phenylpyrazol-3-yl)pyruvic acids (or esters), respectively. 6-Di(tri)fluoromethylcomanic acids (or esters) reacted analogously, forming the corresponding phenylhydrazones with RF group in the side chain. The obtained phenylhydrazones underwent Fischer reaction under acidic conditions, forming the respective 3-(N-phenylpyrazolyl)indoles. In contrast to comanic acid and its ester, the reactions of 2-substituted 4-pyrones occurred non-selectively and gave mixtures of regioisomeric pyrazoles with phenylhydrazone group in the side chain or 3-(N-phenylpyrazolyl)indoles. A mechanism was proposed to explain the effect of solvent on the course of reaction.

Synthesis of 2-pyridones, pyrimidines, and pyrazoles from 1,1,1-trifluoro-4,4-bis(methylthio)but-3-en-2-one

Reactions of 1,1,1-trifluoro-4,4-bis(methylthio)but-3-en-2-one with cyanoacetamide, malonamide, acetoacetamide, amidines, hydrazines, and hydroxylamine gave a number of novel trifluoromethylated heterocyclic compounds containing the methylthio group.

Reactions of (E)-3,3,3-trichloro(trifluoro)-1-nitropropenes with enamines derived from cycloalkanones. A new type of ring-chain tautomerism in a series of cyclobutane derivatives and stereochemistry of the products

Depending on the reaction conditions, the reactions of (E)-3,3,3-trichloro-1-nitropropene with cyclohexanone enamines led to bicyclo[4.2.0]octanes or trisubstituted enamines, which are the ring-chain tautomers capable of reversible transformations. Diastereoselectivity of the reactions of (E)-3,3,3-trichloro(trifluoro)-1-nitropropenes with cycloalkanone enamines were studied, a series of hitherto unknown CX3-containing nitroalkylated enamines and γ-nitro ketones were synthesized, the structures of novel compounds were determined by NMR spectroscopy and X-ray diffraction.

Preparative synthesis of ethyl 5-acyl-4-pyrone-2-carboxylates and 6-aryl-, 6-alkyl-, and 5-acylcomanic acids on their basis

A simple and efficient method for the synthesis of ethyl 5-alkanoyl- and 5-aroyl-4-pyrone-2-carboxylates was developed, which is based on the condensation of 1-R-2-(dimethyl-aminomethylidene)butane-1,3-diones, obtained from 1,3-diketones and dimethylformamide dimethyl acetal, with diethyl oxalate in the presence of NaH in THF. Ethyl 5-acyl-4-pyrone-2-carboxylates were used in the synthesis of 6-R- and 5-RCO-comanic acids.

The Interaction of 2,5-Diethoxycarbonyl-and 5-Benzoyl-2-Ethoxycarbonyl-4-Pyrones with o-Phenylenediamine*

The esters of chelidonic [1] and comanic [2] acids, as well as 5-benzyloxycomanic acid [3], are known to react with о-phenylenediamine, forming the respective pyrido[1,2-a]quinoxalines. The reaction proceeds by pyrone ring opening, with a subsequent recyclization into derivatives of N-(2-aminophenyl)-4-pyridone, which further cyclize to the final products, pyrido[1,2-a]quinoxalines. However, the intermediates of this process have not been described in the literature. Recently we reported a simple method for the synthesis of 2,5-diethoxycarbonyl-4-pyrone 1а [4] and 5-benzoyl-2-ethoxycarbonyl-4-pyrone 1b [5], providing access to these previously scarce compounds for a wide range of investigations. Here we report the first data regarding the interaction of 4-pyrones 1a,b with о-phenylenediamine. It was found that after 1-2 h in ethanol at 0°C the reaction stopped at the stage of pyrone ring opening and gave 85-89% yields of the products 2a,b, which resulted from an attack by amino group at the С-6 atom activated by two carbonyl groups. As indicated by Н NMR spectra, these polyfunctional compounds exist in CDCl3 as three open-chain tautomeric forms in a 76:18:6 ratio (compound 2a) and 76:15:9 ratio (compound 2b). Two of these tautomers (the major forms А and B) are shown in the Scheme, while the structure of the third tautomer was not established. The intermediates 2a,b easily cyclized upon treatment with MeSO3H or refluxing in ethanol, giving new pyrido[1,2-a]quinoxaline derivatives 3a,b (in 55% and 69% yields, respectively), which present interest for medicinal chemistry as potential antimicrobial [1] and antiviral agents [6-8]. This class of compounds also includes the recently introduced anti-HIV drug dolutegravir [6-8]. The Н NMR spectrum of the intermediate 2a features a main set of signals due to the tautomer A with a 2Z,5E configuration of double bonds, which consists of a doublet for the NH proton (δ 12.41 ppm, J = 13.1 Hz), apparently involved in a strong intramolecular hydrogen bond with the ketone carbonyl, a doublet for the

Reactions of 1,1,1-trihalo-3-nitrobut-2-enes with enamines derived from cycloalkanones. Rearrangement of trifluoromethylated 1,2-oxazine N -oxide into 1-pyrroline N -oxides and stereochemistry of the products

Abstract1,2-Oxazine N-oxides derived from (E)-1,1,1-trifluoro-3-nitrobut-2-ene and cyclohexanone enamines underwent spontaneous rearrangement with ring contraction to give 1-pyrroline N-oxides. Reactions of (E)-1,1,1-trifluoro(trichloro)-3-nitrobut-2-enes with N-cyclopent-enylmorpholine resulted in a series of novel CX3-containing nitroalkyl enamines and g-nitro ketones; the stereochemistry of the synthesized compounds were studied by NMR spectroscopy and X-ray diffraction.

Simple synthesis of functionalized 7-aza-2H-chromenes from pyridoxal and nitroalkenes in aqueous medium

A reaction of 1-nitro-3,3,3-trichloro(trifluoro)propenes and β-nitrostyrene with pyridoxal hydrochloride in the presence of sodium hydroxide in aqueous medium gives good yields of new derivatives of 7-aza-2H-chromene system.

Synthesis of 6-(2-hydroxyaryl)-2-pyridones by the reaction of chromones with cyanoacetic, acetoacetic, and malonic acid amides

A reaction of chromones with cyanoacetic, acetoacetic, and malonic acid amides in the presence of sodium ethoxide furnished a number of new 3-substituted 6-(2-hydroxyaryl)-2-pyridones in good yields, including those containing a polyfluoroalkyl group at position 4.

Reaction of 3-cyanochromones with pyridinium phenacylide

The reaction of 3-cyanochromones with Nand C-nucleophiles begins with an attack at C-2 atom with subsequent opening of the γ-pyrone ring and recyclization at the C=O or C≡N groups [1-3]. Nucleophilic 1,2-addition at the cyano group usually does not occur [1], while the reactions with aromatic amines [4] and methylenetriphenylphosphorane (Ph3P=CH2) [5] terminate at the stage of open products 1 and 2. Since the assumption of a number of workers of possible addition of nucleophiles at the cyano group was subsequently shown to be incorrect [1], the reports in the literature on the synthesis of azirines 3a,b from the corresponding 3-cyanochromones 4a,b and pyridinium phenacylide [6] are cast in doubt and require verification.