A convenient synthesis of N-tert-butyl amides by the reaction of di-tert-butyl dicarbonate and nitriles catalyzed by Cu(OTf)₂

Abstract

The utility of Cu(OTf)2 as the catalyst for the synthesis of a series of N- tert-butyl amides in excellent isolated yields via the reaction of nitriles (alkyl, aryl, benzyl, and furyl nitriles) with di- tert-butyl dicarbonate is described. Cu(OTf)2 is a highly stable and efficient catalyst for the present Ritter reaction under solvent-free conditions at room temperature.

Facile preparation of N-tert-butyl amides under heat-, metal- and acid-free conditions by using tert-butyl nitrite (TBN) as a practical carbon source

“…Note that the reported protocols (Scheme 1c) for the conversion of nitriles to N-tert -butyl amides ( 2 ) generally utilize tert -butyl alcohol, tert -butyl-hydrogen peroxide, tert -butyl acetate, tert -butyl bromide, di- tert -butyl dicarbonate or methylpropene as a source of the tert -butyl unit, along with a stoichiometric amount of a mineral acid, Lewis acid or metal ion as a promoter at elevated temperatures. 12–18 Many of these reported procedures, however, are not applicable for scaled-up synthesis of N-tert -butyl amides ( 2 ) due to the rapid decomposition of tert -butyl sources into isobutylene gas under the reaction conditions. 14,19…”

“…We present herein an unprecedented function of TBN as a carbon ( tert -butyl group, Scheme 1d) source for the synthesis of N-tert -butyl amides ( 2 ) from nitriles ( 1 ) and water under very mild reaction conditions (Scheme 1d). Based on the control experiments and literature reports, 12–19 a feasible reaction mechanism has also been derived ( vide infra ).…”

“…Note the lack of effectiveness of many reported methods for the synthesis of N-( tert -butyl)acetamide ( 2b ) and N -( tert -butyl)trideuteroacetamide ( 2c ) from acetonitrile or trideuteroacetonitrile. 12–19 The reactions involving several benzylic nitriles and aryl nitriles were then investigated. Under the optimal conditions with a slightly extended reaction time of 24 h, both benzylic nitriles and aryl nitriles bearing electron-donating groups at the para - or meta -position reacted favourably and produced the anticipated N-tert -butyl amides ( 2i–2l and 2n–2u ) in good to excellent yields (Table 2).…”

“…A plausible reaction mechanism was derived considering the control experiments and previous literature reports (Scheme 4). 12–19…”