HENRY RAPOPORT AND S A T O R U
4330
p H 7.2 and treated with a strong aqueous solution of benzylisothiouronium chloride. The colorless crystalline salt that separated was filtered o f f , washed and recrystallized from hot water. It formed colorless rectangular plates melting at 195-196". Anal. Calcd. for C I Z H I ~ X Z S(CdH303.CsHloO~ S 2 S ) : C, 54.32; H, 4.94; X, 10.56; S, 12.08; OCH8,
[COSTRIBCTIOX FROM
THE
?VIASAMUNE
Vol. 77
11.70. Found: C, 54.11; H , 5.24; N, 10.57; s, 12.83; OCHs, 9.11. The ratio of N/S is the same as that in benzylisothiuronium chloride and confirms the absence of nitrogen in xanthomycinic acid 11 MADISON,WISCONSIS
DEPARTMEST O F CHEMISTRY, CNIVERSITY O F CALIFORSIA, BERKELEY]
The Stereochemistry of 10-Hydroxycodeine Derivatives'z2 B Y HENRY RAPOPORT .4ND SATORU ,\.IASAMUNE RECEIVED APRIL4, 1955 Oxidation of dihydrodesoxycodeine with cold chromic acid in dilute sulfuric acid led to the formation of 10-tmns-hydroxydihydrodesoxycodeine. With manganese dioxide this alcohol was oxidized to the ketone, and reduction of the latter with sodium borohydride gave exclusively 10-cis-hydroxydihydrodesoxycodeine. The relative configuration of the epimers was established by oxazolidone formation in the case of the czs compound. Distinct differences were found between the epimers in regard to hydrogen bonding, partition coefficient, and dissociation constant as well as susceptibility t o hydrogenolysis, Hofmann degradation, and a variety of oxidation procedures.
Cold chromic acid oxidation of a number of codeine derivatives has led in each case to the 10-hydroxy c ~ m p o u n d and , ~ it was the objective of the present work to determine the stereochemistry of the 10-hydroxyl group introduced by this general I rn reaction. For this purpose, lo-hydroxydihydrodesoxycodeine (IIa) appeared to be the ideal compound since the absence of other reactive groups in the molecule should confine reaction to the position under study. The general procedure of chromic acid oxidation i36 '0' CH3d 'O' was applied therefore to dihydrodesoxycodeine (I), P EL IIB conveniently prepared by lithium aluminum hydride hydrogenolysis of p - toluenesulfonylcodeine X very stnall amount of lo-ketodihydrodesoxyfollowed by hydrogenation.? il hydroxy com- codeine (111) ( , W. Stevenson of this Laboratory has found for normorphine, fiK,'D.'IB (morphine, 8 0 3 ) and norcodeine, pKn'D.lfl (codeine, 8.04). I , 2021 (1R.5fl). (XI]V. Prelog and 0. Hbfliger, Helz!. Chin%.A c / ~ 33, studied several acyclic 1,2-aminoalcohols and reached t h e same conclusion, v i z . , the isomer in which the hydroxyl and amino groups have the closer proximity is the stronger base, and this effect is most iirw nounced with terti'iry amines. T h e effects they observed were much smaller than the difference hetween I I a and 1111. I n this regard i t miyht l)e o i iiitcre5t ti, cIee i f the difference ( 0 . 1 P t i linlti i n Iiiiie strength hetwem I ; < a n i 1 l i ~ i i i i r - 2 - a i n i n o c g c l o l l e ~ a (ref. n ~ ~ l 1:)) ci)llld 1,e niiiynifietl v ~ ~ i i \ - e r < i ot no the ierlisjrv : I m i n e < , ;tltllo~iahthi.: ,IilTi~ei~rc ~ ~ n ~ l ~ ~ w~< ii ~ li I ,~l j lc r-111~ iller l l ~111.~11 ~ 1 1 1 : ~ l fi,lln
