Cristina Puigjaner

Modular bis(oxazoline) ligands for palladium catalyzed allylic alkylation: Unprecedented conformational behaviour of a bis(oxazoline) palladium η3-1,3-diphenylallyl complex

New families of enantiopure bis(oxazolines) with 4,5-trans (5 a-g) or 4,5-cis (6 c) stereochemistry at the individual rings have been prepared in high yield. Their eta(3)-allyl palladium complexes (8 a-g, 9 c and 10) have been used as catalytic precursors in allylic alkylation reactions with excellent enantioselectivities (up to 96 %) for the trans oxazoline derivatives, while Pd/6 c system was inactive. NMR studies on palladium eta(3)-1,3-diphenylallyl intermediates (11 a, c and e) showed the presence of syn/syn- and syn/anti-allyl isomers in solution; this resembles the first example of eta(3)-eta(1)-eta(3) isomerism in Pd allylic complexes containing bis(oxazolines) derived from malonic acid.

New polymorphic hydrogen bonding donor-acceptor system with two temperature coincident solid-solid transitions†

The polymorphism study of dibenzylsquaramide reveals the appearance of two forms sharing a solid–solid transition at the same temperature towards the highest melting polymorph.

Ziprasidone malate, a new trimorphic salt with improved aqueous solubility

A new salt of ziprasidone with high aqueous solubility has been discovered as a result of a salt screening and it has been found to exist in three anhydrous polymorphic forms. One of these forms shows the highest aqueous solubility ever reported for ziprasidone salts in combination with a high kinetic stability, becoming a good candidate for further pharmaceutical development.

Cooperative induction in double H-bonding donor/acceptor compounds: Chains vs. ribbons

Two different types of monodimensional crystalline aggregates formed by squaramides, chains and ribbons, have been studied both in the solid state and ab initio with four model compounds. Although ribbons are a priori possible, only covalently forced syn conformations have been observed. Cooperative induction is postulated to explain the preference for chains instead of ribbons in squaramide crystals.

Cross-coupling of a functionalized highly pyramidalized alkene: DSC and NMR study of the [2+2] retrocycloaddition of cyclobutane cross products, hyperstability and pyramidalization of the formed dienes

Abstract The synthesis, chemical trapping and ab initio calculations of the highly pyramidalized 5α,6α:11α,12α-bis(isopropylidenedioxy)pentacyclo[6.4.0.0 2,10 .0 3,7 .0 4,9 ]dodec-8-ene, 25 , are reported. Its cross-coupling reaction with 3,7-dimethyltricyclo[3.3.0.0 3,7 ]oct-1(5)-ene, 1b , gave a cyclobutane derivative, 29 , which on further manipulations gave the cyclobutane derivatives 32 and 33 and the derived [2+2] retrocycloaddition dienes, 31 and 34 . Molecular Mechanics calculations show these dienes to be slightly pyramidalized but highly hyperstable. The neat conversion of 32 and 33 to 31 and 34 , respectively, has been studied by DSC, 1 H NMR and theoretical methods (MM2 and ab initio).

A cocrystal is the key intermediates for the production of a new polymorph of Vorinostat

A new kinetically stable polymorph of Vorinostat has been discovered as a result of a polymorph screening, however an impurity is always formed in its preparation by crystallization. The interaction of Vorinostat with ammonia yields a new cocrystal which transforms easily through thermal desorption into the new polymorph with a high degree of purity.

Polymorphism of (S)-triphenylglycol: kinetic dependent transformation of a new multipolymorphic system

The appearance of six new polymorphic forms of (S)-triphenylglycol and the kinetically dependent transformation observed by DSC by means of quenching from the melt are reported.

The polymorphism of a triarylphosphine oxide: a case of missing isomers

An experimental and computational study of the polymorphism of o-nitrophenyldiphenylphosphine oxide (1) has been carried out. Two polymorphs of 1 have been obtained after a comprehensive screening procedure and their structures have been determined by single crystal diffraction. Both forms present the same racemic mixture of the Ps and Ms enantiomers, where NO2 is in a syn conformation relative to the PO group, thus resulting in the presence of a short PO⋯O2N contact (ca. 2.97 A). The anti conformation has not been found in any of these polymorphs, thus suggesting the attractive nature of the PO⋯O2N intramolecular interaction. However, MP2 computations on various model systems led to the conclusion that this interaction is energetically destabilizing. An energy analysis of all the symmetry-unique pairs found within the first-nearest neighbour of the experimental polymorphs (all with a syn conformation), and of their corresponding (non-observed) anti conformations, reveals a slightly higher stability of the former. Therefore, if the crystallization of both polymorphs of 1 was only dominated by the energetics of this molecule, the syn and anti conformations should both be present in the crystals. The absence of the latter suggests that the final outcome of this crystallization is not solely determined by the 1⋯1 intermolecular interactions. Instead, 1–solvent interactions, the presence of nucleation-driving centres, for instance, in the container–solution interface, and kinetic factors of the nucleation process could also be relevant or play a leading role.

Assembling the puzzle of Apixaban solid forms

An in-depth analysis of the solid forms of the anticoagulant drug Apixaban (APX) has been conducted to sort out the confusion in the scientific and patent literature regarding the solid forms landscape. The nomenclature employed and the accompanying characterization data are often unclear and incomplete, leading to a situation in which apparently the same form has been reported by different authors or claimed by different inventors. A comprehensive solid forms screen and a full and careful comparison with the literature data has been performed to draw a reliable picture of the solid forms landscape of APX.