Carbocyclic functionalization of quinoxalines, their chalcogen congeners 2,1,3-benzothia/selenadiazoles, and related 1,2-diaminobenzenes based on nucleophilic substitution of fluorine

Carbocyclic functionalization of quinoxalines, their chalcogen congeners 2,1,3-benzothia/selenadiazoles, and related 1,2-diaminobenzenes based on nucleophilic substitution of fluorine Full article

Journal

Journal of Fluorine Chemistry
ISSN: 0022-1139

Output data

Year: 2016, Volume: 183, Pages: 44-58 Pages count : 15 DOI: 10.1016/j.jfluchem.2016.01.009

Tags

1,2-Diaminobenzenes; Nucleophilic substitution; Organofluorine; Quinoxalines; 2,1,3-Benzothia/selenadiazoles

Authors

Mikhailovskaya Tatiana F. ¹ , Makarov Arkady G. ^1,2,3 , Selikhova Natalia Yu. ² , Makarov Alexander Yu. ^1,2 , Pritchina Elena A. ^3,4 , Bagryanskaya Irina Yu. ^1,3 , Vorontsova Elena V. ⁵ , Ivanov Igor D. ⁵ , Tikhova Vera D. ¹ , Gritsan Nina P. ^4,6 , Slizhov Yuri G. ² , Zibarev Andrey V. ^1,2,6

Affiliations

1	(Данные Web of science) Russian Acad Sci, Inst Organ Chem, Novosibirsk 630090, Russia
2	(Данные Web of science) Tomsk State Univ, Dept Chem, Tomsk 634050, Russia
3	(Данные Web of science) Novosibirsk State Univ, Dept Nat Sci, Novosibirsk 630090, Russia
4	(Данные Web of science) Russian Acad Sci, Inst Chem Kinet & Combust, Novosibirsk 630090, Russia
5	(Данные Web of science) Russian Acad Sci, Inst Mol Biol & Biophys, Novosibirsk 630117, Russia
6	(Данные Web of science) Novosibirsk State Univ, Dept Phys, Novosibirsk 630090, Russia

Previously unknown mono-, di- and in some cases tri- and tetra- carbocycle-substituted quinoxalines (2-8), 2,1,3-benzothiadiazoles (11, 12, 14-17) and 2,1,3-benzoselenadiazoles (20-25) were synthesized by nucleophilic substitution of fluorine in 5,6,7,8-tetrafluoroquinoxaline (1) and 4,5,6,7-tetrafluoro-2,1,3-benzothia/selenadiazoles (10 and 19, respectively) with methoxide and dimethylamine. In the 1:1 reactions, the nucleophiles attacked selectively the position 6 of 1 or the position 5 of 10 and 19. The regioselective nature of the 1:1 reactions was confirmed by the DFT calculations at the M06-2X/6-31+G(d, p) level of theory. Disubstituted quinoxaline (28), thia- (29) and selena- (30) diazoles bearing two different substituents, i.e. MeO- and Me2N-, were synthesized in a similar way. New substituted 1,2-diaminobenzenes (31-33) were prepared by reduction of corresponding thiadiazoles (12, 14, 15) and isolated in the form of hydrochlorides. Compound 33 was converted into a new quinoxaline (34) by reaction with (PhCO)2. Compounds 5, 7 and 14 were studied for cytotoxicity toward the human cancer cells and effects on the cytochrome P450 mRNA expression. They did not cause any significant modulations in the expression of several cytochrome P450 genes, and 7 was weakly toxic for the Hep2 (carcinoma) and U937 (leukemia) cells, particularly, apoptosis was observed. (C) 2016 Elsevier B.V. All rights reserved.

Mikhailovskaya T.F. , Makarov A.G. , Selikhova N.Y. , Makarov A.Y. , Pritchina E.A. , Bagryanskaya I.Y. , Vorontsova E.V. , Ivanov I.D. , Tikhova V.D. , Gritsan N.P. , Slizhov Y.G. , Zibarev A.V.
Carbocyclic functionalization of quinoxalines, their chalcogen congeners 2,1,3-benzothia/selenadiazoles, and related 1,2-diaminobenzenes based on nucleophilic substitution of fluorine
Journal of Fluorine Chemistry. 2016. V.183. P.44-58. DOI: 10.1016/j.jfluchem.2016.01.009 WOS Scopus РИНЦ OpenAlex

Published print:

Mar 1, 2016

Web of science:	WOS:000374607900007
Scopus:	2-s2.0-85017153971
Elibrary:	29500648
OpenAlex:	W2326147145

DB	Citing
Web of science	33
Scopus	37
OpenAlex	37