DOI: 10.6060/tcct.20165911.5274
Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 2016. V. 59. N 11. P. 40-45

The article is devoted to the reduction of products of the phenothiazine and benzo-morpholine cyanoethylation reaction by sodium borohydride, lithium aluminum hydride and hydrazine monoformiate in diverse conditions. Morpholine cyanoethylation reaction was studied as a model one, as well as benzomorpholine and phenothiazine ones were studied as well. Special attention was paid to the reaction of further reduction of the corresponding ni-triles. The article considers the solution of several synthetic problems: synthesis of the initial heterocycles; cyanoethylation of morpholine by acrylonitrile and selection of the conditions for this reaction (temperature, reaction time, concentrations, catalyst, solvents); cyanoethyla-tion of benzomorpholine and phenothiazine by acrylonitrile in the selected conditions; reduc-tion obtained nitriles by the different reduction systems. It was stated, that adherence of acry-lonitrile to morpholine is more effective when basic phase transfer catalyst was used. Carry-ing out cyanoethylation under phase transfer catalysis conditions (acrylonitrile as a one phase and substrate as a second ones) using tetrabutylammonium hydroxide as a catalyst yielded N (β cyanoethyl)benzomorpholine of 69% and N (β cyanoethyl)phenothiazine of 64% yields. Potassium hydroxide in the polar and nonpolar solvents and copper (II) acetate were also tested as catalysts of cyanoethylation by acrylonitrile. Different reduction systems, such as sodium borohydride / cobalt chloride (II) in methanol, sodium borohydride / cobalt chloride (II) in tetrahydrofuran-water mixture (2:1), lithium aluminum hydride in diethyl ether, lithium aluminum hydride in tetrahydrofuran, hydrazine monoformiate on nickel Raney were tested for the reduction reaction of the obtained nitriles. It was stated that N (β cyanoethyl)benzomorpholine is reduced well to N (3 aminopropyl)benzomorpholine with 70% yield by NaBH4 / CoCl2 system in methanol. His reduction by the other reagents proceeds worse. Attempts to reduce N (β cyanoethyl)phenothiazine failed in any systems be-ing used. Destruction of N (β cyanoethyl)phenothiazine increases with the growth of the basic properties of a reducing system occurred: phenothiazine and diphenylamine were the general products of this reaction. Phenothiazine formation can be explained by reversibility of the re-action of cyanoethylation and elimination of β-cyanoethyl-fragment under the bases influ-ence. The diphenylamine appearance among reaction products in some cases indicates that the substrate reductive desulfurization reaction occurred.

Key words: phenothiazine, benzomorpholine, nitriles reduction

1. Morrissey I. Mechanism of differential activities of ofloxacin enantiomers. Antimicrob. Agents Chemother. 1996. V. 40. N 8. Р. 1775–1784.
2. Mashkovskiy M.D. Medical compounds. 15-th ed. M.: Novaya Volna. 2005. 187 p. (in Russian).
3. Coudert G., Guillaumet G, Loubinoux B. A New Synthesis of 3,4-Dihydro-2H-1,4-benzoxazines using Solid-Liquid Phase-Transfer Catalysis. Synthesis. 1979. V. 1979. N 7. P 541-543. DOI: 10.1055/s-1979-28754.
4. Pozharskiy A.F., Anisimova V.A., Tsupak Ye.B. Practical works on heterocyclic chemistry. Rostov-on-Don: Izd. RSU. 1988. 159 p. (in Russian).
5. Dyumaeva I.V. Synthesis and properties of coordinated d-elements nitriles in addition and substitution reactions and diene synthesis. Extended abstract of dissertation for doctor degree on chemical sciences. M.: A.N. Kosygin Moscow State Textile University. 2010. 45 p. (in Russian).
6. Heininger S. Cupric Acetate Catalyzed Monocyanoethylation of Aromatic Amines. J. Org. Chem. 1957. V. 22. N 10. P. 1213-1217. DOI: 10.1021/jo01361a023.
7. Lopatinskiy V.P., Shekhirev Yu.P., Sutyagin V.M. 9-Vinyl-1,2,3,4-tetrahydrocarbazol. Methods of obtaining chemicals and drugs. Methods of obtaining chemicals and drugs. N 22. M.: IREA. 1970. P. 47-49. (in Russian).
8. Tierney M.T., Grinstaff M.W. Synthesis and Stability of Oligodeoxynucleotides Containing C8-Labeled 2‘-Deoxyade-nosine: Nov-el Redox Nucleobase Probes for DNA-Mediated Charge-Transfer Studies. Org. Lett. 2000. V. 2. N 22. P. 3413–3416. DOI:10.1021/ol006303f.
9. Gowda S., D., Gowda D.C. Application of hydrazinium monoformate as new hydrogen donor with Raney nickel: a facile reduction of nitro and nitrile moieties. Tetrahedron. 2002. V. 58. N 11. P. 2211-2213. DOI: 10.1016/S0040-4020(02)00093-5.
10. Hudlicky M. Reduction in Organic Chemistry. New York: Willey & Sons. 1984. P. 5-11.
11. Pettit G.R., van Tamelen E.E. Desulfurization with Raney Nickel. Org. Reactions. M.: Mir. 1965. P. 380-545 (in Russian).
12. Godefroi E.F., Wittle E.L. The preparation of some derivatives of β-(10-phenothiazinyl)propionic acid and β-(2-chloro-10-phenothiazinyl)propionic acid. J. Org. Chem. 1956. V. 21. N 10. P. 1163–1168. DOI: 10.1021/jo01116a027.
13. Osby J., Heinzman S., Ganem B. Studies on the mechanism of transition-metal-assisted sodium borohydride and lithium aluminum hydride reductions. J. Am. Chem. Soc. 1986. V. 108. N 1. P. 67-72. DOI: 10.1021/ja00261a011.
14. Satoh T., Suzuki S. Reduction of organic compounds with sodium borohydride-transition metal salt systems : Reduction of organic nitrile, nitro and amide compounds to primary amines. Tetrahedron Letters. 1969. V. 10. N 52. P. 4555-4558. DOI: 10.1016/S0040-4039(01)88749-9.
15. Robert N., Brown W. Reduction of Organic Compounds by Lithium Aluminum Hydride. III. Halides, Quinones, Miscellaneous Nitrogen Compounds. J. Am. Chem. Soc. 1948. V. 70. N 11. P. 3738-3740. DOI: 10.1021/ja01191a057.

2016, Т. 59, № 11, Стр. 40-45


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