摘要:
Org . 423 Circular Dichroism and Optical Rotatory Dispersion of some Hexahydro- indanone Derivatives ; Methyl- and Methylene-substituted Steroid Ketones By (Miss) M. J . Brienne, A. Heymes, and J . Jacques, Laboratoire de Chimie organique des Hormones, College de France, Paris 5" G. Snatzke, Organisch-chemisches lnstitut der Universitat, Bonn W. Klyne" and S. R. Wallis, Chemistry Department, Westfield College, London N.W.3 Circular dichroism and optical rotatory dispersion curves of a number of steroid hexahydroindanones have been measured. The compounds were A-nor-5a-androstan-2-ones and 5a-androstan-I 6-ones carrying methyl groups in positions adjacent to carbonyl. The curves are discussed in relation to the probable conformations of the cyclopentanone ring. Some data on related a$-unsaturated ketones are also included.DURING a study on the biological activity of derivatives of A-norandrostane , a number of methylated oxo- steroids carrying the methyl group and the carbonyl group, either in the A-nor ring or in the D ring, were prepared by hydrogenation of the corresponding methylene ketones. The mechanistic problems relative t o this study, and, in particular, the study of the Mannich reactions of various keto-steroids, have been discussed elsewhere .3a The Experimental section of the present paper describes the preparation of the com- pounds (2)-(23) mentioned in ref. 3a. The stereochemistry of most of the saturated ketones obtained in this work has already been disc~ssed.~a The arguments used were based partly on the stereoselectivity of catalytic hydrogenation of the corresponding methylene ketones (attack of hydrogen on an a-face), 1 This paper is Part XXXVI in the Bonn series on c.d.(Part XXXV, G. Snatzke and E. Otto, Tetrahedron, 1969, 25, 2041). I t is also Part LXV in the Westfield College series on 0.r.d. and c.d. (Part LXIV, D. N. Kirk, W. Klyne, and S. R. Wallis, J . Chem. SOG. ( C ) , 1970, 350. 2 J. Jacques and G. Pincus, in ' Hormonal Steroids, Bio- chemistry, Pharmacology, and Therapeutics,' ed. L. Martini and A. Pecile, Academic Press, London and New York, 1962, vol. I, p. 3; G. Pincus and G. Bialy, Recent Progress ii.2 Hormoize Research, 1963, 19, 201; U. K. Banik and G. Pincus, Proc. SOC. Exp. Biol., 1962, 111, 596. and partly on the results of the equilibration of these methyl ketones.The configurations of the dimethyl ketones (13) and (14), and the 17-methyl-16-ketone (19), which have not previously been considered, may be treated in the same way. Significant features of the n.m.r. spectra of these saturated ketones are as follows: (i) The presence of a methyl group at 3p or 3a has no influence on the position of the signal of the lop-methyl group. (ii) The chemical shift of the lop-methyl group is affected by the presence of a 1P-methyl to the extent of about -0.15 p.p.m. Methyl groups a t 17a and 178 affect the chemical shift of the 13p-methyl group (C-18) by ca. +0-053b and -0.20 p.p.m., respectively. These shifts confirm the proposed stereochemistry. (iii) The splitting (or broad- ening) of the signal of the lop-methyl group in certain A-nor-androstane derivatives, already reported by Caspi and his co-workers,* has been observed here in a number of other cases.3 (a) A. Heymes, M. J. Brienne, J. Jacques, D. B. R. Johnston, and T. B. Windholz, Proc. 2nd Internat. Congr. Hormonal Steroids, 1966, p. 232; (b) R. F. Ziircher, Helv. Chim. Acla, 1963, 46, 2054. E. Caspi, S. K. Malhotra, Y . Shimizu, K. Maheshwari, and M. J. Gasic, Tetrahedron, 1966, 22, 595.J. Chem. SOC. (C), 1970 The availability of this range of compounds has made Cotton effects often encountered (a ca. 200) in the possible studies of the Cotton effect (0.r.d. and c.d.) of hexahydroindanones are caused by the skewed nature the methylated hexahydroindanones, and the methylene of the five-membered ring itself.This is equivalent to hexahydroindanones. The data are summarised in saying that the ' second sphere ' 6 around the carbonyl is TABLE 1 C.d. data at + Z O O and at low temperature ( T ) for some saturated ketones All measurements are in the solvent MI,, (methylcyclohexane-isopentane; 1 : 3 vlv) except for those marked *, which are in the The partial band of largest SAE is defined as the algebraic contribution of the methyl group(s) to the c.d. of the corresponding noninethylated ketone; ~ A c = [R](T) is the reduced rotational strength a t temperature T. The indices ( I ) (%) are calculated from At or [R] values, as indicated For definition of I, see p. 427. solvent EPA,,, (ether-isopentane-ethanol; 6 : 5 : 1 v/v). is shown in italics; i = inflection. AC (methylated ketone) -A& (nonmethylated ketone) ; 6[R] is similarly defined.in parentheses. Com- ( T , = 20") 324 312 301 29 1 282i 275i 322 311 300 291i 324 312 301 291i 32% 312 302 2953: 321 320 299 29 1 299 321 309 299 29Oi 324 312 301 291 283i 275i 321 310 300 292 321 309 299 290i 1 4 . A& +3-17 + 5.98 45-91 f4.19 1-2.51 + 2-26 + 5.07 t 5 . 6 9 4- 4.49 + 3.53 + 6.05 + 5- 65 +- 3.83 +- 1-93 + 3.70 + 4.08 + 3.39 + 3.65 + 6.85 + 6.75 + 5-02 + 4.33 + 3.36 + 5.39 + 4-89 + 3.21 -1- 1.46 - 3.20 - 6.05 - 6.08 - 4.38 - 2.75 - 1.56 - 2.34 - 5.07 - 6.38 - 4.63 -3.17 - 5.69 -5.51 -4.12 320 308 298 288 280i 320 309 298 290 317i 305 297 288i 317 305 295 287i 314 304 295 317 306 296 288 320 308 297 289 279i 320 308 298 290i Figures 1 and 2. Representative + 3.65 + 6.49 + 6-28 +- 4.44 + 2-75 3-3.51 + 5.93 + 5.38 + 3.74 +2-16 +4*ll + 4.24 +- 3.28 + 4-39 + 7.5Y + 7-02 +4*75 + 2.73 + 4.67 + 4-53 + 3.96 + 5.78 + 4-82 + 3.15 - 3.62 - 6.27 -6.10 - 4.32 - 2.50 - 3.60 -6.13 - 5.65 - 4.00 Low temp.TI - 181" - 175 - 176 - 175 - 178 - 178 - 180 - 178 curves are shown Rotational Contributions of strengths methyl groups Indices [RJ(+20°) [R](T,) 8Ae(-!-20c) 8[R](+2OL') I ~ , + ~ ~ ( h t ) IT,+ao([Rj) + 19.17 +17*32 + 18.31 -12.3 -5.4 + 16.76 + 14.24 -+ 0.07 -2.42 +2-0 +17*6 +14.23 +13*85 -1.90 -44.94 -3.8 + 2.7 3-13.11 1-15.34 -1.65 -6.06 -7.3 - 14.5 +15.40 +15*34 -0.59 -3.77 -6.7 + 0-4 - 17.57 - 16.58 - 17.07 + 1.8 - 2.9 -16.70 -16.82 +0.39 +0*87 -7.2 -0.7 in dissymmetric. Contrast the situation in cyclohexanones with a local mirror plane (as, for example in the chair It was suggested5 some years ago that the large conformation) where the 'second sphere' is s p - metrical, and dissymmetry can arise only in the ' third As expected from many previous studies of the un- ' W.IClyne, Tehzhedron, 1961, 13, 29; Bull- SOC. chima sphere 9 , giving generally smaller amplitudes. Francs, 1960, 1396. 6 G. Snatzke, Tetvahedron, 1965, 81, 413, 421, 439.Org . (1) a ; R1= OAc, Ra = H b; R1 = OH, R2 = H c; R1 = OH, R2 = Me d ; R1 = RZ = H (2) R1 = morpholino- (3) R1= H, R* = mor- (6) R1= R2 = CH, (4)] R1 = CH,, R2 = H, (7) R = H methyl, R2 = H (5) R1 = H, R2 = CH, (8) R = Me pholinomethyl Me (9) R = CH,Br (11) R1 = H, R2 = Me (14) (10) R = Me (12) R1= Me, R2 = H (13) R1 = R2 = Me All formulae (2)-( 14) are 17/3-acetoxy-~-nor-5a-androstanes except for nos.(7), (lo), and (12) (7a), (lea), and (12a) are 17/3-acetoxy-~-nor-5a-androstanes (7b), (lob), and (12b) are 17j!-hydroxy-~-nor-5a-androstanes methylated ketones the present work shows that the skewed nature of the five-membered ring dominates the magnitude of the Cotton effect, and that the effects of methyl groups, whether direct or indirect, are relatively small. Contributiou of a Methyl Groz~p to the Rotational Strepzgth of Cyclopentanonze Systems.-An intensive study TABLE 2 C.d. data for some saturated ketones All measurements at room temperature (ca. 20'). Values in dioxan measured at Bonn, values in other solvents at Westfield. The partial band of largest is shown in italics; w, m, s indicate weak, medium, and strong fine structure.AAE(M) is defined as the solvent difference, viz.: AE (methanol) -Az (hexane). The amplitudes (a) are taken from Table 3. for the 0.r.d.-c.d. comparison Solvent Dioxan Diossn Methanol Hexane Methanol Hexane Methanol Hexane Methanol Hexane Methanol Hexane Methanol Hexane L X . (nm.) 325 313 302 29% 230 320 309 298 28% 222 298 311 295 300 294 306 295 300 297 306 294 306 AE + 2-56 + 4.50 $- 4.36 3-3-10 + 0.42 + 3.37 + 5.62 + 5.24 + 366 + 0.90 + 5.45w + 5.45s + 4.7 f 3.Sm + 6.4 + 5.2m + 5.3 4-4.7 + 5.5 + 5,4133 - 5.55 - 5.0m Solvent differ- 0.r.d.-c.d. ence comparison AAE (M) Ratio a : AE 0 + 0.9 -k 1.2 +0.6 +0*1 - 0.55 38.9 39.4 40.0 37.2 39.2 39.8 37.4 39.0 39.0 39.4 40.2 42.8 TABLE 3 0.r.d. data for saturated ketones Aa,, ' Group contribution ' = amplitude (a) of compound with a methyl group adjacent to carbonyl ~ z i ~ t u s amplitude of = amplitude in methanol minus amplitude in hexane; w, m, s., indicate weak, unsubstituted analogue; Aa8, ' solvent difference medium, and strong fine structure.0.r.d. in hexane Solvent Forinula Extrema €or hexane) 0.r.d. in methanol p--7 difference A r 1 h(nm.) (MeOH - Compound no. A(nm.) [+] a Aa, extrema a A& 17/3-Hydroxy-~-nor-5a-androstan-3-one 0 (lb) 313 + 11,100 f217 17j3-Hydroxy- 17cr-methyl-~-nor-5~- (lc) 313 +10,850 +218 $1 17/3-Acetoxy-3fl-methyl-~-nor-5cr-androstan- (11) 315 $8,930 + 188 -29 3261276 + 143 $46 17/3-Acetoxy-3~-rnethyI-~-nor-5a-androstan- (10a) 319 +9500 3-212 -5 3281274 +215s -3 17~-Acetoxy-l~-methyl-~-nor-5cr-androstan- (12) 312 + 11,800 f251 + 34 3231274 +208m +43 274 -10,600 androstan-%one a 276 -10,950 2-one 271 - 9850 2-one 276 -11,700 2-one 270 -13,300 androstan-2-one 270 -10,000 androstan-2-one 273 -11,400 1 7fl-Acetoxy- lfl,3p-dimethyl-~-nor- 5a- (13) 312 +9800 3-198 -19 320/273 $183 $15 1 'IS-Acetoxy-1 j3,3a-dimethyl-~-nor-5a- (14) 316 +lO,OOO +214 -3 323/278 +213m + I 5a-Androstan-16-one b (15) 312 -11,500 -237 270 312,150 273 +10,900 17/3-Methyl-5a-androstan- 1 &one (19) 313 -11,400 -223 +14 323/276 -214m -9 a Dr.3.-C. Bloch, Strasbourg. b Prof. D. W. Mathieson, Bradford (formerly School of Pharmacy, London).426 J. Chem. SOC. (C), 1970 3-Me thJ-lene-2-one TABLE 4 C.d. of @-unsaturated ketones Temperature 20"; i = inflection. The partial band of the largest A E ~ ~ ~ . is shown in italics.com- L%r. pound Solvent (nm.) AE A-Xor series 1-Methylene-%one (4) Dioxan 383i +0*70 364i +2*15 349 +2*78 335i +2-33 321i +1.46 Ethanol 341 +2.70 ( 5 ) Dioxan 376 +1.07 360 +2-53 345 +2.75 332 +1.91 216 f0.5 Ethanol 362i +1*79 346 f2-74 334i +2-41 218 f0.4 235 -1.82 236 -1.60 236 -2.3 239 -2.1 202 -1.3 (6) Dioxan 404i +1.20 389 4-2-02 374 +less 360i f l . 3 0 257 -8.2 Ethanol 412i f 0 . 5 0 391i f l . 5 4 375 f 1 . 8 6 229 +1-33 3-Methyl-3-en-2-one (7b) Dioxan 340i -0.90 305i -1.17 Ethanol 331i -1.43 309i -2.65 241 -3.77 211 +10.0 261 -6.15 208 -2.50 327 -1.76 316 -1.73 314 -2.69 1/3,3-Dimethy1-3-en-2-one (8) Dioxan 3341: - 1.38 327 -2.59 316 -2.52 305 -1.68 D-Series 17-Methylene-16-one (18) Dioxan 383i 363 349 334i 236 Ethanol 349 340i 237 210 - 1.19 - 3.08 - 3.60 -2.71 + 3.4 - 3.44 - 3.37 + 2.8 - 1.2 by Ouannes and Jacques' of simple monocyclic cyclopen- tanones has permitted the calculation of standard values for certain preferred conformations (envelope and half- chair).The conformations of the more rigid tram- hexahydroindanones treated in the present paper can now be considered in the light of this discussion. We consider schematically the conformations of the hexahydroindanone systems (A-nor + B rings, and D + c rings; see Figures 3 and 4), in which the cyclo- pentanone ring belongs to the point groups C, and C, (with a plane of symmetry and a two-fold axis of 200 300 A (nm.) FIGURE 1 C.d. curves of (Id) (a-nor-6cc-androstan-2-one) in EPA,,, a t +20° (----- ) and -181" (----) FIGURE 2 C.d. curves of (6) (17~-acetoxy-1,3-dimethylene-~- nor-5a-androstan-2-one) (- ) and (7b) (17/3-hydroxy-3- rnethyl-~-norandrost-3-en-Z-one) (- - - -) in ethanol symmetry respectively). The three conformations (01, 02, 0 3 for ring D and 04, 0 5 , 0 6 for ring A), represent instantaneous states of a molecular motion which can lead from one to the other of two envelope conform- ations (with the ' point ' in the a- and in the @-position 7 C.Ouannes and J. Jacques, Bull. SOG. chim. France, 1965, 3601 ; C. Djerassi, R. Records, C. Ouannes, and J. Jacques, ibid., 1966, 2378.Org. 427 respectively) passing through a half-chair (see Figures 3 and 4). These three conformations follow one another during the pseudo-rotation of the cyclopentane nucleus, and the inolecule can pass from 01 to 0 2 to 03 (or the reverse) by a continuous variation of all the relevant dihedral angles (see Ouannes and Ja~ques,~ conformations 15, 16, and 17).The energetically most favourable conform- ation (probably not symmetrical) between the extremes 01 and 0 3 (or 04 and 06) is decided by a number of factors, among which the position and the nature of the substituents on rings D and A are the most obvious. For reasons which depend on the very nature of the pseudo-rotation itinerary between the three symmetrical 01 02 03 -1cJ3 -491 @*,, -48,l -46,l -28,6 -15,l +46,1 +3V.4 i28.6 ' 0l'- Envelope Half -cha ir 'I]'-Envelope 18 18 \ More negative Less negative FIGURE 3 Conformations of ring D 04 05 06 Me I ' p' Envelope Half chair 'd' Envelope 1v More positive I envelope Less positive envelope FIGURE 4 Conformations of A-nor ring conformations (01, 02, 03; or 04, 05, OS), the half- chair conformation (02 or 05) always has an energy lower than that of at least one of the two envelopes, whatever the substituents on the cyclopentane nucleus.The substituents have the effect of rendering more or less unfavourable one of the two envelope conform- ations, Le., of shifting the conformational preference more markedly towards the envelope of lower energy. 8 C. Altona, H. J. Geise, and C. Romers, Tetrahedron, 1968, 9 A. Moscowitz, in C. Djerassi, ' Optical Rotatory Dispersion,' 24, 13. McGraw-Hill, New York, 1960, p. 150. Altona and his co-workers* have concluded that one of the main factors determining the preferred conform- ation of ring D is strain in ring c, but they give no information about 16-oxo-steroids.In the crystalline state several possible intermediates between the two extreme envelope forms of ring D have been found,* depending on substitution and stereochemistry at the ring junctions. A methyl group attached to a cyclopentanone may influence the Cotton effect in two ways: either (1) by direct perturbation of the chromophore (contribution of the third sphere, according to the Octant Rule), or (2) by changing the conformation of the five-membered ring (second sphere effects). Previous experience 57 indicates that the latter effect should be much greater than the former; this is borne out by the following data. The Cotton effect is usually measured either by (in c.d.) or by the amplitude a (in 0.r.d.) (for 0.r.d.results, see later). All the cyclopentanones investigated in this series showed pronounced vibrational fine structure, and in such cases values of AE or a may not be reliable measures of molecular dissymmetry, because sharpening or broadening of partial bands will apparently increase or decrease the Cotton effect. All comparisons were, therefore, made in terms of reduced rotational strengths which were determined by the device described recently.10 The c.d. curves of all methylated compounds were measured in the solvent ' MIl3' [methylcyclohexane-isopentane (1 : 3)] ; the two un- substituted steroids (la) and (15), however, crystallised from this solvent on cooling and had to be run in the solvent ' EPA551' [ether-isopentane-ethanol (5 : 5 : l)] in order to obtain values at low temperatures.In order to make all comparisons in the same solvent here, we have used throughout this treatment rotational strengths or AE,,~. values at +20". Comparisons of [R] values at low temperature might be preferable because, if con- formational equilibria occur, the most stable conformer will then have the highest population.ll An equilibrium between two or even three of these conformations 01-03 (or 04-06) appears improbable because as noted later changes of [R] or A E ~ ~ . with temperature are small for these saturated ketones. The relative change of the rotational strengths with temperature is best described by the index IT+2o, defined l1 thus : where T is about -180". For a completely rigid com- pound a theoretical estimate l2 gave for the upper limit of 1180+20 a value of ca.15%, and indeed nearly all measured values are within this range ( c j . Table 1). This fact reflects the high rigidity of these steroidal lo G. Snatzke and W. Lohr, 2. analyt. Chem., 1968, 241, 212. 11 A. Moscowitz, in ' Optical Rotatory Dispersion and Circular Dichroism in Organic Chemistry,' ed. G. Snatzke, Heyden & Son, London, 1967, p. 329; G. Snatzke, ibid., p. 335. 12 0. E. Weigang, jun., personal communication.428 J. Chem. SOC. (C), 1970 cyclopentanones, in contrast to the simple monocyclic 3-methyl~yclopentanone,~ which gave I -39%. Table 1 also shows that the indices obtained from rotational strengths, [R], do not parallel exactly those calculated from values; this may be due, at least in part, to changes in the vibrational fine structure of the bands.The Cotton effect of a 2-oxo-~-nor-steroid (I) is strongly positive. Introduction of a 3 p-methyl group [negative octant; as in (ll)] decreases it, whereas a 1p-methyl group [positive octant; as in (12)] gives an increase. A 3a-methyl group on the other hand [as in (lo)], which would be expected from octant projections to have a positive contribution, actually decreases the rotational strength; this effect is even stronger if both l p - and 3a-methyl groups are present (14). A similar ‘ apparent anti-octant contribution ’ is made by the 17p-methyl group in the 16-oxo-compound (19). In accord with earlier experience it can, therefore, be con- cluded that the direct contribution of ‘ third-sphere ’ groups is much smaller than the indirect effects which they make by changing the second sphere (conformation of the ring). The results found can be rationalised in terms of the following suggestions about the conform- ation of ring A (or ring D) in these cyclopentanones.The half-chair conformations 0 2 and 05 must have greater rotational strengths [R] than the envelope con- formations (01, 03, 04, and 06), which are less chiral as seen from the carbonyl group. The value of [R] must decrease continuously on going from the C, (half-chair) form to one of the envelope forms. The schematic drawings of Figure 5 show the conformational trends which it is assumed are initiated by the substituents; they do not pretend to be exact representations of the conformations.If (1A) (Figure 5 ) depicts the con- formation of ring A of the unsubstituted A-nor-steroid (l), a 3p-methyl group (11A) will show strong repulsion with the lop-methyl, and ring A can avoid this by pseudo- rotation towards the ‘ p-envelope ’ (04) as in (11A’) ; the Cotton effect will thus decrease. A I@-methyl group [in (12)] will also tend to be repelled by the lop-methyl (becoming ‘ more equatorial ’ at the same time) ; however, interaction with the 1 l-methylene group will limit this distortion, so that ring A will change nearer to a perfect C, form (12A‘), and [R] will increase. The 3a-methyl group of (10) tends to adopt a ‘more equatorial’ position, and will induce a slight pseudo- rotation opposite to that induced by the lp-methyl; the c.d. again decreases as ring A is distorted to conform- ation (10A’) (‘ a-envelope ’).As the Figure shows [(13A) -+ (13A’)], a 1p- and a 3p-methyl assist each other in such a pseudorotation, and the decrease of [R] is thus greater, if both these groups are present. On the other hand, in the lp,3~-epimer (14) the trends induced by the two methyl groups are in opposite directions; the observed decrease in [R] could not therefore be predicted. We now consider the quasi-enantiomeric series of D ring 16-ketones. Ring D in (15) can adopt a conform- ation, which is approximately the mirror image of that of ring A in the A-nor-%ketones. Owing to the presence of the 17p-methyl group, ring D in compound (19) will pseudorotate more than was the case for the A-nor ring in the comparable structure (12), because a methylene group (corresponding to C-ll), which could interfere, is lacking in (19).Conformation (19D’) (‘ p-envelope ’) will lead to a smaller negative [R] value, which is equivalent to an apparent positive contribution of the 17p-methyl. Intrinsic contributions cannot be attri- buted to the methyl groups themselves, because while, for example, lp- and 17p-methyl groups are situated in a t Q x 77 (15 D) (19 D) (19 D’) FIGURE 5 Schematic octant projections of rings A and D in compounds (l), (lo), (ll), (12), (13), (ls), and (19). For details see Discussion section. The symbols and denote conformational changes by pseudo-rotation (in opposite senses) to relieve non-bonded interactions; e- = methyl group positive and a negative octant, respectively, their total contributions (direct and indirect) with reference to the non-methylated ketones are in both cases $ositive (A[R] +2.6 and +0.9, or Act +34 and +14).The two morpholino-derivatives (2) and (3) both gave positive c.d. values, but no conclusion about the con- formation of ring A can be drawn, because reference compounds with comparable structures are not available. The stereochemistry of these compounds is deduced from the fact that they were obtained under equilibration conditions. In the n.m.r. spectra the presence of the morpholinomethyl group at 3a, l p , or 17p has only a slight influence on the chemical shifts of the methyl groups 18 and 19. The c.d. values for these morpholino- derivatives as well as some values for the other saturated ketones in methanol and hexane solution are given in Table 2.Fine Strzcctztre.-Consideration of the fine structure ofOrg. 429 the c.d. curves of the A-nor-%ketones and 16-ketones in the solvent MI,, reveals inter alia two maxima in each case at about 310 and 300 nm., respectively (cf. ref. 13). For most compounds, the maximum at 310 nm. is more intense. The two exceptions [compounds (11) and (13), for which the maximum at 300 nm. is the more intense] are the compounds carrying a 3p-methyl group, which are expected to give greatest changes in the conformation of ring A. The significance of these details is not clear at the moment. 0 . r . d . iVeaszl.re.ments.-Comparison of 0.r .d. amplitudes and c.d. AE values (for solutions both in methanol and in hexane) gave in all cases ratios of a to AE close to the theoretical value 14 of 40.Little regularity was found in the differences of amplitude between solutions in methanol and hexane. Parallel studies on a wide range of decalones (ref. 15) would lead us to choose hexane (or a mixture of hydrocarbons, such as MI,) as a standard of reference, since it is a non-polar and (largely) non- associating solvent. 01, p-Unsatwated Ketones.-(a) Transoid cyclopent- enones. The n + x * c.d. bands of twisted transoid cyclopentenones can be correlated empirically with their chirality; a 3-en-2-one in the A-nor series gives a negative Cotton effect l6 and both (7) and (8) show the same sign (see Table 4). The second methyl group of (8) will introduce a greater deviation from coplanarity and the n + x* c.d. value is enhanced, as expected.In ethanolic solution (7) gives two further optically active bands at 241 and 211 nm., the first corresponding to the ;I: +7t* absorption; the second is perhaps of n -+ o* origin (cf. some recent results with saturated ketones 17). The characteristics of these c.d. spectra are, therefore, similar to those of cyclohexenones.l* C.d. n + x * and x + x * bands do not always show opposite signs in the case of these enones; compound (7) is, for example, an exception. The presence of two or three bands in the ' K-band region' in these c.d. spectra makes it difficult to apply the rule proposed for the correlation of the helicity of an enone with the sign of its K-band Cotton effect.19 (b) Cisoid mefhylenecyclopentenones.The Cotton effects of very few cisoid cyclopentenones are known, and the R-band c.d. value of 17-acetoxy-~-noroestr-5- en-3-one 2o follows the rule proposed for cisoid cyclo- hexenones6 Dreiding models of the exocyclic methylene ketones (4), (5), (6), and (18), indicate that the angle between the planes of the C=O and the C=C groups is so small that dissymmetry of the first sphere can be neglected. We would then expect the second sphere, which is strongly chiral in these compounds, to deter- mine the sign of the c.d., and indeed the R-band Cotton l3 K. M. Wellmann, Y. H. A. Laur, W. S. Briggs, A. Moscowitz, and C. Djerassi, J . Amer. Chem. SOC., 1965, 87, 66; 0. E. Weigang, jun., J . Chem. Phys., 1965, 43, 3609. l4 S. F. Mason, Quart. Rev., 1963, 1'9, 20.D. N. Kirk, W. Klyne, and S. R. Wallis, J . Chem. SOG. ( C ) , 1970, 350. R. Hanna, T. Riill, and G. Ourisson, Bdl. Soc. chim. FItaPzce, 1961, 1209. effects all have the same sign as the n 3 X* bands in the c.d. spectra of the corresponding saturated compounds [positive for (a), (5), and (6), negative for (IS)]. Eicr-Androstan-16-ones e0 A 15 H (15) I %* H ( 2 R (16) R1 = morpholinomethyl, R2 = H (17) R1 = H, R2 = morpholinomethyl (18) (22) (23) R1= CH,, R2 = Hz R1 = H2, Ra = CH, R1= Re = CH, H H (20) R1= Me, R2 = H (21) R1 + R2 = CH, (19) All formulae (16)-(23) are 5a-androstane derivatives unsub- stituted except in ring D The x + n * c.d. above 230 nm. in all cases has the opposite sign to the R-band. The band a t still shorter wavelengths (ca.215 nm., origin unknown) is negative for both (5) and (18); it could not be measured for (4). The cross-conjugated dienone (6) shows three bands below 300 nm. of roughly the same appearance as has been found, for example, for 1 ,4-dien-3-ones.ls EXPERIMENTAL Preparative Work.-This was all carried out by the French group. M.p.s were determined with a Kofler hot- stage apparatus. Optical rotations in the visible region were recorded for solutions in dioxan with a Perkin-Elmer 141 instrument. 1.r. spectra were obtained with a Perkin- Elmer Infracord 337 spectrophotometer, U.V. spectra with a Perkin-Elmer spectrophotometer, and n.1n.r. spectra, for solutions in deuteriochloroform, with Varian A60 or HA100 instruments, with tetramethylsilane as internal standard; shifts are expressed as 6 values (p.p.m.).(For c.d. and o.r.d., see later). Analyses were carried out by the Service Central de Microanalyse of the C.N.R.S. The ' usual work-up ' indicates extraction of the product into l7 H. H. Perkampus, Angew. Chem., 1968, 80, 613 (Intevnat. Edn.), 7, 626). L. Velluz, M. Legrand, and R. Viennet, Compt. rend., 1966, 261, 1687. 19 C. Djerassi, R. Records, E. Bunnenberg, K. Mislow, and A. Moscowitz, J . Amer. Chem. Soc., 1962, 84, 870. 2o R. M. v. d. Bosch, M. S. de Winter, S. A. Szpilfogel, H. Herrmann, P. Witz, and G. Ourisson, BUZZ. SOC. chim. Fvance, 1963, 1090.430 J. Chem. SOC. (C), 1970 ether (washing with dilute aqueous acid or alkali if appro- priate) , washing with water, drying (Na2S04), and evapor- ation to dryness. Derivatives of ~-Nor-5a-androstan-2-one.*-17p-Acetoxy- 1 f3-mor~hol~nomethy~-~-nor-5a-androstan-2-one (2) and 17p- acetoxy-3a-~~lor~hoZinonzethyl-~-nor-5~-andros€an-2-one (3). A mixture of 17~-acetoxy-~-nor-5a-androstan-2-one (la) (12.0 g.), morpholine hydrochloride (10.2 g.) , and para- formaldehyde (1.92 g.) , in suspension in nitromethane (120 ml.) containing l0N-hydrochloric acid (ca. 0.5 ml.) was heated a t 100"; the mixture rapidly became homogeneous. After 1 hr. nitromethane was evaporated off under reduced pressure. The residue was stirred with water and the precipitate which formed [recovered starting ketone (6.2 g.)] was filtered off and washed with water. The aqueous solution was made alkaline with ammonia, extracted with ether, and worked up in the usual way.The partially crystalline residue (7.2 g.), when triturated with ether, gave a sparingly soluble base (1-6 g.) which yielded the pure 3a-morpholinomethyZ ketone (3) (1.06 g . ) , m.p. 184-185" (from methoxyethanol) , [a]578 + 122", (G 0.22); 6 0.81 [C(18)H3] and 0.865 (broader) [C(19)H3] (Found: C, 71.7; H, 9.6; N, 3.6. C25H39NO4 requires C, 71.9; H, 9-4; N, 304%). The mother liquors from which (3) had been separated were evaporated and treated with hot hexane, and some insoluble base was filtered off. On cooling the isomer (2) crystallised. The product, recrystallised several times from hexane, had m.p. 118-119', [a1578 +130"; 6 0.82 [C(18)H3] and 0.85 [C(19)H3] (Found: C, 71.9; H, 9.2; N, 3-4. C2,H3,N04 requires C, 71.9; H, 9.4; N, 3.4%). The purity of each isomer was verified by t.1.c.analysis on silica gel (hexane-diethylamine, 9 : 1) ; the compound (3), m.p. 185O, is eluted first. 17~-Acetoxy-l-rnethyZene-~-nor-5a-androstan-2-one (4). A solution of the Mannich base (2) (250 mg.; m.p. 117- 11.9') in a 1 : 1 mixture (2 ml.) of acetic acid and acetic anhydride was heated a t 100" for 2 hr. Addition of water gave a product (m.p. 99-100") which yielded the 1- methylene ketone (4) , m.p. 115" (from aqueous methanol), [a]3l3 - 1635" (G 0.16) ; Lax.(EtOH) 229 nm. (c 5500) ; 6 0.84 [C(l8)H3], 0.98 [C(19)H3], and 5-3 and 5.77 [C(1):CH2] (Found: C, 76.0; H, 9.3. C21H3003 requires C, 76-3; H, 9.15%). 17~-Acetoxy-3-methyZene-a-nor-5cr-and~ostan-2-one (5). The Mannich base (3) (160 mg.; m.p. 185') on similar treatment gave the 3-methylene ketone (5), m.p.ll4-115", and [a]313 -1715" (c 0.14); A,, (EtOH) 231 nm. (E 7960); 6 0-81 [C(18)H3], 0.74 [C(19)H3J, and 5.0 and 5.9 [C(3):CH2] (Found: C, 76.45; H, 8-9. C21H3@3 requires C, 76.3; H, 9.15%). 17p-Acetoxy-3-methyZene-~-.~zor-5a-androstan-2-one (5) and 17~-acetoxy-1,3-divnethylene-~-no~-5~-and~ostan-2-one (6). A mixture of 17~-acetoxy-~-nor-5a-androstan-2-one (la) (5.0 g.), morpholine (5.5 g.), paraformaldehyde (1.9 g.), and acetic acid (50 ml.) was heated under reflux for 10 min. It was then treated with dilute hydrochloric acid and extracted with ether. The neutral material in the ethereal solution, * The n.m.r. spectrum of this compound (Id) (100 MHz) shows a doublet at 0.84 p.p.m. ( J 0.9 c./sec.) for the lop-methyl group. The signal of the 13p-methyl group (0.72 p.p.m.) shows a suggestion of splitting.[a1546 +145", [a1436 -k312", [a1364 +7790J and [a1313 +16500 [a1578 +223", [a1546 $-2680, [a1436 +6900J [a1364 f1955", and [a1578 + 142*5"J [a1548 + i73*5", [a1436 +487*5", [a1364 + 1858"j after the usual work-up, yielded an oily fraction (2.9 g.). The acidic aqueous solution was made alkaline with ammonia and extracted with ether; the usual work-up gave an oily basic fraction (4.3 g.). This material was heated with a 1 : 1 mixture (50 ml.) of acetic acid and acetic anhydride a t 100" for 2.5 hr. The cooled mixture was diluted with water, and then treated like the previous crude product, yielding a second neutral fraction (2-0 g.; oil). The two neutral fractions were combined and chromato- graphed on a silica gel column (hexane-ethyl acetate, 7 : 3), yielding the pure dimethylene ketone (6) and fractions enriched either in (5) or in (6).Preparative t.1.c. on silica gel (Merck GF,,,) in hexane-ethyl acetate (7 : 3), after several developments, separated the two products in a pure state. The dimethylene ketone (6) had m.p. 103-104" (from pentane), [aIDz3 +149" (G 0.5); &,(EtOH) 258 nm. (E 8800); 6 0.85 [C(18)H3], 0-89 [C(19)H3], 5-45 and 5.9 [C(l):CH,], and 5.15 and 6.0 [C(3):CH2] (Found: C, 77.3; H, 8.9. C,2H3003 requires C, 77.15; H, 8.8%). 17p-Acetoxy-3-methyZ-~-norandrost-3-en-2-one (7a). The 3-methylene ketone (5) (0.1 g.) , 5% palladium-charcoal (0.1 g.), and cymene (6 ml.) were refluxed for 1.5 hr. The catalyst was filtered off and washed with ether.Evapor- ation of the organic solvents in vacuum yielded the isomeric unsaturated ketone (7a), m.p. 135' (from aqueous methanol), +422" (c 0.06); &,(EtOH) 242 nm. (E 15,100); 6 0.82 [C(18)H3], 1.10 [C(19)H3], and 1.62 [C(3)H3] (Found: C, 76.0; H, 8.85. C21H3003 requires C, 76.3; H, 9.15%). Saponification of the acetate (7a) with sodium hydroxide in methanol-water (4 : 1) yielded the hydroxy-compound (7b) as thin needles, m.p. 143" (from aqueous methanol), (Found: C, 78.8; H, 9-5. C1,H2,02 requires C, 79.1; H, 17P-Acetoxy-1~,3-d~vnethyl-~-norandros€-3-en-2-one (8). The reaction was carried out like the preparation of (7a) from (5) [from (6) (0-35 g.), 5% palladium-charcoal (0.35 g.), and cymene (20 ml.)]. The crude product was purified by preparative t.1.c.on silica gel merck GF254 ; hexane- ethyl acetate (8 : 2); three developments] to give crude (8) (0.2 g.; m.p. SOo); this was recrystallised from aqueous methanol; m.p. 90-92", [aID21 - 18.6" (G 0.8) ; A,,(EtOH) 242 nm. (c 13,900); 6 0.84 [C(18)H3], 1.0 [C(19)H3], 1.10 [d, C(l)H3], and 1.65 [C(3)H3] (Found: C, 76.95; H, 9.6. C2,H3203 requires C, 76.7; H, 9.4%). 1 7 P-A cetoxy-3a-bromomethyZ-~-nor-5a-androstan-2-one (9). A solution of the methylene ketone (5) (250 mg.) in acetic acid (2.5 ml.) containing 10% hydrogen bromide was left overnight. Addition of water precipitated the bronzo- compound (9) (250 mg.); this when recrystallised from ethanol had m.p. 158", +106-5", [a1546 +126-5", [a1436 +284", [a]384 +750", and [a1313 f1330" (G 0.2) (Found: C, 61.2; H, 7.6.C2,H3,Br03 requires C, 61.3; H, 7.6%). 17f3-Acetoxy-3P-r~zethyl-~-nor-5a-androstan-2-one (1 1). The methylene ketone (5) (1.4 g.) was hydrogenated in ethanol (40 ml.) over Brown's catalyst.21 [Nickel acetate (1.75 g.) in water (70 ml.) was treated with aqueous 0- lM-potassium borohydride (21 ml.). The black precipitate was de- canted, and washed with water (three times) and then with ethanol (three times) , by decantation.] The solution was filtered and evaporated; t.1.c. analysis on silica gel G 21 C. A. Brown and H. C. Brown, J . Anzer. Chem. SOG., 1963, 85, 1003. [a], -k20"J [a1578 +12"> [a1436 -250, [a1364 and [a1313 17P-Hydroxy- 3-wi?ethyZ-~-norandrost-3-en-2-one (7b) * [ElD +13", [a1578 +lo', [El436 -42", and [a1364 -106" (c 0.28) 9.8cyo) *Org.431 (hexane-ethyl acetate, 8 : 2) then showed the presence of three components. Preparative t.1.c. of this product (186 mg.) on silica gel G (pulverised with berberine hydro- chloride) gave (i) a compound (12 mg.), probably ( 7 4 , (ii) a mixture (80 mg.) of (loa) and ( l l ) , and (iii) a pure compound (1 1) (46 mg.) . The 3P-methyZ-2-ketone (1 1) had m.p. 130", [a], +137" and [a1364 +812" (c 0.12); 6 0.79 [C(18)H3J, 0.86br [C(19)H3], and 1.07 [d, C(3)H3] (Found: C, 75.4; H , 9.35. C21H3203 requires C, 75.9; H, 9.7%). 17~-Acetoxy-3a-r~zethyZ-~-nor-5a-androstan-2-one (1Oa). A solution of the methyl ketone (1 1) or of the mixture of (1 Oa) and (11) was set aside in acetic acid containing 10% hydrogen bromide for 3 hr. Dilution with water precipi- tated crystalline 3a-methyl-2-ketone (lOa), m.p.124" (from hexane or from aqueous ethanol), [&I5,* + 102*5", [a]36p + 767", and [a]313 +2450" (c 0.14); 6 0-81 [C(18)H3], 0.875br [C(19)H3], and 1.01 [d, C(3)H3] (Found: C, 75.7; H, 9.5. C21H3203 requires C, 75.9; H, 9.7%). 1 7P-Hydroxy-3cr-methyl-~-nor-5a-androstan-2-one ( lob). This was prepared by refluxing (loa) (385 mg,) in ethanol (10 ml.) containing 10N-sodium hydroxide (0.5 ml.) for 30 min. Addition of water precipitated the hydroxy- compound (lob) (277 mg.), m.p. 154" (from aqueous methanol), [a]578 + 132-5', [a1546 + 156.5", [a1436 +356", +940°, and 3-3350" (c 0.08) (Found: C, 78.5; H, 10.2. C1,H3,02 requires C, 78.6; H, 10.4%). 17P-Acetoxy-1 P-methyl-~-nor-5a-androstan-%one (12a). The methylene ketone (4) (830 mg.) was hydrogenated in ethanol (1 5 ml.) over 5% palladium-charcoal (450 mg.) .The catalyst was filtered off and the 1P-methyL2-ketone was precipitated with water, m.p. 134" (from aqueous ethanol), +830", and [a]313 +2560" (c 0.13); 6 0.80 [C(18)H3], 0.71 [C(19)H3], and 1.07 [d, C(1)H3] (Found: C, 76.0; H, 9.7. C21H3203 requires C, 75.9; H , 997%). 17P-Hydroxy- 1 p-methyl-~-nor-5a-androstan-2-one (1 2b). Hydrolysis of the acetate (12a) as for (loa) yielded the hydroxy-ketone (12b), m.p. 164' (from aqueous ethanol), C,9H3002 requires C, 78.6; H , 10-4y0). 17P-Acetoxy-lP,3P-dimethyl (and 1 P, 3a-dirnethyl)-a-nor-5a- androstan-2-ones (1 3) and (14). Method (i). The unsatur- ated ketone (6) (200 mg.) was hydrogenated in dimethyl- formamide (12 ml.) over 5% palladium-charcoal (80 mg.).The catalyst was filtered off, the solution was diluted with water, and the product extracted with ether. T.1.c. analysis [on silica gel G pulverised with berberine hydro- chloride; hexane-ethyl acetate (85 : 15)] showed three components. Preparative t.1.c. under the same conditions (several developments) yielded three fractions : A (30 mg.) (13 + 14), B (50 mg.) (13), and C (70 mg.) (8). Fraction A was treated with 10% hydrogen bromide in acetic acid ( 5 ml.) for 48 hr. Dilution with water and extraction with ether yielded pure (14). Method (ii). The unsaturated ketone (6) (125 mg.) was hydrogenated in ethanol (10 m1.) over Brown's catalyst,21 prepared from nickel acetate (175 mg.) as before: the absorption of hydrogen was very slow.Preparative t.1.c. (as before) separated (14) (43 mg.), (13) (46 mg.), and (8) 17P-A cetoxy-l P, 3P-dimethyl-~-nor-5c-androstan-2-one ( 13) had m.p. 139-140°, [a],25 + l O l " (c 0.1); 6 0.80 [C(18)H3] and 0.74 [C(19)H3] (Found: C, 76.3; H, 10.0. C,,H3,03 requires C, 76.3; H, 9.9%). !X]D +I1Oo, [a1578 +117", [a1546 +140", "1436 +375", [a1364 [@.I578 +145", [a1546 +173", [a1436 $387", [a1364 +993", and +2970" (c 0.16) (Found: C, 78.6; H, 10.2. (8 mg*)* 17P-A cetoxy-l p, 3a-dzunethyZ-~-nor-5u-androstan-2-one (1 4) had m.p. 116-118", [aID25 f72" (c 0.1); 6 0.80 [C(18)H3] and 0.74 [C(19)H3] (Found: C, 76.3; H, 9.9. C22H3403 requires C, 76.3; H, 9.9"/0). Derivatives of 5u-Androstan-16-one (15) .-17p- and 15cc- Mor~holinomethyZ-5~-androstan-16-one (1 6) and (1 7). These compounds were prepared from 5a-androstan-l &one (1 5) (4.3 g.) by the method described for the preparation of (2) and (3).At the end of the reaction, nitromethane was removed, the residue was treated with water, and un- changed starting ketone (2.5 g.) was extracted with ether. (i) A hydrochloride (insoluble in each phase) was filtered off, treated with ammonia and extracted with ether. The Mannich base (16) so obtained (550 mg.) was recrystallised twice from di-isopropyl ether; m.p. 205", - 115" (c 1) ; 6 0.88 [C(18)H3] and 0.81 [C(19)H3] (Found: C, 77.6; H, 10.25. C2,H3,N02 requires C, 77.2; H, 10.5%). (ii) The acidic aqueous phase, from which the hydro- chloride of (16) had been filtered, was made alkaline with ammonia and extracted with ether. On evaporation the product (1.3 g.) crystallised partially when triturated with ether; the crystalline material (0-3 g.) was impure Mannich base (16) (m.p.188-190"). The mother liquors from this were evaporated to dryness and treated with methanol, yielding Mannich base (17) (0.2 g.), m.p. 117-122'; this was recrystallised from aqueous methoxyethanol; m.p. 124O, [aID2O -147" (c 1); 6 0.73 [C(18)H3] and 0.82 [C(19)H3] (Found: C, 77.0; H, 10.4; N, 4.0. C&&gNO2 requires C, 77.2; H , 10.5; N, 3.75%). The purity of the two isomers was verified by t.1.c. analysis (plates prepared with 0*5~-sodium hydroxide instead of water). 17-Methylene-5u-androstan- 16-one (1 8). This was pre- pared from the Mannich base (16) (400 mg.) by the method used for the preparation of (4).The methylene ketone (18) (280 mg.), m.p. 103" (from aqueous methanol), - 197", [a]57822 -251", [ ~ ] ~ ~ ~ 2 2 -712", and [a]36422 -1260" (G 0-6); &,(EtOH) 232 nm. (E 6550); 6 0.94 [C(18)H3] and 0.S25 [C(19)H3] (Found: C, 83.6; H , 10.2. C2,H300 requires C, 83.9; H, 10.6%). 17P-MethyE-5a-androstan-16-0ne (1 9). Hydrogenation of the methylene ketone (18) (280 mg.) by the method used for the preparation of (12a) yielded the 17P-methyZ-16-ketone (19) (175 mg.), m.p. 139" (from methanol), [a]57825 -158" and [a]54625 -187" (G 0.8); 6 0.66 [C(18)H3] and 0.82 [C(19)H3] (Found: C, 83.5; H, 11-05. C20H320 requires C, 83.3; H , 11.2%). 17-Methylene-5a-androstane (21). This compound was prepared by the method used by Dvolaitzky and Jacques 22 for the preparation of 3P-hydroxy-l7-methylene-5~~-andro- stane from 3P-hydroxy-5a-androstan-17-one (isoandro- sterone).5a-Androstan-17-one (2.0 g.) yielded the 17- methyleneandrostane (21) (1.4 g . ) , which was distilled; b.p. 135-175°/0~025 mm. The product, recrystallised from methanol, had m.p. 69-70", +12" (c 0.7); 6 0.77 [C(18)H3] and 0.79 [C(19)H3] (Found: C, 88.5; H, 11.6. CZoH32 requires C, 88-2; H , 11.8%). 17P-Methyl-5a-androstane (20). Method (i) . 17- Methylene-5a-androstane (21) was reduced by the method used for the preparation of (12a). 17P-MethyZandrostane (20) had m.p. 100" (from methanol), [a]5,826 3-7.1" (c 0.7), 6 0.525 [C(18)H3] and 0.785 [C(19)H3] (Found: C, 87.2; H, 12.65. C2oH34 requires C, 87.5; H , 12.5%). The base of m.p. 205" was eluted first. 22 M. Dvolaitzky and J.Jacques, Bull. SOC. chim. Fmnce, 1963, 2793.J. Chem. SOC. (C), 1970 Method (ii). The 17P-methyl-16-ketone (19) (65 mg.), sodium hydroxide pellets (100 mg.), hydrazine hydrate (0.2 ml.), and diethylene glycol (2.5 ml.) were heated under reflux for 2.5 hr., then at 190-195' for 3-5 hr. The mixture was cooled, diluted with water, and extracted with ether. The product (43 mg.) had m.p. 96-98" (from methanol), not depressed by admixture with the compound (m.p. 100') prepared from (21). The i.r. spectra and the g.1.c. retention times were identical (column 5% SE 30 on Chromosorb W 60-80 ; temperature 230'). 17-Methylene-5u-androstan-16-one (18) and 15,17-Di- nzethylene-5a-androstan- 16-one (23). These compounds were prepared from the 16-ketone (15) by the method used for the preparation of (5) and (6). Ketone (15) (500 mg.), morpholine (530 mg.), paraformaldehyde (200 mg.) , and acetic acid (15 ml.) were refluxed for 3 hr. An oil (500 mg.) was isolated, which on treatment with methanol yielded crystals (170 mg.; m.p. 80-84'). These were recrystal- lised from the same solvent, giving a product, m.p. 99- loo", not depressed by admixture with pure 17-methylene- 5a-androstan-16-one (18) (m.p. 103') ; the i.r. spectra were identical. Preparative t .l.c. [silica gel Merck GF,,* ; hexane- ethyl acetate (97 : 3)] of the mother liquors gave, after five developments, the 15,17-dirnethyZeneketone (23) (100 mg.), m.p. log', [u]D22 - 161' (c 0.8) ; a,. (EtOH) 258nm. (E 9150) : 6 0.87 [C(18)H3], 0.87 [C(19)H3], 5.4 and 6.0 [C(15):CH2], and 5.1 and 5-85 [C(17):CH2] (Found: C, 84.4; H, 10.2. C21H,,0 requires C, 84.5; H, 10.l~o). C.d. and 0.r.d. Measuvements.-Studies at Bonn com- prised c.d. measurements for solutions in methylcyclo- hexane-isopentane (1 : 3 v/v) (MIl3) and, in a few cases, in ether-isopentane-ethanol (5 : 5 : 1 v/v) (EPA,,l) for the saturated ketones at room temperature (ca. 20') and at low temperature (ca. - 180') ; solutions of the unsaturated ketones in dioxan and ethanol at room temperature were also studied. Studies at Westfield included 0.r.d. and c.d. measure- ments for solutions both in methanol and in hexane (at room temperature only) ; measurements on the unsaturated ketones were not made at Westfield. C.d. data were obtained at Bonn with the Jouan Dichro- graphes (early model and new model ' 185 '); cells of 2, 1, 0.1, and 0.01 cm. pathlength were used. Low temperature c.d. spectra were measured as described in ref. 23. 0.r.d. and c.d. measurements at Westfield were made with the Bellingham and Stanley-Bendix Spectropolarimeter, Polarmatic '62; for details, see ref. 16. G. S. thanks Miss H. Raeder and Mr. E. Kirmayr for technical assistance and the Deutsche Forschungsgemein- schaft for financial support. The Laboratoire de Chimie organique du CollQge de France is associated with the C.N.R.S. The French group thank Madame LaCombe for the n.m.r. data. W. K. and S. R. W. thank the S.R.C. for a grant. [9/1231 Received, July Zlst, 19691 23 G. Snatzke, D. Becher, and J. R. Bull, Tetrahedron, 1964, 20, 2443; G. Snatzke and E. Schwinum, ibid., 1966, 22, 761.
ISSN:0022-4952
DOI:10.1039/J39700000423
出版商:RSC
年代:1970
数据来源: RSC