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Design and Preparation of Co‐crystals Utilizing the ${{\bf R}{{ \bf 2\hfill \atop \bf 4\hfill}}}$ (8) Hydrogen‐Bonding Motif
Author(s) -
Bernstein Joel,
Novoa Juan J.,
Boese Roland,
Cirkel Sebastian A.
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200902859
Subject(s) - synthon , hydrogen bond , crystal engineering , crystallography , molecule , amine gas treating , substituent , chemistry , acceptor , hydrogen , crystal structure , stereochemistry , organic chemistry , physics , condensed matter physics
An investigation of the feasibility of utilizing a specific, and previously largely unrecognized, hydrogen‐bonded synthon for the design and preparation of co‐crystals is reported. Structural evidence (i.e., >12 000 instances) indicated the robustness of the cyclic ${{\rm{R}}_4^2 (8)}$ hydrogen‐bonded motif containing, in most cases, four individual (either identical or different) molecules, in which the donor substituent (e.g., an amine) can provide two hydrogen‐bond donors, and the acceptor (e.g., a carbonyl oxygen) can provide two hydrogen‐bond acceptors. The energetic robustness of the motif with respect to chemical substitution and charge on the component molecules was investigated and confirmed in a series of fully optimized calculations at the MP2/6‐31+G(d) level. A proof‐of‐concept experiment to prepare a co‐crystal between a prototypical ketone and a primary amine yielded the crystal structure reported herein, in which the hydrogen bonds between the co‐crystal components indeed exhibit exclusively the designed and sought‐after ${{\rm{R}}_4^2 (8)}$ motif.