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positive bromine were used, each isomer gave predominantly one product. trans-4-Methylcyclohexylmercuric bromide was cleaved with bromine in pyridine in air to yield pure trans-4methylcyclohexyl bromide, b.p. 57.0' (9.5 mm.), m.p. 25.5-26.0°, n 2 g . 1.4800, g~ which had a strong characteristic equatorial C-Br infrared band a t 704 cm.-l. Similarly, cis-4-methylcyclohexylmercuric bromide yielded pure cis-4-methylcyclohexyl bromide, b.p. 57.0-57.8' (9.5 mm.), n2'.'D 1.4843, which had a strong characteristic axial C-Br infrared band a t 685 cm.-l. The assignment of structure was made on the basis of the known stretching frequencies for equatorial and axial C-Br linkage^,^ and the physical properties of the isomeric bromides. Within the sensitivity of our methods for detecting each isomer (less than 2%), the reactions in pyridine are quantitatively stereospecific.
would have effects on the infrared and ultraviolet absorption spectra similar to those exhibited by chlorine and bromine atoms a t this position.8 The apparent formation of the a-epimer is interesting since, in comparison with bromo, chloro and methyl substituents, the probability of steric interaction of a 2P-fluorine with the angular methyl group a t Cla is a t a minimum and the probability of electrostatic repulsion between a ea-fluorine and the 3-keto group is a t a maximum.' In contrast to the activity of the above-mentioned fluorohydrocortisone derivatives, the activity of I is undistinguished, being approximately one-third that of hydrocortisone as measured by the liver glycogen, thymus involution and asbestos pellet granuloma inhibition tests in adrenalectomized rats.10 This relatively low activity of I stands in contrast to the high activity of 6a-fluorohydrocortisone' and is interesting when one con(4) D. H. R. B a r t o n , J. E. Page, a n d C. \V, Shopee, J . Chenz. SOC., siders the high activity of both the 2a-methyl" and 6a-methylhydrocortisone derivatives.12 331 (1956). We have prepared other 2-fluor0 steroids by this DEPARTMENT OF CHEMISTRY FREDERICK R . JESSES procedure and have studied the utility of perUNIVERSITY OF CALIFORNIA BERKELEY4, CALIFORNIA LAIRD13. GALE chloryl fluoride for the introduction of fluorine a t RECEIVED DECEMBER 22, 1958 other sites in the steroid molecule. These results will be published in the near future.
FLUORINATED STEROIDS. I. THE SYNTHESIS OF 2a-FLUOROHYDROCORTISONE
(8) (a) R . S . Jones, D. A . Ramsey, F. Herling a n d 6 .Dobriner, THISJ O U R N A L , 74, 2828 (1052); (b) B. Ellis a n d V. Petrow, J . C h c m . Soc., 1179 (1958). (0) See E. J. Corey [THISJ O U R N A L7 ,6 , 175 (1954)l f o r a discussion of t h e factors determining t h e relative stability of epimeric a-I)romo ketones in t h e steroid field. (10) We wish t o t h a n k I.. Bortle, E. Heyder, A. X o n t e f o r t e , IC. Ross a n d I. Ringler of t h e Experimental Therapeutics Research Section of these Idahoratoriesfor these assays. (11) J. A. Hogp, F.H. Lincoln, R . W. Jackson a n d IV. P. Srhneirlcr, THISJOURNAL, 77, 0401 (1085). (12) G. B. Spero, c l ni., ibid., 78, G213 (1956).
Sir : The introduction of fluorine into the 6a-,l positions of the hydrocortisone strucand ture has resulted in dramatic increases in the glucocorticoid activity of this h ~ r m o n e . ~ I t was, therefore, of considerable interest to prepare and test 2a-fluorohydrocortisone (I). Reaction of the sodium salt of 20-ethylenedioxy-2-methoxalyl-ORGANIC CIIENICAL I
