The role of ammonia oxide in the reaction of hydroxylamine with carboxylic esters

Abstract

Theoretical calculations indicate that hydroxylamine can exist in both neutral and zwitterionic (ammonia oxide) forms in aqueous solution, the former being 3.5 kcal mol(-1) more stable. In this report, we have studied the reaction mechanism of hydroxylamine with phenyl acetate and analyzed the role of the zwitterionic isomer. We have observed that the main reaction pathway takes place through the zwitterionic form with a concerted mechanism, not involving the classical tetrahedral intermediate. Attack by the nitrogen atom (via neutral isomer) has a minor contribution and it is also a concerted process. The activation free energy barriers in aqueous solution were calculated at the MP4/TZVPP + diff level for gas phase energies, CPCM for optimization and frequencies, and through single point calculation of the solvation free energy using the SM8 method. Our theoretically predicted barriers are 20.8 and 23.8 kcal mol(-1) for O and N attack, respectively, in very good agreement with the experimental values of 20.4 and 22.3 kcal mol(-1), respectively. Our results support the view that hydroxylamine is a very special nucleophile and the reactivity of this functional group should be further investigated.

4-Cyanobenzenesulfonamides: Amine Synthesis and Protecting Strategy To Compliment the Nosyl Group

“…Treatment of 1 with 3.00 equiv of 10 M aqueous sodium hydroxide in tetrahydrofuran at 50 °C for 24 h afforded no reaction, as did treatment of 1 with 3.00 equiv of hydrazine in tetrahydrofuran at 50 °C for 24 h. Interestingly, treatment of 1 with 3.00 equiv of 50 wt % aqueous hydroxylamine (Figure , eq 4) at 50 °C for 5 h had completely converted 1 to two products identified by LCMS as the amidoxime 26 (hydroxylamine addition) and the primary amide 27 (water addition) in an ∼60:40 ratio. The high level of the hydrolysis product may be explained by O -attack of hydroxylamine, potentially though the tautomer, ammonia oxide, followed by hydrolysis of this activated imidate, a mode of reactivity proposed for hydroxylamine-mediated ester hydrolysis . A sulfonamide 29 (Figure , eq 5), prepared either from the sulfonylation of alanine derivative 28 (97% yield) to give the corresponding sulfonamide 30 (not shown), then alkylation (97% yield, 99.5 to 0.5 er), or through the Mitsunobu reaction of 4 with tert -butyl d -lactate (86% yield, 99.8 to 0.2 er) was found to undergo the deprotection to 31 in 80% yield; however, we isolated 11% of a tertiary amine product 32 , resulting from the migration of the sulfonamide aryl group to the α-carbon of the amino acid.…”

Reactivity and stability of ion pairs, dimers and tetramers versus solvent polarity: SNAr fluorination of 2-bromobenzonitrile with tetramethylammonium fluoride

“…We have named this basis set as 6-31(+)G(d). The solvent effect was included through the SMD [38] method with N,Ndimethylformamide (DMF) solvent, using 240 tesserae for atom to obtain numerically more stable potential of mean force surface [39,40].…”

Solvent selection for chemical reactions: automated computational screening of solvents using the SMD model

“…The PCM method was used in these optimizations with the methanol solvent and atomic cavities with 240 tesserae to generate an accurate and continuous potential of mean force surface. 44,45 The inclusion of the solvent in the optimizations provides more reliable geometries of the highly polar transition state. The use of other polar solvent hardly alters the geometries.…”