84-16-2

Crystalline Solid

Estra Plex,Rowell,US,1956

Estrogen; antineoplastic (hormonal).

50 parts by weight of p-hydroxypropiophenone are dissolved in 200 parts by weight of a 12.5% solution of caustic soda and shaken with 350 parts by weight of 3% sodium amalgam. The sodium salt of the pinacol thereby precipitating is reacted with glacial acetic acid, whereby the free pinacol is obtained (MP 205°C to 210°C, after purification 215°C to 217°C). The yield amounts to 95% of the theoretical. The pinacol is suspended in ether and gaseous hydrogen chloride introduced, whereby water separates and the pinacolin formed is dissolved in the ether, from which it is obtained by evaporation as a viscous oil (diacetate of MP 91°C). The yield is quantitative.
40 parts by weight of pinacolin are dissolved in ethyl alcohol and gradually treated with 80 parts by weight of sodium under reflux. The solution is decomposed with water and the pinacolin alcohol formed extracted from the neutalized solution with ether. The pinacolin alcohol is a viscous oil which is characterized by a dibenzoate of MP 172°C. The yield is 95% of the theoretical.
30 parts by weight of pinacolin alcohol are dissolved in 25 parts by weight of glacial acetic acid and heated for 30 minutes to 135°C to 140°C after having added 20 parts by weight of hydroiodic acid (specific gravity = 1.94) and 5 parts by weight of red phosphorus. The whole is filtered, the solution poured into water, extracted with ether and the ether solution washed with bicarbonate. The oil remaining after distilling off the ether is taken up in chloroform, whereby hexoestrol [α,β-(p,p-dihydroxy-diphenyl)-α,β-diethylethane] crystallizes out. MP after recrystallization from benzene: 185°C. Yield: 20%.

Estrogen

The carcinogen hexestrol is a nonsteroidal synthetic estrogen. Metabolic activation of hexestrol to its quinonewhich reacts with DNA to form analogous depurinating adductsmay be a primary critical event leading to oncogenic mutations and cancer initiation.

Crystallise meso-Hexestero from *benzene or aqueous EtOH (m 185-188o). The meso-dibenzoyl derivative has m 236-237o. The 3RS,4RS(±)-racemate [5776-72-7] crystallises from pet ether, *C6H6/pet ether, Et2O/pet ether, or MeOH/H2O and has m 128-129o . The (±)-dibenzoyl derivative has m 123-124o . The 3R,4R(+)-isomer [26614-21-1] and 3S,4S(-)-isomer [26614-22-2] crystallise from Et2O/pet ether with m 80 -80.5o and have [] D (+) and (-) 17.7o (c 5, EtOH). Their dibenzoyl derivatives have m 116.5o .[Beilstein 6 III 5503, 6 IV 6761.] They have estrogenic activity where optically active forms are more potent and they have antineoplastic activity. [Aboul-Enein et al. Anal Profiles Drug Subst 11 347 1982, J Am Chem Soc 65 4911941.]