Stabilisation of metastable polymorphs: the case of paracetamol form III

YesThe design of a melt synthesis of the first air-stable formulation of the metastable form III of paracetamol is derived from thermo-spectroscopic and thermo-diffraction experiments. Melt crystallisation in the presence of β-1,4-saccharides produces form III selectively and the excipients appear to act as stabilising ‘active’ templates of the metastable polymorph.This article is part of themed collection: Pharmaceutical Solids

2-Thioureido-1H-benzimidazol-3-ium chloride monohydrate

In the title compound, C8H9N4S+·Cl−·H2O, the cation is approximately planar, with a dihedral angle of 7.71 (8)° between the mean planes of the benzoimidazole ring system and the thiourea unit. In the crystal, cations, anions and water molecules of crystallization are linked by O—H...Cl, N—H...O, N—H...Cl and N—H...S hydrogen bonds into a three-dimensional network. π–π stacking is observed between the benzene and imidazole rings of neighbouring molecules, the centroid–centroid distance being 3.5774 (11) Å

Thermomechanical effect in molecular crystals: the role of halogen-bonding interactions

The design and synthesis of mechanically responsive materials is interesting because they are potential candidates to convert thermal energy into mechanical work. Reported in this paper are thermosalient effects in a series of halogen derivatives of salinazids. The chloro derivative, with higher electronegativity and a weaker inter-halogen bond strength (Cl...Cl) exhibits an excellent thermal response, whereas the response is weaker in the iodo derivative with stronger I...I halogen bonding. 3,5-Dichlorosalinazid (Compound-A) exists in three polymorphic forms, two room-temperature polymorphs (Forms I and II) and one high-temperature modification (Form III). The transformation of Form I to Form III upon heating at 328–333 K is a reversible thermosalient transition, whereas the transformation of Form II to Form III is irreversible and non-thermosalient. 3,5-Dibromo- (Compound-B) and 3-bromo-5-chloro- (Compound-C) salinazid are both dimorphic: the Form I to Form II transition in Compound-B is irreversible, whereas Compound-C shows a reversible thermosalient effect (362–365 K). In the case of 3,5-diiodosalinazid (Compound-D) and 3,5-difluorosalinazid (Compound-E), no phase transitions or thermal effects were observed. The thermosalient behaviour of these halosalinazid molecular crystals is understood from the anisotropy in the cell parameters (an increase in the a axis and a decrease in the b and c axes upon heating) and the sudden release of accumulated strain during the phase transition. The di-halogen salinazid derivatives (chlorine to iodine) show a decrease in thermal effects with an increase in halogen-bond strength. Interestingly, Compound-B shows solid-state photochromism in its polymorphs along with the thermosalient effect, wherein Form I is cyan and Form II is light orange

Sequential One-Pot Carbene-Catalyzed Intramolecular Stetter Reaction and Acid-Mediated Condensation: Access to Heteroatom Analogues of π‑Extended Polyaromatic Hydrocarbons

In this Letter, we disclose a simple and effective method to access a variety of phenanthro[9,10-b]furan and 1H-dibenzo[e,g]indole derivatives based on the design of a carbene-catalyzed intramolecular Stetter reaction followed by a Paal–Knorr reaction in one-pot. These compounds are a class of π-extended polycyclic aromatic hydrocarbon (PAH) derivatives containing an oxygen/nitrogen atom. The practical utility of the developed transformation was demonstrated on the gram scales and postsynthetic transformations thereof

Investigating the Recrystallization Behavior of Amorphous Paracetamol by Variable Temperature Raman Studies and Surface Raman Mapping

In situ Raman spectroscopy and Raman mapping are used to monitor the crystallization of amorphous paracetamol in both covered and uncovered geometries, for which different crystallization pathways have been reported previously. The results suggest that surface crystallization predominates in the uncovered samples, leading to forms I and II, whereas in the covered samples bulk crystallization dominates and leads to form III

Efficient multicomponent synthesis of spiro[indoline-3,4′-thiopyran]-2-ones

<p>Synthesis of new thiopyran fused spirooxindoles (spiro[indoline-3,4′-thiopyran]-2-ones) were achieved by a multicomponent reaction of <i>N</i>-methyl isatin, malononitrile/ethyl cyanoacetate, and β-oxodithioester using <i>N,N</i>′-dimethylaminopyridine as the catalyst.</p

Pd-Catalyzed Chelation-Assisted Regioselective and Site Selective Cyclative C–H Annulation of Alkynyl Oximes with Activated Alkynes

Electrophilic cyclization and concomitant C–H annulation constitute an expedient cascade strategy for the construction of multicyclic scaffolds with precise substitutional patterns. We report here a novel Pd-catalyzed cyclative annulation of ynone oxime with activated alkynes. The cascade features a dual regioselectivity including site selective C–H activation and chelation-assisted selective insertion of alkynes. Control experiments together with kinetic experiments give insights into the mechanism

Oxygenative and Dehydrogenative [3 + 3] Benzannulation Reactions of α,β-Unsaturated Aldehydes and γ‑Phosphonyl Crotonates Mediated by Air: Regioselective Synthesis of 4‑Hydroxybiaryl-2-carboxylates

Regioselective synthesis of 4-hydroxybiphenyl-2-carboxylates via the base-mediated oxygenative [3 + 3] benzannulation reaction of α,β-unsaturated aldehydes and γ-phosphonyl crotonates is reported. A hydroxyl group is installed in the final product on the originally phosphorus-bound carbon via a novel oxygenative and dehydrogenative transformation. The reaction proceeds rapidly in an open flask, uses atmospheric oxygen as an oxidant, and affords good yields of substituted biaryl phenols

Simple approach to access tricyclic spiro dihydrofurans in a one-pot reaction

<p>A simple and efficient one-pot protocol is accomplished to access tricyclic spiro dihydrofurans (<b>4</b>) by the reaction of β-enamino ketones (<b>1</b>) and dimedone (<b>2</b>) in ethanol followed by sequential addition of <i>N</i>-chlorosuccinimide at ambient temperature for the first time. The selectivity in desired product formation in good yields is the advantage of this protocol.</p