Synthesis of 2-(9,10-Dihydro-9,10-propanoanthracen-9-yl)-N-methylethanamine via a [4+2] Cycloaddition

Abstract

The synthesis of the tetracyclic molecule 2-(9,10-dihydro-9,10-propano-anthracen-9-yl)-N-methylethanamine (2) as a homologue of the antidepressant 1-(9,10-dihydro-9,10-ethanoanthracen-9-yl)-N-methylmethaneamine (1) was described. The key intermediate 9-(prop-2-en-1-yl)-9,10-dihydro-9,10-propanoanthracen-12-one (7) was successfully synthesized via a [4+2] cycloaddition of α-bromoacrolein and 9-allyl-anthracene, followed by ring expansion and samarium diiodide deoxygenation.

Crystal structure of 9-allyl-4,5-dichloro-12-cyano-9,10-dihydro-9,10-ethanoanthracen-12-yl acetate, C22H17Cl2NO2

“…The recent discovery that some antidepressants show a wide range of pharmaceutical activities such as antidepressants [2], antiproliferative agent against BL cell lines [3] and anti-multi-drug resistance (MDR) activity on cancer cells and the malaria strain P. Falciparum [4][5][6] led many groups work on the synthesis of novel 9,10-dihydro-9,10-ethanoanthracene derivatives [2,[7][8][9][10][11][12][13]. The asymmetric unit of the title structure contains one independent molecule.…”

(4+2) Cycloaddition Reactions of 9-substituted Anthracene Compounds

“…The other was identified by heating with acetic anhydride which gave the previously prepared 9cyano-9,l0-dihydro-9,l0-ethanoanthracene-12methanol acetate (Scheme 11). [54] The Diels-Alder reaction of 9-substituted anthracene was the key steps for the synthesis of some antidepressant drugs and anxiety such as Benzoctamine, maprotiline 55 and a homologues of these compounds bishomobenzoctamine and bishomomaprotiline [56][57][58] .…”

11-Hydroxy-9-(prop-2-en-1-yl)-9,10-dihydro-9,10-propanoanthracen-12-one

“…For background to benzoctamine, see: Wilhelm & Schmidt (1969); Karama et al (2010a). For further synthetic details, see: Karama et al (2010b).…”

“…Benzoctamine is a clinically useful drug for the treatment of anxiety (Wilhelm & Schmidt, 1969) and our research group recently reported (Karama et al, 2010a) the synthesis of bishomobenzoctamine (Karama et al, 2010b) as it is a structural mimic of benzoctamine and was derived from anthrone which might be exhibited antidepressant activity. The title compound is the key intermediate for the synthesis of bishomobenzoctamine and its crystal structure is presented here.…”

“…To 12-Bromo-9-(prop-2-en-1-yl)-9,10-dihydro-9,10-ethanoanthracen-12-carbaldehyde (Karama et al, 2010a) (1 g, 2.85 mmol) in THF (10 ml) was added 1M aqueous NaOH (10 ml). The mixture was stirred at room temperature for 4 h, extracted with ether twice, washed with water, dried with MgSO 4 and the solvent was evaporated in vacuo to yield the crude product.…”