COMMUNICATIONS TO THE EDITOR
Aug. 5, 1960 I
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tion in the gauge and connectors showed i t to be most concentrated a t a silver solder connection and also substantially present in the Bourdon tube. Although some of the vapor appears to have decomposed upon condensation a more substantial fraction has deposited due to its reactivity. These latter observations are perhaps an explanation of the previous unsuccessful attempts to form a volatile Po compound. I n conclusion, the results presented here indicate the formation of a volatile Po compound that subsequently decomposes due to chemical or radioactive decomposition. Further studies are in progress.
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Position of reactor bottom relative to top of Hornyak button (cm.). Fig. 1.-The change of fast neutron distributions resulting from the formation and decomposition of a volatile Po fluoride. The total fast neutron count in ten minutes divided by the FS pressure (330-350 mm.) is plotted against the position (cm.) of the reactor bottom below the top of the Hornyak button.
Ni tube for about 5 hours a t temperatures up to 393". The maximum neutron intensity, now observed a t 12.5 cm. on the graph, indicates movement of the polonium away from the bottom of the tube. Our resolution did not permit differentiation between this observed maximum and the expected maximum a t 10.1 cm. that would correspond to uniform distribution of the polonium in the tube. A further point of importance is that the total neutron yield in curve B is substantially higher than in curve A. This is a necessary result if the Po is present in the vapor rather than as a solid. In the latter case, a t least half of the a-particles do not produce neutrons due to self-absorption or absorption by the walls. With the Po uniformly distributed in the vapor a much larger fraction of the a-particles produces neutrons. An estimate of the increased neutron yield was made by numerical integration of curves A and B. The value for curve B was increased by 23% to allow for the presence of Po vapor in the gauge and connectors. The ratio of this corrected area under curve B to the area under curve A was 1.9. Curve C was measured after first removing 7.7yo of the polonium fluoridefluorine vapor mixture from the reactor a t room temperature and subsequently replenishing the fluorine pressure with tank Fz for the neutron counting. The integrated neutron yield for curve C was 6.4y0 less than curve B, in reasonable agreement with the removal of 7.7y0of the Po as vapor. After the measurements of curve C the tip of the reactor was kept cold overnight with a solid COz bath, after which curve D was measured. The peak neutron yield was now near the bottom of the reactor but the total neutron yield was much less than curve A. Investigation of the Po distribu-
ARGONNEXATIONAL LABORATORYBERNARD WEINSTOCK ILLINOIS CEDRICL. CHERNICK ARGONNE, RECEIVED MAY7, 1960 THE SYNTHESIS OF C-18 FUNCTIONALIZED STEROID HORMONE ANALOGS. I. A PARTIAL SYNTHESIS OF ALDOSTERONE ~~
Sir: We wish to describe a partial synthesis of aldosterone by a method basically different from recently disclosed appr0aches.l Utilizing methods devised in the course of a study of the synthesis of conanines2 3p-hydroxy-5a-pregnane- 11,20-dione (I) was reductively aminated (C~rc"&zH~OH-Pt-K2) to afford 11, m.p. 187189 , [ a I C h+56", f~ found C,76.27; H, 10.85, which was converted (NaOC1) into 111, m.p. 164") [ a I C h f D f82'; found: c, 69.11; H, 9.85. Upon irradiation of I11 in trifluoroacetic acid solution, cyclization (NaOH-CH30H) , and subsequent CH,
FHA
I
HCR
HO*)
R,O IV, RI Ac, Rz = 0 V, R1 = H, Rz = OH
11, R = NHCH, 111, R = NClCH3
0
F Ri TIII, Ri IX, R1 X, R1 X I , Ri XII, Ri 1711,
= OH, Rz = = OH, R1 = = 0, RP = = 0, Rz = = = 0, Rz = 0, Rz =
Hz,R3
= CH(N(CH8)z)CHs Hz, R3 = CH=CHz Hz, R( = CH=CHz Hz, R3 = CHOH-CHzOH Hz,R3 = CHOACCHZOAC 0, R3 = CHOACCH~OAC XIII, R = CHOACCH~OAC X I V , R = CROHCHzOH XV, R = CHOH-CH~OC(C~HE,)~ XVI, R = COCHzOC(CsH6)3 XI'II, R = COCHzOH
(1) K. Heusler, J. Kalvoda, Ch. Meystre, P. Wieland, G. Anner, A. Wettstein, G. Cainelli, D. Arigoni and 0. Jeger, Experientia, 16, 21 (1960); L. Velluz, G. Muller, R. Bardoneschi and A. Poittevin, C o m p f . rend., '260, 725 (1960): D. H. R. Barton and J . M. Beaton, THISJOURNAL, 83, 2641 (1960). (2) J. F. Kerwin, M. E. Wolff, F. F. Owings, B. B. Lewis, B . Blank, A. Magnani and V. Georgian, in preparation.
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acetylation, the conanine I v , m.p. 186-190°, [ a I C h f ~chlorosilane, RsSi*Cl. The results formulated +83", found C, 74.12; H, 9.76, was ~ b t a i n e d . ~ below for optically active a-naphthylphenylmethReduction of IV (LiAIH4-THF) gave V, m.p. ylchlorosilane,l taken in conjunction with the data 174-177", [ C X ] ~ ~ ' D+70°, found: c, 75.79; H , obtained for the lithium aluminum hydride reduc10.75; which formed the corresponding methio- tions, clearly indicate a high degree of stereospecidide VI, m.p. 277-279", [ a I m e t h a n o 4i ~i 0 , found ficity for both hydrolysis and methanolysis reacc, 56.14; H, 8.39. Heating the quaternary um- tions under the conditions specified.2 monium hydroxide form4 of VI afforded VI1 as the HpO LiAIH4 hemimethanolate, m.p. 177-180°, [ a I C h f+74", ~ RaSi*C1-+RaSi*OH-+ RaSi*H found: C , 74.80; H, 10.78; which on treatment with methyl iodide furnished the methiodide, m.p. 260°, [ a I m e t h a n o l ~+25", found: c, 57.04; H, 8.81. CHZOH LiA1134 The latter was heated in DMF containing sodium R3Si*CI+ R&*OCH, -+ R&*H methoxide t o produce VIII, m.p. 145-146", pentane, amine [ C X ] ~ ~ ' 4-45', D found: C , 79.65; H, 10.13; which Iv, [ a ] D +l'io [ a ] D $30" was oxidized (CrO3-acetone) to IX, m.p. 169- [ a ] D 4-6.4' 170.5, [ a I C h f+77", ~ found: C,79.98; H, 9.61. LiAlH, Hydroxylation ( 0 ~ 0 1 )of I X afforded X as the hemi- R3Si*CI----+- R3Si*H (highly stereospecific, see ref. 1) hydrate, m.p. 212-215", [ a I C h+89.2", f~ found: [ a ] D +32" 70.78; H , 9.46; which was acetylated (AczO-Py) [ a ] D -I-6.3" to form X I , m.p. 171-173.5, [ a I C h +f 7~2 O , found: ,4 solution of 31 g. of I in 500 ml. of ether was C , 69.25; H, 8.GG. The latter was oxidized (RuOe added rapidly to 700 ml. of cold water in a %liter in cc14)5to produce XII, m.p. 242-246, [ a I C h f D separatory funnel which was immediately stop+51°, found: C, 67.18; H, 7.88. By use of im- pered and vigorously shaken for 1-2 minutes. The proved methods6 for introducing the A 4 moiety ether layer then was separated, washed four times into 3-keto all0 steroids, XI1 was transformed into with water, and dried over potassium carbonate. 1 2 3 O , found: c, Evaporation of solvent gave 28.0 g. of I1 (found: XIII, m.p. 197-201, [ a I C h f+ ~ 67.47; H, 7.48, which was hydrolyzed (KHC03) Si, 10.6; infrared spectrum showed typical silanol to afford XIV, m.p. 149-151°, found C, 69.71; absorption a t 2.80 and 3.05 microns as well as the H, 7.84. maxima characteristic of the a-naphthylphenylTritylation of XIV ((C6H5)3CC1-Py)gave XV as methylsilyl system). Reduction of I1 with liththe hemihydrate, m.p. 225-229', [ a I C h f D 104", ium aluminum hydride a t 140-145 o using di-n-bufound: C, 78.24; H, 7.09, which was oxidized to tyl ether as solvent gave a 72y0yield of I11 (m.p. XVI, obtained as the hemihydrate, m.p. 230-234", 62-63'; identical with I11 as previously reported' [ a I C h+fl ~ O G o , found: C, 78.90; H, 6.88. Removal except for a somewhat smaller specific rotation). of the protecting group (8OY0 HOAc) gave XVII, A solution of 14 g. of I in 40 ml. of carbon tetra~ found: c, 69.96; chloride (as prepared by chlorination of (-) 111)' m.p_. 211-220°, [ a I C h f+183", 180 H, l.25, (lit7m.p. 212-216, 2 2 3 - 2 3 8 [ a I C h f D was diluted with 100 ml. of pentane and then added 4'). Compound XVII has been converted to al- to a solution containing 10 ml. of methanol, 20 ml. doster~ne.*'~ of cyclohexylamine and 300 ml. of pentane. The (3) E. J . Corey and W. R . Hertler, THISJ O U R N A80, L , 2903 (1958); reaction mixture was swirled for a moment in a E. J . Corey and W . R. Hertler, ibid., 81, 5209 (1959); P. Buchschacher, separatory funnel, washed five times with cold waJ . Kalvoda, D. Arigoni and 0. Jeger, ibid., 80, 2905 (1958). ter, dried over sodium sulfate and evacuated. (4) C j J. Weinstock and V. Boekelheide, ibid., 76, 2548 (1953). Crystallization of the residue from pentane gave ( 5 ) L. hl. Berkowitz and P. N. Rylander, ibid , 80, 6682 (1958). (6) R. M. Evans, J. C. Hamlet, J. S. H u n t , P. G. Jones, A. G. Long, 89% yield of IV (m.p. 64.5-65'; found: Si, 10.2; J . F. Oughton, L. Stephenson, T . Walker and B. M. Wilson, J . C h e m . mol. wt., 274). Reduction of IV with lithium aluSoc., 4356 (1956). minum hydride a t room temperature in ethyl ether (7) J. Schmidlin, G. Anner. J.-R. Billeter, K. Heusler, H . Uebersolution gave 68% yield of 111. wasser, P. Wieland and A. Wettstein, Helv. C h i m . A c t a , 40, 2291 (1957). The high degree of stereospecificity observed for (8) J. von Euw, R . Neher and T. Reichstein, ibid., 88, 1423 (1955). both hydrolysis and methanolysis of optically ac(9) I t is a pleasure to thank Dr. T. A. Geissman and Dr. Joseph tive a-naphthylphenylmethylchlorosilanein ether Weinstock for many helpful discussions. and pentane solvents, respectively, clearly rules RESEARCH A S D DEVELOPMENT MANFRED E. WOLPP out a planar siliconium ion intermediate for these JAMES F. KERWIN DIVISIO?;, SMITH KLINE AND FRENCH LABORATORIES FRANKLIN F. OWINGS reactions in the specified solvents. B. LEWIS BARBARA PHILADELPHIA 1, Rapid hydrolysis of a chlorine function linked to PENNSYLVANIA B. BLANK bridgehead silicon in 1-chloro-1-silabicyclo[2.2.1]THEJULIAN LABORATORIES, ISC. A. MAGNANI FRANKLIN PARK,ILLINOIS V. GEORGIAN heptane3 using ether as the solvent shows that hydrolysis can occur with retention of configuration. RECEIVED MAY16, 1960 Nevertheless, evidence partially summarized below, which will be detailed in later publications, STEREOCHEMISTRY OF CHLORIDE ION provides strong indications that inversion of conDISPLACEMENT FROM SILICON. HYDROLYSIS
+
c,
+
+ *
AND METHANOLYSIS OF AN OPTICALLY ACTIVE ORGANOCHLOROSILANE
Sir : We wish to record the first stereochemical study of the hydrolysis of an optically active triorgano-
(1) L. H . Sommer and C. L. Frye, THISJOURNAL, 81, 1013 (1959). (2) Conditions used were imposed by two factors: rapid racemization of the silanol or methoxysilane in the presenceof acid, and rapid racemization of RaSi*Cl by chloride ion (3) L. H . Sommer and 0. F. Bennett, THIS J O U R N A L 79, , 1008 (1957).
