Benzoxazole and Benzothiazole Synthesis from Carboxylic Acids in Solution and on Resin by Using Ethyl 2‐Cyano‐2‐(2‐nitrobenzenesulfonyloxyimino)acetate and para‐Toluenesulfonic Acid

Abstract

Am etal-free and catalytic methodf or the synthesis of 2-substitutedb enzoxazoles and benzothiazoles from N-protecteda mino acids and carboxylic acids is described. The synthesis of benzoxazole on as olid support is demonstrated by the synthesis of benzoxazole attached to ah uman islet amyloid polypeptide, hIAPP [22][23][24][25][26][27] ,f ragment and benzoxazole derivatives of the side chain of aspartic acido n am odified fragment of Ab 18À21 (amyloid b)p eptide. The reactions proceeded through at wo-step mechanism.T he coupling step is realized with ar elativelyn ew reagent, ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate (ortho-NosylOXY), and the cyclization step takes place thanks to an inexpensive organocatalyst, para-toluenesulfonic acid, under microwavei rradiation. To the best of our knowledge,t his is the first report of the complete synthesis of benzoxazole derivatives of ap olypeptide on aresin solid support.

Preparation of Benzothiazolyl-Decorated Nanoliposomes

“…In order to enable cyclization of 5 , we used acetic acid (AcOH), which favors the cyclization of the reduced free thiol group of 5 to the desired Palm-BTH ( 6 : Figure 2D; 17 min), after 1h stirring of the acidified mixture at rt. This experiment revealed the importance of using an acid as catalyst, in order to effectively enable the cyclization of 2- N -palmitoyl-aminobenzenethiol 5 and the formation of the desired Palm-BTH 6 [42,43]. Herein we selected AcOH, which is an inexpensive, readily available and easily handled reagent.…”

Synthesis of β‐Amino Alcohols Using Ethyl 2‐Cyano‐2‐(2‐nitrobenzenesulfonyloxyimino)acetate (o‐NosylOXY)

“…Initially, the carboxylic acid attacks the sulfonyl center of I , resulting in activated sulphonate ester ( II ) and Oxyma anion. Further this anionic Oxyma attacks on the carbonyl carbon of II and results in the formation of the intermediate III with concomitant release of the sulfonic acid. Finally, the activated Oxyma ester of the carboxylic acid ( III ) reduced to the corresponding alcohols by NaBH 4 .…”

“…Recently, we have reported the use of ethyl‐2‐cyano‐2‐(2‐nitrobenzenesulfonyloxyimino) acetate ( o ‐NosylOXY, I , Figure ) as a new and efficient coupling reagent. We have achieved the conversion of the carboxylic acids to amides, peptides, esters, thioesters, hydroxamates, ureas, heterocyclic compounds such as benzoxazoles and benzthiazoles by using I . Conversion of aldoximes to nitriles was also possible by using I .…”

OxymaPure Coupling Reagents: Beyond Solid-Phase Peptide Synthesis

“…59 o-NosylOXY readily activates carboxylic acids to afford amides, peptides, esters, thioesters, hydroxamates, alcohols and heterocyclic compounds. 60,61 As a salient feature of the reagent, after completion of the reaction it produces only the solid byproducts OxymaPure and 2-nitrobenzene sulfonic acid, which can be recovered easily and reused to prepare the same coupling reagent (Scheme 17).…”