The Diels-Alder reaction is widely used in organic synthesis, since it allows using a variety of dienes and dienophiles to obatin six-membered cycles in one step. Azo compounds, especially with electron deficient substituents, such as the 1,3,5-triazine ring, can interact as active dienophiles in the Diels-Alder reactions. Reactions involving azo-bis-cyanuric chloride are of great interest, as 4,6-dichloro-1,3,5-triazine is an easily functionalized fragment that can be used as a connecting link for combining of different fragments in one molecule and modifying the properties of the compounds.
The inverse electron demand (IED) Diels-Alder reaction of azo-bis-cyanuric chloride has been described by us in its interaction with styrene, while one of its regioizomers has been isolated. However, the careful DFT analysis of the reaction coordinates showed that this reaction always proceeds with intermediate formation of the product of a normal DA reaction. So in fact, azo-bis-cyanuric chloride here plays a role of the formal diene - at first it reacts like dienophile, and then thermodynamically unstable product through [3,3]-sigmatropic rearrangement is converted to the corresponding IED isomer. In this work, we investigated the reaction of azo-bis-cyanuric chloride with unsaturated compounds that do not contain a conjugated bond system (vinyl-ethyl ether and vinyl acetate) and cannot act as a diene itself, and it is shown that it can act as a "true" diene in IED Diels-Alder reaction.
The interaction of azo-bis-cyanuric chloride with vinyl-ethyl ether is rapidly passing at
-35 °C, while its reaction with vinyl acetate requires heating to 100 °C for several hours, which is due to its lower nucleophilicity. In reactions with both substances, only one of the IED Diels-Alder reaction regioisomers was isolated. In order to determine the products structure and the reasons for such regioselectivity, DFT modeling was used to calculate the thermodynamic parameters of possible reaction paths on M06-2X/6-31G(d,p) level as well as spectral parameters of products. It was found that both reactions proceeds with the formation of a kinetically and thermodynamically advantageous product, but in the case of a vinyl-ethyl ether, the selectivity of the reaction is controlled by charge distribution (attack of the azo bond in the vinyl β-position), but in the case of vinyl acetate, another regioisomer is formed (azo bond attack in the vinyl α-position) due to a more complete overlapping and correspondingly strong secondary interaction between the π-orbitals of the reagents in the transition state. The obtained 1H-NMR spectra are in good agreement with the DFT simulated spectra and thermodynamic data.
The structure of the products was confirmed by 1H-NMR, IR, UV spectroscopy and elemental analysis.
1. Brocksom T. J. The Diels-Alder reaction: An update. / Brocksom T. J., Nakamura J.,
Ferreira M. L., Brocksom U. Journal of Braz. Chem. Soc. – 2001. – Vol. 12, No. 5. – P. 597–622.
2. Carruthers W. Cycloaddition Reactions in Organic Synthesis / Carruthers. – Oxford: Pergamon Press,
1990. – 382 с. 3. Fringuelli F. The Diels–Alder Reaction / F. Fringuelli, A. Taticchi. – Chichester: J. Wiley
& Sons, 2002. 4. Corey E. J. Catalytic Enantioselective Diels–Alder Reactions: Methods, Mechanistic
Fundamentals, Pathways, and Applications / E. J. Corey // Angewandte Chemie International Edition. –
2002. – No. 41. – С. 1650–1667. 5. Parr R. G. Absolute hardness: companion parameter to absolute
electronegativity / R. G. Parr, R. G. Pearson. // J. Am. Chem. Soc. – 1983. – No. 105. – С. 7512–7516.
6. Parr R. Density-functional theory of atoms and molecules / R. Parr, W. Yang. – New York: Oxford
University Press, 1989. – 333 с. 7. Willoughby O. A guide to small-molecule structure assignment through
computation of (¹H and ¹³C) NMR chemical shifts. / O. Willoughby, M. Jansma, T. Hoye. // Nat. Protoc. –
2014. – No. 9. – С. 643–660. 8. Loew P. Azo-1,3,5-triazines / P. Loew, C. Weis. // Journal of Heterocyclic
Chemistry. – 1976. – No. 13. – С. 829–833. 9. Smolin E. D. s-Triazines and derivatives / E. D. Smolin,
L. Rapoport. – Stamford: Central Research Division, American Cyanamid Company, 1959. – 644 с.
10. Експериментальні та DFT дослідження взаємодії азо-біс-2,4-дихлоро-1,3,5-триазину зі
стиролом / А. І. Кархут, Х. Б. Болібрух, І. І. Губицька та ін. // Вісник Національного університету
“Львівська політехніка” “Хімія, технологія речовин та їх застосування”. – 2017. – № 868. –
С. 153–160. 11. Frisch M. J., Trucks G. W., Schlegel H. B., Scuseria G. E., Robb M. A., Cheeseman J. R.,
Scalmani G., Barone V., Mennucci B., Petersson G. A., Nakatsuji H., Caricato M., Li X., Hratchian H. P.,
Izmaylov A. F., Bloino J., Zheng G., Sonnenberg J. L., Hada M., Ehara M., Toyota K., Fukuda R.,
Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Vreven T., Montgomery J. A.,
Peralta J. E., Ogliaro F., Bearpark M., Heyd J. J., Brothers E., Kudin K. N., Staroverov V. N.,
Kobayashi R., Normand J., Raghavachari K., Rendell A., Burant J. C., Iyengar S. S., Tomasi J, Cossi M.,
Rega N., Millam J. M., Klene M., Knox J. E., Cross J. B., Bakken V., Adamo C., Jaramillo J., Gomperts R.,
Stratmann R. E., Yazyev O., Austin A. J., Cammi R., Pomelli C., Ochterski J. W., Martin R. L.,
Morokuma K., Zakrzewski V. G., Voth G. A., Salvador P., Dannenberg J. J., Dapprich S., Daniels A. D.,
Farkas O., Foresman J. B., Ortiz J. V., Cioslowski J., Fox D. J., Gaussian 09, Revision B.01 –
Wallingford: Gaussian, Inc., 2009. 12. Zhao Y. The M06 suite of density functionals for main group
thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition
elements: two new functionals and systematic testing of four M06-class functionals and 12 other function /
Y. Zhao, D. Truhlar // Theoretical Chemistry Accounts. – 2008. – No. 120. – С. 215–241. 13. Ditchfield R.
Self‐Consistent Molecular‐Orbital Methods. IX. An Extended Gaussian‐Type Basis for Molecular‐Orbital
Studies of Organic Molecules / R. Ditchfield, W. Hehre, J. Pople // The Journal of Chemical Physics. –
1971. – No. 54. 14 Energies, Structures, and Electronic Properties of Molecules in Solution with the
C-PCM Solvation Model / M. Cossi, N. Rega, G. Scalmani, V. Barone // Journal of Computational
Chemistry. – 2003. – No. 24. – С. 669 – 681. 15. Parr R. Electrophilicity Index / R. Parr, L. Szentpály,
S. Liu. // American Chemical Society. – 1999. – No. 121. – С. 1922–1924. 16. Quantitative
Characterization of the Local Electrophilicity of Organic Molecules. Understanding the Regioselectivity
on Diels–Alder Reactions / L. R. Domingo, M. J. Aurell, P. Pérez, R. Contreras. // J. Phys. Chem. A. –
2002. – No. 106. – С. 6871–6875. 17. Quantitative Characterization of the Local Electrophilicity of
Organic Molecules. Understanding the Regioselectivity on Diels–Alder Reactions / L. R. Domingo,
M. J. Aurell, P. Pérez, R. Contreras. // Tetrahedron. – 2002. – No. 58. – С. 4417–4423.