Indian Journal of Chemistry Vol. 48B, September 2009, pp. 1261-1273 Simple and convenient methods for synthesis, resolution and application of aminonaphthols Mariappan Periasamy*, Shaik Anwar & Meda Narsi Reddy School of Chemistry, University of Hyderabad, Central University P. O., Hyderabad 500 046, India E-mail: mpsc@uohyd.ernet.in Received 11 May 2009; accepted (revised) 15 June 2009 Racemic aminonaphthols are obtained in 70-95% yield by simple and straightforward condensation of benzaldehyde, 2- naphthol and 1° or 2° amines in ethanol solvent under refluxing conditions. The racemic aminonaphthols 1-(- aminobenzyl)-2-naphthol and 1-(-pyrrolidinylbenzyl)-2-naphthol have been resolved using L-(+)-tartaric acid. The racemic 1-(-N-butylaminobenzyl)-2-naphthol and 1-(-piperidylbenzyl)-2-naphthol have been resolved using R-(+)-BINOL and boric acid. The racemic (2-methoxynaphth-1-yl)benzylamine is resolved using dibenzoyl-L-(-)-tartaric acid. The readiliy accessible chiral aminonaphthols are useful for resolution of important moieties like racemic BINOL, ibuprofen and mandelic acid. Keywords: Betti reaction, diastereomeric complexes, L-(+)-tartaric acid, 1,1-bi-2-naphthol, dibenzoyl-L-(-)- tartaric acid, ibuprofen, mandelic acid Despite unprecedented advances in enantioselective transformations, large scale production of enantiopure substances is still heavily dependent upon the separation of diastereomers obtained from racemic mixtures using an optically active resolving agent 1 . In recent years, there has been widespread interest in the development of new methodologies for asymmetric synthesis 2-4 . Though established resolution methods are still widely used in large-scale preparations, especially if both the enantiomers are required, there has not been much interest on the development of new methods of resolution. Herein, it is wished to report the synthesis and resolution of aminonaphthols using chiral resolv- ing agents such as L-(+)-tartaric acid 2, R-(+)-BINOL 3 and dibenzoyl-L-(-)-tartaric acid 4 (Figure 1). Results and Discussion Aminonaphthol 1 is easily prepared by the condensation of 2-naphthol with ammonia and benzaldehyde 5 . Though these derivatives were known since the beginning of the 20 th century, their application in organic synthesis is of recent origin 6,7 . The original Betti base 1 is thermally unstable 5,8 and hence it is not suitable for the preparation of the corresponding N,N-dialkyl derivatives under drastic conditions 9 . Generally, the derivatives of amino- naphthols were prepared by condensation of benzaldehyde, 2-naphthol and amines in ethanol or DCM solvent for 6 days 10,11 , in presence of acidic Al 2 O 3 or LiClO 4 (Ref. 12). Condensation of - naphthol and preformed iminium salts 13 , and photo addition of nucleophiles to 1-alkenyl-2-naphthol also give the aminonaphthols 14 . Accordingly, a simple method has been developed for preparing various derivatives of aminonaphthols following the original Betti procedure 5 , starting from benzaldehyde, 2-naphthol and various amines at 78°C in ethanol solvent (Schemes I and II). In the preparation of aminonaphthols 5-7 using 1° amines, the yields were moderate to good, as the amino- naphthols could react further with benzaldehyde to give the oxazine compounds. However, use of 2° amines gave the products in excellent yield. Efforts were then undertaken on the resolution of some of these aminonaphthols through formation of diastereomeric complexes using readily available, inexpensive chiral resolving agents. It was observed that L-(+)-tartaric acid formed diastereomeric complexes with aminonaphthols 1 and 9 (Scheme III). These diastereomeric complexes are solid derivatives and are readily cleaved hydrolytically. To optimize the reaction conditions, the resolution of 1-(-pyrrolidinylbenzyl)-2-naphthol 9 was initially examined using various solvents like acetone, THF,