Circular Dichroism of Dissymmetric up-Unsaturated Ketones BY R. E. BALLARD, S . F. MASON AND G. W. VANE Chemistry Dept., University of Exeter Received 11th April, 1963 A number of dissymmetric a&unsaturated ketones have been found to give a circular dichroism absorption which changes sign in the frequency region of the long wavelength absorption band. From a study of the variation of the circular dichroism with temperature the phenomenon is shown to be due to rotational isomerism in conformationally-labile monocyclic ketones. The rotational isomers of (-)-carvone are identified, and the enthalpy difference between the isomers is evaluated. A possible vibrational origin of the phenomenon in conformationally-rigid ketones is discussed. A number of steroidal ap-unsaturated ketones have been found to give in the 3000-4000 A region associated with the carbonyl n+n* transition a circular di- chroism absorption which changes sign as the progression in the upper-state car- bony1 stretching vibrational mode moves to higher quantum numbers.ll 2 In the light of the one-electron theory of optical rotatory power,3 this observation indicates that electronic transitions occur from at least two main nuclear configurations of the electronic ground state, one giving the positive and the other the negative circular dichroism. The two nuclear configurations may arise either from the two turning points of a vibration excited in the electronic ground state, or from different conformations or rotational isomers of the molecule in the ground state.The temperature vari- ation of the circular dichroism distinguishes between these two possibilities.On lowering the temperature, the areas of both the positive and the negative circular dichroism bands should decrease on the vibrational turning-point hypothesis, since the population of molecules vibrationally excited in the electronic ground state is reduced, whereas, if rotational isomerism obtains, the circular dichroism band area of one sign should decrease whilst that of the opposite sign should increase, owing to the shift in the equilibrium between the conformations. In generaI, the steroids are fixed in one particular conformation,4 owing to the condensed system of cyclohexane rings in the chair form, so that the vibrational origin of the two nuclear configurations appears, at first sight, to be the more probable.If the vibrational mechanism obtains, the turning-point nuclear con- figurations giving, respectively, the positive and the negative circular dichroism ab- sorption may be identified in a dissymmetric ketone with a known absolute stereo- chemistry, and the particular configuration associated with the larger transition probability would indicate the likely structure of the upper electronic state resulting from the n+n* transition of the ketone. In the present work these possibilities have been investigated, using monocyclic terpenoid ketones, which are less complex and more volatile than the steroids studied previously.l.2 The measurement of the absorption and the circular di- chroism spectra in the vapour phase and in paraffin hydrocarbon solutions is reported for two ap-unsaturated dissymmetric ketones with known 5 absolute stereochemistry, namely, (-)-camone (I) and (-)-8-methoxycarvotanacetone (11).4344 CIRCULAR D I C HRO I S M 0 F U p - U N S A T UR A T ED KE T 0 NE S Both compounds give, in the wavelength region of the n+n* transition centred at 3500A, a circular dichroism absorption which undergoes a change of sign as the progression in the upper-state carbonyl-stretching vibrational mode (v N 1200 cm-1) moves to higher quantum numbers, and, in the region of the n+n* transition of the @unsaturated ketone chromophore near 2350 A, a positive circular dichroism band which is very weak in relation to the intensity of the unpolarized absorption At low temperatures the band area of the positive circular dichroism absorption is enhanced, whilst that of the negative circular dichroism is decreased (fig.1). Thus the change in the sign of the circular dichroism given by (I) and (11) in the 3000- 4000A region is due primarily to rotational isomerism, and it is concluded either (fig* 1)- FIG. the 40 30 20 10 1 I 3500 30'00 2iOO A (A) 1 .-The absorption -.-.-.- and the circular dichroism ~ of (-)-camone (I), and circular dichroism - - - - of (-)-8-methoxycarvotanacetone (11) in methylcyclohexane solution at 290"K, and the circular dichroism - - - - of (-)-carvone (I) at 195°K. that the phenomenon has a different origin in terpenoid and steroid @unsaturated ketones or, more probably, that the steroid ketones are conformationally more labile than is commonly supposed.From the known 5 absolute stereochemistry of (-)-carvone (I) and the observed variation in the circular dichroism of the compound with respect to temperature (fig. 1) it is possible to deduce the nuclear configurations of the two rotational isomers in equilibrium and the enthalpy difference AH between them. The area of a circular dichroism band given by a dissymmetric compound measures the rotational strength of the electronic transition responsible for the absorption of radiation in the wavelength region considered. The rotational strengthR. E . BALLARD, S . F. MASON A N D G . W. VANE 45 R represents 3 the scalar product of the electric, p , and the magnetic, p, dipole moments of the transition, (1) where 8 is the angle between the directions of the two moments.The angle-depend- ency of the rotational strength allows the formulation of rules which connect a particular structural configuration with a given sign of the optical rotatory power. The diene 6 and aP-unsaturated ketone 7 rules associate a positive Cotton effect in the wavelength region of the lowest-energy 71-+71* transition with the non-planar configuration which gives the chromophore the form of a right-handed helix, and the octant rule 8 relates in detail the structural dissymmetry of an optically active ketone to the sign of the rotatory power of the 3000A absorption. Tn a dissymmetric ketone, the nodal planes of the oxygen 2p, lone-pair orbital and the carbonyl antibonding 71% orbital (111) divide the molecular environment of the carbonyl group into eight spatial regions, of which the four rear octants in the -z hemisphere are generally the more important.A group or atom, other than fluorine, placed in the upper-left or the lower-right rear octant (LV), relative to an observer viewing the molecule in the -z direction (111), gives the ketone a positive rotational strength at 3000 A, whereas the corresponding substitution in the upper- right or lower-left rear octant (IV) confers a negative rotatory power upon the ketone in that wavelength region. R = pp cos 0, 7 fy 7 $-.ye 6 IT 0 0 r The positive circular dichroism band at 2350A in the spectrum of (-)-carvone (I) indicates, from the chirality rule 7 for ap-unsaturated ketones, that the carbonyl group and the 1,Zvinyl group of (I) form a segment of a right-handed helix in the dominant rotational isomer.The ap-unsaturated carbonyl chromopliore of (I) assumes the form of a right-handed helix when the 4-propenyl group has an equatorial conformation relative to the cyclohexenone ring (V), whereas the chromophore adopts the form of a left-handed helix if the 4-propenyl group has the axial conformation (VI). The octant rule 8 suggests that the axial isomer (VI) should have a strong nega- tive rotational strength at 3500& and that the equatorial isomer (V) should have only a moderate positive rotational strength in the same wavelength region, so that46 CIRCULAR DICHROISM OF QP-UNSATURATED KETONES the circular dichroism spectra of (I) and (11) measured at room temperature are consistent with an equilibrium mixture consisting predominantly of the equatorial isomer (V) and only a small percentage of the thermodynamically less stable axial isomer (VI).o=c The variation in the circular dichroism absorption with temperature gives the enthalpy difference AH between the two rotational isomers. At the absolute temperature T, the differential decadic molar extinction coefficient for left and right circularly polarized light, (Ae = el-er), is given by AeT = Aem + ( A E ~ - A E ~ ) tanh (AH/2RT), (2) where Ae, and ALEO are, respectively, the limiting high- and low-temperature values of the circular dichroism. On fitting the observed circular dichroism absorptions at different temperatures to eqn. (2) it is found that the enthalpy difference between the rotational isomers, (V) and (VI), of (-)-camone (I) is 2-0 kcal mole-1.This estimate is sensitive to the values of the circular dichroism observed at low temperature, and there is the possibility that an equilibrium composition at higher temperatures is frozen-in on cooling. However, the equilibration of the rotational isomers of (-)-cawone (I) is probably fast at the lowest temperature studied (195"K), since the rate constant for the chair-chair interconversion of cyclohexane 9 is 52.5 sec-1 at 206°K. Moreover, the enthalpy difference between the axial and the equa- torial isomers of methylcyclohexane in the chair form 10 has the comparable value of 1-8 kcal mole-1. Relative to the corresponding equatorial isomers, the axial isomers of methylcyclohexane and (-)-carvone (I) are probably destabilized, owing to steric compression, to a similar degree, for although the propenyl group is larger than the methyl group there are, in the isomer (VI), no axial hydrogen atoms on the same side of the ring as the propenyl group, the carbon atom at the 2- and the 6- position of (-)-carvone (I) being trigonal.EXPERIMENTAL MATE~UALs.--(-)-8-Methoxycar~0tanacetone (11) was prepared from (-)-carvone (I), obtained commercially, according to the directions of Buchi and Erickson,ll as modified by Djerassi et al.12R . E. BALLARD, S . F. MASON AND G . W. VANE 47 SPECTRA.-Absorption spectra were measured with an Optica grating spectrophoto- meter, and the circular dichroism spectra with an instrument constructed in these labor- atories 13 and with a Jouan Dichrograph.The spectra were measured in the vapour phase, and in isopentane, methylcyclohexane, and ethanol solution, using a silica dewar flask fitted with an optical cell for measurements over the temperature range, 195-500°K. The authors wish to thank the Royal Society, Messrs. Albright and Wilson Ltd., and the Imperial Chemical Industries Ltd., for the components used to construct the circular dicliroism spectrophotometer, and the D.S.I.R. for the provision of a Jouan Dichrograph. 1 Velluz and Legrand, Angew. Chem., 1961,73, 603. 2 Mason and Vane, unpublished observations. 3 Mason, Quart. Rev., 1963,17,20. 4 Fieser and Fieser, Steroids (Chapman and Hall, London, 1959). 5 Birch, Ann. Reports, 1950, 47, 190. 6 Moscowitz, Charney, Weiss and Ziffer, J. Amer. Chem. SOC., 1961, 83,4661. 7 Djerassi, Records, Bunnenberg, Mislow and Moscowitz, J. Amer. Chem. Soc., 1962, 84, 870. * Moffitt, Woodward, Moscowitz, Klyne and Djerassi, J. Amer. Chem. SOC., 1961, 83, 2771. 9 Jensen, Noyce, Sederholm and Berlin, J. Amer. Chem. SOC., 1962, 84, 386. 10 Hall, Trans. Faraday Soc., 1959, 55, 1319. 11 Buchi and Erickson, J. Amer. Chem. SOC., 1954, 76, 3493. 12 Djerassi, Osiecki and Eisenbraun, J. Amer. Chem. Soc., 1961, 83,4433. 13 Mason, Mol. Physics, 1962, 5, 343.