I' 0 1 HE E D I T O R
If tlie asyniiiietric sulfur uiitlergoes a displacenittit reaction by inversion and a re-esterification in the same manner, no epimerization should occur. However, if reaction through I1 is rate determining, a subsequent rapid interchange of chloride ions by the sulfinyl chloride with racemization a t the sulfur could account for the epimerization.
I
+
'.'
CI -
I f this picture of the reactioii is correct, equation 1 must be replaced by equation
9.
Here the specific rate coiistants for the forward and reverse reactions of the simple epimerization equation are diminished by that fraction of the racemized sulfinyl chloride that reverts to the epimeric ester from which i t was formed. -Although the accelerating effect of the p-methoxy1 on the rate is relatively small, it suggests an increase in positive charge on the sulfur in the transition state.
Experimental l9 i-Menthyl l-Benzenesulfinate.~-Benzeiiesulfiriyl from 34.7 g. (0.244 mole) of benzeiiesulfinic acid iii mi equal v ~ l ~ nofi edr>-ether was c:tuseti to react with 38.0 g . (0.243 niole) of ~-lTieIithCJ1in 20 ml. of dry pyridine. lieino\xl of the etlier in oncuo 3fter washing with water, dilute hydriichloric acid, twice again with water, and drying over sodium sulfate gave an almost colorless oil. The higher-melting epimer was separated froin the mixture by careful cooling, with solid carbon dioxide, of a solution in three vnlumes of methanol. The colorless crystals, 20 g. (0.071 mole, 297;), of /-menthyl I-benzeiiesulfinate were collected, w-aslicd with cnld, aqueous methanol, and recrystallized from methanol. .inother recrystallization from methanol aiid three froin pentane gave a product of m . p . 49-51', i a j Z 5 D -205.5" ( G 2.0 in acetone), [cx]'~D -210.4' ( 6 1.1 in nitrobeiizene). .1viiI. Colcci. frir ClJl,102S: C . f%.,?l; I€, 8.62; S,11.18. 1;ouiitl: C , 08.6:j; I%, 8.80; S, 11.25. ~~
, 171) .4tialyse., ~ v e r eperlorinerl
b y C1:Lrk Micruanalytic~*lI,almratory,
1
L-,
The oil which rernaiiicd frcini tlic origiilal cryst:tlliz:itioii had not solidified in a refrigerator after thrce n l o n t l i i , but one week after adding hydrogen chloride gas inore solid ester was recovered: 17.4 g. after one recrysta1liz;tti~iii. l-Menthyl I-p-toluenesulfinate was prepared as reported previously,2 except that after separation of the initiallyformed solid ester, a few crystals of t e t r a e t l i y l ~ r m i n o ~ ~ i u i ~ i chloride and some hydrogen cliloride gas were a d d e d . .i second crop was removed after one daj-, zmd retre:atmetit with quaternary chloride and liydrogcri chloride gave yet another crop. Tlie total yield of Lester was 8 0 . 7 ' ; . I-Menthyl I-p-Methoxybenzenesu1finate.-p-Metlirisybenzenesulfinic acid21 (27 g . , f1.157mole) \vas :ttldcd gr.aclually to 21.5 g. (0.18 tnolc) r i f tiiionyl chloride, the excess thionyl chloride \viis removed iii i'aczo, and tlie rc.;itluc cooled :ind diluted ivith 5!)inl. of dry ether. LI'itIi c!i!iliiig, 20 g. (0.128 mole) of I-menthol in 11 g . (0.1 f iiiiilc) of pFi-idine aiid 10 inl. of dry ether WRS added. More ether w t i added and the solution wished with dilute liydrocliloric acid. The ester, which w:is not very soluble in ether, \vas reciivered hy filtration, li~-drogenchloride ~ v x sp solution and it as refrigerated for three nrliich had crystallized alter this time, w:is sepxratcil m d tlic. ether \viis evaporated frrim the filtrate t o give xlditioii:ti product: yield 27.7 g. (0.089 m o l t , Gl'; crystallizations from aqueous acetorie, the 116-117.5' anti :t con,tant r(itatioi1 I J f [ a ] 1.2, acetone), : a ] 2 j ~ 193.5" (c 1.0, n i t r O b ~ l i ~ c l 1 ~ ~ . A n a l . Calcd. for C,;H,fiO S: C, 65.77; X , S . M ; S , 10.33. Found: C, 65.83; H , 8.32; S,10.11. TetraethylaninitJriiurii chloride stock sulutioiis in iiitrobenzene were prepared as previously.2 Care w a i ticccis'try to assure t h a t in the preparation of t h e chloride from the hydroxide no excess of hydrochloric acid was used, as it ~ : i s impossible to remnve hydrogen chloride fro111 the s:dt b y recrystallization. Hydrogen chloride stock solutiolis, in tiitrribenzene, were prepared by passing dry hydrogen chloride into dry iiitrobenzene. Exact concentrations werc determined iinincdiately preceding use, since hydrogen chloride is lost quitc rapidly even from dilute solutiotis in nitrobenzene. The kinetic determinations \yere made :it 25.00 d= 0.05', ;is reported previously. The spent siilutions froin a, scriei of kinetic r u m with i-iiienthyl l-p-toluencsulfin:tte, 111 o n e instance, were comhiiied and the nitrobenzene w:is reinovcd a t 1 0 - 3 mn., a t ,50'. 1niti:Llly 1.0 g. of ester, 0.008 g. o f tetr~ietliylanirii(iiiiurn chloride a n d 0.018 g. of IiycIriiFeii chloride were present. .I residue, 0.8 g., largely crystaliinc, remained, which after recrystallization weighed 0.67 g. :tilt1 had it 11i.p. 1()2-1()~'. .I mixed 1n.p. with pure I-riienth!.l I-p-tiiluenesulfiiiate was undepressed. After distillation of the nitrobenzene, a few rng. of white crystals deposited in tlie side-ami of the distilling flask. T h e odor, m . p . €IO', ;and niixcd 1ii.p. slloivetl these to hc />tcilucnesulfonyl chloride. I-Menthol, dissolved in nitrrJbcllzelle with atlrletl II! (lroget1 chloride and t e t r a e t l i y l a ~ ~ i n ~ o t i cliliiride, urr~ ~ ~ 1111i i changed in rotatioii after 16 hours a t 25'. TROT, S.Y . _~_..___
('rl,xti:i, Ill. ,?!I)
Vol. h l
I3raun m i i TV. K;ii>cr, D c r . , 66B,340 (1923).
(21) L. G a t t e r m a n n , i b i r i , 3 2 , l l l ( ( i (ISOij!
COiMMUNICA1'IONS '1'0T H E E D I T O R
sir:
CONVENIENT NEW PROCEDURES FOR T H E HYDROBORATION OF OLEFINS
Tlie hytlroburatiori reaction provides a ~wri\-ciiient new route from olefinic derivatives to organoboranes,' and to the many derivatives to which orgaiioboranes can be fl) H C Brown and R. C . Subba K a o , THISJ U W R N A I . . 78, SWJ4 (19.iCi). J . O w C h e i i i . , 2 2 , l 1 : j j ( 1 9 . i i ) .
\\'e have tlcscribctl procctlurcs which utilizctl sudiuiii borohydride, diglyme (diethylene glycol dimethyl ether) as solvent, arid boron trifluoridc etherate to liberate diborane from the salt. i t r e have learned t h a t the unavailability of one or inore 12) H. C. Brown and G. Zweifel, THIS Jou~V.41.. 81, % l i , L > l J (1959); H. C. Brown and K. Murray, i b i d . , 81, 4108 (1939); J . 13. Honeycutt. J r , , and J . h l , Riddle, ibid.. 81, 2393 (1959); h I . F. Hawthorne and J . A . D u p o n t . ibid.,8 0 , 5830 (1958).
of the intermediates abroad has created difficulties in applying the r e a ~ t i o n . ~We have established the applicability of numerous other systems, and are led to publish these in the hope that they may provide a wider selection of reagents and solvents. Lithium borohydride is readily soluble in both ethyl ether and tetrahydrofuran. Olefin and lithium borohydride in either solvent may be treated with (1) hydrogen chloride, (2) boron trifluoride or trichloride etherates, or (3) aluminum chloride to achieve hydroboration. A solution of 18.8 g. (200 mnioles) of norbornene and 1.98 g. (90 mmoles) of lithium borohydride in 100 ml. ether a t 0" was treated over a period of 1 hour with 17 g. (0.120 mole) of boron trifluoride etherate. After a second hour a t 0", water was added to destroy residual hydride, alkali added, and the product carefully oxidized with 21 ml. of 39% hydrogen peroxide. There was obtained 15.9 g. of norborneol, m.p. 123-124", 707& yield. Sodium borohydride is essentially insoluble in ethyl ether or tetrahydrofuran. However, treatment of a suspension of sodium borohydride in tetrahydrofuran with hydrogen chloride results in the formation of a solution of diborane in the solvent. Addition of the olefin to this solution results in ready hydroboration. To a well-stirred suspension of 3.0 g. (SO mmoles) of sodium borohydride and 100 ml. tetrahydrofuran at 0" was added over a period of 2 hours 45 ml. of 1.5 hydrogen chloride (BT mmoles) in tetrahydrofuran. To the resulting solution of diborane was added 22.4 g. (200 mmoles) of I-octene. The product was oxidized and isolated as usual: 21 g. of 1-octanol, SOYo, b.p. 98-100° a t 23 mm., n 2 0 D 1.4295. In diglyme solution, sodium borohydride and an olefin may be treated with hydrogen chloride, benzyl chloride, boron halide,' or aluminum chloride' to achieve hydroboration. I n this solvent, sodium hydride and boron trifluoride etherate can also be ~ t i l i z e d . ~ Potassium borohydride is insoluble in these sol vents. However, in two hours at room temperature an equimolar stirred suspension of potassium borohydride and lithium chloride in tetrahydrofuran undergoes metathesis to form a solution of lithium borohydride5 (go?& yield). The solution may be utilized as described above. Finally, lithium aluminum hydride can be utilized in ethyl ether with boron trifluoride etherate3 or with boron trichloride etherate.'j Alternatively, it is possible to utilize an equimolar mixture of borate ester and aluminum chloride as a substitute for boron trichloride. To a solution of 100 mmoles of 1-octene, 30 inmoles of lithium aluiiiinuni hydride and 40 inmoles of methyl borate in 50 ml. of ether at 0" was ( 3 ) Dr. F r a n z S o n d h e i m e r of t h e U'eizmann Institute of Science, Rehovuth, Israel has communicated t h a t he has utilized the action of boron trifluoride on a mixture of olefin and lithium aluminum hydride to overcome this difficulty. This useful modification of the hydroboration reaction by Dr. Sondheimer and his co-workers will be published shortly. ( 4 ) Unpublished research of Dr. B. C. Subba Rao. ( 5 ) R. Paul and N. Joseph, Bidi. SOC. chim.. 550 (1932). ( 8 ) A . E . Finholt, A. C. Bond, Jr., and H. I. Schlesinger, THIS J O U R N A L , 69, 1199 (1917).
added a solution of 40 mmoles of aluminum chloride in 30 ml. of ether. After 1 hour, Vapor Phase Chromatography examination showed 90y0 conversion of olefin to organoborane. Amine-boranes also can serve as hydride in the presence of Lewis acids, but the procedures are less convenient than those already described. RICHARD R . \VETHERILL L A B O R A T O R Y PURDUE UXIVERSITY H E R B E R T BRO\VN INDIANA GEORGE ZWIFEL LAFAYETTE, RECEIVED J U N E 29, 1959
c
STEROIDS.
CXXIX.' A NEW GENERAL ROUTE T O FLUORINATED STEROIDS
Sir: A recent publication2 describing the conversion of a Ag(")-steroid into its 9a-bromo-1 ID-fluoro analog by the use of N-bromoacetamide and anhydrous hydrogen fluoride prompts us to record the synthesis of a number of mono fluoro-bromo steroids by the addition of Br-F to a wide variety of unsaturated steroids. The method involves addition of 1.1 molar equivalents of IS-bromoacetamide to a solution of the steroid in methylene dichloridetetrahydrofuran containing a large excess of anhydrous hydrogen fluoride (25-100 mols) at - SO". After 1 hour a t -SOo the reaction mixtures were kept a t 0" for 2 to 16 hours. This novel fluorination procedure represents by f a r the best route to the biologically important Gar-fluoro steroid hormones. A5-Pregnene-3P,17a-diol-20-one li-acetate (I) afforded 5c~-bromo-GP-fluoropregnane-3fl, lia-diol-20one 17-acetate (11)4 m.p. 200-292" (all mps. uncorr.), [ a ] +5" ~ (all rotns. in CHCl3). Oxidation of I1 in acetone solution with S N chromic acid in aqueous sulfuric acid gave the corresponding C-3-ketone (111)4m.p. 171-1i3", [ a ] +17", ~ converted into 68-fluoro-1ia-acetoxyprogesterone (IV)4 m.p. 207-20So, [.ID -1s' A:"," 232-234 mp E 13,000, by sodium acetate in methanol. Either I11 or IV with hydrogen chloride in acetic acid3a.b gave Ga-fluoro - 17a - acetoxyprogesterone (V) .1s3b8c Similarly A5-pregnene-3P-ol-20-one and A5-pregnene-3P,17a,2 1-triol-20-one 1i,21-diacetate gave the Gp- and thence the Gar-fluoro analogs of progesterone3asc and compound "S" d i a ~ e t a t e . ~ Previous approaches' to Ga-fluoro-A4-3-ketones have always been nia 5a,6a-epoxides obtained by peracid treatment. Such an approach is often precluded with poly-unsaturated steroids; thus, P 3 9 ( 1 1 j 16-pregnatriene-3P-ol 20-one6 led to a complex mixture from which the 5a,Ba-monoepoxide could be isolated only in poor yield. A much higher degree of selectivity was obtained m3s5
(I) Part CXXVIII, A Bowers, I.. C. I b i i m and I1 J. Ringuld. in press. (2) C. H. Robinson, L . F i n c k e n o r , E. P. Oliveto a n d D. Gould, ibid.,81, 2191 (1959). (3) (a) A. Bowers and H. J . Ringold, TetiaiPedioiz, 3 , 14 (1958); (b) A. Bowers a n d H. J. Ringold, ' h i s J O U R N A L . 80, 4.123 (1958), (c) J. A . Hogg, et ai., Chcvaisliy arid I n d i ~ s l r y , 1002 (195s); ( d ) A . Bowers, E. Denot, M . B. Sinchez and H. J. Ringold, 2'clrahedro1t, in press. (4) All new compounds gave satisfactory results upon elemental analysis. ( 5 ) A. Bowers, L. C. Ibifiez and H . J . Ringold, Teliahedrot6, in press. (6) A. Bowers, M. B. Sbnchez, E. Denot, F. S e u m a n n a n d C. Djerassi, manuscript in preparation. T H I S JOURNAL,
