Cyclization of ortho-cyclopropylphenyl benzamides in gas and liquid phases

Abstract

The electron ionization (EI) and collision-induced dissociation (CID) spectra of substituted N-(ortho-cyclopropylphenyl)benzamides 1-7 and N-[ortho-(1-methylcyclopropyl)phenyl]benzamides 8-12 were recorded. In addition to routine bond cleavages, the molecular ions (M+) of 1-12 undergo cyclization into the corresponding 3-aryl-1-alkyl-1-ethyl-1H-benzoxazines and isomeric 5-ethyl-2-oxodibenzoazepines. The presence of a methyl group in the cyclopropyl ring (compounds 8-12) makes the formation of 5-ethyl-2-oxodibenzoazepine less favorable. In accord with mass spectrometric predictions, compound 13 (3-p-tolyl-1-ethyl-1H-benzoxazine) was obtained as a major product of the reaction of N-(ortho-cyclopropylphenyl)-4-methylbenzamide 1 with sulfuric acid. Traces of 5-ethyl-2-oxodibenzoazepine were also detected in gas chromatography-mass spectrometry (GC-MS) analysis of the reaction mixture although the yield was too low to allow its isolation.

Cyclization of the substituted N-(Ortho-cyclopropylphenyl)-N′-aryl ureas and thioureas in the gas phase and solution

“…The spectral conclusions for a representative series of N-(ortho-cyclopropylphenyl)benzamides were used to confirm the presence of the predicted heterocycles in solution. The cyclization products of the molecular ions for these benzamides were identical to those synthesized in the condensed phase [4,5]. In the present study, we continue research in this area, investigating the possibility of rearrangements of substituted N-(ortho-cyclopropylphenyl)-N=-aryl ureas (1-14).)…”

“…According to the data presented and on the basis of our previous observations [3][4][5],°it°is°possible°to°assume°that°the°ortho-effect°plays an important role with heterocycles A 1 and A 2 (represented°in°Scheme°1)°being°the°main°products°of°trans-formation of the original molecular ions. The influence of substituents on the aromatic ring is often unpredictable.…”

“…The cyclization products of the molecular ions for these benzamides were identical to those synthesized in the condensed phase [4,5]. In the present study, we continue research in this area, investigating the possibility of rearrangements of substituted N-(ortho-cyclopropylphenyl)-N=-aryl ureas (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).) and N-(ortho-cyclopropylphenyl)-N=-aryl thioureas (15)(16)(17)(18)(19)(20)(21)(22)(23), structurally related to the earlier studied acetamides [6] and benzamides [4,5].…”

“…In the present study, we continue research in this area, investigating the possibility of rearrangements of substituted N-(ortho-cyclopropylphenyl)-N=-aryl ureas (1-14).) and N-(ortho-cyclopropylphenyl)- N=-aryl thioureas (15-23), structurally related to the earlier studied acetamides [6] and benzamides [4,5]. These compounds were expected to undergo EI induced and acid catalyzed cyclization in a similar manner.…”

“…Substituted N-(ortho-cyclopropylphenyl)-N=-aryl ureas (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and N-(ortho-cyclopropylphenyl)-N=-aryl thioureas (15)(16)(17)(18)(19)(20)(21)(22)(23) possess four nucleophilic sites [N, N=, O (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) or S (15)(16)(17)(18)(19)(20)(21)(22)(23), and the ortho-position of the aromatic ring attached to N=], which are able to attack the charged cyclopropyl moiety. Therefore, at least four heterocycles (P 1 -P 4 ) can be formed in the intramolecular cyclization reaction.…”