A computationally inspired investigation of the solid forms of (R)-1-phenylethylammonium-(S)-2-phenylbutyrate.

Following the computation of a lattice energy landscape which predicted that there should be more stable, denser forms of (R)-1-phenylethylammonium-(S)-2-phenylbutyrate, crystallizations from a range of solvents were performed to search for other polymorphs and investigate the possibility that the known P4(1) structure could be a hydrate. Extensive crystallization experiments from a wide range of solvents gave fine needles or microcrystalline samples. A redetermination of the P4(1) structure by powder X-ray diffraction located all protons, and in conjunction with other experimental and computational evidence showed that the structure was anhydrous. Evidence for two additional forms was found as mixtures with form I. These include an orthorhombic form, possibly a Z' = 3 polymorph, and another as yet unidentified form obtained as a minor component from dichloromethane solution. However, both these forms appear to be metastable with respect to form I (P4(1)), which is therefore probably the most thermodynamically stable form that can be crystallized from solution under ambient conditions. This determination of the solid state behavior of the less readily crystallized member of the diastereomeric salt system (R)-1-phenylethylammonium-(R/S)-2-phenylbutyrate provides a challenge to the theoretical modeling to explain its ideal resolution behavior.

Structural characterization of selenium and selenium-diiodine analogues of the antithyroid drug 6-n-propyl-2-thiouracil and its alkyl derivatives.

The structures of four selenium analogues of the antithyroid drug 6-n-propyl-2-thiouracil [systematic name: 2,3-dihydro-6-n-propyl-2-thioxopyrimidin-4(1H)-one], namely 6-methyl-2-selenouracil, C(5)H(6)N(2)OSe (1), 6-ethyl-2-selenouracil, C(6)H(8)N(2)OSe (2), 6-n-propyl-2-selenouracil, C(7)H(10)N(2)OSe (3), and 6-isopropyl-2-selenouracil, C(7)H(10)N(2)OSe (4), are described, along with that of the dichloromethane monosolvate of 6-isopropyl-2-selenouracil, C(7)H(10)N(2)OSe.CH(2)Cl(2) (4.CH(2)Cl(2)). The extended structure of (1) is a two-dimensional sheet of topology 6(3) with a brick-wall architecture. The extended structures of (2) and (4) are analogous, being based on a chain of eight-membered R(8)(6)(32) hydrogen-bonded rings. In (3) and (4.CH(2)Cl(2)), R(2)(2)(8) hydrogen bonding links molecules into chains. 6-n-Propyl-2-selenouracil.I(2), C(7)H(10)N(2)OSe.I(2) (7), is a charge-transfer complex with a ;spoke' structure, the extended structure of which is based on a linear chain formed principally by intermolecular N-H...O hydrogen bonds. Re-crystallization of 6-ethyl-2-selenouracil or (7) from acetone gave crystals of the diselenides [N-(6'-ethyl-4'-pyrimidone)(6-ethyl-2-selenouracil)(2)(Se-Se)].2H(2)O (9.2H(2)O) or [N-(6'-n-propyl-4'-pyrimidone)(6-n-propyl-2-selenouracil)(2)(Se-Se)] (10), respectively: these have similar extended chain structures formed via N-H...O and C-H...O hydrogen bonds, stacked to give two-dimensional sheets. Re-crystallization of (7) from methanol/acetonitrile led via deselenation to the formation of crystals of 6-n-propyl-2-uracil (11), in which six symmetry-related molecules combine to form a six-membered R(6)(6)(24) hydrogen-bonded ring, with each pair of molecules linked by an R(2)(2)(8) motif.

Synthesis and structures of Se analogues of the antithyroid drug 6-n-propyl-2-thiouracil and its alkyl derivatives: formation of dimeric Se-Se compounds and deselenation reactions of charge-transfer adducts of diiodine.

Four selenium analogues of the antithyroid drug 6-n-propyl-2-thiouracil (PTU), of formulae RSeU, (R = methyl (Me) (1), ethyl (Et) (2), n-propyl (nPr) (3), and isopropyl (iPr) 4), have been synthesized. Reaction of 1-4 with diiodine in a 1:1 molar ratio in dichloromethane results in the formation of [(RSeU)I(2)] (R = methyl (5), ethyl (6), n-propyl (7) and isopropyl (8)). All compounds have been characterized by elemental analysis, FT-Raman, FT-IR, UV/Vis, (1)H-, (13)C-, (77)Se-1D and -2D NMR spectroscopy, and ESI-MS spectrometric techniques. Recrystallization of 4 from dichloromethane afforded (4CH(2)Cl(2)). Crystals of [(nPrSeU)I(2)] (7), a charge-transfer complex, were obtained from chloroform solutions, while crystallization of 6 and 7 from acetone afforded the diselenides [N-(6-Et-4-pyrimidone)(6-EtSeU)(2)] (92 H(2)O) and [N-(6-nPr-4-pyrimidone)(6-nPrSeU)(2)] (10) as oxidation products. Recrystallization of 7 from methanol/acetonitrile solutions led to deselenation with the formation of 6-n-propyl-2-uracil (nPrU) (11). [(nPrSeU)I(2)] (7) was found to be a charge-transfer complex with a Se--I bond. These results are discussed in relation to the mechanism of action of antithyroid drugs.