Stereochemical studies, 88 1. Saturated heterocycles, 83 : Synthesis of stereoisomeric condensed-skeleton 2-imino-substituted 1,3-oxazines

Abstract

Thiourea ( 1a - d , 2a - d ) and urea ( 3a - d , 4a - d ) derivatives have been prepared from cis - and trans -2-aminomethyl-1-cyclopentanols, and -l-cyclohexanols and their N -methyl derivatives with phenyl isothiocyanate and phenyl isocyanate, respectively. Treatment of 1 and 2 with methyl iodide and then with alkali furnished - with the exception of the cis - N -methyl derivative - 2-phenylimino-1,3-oxazines ( 5a , c , 6a - d ). The remarkable fact that the ring closure of trans -2-amino-methyl-1-cyclopentanols gives 1,3-heterocycles with trans -anellation supports the assumption that the trans -1,2-disubstituted-1,3-difunctional cyclopentanes undergo ring closure when 1,3-heterocycles with a delocalized pπ bond system are formed. With thionyl chloride the cis -urea derivatives 3a - d afforded an elimination product ( 8 ), whereas the trans isomers 4 yielded the cis oxazines 5 by inversion. 1H and 13C NMR spectroscopic studies indicated that in 5a - d , the “O-in” conformers are favoured (the methylene group of the hetero ring is equatorial , while the oxygen atom is axial ) and all 3-unsubstituted-2-phenylimino-1,3-oxazines exist exclusively in the tautomeric form with an exo CN bond.