1-(5-Chloro-2,4-dihydroxyphenyl)-2-(4-ethoxyphenyl)ethanone

The structure of the title compound, C16H15ClO4, contains aryl rings which are inclined by 75.6 (1)° to each other. It displays intramolecular O—H⋯O hydrogen bonding between the 2-hydroxy and carbonyl groups, forming a six-membered ring. Furthermore, the 4-hydroxy group, acting as a hydrogen-bond donor, is bound to the O atom of the 2-hydroxy group of another molecule.

The structure of the title compound, C 16 H 15 ClO 4 , contains aryl rings which are inclined by 75.6 (1) to each other. It displays intramolecular O-HÁ Á ÁO hydrogen bonding between the 2-hydroxy and carbonyl groups, forming a six-membered ring. Furthermore, the 4-hydroxy group, acting as a hydrogen-bond donor, is bound to the O atom of the 2-hydroxy group of another molecule.
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: WN2279).

Comment
Phytoestrogens, in particular the soy isoflavones such as daidzein and genistein, have positive impact on human health (Setchell, 1998;Barnes, 1998 andDixon &Ferreira, 2002). High consumption of soy products has been associated with a low incidence of hormone-dependent cancers (Barnes & Peterson, 1995), the symptom alleviation of menopause (Greenwood et al., 2000) and protection against osteoporosis (Anderson & Garner, 1997) as well as cardiovascular disease (Anthony, 2002). Consequently, there is growing interest in using phytoestrogens and synthetic derivatives for the chemoprevention and therapy of these diseases.
One of the synthetic routes to daidzein and its derivatives is via the Freidel-Crafts reaction of resorcinol and phenylacetic acid catalysed by boron trifluoride etherate (Whalley, et al., 2000), giving the deoxybenzoin intermediate. In the preparation of 5-chlorodaidzein, 1-(5-chloro-2,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)-ethanone (2) was obtained (yield 77%) from the coupling of 5-cholororesorcinol with 4-hydroxyphenylacetic acid in boron trifluoride etherate. Surprisingly, the title compound, 1-(5-chloro-2,4-dihydroxyphenyl)-2-(4-ethoxyphenyl)-ethanone (1), was also isolated in small amount (5% yield). Boron trifluoride proves to be such a strong Lewis acid, it not only catalyses the Freidel-Crafts reaction, but also activates the diethyl ether and makes it an electrophile. From the position of ethylation, it can be concluded that (1) is formed from the attack of (2) via 4-hydroxyphenyl to the α-position of the actived diethyl ether, because the 4-OH of the benzyl ring is more nucleophilic than the 2-OH and the 4-OH in the other phenyl ring which bears the electron-withdrawing carbonyl group.
The molecular structure of (1) is conformationally similar to that of deoxyanisoin, MeOC 6 H 4 C(O)CH 2 C 6 H 4 OMe. (Arumugan et al. 2007) with statistically invariant C═O and C-C bond lengths and very similar backbone torsion angles, though C4-O4 in 1 appears to be marginally shorter at 1.347 (3) Å than in deoxyanisoin at 1.378 (1) Å; this may be a consequence of the neighbouring chloro substituent in (1).
supplementary materials sup-2 Refinement All carbon-bound H-atoms were included in calculated positions (C-H distances are 0.98 Å for methyl H atoms, 0.99 Å for methylene H and 0.95 Å for aryl H atoms) and were refined as riding atoms with U iso (H) = xU eq (parent atom), where x = 1.2 for methylene and aryl H atoms, 1.5 for methyl H atoms. The OH hydrogen atoms were located in a difference map and refined isotropically, subject to a distance restraint, 0.98 (1) Å. Fig. 1. The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level. Carbon-bound H atoms have been omitted; H atoms bonded to oxygen are represented as spheres of arbitrary radius.