Polymorphism in Crystalline Cinchomeronic Acid

Abstract

The structural relationship between the two crystal forms of cinchomeronic acid (CA 3,4-dicarboxypyridine) has been investigated by single crystal X-ray diffraction, IR and Raman spectroscopy and solid state NMR spectroscopy, showing that the two polymorphs form a monotropic system, with the orthorhombic form I being the thermodynamically stable form, while the monoclinic form II is unstable. In both forms CA crystallizes as a zwitterion and decomposes before melting. The crystal structure and spectroscopic analysis indicate that the difference in stability can be ascribed to the strength of the hydrogen-bonding patterns established by the protonated N-atom and the carboxylic/carboxylate O-atoms.

Solid‐State NMR Studies on Supramolecular Chemistry

“…distinct motions, ranging from simple C 6 -rotations of benzene-d 6 at low temperatures to rather ill-defined 180 • phenyl flips of fluorobenzene-d 5 . 67 The large CSA associated with the carbonyl resonances in the 13 C cross polarization magic angle spinning (CPMAS) spectrum at room temperature of crystalline Cr(CO) 3 (η 6 -C 6 H 6 ) indicates that the carbonyl moieties are rigid due to crystalline packing constraints. Conversely 13 C carbonyl and deuterium data of Cr(CO) 3 (η 6 -C 6 H 6 ) included in β-CD selectively enriched in 13 C (carbonyl ligand) and 2 D (arene ligand) respectively, 68 show that a fast motion of the guest molecule is present.…”

“…67 The large CSA associated with the carbonyl resonances in the 13 C cross polarization magic angle spinning (CPMAS) spectrum at room temperature of crystalline Cr(CO) 3 (η 6 -C 6 H 6 ) indicates that the carbonyl moieties are rigid due to crystalline packing constraints. Conversely 13 C carbonyl and deuterium data of Cr(CO) 3 (η 6 -C 6 H 6 ) included in β-CD selectively enriched in 13 C (carbonyl ligand) and 2 D (arene ligand) respectively, 68 show that a fast motion of the guest molecule is present. The entire molecule does not rotate isotropically inside the cavity, but with a C 6 rotation around the main molecular axis of symmetry.…”

“…The entire molecule does not rotate isotropically inside the cavity, but with a C 6 rotation around the main molecular axis of symmetry. Interestingly the VT 13 C SSNMR spectra of (η 5 -C 5 H 5 ) 2 Mo 2 (CO) 6 included in γ -CD can only be interpreted by fast motion of one half of the dimer inside the CD cavity, whereas the nonincluded (η 5 -C 5 H 5 )Mo(CO) 3 part is rigid due to strong interatomic interaction with neighboring molecules. 69 Fast motion of the (η 5 -C 5 H 5 )Mo(CO) 3 part inside the hydrophobic cavity is explained by the weaker constrain forces.…”

Solid‐State NMR Investigation of Ligand Mobility and Reactivity in Transition Metal Complexes

“…[31] NMR techniques afford: 1. a unique selectivity that allows the differentiation of chemically distinct sites, including protons, [32] on the basis of the chemical shift; [33] 2. the possibility of investigating the presence (and the strength) of HB from the 1 H chemical shift of hydrogen bonded signals in 1 H MAS experiments [34] or evaluating the protonation state from chemical shift tensor (CST) values obtained from the analysis of low spinning speed spectra; [35] 3. the ability of determining homonuclear ( 1 H-1 H, 13 C-13 C, ...) and heteronuclear ( 1 H-13 C and 1 H-31 P, ...) proximities from 2D spectra; [36] 4. the opportunity of obtaining interatomic distances from the analysis of dipolar spinning sideband obtained from redor-like experiments; [37] 5. the ability of detecting and characterizing polymorphs and intermediate species from the combined analysis of spectral editing and 2D experiments.…”

Didanosine Polymorphism in a Supercritical Antisolvent Process

“…It is well known that advanced solid‐state NMR techniques provide several structural and dynamic data useful in many areas, in particular those concerning polymorphism in pharmaceutical,4, 42 organic,43–45 and in crystal engineering46, 47 fields. Due to recently developed techniques based on the dipole–dipole interaction between homo‐ and heteronuclei,23 solid‐state NMR is becoming essential where X‐ray structures are not available 48, 49.…”