Intermolecular-medium and intramolecular-weak hydrogen bonding chains in the crystals of chiral trifluoromethylated amino alcohols

Abstract

A structural feature of hydrogen bonding chains found in the crystals of trifluoromethylated amino alcohols is reported. Hydrogen bondings of 3-(N,N-dialkylamino)-1,1,1-trifluoro-2-propanols construct chiral spiral hydrogen bonding chains. Lone pairs on the nitrogen atoms of the amino alcohols participate in two hydrogen bondings. Detailed structural analysis of the hydrogen bonds of the 3-(N,Ndimethylamino)-1,1,1-trifluoro-2-propanol suggested that the chain built up with alternating intermolecular-medium and intramolecularweak hydrogen bonds. The medium intermolecular hydrogen bond, which transfers a proton from the hydroxy group to the amino nitrogen, would make a tentative zwitterionic form of the molecule. Then, electrostatic attraction between the charges in the zwitterion centers induced a weak intramolecular hydrogen bond. #

Optical Purifications via Self‐Disproportionation of Enantiomers by Achiral Chromatography: Case Study of a Series of α‐CF3‐containing Secondary Alcohols

“…2). } Similarly to the previously reported crystallographic data for compounds 1b and 1e, 48 there are two important features in the structure of 1a. First, the molecules form an infinite intermolecular hydrogen N-H-O bonding network between hydroxy (donor) and amino (acceptor) groups.…”

Predicting and Tuning Physicochemical Properties in Lead Optimization: Amine Basicities

“…[26] The second example is given for a cyclic and an acyclic representative of a series of 3,3,3-trifluoro-2-hydroxypropylamines ( Figure 17). [34][35][36][37] This functional group has been of interest in medicinal chemistry [35,36] and as a chiral auxiliary in asymmetric synthesis. [37] The measured pK a values of the two hydroxylated amines indicate a pK a shift of approximately À2.3 relative to the corresponding N-propylamines for the combined effects of the CF 3 and the OH group both in b-position to the amine center.…”

“…However, this would be expected if the bulky CF 3 group is assumed to be trans to the amine center, thus forcing the hydroxy group into a gauche orientation, where it could stabilize the protonated form by similar favorable interactions as diagnosed for 3-hydroxypiperidine derivatives. Several X-ray crystal structures for different 3,3,3-trifluoro-2-hydroxypropylamines are available, [34][35][36] all of which show a conformational arrangement of the CF 3 and OH groups as depicted in Figure 17.…”

Pairwise interaction enthalpies of enantiomers of β‐amino alcohols in DMSO + H2O mixtures at 298.15 K

“…It has been also confirmed by Mulla that aminopropanol can form intramolecular hydrogen bond with a six‐membered ring structure. In addition, according to Chang and Katagiri, it has been certainly inferred that 2‐amino‐1‐alcohol forms intramolecular hydrogen bond with a five‐membered ring structure, which is very stable (Scheme ).…”