4160
COMMUNICATIONS TO
THE
HOMOLOGATION OF ALCOHOLS
A NEW ROUTE TO THE CORTICAL SIDE CHAIN
Sir: The conversion of the readily available bromopregnanolones to compounds of the cortical series having a dihydroxyacetone side chain has been achieved. The key steps involve a rearrangement of a tribromoketone and subsequent reduction of the product.
Vol. 71
EDITOR
Sir:
The conversion of an alcohol to the primary alcohol containing one carbon atom more than the original is usually a tedious procedure. We wish to report a simple one-step homologation reaction. The process consists in treating the alcohol with synthesis gas (carbon monoxide and hydrogen) in the presence of a cobalt catalyst under conditions HCBr2 COOH CHs resembling those employed in the oxo reaction. I I I The oxo or hydroformylation reaction consists of the conversion, by means of synthesis gas, of an olefin to a mixture of aldehydes containing one carbon atom more than the starting material. co /R-CH=CH2 CO H2 +R-CH2-CH2I I1 111 CHO R-CH(CH3)CHO. As developed in Germany, a mixture of olefins secured from the HzCOAc HzCOH I I Fischer-Tropsch reaction was usually used as the starting material. The aldehydes resulting from the oxo reaction were then converted in a separate step, to a mixture of alcohols which were of value for detergent manufacture. It has been reported 1 -1 - 2. LiAlH4 2. Os04 , , recently' that olefins may be converted in one V ' IV step directly to the alcohol if the usual oxo reacBromination of pregnan-3(P)-ol-20-one acetate tion is operated a t slightly higher temperatures. (I) with three moles of bromine yields the 17,21, That our homologation reaction need not proceed 21-tribromo derivative (II), m. p. 196' (dec.), via an olefin intermediate followed by a one-step [ c u ] ~ -3.4' ~D (chloroform). Calcd. for C23H33- hydroformylation-hydrogenation is shown by the 03Br3: Br, 40.1. Found: Br, 40.3. Rearrange- fact that benzyl alcohol is converted to p-phenylment with alcoholic potash yields 17-pregnen-3(/3)- ethyl alcohol under our conditions: PhCHzOH CO ---f PhCH2CH20H. Other converol-20-bromo-21-oic acid (111), m. p. 273' (dec.), 2H2 [CUI2'D 41' (dioxane). Calcd. for C21H3103Br: sions we wish to report consist of the formation C, 61.4; H, 7.6; Br, 19.4. Found: C, 62.0; of n-butyl alcohol and of isobutyl alcohol from H, 7.7; Br, 19.1. Reduction of the bromo acid isopropyl alcohol and of isoamyl alcohol from with hydrogen and platinum catalyst gives preg- t-butyl alcohol. n-Propyl alcohol gave a mixture nan-3(/3)-01-21-oic acid, m. p. and mixed m. p., of n-butyl and isobutyl alcohols but the reaction 22OO.l Lithium aluminum hydride reduction of proceeded so slowly at 180' that part of the the methyl ester of I11 yields the unsaturated initial products was transformed by further to higher alcohols. 20-bromo-21-01 (IV), m. p. 253' (dec), [ c u ] ~ ~homologation D We are inclined to believe that the homologa+53' (dioxane). Calcd. for CZ1H3302Br:C, 63.5; H, 8.4. Found: C, 63.4; H, 8.5. Treatment of tion reaction is an acid (HCoC04) catalyzed rethe diacetate of IV with osmium tetroxide in ether action that proceeds v i a a carbonium ion accordyields pregnan-3(P),17(a),21-triol-20-onediace- ing to a mechanism that will be discussed in detail tate (V), m. p. 1 5 3 O , [ C Y ] ~+49' ~ D (dioxane). later. In a typical experiment, t-butyl alcohol (86 g., Calcd. for C25H3806: C, 69.1; H, 8.8. Found: C, 68.8; H, 8.8. Hydrogenation of V gives the 1.3moles) and cobaltous acetate (7.0 g., 0.03 mole) same tetrol obtained by the lithium aluminum were placed in an 0.5-liter stainless steel autohydride reduction of methyl 17-pregnen-3(@)- clave and heated with synthesis gas (3200 p. s. i., a t 160-180° for one and one-half hours 01-21-~atewith subsequent hydroxylation ( O S ~ ~ )lH2:lCO) , isolated as the triacetate, m. p. and mixed m. p. Gas absorption was 89% of the theoretical ac184O, [cY]~*D +55' (chloroform). Calcd. for cording to the equation C~H4207:C, 67.8; H, 8.9. Found: C, 67.4; H, CHa 8.9. I 2Hz CO --f We thank Parke, Davis and Company for their CHs-C-OH I help. CHs CHS-CH-CHI-CH~OH f HzO THEWHITMORE LABORATORIES
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I SCHOOL OF CHEMISTRY AND PHYSICS CHI THEPENNSYLVANIA STATE COLLEGE R.B. WAONER STATE COLLEGE, PENNSYLVANIA JAMES A. MOORE There was obtained a 63% yield of isoamyl alcoRECEIVED NOVEMBER 19,1949
(1) Marker, Crooks and Wagner, THZS JOURNAL, 64, 817 (1942)8
(1) Wender, Levlne and Orchin, Abstracts of the Atlantic City meeting of the American Chemical Society, September 19-23, 1949
