METHODS OF NITROPYRIDINE SYNTHESIS
Keywords:
pyridine derivatives, synthesis of nitropyridines, nitration of pyridine derivatives
Abstract
Background. Pyridine derivatives are widely used in pharmaceuticals, agrochemistry, as well as in the production of new materials. The pyridine and piperidine rings are the main structural fragments of numerous natural alkaloids with a wide spectrum of biological activity. Many of these alkaloids have anticancer and anti-neurological and other medical activities and continue to be valuable research subjects to stimulate drug discovery. Highly efficient methods for the synthesis of various pyridine derivatives and piperidine enantiomers will continue to be in high demand. In this regard, the analysis and systematization of the main results of studies on the synthesis of nitropyridines is an urgent task.
Purpose. To summarize and systematize the main methods for the synthesis of pyridine nitro derivatives from the beginning of the last century to the present.
Materials and methods. To achieve this goal of the study, a review of the scientific literature on the main methods of obtaining nitropyridines was carried out.
Results. This literature review presents the results of experimental studies on the synthesis of pyridine nitro derivatives starting from the first half of the 20th century and up to the present time.
Conclusion. Thus, it was possible to summarize the scattered but rather extensive factual material accumulated to date on the preparation of pyridine nitro derivatives. Several main approaches to the synthesis are considered, starting from aliphatic compounds, by nitration of pyridine and its derivatives, as well as by oxidation of aminopyridines.
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References
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2. Gil’manov R.Z., Falyakhov I.F., Khayrutdinov F.G., Sobachkina T.N., Petrov E.S. Povedeniye 3-aminoproizvodnykh piridina v reaktsii nitrovaniya [Behavior of 3-amino derivatives of pyridine in the nitration reaction]. Vestnik Kazanskogo tekhnologicheskogo universiteta, 2012, pp. 41-43.
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4. Gil’manov R.Z., Falyakhov I.F., Khayrutdinov F.G., Sobachkina T.N., Nikolayev E.A. Povedeniye metoksiproizvodnykh N-okisi piridina v reaktsii nitrovaniya [Behavior of methoxy derivatives of N-oxide of pyridine in the nitration reaction]. Vestnik KTU, 2014, vol. 17, issue 13, pp. 80-82.
5. Falyakhov I.F., Gil’manov R.Z., Khayrutdinov F.G., Bol’shakova T.G., Akhtyamova Z.G., Nikitin V.G. Zakonomernosti nitrovaniya gidroksiproizvodnykh piridina [Regularities of nitration of pyridine hydroxy derivatives]. Vestnik KTU, 2010, pp. 613-616.
6. Falyakhov I.F., Gil’manov R.Z., Khayrutdinov F.G., Sharnin G.P., Akhtyamova Z.G. Zakonomernosti nitrovaniya piridina i yego alkilproizvodnykh [Regularities of nitration of pyridine and its alkyl derivatives]. Vestnik Kazanskogo tekhnologicheskogo universiteta, 2010, pp. 606-608.
7. Falyakhov I.F., Gil’manov R.Z., Sharnin G.P., Khayrutdinov F.G., Sobachkina T.N., Nikitin V.G. Zakonomernosti nitrovaniya aminoproizvodnykh piridina [Regularities of nitration of amine derivatives of pyridine]. Vestnik Kazanskogo tekhnologicheskogo universiteta, 2010, pp. 621-623.
8. Angela R. Sherman, Ramiah Muruganю C–N Bond Making Reactions at a Pyridine Ring. Advances in Heterocyclic Chemistry, 2015, vol. 114, pp. 227-269. https://doi.org/10.1016/bs.aihch.2015.03.001
9. Bakke J.M. Nitropyridines, their synthesis and reactions. J. Heterocycl. Chem., 2005, vol. 42, pp. 463-474. https://doi.org/10.1002/JHET.5570420313
10. Baumgarten H.E., SuH. C.-F., KriegerA.L. Dechlorination of Some Chloronitropicolines. J. Am. Chem. Soc., 1954, vol. 76 (2), pp. 596–599. https://doi.org/10.1021/JA01631A080
11. Bernstein J., Stearns B., Shaw E., Lott W.A. II. Derivatives of 2,6-Diaminopyridine1. J. Am. Chem. Soc., 1947, vol. 69, pp. 1151–1158. https://doi.org/10.1021/JA01197A048
12. David O’Hagan. Pyrrole, pyrrolidine pyridine, piperidine, azepine and tropane alkaloids. Natural Product Reports, 2000, vol. 17(5), pp. 435-46. https://doi.org/10.1039/a707613d
13. De Selms R.C. Unprecedented orientation in the nitration of certain 3-pyridinols. J. Org. Chem., 1968, vol. 33, pp. 478-480.
14. Den Hertog H.J., Combe W.P. Reactivity of 4-nitropyridine-N-oxide: Preparation of 4-substituted derivatives of pyridine-N-oxide and pyridine. Rec. trav. chim., 1951, vol. 70, pp 581-590. https://doi.org/10.1002/RECL.19510700704
15. Den Hertog H.J., Overhoff J. Über die Nitrierung des Pyridins. (Darstellung des 2-Nitropyridins). Rec. trav. chim., 1930, vol. 49, pp. 552-556.
16. Den Hertog H.J., van Weeren J.W. Nitration of 3,5-diethoxypyridine. Rec. trav. chim., 1948, vol. 67, pp. 980-982. https://doi.org/10.1002/RECL.19480671207
17. Francisco Sánchez-Viesca, Martha Berros;Ma. Reina Gómez. Electric hindrance and other factors in 2-aminopyridine nitration. TIP Revista Especializada en Ciencias Químico-Biológicas, 2013, vol. 16(1), pp. 36-41.
18. Hamana M., Yoshimura H. Decomposition of 4-Nitropyridine. J. Pharm. Soc. Japan., 1952, vol. 72, pp. 1051-1054. https://doi.org/10.1248/YAKUSHI1947.72.8_1051
19. Ivanova E.V., Nikishina M.B., Mukhtorov L.G., Perelomov L.V., Atroshchenko Yu.M. Investigation of the fungicidal activity of new derivatives of 7-R-1,5-dinitro-3,7-diazabicyclo[3.3.1]nonan-2-one. Siberian Journal of Life Sciences and Agriculture, 2021, vol. 13, no. 5, pp. 307-320. https://doi.org/10.12731/2658-6649-2021-13-5-307-320
20. José Sebastião Santos Neto, GilsonZen. Ten years of progress in the synthesis of six-membered N-heterocycles from alkynes and nitrogen sources. Tetrahedron, 2020, vol. 76, no. 4, pp. 130876. https://doi.org/10.1016/j.tet.2019.130876
21. Katritzky A.R., Scriven E.F.V., Majumder S., Akhmedova R.G., Vakulenko A.V., Akhmedov N.G., Murugan R., Abboud K.A. Preparation of nitropyridines by nitration of pyridines with nitric acid. Org. Biomol. Chem., 2005, vol. 3, pp. 538-541. https://doi.org/10.1039/B413285H
22. Kirpal A., Reiter E. 3-Nitropyridin und seine Derivate. Ber., 1925, vol. 58, pp. 699-701.
23. Koenigs E., Gerdes H. C., Sirot A. Über die Nitrierung des 3-Äthoxy-pyridins. Ber., 1928, vol. 61, pp. 1022-1030.
24. Koenigs E., Mields M., Gurlt H. Nitrierungsprodukte des γ-Amino-pyridins. Ber., 1924, vol. 57, pp. 1179–1187. https://doi.org/10.1002/CBER.19240570725
25. Kroehnke F., Schaefer H. Die Darstellung des 4-Nitro-pyridins und seine Molekülverbin-dungen mit Phenolen. Chem. Ber., 1962, vol. 95, pp. 1098-1103. https://doi.org/10.1002/CBER.19620950506
26. Ling Y, Hao ZY, Liang D, Zhang CL, Liu YF, Wang Y. The expanding role of pyridine and dihydropyridine scaffolds in drug design. Drug Design, Development and Therapy, 2021, vol. 15, pp 4289-4338. https://doi.org/10.2147/DDDT.S329547
27. Manfred Schlosser. Reactions of Pyridines, Benzopyridines, and Azapyridines with Organomagnesiums and Organolithiums. Metalation of Azines and Diazines, 2013, pp. 171-222. https://doi.org/10.1007/7081_2012_96
28. Pat. DE 568,549. Verfahren zur Darstellung von 2-Alkoxy-5-nitropyridinen / Dr Erich H. заявл. 12.01.1932; опубл. 21.01.1933.
29. Pennington L.D., Moustakas D.T. The necessary nitrogen atom: A versatile high-impact design element for multiparameter optimization. J Med Chem., 2017, vol. 60 (9), pp. 3552–3579. https://doi.org/10.1021/acs.jmedchem.6b01807
30. Prudel C., Huwig K., Kazmaier U. Stereoselective Allylic Alkylations of Amino Ketones and Their Application in the Synthesis of Highly Functionalized Piperidines. Chem. Eur. J., 2020, vol. 26, pp. 3181–3188. https://doi.org/10.1002/chem.202000051
31. Renat H. Mizzoni. Nitropyridines and Reduction Products (Except Amines). 2008, pp.1-40. https://doi.org/10.1002/9780470186725.ch1
32. Sagitullina G.P., Garkushenko A.K., Silina E.O., Sagitullin R.S. Nitropyridines. 7*. Synthesis of nitropyridines from nitro-malonic dialdehyde. Chemistry of Heterocyclic Compounds, 2009, vol. 45 (8), pp. 948-951. https://doi.org/10.1007/S10593-009-0366-8
33. Suzuki H., Iwaya M., Mori T. C-Nitration of pyridine by the kyodai-nitration modified by the Bakke procedure. A simple route to 3-nitropyridine and mechanistic aspect of its formation. Tetrahedron Lett., 1997, vol. 38, pp. 5647-5650. https://doi.org/10.1016/S0040-4039%2897%2901229-X
34. Takahashi T., Yamamoto Y. Syntheses of Heterocyclic Compounds of Nitrogen. J. Pharm. Soc. Japan., 1949, vol. 69, pp. 408.
35. Tohru Takei, Takumi Ohki, Yosuke Harada, et al. Preparation of dibromopyridines having –(CH2)m–SO3Na groups as monomers for new polypyridines. Tetrahedron Letters, 2012, vol. 53, pp. 5907. https://doi.org/10.1016/J.TETLET.2012.08.086
36. Vitaku E., Smith D.T., Njardarson J.T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among US FDA approved pharmaceuticals. J Med Chem., 2014, vol. 57(24), pp. 10257–10274. https://doi.org/10.1021/jm501100b
37. Von Schichk O.V., Binz A., Schulz A. Derivate des 3-Amino-pyridins. Ber., 1936, vol. 69, pp. 2593-2605. https://doi.org/10.1002/CBER.19360691202
38. Weidel H., Murmann E. Zur Kenntniss einiger Nitroverbindungen der Pyridinreihe. Monatshefte für Chemie, 1895, vol. 16, pp. 749-759. https://doi.org/10.1007/BF01519024
2. Gil’manov R.Z., Falyakhov I.F., Khayrutdinov F.G., Sobachkina T.N., Petrov E.S. Povedeniye 3-aminoproizvodnykh piridina v reaktsii nitrovaniya [Behavior of 3-amino derivatives of pyridine in the nitration reaction]. Vestnik Kazanskogo tekhnologicheskogo universiteta, 2012, pp. 41-43.
3. Gil’manov R.Z., Falyakhov I.F., Khayrutdinov F.G., Nikitin V.G., Petrov E.S., Nikolayev E.A. Osobennosti nitrovaniya N-okisey piridina [Features of nitration of N-oxides of pyridine]. Vestnik KTU, 2014, pp. 19-20.
4. Gil’manov R.Z., Falyakhov I.F., Khayrutdinov F.G., Sobachkina T.N., Nikolayev E.A. Povedeniye metoksiproizvodnykh N-okisi piridina v reaktsii nitrovaniya [Behavior of methoxy derivatives of N-oxide of pyridine in the nitration reaction]. Vestnik KTU, 2014, vol. 17, issue 13, pp. 80-82.
5. Falyakhov I.F., Gil’manov R.Z., Khayrutdinov F.G., Bol’shakova T.G., Akhtyamova Z.G., Nikitin V.G. Zakonomernosti nitrovaniya gidroksiproizvodnykh piridina [Regularities of nitration of pyridine hydroxy derivatives]. Vestnik KTU, 2010, pp. 613-616.
6. Falyakhov I.F., Gil’manov R.Z., Khayrutdinov F.G., Sharnin G.P., Akhtyamova Z.G. Zakonomernosti nitrovaniya piridina i yego alkilproizvodnykh [Regularities of nitration of pyridine and its alkyl derivatives]. Vestnik Kazanskogo tekhnologicheskogo universiteta, 2010, pp. 606-608.
7. Falyakhov I.F., Gil’manov R.Z., Sharnin G.P., Khayrutdinov F.G., Sobachkina T.N., Nikitin V.G. Zakonomernosti nitrovaniya aminoproizvodnykh piridina [Regularities of nitration of amine derivatives of pyridine]. Vestnik Kazanskogo tekhnologicheskogo universiteta, 2010, pp. 621-623.
8. Angela R. Sherman, Ramiah Muruganю C–N Bond Making Reactions at a Pyridine Ring. Advances in Heterocyclic Chemistry, 2015, vol. 114, pp. 227-269. https://doi.org/10.1016/bs.aihch.2015.03.001
9. Bakke J.M. Nitropyridines, their synthesis and reactions. J. Heterocycl. Chem., 2005, vol. 42, pp. 463-474. https://doi.org/10.1002/JHET.5570420313
10. Baumgarten H.E., SuH. C.-F., KriegerA.L. Dechlorination of Some Chloronitropicolines. J. Am. Chem. Soc., 1954, vol. 76 (2), pp. 596–599. https://doi.org/10.1021/JA01631A080
11. Bernstein J., Stearns B., Shaw E., Lott W.A. II. Derivatives of 2,6-Diaminopyridine1. J. Am. Chem. Soc., 1947, vol. 69, pp. 1151–1158. https://doi.org/10.1021/JA01197A048
12. David O’Hagan. Pyrrole, pyrrolidine pyridine, piperidine, azepine and tropane alkaloids. Natural Product Reports, 2000, vol. 17(5), pp. 435-46. https://doi.org/10.1039/a707613d
13. De Selms R.C. Unprecedented orientation in the nitration of certain 3-pyridinols. J. Org. Chem., 1968, vol. 33, pp. 478-480.
14. Den Hertog H.J., Combe W.P. Reactivity of 4-nitropyridine-N-oxide: Preparation of 4-substituted derivatives of pyridine-N-oxide and pyridine. Rec. trav. chim., 1951, vol. 70, pp 581-590. https://doi.org/10.1002/RECL.19510700704
15. Den Hertog H.J., Overhoff J. Über die Nitrierung des Pyridins. (Darstellung des 2-Nitropyridins). Rec. trav. chim., 1930, vol. 49, pp. 552-556.
16. Den Hertog H.J., van Weeren J.W. Nitration of 3,5-diethoxypyridine. Rec. trav. chim., 1948, vol. 67, pp. 980-982. https://doi.org/10.1002/RECL.19480671207
17. Francisco Sánchez-Viesca, Martha Berros;Ma. Reina Gómez. Electric hindrance and other factors in 2-aminopyridine nitration. TIP Revista Especializada en Ciencias Químico-Biológicas, 2013, vol. 16(1), pp. 36-41.
18. Hamana M., Yoshimura H. Decomposition of 4-Nitropyridine. J. Pharm. Soc. Japan., 1952, vol. 72, pp. 1051-1054. https://doi.org/10.1248/YAKUSHI1947.72.8_1051
19. Ivanova E.V., Nikishina M.B., Mukhtorov L.G., Perelomov L.V., Atroshchenko Yu.M. Investigation of the fungicidal activity of new derivatives of 7-R-1,5-dinitro-3,7-diazabicyclo[3.3.1]nonan-2-one. Siberian Journal of Life Sciences and Agriculture, 2021, vol. 13, no. 5, pp. 307-320. https://doi.org/10.12731/2658-6649-2021-13-5-307-320
20. José Sebastião Santos Neto, GilsonZen. Ten years of progress in the synthesis of six-membered N-heterocycles from alkynes and nitrogen sources. Tetrahedron, 2020, vol. 76, no. 4, pp. 130876. https://doi.org/10.1016/j.tet.2019.130876
21. Katritzky A.R., Scriven E.F.V., Majumder S., Akhmedova R.G., Vakulenko A.V., Akhmedov N.G., Murugan R., Abboud K.A. Preparation of nitropyridines by nitration of pyridines with nitric acid. Org. Biomol. Chem., 2005, vol. 3, pp. 538-541. https://doi.org/10.1039/B413285H
22. Kirpal A., Reiter E. 3-Nitropyridin und seine Derivate. Ber., 1925, vol. 58, pp. 699-701.
23. Koenigs E., Gerdes H. C., Sirot A. Über die Nitrierung des 3-Äthoxy-pyridins. Ber., 1928, vol. 61, pp. 1022-1030.
24. Koenigs E., Mields M., Gurlt H. Nitrierungsprodukte des γ-Amino-pyridins. Ber., 1924, vol. 57, pp. 1179–1187. https://doi.org/10.1002/CBER.19240570725
25. Kroehnke F., Schaefer H. Die Darstellung des 4-Nitro-pyridins und seine Molekülverbin-dungen mit Phenolen. Chem. Ber., 1962, vol. 95, pp. 1098-1103. https://doi.org/10.1002/CBER.19620950506
26. Ling Y, Hao ZY, Liang D, Zhang CL, Liu YF, Wang Y. The expanding role of pyridine and dihydropyridine scaffolds in drug design. Drug Design, Development and Therapy, 2021, vol. 15, pp 4289-4338. https://doi.org/10.2147/DDDT.S329547
27. Manfred Schlosser. Reactions of Pyridines, Benzopyridines, and Azapyridines with Organomagnesiums and Organolithiums. Metalation of Azines and Diazines, 2013, pp. 171-222. https://doi.org/10.1007/7081_2012_96
28. Pat. DE 568,549. Verfahren zur Darstellung von 2-Alkoxy-5-nitropyridinen / Dr Erich H. заявл. 12.01.1932; опубл. 21.01.1933.
29. Pennington L.D., Moustakas D.T. The necessary nitrogen atom: A versatile high-impact design element for multiparameter optimization. J Med Chem., 2017, vol. 60 (9), pp. 3552–3579. https://doi.org/10.1021/acs.jmedchem.6b01807
30. Prudel C., Huwig K., Kazmaier U. Stereoselective Allylic Alkylations of Amino Ketones and Their Application in the Synthesis of Highly Functionalized Piperidines. Chem. Eur. J., 2020, vol. 26, pp. 3181–3188. https://doi.org/10.1002/chem.202000051
31. Renat H. Mizzoni. Nitropyridines and Reduction Products (Except Amines). 2008, pp.1-40. https://doi.org/10.1002/9780470186725.ch1
32. Sagitullina G.P., Garkushenko A.K., Silina E.O., Sagitullin R.S. Nitropyridines. 7*. Synthesis of nitropyridines from nitro-malonic dialdehyde. Chemistry of Heterocyclic Compounds, 2009, vol. 45 (8), pp. 948-951. https://doi.org/10.1007/S10593-009-0366-8
33. Suzuki H., Iwaya M., Mori T. C-Nitration of pyridine by the kyodai-nitration modified by the Bakke procedure. A simple route to 3-nitropyridine and mechanistic aspect of its formation. Tetrahedron Lett., 1997, vol. 38, pp. 5647-5650. https://doi.org/10.1016/S0040-4039%2897%2901229-X
34. Takahashi T., Yamamoto Y. Syntheses of Heterocyclic Compounds of Nitrogen. J. Pharm. Soc. Japan., 1949, vol. 69, pp. 408.
35. Tohru Takei, Takumi Ohki, Yosuke Harada, et al. Preparation of dibromopyridines having –(CH2)m–SO3Na groups as monomers for new polypyridines. Tetrahedron Letters, 2012, vol. 53, pp. 5907. https://doi.org/10.1016/J.TETLET.2012.08.086
36. Vitaku E., Smith D.T., Njardarson J.T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among US FDA approved pharmaceuticals. J Med Chem., 2014, vol. 57(24), pp. 10257–10274. https://doi.org/10.1021/jm501100b
37. Von Schichk O.V., Binz A., Schulz A. Derivate des 3-Amino-pyridins. Ber., 1936, vol. 69, pp. 2593-2605. https://doi.org/10.1002/CBER.19360691202
38. Weidel H., Murmann E. Zur Kenntniss einiger Nitroverbindungen der Pyridinreihe. Monatshefte für Chemie, 1895, vol. 16, pp. 749-759. https://doi.org/10.1007/BF01519024
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Published
2021-12-30
How to Cite
Ivanova, E., Nikishina, M., Mukhtorov, L., Shahkeldyan, I., & Atroshchenko, Y. (2021). METHODS OF NITROPYRIDINE SYNTHESIS. Siberian Journal of Life Sciences and Agriculture, 13(6), 177-200. https://doi.org/10.12731/2658-6649-2021-13-6-177-200
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Scientific Reviews and Reports
Copyright (c) 2022 Evgeniya V. Ivanova, Maria B. Nikishina, Loik G. Mukhtorov, Irina V. Shahkeldyan, Yuri M. Atroshchenko
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