KARLINER, BUDZIKIEWICZ, AND DJERASSI
710
Reduction of the da4,4-Dimethylestr-5-encrude crystalline alkylated material (24 mg), mp 125-130°, obtained by da-methylation of 4-methyl19-nortestosterone acetate (9) was reduced with a solution of sodium (200 mg) and hydrazine (0.6 ml) in diethylene glycol WOE-Kishner
17p-01-J-one Acetates.-The
VOL.31
(3 ml). Analogous treatment as described above gave an oily material (27 mg) which was chromatographed on alumina (8 9.) Elution with pentane-ether (13:l) gave 8 mg of material, mp 14P146', which consisted mainly of 4&methyld34a-methylestr-5-en-17p-01 acetate (17) (see discussion).
Mass Spectrometry in Structural and Stereochemical Problems. XC1.l The Electron Impact Induced Elimination of Water from 3-Hydroxy Steroids J. KARLINER, H. BUDZIKIETVICZ, AND CARL DJERASSI Department of Chemistry, Stanford University, Stanford, California Received August 31, 1966 One of the ubiquitous fragmentation modes of 3-hydroxy steroids is the loss of 33 mass units (methyl radical plus water). By deuterium labeling in the chnlestane series it could be shown that in the cme of the axial 3aalcohol the M - 15 ion loses water exclusively by 1,3 elimination of the hydroxyl function and the la- and the S ~ h y d r o g e natoms, respectively. The 3@-alcoholshows more random loss of water after elimination of the C-19 methyl group. An explanation for this apparently inconsistent behavior is given,
Studies of cyclic alcohols (cyclopentanoP and cyclohexano13i4)have shown that electron impact induced loss of water occurs as a 1,3 or 1,4 elimination. However, it could not be determined with these model compounds whether this reaction occurs in a stereospecific manner. In the steroid series studies of this type seemed feasible and our results are reported herewith. The spectrum of 5a-androstan-3p-01 shows a prominent M - 18 peak and would, therefore, have been suitable for our studies. We wanted, however, to rule out any possible falsification of the results by thermal loss of water prior to electron impact and chose, therefore, a different substance. The M - 18 fragment in the case of cholestan-3a- and -3p-01 is negligible when direct insertion of the sample in the ion source is used.6*s However, loss of water can be observed (see Figure 1)starting from the M - 15fragment (supported by appropriate metastable ion at m/e 338.0, calcd 337.8), and we chose this process for our further studies. The data obtained with various deuterium-labeled analogs of cholestan-3a-01 are given in Table I (the estimated error is *2%). These results show that no 1,2 elimination occurs in this fragmentation process. Most of the deuterium lost stems from the 5a-position, while comparison of the 1,1,3@-&and the la-dl analogs shows that some deuterium comes from the la-position. Assuming that the total (about 80%) accounts for all the loss of water from the M - 15 species, an isotope effect of 0.8 has to be invoked which lies well within the observed range.'v8 The driving force of this sequence is apparently the stabilization of the C-19 (1) Paper XC: A. H. Jackson, G. W. Kenner, H. Budaikiewica, C. Djerassi, and J. M. Wibon, Tetrahedron, in press. (2) P. Natalie, BUZZ. Soc. Chim. Beleee, 69, 224 (1960). (3) C. G.McDonald, J. S. Shannon, and G. Sugowdz, Tetrahedron Letters, 807 (1963). (4) H.Budzikiewica, 2. Pelah, and C. Djerassi, Monafah., 91, 158 (1964). (5) J. F. Lynch, J. M. Wilson, H. Budzikiewica, and C. Djersssi, Ezperientia, 1% 211 (1963). (6) Using the conventional heated all-glsaa inlet system, a substantial M 18 peak is observed in the msss spectrum which must be due to thermal loss of water, since the 2,2,4,4-& analogs showed that here entirely 1,2 elimination occurred. (7) D.H.Williams, H. Budaikiewicz, and C. Djersssi, J . Am. Chem. Soc., 86,284 (1964). (8) F. H. Field and J. L. Franklin, "Electron Impact Phenomena," Academic Press Inc., New York, N. Y., 1957,Chapter 5.
-
ORIGIN(%)
TABLE I HYDROGEN IN M
-
34 FRAQMENT OF LABELED CHOLESTAN-3a-OLS OF
M
Compound
- 34 (CHI + HDO)
Cholestan-Sa-01 Cholestan-3a-ol-2,2,4,4-d~(V) Cholestan-3cu-ol-1,1,3p-d3 (XIX) Cholestan-3~01-la-dl(IX) Cholestan-3a-ol-5cu-dl (XIII)
0 0 7&2 4.5=?=2 73 2
*
carbonium ion by conjugation with a cyclopropane ring. Preferential loss of the 5a-hydrogen (from a tertiary position) compared with the secondary l a locus has its parallel in other fragmentation^.^
a,
M-15
H b,M-33
C,
M-33
The analogous data for the isomeric cholestan-3~-01 are compiled in Table I1 and show that this compound follows different fragmentation paths. No loss of deuterium is observed from the la-, 2-, 3a-, or 4-positions, while elimination from the lp- and 5a-(!) position totals only about 40%. On the assumption that the same isotope effect operates as in the 3a-hydroxy isomer, only about one-half of the loss of water from 15 ion is accounted for and the remaining the M hydrogen must be abstracted from carbon atoms other than in ring A.
-
(9) C. Beard, J. M. Wilson, H. Budsikiewica, and C. Djerassi, J . A m . Chem. ~ o c . ,8S, 269 (1964).
XIARCH
ELIMINATION OF W A T E R
1966
711
FROM 3 - H Y D R O X Y S T E R O I D S
SCHEME I
f-
R
I
I1
VII, R = O VIII, R = ...H ,OH
VI
111, R=O XV, R = /OH ...H
..OH V, R = -
IX,
H '
&
4
ACO
X
XIV
,OH
4
AcO XII, R = ...H ,OH
XI
XIII, R =
O Y XH?
R =H''*
,,OH LH
D H XV, R = O
XVII
OH XVI, R = -
