ATOV.
20, 1958
INFRARED SPECTRA O F
Anal. Calcd. for C24Ha404: C, 74.58; H, 8.87; 0, 16.55. Found: C, 74.28; H, 8.89; 0, 17.04. The above enol ether X I 1 1 (1.0 g.) in 25 cc. of dioxane was added to o,5 g , of calciuIll in 250 cc. of liquid ammonia and after stirring for 30 min., 4.0 g. of ammonium chloride was added and the product isolated in the usual manner,
[CONTKJBUTION FROM
THE
HYDROXYSTEROIDS
6121
After heating under reilux for 1 hr. with 5 cc. of concd. hydrochloric acid, 10 cc. of water and 25 cc. of methanol, 19-norprogesterone (VIII) (0.27 g., m.p. 140-142’) was obtained after passage through a short column of alumina and recrystallization from acetone-hexane* APDO. POSTAL 2679, MEXICO,D. F.
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH A N D THE DIVISION OF PURECHEMISTRY O F THE NATIONAL RESEARCH COUNCIL OF CANADA] ’
The Infrared Spectra of Hydroxysteroids below 1350 Cm.BY R.
NORMAN JONES
AND
GLYNROBERTS
RECEIVED JUXE 17, 1958 Characteristic absorption bands in the range 1350-650 cm.-’ are reported for steroids hydroxylated a t C(31, C( 17) and C(20). The bands are observed in the monohydroxy compounds and in steroids containing additional hydroxy, acetoxy and ketonic groups, provided the functional groups are well separated. The general implications of these and similar bands in the spectra of ketones and acetates also are considered.
In preceding papers2p3i t has been shown that many of the prominent bands occurring between 1350 and 650 cm.-l in the infrared spectra of steroid ketones and acetates depend specifically on the position and stereochemical arrangement of the functional group. Where the steroid contains two or more functional groups it is often possible to distinguish bands characteristic of each group. This applies most generally where the functional groups are well separated so that interaction effects are reduced. Examples have been given where one functional group is a t C(3) and the other a t C(17) or C(20). The spectra of a large number of steroid alcohols have now been surveyed in a similar fashion, and for these compounds also many of the infrared absorption bands in the 1350-630 cm.-’ range are observed to fall within narrow frequency ranges for steroids containing the same hydroxy substituent. Experimental Methods and Results The spectra were measured on Perkin-Elmer model 112 and model 21 spectrometers using sodium chloride prisms. The bands common to the various compounds of the same type are listed in Table I and the frequency ranges of the bands common to the compounds of the same type are summarized in Table 11. A representative spectrum of each type of steroid alcohol is illustrated i n Figs. 1-11. The common bands are cross-referenced between figures and tables by the letters A, B, etc., but it must be emphasized that these letters are assigned for identification purposes only, and no relationship is implied between bands carrying the same letter on different figures. The bands are classified in Tables I and I1 into categories I, I1 and 111. The basis of this classification was discussed it1 connection with ketone spectra.2 Category I bands provide the main functional group identification; category I1 hands usually stand out in the spectra and are useful for secondary confirmation of the structure. The category 111 bands are generally weaker and tend to be obscured by other absorption in the spectra of steroids containing more than one functional group. Most of the spectra were measured in carbon disulfide solution, but, because of the low solubility of many hydroxy steroids in this solvent, data for chloroform solutions a t 1 mm. path length and for potassium bromide disper(1) Published as Contribution No. 4919 from the Laboratories of the h’ational Research Council of Canada, and No. XXXI in the series “Studies in Steroid Metabolism.” (2) R. N. Jones, F. Herling and E. 12. Katzenelleubogen, THis JOTJRNAL, 7 7 , 651 (19j5). (3) R . N. Joues and 13 Herliug, i b d , 7 8 , 1153 (195b).
sions also are included in Table I. The spectra of some hydroxysteroids in potassium bromide disks have been shown to be sensitive to the conditions under which the disk is prepared$ therefore the frequency ranges given in Table I1 are based only on measurements in carbon disulfide solution. The majority of the spectra discussed in this paper have been published in an atlas616and in the right hand column of Table I references are given to the corresponding atlas chart numbers. In some instances the band positions given in Table I are taken from measurements made with the model 112 spectrometer under higher resolution than the curves published in the atlas; this accounts for small frequency differences of the order of 1 3 cm.-l between the band positions listed in Table I and those which would be interpolated from the atlas charts for the same compounds.
Discussion 3-Hydroxysteroids.-The most prominent band in the spectra of 3-hydroxysteroids occurs between 1056 and 999 cm.-l. This band is outstandingly intense with & in the range 160-220. The corresponding bands in steroids hydroxylated a t C(17) or C(20) have e!& in the range 60-120. This band is presumed to involve principally a C-0 stretching motion, and, in accordance with this, i t is observed that the band position is affected only slightly by replacement of the hydroxy hydrogen atom with deuterium.’ The position of the band within the range depends on the stereochemistry a t C(3) and C(5).8-10 The ranges previously assigned to this band in the various conformational isomers of 3-hydroxy steroids have been revised slightly as a result of the present investigation, and the new values are summarized in the second column of Table 111. 3-Hydroxysteroids also exhibit several bands between 1015 and S90 cm.-l; these, though weak, are usually sharp and can be useful as confirmatory ( 4 ) G. Roberts, Ana;. Chem., 29, 911 (1957).
(5) K . Dobriuer, E.R . Katzenellenbogen and R. N. Jones, “Infrared Absorption Spectra of S t e r o i d s A n Atlas,’’ Interscience Publishers, Inc., New York, N. Y., 1953. ( 6 ) G. Roberts, B. Gallagher and R . N. Jones, “Infrared Absorption Spectra of Steroids-An Atlas, Volume 11,” Interscience Publishers, Inc., New York, N. Y., 1958. (7) R. N. Jones, H. E. Hallam and J. Mateos, unpublished observation. (8) A. R. H. Cole, R. N. Jones and K. Dobriner, THISJOURNAL, 74, 5571 (1952). (9) H.Rosenkrantz and 1,. Zablow, ibid., 76,903 (1953). (IO) H.17osenkrautz and 1’. Skogstrom, ;bid,, 77, 2237 (1955).
012%
K.XORXIAN JONES
AND
Vol.
GLYNR U B E R T ~
GROUP FREQUI3XCIES IN 'IHE
'rAl3I.E I.--CHARACTERISTIC
Solveni
.~Ildr(JStal1-3a-Ol(lilg. 1 )
CS2
.Illopregnaii-3ru-o1 Cholestaii-3a-c~l A16-.indrosten-3a-01 .\ndrostaii-3a-ol-l;-one .\llopregnan-3a-ol-20-one ~ l i i d r o s t a n e - 3 a , l ~ 0 - d i17-acetate ol Allopreg1iane-3a,200-diol 20-"xtutc Atidrostane-3cu,17P-diol Xllopregiiane-3~,20a-dicil
CS. CS? CS::
CS? c Sz
c S?
.z
1242 1283 1242 1283" 1243 1242 1284 128X' 1%40*' 1285 1240 1288"
6 C S2 CIIC13/KBr~ KBr 1275"
1 111
Ahidrostaii-3p-ol (Fig. 2 ) .~llopregnan-3/3-ol C holestan-3/3-01 Ergostan-3P-01 AZ2-Stigmasten-30-o1 Androstan-38-ol-l7-(1iie A~llopregnan-3/3-ol-20-o~~c Androstane-3p, l7a-diol Androstane-3P,178-diol Allopregnane-38,20~~-diol
Etiocholan-3a-ol (Fig. 3) Pregnan-30-01 Coprostan-3a-ol A'6-Etiocholen-:ja-o1 Etiocholan-3a-ol-17-one Pregnan-3u-ol-20-oric 170-Pregnan-3a-ol-20-oiie Etiocholane-3a,17P-diol 17-xetcitc Etiocholan-3a,l7a-diol Etiocholanc-3a,178-diol Pregnane-3a,20a-diol
CS2 CS? cs2
CS2 cs2
CS2
CS, CS2
CS* CS2
cs* CS2
1)
I1
11
l2lil
1163 116-1 1164 1163
1216 1216 1215 1212 1211'" 121: Cli1''
1113-L 116tj 1 lCl3''
1,735' 1239'
121.7
1166
1211-
I137
R
c
111
111
1) I11
i
llii7'
I< I1
I.
IC 111
11
11. 1210' 1214 1210 1210 1210 1203' 1211tfk 1202
1250 1'30 1234 1252 1232 12:ii 125ij
12'2 1223 122? 1222 1222 1219 1220
135;.
h
1278
lzLil
h
1212s
A
I3 111
C I11
1)
111
E I1
1278 1278 1273 1273 1282 1280 1280 h
CIIC13/KBra 1270 CIICla/KBrZ 1280' CHCIJ/KBrb 1279"
12!il 1264 1264 1863 1265' 1'61 1260 J
1260 1265c,' 1262
n
125u 1150
125fi 1262 12651 h
125; i li
1244' 1255
c
IT1
121ti 1218 l2lii 1219 2215"' 1219"' 1217" 1220" 1211 2,710 1217'
(;
I1
I)
€:
I1
I1
1300 1304 1302 1301 1305
1270 1276 1276 1274 1278'
1252 1251 1249 1249 1232'
h
2 242
1218 1220 1215 1219 1218 1225
c
1J
I
I1 I
Ill
3u-H>drouy-5J1079 1108
1108" 1108 1105 1105" 1106 1110 1109" 1108 1110' 1113 I 111
I11
(.
I1
3@-Hydroxy4a1163 1132 1167 1132 1168 1132 1168 1130 1168 1132 1170' 1128' 1134 1170 113: e 1132' 1167' I c; 111
111. 1170 1171 llG9 1167 1168l 1175'" 1165 1171 1162 ll65'*' 117l8
A 111
II
F I11
I. 3a-Hydroxy-5aIll6 1070 10'9 107X 1081 Ill2 1071 l(J;3;3 1120 loti5 1032 1131' 1121' l(JX2 l(J27 1071" 10'9 1118 l(I74O lun.' 1116" h 10.12 I llii" liI(j7 l03Y Ill8 i(100~ 1037 2120
1293 1273 1303' 1274 1291 1270 1292 1270 1293 1270 1292' 1272 1289"& 127(j I275 1293
CSZ CHC13/KBri CHCl, CHC13/KBr~ 1300
c S2
111
1282
C1lnr;rcterirtic buiirl,
c
B
I11
so
1082 1088 lox7c 108d' 108Sm 1089"' 1088 1087 1085 1090c (;
111
IY. 38-Hydroxy-50Etiocliolaii-3fl-ul ( F i g . 4 ) Pregnaii-3,B-ol Coprosta11-30-ol ~ 1 c -tiocliolcn-3@-ol E Etiocliolan-3~-ol-l7-o11~ Pregnane-38, 17a-tliol-2O-olie
CSZ
C s. CSY
CSr CSZ
C13C13/K(Urt 1304 Solvent
1 I11
1%
I I1
111
I1
1107 1162 1167 1162 1102 11G6
v. CSJ
1292
l86X
1% 1
1217
CSL CSP
1290 1283 1286 1288 1288' 1292" 1292
1272 1272 1269 1270 1265 1273 1268'
1238 1258 1261 1252 1254l 7 25(i 1252
12113 1220
CS*
cs2 CSe C S* CS2
CHClj CI-ICls CHIC13 KBr
1212 1215 1216
1217 1213
1135 1138 1134 1138 1134 Ill2 I 111
1117 1122 1122 1120 1118" 111.; (
111
1191 1191 1191 1189 1193 1188 1191"' 1189
B@-IIydru\\-Aa 1172 11.34 1172 1126 11X3 1170 1165 1130 1165 1139 1170' 1134 1171"' 11.31 1131' e 113; 1167'
1192
ll7.j
L
'
11:3i I2bi
I'
lY20
11.jG
Nov. 20, 195s
INFRARED SPECTRA OF
INFRARhD SPECTRA UF and categoriesa H I I I1
steroids 1001 973 973 1001 1002 974 1001 970 999 973 1001 973 1004 1003 976 1001 975" 97g5 101OS II
1 I
I1
steroids 1072 1078 1072 1075 1074 1078" 1075"' 1075 1069' 1O7Os
1038 1037 1036 1037 1035 1037 1037 1035 1043 1033
H
J
11
952 957 960 959 964' 962" 962" 962'' 960' 954-" J
I11
1009 1011 1010 lollc h
1009' 101OC 1010 1012' 10105 11
1035 1038 1037 1038 1038 1035 1037 1037" 1034 1032' 1030
1009 1014 1012 1010 1007' 1012 1012 1013 1012 100ic lolls
H 111
I 111
1074 1076 1072
1060 1062 1060
h
h
steroids 1063 1066 1066 1065 1060 1066 1066 1070" 1063 1069' 106T steroids
1075" lO(j.5" 1083"a lO(i1 >I I1 I
r
111
steroids 110'3 l(JZ1 1082 1111 ll0Y 1082 1105 1080" 109@ 1094O 1110' 1084 1109 * 1110' 1082' 1102 1079" 1100" 1077" 1105" 1085 1088 1102
6123
HYDROXYSTEROIDS BELOIV 1350 CY.-'
I I
I1
HYDROXYSTEROIDS
J
K I1
L I1
927 932 934 935 924 928 928 933"
907 907 909 904 907 907 908 906' 908" 909
896 896 901C 90 1 896 895 900 898 900 90l8
886 882 886 886 884 882"
L I1
hI
975 976 975 975
953 954 954 957 957 953 951"' 954 954? 954r28
925 h
IC I1
990 990 990 991 991" 989 993 994 992 994s K 11
0
974 978 979 977 978" I,
TI
952 945 940 943 947 952 932 947" 949 946' 946
912 912 913 916 920 908" 908 914' 912 917' 914'
1
K 111
I1
1030 1032 1033 1033 103x 1031
998 1000 1000 1002 100(jt 1002
983 986 984 982 980
I
E:
1031 I049 1049 1051 1040 1056' 1047 1054 1045 1030' 1048 1055
T
L
AI 111
N
I11
111
R 111
796 796 796 794 795 795 795 794 795 797
722 728 728
701 701 701
881 885' 877"
825 827 826 831 829' 828 822 825 823 832
N I1
0 I11
F 111
903 901 904 904 908 901 900 898 906' 90Y
796 798 795 796 795 796 796 801
I11
d
I1
M I1
P
0 111
934 936 936 937 935 935 936 936 e
932
(2
0
726 728
72Y h
724"
Chart number steroid
1n
atlas686
23 335 38 28 135 444
0
702 TOO 699 699
..
..
h
ti5 369
696
(2
111
733 738 734 734
25 337 40 51 59 137 150 67 360 74
1
734 732 727
e
e
790
736
N 111
898 899 900 893 898 809 899 897" 899 898'
834 832 831 835 8291
89gS
829
31 345 49 34 144 158 452
d
838 833" 841
.. 364 il
830'
-3
l i
11
N
JI
111
98.5
960 960 959 962 959 906
949 950 950' 952' 946 953"
1J
I, 111
RI I1
N
I1
111
P I1
1u19 I019 1023 1022 1020 1025 1021 1020 1021 1028' 1021 1026
1007 1007 1007 1007 1005 1006' 1007 1008 1008 1010" 1006 1012
078 982 986 986 988 979 985 986 971 980' 986 077
'351 9 53 954 953 956 954 953 958 955 955' 955 957
911 935 936 934 932' 938
840 840 840 838 836 841
h
d
933
838 835 837 835 832
0 111
932 928 928 925 930 931
o
e
939 e
937
P
I1
111
Q
R 111
S I11
T I11
U I11
908 913 916 906 910 912
879 881 880 880 879 880
832 830 828 834 825' 830
782 788 787
732 740 735 745 740
700 703 702 703 708' 704
? I
812 806 804" 805? 806 805 805' 809'
788
R I1
S 111
70G 798 798 800 798 798 798 800
735 740 73fi 740 740 742 738 739
e
e
a
e
805
79s
B
e
..
33 37 50
.. 146 180
27 339 41 58 368 139
.. 235 68 69
.. 359
6124
Vol. xo A I11
csz
cS*
csz
CIIC13/KBri CHCla CHC13
n
xi
124G 1250' 1242
1134 1132' 1133'
1253
1135
"
11?2 1134
A Ill
li 111
Allopregnaii-20~-oI(Fig. 9) rllloprcgnatr-20~-ol-3-orlc
Pregiinii-20a-ol (Fig. IO) Preg1ian-20~-ol-3-one IJregnniie-3u,20iu-diol
I'regnoii-208-01 (Fig. I 1) Preg1ian-20p-ol-3-one
CS2
es,
12iO 1266'
IlW 11682
T h e Libsrir1)tiutiin tliis region n a s t i n t n i c i . < u i n ( l . Jiiflecticiii. a For significance of categories 5ec test. h Broad band. Figures for incnsuretion obscured by the strong band associated with the uriwturated group. l3;riid not observed. associztec! Tvith tlie 20-ketoiic associated with the 3-ketone group? 2 Also associated with the 17-ketone groiip.' nL Aklsc~ with the 20-acetosy group.3 p Also associated with the 3-hydroxy group (see lliis table, sections I--\-). Also nwiciatctl sections IX-SII).
evidence for the stereochemistry a t C(3) a i d C ( 3 ) . Some of these bands have been noted previously by Iiosenkraiitz and Skogstrom, and they are suiiiniarizecl in the columns to the right of Table 111. The ~-3P-liydroxysteroids also have characteristic bands between 550 and 700 cixi.-l associated with tlic unsaturated linkage.11 17-Hydroxysteroids.-Our observations on steroids hydroxylated at C(17) are restricted to the 17a-hydroxy compounds of the Clg-series. The spectra of androstan-17P-01 and etiocholan-17P-01 are shown in Figs. 6 and 7. A11 the 17P-hydroxy compounds have a medium-strong band between 1059 and 1046 cm.-1 (band D of Fig. G and band H (I1) I1 I I i r ~ c h n i d i i n 'liiis ,
JOLKYAI,
7 4 , 6397 (1!152)
of Fig. 7); this is probat-ly a ''C'-0stretcliirig b~rntl" and is useful for differentiating these coinpountl.; from those hytlro.;yl.itetl a t C(3). The positioii of this band is not sigiiiiicantly different iii colllpoulltls of the 5,- and 5P-scries, or in compounds coiitainiiq a ,A4- or A5-bond. The spectra shown in Figs. G ant1 7 are readily distinguished, but the differences between them depend mainly on small frequency shifts and intensity changes and are not consistent when other functional groups are also present. The infrared spectrum therefore does not provide a satisfactory means for differentiating between 17p-hydroxy compounds of the 5,- and 5p-series. spectra of thc 20$20-Hydroxysteroids.-The 11) droxysteroids mc 1i:tve ex,irnirirtl :ire dis-
Nov. 20, 1955
INFRARED SPECTRA OF HYDROXYSTEROIDS
6125
Continued) H I1
steroids 956 916 953 913 95ik 917 9629 954' 960 920 H I
I I1
steroids 1052 1030 1050 1028 1054 1032' 111
steroids 1067 1067 1067 1066 1070 H I11
I
T
1012 1010 1016*~" 1010' 1010 I
111
1
I1
steroids 1088 1064 1091 1072 1090c~' 1067' H I1
111
889
824 828 827 529'
I,
h
88jq
889 890
'
11
985 985' 587
29 128
..
65 360 362
0
K
L
111
I11
950 950 946*
918 918 517'
M 111
898 898 898'
N 111
35 142 71
830 82Sbsk 830'
111
steroids 1030 1012 1028 1010 H 11
111
I
Hydroxysteroids 915 828 920' 828 e 914 H I1
K
I I11
I I1
steroids 998 970 992 968
130 427 69
'
111
I11
K
L
M
N 111
0 111
P 111
996" 999 988" 995' 994
976
929 930' 928 920 5324
906 902 906" 901' 902
889 890 888 888
875
977" 978' 978
957 954 956 954 954'
J
K I
L TI1
M
I11
111
N 111
1002 998
965 902
936 932
908 904
876 882
826'
I
K I11
L
hl
0
P
I11
I11
876
725 725
h
I
I11
I
I11
hI11
895 898 898'
1008 1012 loll'
987 990 990"
952 956 958
910 916 914
L
AI
111
K 111
I11
1x1
952 952
897 899
877 877
828b 82Sk
883 0
111
&30
875
877 877' 872
Q
111
725 727 726" 724R "
341 44 1 369 74
P 111
722 722
343 442
348 *. 77
350
f Absorption obscured by the strong ester band. 0 Absorpe The absorption in this region was obscured by the solvent. ments made on KBr disks are italicized. f This band was not resolved in the curve shown in the "Steroid Atlas."6*6 Ir Also groupZ Also associated with the 3-acetoxy group.3 Also associated with the 17-acetoxy group.3 p Also associated with the 17-hydroxy group (see this table, sections VI-VIII). a Also associated with the 20-hydroxy group (see this table,
tinguished by the medium-strong band a t 11001090 cm.-'; these show predominantly in the spectra of the mono-alcohols (band F of Fig. 9 and band D of Fig. 11). The 20a-hydroxy steroids have no comparable band in this part of the spectrum and their strongest band appears a t 10161008 cm.-l (band I of Fig. 8 and band J of Fig. 10). The 20a-hydroxysteroids of both the 5a- and 5Pseries have a characteristic band a t 957-952 cm.-l (band L of Figs. 8 and 10). The 20P-hydroxysteroids of the 5a-series have a strong band a t 965-962 cm.-l (band K of Fig. 9), but in the 5P-series this band is not so prominent (band I of Fig. 11). These differences in the spectra of 20a- and 20P-hy-
droxysteroids between 970 and 950 cm.-' have been noted also by Wiggins and Klyne.I2 No systematic differences are observed between the spectra of 20a-hydroxysteroids of the 5,- and 5fl-series and the situation is similar to that of the 17P-hydroxy compounds discussed above. The spectra of the 20P-hydroxysteroids of the 5a- and 5P-series show more pronounced differences, notably between 1050and 900 an.-' where the 58-compound shows a series of sharp peaks (bands FH, J, K of Fig. 11). The spectra of the 20P-hydroxysteroids therefore appear t o be more sensitive to the stereochemistry a t C(5) than do either the (12) H. S. Wiggins and W. Klyne. Chemistry & I n d u s f r y , 1448 (l
