Synthesis and Structural Characterization of Substituted 2-Phenacylbenzoxazoles

Abstract

1H and 13C NMR spectra of eleven 2-phenacylbenzoxazoles (ketimine form) show that their CDCl3-solutions contains also (Z)-2-(benzo[d]oxazol-2-yl)-1-phenylethenols (enolimine form). Intramolecular hydrogen bonding in the latter tautomer was found to be significantly weaker than that one in respective (Z)-2-(2-hydroxy-2-phenylvinyl)pyridines. Integrals of the 1H NMR signals were used to evaluate the molar ratio of the tautomers. Strong electron-donating substituents were found to stabilize the ketimine tautomer. pKT (negative logarithm of the equilibrium constant, KT = [ketimine]/[enolimine]) was found to be linearly dependent on the Hammett substituent constant σ. The results of the MP2 ab initio calculations reveal enolimine including an intramolecular OH···N hydrogen bond to be the most stable form both with electron-donor and electron-acceptor substituents. The stability of ketimines is an intermediate of those found for enolimines and enaminones i.e., (E)-2-(benzo[d]oxazol-2(3H)-ylidene)-1-phenylethanones. 13C CPMAS NMR spectral data reveal that in the crystalline state the ketimine tautomer is predominant in p-NMe2 substituted congener. On the other hand, enolimine forms were detected there when the substituent has less electron-donating character or when it is an electron-acceptor by character.

Tautomeric Equilibria in Solutions of 2-Phenacylbenzimidazoles

“…The aforementioned syntheses are characterized by low yield; therefore, 2-phenacylbenzimidazoles were prepared by treating methylbenzimidazole 1 with benzoyl chlorides in the presence of triethylamine followed by thermal decomposition of formed (Z)-2-(1-benzoyl-1H-benzo[d]imidazol-2-yl)-1-phenylvinyl benzoates 2a-i (Scheme 2) [5,7,11]. In order to compare 2-phenacylbenzimidazoles with 2-phenacylbenzoxazoles and 1-methyl-2-phenacylbenzimidazoles studied earlier [1,2], the NMR spectra of the former compounds should be recorded from their deuterated chloroform solutions. Unfortunately, the crystals were sparingly soluble in that solvent, so it was substituted with DMSO-d 6 .…”

“…13 C CPMAS NMR spectra proved that in the crystalline state the ketimine tautomer K is predominant only in the p-NMe 2 substituted congener. On the other hand, enolimine forms O were detected when the substituent had less electron-donating character or when it had an electronaccepting nature [1].…”

“…It was found recently that in chloroform solution 2-phenacylbenzoxazoles (K in Scheme 1, X = O) are in equilibrium with (Z)-2-(benzo[d]oxazol-2-yl)-1-phenylethenols (enolimines, O) [1]. Strong electron-donating substituents in the benzene ring were found to stabilize the K tautomer.…”

“…Since the -N=C(-)CH 2 CO-moiety also is present in 2-phenacylbenzimidazoles (Scheme 1, X = NH), these compounds and 2-phenacylbenzoxazoles and 1-methyl-2phenacylbenzimidazoles are expected to behave similarly. However, in drawing such conclusions one has to be very careful: minor modifications in the molecule may affect the tautomeric equilibria significantly [1][2][3]. Such understanding prompted us to see the effect of substitution of the ring oxygen atom in 2-phenacylbenzoxazoles and NCH 3 group in 1-methyl-2-phenacylbenzimidazoles by the NH group on their susceptibility to proton transfer.…”

“…Tautomerism of 2-phenacylbenzimidazoles has been already studied by the NMR methods: 2-phenacylbenzimidazoles (ketimines K) in DMSO-d 6 solution were found to equilibrate with 2-(1,3-dihydro-2H-benzo[d]imidazol-2ylidene)-1-phenylethan-1-one (enaminones) [4]. Since an unequivocal distinguishing between enolimines O and enaminones E (any of these two forms can be present in solution), based only on the simple NMR spectra, may be difficult [1][2][3], ab initio calculations were performed in the present paper in order to support or deny the earlier conclusions [4]. The substituent effect on tautomerism of such derivatives is always significant [1][2][3], so the series of substituted 2-phenacylbenzimidazoles is worth further study.…”