Ring Transformation of 1,2‐Disubstituted 4(1H)‐Quinazolone Oximes to 3,5‐Disubstituted 1,2,4‐Oxadiazoles

Abstract

In basic media 0-Benzoyl-and 0-acetyl-2-benzylaminobenzamide oxime (Sb,c) give 5-substituted 3-(2-benzylaminophenyl)-1,2,4-oxadiazoles (9a, b), while on heating in pure water 2-amino-1-benzylbenzimidazole (10) is formed. Reaction of 2dN-acylbenzy1amino)benzonitrile (12) with hydroxylamine, or treatment of O-acyl-2-(N-benzoylbenzylamino)benzamide oximes (Sf, g) with acid give the novel 1,2-disubstituted 4(iH)-quinazolone oximes 13, which isomerize on heating with alkali by an ANRORC mechanism to the 1,2,4+xadiazoIes 9a,b.Recently, we reported the transformation of 3-(l-aminopropyl)-l,2,4-oxadiazoles (1) to a-acylaminopropionamide oximes (3). As an intermediate the cyclic amide oxime 2 was postulated (Scheme I)'). 3In this paper we report a ring transformation of similar character but of opposite direction, i. e. the conversion of 2 to 1 involving the formation of an aminooxadiazole 9 from a cyclic amide oxime 13.It was also recently reported by us that the monoacyl derivatives 4 and 5 of 2-aminobenzamide oxime are transformed, depending on pH, to various heterocycles, among others in acidic media to quinazoline-3-oxides2). We assumed that the latter are formed by an electrocyclic reaction from the benzoxdiazepin intermediate 6 which -in turnare produced from 4 or 5 by loss of water. Regarding the whole process, an important role can be attributed to the possibility that the N(l) = C(2) bond can be formed from the aromatic amino group (Scheme 2).Neither reaction 4 -+ 7 nor pathways involving 6 as an intermediate are in accord with concepts put forward in the literature concerning the formation of 7 and the related quinazoline-3-oxides ' ). 5 COPhIn order to clarify this situation we intended to prepare 2-benzylaminobenzamide oxime (8a) and its 0-and N-acyl derivatives 8b-e and study their ring closure. In these compounds the formation of the C(l)=N(2) bond from the aromatic amino group is precluded and therefore, according Chem. Ber.

Oximes of six-membered heterocyclic compounds with two or three hetero-atoms: I. Synthesis and structure (review)

“…Thermolysis of 6-amino-1,2-dihydro-3H-quinazolines 36 gives the quinazoline oximes 37 as the only products [37]. In an acidic or basic medium the N-benzoyl derivatives of the oximes of 2-aminobenzamides undergo cyclization to quinazolone oximes [38,39]. For example, the amidoxime 38 is easily transformed into the corresponding quinazolone 4-oxime 39 with a yield of 67%.…”

“…For example, the amidoxime 38 is easily transformed into the corresponding quinazolone 4-oxime 39 with a yield of 67%. The reaction of the nitrile 40 with hydroxylamine also leads to the formation of a substituted quinazolone 4-oxime 41 [39]. The classical method for the synthesis of pyrimidine amidoximes is based on the reaction of the nitrile with hydroxylamine hydrochloride in an aqueous solution of K 2 CO 3 [43], Na 2 CO 3 /H 2 O [44], ethanol [45], Et 3 N/MeOH [46], or i-Pr 2 NEt/DMF [47].…”

“…The structure of the Z- [131] and E- [132] isomers of the oximes of 4-pyrimidinecarbaldehyde, 1-benzyl-2-phenyl-1H-quinazolone [39], and the solvate of 3-(1-hydroxyiminoethyl)-1-phenyl-4-hydro-1,2,4-triazine-5,6-dione with methanol [133], the E-isomer of 1-(3-methylsulfanyl-1,2,4-triazin-5-yl)ethanone O-acryloyloxime [134], and the palladium complex of 3-acetyl-5-benzyl-1-phenyl-4,5-dihydro-1,2,4-triazin-6-one oxime [135,136] was confirmed by the data from X-ray crystallographic analysis.…”

Synthesis of polyhalo 2-aryl-4-aminoquinazolines and 3-amino-indazoles as anti-cancer agents

“…[10][11][12][13] The potent bioactivity and low toxicity of these derivatives have received increasing attention. Up to now, many methods have been used to synthesize 4-aminoquinazolines, including 2-bromobenzonitrile reacting with amidines, 2 benzonitrile, benzoic acid and formimidamide with 2-aminobenzonitrile, [14][15][16] the ring-closing reaction of (Z)-N-(amino-(2-amino-phenyl)-methylene)-benzamide and 2-(benzyl-amino)-enzonitrile, 17,18 the amination reaction of 4-chloro-uinazoline and the reduction of 4-azidoquinazoline, etc. [19][20][21] However, heavy metal reagents or catalysts such as Pd/C and copper salts were often needed by these procedures.…”

“…[19][20][21] However, heavy metal reagents or catalysts such as Pd/C and copper salts were often needed by these procedures. 16,17 In addition, it requires multistep reactions and complex experimental processes 17,20 and, more importantly, the synthesis methods and activity study of highly functionalized 4-aminoquinazolines is very limited.…”