gem-Diol and Hemiacetal Forms in Formylpyridine and Vitamin-B₆-Related Compounds: Solid-State NMR and Single-Crystal X-ray Diffraction Studies

Abstract

The gem-diol moieties of organic compounds are rarely isolated or even studied in the solid state. Here, liquid- and solid-state NMR, together with single-crystal X-ray diffraction studies, were used to show different strategies to favor the gem-diol or carbonyl moieties and to isolate hemiacetal structures in formylpyridine and vitamin-B-related compounds. The change in position of the carbonyl group in pyridine compounds had a clear and direct effect on the hydration, which was enhanced by trifluoroacetic acid addition. Because of their biochemical importance, vitamin-B-related compounds were studied with emphasis on the elucidation of the gem-diol, cyclic hemiacetal or carbonyl structures that can be obtained in different experimental conditions. In particular, new racemic mixtures for the cyclic hemiacetal structure from pyridoxal are reported in trifluoroacetate and hydrochloride derivatives.

Paramagnetic solid-state NMR assignment and novel chemical conversion of the aldehyde group to dihydrogen ortho ester and hemiacetal moieties in copper(ii)- and cobalt(ii)-pyridinecarboxaldehyde complexes

“…In particular, nitrogen heterocycles such as imidazole and pyridine molecules containing carbonyl or its hydrated groups known as gem-diols are widely used, due to their coordination properties, [1][2][3][4] especially in catalysis and environmental chemistry. Working with this kind of system is a challenge since the instability of gemdiol [5][6][7][8][9][10] creates uncertainty over the form of the ligand, hence careful characterization is particularly important. 9,[11][12][13][14] Taking into account the key role of NMR spectroscopy in characterizing the chemical structure of new compounds, copper and cobalt complexes containing this type of ligand are a challenge for this technique.…”

gem‐Diol‐Type Intermediate in the Activation of a Ketone on Sn‐β Zeolite as Studied by Solid‐State NMR Spectroscopy

“…In organic synthesis, the attack of oxygen‐containing nucleophiles (e.g., H 2 O and OH − ) on the carbonyl group of aldehydes and ketones usually leads to an unstable gem ‐diol structure . Recently, stable gem ‐diol‐type species were identified in carbonyl‐containing organic compounds, such as formylpyridine and imidazole derivatives, which have 13 C signals in the range of 70–100 ppm. Thus, it is most likely that the ‐OH group of the open Sn site is involved in the nucleophilic attack on the carbonyl group of adsorbed [2‐ 13 C]acetone producing a gem ‐diol‐type species, which probably resonates at 76 ppm in the 13 C NMR spectrum.…”

“…[18] To explore the interaction of alcohol with the Sn site, 13 Clabelled [2-13 C]isopropanol was deliberately adsorbed on Sn-b zeolite.Asshown in the 13 CNMR spectrum ( Figure S2), both the physisorbed isopropanol and isopropyl alkoxy species generated by the dehydration of isopropanol are observed on the zeolite,which produce methenyl signals at 69 and 72 ppm, respectively.I no rganic synthesis,t he attack of oxygencontaining nucleophiles (e.g., H 2 Oand OH À )onthe carbonyl group of aldehydes and ketones usually leads to an unstable gem-diol structure. [19] Recently,s table gem-diol-type species were identified in carbonyl-containing organic compounds, such as formylpyridine [20] and imidazole [21] derivatives,which have 13 Cs ignals in the range of 70-100 ppm. Thus,i ti sm ost likely that the -OH group of the open Sn site is involved in the nucleophilic attack on the carbonyl group of adsorbed [2- 13 C]acetone producing a gem-diol-type species,w hich probably resonates at 76 ppm in the 13 CNMR spectrum.…”

Generation and Stability of the gem-Diol Forms in Imidazole Derivatives Containing Carbonyl Groups. Solid-State NMR and Single-Crystal X-ray Diffraction Studies

“…Understanding the chemistry of gem -diols is crucial for the development of synthetic methods to obtain new organic ligands, which are often used for the design of single-molecule magnets and metal complexes. − A high number of metal complexes bearing gem -diols has been reported, − in which the presence of these moieties is generally demonstrated by single-crystal X-ray diffraction. − As a rule, the stability of this functional group is not studied in the free ligand before the preparation of the metal complex.…”

“…As for biochemistry aspects, solution-state NMR and X-ray crystallography experiments have been used to confirm the formation of gem -diol and hemiacetal structures, for example, as intermediate structures in the binding of α-chymotrypsin with a macrocyclic peptidomimetic aldehyde . Particularly, X-ray studies have been conducted to elucidate the structure of a gem -diol intermediate in the catalysis exerted by the HIV-1 protease. , Furthermore, solid-state NMR (ss-NMR) is a useful methodology to elucidate the chemical composition of mixtures in which both gem -diol and carbonyl forms are present . In the latter cases, on the one hand, high-performance liquid chromatography techniques may be used; however, dissolution of the sample in acid/water mixtures and proper optimization of the chromatographic system are required.…”