Antisolvent addition at extreme conditions

This article describes the use of antisolvent addition at high-pressure to aid precipitation and recovery of high-pressure phases to ambient pressure. Paracetamol (PCM) was used as a model system to demonstrate the principle due to the extensive literature of paracetamol at high-pressure and ambient pressure. We have observed that we are able to recover the orthorhombic form of paracetamol to ambient pressure using this technique, although solvent-mediated transformations are a hurdle. During this investigation we observed a new methanol solvate of paracetamol that is simlar in structure to the known form. The methanol solvate is stable to 0.2 GPa before transformation to the orthorhombic form that is known to be the stable form at high pressure

Sweet like chocolate

In the July issue of Acta Crystallographica Section C, Nicholls et al. (2019[Nicholls, D., Elleman, C., Shankland, N. & Shankland, K. (2019). Acta Cryst. C75, 904-909.]) report the discovery of a new polymorph of αβ-D-lactose through the oven drying of concentrated aqueous solutions of D-lactose. The authors inter­est in this system was piqued in relation to the properties of chocolate crumb and the process by which the crumb is made. The drying process by which the crumb is produced is a potential mine of inter­esting solid-state transformations and in this case the authors simplified the system from a complex mixture of milk and sucrose to a concentrated aqueous solution of lactose. This simplification of the system has enabled the authors to focus in on the phase transitions that occur in the system and analyse the crystallization products with high-quality crystallographic information. Lucky for Acta Crystallographica Section C that such a delicious structural study was published here

Supramolecular hair dyes : a new application of cocrystallization

The manuscript presents the first report of hair dyes of various colors formed by the cocrystallization reactions. Unlike the most popular oxidative hair dye (OHD) products, these dyes are NH3 free and do not require H2O2 as a color developer. The importance of these new hair dyes products is further enhanced by recent reports which indicate that some of the OHDs may be carcinogeni

Hidden solvates and transient forms of trimesic acid

This article discusses the formation of trimesic acid (TMA) solvates with ethanol, isopropyl alcohol and dimethylformamide via liquid-assisted grinding and slurry experiments. Through the use of X-ray diffraction methods, we highlight the formation of a new ethanol solvate of TMA that completes the series of alcohol solvates observed, a temperature-induced phase transition in the isopropyl alcohol solvate between 233 K and 243 K, and a transient 1:3 solvate with dimethylformamide that mimics a previously identified dimethylsulfoxide solvate. The alcohol structures possess a TMA framework that is geometrically similar where the intermolecular energies between TMA molecules are equivalent. We have observed that increasing the length of the alcohol induces an increase in the distortion of the TMA framework to accommodate the longer alkyl tails

Crystal structure of a mixed solvated form of amoxapine acetate

The mixed solvated salt 4-(2-chloro­dibenzo[b,f][1,4]oxazepin-11-yl)piperazin-1-ium acetate-acetic acid-cyclo­hexane (2/2/1), C17H17ClN3O+·C2H3O2-·C2H4O2·0.5C6H12, crystallizes with one mol­ecule of protonated amoxapine (AXPN), an acetate anion and a mol­ecule of acetic acid together with half a mol­ecule of cyclo­hexane. In the centrosymmetric crystal, both enanti­omers of the protonated AXPN mol­ecule stack alternatively along [001]. Acetate anions connect the AXPN cations through N-H...O hydrogen bonding in the [010] direction, creating a sheet lying parallel to (100). The acetic acid mol­ecules are linked to the acetate anions via O-H...O hydrogen bonds within the sheets. Within the sheets there are also a number of C-H...O hydrogen bonds present. The cyclo­hexane solvent mol­ecules occupy the space between the sheets

Continuous cocrystallization of benzoic acid and isonicotinamide by mixing-induced supersaturation : exploring opportunities between reactive and antisolvent crystallization concepts

This study combines reactive and antisolvent crystallization concepts via mixing-induced supersaturation to demonstrate a wider range of options for solvent system selection in multicomponent crystallization. This approach was applied to investigate continuous crystallization of 1:1 and 2:1 cocrystals of benzoic acid and isonicotinamide. Design of Experiments was used to identify conditions where pure cocrystal phases are obtained and a continuous mixing-induced cocrystallization process was implemented to selectively produce either 1:1 or 2:1 cocrystals

Compression of glycolide-h4 to 6 GPa

This study details the structural characterisation of glycolide-h4 as a function of pressure to 6 GPa using neutron powder diffraction on the PEARL instrument at ISIS Neutron and Muon source. Glycolide-h4, rather than its deuterated isotopologue, was used in this study due to the difficulty of deuteration. The low-background afforded by Zirconia-Toughened Alumina (ZTA) anvils nevertheless enabled the collection of data suitable for structural analysis to be obtained to a pressure of 5 GPa. Glycolide-h4 undergoes a reconstructive phase transition at 0.15 GPa to a previously identified, form-II, which is stable to 6 GPa

Templated deprotonative metalation of polyaryl systems : facile access to simple, previously inaccessible multi-iodoarenes

The development of new methodologies to affect non-ortho functionalization of arenes has emerged as a globally important arena for research, which is key to both fundamental studies and applied technologies. Here, a range of simple arene feedstocks (namely, biphenyl, meta-terphenyl, para-terphenyl, 1,3,5-triphenylbenzene and biphenylene) are transformed to hitherto unobtainable multi-iodoarenes via a s-block metal sodium magnesiate templated deprotonative approach. These iodoarenes have potential to be used in a whole host of high impact transformations, as precursors to key materials in the pharmaceutical, molecular electronic and nanomaterials industries. Proving the concept, we have transformed biphenyl to 3,5-bis(N-carbazolyl)-1,1’-biphenyl, a novel isomer of 4,4’-bis(N-carbazolyl)-1,1’-biphenyl (CPB) which is currently widely employed as a host material for organic light-emitting diodes, OLEDs

From discovery to scale-up: alpha-lipoic acid : nicotinamide co-crystals in a continuous oscillatory baffled crystalliser

The crystalline nutritional supplement alpha-lipoic acid degrades rapidly on exposure to temperatures above its melting point 65 degrees C and to light. A small-scale experimental co-crystal screen has produced three novel co-crystals of alpha-lipoic acid that each display enhanced thermal stability and differences in aqueous solubilities compared to alpha-lipoic acid. In each case, the initial screening procedure produced tens of milligrams of material enabling initial identification, characterisation and crystal structure determination. The structure of the alpha-lipoic acid : nicotinamide co-crystal was determined by single crystal X-ray diffraction and used for subsequent phase identification. Scale-up of the co-crystallisation process of alpha-lipoic acid with nicotinamide was then investigated in a continuous oscillatory baffled crystalliser. Over 1 kg of solid co-crystals was produced using a continuous crystallisation process in a continuous oscillatory baffled crystalliser at a throughput of 350 g h-1 yielding a purity of 99% demonstrating this as an effective route to rapid scale-up of a novel co-crystal system

From discovery to scale-up: alpha-lipoic acid : nicotinamide co-crystals in a continuous oscillatory baffled crystalliser

The crystalline nutritional supplement alpha-lipoic acid degrades rapidly on exposure to temperatures above its melting point 65 degrees C and to light. A small-scale experimental co-crystal screen has produced three novel co-crystals of alpha-lipoic acid that each display enhanced thermal stability and differences in aqueous solubilities compared to alpha-lipoic acid. In each case, the initial screening procedure produced tens of milligrams of material enabling initial identification, characterisation and crystal structure determination. The structure of the alpha-lipoic acid : nicotinamide co-crystal was determined by single crystal X-ray diffraction and used for subsequent phase identification. Scale-up of the co-crystallisation process of alpha-lipoic acid with nicotinamide was then investigated in a continuous oscillatory baffled crystalliser. Over 1 kg of solid co-crystals was produced using a continuous crystallisation process in a continuous oscillatory baffled crystalliser at a throughput of 350 g h-1 yielding a purity of 99% demonstrating this as an effective route to rapid scale-up of a novel co-crystal system