AQUEOUS SOLUTION OF N-METHYLMORPHOLINE-N-OXIDE AS A NEW MEDIUM FOR ALKYLATION OF HETEROCYCLIC COMPOUNDS
Abstract
This work provides a review of the scientific literature on the study of the alkylation of heterocyclic compounds with various haloalkanes in the N-methylmorpholine-N-oxide-water system. Due to the fact that the alkylation reaction of heterocyclic compounds has been studied in the N-methylmorpholine-N-oxide-water system, we consider it necessary to develop the most optimal and technologically easily realizable method for obtaining N-methylmorpholine and, on its basis, N-methylmorpholine-N-oxide (NMO). In this regard, azoles are unique objects for studying the processes of alkylation with various haloalkanes, which opens up broad prospects for the synthesis of new functionally substituted derivatives. Alkylation of pyrazoles with E/Z 1,3-dichlorobut-2-enes in the NMO/H2O system in the presence of sodium hydroxide leads to the formation of a mixture of E/Z isomers in a ratio of 9:1. It has been shown that this technique makes it possible to replace phase transfer catalysis. The choice of 1,3-dichlorobut-2-ene was justified by the fact that it is formed in large quantities as a waste in the production of chloroprene rubber. In order to synthesize individual isomers of 3-methyl- and 5-methylpyrazoleacetic acid, we studied the alkylation of 3(5)-methylpyrazole with chloroacetonitrile in the NMO/H2O system in the presence of sodium hydroxide. However, it was found that under the chosen conditions, the alkylation of 3(5)-methylpyrazole with chloroacetonitrile does not proceed. We modified the conditions and studied the alkylation process in anhydrous solution of NMO, which led to the formation of the expected product with a yield of 60%. The review considered the alkylation of imidazole with 1,2-dichloroethane using phase transfer catalysis in the NMO/H2O system without isolation of the monoalkylated product. In the course of the alkylation reaction of imidazole with 1,2-dichloroethane, it was found that in the presence of sodium hydroxide, alkylation is accompanied by in situ dehydrochlorination of the resulting chloroethylimidazole, which makes it possible to synthesize 1-vinylimidazole without the use of explosive acetylene. Alkylation of 3-nitro-1,2,4-triazole with haloalkanes is usually carried out in aprotic solvents, which complicates the isolation of the final products. In the published works, we studied the alkylation of 3-nitro-1,2,4-triazole with allyl bromide, propargyl bromide, and 1,2-dibromoethane in the NMO/H2O system. The system chosen facilitates the isolation of the final products from their reaction medium. When studying the alkylation of 3-nitro-1,2,4-triazole with 1,2-dichloroethane in the NMO/H2O system, it was found that, under the selected conditions, the alkylation of nitrotriazole does not proceed. Probably, water prevents the alkylation of the sodium salt of nitrotriazole; apparently, this is the reason why aprotic solvents are usually used in the alkylation of nitrotriazole. In anhydrous NMO solution, alkylation of 3-nitrotriazole led to the formation of chloroethyl-3-nitrotriazole with a yield of 67%. Alkylation of secondary amines (morpholine, piperidine, pyrrolidine) with haloalkanes was carried out in NMO/H2O systems. It was found that the yields of the alkylation products are higher than the yields of the corresponding products obtained under the phase transfer catalysis conditions. The results obtained allow us to assert that we have proposed a new medium for carrying out nucleophilic reactions in organic synthesis.
References
Gaile A.A., Somov V.E., Zalishchevsky G.D. Morpholin and its derivatives. SPb.: Khimizdat. 2007. P. 3-330 (in Russian).
Chanzy H., Nawrot S., Peguy A., Smith P., Chevalier J. Phase behavior of the quasiternary system N-methylmorpholine-N-oxide, water, and cellulose. J. Polymer Sci.: Polymer Phys. Ed. 1982. N 20(10). P. 1909–1924. DOI: 10.1002/pol.1982.180201014.
Fink H.P., Weigel P., Purz H., Ganster J. Structure formation of regenerated cellulose materials from NMMO-solutions. Progress Polymer Sci. 2001. N 26(9). P. 1473–1524. DOI: 10.1016/s0079-6700(01)00025-9.
Rosenau T., Potthast A., Sixta H., Kosma P. Radicals derived from N-methylmorpholine-N-oxide (NMMO): structure, trapping and recombination reactions. Tetrahedron. 2002. N 58(15). P. 3073–3078. DOI: 10.1016/s0040-4020(02)00163-1.
Klobukowski E.R., Angelici R.J., Woo L.K. Bulk Gold-Catalyzed Oxidations of Amines and Benzyl Alcohol Us-ing Amine N-Oxides as Oxidants. Catal. Lett. 2012. N 142(2). P. 161–167. DOI: 10.1007/s10562-011-0758-0.
Demlov E., Demlov Z. Interphase catalysis. M.: Mir. 1987. 485 p. (in Russian).
Goldberg Yu.M. Selected chapters of phase transfer catalysis. Riga: Zinaiyte. 1989. 553 p. (in Russian).
Yanovskaya L.A., Yufit S.S. Organic synthesis in two-phase systems. M.: Khimiya. 1982. 184 p. (in Russian).
Keglevich G., Grün A., Bálint E. Microwave Irradiation and Phase Transfer Catalysis in C-, O- and N-Alkylation Reactions. Curr. Org. Synth. 2013. N 10(5). P. 751–763. DOI: 10.2174/1570179411310050006.
Zakaryan G.B., Hayotsyan S.S., Ayvazyan A.G., Tamazyan R.A., Panosyan H.A., Danagulyan G.G., Attaryan H.S. Alkylation of 3-nitro-1,2,4-triazole in aque-ous alkaline medium in the presence of N-methylmorpholine N-oxide and verification of the struc-ture of the reaction products. Chem. Heterocycl. Comp. 2016. N 52(4). P. 253–256 (in Russian). DOI: 10.1007/s10593-016-1870-2.
Hasratyan A.H., Alexanyan A.G., Khachatryan H.N., Zakaryan G.B., Hayotsyan S.S., Danagulyan G.G., Attaryan H.S. Aqueous N-methylmorpholine N-oxide as a new medium for alkylation of pyrazoles. Chem. Heterocycl. Comp. 2018. N 54(7). P. 751–754 (in Russian). DOI: 10.1007/s10593-018-2342-7.
Hasratyan A.G. Alkylation of phenol with haloalkanes under conditions of phase transfer catalysis and in the N-methylmorpholine N-oxide / water system. Khim. Zhurn. Armenii. 2019. V. 72. N 3. P. 321-329 (in Russian).
Zakaryan G.B., Hayotsyan S.S., Attaryan H.S., Hasratyan G.V. Alternative reaction medium for aminoethanol alkylation. Russ. J. Gen. Chem. 2016. N 86(5). P. 1195–1198. DOI: 10.1134/s1070363216050364.
Zakaryan G.B., Hayotsyan S.S., Attaryan H.S., Hasratyan G.V. Dehydrochlorination of 1-(2-chloroethyl)azoles in aqueous solution of N-methylmorpholine N-oxide. Russ. J. Gen. Chem. 2016. N 86(2). P. 414–416. DOI: 10.1134/s1070363216020377.
Hasratyan A.H., Bagdasaryan G.A., Hayotyan S.S, Attaryan H.S Reactions of secondary amines with di-chlorocarbene generated in aqueous–alkaline medium in the presence of N-methylmorpholine N-oxide. Russ. J. Org. Chem. 2018. V. 54. N 6. P. 959-960. DOI: 10.1134/s1070428018060258.
Bobranski B., Konieczny M. Synthesis of new bis-quarternazy ammonium salts. Dissert. Pharmacy. PAN. 1963. V. 15. N 3. P. 263-273.
Sugi Yoshihizo, Matsuda Akio, Bando Kenichiro, Muruto Kazuhia The cobalt catalyzed reductions using carbon monoxide and water. The N-alkylation of mor-pholine by carbonyl compouds. Chem. Lett. 1979. N 4. P. 3636-364. DOI: 10.1246/cl.1979.363.
Gurbanov P.A., Askerov N.D., Khodzhaev G.Kh. Conjugated. Halogenation of olefins and their derivatives with oxygen-containing compounds. Baku: 1973. P. 121-128 (in Russian).
Markosyan A.J., Baghdasaryan G.A., Hovhannisyan G.P., Attaryan H.S., Hasratyan G.V. Waste-free technology for N-methylmorpholine synthesis. Russ. J. Appl. Chem. 2013. N 86(6). P. 845–847. DOI: 10.1134/s1070427213060104.
Asratyan A.G., Baghdasaryan G.A., Markosyan A.J., Hayotsyan S.S., Attaryan O.S. Development of a waste-free technology for producing N-methylmorpholine-N-oxide (monohydrate). Khim. Zhurn. Armenii 2017. V. 70. N 1-2. P. 276-280 (in Russian).
Attaryan O.S., Asratyan G.V., Eliazyan G.A., Panosyan G.A., Kinoyan F.S., Darbinyan E.G. Phase-transfer catalyzed alkylation of pyrazoles and 1,2,4-triazole with cis- and trans-1,4-dichloro-2-butenes. Chem. Heterocycl. Comp. 1989. N 25(4). P. 414–420. DOI: 10.1007/bf00480755.
Attarian O.S., Matsoyan S.G., Martirosyan S.S. Synthesis of N-Vinylpyrazoles. Chem. Heterocycl. Comp. 2005. N 41(4). P. 452–455. DOI: 10.1007/s10593-005-0170-z.
Asratyan G.V., Attaryan O.S. Alkylation of NH-heterocycles with dihaloalkanes under conditions of phase-transfer catalysis. Khim. Zhurn. Armenii 2007. N 60 (4). P. 749-761 (in Russian).
Badasyan E.B., Rakhmankova T.N. Fundamentals of chloroprene rubber synthesis technology. M.: Mir. 1971. 53 p. (in Russian).
Ramzeeva N.P., Lidak M.Yu., Goldberg Yu.Sh., Shimanskaya M.V. Alkylation of 6-substituted α-bromo-ω-haloalkanes under IFC conditions. J. Org. Chem. 1988. V. 24. N 5. P. 1090 (in Russian).
Tarrago G., Ramdani A., Elguero J., Espada M. Orientation de la réaction d’alkylation des pyrazoles dans des conditions neutres et en catalyse par transfert de phase. J. Heterocycl. Chem. 1980. N 17(1). P. 137–142. DOI: 10.1002/jhet.5570170128.
Martirosyan S.S., Attaryan O.S., Grigoryan R.T., Papoyan G.A., Kinoyan F.S., Asratyan G.V., Matsoyan S.G. Synthesis and properties of 1- (β -bromoethyl) pyrazoles. Khim. Zhurn. Armenii 2004. V. 57. N 3. P. 95-104 (in Russian).
Asratyan G.V., Attaryan O.S., Pogosyan A.S., Eliazyan G.A., Darbinyan E.G., Matsoyan S.T. Alkylation of azoles with β-functionally substituted haloalkyls under con-ditions of phase transfer catalysis. Russ. J. Appl. Chem. 1986. N 6. P. 1296-1300 (in Russian).
Attaryan O.S., Martirosyan S.S., Panosyan G.A., Matsoyan S.G. Synthesis of N-(2-vinyloxyethyl)pyrazoles. Russ. J. Gen. Chem. 2004. N 74(8). P. 1264–1266. DOI: 10.1007/s11176-005-0149-6.
Baltayan A.O., Rstakyan V.I., Antanosyan S.K., Kinoyan F.S., Attaryan O.S., Asratyan G.V. Alkylation of pyrazoles with ethylene chlorohydrin under phase transfer catalysis. Russ. J. Gen. Chem. 2009. N 79(11). P. 2417–2419. DOI: 10.1134/s107036320911022x.
Elguero J., Jacqiero R., Tarrago D., Hong Cund M. Tien Duc. N. Recherches dans la serie des azoles. Etude dimethyl-1,3 et -1,5pyrazoles et the leurs derives bromes. Bull. Soc. Chem. France. 1966. P. 293-302.
Attaryan O.S., Eliazyan G.A., Asratyan G.V., Panosyan G.A., Darbinyan E.G., Matsoyan S.G. Synthesis and polymerization of 4-halogenated 1-vinyl-3-methyl- and 1-vinyl-5-methylpyrazoles. Khim. Zhurn. Armenii 1986. V. 39. N 8. P. 511-516 (in Russian).
Attaryan O.S., Baltayan A.O., Sagatelyan R.E., Takmazyan K.T. Synthesis of 1-(2-aminoethyl)pyrazoles under phase-transfer catalysis. Russ. J. Gen. Chem. 2008. 78(1). P. 136–138. DOI: 10.1134/s1070363208010234.
Attaryan O.S., Baltayan AYa.O, Matsoyan S.G. Synthesis of 1-carboxyethyl-3-methyl and 1-carboxyethyl-5-methylpyrazoles. J. Arm. Chem. 2005. V. 58. N 4. P. 68-70 (in Russian).
Rstakyan V.I., Hakobyan A.E., Zakaryan G.B., Hayotsyan S.S., Attaryan H.S., Asratyan G.V. Alkyla-tion of pyrazoles with ethyl chloroacetate under phase-transfer catalysis and hydrolysis of the esters obtained. Russ. J. Gen. Chem. 2014. N 84(8). P. 1641–1643. DOI: 10.1134/s1070363214080350.
Badalyan K.S., Asratyan A.G., Attaryan O.S. Aqueous hydrolysis of pyrazol-1-ylacetates. Russ. J. Gen. Chem. 2012. N 82(5). P. 946–946. DOI: 10.1134/s107036321205026x.
Hasratyan A.H. NMO/H2O system as a new medium for nucleophilic reactions. 9th Global Chemistry Congress. July 23-24. 2018. Lisbon. Portugal. P. 31.
Bejot R., Carroll L., Bhakoo K., Declerck J., Gouverneur V. A fluorous and click approach for screening potential PET probes. Evaluation of potential hypoxia biomarkers. Bioorg. Med. Chem. 2012. N 20(1). P. 324–329. DOI: 10.1016/j.bmc.2011.10.084.
Díez-Barra E., La Hoz A.D., Sánchez-Migallón A., Tejeda J. Synthesis of N-Alkylpyrazoles by Phase Transfer Catalysis Without Solvent Without Solvent. Synth. Commun. 1990. N 20(18). P. 2849–2853. DOI: 10.1080/00397919008051498.
Diez-Barra E, Hoz A., Loupy A., Sanchez-Migallon A. Selective Allylation and Propargylation of Azoles by Phase Transfer Catalysis in the Absence of Solvent. Heterocycles. 1994. N 38(6). P. 1367. DOI: 10.3987/com-94-6701.
Zakaryan G.B., Hayotsyan S.S., Attaryan H.S., Hasratyan G.V. Alternative reaction medium for the synthesis of 1-propargylpyrazoles. Russ. J. Gen. Chem. 2015. N 85(7). P. 1773–1774. DOI: 10.1134/s1070363215070348.
Dou H.J.M. Metzger Catalyse par transfert de phase en serie heterocyclique. N-alkylation des pyrazole et imidazole. J. Bull. Soc. Chim. France. 1976. N 11. P. 1861.
Pilarski B. A new method forN-alkylation of imidazoles and benzimidazoles. Liebigs Annalen Der Chemie. 1983. N 1983(6). P. 1078–1080. DOI: 10.1002/jlac.198319830619.
Claramunt R.Ma., Elguero J., Garceran R. Synthesis by Phase Transfer Catalysis of N-Benzyl, N-Diphenylmethyl and N-Triphenylmethyl Azoles and Benzazoles. Proton NMR and Chromatographic Data as a Tool for Identification. Heterocycles. 1985. N 23(11). P. 2895. DOI: 10.3987/r-1985-11-2895.
Galons H., Bergerat J., Combet-Farnoux C., Miocque M., Decods G., Bram G. Selective N-Prop-2-ynylation of Heterocycles induced by Solid-Liquid Phase Transfer Ca-talisis without Solvent and use of Solid Inorganic Sup-ports. J. Soc. Chem. Commun. 1985. N 23. P. 1730. DOI: 10.1246/cl.1979.363.
Claramunt R. M., Elguero J., Meco T. N-polylazolylméthanes. III. Synthèse et étude rmn du proton des dérivés du méthylène-1,1′ diimidazole et du méthylène-1,1′ dibenzimidazole. J. Heterocycl. Chem. 1983. N 20(5). P. 1245–1249. DOI: 10.1002/jhet.5570200519.
Salmone J.C., Yaroslavsky S. Selective catalytic effects of strongly ionizing polications on esters solvalis 1-vinilimidazole polimer. J. Am. Chem. Soc. 1996. 90 (30). P. 657-656.
Yunnikova L.P., Likhareva Yu.E., Balandina S.Yu. N-Tropylation of arylamines. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2019. V. 62. N 2. P. 79-84 (in Russian). DOI: 10.6060/ivkkt.20196202.5751.
Khachatryan S.F., Attaryan O.S., Matsoyan M.S., Kinoyan F.S., Asratyan G.V. A new method for the syn-thesis of N-vinylimidazole. Khim. Zhurn. Armenii 2005. V. 58. N 1-2. P. 134-136 (in Russian).
Hasratyan А.H., Suqoyan A.A., Danagulyan G.G., Attaryan H.S. Alkylation of imidazole with dichloro-ethane and dehydrochlorination of the in-situ obtained 1-(2'-chloroethyl)imidazole to 1-vinylimidazole in an aque-ous alkaline medium in the N-methylmorpholine N-oxide system using phase transfer catalyst. Khim. Zhurn. Arme-nii 2019. V. 72. N 4. P. 517-522.
Shostakovsky M.F., Skvortsova G.G., Glazkova N.P., Domnina E.S. Vinylation of imidazole with acetylene in the presence of caustic potassium. Chem. Heterocycl. Comp. 1962. N 6. P. 1070 (in Russian).
Bagal L.I., Pevzner M.S., Frolov A.N., Sheludyakova N.I. Synthesis of nitro derivatives of 1,2,4-triazole, 1,3,4-thiadiazole, tetrazole, 1,3,4 –oxadiazole and pyrazole by non-catalytic replacement of the diazo group with a nitro group. Chem. Heterocycl. Comp. 1970. N 2. P. 259-264 (in Russian).
Bagal L.I., Pevzner M.S., Sheludkova N.I., Kerusov V.M. Alkylation of nitro derivatives of 1,2,4-triazole. Chem. Heterocyclic. Comp. 1970. N 2. P. 265-268 (in Russian).
Kofman T.P., Manuilova V.I., Pevzner M.S., Timofeeva T.N. α-Oxides in reactions with nh acids of the heterocyclic series. II. Alkylation of 3,5-dinitro-1,2,4-triazole with olefin oxides. Chem. Heterocycl. Comp. 1975. N 11(5). P. 612–614 (in Russian). DOI: 10.1007/bf00480491.
Kofman T.P., Kartseva G.Yu., Namestnikova V.I., Paketina E.A. 5-amino-3-R-1,2,4-triazoles in reaction with 3,5-dinitro-1,2,4-triazole derivatives. Russ. J. Org. Chem. 1998. V. 34. N 7. P. 1084-1090.
Kofman T.P., Kartseva G.Y., Glazkova E.Y. 5-substituted 3-nitro-1-trinitromethyl-1,2,4-triazoles. Russ. J. Org. Chem. 2008. N 44(6). P. 870–873. DOI: 10.1134/s107042800806016x.
van der Marel G., Veeneman G., van Boom J.H. Synthesis of 5′-phosphorylated DNA fragments. Tetrahedron Lett. 1981. V. 22. N 15. P. 1463-1466. DOI: 10.1016/S0040-4039(01)90351-X.
Kofman T.P., Trubitsyn A.E., Dmitrienko I.V., Glazkova E.Y., Tselinskii I.V. Synthesis and properties of 1-dinitromethyl-3-R-1,2,4-triazoles. Russ. J. Org. Chem. 2007. N 43(5). P. 758–764. DOI: 10.1134/s1070428007050193.
Zhang Y., Chu T., Gao X., Liu X., Yang Z., Guo Z., Wang X. Synthesis and preliminary biological evaluation of the 99mTc labeled nitrobenzoimidazole and nitrotriazole as tumor hypoxia markers. Bioorg. Med. Chem. Lett. 2006. 16(7). P. 1831–1833. DOI: 10.1016/j.bmcl.2006.01.001.
Zhou L., Ino A., Dai W.-M., Nishimoto S. Evidences for adduct formation between intracellular non-protein thiols and nitroazoles possessing an α,β-unsaturated carbonyl side chain and the effects on radiosensitization of hypoxic cells. Bioorg. Med. Chem. 1999. 7(11). P. 2591–2598. DOI: 10.1016/s0968-0896(99)00187-x.
Hay M.P., Lee H.H., Wilson W.R., Roberts P.B., Denny W.A. Hypoxia-Selective Antitumor Agents. 10. Bis(nitroimidazoles) and Related Bis(nitroheterocycles): Development of Derivatives with Higher Rates of Meta-bolic Activation under Hypoxia and Improved Aqueous Solubility. J. Med. Chem. 1995. 38(11). P. 1928–1941. DOI: 10.1021/jm00011a013.
Attaryan O.S., Hasratyan G.V., Eliazyan G.A., Darbinyan E.G., Matsoyan S.G. Synthesis and polymerization of vinyl derivatives of 1,2,4-triazole, 3-nitro-1,2,4-triazole and tetrazole. Khim. Zhurn. Armenii 1986. V. 39. N 10. P. 630-635 (in Russian).
Sukhanov G.T., Sakovich G.V., Sukhanova A.G., Filippova J.V., Oleshchenko J.Y. Reactions of 3-nitro-1,2,4-triazole derivatives with alkylating agents. Alkylation of 3-nitro-5-R-1,2,4-triazoles with derivatives of diethylene glycol in the presence of alkali. Chem. Het-erocycl. Comp. 2011. N 47(1). P. 55–59 (in Russian). DOI: 10.1007/s10593-011-0719-y.
Sukhanov G.T., Lukin A.Y. Reaction Of 3-Nitro-1,2,4-triazolederivatives with Alkylating Agents. 1. Alkylation in the Presence of Alkali. Chem. Heterocycl. Comp. 2005. N 41(7). P. 861–865 (in Russian). DOI: 10.1007/s10593-005-0239-8.
Kofman T.P. Heterylation of 3-R1 -5-R2 -1,2,4-Triazoles with Derivatives of 3,5-Dinitro-1,2,4-Triazole. Russ. J. Org. Chem. 2001. N 37(8). P. 1158–1168. DOI: 10.1023/a:1013100716588.
Middleton R.W., Monney H., Parrick J. N-Methylation of Heterocycles with Dimethylformamide Dimethyl Ace-tal. Synthesis. 1984. N 9. P. 740–743. DOI: 10.1055/s-1984-30953.
Holzer W. Spectral and structural assignments with various N-substituted 1,2,4-triazoles. Noe difference spectroscopy as a powerful tool. Tetrahedron. 1991. N 47(29). P. 5471–5480. DOI: 10.1016/s0040-4020(01)80980-7.
Pevzner M.S. Production of 1,2,4-triazole-high energy compounds. Ros. khim. zhurn. 1997. N 41 (2). P. 73-83 (in Russian).
Melnikov A.A., Varyagina L.G., Gidasnov B.V. Proceedings of the VI All-Union Meeting on the Chemistry of Nitro Compounds. M.: Izd-vo AN SSSR. 1979. P. 73 (in Russian).
Hasratyan A., Sukoyan A., Shakhatuni A., Danagulyan G., Attaryan H. Nucleophilic substitution of the nitro group in 1-substituted 3-nitro-1H-1,2,4-triazoles in ethanolic potassium hydroxide. Chem. Heterocycl. Comp. 2020. 56(8). P. 1100–1102 (in Russian). DOI: 10.1007/s10593-020-02780-8.
Tiecco M. Radical ipso attack and ipso substitution in aromatic compounds. Acc. Chem. Res. 1980. 13(2). P. 51–57. DOI: 10.1021/ar50146a004.
Adam W., Ma̧kosza M., Staliński K., Zhao C.-G. DMD Oxidation ofin-Situ-Generated σHAdducts Derived from Nitroarenes and the Carbanion of 2-Phenylpropionitrile to Phenols. The First Direct Substitution of a Nitro by a Hydroxy Group. J. Org. Chem. 1998. N 63(13). P. 4390–4391. DOI: 10.1021/jo980173v.
Petrov A.Y., Rusinov V.L., Chupakhin O.N. Synthesis of 6-halo-4,7-dihydro-7-oxo-1,2,4-triazolo[5,1-c][1,2,4]triazines by replacement of the nitro group. Chem. Heterocycl. Comp. 1982. N 18(9). P. 992–992 (in Russian). DOI: 10.1007/bf00513451.
Kofman T.P., Pevzner M.S., Zhukova L.N., Kravchenko T.A., Frolova T.M. Methylation of 3-nitro-1,2,4-triazol-5-one. Russ. J. Org. Chem. 1980. V. 16. P. 420 (in Russian). DOI: 10.1002/chin.198024180.
Nara H., Kaieda A., Sato K., Naito T., Mototani H., Oki H., Kori M. Discovery of Novel, Highly Potent, and Selective Matrix Metalloproteinase (MMP)-13 Inhibitors with a 1,2,4-Triazol-3-yl Moiety as a Zinc Binding Group Using a Structure-Based Design Approach. J. Med. Chem. 2017. N 60(2). P. 608–626. DOI: 10.1021/acs.jmedchem.6b01007.
Brandsma L., Verkruijsse H.D. 8. Synthesis of acetylenes, - allenes and cumulene. Studies in organic Chemistry. 1981. P. 228.
Biçak N., Senkal B. F. Synthesis and polymerization of N,N-diallyl morpholinium bromide. Eur. Polymer J. 2000. N 36(4). P. 703–710. DOI: 10.1016/s0014-3057(99)00115-9.
Biçak N., Soydan A.B., Gakaloglu S. Synthesis of N-allyl morpholine and its copolymers with sylfur dioxide and sterene. Designed Monom. Polym. 1998. N 3. P. 305-313. DOI: 10.1163/156855598X00035.
Badalyan K.S., Sukoyan A.A., Bagdasaryan G.A., Asratyan A.G., Bichakhchyan L.A., Danagulyan G.G., Attaryan O.S. Alkylation of secondary amines (morpholine, piperidine, pyrolidine) in an aqueous alkaline medium under MPA conditions and in the NMO/H2O system. Khim. Zhurn. Armenii 2020. V. 73. N 2-3. P. 223-233 (in Russian).
