Liquid-phase synthesis of 2-substituted benzimidazoles, benzoxazoles and benzothiazoles

A novel acid fluoride for use in the liquid-phase synthesis of substituted benzimidazoles, benzoxazoles and benzothiazoles was developed. Its synthetic utility is exemplified by a structurally diverse set of aromatic heterocycles. Final cleavage is achieved by treatment with sodium methoxide in methanol for 12 h. The corresponding benzimidazoles, benzoxazoles and benzothiazoles were obtained in good isolated yields (22-62%, four steps).     

Synthesis and optical properties of 5-substituted 2-(2-tosylaminophenyl)benzoxazoles

Various 5-substituted 2-(2-tosylaminophenyl)benzoxazoles were synthesized. The presence of intramolecular hydrogen bonding, the strength of which depends on the nature of the substituent, was shown by means of the IR spectra of the investigated series of compounds. A correlation between v _NH and the Taft substituent constants was found. The investigated benzoxazoles have fluorescence in the yellow-green region of the spectrum; an anomalously large Stokes shift is characteristic for them. The position of the fluorescence spectrum depends on the strength of the hydrogen bond: when it becomes weaker, the spectrum is shifted bathochromically.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 472–478, April, 1973.     

Synthesis of benzoxazoles from imino esters I. 2-Alkyl(aryl)-substituted benzoxazoles

It is found that condensation of esters of iminocarboxylic and iminoperfluorocarboxylic acids with o-aminophenol is a convenient general method for preparing 2-alkyl, 2-perfluoroalkyl, and 2-aryl substituted benzoxazoles. Hydrochlorides of esters of iminocarboxylic acids react smoothly with o-aminophenol even at room temperature. Condensation of esters of iminoperfluorocarboxylic acids, whose hydrochlorides are unstable, is suitably carried out in the presence of an equimolecular quantity of the corresponding perfluorocarboxylic acid. 2-Alkyl(aryl) substituted benzoxazoles can also be obtained by heating o-aminophenol with esters of iminocarboxylic acids in the form of free bases. Esters of iminoperfluorocarboxylic acids also react similarly. Under similar conditions diesters of bisiminocarboxylic and bisiminoperfluorocarboxylic acids and o-aminophenol give, -di(benzoxazolyl-2) alkanes, and, -di(benzoxazolyl-2) perfluoroalkanes respectively.The synthetic part of the work was communicated at the conference on Heterocycles in Organic Synthesis, Kiev, June 1964. For a preliminary communication see [1].     

Synthesis of benzoxazoles from imino esters I. 2-Alkyl(aryl)-substituted benzoxazoles

It is found that condensation of esters of iminocarboxylic and iminoperfluorocarboxylic acids with o-aminophenol is a convenient general method for preparing 2-alkyl, 2-perfluoroalkyl, and 2-aryl substituted benzoxazoles. Hydrochlorides of esters of iminocarboxylic acids react smoothly with o-aminophenol even at room temperature. Condensation of esters of iminoperfluorocarboxylic acids, whose hydrochlorides are unstable, is suitably carried out in the presence of an equimolecular quantity of the corresponding perfluorocarboxylic acid. 2-Alkyl(aryl) substituted benzoxazoles can also be obtained by heating o-aminophenol with esters of iminocarboxylic acids in the form of free bases. Esters of iminoperfluorocarboxylic acids also react similarly. Under similar conditions diesters of bisiminocarboxylic and bisiminoperfluorocarboxylic acids and o-aminophenol giveα, ω-di(benzoxazolyl-2) alkanes, andα, ω-di(benzoxazolyl-2) perfluoroalkanes respectively.     

Organosilicon derivatives of 2-mercapto-substituted benzoxazoles,benzothiazoles and benzimidazoles

The interactions of sodium salts of 2-mercaptobenzoxazole, 2-mercaptobenzothiazole and 2-mercaptobenzimidazole with (chloromethyl)trimethyl-, chloromethyl(dimethoxy)methylor (chloromethyl)trimethoxysilanes have been shown to result in the corresponding previously unknown (2-heterylthiomethyl)triorganylsilanes. Transetherification of (2-heteryl-thiomethyl)trimethoxysilanes with triethanolamine gives 1-(2-benzoxazolylthiomethyl)-, 1-(2-benzothiazolylthiomethyl)- and 1-(2-benzimidazolylthiomethyl)silatranes. The reaction of the corresponding alkoxysilanes with boron trifluoride etherate leads to (2-benzoxazolylthiomethyl)- and (2-benzothiazolylthiomethyl)-substituted trifluorosilanes and methyldifluorosilanes having a dragonoid chelate structure. By the hydrolysis of (2-heterylthiomethyl)trimethoxysilanes, new organosilicon sorbents, poly(2-heteryl-thiomethyl)silsesquioxanes have been synthesized.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1965–1969, November, 1993.     

Diversity oriented synthesis of benzoxazoles and benzothiazoles

A combinatorial synthetic route yielding benzoxazoles and benzothiazoles is described. The use of o-halophenylisocyanides in the Ugi reaction (U-4CR) followed by a copper-catalyzed cyclization affords the benzoxazole as well as the benzothiazole moiety in good yield and high diversity.     

Photochemical synthesis of 2-substituted benzothiazoles

The photochemical reaction of 1 -indolethiocarbanilides 1 , di- and tri-substituted thioureas 3–5 and 4,4 -di-methyl-2,6-dioxothiocyclohexanecarboxanilides 9 affording the respective benzothiazoles are described.     

Cyclization of alpha-Oxo-oximes to 2-substituted benzoxazoles

Reactions of oximes 9, 17, and 19 with electrophiles 15a-f and 24 in the presence of anhydrous potassium carbonate or triethylamine give 2-substituted condensed ring oxazoles 10, 16a-c, 18a-d, 20a-c, and 25 in a new general route to these compounds.     

Oxidative cyclization of thiophenolic and phenolic Schiff's bases promoted by PCC: a new oxidant for 2-substituted benzothiazoles and benzoxazoles

Pyridinium chlorochromate (PCC) supported on silica gel effects the oxidative cyclization of structurally diverse thiophenolic and phenolic Schiff's bases, thereby providing an efficient and convenient method for the synthesis of a library of 2-arylbenzothiazoles and 2-arylbenzoxazoles.     

Synthesis and activity mechanism of some novel 2-substituted benzothiazoles as hGSTP1-1 enzyme inhibitors$

Abstract

Human GSTP1-1 is one of the most important proteins, which overexpresses in a large number of human tumours and is involved in the development of resistance to several anticancer drugs. So, it has become an important target in cancer treatment. In this study, 12 benzothiazole derivatives were synthesized and screened for their in vitro inhibitory activity for hGSTP1-1. Among these compounds, two of them (compounds #2 and #5) have been found to be the leads when compared with the reference drug etoposide. In order to analyse the structure–activity relationships (SARs) and to investigate the binding side interactions of the observed lead compounds, a HipHop pharmacophore model was generated and the molecular docking studies were performed by using CDocker method. In conclusion, it is observed that the lead compounds #2 and #5 possessed inhibitory activity on the hGSTP1-1 by binding to the H-site as a substrate in which the para position of the phenyl ring of the benzamide moiety on the benzothiazole ring is important. Substitution at this position with a hydrophobic group that reduces the electron density at the phenyl ring is required for the interaction with the H side active residue Tyr108.     

Synthesis of 2-pyranosyl benzothiazoles, benzimidazoles and benzoxazoles via nucleophilic addition reactions of pyranosyl nitrile oxides

Reaction of per-O-acetylated-β-d-pyranosyl nitrile oxides, generated by dehydrochlorination of the corresponding hydroximoyl chlorides, with 2-aminothiophenol afforded 2-(β-d-pyranosyl)benzothiazoles. 1,2-Diaminobenzene and 2-aminophenol reacted similarly to yield 2-(β-d-pyranosyl)benzimidazoles and 2-(β-d-pyranosyl)benzoxazoles, respectively. The structures of 2-β-d-glucopyranosylbenzimidazole (17), 2-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)benzimidazole (19) and the xylopyranosyl thiohydroximate 13 were established by X-ray crystallography.     

Synthesis of 2,5′-substituted 2′,5-bipyrimidines

Reaction of 5-substituted-2-methylpyrimidines with the Vilsmeyer complex followed by condensation of the resulting immonium salts and acroleins with aromatic amidines has given liquid crystalline 2,5-bipyrimidines.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 804–807, June, 1990.     

Iodine-mediated cyclisation of thiobenzamides to produce benzothiazoles and benzoxazoles

Synthesis of benzothiazoles by reaction of iodine with thiobenzamides, which do not possess an ortho alkoxy or ester group, is described. The unlikely synthesis of benzoxazoles from reaction of 2-alkoxythiobenzamides with iodine is also reported.     

Synthesis of 2-(imidazolylamino)benzothiazoles

Treatment of derivatives of 5-phenylthioureido-3H-imidazole-4-carboxylic acid with bromine afforded 2-(imidazolylamino)benzothiazoles.     

Synthesis,antimicrobial activity and QSAR studies of 2,5-disubstituted benzoxazoles

In this study, a new series of 2,5-disubstituted benzoxazoles was synthesized and their structures were elucidated by elemental analysis, MASS, ¹H-NMR, ¹³C-NMR and IR spectral data. Newly and previously synthesized 2,5-disubstituted benzoxazole derivatives were evaluated for antibacterial and antifungal activity against standard strains and their drug-resistant isolates. Microbiological results showed that the compounds presented a large spectrum of activity having MIC values of 250–7.8 µg mL^?1 against the tested microorganisms. Among the newly synthesized derivatives 3–22, compound 11 was the most active against Candida krusei out of all; however, it was one dilution less potent than standard drug fluconazole. In addition, all the new and previous compounds were more active than standard drugs ampicillin trihydrate and rifampicin against Pseudomonas aeruginosa and its gentamicin-resistant isolate. The 2D-QSAR (Quantitative Structure–Activity Relationship) analysis of a set of newly and previously synthesized benzoxazoles tested for growth inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) was also performed by using multivariable regression analysis. The activity contributions for substituent effects of these compounds were determined from the correlation equation for predictions of the lead optimization.     

Peroxide-mediated oxidative coupling of primary alcohols and disulfides: Synthesis of 2-substituted benzothiazoles

A peroxide-mediated protocol for the synthesis of 2-substituted benzothiazoles was developed, starting from bis(o-aminophenyl) disulfides and primary alcohols. Eleven differently 2-substituted benzothiazoles were prepared in moderate to excellent yields using di-tert-butyl peroxide (DTBP) as an oxidant.