Benzyl Acetylcarbamate Potassium Salt (BENAC-K): A Simple Nucleophilic N-Acetamide Equivalent

Abstract

Benzyl acetylcarbamate potassium salt (BENAC-K) has been developed as a simple nucleophilic acetamide equivalent. A broad variety of alkyl halides were converted into benzyloxycarbonyl-protected N-alkylacetamides in high yields by simple treatment with an almost equimolar (1.1 equiv) amount of BENAC-K in a polar solvent.

<i>p</i>-Methoxy- and 2,4-Dimethoxybenzyl <i>N</i>-Acetylcarbamate Potassium Salts: Versatile Reagents for <i>N</i>-Alkylacetamide and <i>p</i>-Methoxy- and 2,4-Dimethoxybenzyl Carbamates

“…The high reactivity of Moz toward hydrogenation is similar to that of the Cbz group in a previous report. 18) The selective removal of acetyl groups was demonstrated using α-amino acid derivatives 12a-b and 13a-b (Fig. 4c).…”

“…41) Their stability is sufficient for practical use, in contrast to that of t-butyl acetylcarbamate potassium salt (Boc(Ac) N − K + ), which could not be developed as a reagent because of its hygroscopic nature. 18) Reactions using PM-and 2,4-DM-BENAC-Ks (1a-b) were performed in dimethylformamide (DMF) without additives according to the optimized reaction conditions in our previous reports 18) for the original BENAC-K (Fig. 3), and the substrate scope for the substitution reactions using 1a-b was comparable to that of BENAC-K. For example, a variety of primary alkyl halides, including benzyl 3-bromopropyl ether, lauryl bromide, isobutyl bromide, and cyclohexyl bromide, were subjected to alkylation in DMF at 60-80 °C (entries 1-8).…”

“…Significantly, the formation of O-alkylated byproducts was suppressed to provide alkylated products 13a-b and 15a-b in practical yields when reactions were conducted in a less-polar solvent using 18-crown-6 (entries 17, 18, 25, and 26). 18) We speculated that the reactivity of a "hard" oxygen nucleophile diminished because the alkyl halide and triflate were less polarized in apolar solvents.…”

“…4a). The Cbz group of 16, which is a product of 3-bromopropyl benzyl ether and BENAC-K, 18) was removed by trifluoroacetic acid at room temperature. However, 16 was unreactive under milder acidic conditions using formic acid, which readily cleaved the Moz group of 5a after 1 h. The Dmoz group was sensitive in less acidic conditions, such as acetic acid in CH 2 Cl 2 or a catalytic quantity of TsOH•H 2 O in MeOH-CH 2 Cl 2 co-solvent.…”

“…To address the aforementioned issue, we recently developed a benzyl N-acetylcarbamate potassium salt (BENAC-K) as a simple and useful reagent for the construction of N-alkylacetamide moieties from alkyl halides and alkyl sulfonates [17][18][19] (Fig. 2A).…”