Synthesis and Antimicrobial Activity of Methyl 2‐(2‐(2‐Arylquinazolin‐4‐yl)sulfanyl)acetylamino Alkanoates

Abstract

A series of methyl 2-(2-(2-arylquinazolin-4-yl)sulfanyl)acetylamino alkanoates have been developed on the basis of the S-chemoselective reaction of 2-arylquinazolin-4(3H)-thione with ethyl chloroacetate and N,N 0 -dicyclohexylcarbodiimide coupling method with amino acid ester hydrochloride. The precursor 2arylquinazolin-4(3H)-thione was prepared by a new thiation method from 2-arylquinazolin-4(3H)-one by a two-step reaction that includes chlorination and then the reaction with N-cyclohexyldithiocarbamate cyclohexyl ammonium salt. The antimicrobial activity of the synthesized compounds was tested in vitro via paper-disc agar-plate method against two bacterial strains Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli and a pathogenic yeast Candida albicans. Most synthesized compounds showed remarkable antibacterial activity against E. coli overpassing the standard reference antibiotics applied: tetracycline, erythromycin, and novobiocin. On the other hand, most synthesized compounds gave moderate antifungal activity against pathogenic yeast C. albicans. Scheme 1. Synthesis of 2-((2-arylquinazolin-4-yl)thio)acetic acid 6a-b.

Domino synthesis of pyrimido and imidazoquinazolinones

“…The target compound N ‐alkyl 2‐aryl quinazolin‐4‐amines could be easily prepared by the reaction of benzyl amine with chloroquinazoline in DMF for at 100°C for 12 hours. This is the most reliable classical method for this preparation; however, this method suffers from two aspects: first, amines used for this reaction should be of high boiling points such as benzyl amine (other amines normally of low boiling point did not give the desired product); second, we realize in Scheme that this reliable method of preparation of chloroquinazoline from anthranilic acid occurs in a five‐step sequential reactions and sixth step for the reaction with benzyl amines, Scheme …”

“…This is the most reliable classical method for this preparation; however, this method suffers from two aspects: first, amines used for this reaction should be of high boiling points such as benzyl amine (other amines normally of low boiling point did not give the desired product); second, we realize in Scheme 1 that this reliable method of preparation of chloroquinazoline from anthranilic acid occurs in a five-step sequential reactions and sixth step for the reaction with benzyl amines, Scheme 1. [11,12] Following the main definition of domino reaction reveals synthesis of complex structures by the addition of two or more active substrates and the formation or cleavage of two or more bonds in a single operation without isolation of intermediates, minimal time, maximum selectivity, and high atom economy. [1] We found it interesting to prepare N-alkyl-2-arylquinazolin-4-amines 7a-d and 10b from the corresponding N-(2-cyanophenyl)-substitutedbenzamides 8a-d.…”

“…The starting substituted N ‐(2‐cyanophenyl)benzamides 8a‐d were prepared according to the reported method . Also, starting compounds 1‐6 were prepared according to reported literature …”

“…The methylene chloride solution was washed several times with ice‐cold ammonia solution 5% (20 mL) then dried over sodium sulfate. The methylene chloride solution was filtered, evaporated, and gave chloroquinazoline derivatives 6a‐d in a pure state and was used without further purification …”

“…[18] Also, starting compounds 1-6 were prepared according to reported literature. [11,12] 3.1.1 | General procedures for preparation of 4-chloro-2-aryl-3,4-dihydroquinazolines 6a-d…”