Stereostructural behaviour of N–N atropisomers: Two conglomerate crystallisations and a crystallisation-induced deracemisation† Richard J. Arthur, a Michael P. Coogan, * a Meritxell Casadesus, a Robert Haigh, a D. A. Headspith, b M. Grazia Francesconi b and Rebecca H. Laye c Received 12th September 2008, Accepted 14th November 2008 First published as an Advance Article on the web 9th December 2008 DOI: 10.1039/b814424a The solid state behaviour of a number of compounds which show hindered rotation around an N–N bond, in some cases leading to axial chirality is described. A diacyl hydrazine, bisanthranoly hydrazine, 1 crystallises in the chiral space group P2 1 2 1 2 1 , presenting an example of conglomerate crystallisation. A tetra-acyl hydrazine derived from lactic acid, 2, shows kinetic resolution by crystallisation, as of the two isomers observed in the solution NMR, only one crystallises, again in the space group P2 1 2 1 2 1. Two cyclic acyl hydrazines in the form of biquinazolinones are studied: 2,2 0 diphenyl-3,3-biquinazolinone, 3 crystallises in the achiral space group Pbca, while 3,3 0 -dimethyl-2,2 0 -biquinazoline-4 0 -thio-4-one, 4 crystallises in the chiral space group P2 1 giving another example of a conglomerate crystallisation. The single crystal structures of each of the species have been compared to powder XRD data to confirm that the single crystal structures are representative of the bulk material. Introduction Conglomerate crystallisation 1 is that phenomenon whereby a sample in the melt or solution which consists of a mixture of two enantiomers spontaneously separate during the crystal- lisation process to form a physical mixture of crystals each of which contains only a single enantiomer. Conglomerate crystal- lisation must, by definition, occur in one of the 65 chiral space groups, and the observation of single crystals grown from a racemic solution showing a chiral space group is an indication of conglomerate crystallisation. In systems in which the liquid state species is capable of racemisation, conglomerate crystal- lisation may lead to chiral symmetry breaking by a crystal- lisation-induced deracemisation (CID) or, historically, an ‘asymmetric transformation of the second kind’. 2 Asymmetric transformation is defined by IUPAC as ‘‘The conversion of a racemate into a pure enantiomer or into a mixture in which one enantiomer is present in excess, or of a diastereoisomeric mixture into a single diastereoisomer or into a mixture in which one diastereoisomer predominates. This is sometimes called dera- cemization.’’ When this transformation is induced not by chemical means but by a crystallisation process it is referred to as an asymmetric transformation of the second kind, and involves the preferential, self-seeding crystallisation of one isomer from an interconverting mixture in solution (Fig. 1). 2 Such processes are of great philosophical as well as practical interest as they provide a potential model for the amplification of chirality which is presumed to have been involved in the generation of biohomochirality. 3,4 As with all crystallisation phenomena, it is difficult to predict such behaviour and thus applications, while extant, are not numerous. Amongst the notable applications in the field of deracemisation are the asymmetric transformations of binaphthalene, 5 and one involved in the synthesis of the anti- Alzheimer’s molecule, Galanthamine (Fig. 2). 6 One of the best known cases in the field of coordination chemistry is the spon- taneous generation of chirality in Werner’s complexes (Fig. 3), 7 although the generality of this conglomerate crystallisation has recently been questioned. 8 Finally, it is important that Fig. 1 Crystallisation induced deracemisation. Fig. 2 Deracemisation of Glanathamine. a School of Chemistry, Cardiff University, Park Place, Cardiff, Wales/Cymru, UK CF10 3AT. E-mail: cooganmp@cf.ac.uk b Department of Chemistry, The University of Hull, Cottingham Road, Kingston upon Hull, UK HU6 7RX c Department of Chemistry, University of Sheffield, Sheffield, UK S3 7HF † CCDC reference numbers 702071–702074. For crystallographic data in CIF or other electronic format see DOI: 10.1039/b814424a 610 | CrystEngComm, 2009, 11, 610–619 This journal is ª The Royal Society of Chemistry 2009 PAPER www.rsc.org/crystengcomm | CrystEngComm Published on 09 December 2008. Downloaded by University of Hull on 28/08/2014 16:00:42. View Article Online / Journal Homepage / Table of Contents for this issue