Том 55, № 4 (2019)

Schiff bases derived from α-alanine methyl ester and aromatic aldehydes reacted with methyl vinyl sulfone in toluene at 20°C in the presence of silver acetate and 1.5 equiv of triethylamine to give the corresponding 1,3-dipolar cycloaddition products, methyl (2S*,4S*,5S*)-5-aryl-4-methanesuffonylpyrrolidine-2-carboxylates containing a small impurity (8–25%) of diastereoisomeric (2S*,4R*,5S*)-5-aryl-4-methanesulfonylpyrrolidine-2-carboxylates. The same compounds were formed when the reaction was carried out in boiling toluene, but in this case the (4S*)-diastereoisomer was the minor product. The stereoselectivity of the cycloaddition reactions was interpreted by DFT/PBE calculations of the energies of the final products and transition states.

Three-component condensation of ethyl acetoacetate with formaldehyde and alkanethiols in the presence of 0.1 equiv of sodium hydroxide afforded ethyl 2-[(alkylsulfanyl)methyl]-3-oxobutanoates, and analogous reaction with phenylmethanethiol led to the formation of ethyl 2-[(benzylsulfanyl)methyl]-2-(hydroxymethyl)-3-oxobutanoate. The condensation products reacted with hydrazine hydrate in ethanol at room temperature to give 4-{[alkyl(or benzyl)sulfanyl]methyl}-5-methyl-2,4-dihydro-3H-pyrazol-3-ones which were shown to exist in DMSO-d₆ mainly as 1H-pyrazol-5(3)-ol tautomers.

Tetracyanoethylene adducts of cycloalkanones, 1-(2-oxocycloalkyl)ethane-1,1,2,2-tetracarbonitriles, reacted with aqueous ammonia at room temperature to give, depending on the cycloalkane ring size and reaction conditions, three types of nitrogen-containing heterocyclic compounds. The reaction of tetracyanoethylene-cyclohexanone adducts with 20–25% aqueous ammonia afforded 10,11-diazatricyclo[5.3.2.0^1,6]-dodec-8-ene derivatives, whereas their seven- and eight-membered analogs were converted to pyrrolo[3,4-c]-pyridines under similar conditions. Treatment of 1-(2-oxocyclooctyl)ethane-1,1,2,2-tetracarbonitrile with 10–15% aqueous ammonia led to the formation of 2,5-diamino-3-(2-oxocyclooctyl)-3H-pyrrole-3,4-dicarbonitrile as a mixture of two diastereoisomers.

A one-step procedure has been developed for the synthesis of previously unknown ethyl 5-(arylcarbamoyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylates by reaction of ethyl 2-cyano-3-ethoxyprop-2-enoate with acetoacetanilides in the presence of a catalytic amount of piperidine in ethanol at room temperature.

Double Mannich bases obtained from α-indanone and α-tetralone contain a bis-β-amino ketone fragment and are promising intermediate compounds for the synthesis of nitrogen heterocycles via reactions with dimethyl acetylenedicarboxylate and methyl propiolate. The products of these reactions are determined by the activated acetylene structure. The reaction begins with attack of the activated acetylenic compound on the tertiary nitrogen atom of the Mannich base to give 1,3-zwitterionic intermediate. The subsequent domino reaction is driven by neutralization of the charge on the nitrogen atom through formation and/or rupture of several C–C bonds. Intramolecular attack of the negatively charged center of the 1,3-zwitterion derived from the indanone base and dimethyl acetylenedicarboxylate on the carbonyl carbon atom of the indanone fragment is followed by domino process, leading to the formation of dimethyl 2-methyl-1,2-dihydro-9H-indeno[2,1-c]-pyridine-3,4-dicarboxylate. The reaction of the same Mannich base with methyl propiolate involves 1,3-sigma-tropic rearrangement with neutralization of the positive charge on the nitrogen atom in the intermediate structure and negative charge transfer to the carbonyl oxygen atom. Next follows aldolization/crotonization with the second β-amino carbonyl fragment to produce methyl 2′-methyl-1-oxo-1,1′,2′,3,5′,11′-hexahydrospiro-[indene-2,6′-indeno[2,1-c]azocine]-4′-carboxylate. One more reaction direction leading to the formation of linear enamines via intramolecular proton migration from the indan fragment to the C-anionic center in the 1,3-zwitterion with simultaneous elimination of 2-methylideneindan-1-one has been revealed by HPLC/MS analysis of both reaction mixtures. Such enamines, methyl 3-{methyl[(1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]amino}prop-2-enoate and dimethyl (2Z)-2-{methyl[(1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)-methyl]amino}but-2-enedioate, were isolated in the reactions of activated acetylenic compounds with the Mannich base derived from tetralone. Previously described synthesis of 1-azabicyclo[3.3.1]nonanes from Mannich bases has been reproduced, and detailed analysis of the reaction mixtures has revealed products resulting from elimination of one alkylaryl group from the zwitterionic intermediate. The formation of linear enamines, dimethyl (2Z)-2-[methyl(3-oxo-3-phenylpropyl)amino]but-2-enedioate and dimethyl (2Z)-2-{methyl-[3-oxo-3-(thiophen-2-yl)propyl]amino}but-2-enediate, suggests facile retro-aldol reaction of 3-aroyl-4-aryl-1-methylpiperidin-4-ols as the necessary step. PASS online predicted diverse biological activities of all newly synthesized compounds with a probability of 65–80%.

1-Imidoylbenzotriazoles [N-aryl-1-(1H-benzotriazol-1-yl)-2,2,2-trifluoroethan-1-imines] reacted with tosylmethyl isocyanide according to van Leusen’s procedure to give difficultly accessible 1-aryl-4-(4-methylbenzenesulfonyl)-5-(trifluoromethyl)-1H-imidazoles in good yields (81–94%). The initial imidoylbenzotriazoles were conveniently synthesized by reaction of sodium benzotriazolide with the corresponding imidoyl chlorides in THF. The reactions were carried out with a wide series of imidoylbenzotriazoles containing various electron-donating and electron-withdrawing substituents in the N-aryl fragment.

Computer simulation of conformational transformations of 5-ethyl-5-hydroxymefhyl-2,2-dimefhyl-1,3-dioxane in the gas phase, as well as in mixtures with chloroform, DMSO, benzene, and water, has been performed at the DFT PBE/3ζ level of theory. The conformational equilibrium involves chair conformers with axial and equatorial hydroxymethyl group and 2,5-twist structure. The chair conformer with equatorial hydroxymethyl group predominates in benzene and DMSO, whereas the major conformer in the gas phase and in chloroform and water is that with axial hydroxymethyl group. The results of calculations were confirmed by the two-dimensional NMR spectra (NOESY) recorded from solutions in DMSO-d₆ and CDCl₃.

Four potentially biologically active 31-, 32-, and 33-membered macroheterocycles with ester and hydrazide fragments have been synthesized by [1 + 1]-condensation of ethane-1,2-diyl bis(10-oxoundecanoate) with malonic, glutaric, L-(+)-tartaric, and pyridine-2,6-dicarboxylic acid dihydrazides. The product structure has been confirmed by IR, NMR, and mass spectra.

The alkylation of 5-R-tetrazoles (R = H, Me, Ph) with 3-chlorobut-2-en-1-ol was studied in 1,2-dichloroethane, chlorofom, and methylene chloride in the presence of boron trifluoride—diethyl ether complex, as well as in trifluoroacetic acid and in ethyl acetate in the presence of sulfuric acid. The reaction in 1,2-dichloroethane catalyzed by BF₃ · Et₂O gave 70–80% of the alkylation products containing no less than 99% of the 2-substituted isomer.

Reactions of α-halocarboxylic acid amides with 3 equiv of hydroxylamine hydrochloride in the presence of bases involves formation of products of nucleophilic substitution of the halogen atom and their subsequent oxidation to the corresponding oximes. This one-pot transformation can be accomplished in various aprotic solvents or ethanol at 80°C. Dimethyl sulfoxide as solvent ensures the highest selectivity for the oxidation products. The yields of N-substituted 2-(hydroxyimino)carboxylic acid amides range from 22 to 92%.

Three novel dendritic phenothiazine derivatives consisting of a biphenyl core, phenothiazine branching units, and terminal 3,7-di-tert-butylphenothiazine fragments have been synthesized starting from 3,7-di-tert-butylphenothiazine, 4,4′-diiodobiphenyl, and 3,7-diiodophenothiazine. The product structure was confirmed by IR and ¹H NMR spectra.

The direct construction of C-O bond by C-H activation is a highly efficient and practical method for the synthesis of esters, ethers, and hydroxy compounds. As compared to the conventional method of mutual functional group conversion, the C-H activation method provides not only improved atomic economy and reduced number of synthetic steps but also greatly improved overall yield of multistep syntheses. Studies of C-H activation to construct C-O bonds are crucial in the field of organic synthesis and catalysis research, and they have already been one of the research hotspots in related fields. According to the current trends in the development of C-H activation, different reaction types and different reaction conditions are classified in this review, and the latest advances in C-H activation to form C-O bonds are discussed.