The Origin of the Birch Reduction A. J. Birch Australian National Universitv Canberra The cortical and sex hormones belong to the same chemical group (I), the varying biological activities heing defined by oxygenated groups attached a t position 17. All of the highly active compounds have the cyclohexenone A-ring, except the female hormone estrone, which has a phenolic A-ring. In 1940, the RAF was led to believe that German fighter pilots were heing given cortical hormones (e.g. I, R,R'= CH3, R"=COCHzOH) or biologically active substitutes, and wanted similar ones. I was part of a team in Oxford, with Sir Robert Robinson making possible substitutes hased on the female hormone analog stilhestrol, and containing the characteristic cortical side-chain, COCHzOH. The products were female hormones, not corticoids, and I rethought the problems of total synthesis of analogs. The six-membered rings of (I) suggest aromatic starting materials, hut the use of such.precursors is severely limited by the quaternary nature of the carbons carrying R,R' =CH3. However, Dirscherl (I) had already shown that hydrogenated estrone, which necessarily only has R = H , and also has a saturated A-ring known to he unfavorable for activity, was nevertheless a weakly active male sex hormone. The question arose whether the series with R= H, but with the potent cyclohexenone A-ring might he a s active as the natural series. Accordingly I sought methods for the partial reduction of a n aromatic ring, a process not possible by the standard methods of catalytic reduction, since the desired compounds are more readily reducible than the starting materials. Clues were provided from several directions. Cornforth (21 had reduced 2-methoxynaphthalene with sodium and ethanol to a dihydro derivative, which as an enol-ether, was converted by acid into 2-tetralone. A process of this type could not he carried out on a single benzene ring (the metal-electron addition to the ring does not compete with hydrogen evolution). An accidental observation by Wooster (3) showed that benzene by simultaneous action of sodium and ethanol in liquid ammonia gives dihydrohenzene. A similar reaction which I carried out with anisole, and shortly afterwards with the model for estrone methyl ether, methoxytetralin (II) (4:. showed that the desired product was obtained, converted by acid into the model cyclohexenone type (Ill). In the meantime Ehrenstein (5) had provided further stimulus by the partial synthesis of an active 19-norprogesterone isomer. Considerable delay followed in application of the reduction to steroids, because of the problem of obtaining estrone and because of the insolubility in ammonia of its methyl ether. Finally, however. 19-nortestosterone (I, R = H , R'=CH3, R"=OH) was made and was found to he bioloaically active (6). I t was the first synthetic potent androgen. o t h e r analogs followed, including those of the progestational hormones (71, now used as oral 458 / Journal of Chemical Education
contraceptives. The cortical analog proved to he inactive. For a more detailed survey of these developments see (8). The reduction process proved to he generally useful in synthesis (9). leading readily to otherwise inaccessible compounds. Literature Cited
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(11 Dirscherl. L.. Kraur. J.. and Vora. H. E.. Z Ph.v~ioi.Chem 241. 1,1936). 121 Cornforth. J. W.. Cornionh. R. H.. and Rnhinson. R . J Chcm Soc, 689119421 191 Wonsier. C. H.,and G n d h y , K . L . J Amsr Chem Sor 69, 596 119371. (4) Rirch. A . I . J . Chrm Snc. 430118M). 151 Rhrenriein.M..J Or# Chpm .9.435(19441. 16) Birch. A. d.. and Mukherji. S. M.. J T h e m Soc.. 2111 ,19491: Birch, A. J.. J. Chsm. Soc. 567 119iUI:AnnuaiRep Chem Snc. 47.2101lWO). C.. S c i e n ~151. ~ lOii119661. l i l SPPD~FT~SS~. (81 Rireh. A . L J R m Sor N S W IM.linprewl1191~). 191 Birch. A I.. and Subba Rao. G.. inmAdvances in Organic Chemistry." (Editor: S. 1-65. Taylnr.R.C.l..lohn W i l e ~ & S u n s . I n e . . N ~ w Y o r k .19i2,pp.
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Cagliostro in Basle Lydia Mez Museum of the History of Pharmacy Basle, Switzerland Between 1781 and 1788 a personality of almost intemational fame was a frequent guest in the palatial dwellings of the rich dignitary Jacob Sarasin in Basle. Sometimes the courtyard of Sarasin's house was full of sick people seeking advice and help from the famous stranger, Alessandro Count Cagliostro. He was horn as Giuseppe Balsamo in Palermo in 1743 and educated in the monastery of the Bonfratelli near Caltagirone where he also worked in the dispensary and gathered great knowledge of pharmacy. Later when he was expelled by the monks for blasphemy he went to Messina to work with an alchemist (I). Master and pupil found a process to make from pulp a kind of artificial silk. But their reputation was none too gwd and the town-fathers, instead of profiting from this discovery, forced the two alchemists to leave Messina. The gifted Balsamo started to use his great knowledge in chemistry to swindle people; he "made" gold and outsized diamonds. He also changed his name from Balsamo to Count Cagliostro. He and his pretty wife whom he had married in Rome around 1771, lead a vagrant life which brought them into contact with nearly all the famous people in Europe (1). The 18th century, although called "The Age of Reason"
This column is a series of shan articles on the less known events that contributed to important and interesting developments in chemistry. Living scientists are encouraged to write their own story behind the story. Manuscripts, of about two double-spaced, typewritten pages, and other inquiries should be addressed to the column editor, Dr. John Wotiz, Department of Chemistry and Biochemistry, Southem Illinois Universitv. Carbandale, Illinois 62901.
