Application of Carbon- 13 Nuclear Magnetic Resonance Spectrometry to the Study of Isomer and Conformer Ratios of Dichlorocyclohexanes in Their Mixtures 0. A. Subbotin” and N. M. Sergeyev NMR Laboratory, Department of Chemistry, Moscow State University, Moscow, U.S.S.R.
A procedure less complex than that of Russel et al. [J. Am. Chem. SOC.,85, 2988 (1963)l for the determination of the isomer content of mixtures formed by chlorination of chlorocyclohexane with molecular chlorine is described. The method utilizes analysis of 13C NMR data. Information about the conformer content is also obtained.
The solution of many problems pertaining to reactivities and conformational aspects of multisubstituted alicyclic compounds has been hindered by the lack of adequate analytical methods and the difficulties in isolation of pure isomers. Chlorination of chlorocyclohexane with molecular chlorine is a typical problem solved previously by Russel e t al. (I) only by using a very complex and time-consuming procedure which includes the preparation of each of the isomers. In the present paper, we describe a solution of same problem by using I3C NMR spectrometry. We wish to show that not only the isomer content determination becomes much simpler but also, in addition to what has been found ( I ) , the conformer contents for each of the isomers can be measured. At the same time, it becomes quite obvious that only the conformational properties of the flexible systems are of primary importance in the explanation of their reactivities. Although the substantially more resolved structure of the proton noise decoupled I3C NMR spectra in comparison with that of the PMR allows one to consider the former spectra as a potentially more effective analytical technique ( 2 ) ,as yet surprisingly few papers have been devoted to analytical applications of 13C NMR. This may be explained by the difficulties of the complete analysis of proton decoupled I3C NMR spectra and by the spectral intensity anomalies due to the nuclear Overhauser effect and partial saturation of the signals while using the pulse technique ( 3 ) . Still it is obvious that in many cases these difficulties may be overcome by using a variety of assignment approaches, independent GLC or PMR control, and optimization of the pulsed Fourier transform (FT) 13C NMR experiment ( 4 ) . On tentative grounds, one can also suppose that the nuclear relaxation parameters would be less different if the products of similar structures are compared (Le., the isomers, the conformers, the isotopomers, etc.). This assumption has already led to success in some cases (5-9) and also has been used in the present study.
EXPERIMENTAL Carbon-13 FT NMR spectra have been measured on a Varian XL-100-15 spectrometer, resonance frequency for carbon-13 nuclei being 25.16 MHz. *H heteronuclear lock, 12-mm 0.d. sample tubes, and proton noise decoupling were used in the experiments. In order to obtain more reliable integral peak intensities, we used pulse delay equal to 8-10 sec and pulse widths of ca. 70 psec that correspond to tipping angles of about 50’. These conditions proved satisfactory for determination of equilibrium constants in the case of monohalosubstituted cyclohexanes (10).
The mixture was obtained by chlorination of chlorocyclohexane with molecular chlorine using a procedure similar to that previously described by Russel et al. ( I ) . This mixture was distilled to remove unreacted chlorocyclohexane and further used in the experiments. The low-temperature measurements were performed with CS2 as solvent.
RESULTS AND DISCUSSION The mixture under study can in principle consist of six isomers (cis and trans isomers of 1,2,-, 1,3,-, and 1,4-types) which give nine nonequivalent stereochemically-rigid conformers shown in Figure 1 [e.g., the 1,2-trans isomer is the inversion averaged product of two conformers, ee (I) and aa (II)]. A t low temperatures, one may expect the ring inversion to be slow enough to make separate conformers observable. In accord with previous data by Russel et al. ( I ) , the I3C NMR spectra proved to be very complex, indicating the presence of most of the isomers. The full analysis of the spectra will be only briefly outlined here. We used the “self-consistent” procedure which included the following steps: (a) Carbon chemical shifts associated with the stereochemically-rigid conditions (Le., with conformers) were calculated on the basis of the additive approach involving the substituent shifts reported for the axial and equatorial orientations (IO).The resulting shifts have been compared with the data obtained from the low-temperature spectrum (-90 “C) and some evident assignments have been made (e.g., for 1,3 isomers). (b) Several characteristic differences between chemical shifts of carbon atoms subjected to similar nonadditive corrections were calculated and then used (e.g., for 1,2 isomers). (c) The integral peak intensities and symmetry considerations were also applied. ( d ) Analysis of the dynamic effects in both the slow and fast ring inversion limits proved to be very useful for the assignment (e.g., the signals of the cis- 1,3 isomer do not practically depend upon temperature, suggesting only one conformer to be present in the mixture a t all temperatures). (e) The inversion averaged chemical shifts of the various isomers were obtained by using the conformational content ratios. Comparison of the experimental and predicted chemical shifts (see the Figure) shows that the additive approach leads to reliable results in all cases except for the substituted carbons in 1,2 isomers where the calculated values lie a t substantially higher fields than the experimental ones. This additional displacement turned out to be equal to -4.75 and -6.75 ppm for axial and equatorial conformers, respectively. Note that similar highfield deviations (relative to the estimates based on the additive scheme) were found for other 1,2-dichloro substituted compounds such as 1,2-dichlorocyclooctanes ( 9 ) , 1,2-dichlorobenzene ( 2 ) . They can be termed as “ortho-effect”. Isomer contents resulting from the assignment and the application of the integral peak intensities are included in Table I. These values show general agreement with Russel’s data ( I ) . The slight differences may be attributed to nonidentity of the samples. Furthermore, the conformer contents were found from the low-temperature spectra reANALYTICAL CHEMISTRY, VOL. 48, NO. 3, MARCH 1976
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15.92
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110.781
Figure 1. Experimental and calculated (in parentheses) carbon-1 3 chemical shifts for the various conformers of dichlorocyclohexane (in ppm, relative to TMS)
This observation supports the data obtained by Abraham and Rossetti from the low-temperature PMR spectra (12,
Table I. Isomer and Conformer Content for Dichlorocyclohexanes from 3C NMR Integra1 Peak Intensities Isomer
cis-1,2 trans-l,2 cis-1,3 trans- 1,3 cis-1,4 trans- 1,4 a
Conformers
I11
I IV VI IX VI1
I11 I1 V VI IX VI11
AGaa-ee,
14).
(kcal/mol)Q
Isomer, %b
Degenerate 0.47 Above 1.5 Degenerate Degenerate
17 2 25 25 19
0.03 14 At T = 1 9 3 K, AGQa-ee = G a , - G e e . b At room tem-
perature. sulting in the determination of three nondegenerate ring inversions (Le,, for the trans- 1,2 cis-1,3-, and trans-1,4 species). In accord with the theoretical predictions by Allinger et al. ( I I ) , the diequatorial ( e e ) form turned to be predominant in the case of the trans-1,2 isomer (AG = G,, - Gee = 0.47 kcal/mole). While measuring other mixtures prepared under somewhat different conditions, we found that the isomer contents affected the conformational equilibria, owing probably to the effects of the medium [see also ref. (12)].In case of the cis-1,3 isomer, the conformational equilibrium proved to be shifted completely towards the ee-form (more than 95%). Similar trends have been established previously by Bailey et al. (13) while attempting to detect axial conformer of l-chloro-3,3-dimethylcyclohexane. In this case, the predominance of the ee-form is attributed to the 1,3-syn diaxial repulsion. In contrast, for trans1,4 isomer both of the forms are almost equally populated indicating a mechanism for stabilization of diaxial form.
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Thus, the present results clearly demonstrate that I3C NMR spectrometry proved to be a very promising method for fast analysis of multicomponent isomer mixtures with parallel determination of the conformer ratios in the case where the isomers are flexible.
ACKNOWLEDGMENT We are grateful to T. I. Usmanov for his help in the preparation of the mixtures under study.
LITERATURE CITED (1) G. C. Russel, A. Ito, and R. Konaka, J. Am. Chem. SOC., 85, 2988 (1963). (2) G. C. Levy and G. L. Nelson, "Carbon-13 Nuclear Magnetic Resonance for Organic Chemists", Wiley Interscience, New York, 1972. (3) R. Freeman and H. D. Hill, J. Chem. Phys., 4, 366 (1971). (4) D. Jones and H. Sternlicht, J. Mag. Reson.. 8 , 167 (1972). (5) F. A. L. Anet, C. H. Bradley, and G. W. Buchanan. J. Am. Chem. SOC., 93, 258 (1971). (6) F. A. L. Anet and V. Basus, J. Am. Chem. SOC., 94,5318 (1972). (7) H.J. Schneider and V. Hoppen, Tetrahedron Len., 579 (1974). (8) H.J. Schneider, T. Keller, and R. Price, Org. Mag. Reson., 4, 907 (1972). (9) A. D. Litmanovitch, N. A. Plate, N. M. Sergeyev, 0.A. Subbotin. and T. I. Usmanov, Dokl. Akad. NaukSSSR, 210, 114 (1973). (10) 0.A. Subbotin and N. M. Sergeyev, J. Am. Chem. SOC., 97, 1080 (1975). (11) N. L. Alllnger, J. A. Hirsch, M. A. Miller, and J. J. Tuminski, J. Am. Chem. SOC.,91, 337 (1969). (12) R. J. Abraham and 2. L. Rossetti, Tetrahedron Left.,1972, 4965. (13) D. S.Bailey, J. A. Walter, and J. E. Lambert, J. Am. Chem. SOC., 94, 177 (1972). (14) R. J. Abraham and 2 . L. Rossetti, J. Chem. SOC., Perkin Trans., 582 (1973).
RECEIVEDfor review July 23, 1975. Accepted September 11, 1975.
