SYNTHESIS OF NEW DERIVATIVES OF 3-AZABICYCLO[3.3.1]NONANES BASIS ON N-(2-HYDROXY-3,5-DINITROPHENYL)ACETAMIDE σ-ADDUCT
Abstract
A number of new derivatives of N-(3-R-1,5-dinitro-8-oxo-3-azabicyclo[3.3.1]non-6-en-7-yl)acetamides have been synthesized by Mannich condensation of hydride σ-adduct of the N-(2-hydroxy-3,5-dinitrophenyl)acetamide with formaldehyde and primary amines. The synthesis was carried out with two stages. In the first stage, under the action of sodium tetrahydride borate on a solution of N-(2-hydroxy-3,5-dinitrophenyl)acetamide, the C = C bonds of the aromatic ring were reduced to form a 3-charge hydride adduct. The resulting diaduct was isolated from the solution and, while cooling with ice, was introduced into Mannich-condensation with formaldehyde and a solution of the primary amine or amino acid. When the reaction mixture was acidified with dilute orthophosphoric acid to pH 4–5, precipitates of the target products precipitated. After recrystallization from ethanol, the yield of the target products, depending on the substituent at the nitrogen atom, ranged from 55 to 90%. This method is distinguished by relative simplicity, availability of reagents and allows under mild conditions to transfer from the aromatic system activated by nitro groups to 3-azabicyclo[3.3.1]nonane derivatives, containing promising from the point of view of further functionalization nitro, carbonyl and amino groups. The structure of the compounds obtained was proved by IR, 1H-, 13C-, two-dimensional correlation NMR spectroscopy, as well as elemental analysis data. In the IR spectra of the obtained substances, the characteristic absorption bands of amide I (1629-1633 cm-1) and amide II (1560-1570 cm-1), as well as antisymmetric (1549-1556 cm-1) and symmetric (1370-1377 cm-1) oscillations of nitro groups were observed. In the NMR spectra in the weakest field, the broadened signal of the proton NH is observed (δ 9.51-9.57 ppm), followed by the singlet signal of the proton at the double bond (δ 8.15-8.16 ppm). The protons of the methylene groups of the bicyclic system are diastereotopic. Therefore, their signals are mutually split into broadened doublets located in the region of 2.66–3.46 ppm.
References
Perumal R.V., Adiraj M., Shanmugapandiyan P. Syn-thesis, analgesic and antiinflammatory evaluation of substi-tuted 4-piperidones. Indian Drugs. 2001. V. 38. N 3. P. 156-159.
Xaiver J.J.F., Krishnasamy K., Sankar C. Synthesis and antibacterial, antifungal activities of some 2r,4c-diaryl-3-azabicyclo[3.3.1]nonan-9-one-4-aminobenzoyl hydrazones. Med. Chem. Res. 2012. V. 21. N 3. P. 345-350. DOI: 10.1007/s00044-010-9528-6.
Kodisundaram P., Duraikannu A., Balasankar T., Am-bure P.S., Roy K. Cytotoxic and Antioxidant Activity of a Set of Hetero Bicylic Methylthiadiazole Hydrazones: A Structure-Activity Study. Int. J. Mol. Cell. Med. 2015. V. 4. N 2. P. 128-137.
Premalatha B., Bhakiaraj D., Elavarasan S., Chellakili B., Gopalakrishnan M. Synthesis, spectral analysis, in vitro microbiological evaluation and antioxidant properties of 2, 4-diaryl-3-azabicyclo[3.3.1]nonane-9-one-O-[2,4,6-tritertiarybutyl-cyclo-hexa-2,5-dienon-4-yl]oximes as a new class of an-timicrobial and antioxidant agents. J. Pharm. Res. 2013. V. 6. N 7. P. 730-735. DOI: 10.1016/j.jopr.2013.07.007.
Williams S.G., Bhadbhade M., Bishop R., Ung A.T. An alkaloid-like 3-azabicyclo[3.3.1]non-3-ene library obtained from the bridged Ritter reaction. Tetrahedron. 2017. V. 73. N 2. P. 116-128. DOI: 10.1016/j.tet.2016.11.057.
Fattorusso E., Taglialatela-Scafati O. Modern alkaloids: structure, isolation, synthesis, and biology. John Wiley & Sons. 2008. 691 p.
Lazny R, Wolosewicz K, Ratkiewicz A, Pioro D, Stocki M. Synthesis and isomer distribution of 2-alkyltropinones and 2-alkylgranatanones. Tetrahedron. 2014. V. 70. N 3. P. 597-607. DOI: 10.1016/j.tet.2013.12.008.
Mascavage L.M, Jasmin S, Sonnet P, Wilson M, Dalton D. Ullmann's Encyclopedia of Industrial Chemistry. KGaA, Weinheim: WileyVCH Verlag GmbH & Co. 2010. V. 2. P. 326-428. DOI: 10.1002/14356007.a01_353.pub2
Mukhtorov L.G., Blokhin I.V., Atroshchenko Yu.M., Shakhkeldyan I.V., Shumsky A.N. Synthesis of 3-substituted N- (1,5-dinitro-8-oxo-3-azabicyclo [3.3.1] non-6-en-7-yl) forma-mides. Izv. TulGU. Yestestv. nauki. 2017. N 1. P. 33-43 (in Russian).
Morozova E.V., Yakunina I.E., Blokhin I.V., Shakh-keldyan I.V., Atroshchenko Yu.M. Synthesis of 2,6-diazatricyclo-dodecanes based on 2-hydroxy-3,5-dinitropyridine. Russ. J. Org. Chem. 2012. V. 48. N 10. P. 1384-1385.
Ivanova E.V., Blokhin I.V., Fedyanin I.V., Shakh-keldyan I.V., Atroshchenko Yu.M. Synthesis of tricyclic systems based on the σ-adduct of 2-hydroxy-3,5-dinitropyridine with acetone. Russ. J. Org. Chem. 2015. V. 51. N 4. P. 498-503. DOI: 10.1134/S1070428015040065.
Morozova E.V., Yakunina I.E., Kobrakov K.I., Blokhin I.V., Shumsky A.N., Atroshchenko Yu.M. Anionic ad-ducts of 2-hydroxy-3,5-dinitropyridine in Mannich conden-sation. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 2013. V. 56. N 10. P. 23-25 (in Russian).
Ivanova E.V., Fedyanin I.V., Surova I.I., Blokhin I.V., Atroshchenko Yu.M., Shakkeldyan I.V. Amino and hy-droxymethylation of hydride adducts of 2-hydroxy-3,5-dinitropyridine. Chem. Heterocycl. Compd. 2013. V. 49. N 7. P. 1073-1081. DOI: 10.1007/s10593-013-1338-6.
Surova I.I., Ivanova E.V., Atroshchenko Yu.M., Pestsov G.V., Kobrakov K.I. Synthesis and fungicidal activity of 2-methoxy-7-R-1,5-dinitro-3,7-diazabicyclo[3.3.1]non-2-ene. Butlerov Soobshch. 2017. V. 51. N 8. P. 65-70 (in Russian).
Irwin A.P., William M.D. Derivatives of picramic acid and some of their rearrangements. J. Amer. Chem. Soc. 1938. V. 60. N 4. P. 925-927. DOI: 10.1021/ja01271a048.
Atroshchenko Yu.M., Blokhin I.V., Ivanova E.V., Kov-tun I.V. Experimental and theoretical study of the physico-chemical properties of hydride σ-adducts based on 2-hydroxy-3,5-dinitropyridine. Izv. TulGU. Yestestv. nauki. 2013. N 3. P. 244-252 (in Russian).
Blokhina N.I., Atroshchenko Yu.M., Gitis S.S., Blokhin I.V., Grudtsyn Yu.D., Andrianov V.F., Kaminskii A.Ya. Reactions of aromatic nitrocompounds. LXXII. Anionic σ-complexes of nitroarenes in the azocoupling reaction. Russ. J. Org. Chem. 1998. V. 34. N 4. P. 499-501.
Atroshchenko Yu.M., Nasonov S.N., Gitis S.S., Kamin-skii A.Ya., Mel'nikov A.I., Shakhkel'dyan I.V. O vzai-modeystvii 1,3,5-trinitrobenzola s tetragidridoboratom natri-ya. Zhurn. Org. Khim. 1994. V. 30. N 4. P. 632 – 633 (in Russian).
Klepikova S.G., Yu V.K., Fomicheva E.E., Mukhasheva R.D., Praliev K.D., Berlin K.D. 1H-NMR spectroscopy in the study of the three-dimensional structure of 7-alkoxyalkyl- 3-thia-7-azabicyclo-[3.3.1]nonan-9-ones and some of their derivatives. Chem. Heterocycl. Compd. 2008. V. 44. N 11. P. 1398- 1403. DOI: 10.1007/s10593-009-0188-8.
Park D.H., Jeong Y.T., Parthiban P. A complete 1D and 2D NMR studies of variously substituted 3-azabicyclo[3.3.1]nonan-9-ones. J. Mol. Struct. 2011. V. 1005. N 1. P. 31-44. DOI: 10.1016/j.molstruc.2011.08.006.
Parthiban P., Rathika P., Park K.S., Jeong Y.T. Synthe-sis, complete NMR spectral assignments, and antifungal screening of new 2, 4-diaryl-3-azabicyclo[3.3.1]nonan-9-one oxime derivatives. Monatsh. Chem. 2010. V. 141. N 1. P. 79-93. DOI: 10.1007/s00706-009-0221-8.
