Fluorinated benzazoles and benzazines

Abstract

The review surveys the recently obtained data on the synthesis of fluorinated benzazoles and benzazines. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:579–594, 2006; Published online in Wiley InterScience (http://www.interscience.wiley.com). DOI 10.1002/hc.20281

Fluorine-Containing Benzimidazoles and Their [a]- and [b]Heteroannelated Derivatives: Synthesis and Biological Activity (Review)

“…The action of heat on the pyrimidobenzimidazoledione 124a in the presence of phosphorus oxychloride followed by reaction with ammonia in methanol gives the pyrimido[1,6-a]benzimidazoles 127a,b. The reaction of 5,6-difluoro-2-hydrazino-1-methylbenzimidazole (128) with the acrylates 130a,b in toluene at room temperature leads to the formation of ethyl 3-[2-(benzimidazol-2-yl)hydrazino]-2 _ polyfluorobenzoylacrylates 131a,b [68][69][70]. The ability of these compounds to undergo amine-imine tautomerism made it possible to realize their cyclization by heating in acetonitrile in the presence of reagents that bond with hydrogen fluoride: diazobicycloundec-7-ene (DBU), KF, or triethylbenzylammonium chloride.…”

Fluoroarenes in the synthesis of benzoannulated nitrogen-containing heterocycles

“…Finally, cycliza tion of the latter yields 2 substituted 5,6,8 trifluoro and 5,6,7,8 tetrafluoro 4H 1,3,4 benzothiadiazines 56 (Scheme 22). 44 2,3,4 Trifluoronitrobenzene (57) is a starting material for the preparation of (S) (-) 7,8 difluoro 3 methyl 3,4 dihydro 2H [1,4]benzoxazine (58), the most important intermediate in the synthesis of the antibacterial drug levofloxacin. Several routes to fluoro containing stereo isomers of 3 methyl and 2 methyl 2H [1,4]benzoxazines were proposed.…”

“…44 2,3,4 Trifluoronitrobenzene (57) is a starting material for the preparation of (S) (-) 7,8 difluoro 3 methyl 3,4 dihydro 2H [1,4]benzoxazine (58), the most important intermediate in the synthesis of the antibacterial drug levofloxacin. Several routes to fluoro containing stereo isomers of 3 methyl and 2 methyl 2H [1,4]benzoxazines were proposed. 45 For instance, compound 57 reacts with (R) propane 1,2 diol in THF in the presence of NaH to give a mixture of (R) 3,4 difluoro 2 (2 hydroxypropoxy) nitrobenzene and (R) 3,4 difluoro 2 (1 hydroxypropan 2 yloxy)nitrobenzene in the ratio 3 : 2.…”

“…Introduction of F atoms into organic molecules, especially into those fragments that are respon sible for their biological activity, becomes an important aspect of pharmaceutical investigations, which in turn stimulates a search for new methodologies of the synthe sis of diverse fluoro containing compounds. [1][2][3][4][5][6][7][8] The volume of the fluorine atom is close to that of the hydrogen atom; when the latter is replaced by a F atom, the primary metabolism of organic substances usually remains unchanged since enzymes in biological systems often do not distinguish between these compounds (mimicry effect). However, because C-F bonds are stron ger than C-H bonds, their degradation is hindered and further metabolism proceeds anomalously.…”

Microwave-assisted synthesis and evaluation of antibacterial activity of novel 6-fluoroaryl-[1,2,4]triazolo[1,5-a]pyrimidines

“…The US Center for Disease Control and Prevention (CDC) has classified "high priority antibioticresistant bacteria" that include Mycobacterium tuberculosis (MDR, XDR), Neisseria gonorrhoeae, It is known that fluorine-containing heterocycles, especially fluoroquinolones, have gained attention as effective antibacterial agents. [15][16][17][18][19] We have recently elucidated how a fluorine atom (or CF3-group), incorporating at various positions a 5-(fluoroaryl) substituent in 4-(hetero)arylpyrimidines can affect their antibacterial activity against Mycobacterium tuberculosis and other pathogenic strains such as M. avium and M. terrae. 20 In this communication we report the synthesis of novel 6-fluoroaryl substituted [1,2,4]triazolo [1,5-a]pyrimidines using microwave-assisted Suzuki cross-coupling, and present data on their antimicrobial activities in vitro against Mycobacterium tuberculosis H37Rv and the gram-negative Neisseria gonorrhoeae ATCC 49226 bacteria.…”