Estra Plex,Rowell,US,1956
Nonsteroidal synthetic estrogen
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%.
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.]
