General and efficient synthesis of benzoxazol-2(3H)-ones: evolution of their anti-cancer and anti-mycobacterial activities

Abstract

A novel class of benzo [d]oxazol-2(3H)-one derivatives have been synthesized and evaluated their in vitro cytotoxicity against human pancreatic adenocarcinoma and human non small cell lung carcinoma cancer cell lines. Many of these compounds were found to display excellent to moderate activity. Among them, 6b, 6l, 6n and 6x are identified as lead molecules. In particular, 6l and 6n were found to be potent against 10 pancreatic cell line whereas the 6x was found to be effective against human non small cell lung carcinoma cell line. Conversely, the compounds 6l-x were found to ineffective against Mycobacterium tuberculosis. Of various molecules, 6h showed a promising anti-mycobacterial activity, which is equal to the IC 50 value of ciprofloxacin. Off White solid; 92% yield, m.p. 216-218 o C; 1 H NMR (400 MHz, DMSO): δ 10.35 (s, 1H), 8.41 (d, J = 7.2 Hz, 2H), 8.04 (s, 1H), 8.19 (d, J = 7.0 Hz, 2H), 7.59 (d, J = 8.2 Hz, 2H), 7.57 (m, 1H), 7.52 (s, 1H), 7.45 (m, 4H), 4.52 (m, 1H), 1.51 (d, J = 6.8 Hz, 6H);

Continuous-Flow Hofmann Rearrangement Using Trichloroisocyanuric Acid for the Preparation of 2-Benzoxazolinone

“…2-Benzoxazolinone and more generally benzoxazolone derivatives are valuable moieties for the preparation of a range of important biologically active materials. Benzoxazolone derivatives have found promise as anticancer, , antimycobacterial, , anti-HIV-1, anticonvulsant, − anxiolytic, and insecticide agents . Classical methodologies for their preparation start from 2-aminophenol employing carbonic acid derivatives such as phosgene, , carbonates, , carbamates, , urea, − or carbon dioxide .…”

“…Benzoxazolone derivatives have found promise as anticancer, , antimycobacterial, , anti-HIV-1, anticonvulsant, − anxiolytic, and insecticide agents . Classical methodologies for their preparation start from 2-aminophenol employing carbonic acid derivatives such as phosgene, , carbonates, , carbamates, , urea, − or carbon dioxide . Alternative preparation methods exploiting Pd-catalyzed oxidative carbonylation, , metal-catalyzed CH amidation, − visible-light-induced CH amination, and Curtius rearrangement have also been developed over the past years.…”

PIFA-Mediated Tandem Hofmann-Type Rearrangement and Cyclization Reaction of α-Acyl-β-aminoacrylamides: Access to Polysubstituted Oxazol-2(3H)-ones

“…Oxazol-2­(3 H )-ones constitute the key units of many natural products and designed molecules along with diverse bioactivities, such as antibacterial, antitumor, cyclooxygenase-2 inhibitory, neuroleptic, and herbicidal activities (Figure ). − In addition, they are widely used as important building blocks and versatile intermediates for complex molecule construction in organic chemistry and medicinal chemistry. , In this context, many synthetic approaches have been established for oxazol-2­(3 H )-ones and their fused analogues, including (i) Lewis-acid- or Lewis-base-catalyzed condensation of 1,2-aminoketones with carbonyl compounds, (ii) transition-metal-catalyzed cyclization of the N -alkynyl tert -butyloxycarbamates, , (iii) cycloaddition of secondary propargyl alcoholes with isocyanates or carbon dioxide and amines, (iv) cycloaddition of α-hydroxyl ketones with isocyanates or carbamates, (v) Brønsted-acid-catalyzed cyclization of β-amino-1,4-enols, (vi) transition-metal-catalyzed coupling- isomerization-elimination of propargyl carbamates with acid chlorides, (vii) transition-metal-catalyzed cyclization of β,β-dihaloenamides, and (viii) cyclization of 2-amino-phenols with different carbonylating reagents . Alternatively, some functionalized oxazol-2­(3 H )-ones have also been prepared via oxidation of 2-oxazolidones or modification of the preconstructed oxazol-2­(3 H )-one skeleton …”