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

Abstract

Electron ionization (EI), chemical ionization (CI), tandem mass spectrometry, high-resolution measurements, and labeling studies as well as quantum chemical calculations were used to understand the behavior of the molecular radical cations (EI) and protonated molecules (CI) of substituted N-(ortho-cyclopropylphenyl)- N=-aryl ureas and N-(ortho-cyclopropylphenyl)-N=-aryl thioureas in a mass spectrometer. Fragmentation schemes and possible mechanisms of primary isomerization were proposed. According to the fragmentation pattern, formation of the corresponding benzoxazines and benzothiazines was considered as the major process of isomerization of the original M ϩ· and MH ϩ , although some portions of these ions definitely transformed into other structures. M ass spectrometry has been proven to be a powerful, rapid method for the prediction of the direction and yields of monomolecular reactions of organic compounds in solution [1]. Previously, we successfully used mass spectrometry to study cyclization of various diazo compounds [2] and orthosubstituted phenylcyclopropanes [3]. 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).) 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 (1-14) and N-(ortho-cyclopropylphenyl)-N=-aryl thioureas (15-23) possess four nucleophilic sites [N, N=, O (1-14) or S (15-23), 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.

Cyclization of 2-Acyl- and 2-Thioacylamino-Benzylcyclopropanes in the Gas Phase and Solution

“…Introduction Earlier we have reported the experimental results on the predictive power of mass spectrometry [1], which allows estimation of the directions and yields of monomolecular chemical reactions in solution. A spectacular example involves acid catalyzed cyclization of ortho-substituted phenylcyclopropanes with formation of five-seven-membered heterocycles [2][3][4]. The realization of intramolecular cyclization processes proposed on the basis of the fragmentation pattern induced by electron ionization was successfully confirmed by observation of the corresponding reactions in solution.…”

Gas‐phase study of the stability of α‐substituted cyclic amino nitriles under electron ionization and electrospray ionization and fragmentation peculiarities of cyclic ketimines

“…Mass spectrometry (MS) has been shown to be a valuable and rapid method to conduct monomolecular reactions in the gas phase 8,9 . It allows structures of heterocyclic compounds to be elucidated 10 and these gas‐phase reactions often demonstrate similarities to reactions in solution, sometimes predicting the directions and yields of chemical reactions in solution 10–13 . Positive ions in electron ionization, chemical ionization, and electrospray ionization allow 8,9 the study of monomolecular reactions carried out in solution and initiated by thermolysis, photolysis or acid‐catalysis 8,9 .…”