Efficient Synthesis and Spectroscopic Analysis of 8-Nitro Spiro C-3-Annulated 2-Benzazepines and their N-Oxides

Alexey Varlamov; Vladimir Kouznetsov; Fedor Zubkov; Alexey Chernyshev; Grigorii Alexandrov; Alirio Palma; Leonor Vargas; Sandra Salas

doi:10.1055/s-2001-13403

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Efficient Synthesis and Spectroscopic Analysis of 8-Nitro Spiro C-3-Annulated 2-Benzazepines and their N-Oxides

Alexey Varlamov*^a, Vladimir Kouznetsov^b, Fedor Zubkov^a, Alexey Chernyshev^a, Grigorii Alexandrov^a, Alirio Palma^b, Leonor Vargas^b, Sandra Salas^b
^a Department of Organic Chemistry, Russian Peoples Friendship University, Moscow, 117923, Russia
^b Laboratory of Fine Organic Synthesis, School of Chemistry, Industrial University of Santander, A.A. 678, Bucaramanga, Colombia

Abstract

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Abstract

Nitroderivatives 9a-g have been prepared with great C-8 regioselectivity by allowing the corresponding 1,2,4,5-tetrahydrospiro[3H-2-benzazepine-3,1"-cycloalkanes] 8a-g to react with potassium nitrate and concentrated H₂SO₄. The oxidative reaction of a nitrogen-carbon bond in spirobenzazepines 8 and 9 was performed with H₂O₂ and catalytic amounts of sodium tungstate at room temperature affording nitrones 10a-d in moderate to high yields. Stereochemical assignments for all the 2-benzazepine derivatives obtained were derived from a full analysis of the ¹H NMR spectroscopic data and an X-ray crystallographic analysis of 1,5-dimethyl-8-nitro-1,2,4,5-tetrahydrospiro[3H-2-benzazepine-3,1"-cyclohexane] 9c. These data indicate that the 2-benzazepines 8-11 in solution present the azepine ring preferably in the chair conformation, with the methyl substituent at C-5 disposed equatorially.

Key words

2-benzazepines - regioselective nitration - homoallyl-amines - nitrones

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References

1 Lewis JR. Nat. Prod. Rep. 1996, 13: 171

2 Barton DHR. Kirby GW. J. Chem. Soc. 1962, 806

3 Naohiko H. Hiroshi J. Tamio M. Tetsuro S. Masao T. Shojiro U. J. Chem. Soc. C 1968, 2947

4 Holton RA. Sibi MP. Murphy WS. J. Am. Chem. Soc. 1988, 110: 314

5 Maelicke A. Albuquerque X. Drug Discovery Today 1996, 1: 53

6 Sawa Y. Kato T. Masuda T. Hori M. Fujimura H. Pharm. Bull. 1975, 23: 1917

7 Hyttel J. J. Pharmacol. 1983, 91: 153

8 Fuller RW. Molloy BB. Hemrick SK. Biochem. Pharmacol. 1978, 28: 528

9 Miller WH. Alberts DP. Bhathagar PK. Bondinell WE. Callahan JF. Calvo RR. Cousins RD. Erhard KF. Heerding DA. Keeham RM. Kwon C. Manley PJ. Newlander KA. Ross ST. Samanen JW. Uzinskas IN. Venlarskey JW. Yuan CCK. Haltiwanger RC. Gowen M. Hwang SM. James IE. Lark MW. Rieman DJ. Stroup GB. Azzarano LM. Salyers KL. Smith BR. Ward KW. Johanson KO. Huffman WF. J. Med. Chem. 2000, 43: 22

10 Kasparek S. Adv. Heterocycl. Chem. 1974, 117: 45

11 Renfroe B. Harrington C. Proctor GR. In Heterocyclic Compounds. Azepines, Part 1, Vol. 43: Rosowsky A. Wiley & Interscience; New York: 1984. p.671-708

12 Crunewald GL. Dahamkar VH. J. Heterocycl. Chem. 1994, 31: 1609

13 Ishira V. Tanaka T. Miwatashi S. Fujishima A. Goto C. J. Chem. Soc., Perkin Trans. 1 1994, 2993

14 Black DSC. Crozier RF. Daris VC. Synthesis 1975, 205

15 Tufariello JJ. Acc. Chem. Res. 1979, 12: 396

16 Bernotas RC. Adams G. Carr AA. Tetrahedron 1996, 52: 6519

17 Bernotas RC. Craig TE. Carr AA. Nieduzak TR. Adams G. Ohlweiler DF. Hay DA. Bioorg. Med. Chem. Lett. 1996, 6: 1105

18 Kuznetsov VV. Lantsetov SV. Aliev AE. Varlamov AV. Prostakov NS. Zh. Org. Khim. 1992, 28: 74

19 Kouznetsov V. Palma AR. Salas S. Vargas LY. Zubkov F. Varlamov A. Martínez JR. J. Heterocycl. Chem. 1997, 34: 1591

20

Atomic coordinates for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre. The coordinates can be obtained, on request, from the Director, Cambridge Crystallographic Centre, 12 Union Road, Cambridge CB2 1EZ, UK.

21 Murahashi SI. Mitsuku H. Shiota T. Tsuda T. Watanabe S. J. Org. Chem. 1990, 55: 1736

22 Varlamow A. Zubkov F. Chernyshev A. Kouznetsov V. Palma A. Khim. Geterotsikl. Soedin. 1999, 223