Nov. 5 , 1952
CH.IR.\CTERIZ.~TION 01:A 6 - I J ~ ~ . STEROIDS ~ ~ ~ ~ ~ R Y; INFRARED \ ~ ~ n SPRCTROSCOPY 5357
[ COVTRIBUTION FROM THE DEPARTMENT OF MEDICINE, WESTERNRESERVEUNIVERSITY, AND
THE
LAKESIDEHOSPITAL
The Characterization of LAK unsaturated Steroids by Infrared Spectroscopy' BY H. HIRSCHMANN RECEIVED JANUARY 17, 1952 Examination of 5.5 olefinic and of 13 non-ethenoid steroids in the 12p region of infrared radiation disclosed that A6-3pacetoxy compounds with the usual spatial arrangement of the steroid nucleus and without other functional groups in the vicinity of the double bond exhibit two bands near 800 and 812 cm.-'. Changes in the configuration or nature of the substituent a t C-3 cause shifts in the position of the higher frequency band. At least one of these peaks (800 cm.-l) is ascribed to the out-of-plane bending vibrations of the hydrogen a t C-6 The twin bands of the A6-3~-acetoxysteroidswere not and A14-unsaturated steroids, seen in their reduction products or in the acetates of other olefins. Observations on A'-, while still rather limited in number, suggest that these trisubstituted olefins too can be characterized by measurements in the gOO-cm.-I region. Introduction of a substituent or double bond a t a carbon atom adjacent t o the trialkylated olefin can profoundly alter the spectrum in this range and reduce absorption intensity well below that of the fairly strong peaks that were seen in this region with some dialkylated olefins or with certain non-ethenoid steroids. Spectral changes were smaller if the substituted carbon atom was farther removed from the double bond but slight shifts could still be detected if the two sites were separated by 4 carbon atoms
During earlier investigation? we had occasion to measure the infrared transmission spectra of several 3-6: unsaturated steroids. It was observed that these compounds showed two fairly intense bands near 800 and 812 cm.-' which disappeared upon reduction. Since the out-of-plane bending vibrations of a hydrogen atom attached to a trisubstituted olefin quite generally give rise to a strong absorption band in the region between 800 and 840 cm.-I it seemed probable that a t least one of these bands was brought forth by the presence of the 3-6 double bond. To test the diagnostic possibilities of this region these observations have now been extended. The results are presented in the accompanying tables in which all peaks observed in the region between 790 and 840 cm.-' have been recorded regardless of their significance for the characterization of unsaturated steroids. A5-Steroids.-It is apparent (Table I) that Aj-3P-acetoxy steroids with the normal configuration of the nucleus and without other substituents in the vicinity of the double bond show two peaks near 800 and 812 cm.-'. The maximum a t 800 cm.-I is generally more intense but as indicated in Fig. 1 the relative heights of these peaks can vary considerably. If observations are confined to measurements on solutions (which quite generally give more consistent results than solids) nine 3P-acetoxysteroids, variously substituted a t C-17 and in the side chain, absorbed a t either 800 or 801 and a t 812 or 813 ern.-'. The most remote substituents which caused slight shifts of the absorption frequencies were found a t C-16. Four 16a-oxygenated substances (compd. 3, 9-11) absorbed a t 803 while diosgenin acetate (compd. 13) in which the func( I ) This investigation has been supported by grants from the I l a n n a Research Fund and from the American Cancer Society on the recommendation of t h e Committee on Growth. A summary of this work wa9 given a t the 43rd annual meeting of the American Society of Biological Chemists (Fedeinlion Proc., 11, 230 (19.j2)). Supplementary d a t a were presented a t the Colloquium, Synthesis and Metaholism o l Adrenal Cortical Steriods, of the Ciha Foundation in London in July, 1952. T h e proceedings of this conference are scheduled lor publication. (2) (a) H. Hirschmann and F. B. Hirschmann, J . B i d C h r m . , 187, 1.17 (19.iO); (I-) H. Hirschmann. F. B. Hirschmann and hf. A. Dau.;, T H r s J O U R K A I . , 1 4 , 339 ( I Q . ; ? ) ; a n d unpublished d a t a from this Laboratory. ( 8 ) D. Barnard. I. Rateman. A . J Harding, H. P. Koch, N. Sheppard and C:. B. B. 51. Sutherland, . I . C h f m . Snr , 91.-1 (1950); i b i d . , rrferenrrs tn t h e enrlier literatiire.
90
80
Fig. 1.-Infrared transmission spectra in C&: curve A, 3~,20~~-diacetoxy-17a-hydroxy-A~-pregnene; curve B, 38acetoxy-As-androstenone-17; curve C, 3p-acetoxyandrostanone-17. Curve A is drawn with respect to the ordinate a t the left; the ordinate for curve C is displaced by $2 from that of curve B which is given on the right.
tional group a t C-16 is P-oriented4has the lower frequency peak a t 797 cm.-l. Compounds 15 and 16 which are substituted adjacent to the double bond lack the peak near 800 cm.-'. Frequency shifts (4) H. Hirschmann, F. B. Hirschmann and M. A. Daus, J . Bioi. Ch#m., 178, 781 (1949).
5358
Vol. 74
Subst.
No.
at
'2-3
Compoouda
Maxima in CS1,b cm. - 1
Steroids
1 P-OAC
2 P-OAC 8 6-OAC 4 8-OAC 5 P-OAC G P-OAC 7 P-OAC 8 3-OAc 9 P-OAC 10 P-OAC 11 S-OAC 12 $-OAc 13 14 13 IO
ti
P-OAC P-OAC B-OAc P-OAC B-OAc
1s
. .
IC)
+3-orr
@-OH $-OH 22 &OH 2:3 @-OH 24 P-OMe 25 @-0hZe 20 21
26 27
P-OMe @-OB2 8-C1
28 29 p-c1 30 B-Cl 3 1 a-OAc 32 a-011
3 p-Acetoxy-A6-androstenone-17 3 P-A~etoxy-4~-androstenone17 3 8,17 P-Diacetoxy-A6-androstene 3~ , 1 6 a , 1 7 ~ - T r i a c e t o x y - A 6 - ~ r ~ ~ l r o s t ~ ~ ~ e 3P,20a-Diacetoxy-A5-pregnene 3/3,20a-Diacetoxy- 1Ta-hydroxy- A5-pregnen e 3~,20~-Diacetoxy-l7a-hydroxy-A5-pregiie~ie 3p-Acetoxy-l7a-hydroxy-A6-pregnenon e - 2 1 3P,21-Diacetoxy-A5*l7-pregnadieneC 3P, 16a,2Oa-Triacetoxy- A6-pregnene 3@, 16a,20P-Triacetoxy-A5-pregnene 3 ~-Acetoxy-16a-benzylo~y-~5-preg~~er~o~ie-2D Methyl 3P-acetoxy-A5-choleiiate Methyl 3/3-acetoxy-A5-cholenatc 3~-Acetoxy-22-iso-A5-spirosteiir. 3 @-Acetoxy-A5-cholestene 3 ~,icu-Diacetoxy-As-cholesteii~~ 3 ~,7~-Diacetoxy-A5-cholest eiie 3 P-Acetoxy-A.","-stigmatatliciie A5-Cholesteried 3 /3-Hydroxy-A5-androstenone-1T 3 /3-Hydroxy-A6-androstenoiie-li 3/3,l6a,l7~-Trihydroxy-AG-aiidrosteiie 3p-Hydroxy-20a-acetoxy-A5-preg~~ei~e Methyl 3 P-hydroxy-A5-choleiiate 3 @-Hydroxy-A5-cholestene 3~-Methoxy-lGa,l7~-dihydroxy-A~-~~iidrostei1e 3 ~ - M e t h o x y - l f i ~ , 1 ~ 3 - t l i h y t i r o ~ y - ~ ~ - ~ i 1 i r I6,17 lrostrlle acetonide" 3p-~Iethosy-A5-cliolesterlc ene 3 p-Be~izoxy-~~-cliolest 3 p-Chloro-A5-androsteiioiie-17 3 ~-Chloro-20cu-acetox~~-A~-~~reg11e1ie 3~-Chloro-As-choleste~ie 3cu-Acetoxy-Aj-choleslenr .~~cr-I-Irtlrosr-3"cholesterle
800 S798 xu0
80.7 801 800
800 S 801 800
803 803 803 801 Xi99
797 801
813 812 812 813 812 812 813 814 812 814
( 822 1 (820)
831 834 829
XI6 835
-
814 814 812117
829 17, (830)i 830 (829) 831 i
829 w 82 5 (829)i
813
814 812 1v
837 -838 835 w 835 w 836 -841 w 840 839 -840
IT
812
801
815 \v 812 so9 w
799 7.99 807 S800 805 i Ti98 808 800 806 i YO0 (806'1 i 80 1 S 800 808 801 809 800
(823)
832 w 829 TI 833 831 835
(825) i 827 i
SO0
800 797 79 P
844 835 840 839 840
829
835 839 4 3 7 1Y
806 i
so1 (809)i 8011
-840 \v
x-to 821 82 1 821
822 8.70
mri 829 83 1 a Details concerning the use of the terms a and p have been given previously.2n,21 The naming of sapogenins as derivatives of spirostane follows suggestions of G. Rosenkranz and C. Djerassi ( S u t u r e , 166, 104 (1950)). i, Data marked a s S were obtained on mulls with Nujol; those as S on solids without a11 embedding medium. Details concerning the use of symholi denoting band interisity are given in the Experimental section. e It is possible that the double bond at C-17 which has the transconfiguration (see footnote n to Table I1 and B. Koechlin and T. Reichsteiii, H e h . C'hinz. .4ctu, 26, 132P (1943)) makes a D a t a by Rladon, contribution to the absorption a t 812 cin. since the intensity of the band is greater than in ro~npound1 i'i ( 1 2 . , 6 do not list a peak a t 809 c 1 1 1 . - ~ . e Iri additiori shoulder extending t o XI2 en:. l .
appear to be associated also with changes in the shape of the steroid nucleus. Departures from the normal pattern were seen if the strain a t the juncture of rings C and I3 is released by ring enlargement (compd. 33) or by ring cleavage (compd. 34) and were larger in the case of diacetyldihydrojervine (compd. 35) for which a 5-membered ring C has been postu1ated.j Changes in the substituent at C-3 have little effect on the peak near ROO crn.-l but displace the higher frequency hand. In Whvtlroxy and 3p(7) J
Fried, 0 Wintersteiner, 11 \ f , w r e T1 rrirs l o ~ ~ i 73, ~ ~?'I70 ~ r ~ ,1 ' 1 7 1 ~
Rliiipqherg
I 1 liriin anrl A
methoxy compounds this peak appeared near SO; c1m-l. It possessed low intensity in several conipounds and was absent in one (compd. 2 3 ) . 'The shifts were larger in the spectra of the Bcu-oxygenated arid 8P-chlorinated compounds. The frequencies of the latter (3 examples) were again found to be reproducible (800 and 821 cm.-'). Other Unsaturated Steroids.-The twin bands of the A5-3P-acetoxycompounds have not been observed with the acetates of other unsaturated steroids. -1rather close approach to this pattern may be expected for the acetate of compound cis~17-pre~iienol-Xcu-o~i~-11 hut if this should he t htt
ABSORPTIONMAXIMA No.
A at
TARLE I1 OTHER TRISUBSTITUTED OLEFINS
OF
Compound"
Maxima in CSz,b cm
- 1
810 3 fi-Acetoxy-A4-cholesteue 4-5 805 w 3 fi-Hyd
