~ C O S T R I R I J T I O NFROM TIIE
DIVI~IOV OD
P U R R CIIEMISTRY O F THE XATIONAL
RESEARCH COUNCIL
O F CANADA]
The Characterization of Methyl and Methylene Groups in Steroids by Infrared Spectrometry. 11. Methyl and Methylene Bending Frequencies in Steroids Labeled with Deuterium1 KECEIVED APRIL 11. 1952 I t has been shown previously that the major absorption bands between 1350 and 1500 cni.-l in the infrared spectra of iteroids can be associated with the presence of specific methyl and methylene groups in the molecule. Steroids have beeii Irepared i n which CHI and CHI groups at selected positions have been replaced by CDI and CD3 groups. It is observed that the absorption bands which have been assigned to specific methyl and methylene groups disappear when these groups are deuterized but there are no other significant changes produced in this region of the spectrum. These effects are interpreted as confirming the assignment of these bands to C-H bending vibrations which are localized in the methyl and methylene groups in question and which exhibit negligible coupling with methyl and methylene groups at neighboring positions, or with t h e skeletal vibrations of the ring system. The effects of introdtiring deuterium on the absorption of steroids in other regions of the infrared spectrum are also noted.
From a nonnal coijrdinate vibration analysis of I n the work to be described in this paper deu(runs-n-butane and other siniple aliphatic hydro- teriuin atoms were introduced, for the most part, carbons i t has been established3 that the C--1-1 a t relatively labile positions either by specific bending vibrations of methyl antl methylene groups chemical reactions or by enolization in alkaline occur between 1350 a n t l 1473 ciii.--'. In the solution. When the spectra of the normal and preceding paperi all the prominent absorption tieuterized steroids were compared it was observed hands in. thisdregion of the spectra of steroiils have that certain bands present in the spectra of the hren attributed to such methyl and inethylene tionrial steroids disappeared on deuteration. In group vibrations, and it has been assumed tacitly a11 cases the bands which disappeared were those that the bending vibrations of each methyl and which had been assigned to vibrations localized in inethylene group in the steroid molecule is inde- the methyl or methylene groups which had been peiident of the bending vibrations of similar ncigli- specifically deuterized. boring groups. Experimental This hypothesis appears to fit the experimental The spectra were measured under conditions identicnl facts well, but such absence of coupling between the C---Hvibrations of adjacent groups w:is h:irtlly to with those described in the preceding p ~ b l i c a t i o n . ~T h e niethotls employeti for the preparation of the deuterized be anticipated on the basis of molecular vibrational compounds will be briefly noted in the course of the discustheory. It was therefore considered advisable to sion. Details of their preparation, and evidence of strucattempt to obtain more direct experimental evi- ttire will he priblished elsewhere.12 dence for the localization of these vibrations in Results and Discussion specific groups. This has been done by study of Steroid Acetates.-The effect of introducing the spectra of steroids in which the CHy and CH3 groups postulated to give rise to specific ab~c~rptioiideuterium into the acetoxy group of steroid acetates was selected for a preliminary study, in view bands have been selectively deuterized. of the ease with which such compounds can be Previous investigators have prepared steroids . prepared by acetylation of the steroid alcohol with enriched in deuterium by catalytic exchange, by direct reduction with deuterium on a platinum acetic anhydride-ds. In the nornial acetates13 the two strong bands catalyst8-10 and by reduction of bromosteroids and steroid ethylene mercaptols with deuterized Kaney which occur near 1373 and 1365 cm.-l (bands L iiickel." These reactions were uiiciertaken with and N)13have been attributed to vibrations of the the object of introducirig deuteriuni into tightly acetoxy methyl group. In Figs. 1 and 2 the spectra bound positions to serve :IS label5 in studies of of the nonnal and tricleuteroacetates of cyclohexanol, mdrostanol-3a, androstanol-1TP and pregsteroid metabolism. nanol-20a are shown. In each case the spectruni (1) Presented, in part, a t a Symposiiiiii on the Infrared S w c t r u 5cvpp o f 1,arge hlolec~iles,D i v i a i o n of Phy\ical and lnorganir Chtrnisof the trideuteroacetate lacks the strong bands t r y . American Chemical Society, Boston. Rlass., April 3rd. l < l ~ l , near 1365 and 1375 crn-l but otherwise resembles Piiblished a.; Contribution h-o,28.58 from the l.alx~ratoi-i?~ ,st .I'l~rT u the spectrum of the noniial acetate very closely. ti,.Cr-Ia IS,C'L). ~ C E I ~ ~ C O ~ C I J ~ . C D : ; s , c 1) I .c 1). , co .CI~)? .C1) ,'I
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methyl and methylene groups must be somewhat arbitrary when based solely on the positions of the maxima and a rough comparison of relative band intensities. Lordz0has observed that caution must be exercized in the comparison of the infrared spectra of normal and deuterized organic compounds, as the lowering of the C-H stretching and bending frequencies which occur on deuterations may cause changes in coupling with skeletal and other vibrations, leading to changes in the spectra which cannot be related in ;I simple fashion to the C--€I bond directly involved. In the work discussed in this paper complications of this kind are improbable, since the interpretations are based solely on the disappearance of C-H vibrations and not on the assignment of new bands in the deuterized compounds to CD, or CDa groups. Furthermore, it is unlikely that any fundamental C-C skeletal Vibrations occur a t frequencies SUEciently high to interfere in this region of the spectrum. Acknowledgments.--We are grateful to the late Ilr. Konrad Dobriner of the Sloan-Kettering Institute for helpful discussion and encouragement during the course of these investigations. M'r also wish to thank Dr. L. C. Leitch of the National Research Council and Drs. T. F. dallagher and D. K . Fukushima of the Sloan-Kettering Institute for advice in the preparation of the deuterized compounds, and Drs. F. Lossing and R. Jailer for mass spectrometry analyses. Gifts of compounds from Dr. E. B. Hershberg of the Schering Corporation arid Dr. C . K . Scholz of Ciba Pharmaceutical Products, Inc., are also grntefully acknowledged.
wi 11-1 the iiietliyl group, paralleling exactly thc behavior (it' similarly located groups in steroids. In tliethyl ketone, however, there is a band a t 1462 c m - l identified with the methyl groups, and a band a t 1357 cni. - l identified with the methylene group. I t must therefore be emphasized that although there may be good reasoris t o anticipate that characteristic group frequencies of general application may ultiitiately bc established for this region of the spect m11,circumspection must be exercised in extendiiig t o CJther classes o f compounds the correlations cstablished in these papers for steroids; particularly must this be so where widely different ratios of inethyl to rnethylciie groups in the molecule :Ire encountered, and where elements other than oxygen, hydrogen and carbon are present. In more recent studies of the spectra of both steroids and simpler compounds greater attention is being given to the accurate control of sample concentration, cell thickness and effective slit width, so t l u t the curves may he computed as apparent molecular extinction coefficients. This makes possible LL more rigorous interpretation of the absorption, especially in regions such as the A, B, C, C' and OTTAWA,CAXADI where, because of overlapping ~ i i i i r i i tof lwntls to indi\.-idual
