Reactions of the Cumyloxyl and Benzyloxyl Radicals with Tertiary Amides. Hydrogen Abstraction Selectivity and the Role of Specific Substrate-Radical Hydrogen Bonding

Abstract

A time-resolved kinetic study in acetonitrile and a theoretical investigation of hydrogen abstraction reactions from N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA) by the cumyloxyl (CumO(•)) and benzyloxyl (BnO(•)) radicals was carried out. CumO(•) reacts with both substrates by direct hydrogen abstraction. With DMF, abstraction occurs from the formyl and N-methyl C-H bonds, with the formyl being the preferred abstraction site, as indicated by the measured kH/kD ratios and by theory. With DMA, abstraction preferentially occurs from the N-methyl groups, whereas abstraction from the acetyl group represents a minor pathway, in line with the computed C-H BDEs and the kH/kD ratios. The reactions of BnO(•) with both substrates were best described by the rate-limiting formation of hydrogen-bonded prereaction complexes between the BnO(•) α-C-H and the amide oxygen, followed by intramolecular hydrogen abstraction. This mechanism is consistent with the very large increases in reactivity measured on going from CumO(•) to BnO(•) and with the observation of kH/kD ratios close to unity in the reactions of BnO(•). Our modeling supports the different mechanisms proposed for the reactions of CumO(•) and BnO(•) and the importance of specific substrate/radical hydrogen bond interactions, moreover providing information on the hydrogen abstraction selectivity.

Absolute Rate Constants for Hydrogen Atom Transfer from Tertiary Amides to the Cumyloxyl Radical: Evaluating the Role of Stereoelectronic Effects

“…41 When the decrease in k H observed on going from DMA to DEA, which largely reflects HAT from the α-C−H bonds of the Nalkyl groups, is taken into account, a similar decrease in reactivity should also be observed for HAT from the α-C−H bonds of the N-alkyl groups on going from DMF to DEF. The almost identical k H values measured for the reactions of CumO…”

“…• and DMA, 41 combined with the observation that the C−H bonds of tert-butyl groups display an extremely low reactivity toward alkoxyl radicals, 56 indicate that HAT from TMP to CumO…”

“…• with DMA in acetonitrile solution, 41 HAT preferentially occurs from the N-methyl group that is in a trans relationship to the carbonyl group. This result is in line with the 2.1 kcal mol −1 lower BDE value calculated for the α-C−H bonds of the trans N-methyl group in comparison to those of the group in the cis arrangement.…”

“…Also included in this table are the k H values measured previously for the reactions of CumO • with DMF and DMA. 41 In order to provide a better understanding of the HAT selectivity observed in the reactions of CumO…”

“…The calculated BDEs for the different C−H bonds of these substrates are displayed in Table 2, together with the previously calculated values for DMF and DMA. 41 …”