Different packing motifs of isomeric (E)-N′-(halophenylmethylidene)-N-methyl-2-(thiophen-2-yl)acetohydrazides controlled by C—H...O interactions

The crystal structures of three isomeric (E)-N′-(chlorophenylmethylidene)-N-methyl-2-(thiophen-2-yl)acetohydrazides (C14H13ClN2OS) are described, with the Cl atom inortho(I),meta(III) andpara(IV) positions in the benzene ring. Theortho-bromo derivative (II) (C14H13BrN2OS), which is isostructural with its chloro congener (I), is also reported. Molecules (I)–(III) have similar conformations, which approximate to L-shapes, as indicated by their N—C—C—Ct(t = thiophene) torsion angles of −90.1 (3), −91.44 (18) and −90.7 (9)°, respectively. The conformation of (IV) is different, with an equivalent torsion angle of −170.75 (11)° corresponding to a more extended shape for the molecule. The thiophene ring in each structure features `flip' rotational disorder. The packing for (I) and (II) features inversion dimers, linked by pairs of C—H...O interactions, which generateR22(14) loops. In the crystal of (III), [010]C(8) chains arise, with adjacent molecules linked by pairs of C—H...O hydrogen bonds. The packing for (IV) features unusually short C—H...O interactions arising from an H atom attached to the benzene ring (H...O = 2.18 Å), which lead toC(9) [301] chains. Hirshfeld fingerprint percentage contact contributions are similar for the four title compounds.

Crystal structures of 6-chloroindan-1-one and 6-bromoindan-1-one exhibit different intermolecular packing interactions

The two title compounds are analogs of 1-indanone that are substituted at the 6-position with chlorine and bromine. Although very similar in molecular structure, the crystal structures are not isomorphous and reveal that 6-chloroindan-1-one, C9H7ClO (I), and 6-bromoindan-1-one, C9H7BrO (II), exhibit unique intermolecular packing motifs. The molecules of the chloro analog (I) pack with a herringbone packing motif of C—H...O interactions, whereas the bromo derivative (II) packs with offset face-to-face π-stacking, C—H...O, C—H...Br and Br...O interactions. Compound (II) was refined as a two-component non-merohedral twin, BASF 0.0762 (5).

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

Enantioenriched promethazine and ethopropazine were synthesized through a simple and straightforward four-step chemoenzymatic route. The central chiral building block, 1-(10H-phenothiazin-10-yl)propan-2-ol, was obtained via a lipase-mediated kinetic resolution protocol, which furnished both enantiomeric forms, with superb enantioselectivity (up to E = 844), from the racemate. Novozym 435 and Lipozyme TL IM have been found as ideal biocatalysts for preparation of highly enantioenriched phenothiazolic alcohols (up to >99% ee), which absolute configurations were assigned by Mosher’s methodology and unambiguously confirmed by XRD analysis. Thus obtained key-intermediates were further transformed into bromide derivatives by means of PBr3, and subsequently reacted with appropriate amine providing desired pharmacologically valuable (R)- and (S)-stereoisomers of title drugs in an ee range of 84–98%, respectively. The modular amination procedure is based on a solvent-dependent stereodivergent transformation of the bromo derivative, which conducted in toluene gives mainly the product of single inversion, whereas carried out in methanol it provides exclusively the product of net retention. Enantiomeric excess of optically active promethazine and ethopropazine were established by HPLC measurements with chiral columns.

Synthesis and Crystal Structures of the P,N-Substituted Ferrocenes [Fe{η5-C5H4–P(S)Ph2}(η5-C5H4–NHCH2tBu)] and [Fe(η5-C5H4– PPh2)(η5-C5H4–NHCH2tBu)]

The P,N-substituted ferrocene [Fe{η5-C5H4-P(S)Ph2}(η5-C5H4-NHCH2tBu)] was prepared in six steps from the bromo derivative [Fe{η5-C5H4-PPh2}(η5-C5H4-Br)]. Its reductive desulfurisation with Raney nickel afforded the corresponding phosphino-substituted derivative [Fe(η5-C5H4- PPh2)(η5-C5H4-NHCH2tBu)]. Both compounds have been structurally characterised by singlecrystal X-ray diffraction studies.