ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 3, pp. 354–357. © Pleiades Publishing, Ltd., 2012. Original Russian Text © A.V. Afonin, D.V. Pavlov, I.A. Ushakov, E.P. Levanova, G.G. Levkovskaya, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 3, pp. 362–364.

354

Stereospecificity of 13C Shielding Constants in Acetone Azine as a Tool for Configurational Assignment of Ketone Azines

A. V. Afonin, D. V. Pavlov, I. A. Ushakov, E. P. Levanova, and G. G. Levkovskaya

Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia

e-mail: andvalaf@mail.ru

Received July 24, 2011

Abstract—According to the 13C NMR data, the chemical shift of the methyl carbon atom in acetone azine in the trans position with respect to the lone electron pair on the neighboring nitrogen atom is lower by 7 ppm than that of the methyl carbon atom in the cis position. The corresponding direct 13C–13C coupling constant for the trans-methyl groups is lower by 10 Hz as compared to the cis-methyl groups. The experimental spectral data are reproduced well by nonempirical quantum-chemical calculations. The observed stereospecificity of 13C chemical shifts and 13C–13C coupling constants may be used as an effective tool in configurational analysis of various ketone azines.

We previously synthesized a representative series of ketazines and aldazines and studied their physico-chemical properties [1, 2]. Due to the presence of two azomethine moieties in their molecules, ketazines can exist as three configurational isomers, E,E, Z,Z, and E,Z (structure A).

oxime for which stereospecificity of NMR parameters was well studied. The reliability of the experimental data was confirmed by theoretical calculations.

DOI: 10.1134/S1070428012030037

R1R2

NN

R2R1

E,E-A

R1 R2

NN

R2 R1

Z,Z-A

R1R2

NN

R2 R1

E,Z-A

However, no configurational analysis of azines syn-thesized in [1, 2] was performed, and spectral param-eters ensuring reliable configurational assignments of these compounds were not determined. As shown pre-viously, analysis of stereochemical dependences of 1H and 13C shielding constants is a promising method for studying steric and electronic structures of com-pounds having an azomethine group [3–7]. Therefore, in the present work we examined the 13C NMR spec-trum of acetone azine and measured direct 13C–13C coupling constants in its molecule with a view to find indicator parameters ensuring simple and reliable assignment of configuration of ketazines. The obtained data were compared with those found for acetone

MeMe

NX

I, II

123

I, X = N=CMe2; II, X = OH.

The 13C NMR parameters of acetone azine (I) and acetone oxime (II) are collected in table. It is seen that the four methyl groups in acetone azine (I) are magnetically nonequivalent in pairs, and they appear in the 13C NMR spectrum as two signals characterized by considerably different chemical shifts. Nonequivalence of the methyl groups in one azomethine fragment of molecule I is determined by their spatial orientation with respect to the second azomethine moiety (struc-ture B). In order to assign 13C signals of methyl groups we measured direct 13C–13C coupling constants. It is known that direct 13C–13C couplings exhibit a strong stereochemical relation to spatial orientation of the lone electron pair (LEP) on the neighboring nitrogen atom and that the direct coupling constant for the C–C bond in the cis position with respect to the LEP is considerably larger than the coupling constant for the

STEREOSPECIFICITY OF 13C SHIELDING CONSTANTS IN ACETONE AZINE

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

355

Parameters of the 13C NMR spectra of acetone azine (I) and acetone oxime (II)

Compound no.

Chemical shifts δC, ppm Coupling constants J, Hz

C1 C2-trans C3-cis Δδ = δC2 – δC3 C1–C2 (trans) C1–C3 (cis) ΔJ = J1, 2 – J1, 3

I 159.18 a158.82a

17.12 a19.64a

24.54 a29.00a

–7.4 a–9.4a

40.00 b41.39b

50.20 b51.59b

–10.2 b–10.2b

II c155.26c a156.56a

c14.95c a14.08a

c21.81c a22.47a

–6.9 a–8.4a

d41.2d0 e40.95e

d49.8d0 e51.40e

0–8.6 e–10.5e

a Calculated by the GIAO method at the MP2/6-311G(3df,p) level of theory as the difference of shielding constants for compounds I and II and TMS. b Calculated by the CP-KS method at the B3LYP/6-311G(3df,p) level of theory. c Data of [19]. d Data of [10]. e Calculated in terms of the second-order polarization propagator approximation (SOPPA) [11].

trans-oriented bond [8–11]. For example, the direct 13C–13C coupling constant for the cis-C–C bond in acetone oxime (II) is larger by 8.6 Hz than the direct 13C–13C coupling constant for the trans-methyl group (structure C; see table).

NOH

MeMe

NN

MeMe

cis

φ

trans MeMe

transcis

B C

cis trans

Analogous pattern is observed for acetone azine (I). One direct 13C–13C coupling constant with methyl carbon atom is larger than the other by 10.2 Hz (40.0 and 50.2 Hz; see table). Therefore, the larger coupling constant (50.2 Hz) and the corresponding signal at δC 24.5 ppm belong to the methyl groups oriented cis with respect to the LEP on the neighboring nitrogen atom (structure B). The trans-methyl groups are char-acterized by a 1JCC value of 40.0 Hz and by a chemical shift δC of 17.1 ppm. Thus the shielding constants for methyl groups in acetone azine (I), which determine the experimental 13C chemical shifts, are stereo-specific. Carbon nuclei in the trans-methyl groups are more shielded (by 7.4 ppm) than those in the cis-methyl group. Analogous relation is observed for acetone oxime (II): the chemical shift of the trans-methyl carbon nucleus is lesser by 6.9 ppm than that of the cis-methyl carbon nucleus (see table).

The observed stereochemical dependences of the 13C NMR parameters of acetone azine (I) are well reproduced by quantum-chemical calculations. The

calculations were performed with the aid of Gaussian software package [12]. The geometric parameters of acetone azine molecule (I) were optimized at the MP2 level of theory using 6-311G(d,p) basis set with account taken of electron correlation. The global energy minimum of molecule I corresponds to the gauche conformation with trans orientation of the azomethine groups (the dihedral angle φ between the –C=N– planes is 127.5°; structure B). This result is consistent with the data for acetone azine (I) obtained previously by calculations with a smaller basis set [13]. Table contains the 13C chemical shifts calculated by the gauge-invariant atomic orbitals (GIAO) method [14] and the 13C–13C coupling constants calculated by the coupled perturbed Kohn–Sham method (CP-KS) [15]. The calculation levels are also given. The cal-culations predict increase of the chemical shift of the methyl carbon nucleus by 9.4 ppm and of the corre-sponding direct 13C–13C coupling constant by 10.2 Hz in going from trans to cis orientation of the methyl group. Analogous results were obtained by theoretical calculations of δC and 1JCC values for acetone oxime (II): the chemical shift and the direct coupling con-stant for the trans-methyl group are lower by 8.4 ppm and 10.5 Hz, respectively, than those calculated for the cis-methyl group (see table).

Stereospecificity of direct 13C–13C coupling con-stants and 13C chemical shifts in ketone oximes has found application in numerous structural studies. Con-figuration of a series of ketone oximes with alkyl, aryl, heterocyclic, and acetylenic substituents was assigned on the basis of 1JCC values [11, 16–18]. Analogous structural information was obtained by analysis of

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

AFONIN et al. 356

carbon chemical shifts of ketone oximes with various substituents [3–7, 19–22]. As follows from the experi-mental data and the results of quantum-chemical cal-culations, stereochemical behavior of the parameters δC and 1JCC of acetone azine (I) and acetone oxime (II) conforms to a common relation. Therefore, direct 13C–13C coupling constants and 13C chemical shifts can be effectively used to determine configuration of ketazines. Larger δC and 1JCC values belong to that ketazine isomer in which the CH3 group is oriented cis with respect to the LEP on the neighboring nitrogen atom, whereas lower values are typical of the isomer with trans-oriented CH3 group.

Taking into account that the intensity of the major signal in the 13C NMR spectrum is higher by two orders of magnitude than the intensity of satellite signals used for the determination of 13C–13C coupling constants, it is more appropriate to use 13C chemical shifts in configurational analysis. However, in case of ambiguity due to the presence of only one isomer, the problem of configurational assignment may be solved by additional measurement and calculation of direct 13C–13C coupling constants.

EXPERIMENTAL

Acetone azine was synthesized according to the procedure described in [1, 2]. The 13C NMR spectrum of acetone azine (I) was recorded on a Bruker Avance 400 spectrometer at 101.6 MHz from neat liquid; hexa-methyldisiloxane was used as internal reference. The direct 13C–13C coupling constants were measured from satellite signals at natural concentration of magneti-cally active 13C isotope.

This study was performed under financial support by the Russian Foundation for Basic Research (project no. 11-03-00 423-a).

REFERENCES

1. Russavskaya, N.V., Grabel’nykh, V.A., Levanova, E.P., Sukhomazova, E.N., and Deryagina, E.N., Russ. J. Org. Chem., 2002, vol. 38, p. 1498. 2. Rozentsveig, I.B., Popov, A.V., Kondrashov, E.V., and Levkovskaya, G.G., Russ. J. Org. Chem., 2009, vol. 45, p. 794. 3. Afonin, A.V., Demina, M.M., Kon’kova, T.V., Mare- ev, A.V., Simonenko, D.E., Ushakov, I.A., and Medve- deva, A.S., Russ. J. Org. Chem., 2007, vol. 43, p. 1726. 4. Afonin, A.V., Ushakov, I.A., Simonenko, D.E., Shmidt, E.Yu., Zorina, N.V., Ivanov, I.A., Vasil’tsov, I.A.,

and Mikhaleva, A.I., Khim. Geterotsikl. Soedin., 2008, p. 1523. 5. Afonin, A.V., Pavlov, D.V., Mareev, A.V., Simonen- ko, D.E., and Ushakov, I.A., Magn. Reson. Chem., 2009, vol. 47, p. 105. 6. Afonin, A.V., Pavlov, D.V., Ushakov, I.A., Schmidt, E.Yu., and Mikhaleva, A.I., Magn. Reson. Chem., 2009, vol. 47, p. 879. 7. Afonin, A.V., Ushakov, I.A., Pavlov, D.V., Ivanov, A.V., and Mikhaleva, A.I., Magn. Reson. Chem., 2010, vol. 48, p. 685. 8. Krivdin, L.B., Kalabin, G.A., Nesterenko, R.N., and Trofimov, B.A., Zh. Org. Khim., 1984, vol. 20, p. 2477. 9. Krivdin, L.B., Kalabin, G.A., Nesterenko, R.N., and Trofimov, B.A., Tetrahedron Lett., 1984, vol. 25, p. 4817. 10. Zinchenko, S.V., Shcherbakov, V.V., Sal’nikov, G.E., Krivdin, L.B., and Kalabin, G.A., Zh. Org. Khim., 1989, vol. 25, p. 684. 11. Shcherbina, N.A., Istomina, N.V., and Krivdin, L.B., Russ. J. Org. Chem., 2005, vol. 41, p. 1103. 12. Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuse- ria, G.E., Robb, M.A., Cheeseman, J.R., Montgo- mery, Jr., J.A., Vreven, T., Kudin, K.N., Burant, J.C., Millam, J.M., Iyengar, S.S., Tomasi, J., Barone, V., Mennucci, B., Cossi, M., Scalmani, G., Rega, N., Petersson, G.A., Nakatsuji, H., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Klene, M., Li, X., Knox, J.E., Hratchian, H.P., Cross, J.B., Bakken, V., Adamo, C., Jaramillo, J., Gom- perts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi, R., Pomelli, C., Ochterski, J.W., Ayala, P.Y., Morokuma, K., Voth, G.A., Salvador, P., Dan- nenberg, J.J., Zakrzewski, V.G., Dapprich, S., Daniels, A.D., Strain, M.C., Farkas, O., Malick, D.K., Rabuck, A.D., Raghavachari, K., Foresman, J.B., Ortiz, J.V., Cui, Q., Baboul, A.G., Clifford, S., Cios- lowski, J., Stefanov, B.B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, I., Martin, R.L., Fox, D.J., Keith, T., Al-Laham, M.A., Peng, C.Y., Nanayak- kara, A., Challacombe, M., Gill, P.M.W., Johnson, B., Chen, W., Wong, M.W., Gonzalez, C., and Pople, J.A., Gaussian 03, Wallingford CT: Gaussian, 2004. 13. Kobychev, V.B., Vitkovskaya, N.M., Pavlova, N.V., Shmidt, E.Yu., and Trofimov, B.A., Zh. Strukt. Khim., 2004, vol. 45, p. 792. 14. Ditchfield, R., Mol. Phys., 1974, vol. 27, p. 789. 15. Peralta, J.E., Barone, V., Contreras, R.H., Zaccari, D.G., and Snyder, J.P., J. Am. Chem. Soc., 2001, vol. 123, p. 9162. 16. Krivdin, L.B., Kalabin, G.A., Korostova, S.E., Shev- chenko, S.G., and Trofimov, B.A., Izv. Akad. Nauk SSSR, Ser. Khim., 1984, p. 2832.

STEREOSPECIFICITY OF 13C SHIELDING CONSTANTS IN ACETONE AZINE

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

357

17. Shcherbina, N.A., Istomina, N.V., Krivdin, L.B., Shmidt, E.Yu., Mikhaleva, A.I., and Trofimov, B.A., Russ. J. Org. Chem., 2007, vol. 43, p. 872. 18. Chernyshev, K.A., Krivdin, L.B., Larina, L.I., Kon’ko- va, T.V., Demina, M.M., and Medvedeva, A.S., Magn. Reson. Chem., 2007, vol. 45, p. 661. 19. Hawkes, G.E., Herwig, K., and Roberts, I.D., J. Org. Chem., 1974, vol. 39, p. 1017.

20. Geneste, P., Durand, R., Kamenka, J.M., Beierbeck, H., Martino, R., and Saunders, J.K., Can. J. Chem., 1978, vol. 56, p. 1940. 21. Pandiarajan, K., Mohan, R.T.S., and Hasan, M.U., Magn. Reson. Chem., 1986, vol. 24, p. 312. 22. Afonin, A.V., Ushakov, I.A., Tarasova, O.A., Shmidt, E.Yu., Mikhaleva, A.I., and Voronov, V.K., Russ. J. Org. Chem., 2000, vol. 36, p. 1777.