Chiral benzimidazole-derived mono azacrowns: synthesis and enantiomer recognition studies with chiral amines and their ammonium salts Anita Pandey, Hasan Mohammed, Anil Karnik ⇑ Department of Chemistry, University of Mumbai, Vidyanagari, Santacruz (East), Mumbai 400098, India article info Article history: Available online 7 June 2013 abstract Benzimidazole fused chiral mono aza-15-crown-5 2, was obtained in a single step from (S)-()-2-(a- hydroxyethyl) benzimidazole 1. This new class of aza-crown has a unique structure with the chiral unit being held in a stable conformation due to adjacent benzimidazole ring contributing to its stereodiscrim- ination ability. The interactions between the host aza-crown and enantiomerically pure amine guests in ionic and neutral forms exhibited the enantio-discrimination ability. The preliminary evaluation of the chiral sensing was monitored using 1 H NMR and circular dichroism (CD) analysis of the complexes at their molar equivalence. The binding parameters were determined using electronic absorption spectroscopy. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction Understanding and unravelling the concepts of the origin of life and the associated physiological processes are at the heart of chiral recognition. 1–3 Synthetically designed chiral receptors to study the stereochemical integrity of biologically significant molecules such as amino acids, sugars, drugs etc, and are being continuously devel- oped world wide. It is possible to identify certain structural fea- tures that are desired for high levels of enantio-discrimination. Among these the cavity size, 4 symmetry, 5 additional binding sites, 6 conformational rigidity, 7 and availability of a p-rich unit near the stereogenic center are considered to be essential features for the prospective receptors. 8 Molecular recognition in the neutral state of the guest is relatively uncommon. 9–11 Amines are a group of small molecules found extensively in biosystems and in drugs of abuse and therapeutic relevance. Thus monitoring the chemical and enantiomeric purity/assay of amines has gained wide recogni- tion in biochemistry. 12 Chiral recognition is a stringent measure of small energetic differences between diastereomeric complexes and is a consequence of dissimilar extents of stereochemical interac- tions between a receptor and guest enantiomers. Enantiomerically pure chiral macrocycles have proven to be useful synthetic hosts for chiral discrimination. 13–15 Heterocycles containing chiral macrocycles are interesting as they offer multiple ligating sites in addition to aromatic p–p interactions. Crown ethers 16–18 and azacrown ethers have gained importance as an efficient class of sensors for metal ions and (alkyl) ammonium ions. 19–21 Azacrowns offer several advantages such as better binding with wider range of cations, including the softer metal cations and a binding to the neutral guests; these features are noticeably different from oxacrown ethers. 22,23 Several chiral azacrowns with heterocylic residues such as pyridine, pyrimidine, and phenazine have been developed and investigated for their rec- ognition abilities toward chiral amines and amino acids in their neutral and ionic forms. 16–18 2. Benzimidazole as a chiral synthon For the practical development of a receptor two considerations are vital; the availability of inexpensive synthons and high yielding simple synthetic protocols. Benzimidazole motifs have found wide applications in chemosensing, catalysis, and pharmaceuticals and so on. The fabrication of benzimidazole derivatives and their appli- cations in chiral processes have been an area of interest for us, with one of the most successful applications being the kinetic resolu- tions of racemic amines and aminoester. 24,25 Earlier experience in the development of crown ether containing furo-fused BINOL and its effective performance as a chiral discriminator of amines and aminoesters 26 motivated us to synthesize chiral azacrown ether containing a benzimidazole ring as a heterocyclic residue. (S)-()-2-(a-Hydroxyethyl) benzimidazole 1 can be obtained conveniently 27,28 in a single step reaction between o-phenylenedi- amine and (S)-lactic acid. This molecule has good configurational stability. The molecule offers a b-hydroxy amino moiety, which has been used extensively for construction of several azacrowns. 29 A noteworthy feature of the proposed azacrown molecule, is the mutually shared C–N bond between the heterocycle and the 0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetasy.2013.04.021 ⇑ Corresponding author. Tel.: +91 22 265206091x585; fax: +91 22 26528547. E-mail address: avkarnik@chem.mu.ac.in (A. Karnik). Tetrahedron: Asymmetry 24 (2013) 706–712 Contents lists available at SciVerse ScienceDirect Tetrahedron: Asymmetry journal homepage: www.elsevier.com/locate/tetasy