A synthesis of some novel 4,5-dihydroazepines by the reaction of oxazolium 5-oxides with 1,2-dicyanocyclobutene

Heating primary or secondary α-amino acids in acetic anhydride in the presence of 1,2-dicyanocyclobutene leads to 4,5-dihydroazepines via the intermediacy of mesoionic oxazolium 5-oxides.     

7-azaindole derivatives

A new method for synthesizing 5- and 7-azaindoles is given, -Chlorobutyronitrile and malonyl chloride give 2, 4, 6-trichloro-3-(ß-chloroethyl) pyridine, which is cyclized with ammonia to 4, 6-dichloro-7-azaindoline and 4, 6-dichloro-5-azaindoline. 6-Chloro derivatives of 7-azaindolines are not dehydrogenated by chlorainil, but 2, 3-dichloro-S, 6-dicyanobenzoquinone converts them to 6-chloro-7-azaindoles. It is shown that sodium in liquid ammonia is an effective means of dehydrogenating the 5-azaindoline to 5-azaindole. In this case, dehydrogenation of 4, 6-dichloro-7-azaindoline is followed by dehalogenation.For Part IX see [1].     

A reliable synthesis of 1,1-dimethylpyrazolium 5-oxides

Reliable syntheses of compounds having the novel 1,1-dimethylpyrazolium 5-oxide ring system are reported. The method involves treating the dimethylhydrazone of a β-ketoester with a small amount of concentrated sulfuric acid or other catalyst and heating under reduced pressure for 1–24 hours. In this manner two new members of the series have been prepared and characterized.     

Investigation of the protonation of 5-azaindole derivatives by pmr spectroscopy

The protonation of some 5-azaindoles and 5-azaindolines by trifluoroacetic acid in media with different dielectric constants was studied by PMR spectroscopy. Protonation occurs at the nitrogen atom of the pyridine ring. The structures of the monocations of 5-azaindole, 5-azaindoline, and their 1-phenyl derivatives correspond to a considerable contribution of the quinoid structure with transfer of positive charge to the nitrogen atom of the pyrrole fragment of the molecule. On the basis of an investigation of the chemical shifts of the protons of 1-phenyl-5-azaindole and 1-phenyl-5-azaindoline on the trifluoroacetic acid concentration in methylene chloride, acetonitrile, and deuteroacetone, a protonation mechanism in which transfer of a proton from the donor to the acceptor in slightly polar media occurs through the formation of a hydrogen-bonded complex of the base with the acid is proposed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 767–772, June, 1973.     

A novel and facile synthesis of mesoionic 1,2,4-triazolium-3-thiolate derivatives

Mesoionic 1,2,4-triazolium-3-thiolate derivatives were synthesized from the reaction of N-substituted-2-phenylhydrazinocarbothioamides with tetracyanoethylene (TCNE) to give tricyanovinyl intermediates, followed by heterocyclization to afford 5-(1-amino-2,2-dicyano-vinyl)-4-substituted-1-phenyl-4H-1,2,4-triazol-1-ium-3-thiolates in 67–76% yields. The structures of the products have been confirmed unambiguously by single crystal X-ray structure analyses. A rationale for the formation of the products is presented.     

Studies on mesoionic compounds,II. The solvent effect on the electronic absorption spectra of mesoionic 2,3-diaryl-2H-tetrazolium-5-thiolate derivatives

The electronic absorption spectra of 2,3-di(2-fluorophenyl)-, 2,3-di(4-fluorophenyl)-, 2,3-di-(2-chlorophenyl)-, 2,3-di(2-methylphenyl)-, 2,3-di(4-methylphenyl)- and 2,3-di(2-methoxyphenyl)-2H-tetrazolium-5-thiolates have been measured in pure and mixed solvents. They were found to exhibit three characteristic absorption bands at 480-380 nm, near 250 and near 210; the longest wavenlength band of which was assigned to an n → π* transition.     

1-Hetaryltriazenes in the synthesis of condensed mesoionic 1,2,3-triazolio-5-olates

Condensed mesoionic 1,2,3-triazoles containing an aryl or hetaryl substituent at N₍₂₎ in the ring have been synthesized by intramolecular condensation. Dedicated to Academician M. G. Voronkov on his Eighty-Fifth Birthday. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1714–1719, November, 2006.     

Convenient synthesis of 5-trifluoroacetylated imidazoles by ring transformation of mesoionic 1,3-oxazolium-5-olates

Mesoionic 4-trifluoroacetyl-1,3-oxazolium-5-olates (1), obtained from the reaction of N-acyl-N-alkylglycines (2) with trifluoroacetic anhydride, react with amidines to give 5-trifluoroacetylimidazoles (3) in moderate yield. The novel ring transformations of 1 into 3 occur via an initial attack of amidines on the C-2 position of the ring.     

Amide derivatives of 4-azaindole: Design,synthesis, and EGFR targeting anticancer agents

Abstract

A series of amide derivatives of azaindole-oxazoles (11a-n) were designed and synthesized and their structures were confirmed by ¹HNMR, ¹³CNMR and mass spectral analysis. Further, these derivatives were screened for their anticancer activity against human cancer cell lines viz; MCF7 (breast), A549 (lung) and A375 (melanoma). In vitro anticancer activity screening indicated that most of the hybrids exhibited potent inhibitory activities in a variety of cancer cell lines. Among the compounds 11d, 11e, 11f, 11j, 11k, 11l, 11m, and 11n were exhibited more potent activity than standard, in those mainly two compounds 11m and 11j were exhibited excellent activity in MCF-7 cell line with IC₅₀ values 0.034 and 0.036?µM. Moreover, all these compounds were carried out their molecular docking studies on EGFR receptor results indicated that two potent compounds 11m and 11j were strongly binds to protein EGFR (PDB ID: 4hjo). It was found that the energy calculations were in good agreement with the observed IC₅₀ values.     

The enantioselective synthesis of alpha-amino acid derivatives via organoboranes

Optically active (S)-alpha-amino acids are prepared in 54-95% ee (12 cases) by reaction of the Schiff base acetate of glycine tert-butyl ester with B-alkyl-9-BBN derivatives in the presence of the Cinchona alkaloid, cinchonidine, and base. The enantiomeric (R)-alpha-amino acids are available in 59-92% ee (3 cases) by using cinchonine as the chiral control element.     

Absence of triazirine intermediates in the photolytic formation of azides from mesoionic 3-substituted 1,2,3,4-oxatriazolylio-5-oxides : Isotope labelling experiments

Irradiation of 3-phenyl-1,2,3,4-oxatriazolylio-5-oxide (1) leads to formation of CO₂, N₂O, phenyl azide and phenyl isocyanate. The two latter compounds are observed only in low yields because of secondary photolytic reactions. Photolysis in CCl₄ or Cl₂CCCl₂ of 2-¹⁵N labelled (1) leads almost exclusively to the formation of 3-¹⁵H labelled phenyl azide identified by IR spectroscopy on comparison with authentic 1-¹⁵N, 2-¹⁵N and 3-¹⁵N labelled phenyl azides, respectively. These results show that phenyl azide is formed photolytically from (1) via phenyl migration and not via “antiaromatic”, phenyl triazirine (2).     

The synthesis and reactions of certain pyridazine 1-oxides

Nucleophilic displacement reactions under acidic and basic conditions have been studied with 4,6-dinitro-3-methoxypyridazine 1-oxide ( 1 ) and with 6-chloro-3-methoxy-4-nitropyridazine 1-oxide ( 2 ). Depending on the nature of the nucleophilic reagent and the conditions of the reaction we have found that the chloro group, the nitro group, as well as the methoxy group of 1 and 2 may be displaced by the nucleophile. This type of compound possesses significant in vitro antifungal activity.     

N-Lithium derivatives of aliphatic amines in the synthesis of 1-alkyl-2-phenyldiazene 2-oxides

Magnesium derivatives of aliphatic amines containing -hydrogen atoms, in contrast to t-BuNHMgBr, do not form phenylaliphatic diazene oxides upon reaction with nitrobenzene, but rather reduce it to azobenzene and azoxybenzene. Asymmetric diazene oxides are formed when the magnesium derivatives are replaced by lithium derivatives. The reaction of t-BuNHLi with dimethylnitramine gives 1,3,5-trimethyl-1,3,5-triazacyclohexane.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1452–1454, June, 1991.     

Convenient access to C-2 or C-5 substituted 4-azaindole derivatives

Functionalization at C-2 and C-5 of N-benzenesulfonyl-4-azaindole 1 was performed by lithiation reactions and original palladium-catalyzed chemistry. It led to very useful new substituted 4-azaindole derivatives in fair to high yields.