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Crystal structures of four δ‐keto esters and a Cambridge Structural Database analysis of cyano–halogen interactions
Author(s) -
Kamal Kulsoom,
Maurya Hardesh K.,
Gupta Atul,
Vasudev Prema G.
Publication year - 2015
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.304
H-Index - 17
ISSN - 2053-2296
DOI - 10.1107/s2053229615017106
Subject(s) - halogen , chemistry , halogen bond , crystal structure , hydrogen bond , intermolecular force , crystal engineering , crystal (programming language) , stereochemistry , molecule , medicinal chemistry , crystallography , supramolecular chemistry , organic chemistry , alkyl , computer science , programming language
The revived interest in halogen bonding as a tool in pharmaceutical cocrystals and drug design has indicated that cyano–halogen interactions could play an important role. The crystal structures of four closely related δ‐keto esters, which differ only in the substitution at a single C atom (by H, OMe, Cl and Br), are compared, namely ethyl 2‐cyano‐5‐oxo‐5‐phenyl‐3‐(piperidin‐1‐yl)pent‐2‐enoate, C 19 H 22 N 2 O 3 , (1), ethyl 2‐cyano‐5‐(4‐methoxyphenyl)‐5‐oxo‐3‐(piperidin‐1‐yl)pent‐2‐enoate, C 20 H 24 N 2 O 4 , (2), ethyl 5‐(4‐chlorophenyl)‐2‐cyano‐5‐oxo‐3‐(piperidin‐1‐yl)pent‐2‐enoate, C 19 H 21 ClN 2 O 3 , (3), and the previously published ethyl 5‐(4‐bromophenyl)‐2‐cyano‐5‐oxo‐3‐(piperidin‐1‐yl)pent‐2‐enoate, C 19 H 21 BrN 2 O 3 , (4) [Maurya, Vasudev & Gupta (2013). RSC Adv. 3 , 12955–12962]. The molecular conformations are very similar, while there are differences in the molecular assemblies. Intermolecular C—H...O hydrogen bonds are found to be the primary interactions in the crystal packing and are present in all four structures. The halogenated derivatives have additional aromatic–aromatic interactions and cyano–halogen interactions, further stabilizing the molecular packing. A database analysis of cyano–halogen interactions using the Cambridge Structural Database [CSD; Groom & Allen (2014). Angew. Chem. Int. Ed. 53 , 662–671] revealed that about 13% of the organic molecular crystals containing both cyano and halogen groups have cyano–halogen interactions in their packing. Three geometric parameters for the C— X ...N[triple‐bond]C interaction ( X = F, Cl, Br or I), viz. the N... X distance and the C— X ...N and C—N... X angles, were analysed. The results indicate that all the short cyano–halogen contacts in the CSD can be classified as halogen bonds, which are directional noncovalent interactions.