Tautomerism of quinazolin-4-ones with 2,3-annulated hydrogenated 1,3-diazaheterocycles. Synchronous and asynchronous double proton transfer in cyclic hydrogen-bonded associates

Abstract

It was shown by quantum chemical methods and 1 H NMR spectroscopy that in the series of prototropic tautomeric quinazolin 4 ones with hydrogenated 1,3 diazaheterocycles annulated at positions 2 and 3, namely, imidazole, pyrimidine, or [1,3]diazepine (compounds 1-3, respectively), the 1H tautomeric form strongly predominates in the gas phase and in solutions regardless of the nature of these cycles. Tautomerization of tricycles 1-3 occurs via the intermolecular mechanism to form as intermediates hydrogen bonded cyclodimers of these compounds or their cyclosolvates with proton donor solvents. The key step of the reaction is the intraassociated concerted double proton transfer, which can proceed in nearly synchronous and asynchronous modes. In particular, double proton transfer in cyclodimers of quinazolinones 1-3 is asynchronous and proceeds with the formation of solvate stabilized polar transition states, which are similar in structure to ionic intermediates of the nonconcerted double proton transfer.Key words: 2,3 dihydroimidazo[2,1 b]quinazolin 1(10)H 5 one, 1,2,3,4 tetrahydropyr imido[2,1 b]quinazolin 1(11)H 6 one, 2,3,4,5 tetrahydro[1,3]diazepino[2,1 b]quinazolin 1(12)Н 7 one, tautomerism, transition states, homocyclodimers, heterocyclodimers, synchronous double proton transfer, asynchronous double proton transfer, cyclic hydrogen bonded associates.Tricyclic quinazolin 4 ones 1-3 with 2,3 annulated hydrogenated imidazole, pyrimidine, and diazepine heterocycles are interesting objects with structural simi larity to hydrogenated imidazo and pyrimido[1,2 a]benz imidazoles. A series of the latter includes promising pharma cologically active compounds. 1-8 They are also promising as objects for investigation of the influence of intermo lecular hydrogen bonds on the reactivity of heterocycles. 9The data on the biological activity of various N substi tuted quinazolinones 1 and 2 are