Aug., 1951
COMMUNICATIONS TO THE EDITOR
4053
11,2O-dione(II); m.p. 290-292' (all m.p.s. are un- derivatives, is not applicable in the bile acid series, corrected); found: C, 72.98; H, 9.74; ( ( Y ) ~4-43 ~ D since we have found that methyl A7~9(11)-lithochol(dioxane). Bromination of I1 in chloroform and adienate reacts with performic acid to give methyl subsequent treatment of the 21-bromo derivative 3a-formoxy-7-keto- As-cholenate, m.p. 164-166', ~ Di, XEtoH 255 mp, log e 3.85 (Anal. (m.p. 238-240'; found: Br, 18.39) with sodium [ a ]-1.6' Calcd. for C26H3806:C, 72.52; H, 8.90. Found: acetate afforded aZZopregnane-3~,17a,21-triol-l1,20dione-21-acetate, 111; m.p. 233-235'. The latter C, 72.22; H, 9.12) in 63% yield; the hydroxy acid on oxidation with N-bromoacetamide in methanol melts a t 209-210°, [CY]D -38' Di, (Anal. Calcd. for was transformed into allopregnane- 17a,2 1-diol- C24H3604: C, 74.19; H, 9.34. Found: C, 74.57; H, 9.33). 3,11,20-trione (IV); m.p, 229-233'; ( a ) 2 4+loo' ~ A fourth method, applicable in both series, con(CHCL); found: C, 68.46; H, 7.68 which proved to be identical with a sample prepared by the sists in reaction of a diene (I) with excess N-bromohydrogenation of cortisone acetate with palladium succinimide in aqueous t-butanol and addition of in methanol containing potassium hydroxide. silver nitrate followed by chromic acid. The reBromination and dehydrobromination of the allo- sulting As-ene-7,11-dione I V is convertible through dihydrocortisone acetate by a procedure to be described in detail later produced cortisone acetate characterized by its melting point, optical rotation, ultraviolet and infra-red absorption spectra. COCHI
COCH, L
I
IV
I1
I11
v
VI
V to VI as previously described'; alternately, a t least with methyl 3a-acetoxy-7,ll-diketocholanate, V is convertible to VI by Raney nickel reduction of the 7-cycloethylenemercaptol derivative, m.p. Complete details for the conversion of ergosterol, 162-163.5', [a]D +27.6' Di (Anal. Calcd. for diosgenin, stigmasterol and cholesterol to cortisone C29H440&: C, 64.89; H, 8.26; S, 11.96. Found: acetate will be published in this Journal. C, 65.20; H, 8.49; S, 11.86). (430 J. M. CHEMERDA Methyl 3 a-acetoxy- A7~9(11)-lithocholadienate E. M . CHAMBERLAINmg.), processed as indicated, gave 152 mg. of crude MERCK& Co., INC. RAHWAY,NEWJERSEY E. H. WILSON Max TISHLER IV, XEtoH 272 mp (3.77), which on reduction gave 90 mg. of pure V, m.p. 161-162' (no depression RECEIVED JULY13, 1951 with previous sample; identical I R spectra), [a]D 26.7' Di (Anal. Calcd. for C27H4006: c, A FURTHER METHOD FOR PRODUCTION OF 70.40; H, 8.75. Found: C, 70.71; H, 8.96). 1 1-KETOSTEROIDS FROM A'~""'-DIENES The reaction with NBS results in development of Sir : strong absorption a t about 255 mp; when the Three methods have been recorded for con- excess reagent was destroyed and the crude bromo version of A7$9(11)-dienes into the corresponding derivative extracted and debrominated, the prod1l-ketosteroids.1B2J3 The first method' was shown uct, m.p. 179-180°, XEtoH 254, 310 ml* (3.88, 2.84) to be applicable in both the cholestane and copro- corresponded closely to methyl 3a-acetoxy-7-ketostane series; the third, demonstrated wit4 sterol As-cholenate' (no depression) and not a t all to the isomeric 11-ketone4; hence I1 is a probable inter(1) L. F. Fieser, J. E. Herz and W. Y.Huang, THIS JOURNAL, 78, mediate. 2397 (1951). The by-product of the oxidation (no ultraviolet absorption) described as methyl 3rr-acetoxy-7,8-oxido-A~(~~)-cholenate, As applied to A7~9(111~22-ergostatrienyl acetate, actually is methyl 3rr-acetoxy-7-keto- Ag(ll)-cholenate,since on reducthe reaction sequence afforded a crude enedione tion with sodium borohydride it yields an alcohol, m.p. 111-115°, that on reduction with zinc and acetic acid gave [ a ] +57.5' ~ Di, XChf 2.91, 5.80r (Anel. Calcd. for CzrHdzOs: C, 7,ll-diketo-A22-erogostenylacetate, m.p. 197-199', 72.61; H, 9.48. Found: C, 72.56; H , 9.45), that on dichromate oxidation is reconverted to the starting material. The by-product can [ a ] D -29.5' chf ( A d . Calcd. for C~OH&: c , be isomerized to the conjugated isomer and the latter converted into 76.55; H, 9.85. Found: C, 76.47; H, 9.77), in the starting diene for recycling, by reduction of the free acid with, agreement with the properties reported.2 A7,9(11)sodium and amyl alcohol followed by acid dehydration. Cholestadiene-3p-01 benzoate was converted simi(2) E. M.Chamberlain, W. V. Ruyle, A. E. Erickson, J. M. Chemerda, L.M. Aliminosa, R . L.Erickson, G. E. Sita and M.Tishler, ibid., larly to the As-ene-7,ll-dione benzoate,' m.p. 15573, 2396 (1951). 15S0, [ a ] +46' ~ Di, kEtoH 269 mp, log e 3.80 (3) G. Stork, J. Romo, G. Rosenkranz and C. Djerassi, ibid., 78,
+
3546 (1951).
(4) H. Heymann and L. F. Fieser, THISJOURNAL, 78,4054 (1951).
COMMUNICATIONS TO TIIE EDITOR
4054
(Anal. Calcd for C34H4604: C , 78.72; H, 8.94. Found: C, 78.14; HI 8.98); this on reduction gave cholestane-3/3-ol-7,1l-dionebenzoate, m.p. and mixed m.p. with previous sample 197-199'.
1701.
72
X more detailed report of the results will be published.
CENTRAL RESEARCH DEPARTMENT LYLEJ. HALS MINNESOTA MINING81 MANUFACTURIKG THOMAS S . REID Lours F . FIESER COMPANY GEORGE H. SMITH, JR. CONVERSE MEMORIAL LABORATORY JOHN C . BABCOCK ST. PAUL,MINNESOTA RECEIVED JULY 2, 1951 HARVARD UNIVERSITY JOSEF E. HERZ CAMBRIDGE 38, MASSACHI'SETTS WEI-YUANHUANC WILLIAMP. SCHNEIDER RECEIVED Jrrtv 16, 1951 CORRELATION OF A SYNTHETIC STEROID WITH AN INTERMEDIATE TO CORTISONE Sir: THE PREPARATION OF TERMINALLY UNSATURATED The method reported for the production of PERFLUORO OLEFINS BY THE DECOMPOSITION OF 11-keto1*2and 110-hydroxy steroids2 from 9,11THE SALTS OF PERFLUORO ACIDS ethylenes is clearly inapplicable to natural (A 'B Sir:
trans) sterols but might, we thought, be useful in total synthesis if it could be shown applicable to compounds with shortened side chains. We hence converted methyl 3 a-acetoxy- A'("' e t i ~ c h o l a n a t e(I) ~ prepared from a sample of 3ahydroxy-1 1-ketoetiocholanic acid kindly supplied by CEF2TL*ICFrCFzCOJ4 --+ CvF2n+1CF=CF> f COS + MF Dr. Max Tishler (Merck 81 Co.), with perbenzoic The sodium salts have been found to give the acid to the oxide, needles from methanol, m.p. 166.9167.4') [ a ] D +68.4' Chf (Anal. Calcd. for Czsmost satisfactory yields. C, 70.74; H, 8.77. Found: C, 70.47; The salts were prepared by neutralizing an H&: aqueous solution of the perfluoro acid with sodium H I 8.74), and by niethoxide-catalyzed methanolysis hydroxide and were dried by heating in air a t 100' obtaiiied the sa-hydroxy oxide 11, m.p. 149.8for S hours. The decarboxylation reaction was 131.0', [ a ] D f4S.g' Chf (Anal. Calcd. for Czlcarried out in a distilling flask heated in a furnace. HS2O4: C , 72.38; H I 9.26. Found: C, 72.20; Gaseous products were collected in traps cooled H, 9.50). Oxidation with sodium dichromate in by liquid air or Dry Ice-acetone. Heat was gradu- glacial acetic acid furnished the 3-ketone, m.p. [ a ] D +29.4' Chf ally applied to the flask. Decomposition occurred 128-130' and 138.0-139.8', a t a controllable rate a t a furnace temperature of (Anal. Calcd. for CZ1H3004: C, 72.80; H, 8.73. 200-300'. The reactions were carried out a t Found: C, 72.82; HI 8.85), and chromic anhydride atmospheric pressure except where the product in aqueous acetic acid converted the keto oxide to olefin boiled above room temperature, as in the methyl 3P-hydroxy-3a,9a-oxido- 11-ketoetiocholan~ Chf, case of CSFls-1 from sodium perfluorocaprate, when ate (III), m.p. 174.8-176.0°, [ a ]+134.6' reduced pressure was used. C, 2.92, 3.83, 5.86p (Anal. Calcd. for C21H&: For example, in the pyrolysis of sodium perfluoro- 69.58; H, 8.34. Found: C, 89.30; H, 8.44); butyrate decomposition occurred a t 345-253'. acetate (acetic anhydride-boron fluoride), m.p. From 723 g. of salt, 590 g. of product was collected 123.8-125.3', [CY]D +13>' Chf ( A n d . Calcd. for in the cold trap. Infrared analysis indicated this C2SRH3206: C, 68.29; H, 7.97. Found: C, 68-01; to consist of 50 mole c/b COa and 50 mole 9; CaF6. H, 8.09). Cleavage of I11 with dry hydrogen After passage of the gases through aqueous base, bromide gave the known methyl 8,11 -diketo12a-bromoethiocholanatei (IV), which was de455 g. of C3Fs (99% yield) boiling at -29' was obtained. Terminally unsaturated perfluoro brominated4 to methyl 3,l l-diketoeti~cholanate~ olefins containing 2, 3 , 4 , 5 and 9 carbon atoms, pre- (V) map. 183.8-186.2', [.ID +92.4' Chf; mixed pared by this procedure, are described in the table. m.p. determination with an authentic sample and if-e have found that salts of the perfluorocarboxylic acids can be decarboxylated to give the 1-perfluoroolefins in good yield. This reaction appears to be unique with the salts of the perfluoro acids.
TABLE I TERMINAL PERPLUORO OLEFINS Compound
CF2=CF2 CF&!F=CF% CFsCF2CF=CFz
CFj( CF~)~CF=CFL CFs(CFz)&F=CFz
Molecular wt. Found Calcd.
99 150 201 250
..
100 150 200 250 450
-
B.P., "C.
730-745 mm.
-76 to
- 29
- 75
- 2 to - 1 29 t o 30 123 t o 124
The olefins were identified by molecular weight, boiling point, infrared spectra, the preparation of chemical derivatives, or oxidation to perfluoro acids containing one less carbon atom than the olefin. They have in common an infrared absorption peak a t 1795 an.-' which is characteristic of the double bond in &Fzn +lCF=GFa.
Fluorine, % Calcd. Found
.. ..
.. ..
76.0 76.0 76.0
75.9 75.9 75.5
Anal.
Carbon, '% Calcd. Found
..
..
.. 24.0 24.0 24.0
24.2 24.1 24.0
.
I
comparison of infrared spectra and rotations indicated identity. (1) L. F. Fieser, H. Heymann and S. Rajagopalan, TXISJOURNAL,
7a,2307 (1950). (2) H. Heymann and L. F. Fieser, ibid., 78, in press (1851). (3) A. Lardon and T Reichstein, Hclo. Chim. A c f o , 18. 1420 (1945). (4) A. Lardon and T. Reichstein, ibid., 46, 705 (1943).
