July 5, 1959
COMMUNICATIONS TO
THE
EDITOR
3485
log E 4.35). Similarly, progesterone, 17a-hydroxyprogesterone caproate and '3"17,21-diacetate were converted to their respective 6a-chloro derivatives 111, IV and V. Conversion of I1 t o its 1-dehydro analog VI COXTRIBUTIOS KO, 2461 GATESAND CRELLINLABORATORIES JOHN H. RICHARDS was accomplished by selenium dioxide oxidation. Treatment of I with N-bromosuccinimide in CALIFORNIA INSTITUTE O F TECHNOLOGY PASADENA, CALIFORXIA E. ALEXANDERHILL^ aqueous buffered acetone yielded 6&bromo-l7aacetoxyprogesterone (m.p. 178-180°, [ a ] ~ (7) M. D. Rausch, E. 0. Fischer and H. Gruhert, Chem. and I n d . , O o , Xma, 246 mp, log E 4.14) inverted by acid to the 756 (1958). a-derivative VI1 ( A = 1). Bromination of 1(8) J. H. Richards and D. C. Garwood, unpublished results. dehydro-17a-acetoxypr~gesterone~ with N-bromo(9) National Science Foundation Predoctoral Fellow. succinimide in carbon tetrachloride gave the 6PRECEIVED MAY6, 1969 bromo derivative (m.p. 170-172" [ff]D +23", Xmax 250 mp, log E 4.24) inverted by acid to 1dehydro-6a-bromo-17cu-acetoxyprogesterone (VSTEROIDS. CXXVII.' 6-HALO PROGESTATIONAL 111) ( A = 6). AGENTS 6 - Dehydro - 6 - chloro - 17a - acetoxyprogesteSir: rone (IX) and 6-dehydro-6-chloro-"S" diacetate 17a-Acetoxyprogesterone 3-ethyl enol ether (I) (X) were obtained by chloranil oxidationsf of I1 (rn.p. 160-163", [ a ] D -146" (all rot. in CHC13), and V, while selenium dioxide oxidation of I X and Xgt,"," 241 mp, log E 4.32)2 on reaction with N- X yielded the 6-~hloro-A~~~~~-trienones XI and XII. chlorosuccinimide gave 6~-chloro-17a-acetoxypro- In multi-dose Clauberg assays3 it was found that gesterone (A = 0.5)3 (m.p. 221-222", [ a ]- l~o o , the progestational activity of 6a-chloro-17a-aceXmax 239 mp, log E 4.19) inverted by hydrogen toxyprogesterone was increased by AI- or by A6-
stances toward electrophilic substitution as judged by ease of acylation7 and by competitive acetylations.8 The reactivity order in this case is ferrocene > ruthenocene > osmocene.
TABLE I
Compound
17a-Ethynyl-19-nortestosterone 17a-Acetoxyprogesterone 6a-Methyl-17a-acetoxyprogesterone~~8 6-Dehydro-6-methy1-17a-acetoxyprogesteror1e~ 1-Dehydro-6a-fluoro-17a-acetoxyprogesterone 6-Dehydro-6-fluoro-17a-acetoxyprogesterone 6a-Chloro-17a-acetoxyprogesterone (11)
M.p. OC.
[u]DCHCla
EtOH max. (md
log e
Oral progert. 4 activity (Clauberg assay)
1 0.07
6a-Chloroprogesteronc ( I 11) 6a-Chloro-17a-hydroxyprogesterone caproate (IV) l-Dehydro-6a-chloro-17a-acetoxyprogesterone (VI) 6-Dehydro-6. chloro-17a-acetoxyprogesterone ( IX) 1,6-Bisdehydro-6-chloro-17a-acetoxyprogesterone (XI)
polyrnor. 183-184 2 15-2 16 130-132 Oil 203-205 212-214 168-170
6cu-Chloro-"S" diacetate (V) 6-Dehydro-6-chloro-"S" diacetate (X) 1,6-Bisdehydro-6-chloro-"S" diacetate (XII)
197-198 248-250 201-203
f34" +37O -36'
6a-Bromo-17a-acetoxyprogesterone (VII) 1-Dehydro-6a-hromo-17a-acetoxyprogesterone( V I I I )
163-166 172-175
f42" -7O
+400
+133' +zoo
-77"
t8" -83'
236
4.20
237 238 24% 285 229 258 297 237 285 228 260 295 236 244
4.19 4.15 4.21 4.36 4.00 4.00 4.03 4.19 4.31 4.00 4.03 4.07 4.12 4.15
2-3 12 6 15 2-3
8 50 35
0.5 1.5 1
1 6
This substance was first described by J. C. Bahcock, E. S. Gutsell, M. E. Herr, J. ,4.Hogg, J. C. Stucki, L. E. Barnes and W. E. Dulin, THISJOURNAL, 80, 2904 (1958).
chloride-acetic acid to 6a-chloro-17a-acetoxyprogesterone (11) ( A = 2-3); I1 ethyl enol ether (d = 1) (m.p. 180-181°, [ f f ] D -146" Xmax 251 p , (1) Paper CXXVI, A Bowers, E. Denot, R . Urquiza and L. M. Sanchez Hidalgo, Tetrahedron, in press (1959). (2) Correct elemental analyses were obtained for all new compounds. (3) Clauberg assays, by t h e Endocrine Laboratories, A = oral progestational activity, 17a-ethynyl-19-nortestosterone(Norlutin) = 1.
double bond introduction with the latter modification inducing the more pronounced effect. T h e oral progestational activity of IX was 50X that of Norlutin or 7 0 0 X that of 17a-acetoxyprogesterone and would thus appear to be the most potent (4) M.p. 229-230°, [u]D +19O, Xmax 243 m r , log c 4.20. (5) A. J. Agnello and G. Laubach, THIS JOURNAL, 79, 1257 (1957). (6) H.J. Ringold, J. Perez Ruelas, E. Batres and C. Djerassi, i b i d . , 81, io press (1959).
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BOOKREVIEWS
VOl. 81
progestational agent yet d e s ~ r i b e d . ~The effect of dehydrogenation a t C-1 and C-6 was not cumulative (XI, A = 35). Inhibition of ovulation in the rabbit with this series of compounds was found to parallel closely the Clauberg assays.
mmoles of azomethane was decomposed by a 45minute ultraviolet irradiation in the presence of 4.57 niillimoles of SiH4 and 1.52 millimoles of RC13. A G7yo yield of diborane (0.51 millimole) was isolated. Reactions thus far have all been carried out a t room temperature. (7) For the progestational activity of 1- and 6-dehydro-&methylSince methane was among the products and no 17a-acetoxyprogesterone derivatives, see ref. 6. methyl chloride was observed, i t appears that the H. J. RINGOLD first step involves the attack of the methyl radical RESEARCH LABORATORIES E. BATRES A. BOWERS on SiH4 rather than on BCI3. It then seems probSYNTEX,S. A. APDO. POSTAL 2679 J. EDWARDS able that the reaction continues by a radical chain J. ZDERIC mechanism to the ultimate formation of diborane. MBxrco, D. F. The probability of methyl radical attack on SiH, RECEIVED APRIL30, 1959 was substantiated by noting only partial recovery of silane when mixtures of silane and azomethane were irradiated with ultraviolet light. X o attempt FORMATION OF DIBORANE FROM has yet been made to identify products of this reBORONTRICHLORIDE AND MONOSILANE’ action. The clear, viscous, non-volatile reaction product Sir: was soluble in carbon disulfide and an infrared Calculations based on bond energies indicate spectrum showed absorption a t 3.9 microns, that the formation of diborane by reaction of silane indicating the presence of boron-hydrogen bonds. and trichloroborane should be slightly exothermic. Removal of the carbon disulfide left a material A radical chain process seemed to offer a promising soluble in dilute sodium hydroxide, giving a solumechanism for achieving hydride transfer. It was tion which reduced silver nitrate. Prolonged exsubsequently found that mixtures of SiH4 and BC13 posure of the original material to air converted it do react in the presence of methyl radicals to to a water-soluble, white solid. produce diborane in good yield. Using the photoExperiments are presently being carried out to chemical decomposition of azomethane as a source determine optimum conditions for this reaction. of methyl radicals, the reaction products were Other radical initiators may be more suitable and found to be diborane, methane and both mono- will be investigated along with the possibilities of and dichlorosilane. In addition, a considerable using substituted silanes and other boron halides. amount of non-volatile substance was produced This research was supported in part by the in the reaction. In a typical experiment 0.10 United States Air Force under Contract AF33(616)-5827, monitored by the Aeronautical Research (1) Contribution No. 881 from the Department of Chemistry, Laboratory, Wright Air Development Center. Indiana University. (2) The photodecomposition of azomethane occurs readily in Pyrex vessels with radiation of wavelength less than 3060 A. T h e quantum yield passes through a maximum in the region 3660 to 3350 A . ; cf G. S. Forbes, L. J. Heidt and D. V. Sickman. THISJOTIRNAL, 67,1935
(1935).
DEPARTMENT OF CHEMISTRY INDIANA UNIVERSITY RILEYSCHAEFFER INDIANA LOUISRoss RLOOMINGTON, RECEIVED APRIL 23, 1959
BOOK REVIEWS Low Temperature Physics and Chemistry. Proceedings of the Fifth International Conference on Low Temperature Physics and Chemistry Held a t the University of Wisconsin, Madison, Wisconsin, August 26-31, 1957. Edited by JOSEPH R. DILLINGER. The University of Wisconsin Press, 811 State Street, Madison, Wis. 1958. xsv 676 pp, 16 X 21 cm. Price, $6.00. The Madison Conference on Low Temperature Physics and Chemistry was attended by four hundred and forty scientists from fourteen different countries. This book contains the essential content of two hundred and twenty-four papers which were presented. It is impressive evidence not only of the recent growth in quantity of low temperature research but also of the increasing variety of experiments now being carried on in the region near Absolute Zero. Such polar explorations have not only uncovered phenomena such as superconductivity and superfluidity exclusively associated with conditions of low thermal energy; but they are also contributing to many other fields ranging from the thermal, magnetic and electric aspects of the solid state to nuclear behavior; even the possibilities of technical applications of low temperature such as superconducting cornputor elements are being investigated.
+
This volume will be valuable to many people in many different ways. First, it gives a quick and yet quite comprehensive bird’s eye view of the present state of cryogenic research, a perspective which is enhanced by twenty-six invited papers which are presented a t greater length than the contributed papers and form a framework about which the latter papers fall naturally into groups. In the second place, the papers include a number of important ideas and experiments which are opening up really new vistas; in many cases references are given to places where more complete discussion may be found. Finally there are the reports on work which is the continuation of research already in progress for some years. Naturally, the completeness and quality of the papers vary; but the editing is excellent throughout. The process used for printing makes a readable book, although the illustrations are not as clear as in a normal printed text. Regarding the topics covered, first there are several dozen papers on the experimental and theoretical aspects of super5uidity and superconductivity. h report by Pellam on a super5uid “wind tunnel” is especially intriguing. Chemists may be glad to see the section on temperature scale and measurement which has a bearing on many thermodynamic
