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Issue 11, 1989
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Kinetics and mechanism of the cyclisation of 2′,6′-dihydroxychalcone and derivatives


pH–Rate profiles are reported for the cyclisation in water to 5-hydroxyflavanones of 2′,6′-dihydroxychalcone (1) and its 4-methoxy (2), 3,4-dimethoxy (3), 3,4,5-trimethoxy (4), 2,4,6-trimethoxy (5), 4-chloro (6), and 3,4,4′-trimethoxy (8) derivatives. As for the previously studied 2′,6′-dihydroxy-4,4′-dimethoxychalcone (7), rate coefficients are established for acid-catalysed cyclisation of neutral chalcone, for unimolecular cyclisation of the neutral, monoanionic, and dianionic chalcone, and for the base-catalysed reverse ring-opening reaction. Cyclisation of the monoanion of 2′,6′-dihydroxychalcone is almost 40 times faster than that of the monoanion of the 2′-hydroxy-6′-methoxychalcone (10) and is also estimated to be about ten times faster than that of the reactive monoanion of 2′,4′-dihydroxychalcone. These are the first calculations of the enhancement of rate of monoanion cyclisation by the 6′-OH group. The effect is only small, and is suggested to arise largely from stabilisation of the transition state for ketonisation by hydrogen bonding to enolate oxygen. Other reactivity differences amongst the chalcone monoanions are also discussed. Enthalpy and entropy of activation data are reported for monoanion cyclisation of (1), (2), and (4)–(6). Rate coefficients for the cyclisation of the chalcone monoanions are almost identical for (1)–(4) and (6) in water but not in deuterium oxide: kinetic hydrogen isotope effect (KIE) values are 3.4 (1), 5.7 (2), 4.9 (3), 3.0 (4), 7.5 (5), 2.9 (6), and 5.0 (8). For chalcones (2) and (7), the KIE values of which are both 5.7, the amounts of H versus D incorporation at the flavanone 3-carbon for monoanion cyclisation in H2O/D2O mixtures were established by mass spectroscopy. This gave product (or ‘discrimination’) isotope effect (PIE) values of 7.9 for (2) and 3.8 for (7), suggesting for (2) but not (7) an inverse isotope effect contribution to KIE from sources other than rate-limiting proton transfer to carbon. Monoanion cyclisation of (1) in D2O was established by 1H n.m.r. as involving almost equal amounts of anti and syn addition of 2′-O to the enone double bond. Reactivity differences amongst the chalcones for reactions other than monoanion cyclisation are only briefly considered.

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Article information

J. Chem. Soc., Perkin Trans. 2, 1989, 1623-1632
Article type

Kinetics and mechanism of the cyclisation of 2′,6′-dihydroxychalcone and derivatives

C. O. Miles and L. Main, J. Chem. Soc., Perkin Trans. 2, 1989, 1623
DOI: 10.1039/P29890001623

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