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Anal. Found: C, 29.35, 29.45; H, 6.86, 6.92; N (Dumas), 9.21; S04- (as barium sulfate), 28.26, 28.44. Acknowledgment.-We wish to express our appreciation to Dr. Means' group for the microanalyses, to Mr. Kersey for the biological assays and to Mr. Carboni for certain technical assistance.
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Vol. 72
to the 2,4-dibromo derivative (V) (m. p. 183-185' [ a I z 00'~ . Calcd. for CzlH3003Br2: C, 51.44; H, 6.17. Found: C, 51.64; H, 5.88). Twenty hours of refluxing with sodium iodide in acetone yielded 2-iodo-17a-hydroxyprogesterone (m. p. 112-115', [aI2O~ 71°, maximum 244 mp (log E 4.15). Calcd. for C21Hz9031: I, 27.81. Found: I, 28.32), which without isolation on deiodination CONTRIBUTION FROM afforded 17a-hydroxyprogesterone (VI) (m. p. RESEARCH LABORATORIES CHAS.PFIZERAND Co., INC. PETERP. REGNA 220-222', [ a ] " ~ 103' (acetone), maximum 241 FRANCIS BROOKLYN, NEWYORK X. MURPHY mp (log E 4.30)). The present method, in addiRECEIVED DECEMBER 9, 1949 tion to ready availability of starting materials and good yields, has the marked advantage over the STEROIDS. 11.' A METHOD FOR THE CONVER- corresponding normal ketones in that from each saturated 3-ketoallosteroid (e. g., IV), three unSION OF ALLO-STEROIDS INTO A '-3-KETO STEROIDS saturated ketones of interest for clinical trial can be prepared: in addition t o VI, V on collidine Sir : The current interest in corticosteroids as pos- treatment afforded the interesting A'p4-!regnadisible therapeutic agents in arthritis has made the en-17a-ol-3,20-dione (m. p. 232-234 , [ a I z 0 ~ 38.5', maximum 244 mp (log E 4.14). Calcd. availability of starting materials extremely imporfor Cz1H2803. C, 76.79; H, 8.59. Found: C, tant. Since the majority of the abundant steroidal plant sapogenins, representing a potentially un- 76.96; H, 8-21), while the monobromination limited source for 20-keto-pregnanes, either be- product of IV on dehydrobromination yielded the long to the allo series or possess a As-3-hydroxy AI-isomer of VI, A1-allopregnen-17a-01-3,20-di71°, maximum grouping, which in turn is convertible in nearly one (m. p. 254-257', [aIz0D quantitative yield into the 3-ketoallosteroid sys- 230 mp (log E 4.05). Calcd. for C21H3003: C, tem (I), it has become an urgent matter to de- 76.32; H, 9.15. Found: C, 76.49; H,9.33). Details, applications and extension of this velop a general procedure for the transformation method to other cortical hormones and analogs of I into the essential A4-3-ketomoiety. We have observed that while 3-keto-4-bromo- will be reported shortly. LABORATORIES G. ROSENKRANZ steroids of the normal series (rings A/B cis) do not RESEARCH S. A. ST. KAUFMANN react with sodium iodide in acetone solution, 2- SYNTEX, MEXICOCITY,D. F. J. PATAKI bromo-3-ketoallosteroids (rings A/B trans) readily CARLDJERASSI react to yield the corresponding iodo derivatives, RECEIVED DECEMBER 5, 1949 which on treatment with zinc dust in ethanol, chromous chloride in acetone, or even short boiling w'th collidine regenerate the saturated 3-keto- NITROGEN FIXATION IN AN ULTRASONIC FIELD allosteroids. When applied to 2,4-dibromo-3ketoallosteroids (11), obtainable in high yield Sir : Our observations on the oxidative fixation of from I, short boiling with sodium iodide affords a molecular nitrogen in ultrasonic field have led to 2-iodo-4-bromo-3-ketoallosteroid (e. g., 2-iodo-4bromoandrostan-17-01-3-one 17-hexahydrobenzo- results which are of special interest in the connecate, m. p. 146-149'. Calcd. for C26H3803BrI: C, tion of biological nitrogen fixation. The experiments were carried out in water solu51.58; H, 6.33. Found: C, 51.71; H, 6.35), which on refluxing with collidine suffers simulta- tion at ordinary pressure; radiating surface of neous dehydrobromination and deiodination to the vessel was 42 mm. in diameter; radiation inlead directly to the required A4-3-ketosteroid. tensity in the radiation point was 10 W/sq. cm., Even more strikingly, if I1 is refluxed with sodium frequency 300 kc./sec. The hydrogen and nitroiodide in acetone solution for twenty hours, there gen gases were led to the other side of the solution is obtained in good yield a 2-iodo- A4-3-ketosteroid a t the rate of about 1 l./min., carbon monoxide (111), which is smoothly transformed to the A4-3- gas 0.4 l./min. Thus, oxygen was present in the ketosteroid. The generality of this method has al- solution in each experiment. The nitrogen fixation in ultrasonic field does ready been demonstrated in five diverse instances in this Laboratory and will be exemplified here by not, a t least essentially, depend on the hydrogen the preparation of the important adrenal hormone ion concentration of the solution as far as the total amount of fixed nitrogen, nitrite plus nitrate N 17a-hydroxyprogesterone. N-Bromoacetamide oxidation of allopregnane- (other N-compounds have not been found), is 3~,17a-diol-20-one2 gave a high yield of allopreg- considered. On the other hand, the mutual relanan-17a-ol-3,20-dione ( I v ) (m. p. 251-253', [aI2OD tion of nitrite and nitrate N is decided by the pH 24'), which on dibromination in acetic acid led of the solution (Figs. 1 and 2). These results explain the observation of Loiseleur' on the rapid (1) Paper I, THISJOURNAL, 71, 3689 (1949). (1) Loiseleur, Corn);. rend.. 518, 876 (1944). (2) Kritchevsky and Gallagher, J . Biol. Ckcm., 179, 607 (1949).
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