Correspondence between Molecular Functionality and Crystal Structures. Supramolecular Chemistry of a Family of Homologated Aminophenols

Abstract

The crystal structures and packing features of a family of 13 aminophenols, or supraminols, are analyzed and correlated. These compounds are divided into three groups: (a) compounds 1-5 with methylene spacers of the general type HO-C6H4-(CH2)n-C6H4-NH2 (n = 1 to 5) and both OH and NH2 in a para position; (b) compounds 1a, 2a, 2b, 2c, and 3a in which one or more of the methylene linkers in 1 to 3 are exchanged with an S-atom; and (c) compounds 2d, 1b, and 6a prepared with considerations of crystal engineering and where the crystal structures may be anticipated on the basis of structures 1-5,1a, 2a, 2b, 2c, and 3a. These 13 aminols can be described in terms of three major supramolecular synthons based on hydrogen bonding between OH and NH2 groups: the tetrameric loop or square motif, the infinite N(H)O chain, and the beta-As sheet. These three synthons are not completely independent of each other but interrelate, with the structures tending toward the more stable beta-As sheet in some cases. Compounds 1-5 show an alternation in melting points, and compounds with n = even exhibit systematically higher melting points compared to those with n = odd. The alternating melting points are reflected in, and explained by, the alternation in the crystal structures. The n = odd structures tend toward the beta-As sheet as n increases and can be considered as a variable series whereas for n = even, the beta-As sheet is invariably formed constituting a fixed series. Substitution of a methylene group by an isosteric S-atom may causes a change in the crystal structure. These observations are rationalized in terms of geometrical and chemical effects of the functional groups. This study shows that even for compounds with complex crystal structures the packing may be reasonably anticipated provided a sufficient number of examples are available.

A discussion on the solid state organization of 4-pyridyl imino compounds and on the co-crystallization between their molecular precursors

“…23 It is well known that the OH and NH 2 groups are, from a structural point of view, complementary. 11 (Fig. 9).…”

Dimorphs of 4′-amino-4-hydroxy-2′-methylbiphenyl: Assessment of likelihood of polymorphism in flexible molecules

“…The best (kinetically favoured) interaction pattern is the O-H … N-H … O-H … chain, which is seen across a wide variety of compounds among the 25 or so aminophenols we have studied. [8][9][10][11] Form I, a kinetic crystal which retains this pattern is a result of this fact. Alternatively, and to achieve the most favourable crystal packing for a linear aminophenol like 2 (this packing being any supramolecular cyclohexane chair), the system dispenses with the infinite O-H … N-H … O-H … chain, and the unexpected O-H … O and N-H … N interactions make their appearance.…”

“…The commercially available 4-methoxybenzeneboronic acid was subjected to Suzuki coupling with 2-bromo-5-nitrotoluene as described elsewhere. 9 The structure solution and refinements were carried out using SHELXTL programs. 14 In all cases the hydroxy and amino H-atoms were located in difference Fourier maps and refined isotropically.…”

Aplicações Tecnológicas do Polimorfismo Farmacêutico

“…A presença de grupos receptores e doadores de ligações de hidrogênio intermoleculares, a existência de anéis aromáticos aptos a interagirem através de contatos do tipo - e a presença de grupos hidrofóbicos são algumas das principais funcionalidades supramoleculares que devem ser levadas em consideração durante o exercício de predição da viabilidade de cristais moleculares ocorrerem [35][36][37][38] . As possibilidades conformacionais dos componentes constituintes do cristal devem também ser analisadas no momento da seleção e triagem de candidatos aos ensaios de cristalização de fármacos 39,40 .…”