M534 - Synthesis of 4-Amino-1,7,8,9-tetramethyl-4-aza-tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione

Molbank 2007, M534

http://www.mdpi.org/molbank/

Synthesis of 4-Amino-1,7,8,9-tetramethyl-4-aza-tricyclo[5.2.1.0^2,6]dec-8-ene-3,5-dione

Marta Struga ^* and Jerzy Kossakowski

The Medical University, Department of Medical Chemistry, 3 Oczki Str., 02-007 Warsaw, Poland; Tel/Fax: (+4822)-628-06-79

*Author to whom correspondence should be addressed. E-Mail: [email protected]

Received: 27September 2006 / Accepted: 16 January 2007 / Published: 31 May 2007

Keywords: 1,7,8,9-Tetramethyl-4-oxa-tricyclo[5.2.1.0^2,6]dec-8-ene-3,5-dione, 4-Amino-1,7,8,9-tetramethyl-4-aza-tricyclo[5.2.1.0^2,6]dec-8-ene-3,5-dione, hydrazine hydrate

Various imide derivatives of 1,7,8,9-tetramethyl-4-aza-tricyclo[5.2.1.0^2,6]dec-8-ene-3,5-dione (2) have been reported and shown to exhibit an anxiolytic activities [1].

Starting materials e.g. 1,2,3,4-tetramethyl-1,3-cyclopentadiene, and furan-2,5-dione were commercially available reagents.

1,7,8,9-Tetramethyl-4-oxa-tricyclo[5.2.1.0^2,6]dec-8-ene-3,5-dione (1).

The synthesis of (1) was performed from 1,2,3,4-tetramethyl-1,3-cyclopentadiene and furan-2,5-dione according to the method described previously [2]. (Lit. m.p. 108-109⁰C. Yield 68 %.)

White crystals, yield 76 %.

Melting point: 110ºC.

¹H NMR (400 MHz, CDCl₃) δ (ppm): 3.35 (s, 2H, CH-C=O); 3.29 (s, 12H, CH₃); 2.72 (s, 2H, CH₂).

¹³C-NMR (100 MHz, CDCl₃) δ (ppm): 171.3, 138.4, 137.6, 63.9, 56.3, 54.4, 16.6, 11.0.

ESI MS: m/z = 243.3 [M + Na]⁺ (100%).

Elemental Analysis: Calculated for C13H16O3 (220.26): C, 70.89 %; H, 7.32 %. Found: C, 70.92 %; H, 7.23 %.

4-Amino-1,7,8,9-tetramethyl-4-aza-tricyclo[5.2.1.0^2,6]dec-8-ene-3,5-dione (2).

A mixture of anhydride 1 (0.01 mole) and hydrazine hydrate (80% water solution) (10 ml) was refluxed for 5 h. The solvents were evaporated. The residue was purified by a column chromatography (silica gel, chloroform/methanol 19:1) to give compound 2.

White crystals, yield 89 %.

Melting point: 161ºC.

¹H NMR (400 MHz, CDCl₃) δ (ppm): 4.52 (s, 2H, NH₂); 3.02 (s, 2H, CH-C=O); 1.53 (s, 6H, CH₃); 1.47 (s, 6H, CH₃); 1.33 (dd, 2H, CH₂).

¹³C-NMR (100 MHz, CDCl₃) δ (ppm): 174.4, 137.6, 63.6, 55.2, 51.9, 17.1, 10.9.

ESI MS: m/z = 257.2 [M + Na]⁺ (100%).

Elemental Analysis: Calculated for C13H18O2N2(234.3): C, 66.07 %; H, 8.53 %; N, 11.85 %. Found: C, 66.32 %; H, 8.32 %; N, 11.89 %.

References:

1. Kossakowski, J.; Kuśmierczyk, J. Acta Pol. Pharm. 1999, 56, 94.

2. Mironov, V.A.; Sobolev, E.V.; Elizarova, A.N. Tetrahedron 1963, 19, 1939.