COMMUNICATIONS TO THE EDITOR
662
Anal. Calcd. for CSSHUO~:C, 71.02; H,7.95. Found: C, 70.92;H.7.88. bisnor-Cholyl benzoyl ketone 7,12-diacetate, m. p. 201-203.5': [ a b 4-80". Anal. Calcd. for CwH&: C, 72.-05;H, 8.18. Found: C, 72.16; H, 8.34. 2-bisnor-Cholyl-3-phenyl-quinoxaline triacetate, m. p. 217-218.5'.
A NEW METHOD FOR THE DEGRADATION OF BILE ACID DERIVATIVES
Sir: 1 wish to report in outline form a promising new procedure for degrading the characteristic y-substituted n-valeric acid side chain (I) of tlie bile acids and their derivatives in the preparation of suitable starting materials for steroid hormone partial syntheses. The excellent method of Gilman and Nelson' when applied to the acid chloride of I provides the phenyl ketone (11) in 70 to 75% yield if diphenylcadmium is used. Bromination of the ketone yields a mixture of isomeric 23-bromc compounds (111) which upon acetolysis forms the corresponding 23-acetoxy derivatives (IV). The latter, after hydrolysis to the a-ketols, can be oxidized
Vol. 66
Work now in progress indicates that the application of this degradation scheme to substituted nor-bile acids will result in the formation of pregnane-20-one derivatives in much higher yields than heretofore obtainable. NATIONAL TNSTITUTE OF HEALTH BETHESDA, MARYLAND ROBERTP. JACOBSEN RECEIVED MARCH21, 1944 DESTRUCTION OF RIBOFLAVIN IN MILK BY SUNLIGHT'
(R = Substituted steroid ring system) CH3 CIia \ \CHCH2CH2COOH + ')CHCHLX2COC'eH6 --+ / d R i I1 0.ic Br c w 1 CHI 1 \ C H C H ~ C H C O C ~ H---f ~ ) C H C R ~ C H C O C ~+ H~ / T I(>R 111 11 OAc CHI CHI I )CHCH&OCOC6H6 ---f >CHCH=CCOCsHs
Sir: The phenomenon of photochemical destruction of riboflavin has been adequately demonstrated by Gyorgy and coworkers2 and R O S C Oand ~ , ~more recently by Williams and Cheldelir~.~The latter workers demonstrated that as much as 26% of the riboflavin of milk was destroyed by light when the milk was exposed for as short a time as five minutes a t 100'. These findings suggested that in all probability appreciable amounts of riboflavin would be lost in milk bottled in the standard type retail glass milk bottle when exposed to sunlight a t ordinary temperatures. Experiments were conducted from mid-morning with copper sulfate in aqueous pyridine to the CY- until mid-afternoon on sunny days. Fresh milk diketone (V) in 65 to 70% over-all yield from the obtained the same day was bottled in pint milk tnonoketone. Acetylation of the diketone then bottles with the usual type cap and exposed to diforms the expected enolacetate (VI) which is suit- rect sunlight on an open porch. Riboflavin concenable for oxidative cleavage to bisnor-acid deriva- trations were determined fluorometrically with the tives. Coleman electronic photometer (Model 12), using Of the many new compounds which have been essentially the technic of Hand6except that 10 cc. characterized in the course of these studies, those TABLE I arising as intermediates in the degradation of cholic acid are typical : DESTRUCTION OF RIBOFLAVIN IN MILKBY SUNLIGHT 111) Cholophenone (,nor-cholyl phenyl ketone), m. p
174-176.5'; [ c t l Z 0 ~+26°.2 Anal. Calcd. for CaoH4,04.1/~H20:C , 75.43; 11, 9.50. Pound: C, 75.35; H, 9.48. Cholophenone triacet.atr. 111. p. 120 3-121'; [ N ] ~ O ~ \ $79" Cholophenone 2,~-dirlilrophenq-lhydrazone: ni 1 1 221-222.5" Cholophenone oxime, m . p. 211-217" dec (111) 23(~)~-Bromo-cholophenone triacetate, m . p. 108.5111.5": raI2'D +95". Anal. Calcd. for C ~ ~ H W 07Br.H20:'C, 62.51; H, 7.43. Found: C, 6 2 2 6 ; H , 7.19. Calcd. for C86H190,Br: C, 64.18; H , 7.33. Found: (sintered in zucuo), C, 64.05; H,
Series
1
II hr. exposure,
rlcc.
%
1.86
1.13
39
I 51
0.9'; 1 13 1 40 1.60
1 98
ri
2 29 2.29 0.83 1.94 2.43 2 60 1.28
I11
IT
7 2.5
(IV) 23(~)~~Acetoxy-cholophenone triacetate, m. p. 180182'; [CYJ*OD -10'. Anal. Calcd. for CSH&. 1/2Hz0: C, 68.96; H, 8.07. Found. C, 69.15; EX, 8 (39. bzsnor-Cholyl benzoyl ketone triacetate, m p . 1660(V) 169' (after drying, 161 5-166') [cl]*'D 192
Original riboflavin content, ricc.
Riboflavin content after
0.38
1.30 1 65 1.90
0.66
Destruction
ar;
13 39
30 31 33 8'
2: 48
(1) Published with the approval of the Director of t h e North Carolina Agricultural Experiment Station as Paper No. 182 of the Journal series. (2) P. Ggargy, R. Kuhn and T. Wagner-Jauregg, X0turwissenAchafl, 21, 560 (1933). (3) hl. H Roscoe, Biochcm. 3 . . 27, 1540 (1933) '4) R.K V.'illinm.; anti \- H Cheldelia. Science, 96,2% (,I9421 .->, i-3
il
iiur.ti
i u d /,.Hi i..hrn:
iW*/
I?,[
11. .30ii Il939;
