A New Synthesis of an Amino Acid Based Sweetener

Properties and Synthetic Utility ofN-Substituted Benzotriazoles

“…The preparation of such condensation products directly from an amide, aldehyde, and benzotriazole was first thought to be limited to primary amides, to give 139 but was later applied also to secondary amides to give 142 . The reaction conditions required are more vigorous than for amines probably due to the lower nucleophilicity of amides compared to amines. − Primary amides react on refluxing in dry toluene with azeotropic removal of water, but secondary amides require the use of catalytic amounts of p -toluenesulfonic acid, or carrying out the reaction in aceticacid to give the benzotriazole adducts 142 (Scheme ). Formaldehyde and other aldehydes (R 3 ≠ H) can be used.…”

“…The reaction conditions required are more vigorous than for amines probably due to the lower nucleophilicity of amides compared to amines. [126][127][128][129][130][131][132] Primary amides react on refluxing in dry toluene with azeotropic removal of water, but secondary amides require the use of catalytic amounts of p-toluenesulfonic acid, or carrying out the reaction in acetic (145) in nearly quantitative yields (Scheme 57). 134 Reaction of carbamates with an aldehyde and benzotriazole requires p-toluenesulfonic acid as catalyst in toluene with azeotropic removal of water.…”

“…Cyanide anion, as expected, displaces the benzotriazole anion giving R-acylamino nitriles 814. 129,346 In Scheme 254 (Table 92), a novel benzotriazole-assisted method of peptide elongation is shown with the amidoalkylation of the cyanide anion as the key step. This reaction is combined with a smooth hydrolysis of the cyanide group into amide which completes the peptide cycle.…”

Benzotriazole-mediated amidoalkylations of nitroalkanes, nitriles, alkynes and esters

“…Benzotriazole mediated amidoalkylations introduced in 1988, 6 offer advantages over previously reported methods as was already demonstrated for the amidoalkylation of (i) Grignards, 6 (ii) malonates and acetoacetates, 7 (iii) cyanide anion, 8 (iv) mercaptans and alcohols, 9 (v) electron-rich (hetero)aromatics, 10 and (vi) amines 11 (Scheme 1).…”

Preparation of β-Amido Ketones and Aldehydes via Amidoalkylation of Enamines, Enol Silyl Ethers, and Vinyl Ethers

“…Amidoalkylations, which have been used widely in organic synthesis, 11a,b have provided many β-amidocarbonyl compounds. 12a-e Our previous work has demonstrated N -(1-benzotriazol-1-ylalkyl)amides to be versatile reagents for the amidoalkylation of malonates and acetoacetates, reactive aromatics, cyanide anion, mercaptans, alcohols, ammonia, ethyl diphenylphosphinite anion, primary and secondary amines, and triallylstannanes 22a,b giving in each case the expected products. We have previously reported one example that used an N -(benzotriazol-1-ylmethyl)benzamide to react with isopropenyl acetate to afford a β-amido ketone in relatively poor yield .…”