INTERMEDIATES IN THE PAAL-KNORR SYNTHESIS OF FURANS

New experimental evidence for the mechanism of the Paal-Knorr reaction involving the acid-catalyzed cyclization of a 1,4-diketone to form a furan is reported. In aqueous or alcoholic solutions containing hydroc hloric acid and in chloroform containing boron trifluoride-etherate d, l- and meso-3,4-diethyl-2,5-hexanediones (2r and 2m) cyclize at unequa l rates; the stereochemical configuration of the unchanged done is pre served during the reaction. This disagrees with the commonly accepted mechanism involving the ring closure of the rapidly formed monoenol (1 1b) followed by loss of water. A pathway involving the rapid protonati on of one of the carbonyls followed by the electrophilic attack on the protonated carbonyl by the enol being formed at the other carbonyl gr oup (10c) is proposed to account for the difference in reaction rates between the diastereomers of 3,4-disubstituted 2,5-hexanediones (1-3). The following results also seem to support the intermediacy of 10c. T he presence of two isopropyl groups in 3,4-diisopropyl-2,5-hexanedione (3) considerably reduces the rate of cyclization, The catalytic const ants k(H)(+) for the cyclization of 2r and 2m are larger than the cons tants for enolization of methyl ketones. The diastereomers of 2,3-dime thyl-and 2,3-diethyl-1,4-diphenyl-1,4-butanediones (4 and 5), which co uld enolize only toward the center of the molecule, also react at diff erent rates. The d,l and meso dideuterio analogs (d(2)-4r and d(2)-4m) exhibit a primary isotope effect during cyclization. The order of cyc lization of 1,4-diphenyl-1,4-butanedione (6) and its analogs (7-9) rev eals that the presence of electron-donating groups facilitate the reac tion.