June 20, 1959
3157
COMhIUNICATIONS TO THE EDITOR
pyridine-dimethylfornianiide provided Ga-fluoro16c~-methyl-A~.~(~~)-pregnadiene3,20-dione- 17a ,21diol 21-acetate (m.p. 188-190', [ a ] D +74' ( d l rotations in CHC13), Azt,"," 235, log E 4.17; Anal. found for C24H3105F: C, 69.28, H, 7.24,F, 3.99), which was treated with N-bromoacetamide in aqueous dioqane in the presence of perchloric acid7 and the bromohydrin cyclized directly with potassium acetate in acetone to afford 6a-fluoro-16a-methylOP,1 l/3-oxido-A4-pregnene-3,20-dione-17,2 1-diol 21acetate (m.p. 188-191'). Opening of the epoxide with hydrogen fluoride in methylene chloride-tetrahydrofurans led to 6 a ,9 a-difluoro- 16a-methylhydrocortisone acetate (11) (m.p. 255-260', [ a ] D +113', 234 mp, log E 4.22;Anal. found for C24H3206F2: C, 63.15; H, 6.96; F,S.Ol), while oxidation of I1 with selenium dioxidegprovided 6a,-
hydrocortisone acetate (IV) l e 3 and &,Sa-difluoroprednisolone acetate (V) are summarized in the accompanying table. Pronounced sodium excretion was exhibited by I, I1 and I11 in the rat." l e 3
(11)'Salt assays in adrenalectomized r a t s without sodium chloride load, subcutaneous route. W e are indebted t o Dr. E. Rosemberg and Dr. R . I. Dorfman, Worcester Foundation for Experimental Biology, for these assays.
RESEARCH LABORATORIES SA. J. A. EDWARDS SYHTEX, H. J. DJERASSI RIXGOLD APDO. POSTAL2679 CARL MEXICO,D.F. RECEIVED MARCH20, 1959 MASS SPECTROMETRIC EVIDENCE FOR HEPTABORANE
Sir :
I n mass spectrometric examination of tetraborane prepared by the method of Klein, Harrison and Soloc=0 monl mass number versus intensity patterns were found corresponding to BeHlo, B6H9 and BbHll, B4H10 and with the B4H10 pattern accounting for / X 94to 97% of the total pressure. In addition] a new group of peaks was observed from mass numbers 0 77 through 89 with the principal peak a t 83. In F 5 of 6 samples examined there was no evidence of I, X = H,R = CHI higher boranes up to mass number 150. I n the 11, X = F,R = CH3 111, X = F,R = CH3 with 1-2-double bond sixth sample, a small amount of octaborane was IV, X = F,R = H found. The samples were obtained from three V, X = F,R = H with 1-2 double bond separate preparations of tetraborane. Oa-difluoro-1Ga-methylprednisolone acetate (111) Spectra were obtained using a Model 21-620 (m.p. 2G0-264', [ a ] +91', ~ "::A: 237 mp, log E Consolidated Electrodynamics Corporation mass 4.16; Anal. found for C24H3~06F2.CH3COCH3: spectrometer with a modified d.c. amplifier circuit C, 63.90,H , 7.40). This latter substance com- for greater sensitivity. The patterns from mass bines in one molecule four substituents (A1-double 77 through 89 for the 5 samples and the sixth with bond,'O 6 a - f l ~ o r i n e , ' . ~Oa-fl~orine,~ ,~ 16a-methyl the octaborane subtracted were identical within group4s5) known to increase individually anti-in- the limits of instrument reproducibility. The flammatory activity. height of the peak a t mass 83 was over SO recorder 0.3 for each sample. The repreunits read to TABLE I Antisentative pattern obtained is shown in Fig. 1. inflamYH20Ac
jyy-
*
Compound
Fa-Fluoro-16a-methylhydrocortisone acetate
matorya activity j b
(1) Ga,9a-Difluoro-lFa-methylhydrocortisone 50 acetate (11) Ga,9a-Difluoro-l6a-~tietliylprednisoloneace12oc t a t e (111) &,Sa-Difluorohydrocortisone acetate ( I V ) 100" h,Sa-Difluoroprednisolone acetate ( V ) 200b Assays in immature adrenalectomized rats, cotton pellet implant, h~-dr(~cortisone acetate = 1. * .4ssnys by l l r . K. I. Dorfnian, The Worcester Foundation for ExprriAssays by the Endocrine mental Biologv; oral route. Laboratories, Madison, Wisconsin; subcutaneous route.
Preliminary biological data covering these three substances (I, 11, 111) as well as 6a,9a-difluorofully characterized and analyzed, b u t t h e d a t a were n o t included f o r reasons of editorial policy. (7) J. Fried and E. F. Sabo, THISJ O U R N A L , 79, 1130 (1957). ( 8 ) R. F. Hirschmann, R . Miller, J. Wood a n d R . F. Jones, ibid., 78, 4956 (1956). (9) H. J. Ringold, G. Rosenkranz and F. Sondheimer, J . O r g . Chem., 21, 239 (1950); C. hleystre, H. F r e y , W. Voser and A. Wettstein, Helv. Chi" A c l n , 39, 731 (19%); S. A. Szpilfogel, T. A . P. Posthumus, A I . S. D e Winter and D. A. Van Dorp., Rec. T r a v . Chim., 7 5 , 475 (1936); K. Florey a n d A. R. Restivo, J . Ovg. Chem., 22, 406 (1957). (10) H. L. Herzog, A. Nobile, S. Tolksdorf, W. Charney, F . B. Hershherg, P. L. Perman a n d M. hl. Pechet, Science, 121, 176 (1955).
MASS
NUMBERS.
Fig. 1.
The range of mass numbers would necessitate a &-compound and the sharp cutoff a t mass SO would indicate a minimum formula of B7H12. This formula does not fit either the stable B,H, + 4 series or the less stable B,H, + 6 series proposed by Wiberge2 The parent peak of the proposed B7H13 compound from Wiberg's B,H, + 6 series (1) M. J. Klein, B. C. Harrison and I. J. Solomon, THISJ O P R N A L . 80, 4149 (1958). (2) E. Wiberg, Be?., 69B,2816 (1930).
COMMUNICATIONS TO THE EDITOR
3158
either may be too small in intensity to be seen or may be absent entirely. From this consideration it would seem t h a t B7HI3is a likely formula. The possibility of a B7 compound has been mentioned previously from mass spectral d a t a 3 but no pattern or formula was reported because of the masking effect of higher boranes present. After submission of this communication, our attention was called to a report of Professor Riley Schaeffer at the Boston meeting of the American Chemical Society (April 6-10, 1959) t h a t he had evidence for a heptaborane. H e reported mass peaks up to 91 with a minimum formula B7H14 and, therefore, suggested t h a t the hydride may be B7Hl5,
ates have an intermediate p value (Table I) indicating t h a t the cyclopropane ring is better than a dimethylene group b u t poorer than an ethylenic unit in transmitting electronic effects. This is in agreement with the dipole moment work but a t variance with the data obtained from ionization constants. In Table I the p values for the ionization of the acids and for the alkaline hydrolysis of the esters are compared. I n Table 11 are the rate constants for four ethyl trans-2-phenylcyclopropanecarboxylates prepared from acids which have the same physical constants as those previously rep0rted.j TABLE I COMP~4RISONO F KEACTIOX CONSTASTS p-Ester +Acid Series hydrolysis ionization
(:3) R . E Uickerson, P. J. lVheatle>-, P. A . Howell and lV. S . Lipscomb. J . Cheiii. P h j z , . 27, 200 (195i).
DEPARTMEST OF CHEMISTRY
REXSSELAER POLYTECHSIC 1SSTITUTE
truns- Ciiiiiainic trc~ns-2-Plieiiylc~clopropalle
ROBERTIT.SCHAEFER
KESNETHH. LUDLUM STEPHES E. WIBERLFY RECEIVED APRIL 10, 1959
TROY, SEIV YORK
TRANSMISSION OF ELECTRONIC EFFECTS BY T H E CYCLOPROPANE RING. RATES O F ALKALINE HYDROLYSIS O F S O M E ETHYL +SUBSTITUTED 2-PHENYLCYCLOPROPANECARBOXYLATES
( 1 1 See, for examlile, IV, IT'. Rohertsi3n J 1;. Llusic a n d 1.'. A. Xlatsen. THISJ O U R N A I - . 7 2 , J2ii0 (1930); G W. C a n n o n , A . A . Santilli a n d P. Shenian, ibid., 81, lfiO0 (1959). and references therein ( 2 ) L. I. Smith a n d E. R . Rogier, i b i d . , 73, 38-10 (1951); R . €1. IZastman a n d S . K . Freeman. z b i d . , 77, Gii.12 (1955), and preceding papers. i:3) R. I . Sl)inrad, ibici.. 68, G17 i l Y - l ! i ) , 11. T . Rogers and J . D . lioherts, %bid.. 68, 843 ( 1 9 4 t i ) . (4) R. W. Kierstead, R . P. Linstead a n d B . C .I
