First Case of Ring-Chain Tautomerism of N-Unsubstituted 1,2,3,4-Tetrahydroquinazolines

Abstract

Goblyos et al. [1] have shown that ring–chain tautomerism is a characteristic feature of arylidene derivatives of 2-methylaminophenylamine with a substituent at the benzylic nitrogen atom. 1,2,3,4-Tetrahydroquinazoline structure has been assigned to the products of the reaction of aldehydes and ketones with 2-methylaminophenylamine [2, 3]. In previous work [4], we reported the tendency of imines of β-dicarbonyl compounds such as diketones, keto esters, and keto amides to exist as enamines. This suggested ring–chain tautomerism among the corresponding 2-methylaminophenylamine derivatives. In the present communication, we report the first example of such tautomerism A' . B for 3-(2-aminobenzylimino)-1-morpholin-4-yl-1-butanone (1), which is the product of the condensation of 2-methylaminophenylamine with acetoacetic acid morpholide. NMR spectral data indicate the instantaneous establishment of the A' . B equilibrium. The signal for sp-hybrid atom C(2) at 66.75 ppm serves as a characteristic feature for cyclic form B. Structure A should be eliminated due to the lack of a signal for the corresponding methylene group in the H NMR spectrum. All the signals of the linear form are in complete accord with structure A', which represents a cis isomer as indicated by NOE spectra. The nuclear Overhauser effect is observed for the signal of the C=C–H proton upon irradiation of the methyl protons, which indicates their cis orientation. Intramolecular hydrogen bonding between the NH proton and carbonyl group oxygen atom stabilizes the cis form. The nature of the solvent has a significant effect on the ratio of the tautomeric forms. The linear form predominates in DMSO-d6, while the ring form predominates in CDCl3. This phenomenon is well known for many tautomeric systems involving 1,3-dicarbonyl derivatives [4] (Scheme 1). We should note that the A' . B equilibrium differs fundamentally from the tautomerism of 1-substituted 2-methylaminophenylamines [1], in which the imine form participates at the anilinic nitrogen atom rather than the benzylic nitrogen atom. The NMR spectra were taken on a JEOL JNM-A-500 spectrometer. The H NMR spectra were taken at 500 MHz and the C NMR spectra were taken at 125 MHz, in DMSO-d6 at 30°C and in CDCl3 at 25°C. The 1D measurements involved NOE and determination of the major parameters of these spectra. The homonuclear H– H correlations involved the phase-sensitive DQF-COSY method, while the H–C heteronuclear correlations were determined by the HMQC method (for correlations through one bond, J1 = 145 MHz) and HMBC method (for correlations through two bonds, J2,3 = 8 Hz) with gradient selection. All the spectra were taken using standard pulse sequence sets.