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-oxodibe… Show more
“…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).)…”
mentioning
confidence: 61%
“…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.…”
Section: Resultsmentioning
confidence: 88%
“…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].…”
mentioning
confidence: 75%
“…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.…”
mentioning
confidence: 96%
“…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.…”
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.
“…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).)…”
mentioning
confidence: 61%
“…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.…”
Section: Resultsmentioning
confidence: 88%
“…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].…”
mentioning
confidence: 75%
“…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.…”
mentioning
confidence: 96%
“…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.…”
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.
2‐Isocyanoacetophenone (3a) was found to be an easily accessible starting material for the unexpected formation of various heterocyclic systems. Thus, a hitherto unknown rather unstable 4‐methylene‐4H‐benzoxazine derivative 4, which could be characterized by NMR spectroscopy, was formed in situ by the reaction of 3a in the presence of weak acids. In the presence of benzylamines, a new class of 3,4‐dihydroquinazoline derivatives 6 and their oxidation products, quinazolin‐4‐ones 9, were obtained. The starting materials and products were completely characterized by spectroscopic and X‐ray analysis. The scope and limitations of these cyclization reactions were investigated under various reaction conditions. High‐level quantum chemical calculations were carried out to elucidate the mechanisms leading to scaffolds 4 and 6. The calculations suggest that the formation of 4 and 6 involves the generation of an unusual six‐membered N‐heterocyclic carbene or its C‐protonated form as a reaction intermediate, followed by tautomerisation. This mechanism might also be applicable to other isocyanide cyclization reactions.
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