Dual space divergence in small molecule quasiracemates: benzoyl leucine and phenylalanine assemblies

Abstract

Quasiracemic materials constructed with two points of structural difference were used to understand the role molecular shape plays in molecular assembly. Hot stage, crystallographic, and occupied cavity space assessments provide...

Benzoyl Valine Quasiracemates: Pairing CF3 Quasienantiomers with H to t-Butyl

“…This observation follows an increase in the number of hydrogen-bond donor and acceptor atoms available with 4 . For amides 2 and 3 , the solitary N–H···OC hydrogen bonds create C(4) graph set patterns, , whereas systems of 4 incorporating amino acid components generate extensive networks of R 2 2 (10) and C(7) or R 2 2 (8) and C(4) N–H···O and O–H···O interactions . Similar to the effect of a larger chemical framework on crystal lattice stabilization ( e.g., 2 to 3 ) we also anticipated additional hydrogen-bond acceptor and donor atoms would translate to improved crystal stabilization.…”

“…This observation follows an increase in the number of hydrogen-bond donor and acceptor atoms available with 4. For amides 2 and 3, the solitary N−H 21 Similar to the effect of a larger chemical framework on crystal lattice stabilization (e.g., 2 to 3) we also anticipated additional hydrogen-bond acceptor and donor atoms would translate to improved crystal stabilization.…”

“…Without adequate topological descriptors, our group and others , have extensively used the property of volume to compare molecules and functional groups. The volumes for substituents X were compiled from previous reports. , While evaluating volumes provides a quantitative and easy tool for quasienantiomer comparison, this structural parameter does not directly represent the shape space of substituents or molecules.…”

“…Because the design strategy includes pairing 1 -CF 3 with sets of quasienantiomers, where X = H, F, CH 3 , Cl, Br, NO 2 , I, and t -Bu (Figure ), it is expected that the systematic use of molecular shape to molecular assembly will provide critical insight into the molecular recognition profiles of these materials. Our recent experience of cocrystallizing diarylamide , ( 2 ) and naphthylamide ( 3 ) quasiracemates proved more challenging compared to systems constructed from the benzoyl leucine and phenylalanine ( 4 ) architectures. This observation follows an increase in the number of hydrogen-bond donor and acceptor atoms available with 4 .…”

“…This work probes the shape space of quasiracemic materials , and their ability to assemble pairs of topologically comparable but chemically unique quasienantiomeric components constructed from benzoyl valine ( 1 ) molecular frameworks (Scheme ). Similar to recent reports from our group describing the quasiracemic behavior of 2, 3 and 4-substituted diarylamide , ( 2 ), 4-substituted naphthylamide ( 3 ) and 4-substituted benzoyl leucine/phenylalanine ( 4 ) systems, the framework based on 1 consists of chiral components (valine) and easily derivatized benzoyl components in the 4-position that, together, promote the construction of homologous sets of quasienantiomeric building blocks. Progress from using molecular architectures based on 2 and 3 to benzoyl valine 1 offers a fundamental change in the quasiracemate design approach, where increased crystal lattice stabilization is achieved by creating more extensive hydrogen-bond networks via an added carboxyl group.…”