Medium Effect on the Rotational Barrier of Carbamates and Its Sulfur Congeners

Abstract

The solvent effect on rotation about the conjugated C-N bond has been studied for methyl N,N-dimethylcarbamate (1), S-methyl N,N-dimethylthiocarbamate (2), O-methyl N,N-dimethylthiocarbamate (3), and methyl N,N-dimethyldithiocarbamate (4). The present investigation included experimental determination of activation parameters (DeltaH, DeltaS, and DeltaG) combined with theoretical calculations via both quantum and classical approaches. Rotational barriers were measured through dynamic NMR experiments in solvents of varied polarity and proton donor ability. In the less polar solvents, the values were 15.3+/-0.5 (CS2), 14.0+/-1.1 (CS2), 17.5+/-0.4 (CCl4), and 14.6+/-0.5 kcal/mol (CCl4) for 1, 2, 3, and 4, respectively. Upon changing to an aqueous solution, the greatest variations occurred for 2 and 4, whereas for 1 and 3, there was no observable effect. Quantum chemical calculations at the HF/6-311+G(2d,p) and B3LYP/6-311+G(2d,p) levels, with the inclusion of solvation effects via the isodensity polarizable continuum model (IPCM), correctly reproduced the experimentally observed trends but failed to account for some of the measured rotational barrier's magnitudes. Hydrogen-bonding effects were included by performing molecular dynamic simulations. For these latter calculations, it was necessary to parametrize the force field against energies of water-solute complexes calculated at B3LYP/6-31+G(d,p). Through the results of radial distribution functions, solution rotational barriers could be calculated, presenting good agreement with experimental determinations and revealing the role of hydrogen bonding. Interestingly, only for 2, the rotational barrier is predicted to increase as a result of complexation with water. For the remaining compounds, hydrogen bonding causes the barrier to decrease, contrasting with most of the molecular systems studied up to now.

Hindered Rotation in Some Organic Dithiocarbamates

“…As for chemical shift assignments, kinetic data obtained in this work for Me 2 N-CSSEt (especially G # ) are in good agreement with those of Sandström for Me 2 N-CS-SMe (66.5 ± 2 kJmol −1 in CDCl 3 and 65.2 ± 1.7 kJmol −1 in o-dichlorobenzene [ODC]) 4 and of Pontes et al 10 (62.4 ± 0.8 kJmol −1 in C 6 D 6 and 66.6 ± 0.8 kJmol −1 in DMSO-d 6 ). As expected, the high rotation barriers obtained for dithiocarbamates 1-5 are consistent with hindered rotation involving disruption of the N-CS partial double bond.…”

“…6 For example, N-methylation of aromatic secondary amides or ureas causes a dramatic loss of their biological activity due to conformational change of the structures. 7 Other functional groups such as dithiocarbamates are expected to display similar properties, but a few conformational studies have been devoted to them 4,[8][9][10] or to some of their metal complexes. 8,11 We were even surprised to find in the literature a confusion with the broadened doublet at 4.61 ppm in the 1 H NMR spectrum of PhCH 2 NHCSSEt, which was assigned to NH proton resonance instead of CH 2 N of the minor conformer.…”

Rotational barriers of carbamate‐protected amine crosslinkers for hydrogels: A combined experimental and computational study

“…Theoretical studies on the rotational barriers of carbamates reported two possible transition states TS 1 and TS 2 , where the lone pair on the pyramidalized nitrogen is anti or syn to the carbonyl oxygen (Scheme ) . For methyl N , N ‐dimethylcarbamate, representing a typical carbamate, all quantum chemical calculations involving basis sets beyond 3‐21G* agree with each other in terms of the relative stability of the two transition states, i.e., that TS 1 is lower in energy than TS 2 , whereas the barrier heights depend slightly on the details of the level of theory and basis set used.…”

“…By dynamic NMR (DNMR) experiments, the rotational barriers can be estimated by lineshape analysis or from the coalescence temperature T C , i.e., the temperature where the exchange is fast enough that both rotamers are indistinguishable by NMR. Such DNMR studies have been carried out for amides, thioamides, amidines, carbamates, and thiocarbamates . The influences of different substituents on the rotational barriers have been extensively studied for amides (e.g., DMF) and amino acid derivatives, while carbamates are much less explored.…”

N-(2-Hydroxypropyl)formamide and N-(2-hydroxyethyl)-N-methylformamide as two new plasticizers for thermoplastic starch

“…When an N atom was attached to a double bond (as in >NAC@O), its lone pair electron can delocalize over the p system forming an approximately planar three-atom framework (Pontes, Basso, & dos Santos, 2007). Due to the barrier to internal rotation around the NAC(O) bond in amides, H, O, C, N and atoms attaching Fig.…”