Microwave-assisted clean synthesis of amides via aza-wittig reaction under solvent-free condition

Abstract

O acoplamento de fosfazenos com cloretos de acila ou anidridos carboxílicos mediado por microondas na presença de fosfito de etila foi realizado, resultando nas correspondentes amidas, de maneira limpa e com bons rendimentos. Ao contrário das metodologias anteriores, que empregam solventes clorados, benzeno (cancerígeno), etc, este protocolo é eco-amigável, rápido e simples.A solvent-free microwave-assisted coupling of phosphazenes with acyl chlorides or carboxylic anhydrides in presence of triethylphosphite has been accomplished resulting in a clean synthesis of amides in good yields. Unlike the prevailing time-consuming solution phase methodologies employing chlorinated solvents, benzene (carcinogenic), etc, the present protocol is an eco friendly, rapid and simple approach. Keywords: microwave, solution phase, solvent-free, amide, aza-wittig IntroductionAmide is an ubiquitous functionality prevalent in natural products, peptides and potential drugs. 1 In view of this, extensive research towards developing elegant protocols for amide bond formation is in progress wherein attempts are being continuously made to eradicate the difficulties and limitations enveloped with the prevailing methods.Generally, the most relevant methodologies involve solution phase approach wherein the limitations associated with the polarity, refluxing temperature and the toxicity of the solvent/additives restrict their broad scope and question their eco-friendliness. Also, the components employed and formed as the by-products in the protocols play vital role in deciding the rate of the amide bond formation. Thus, all these aspects are to be considered in accomplishing timeconscious, eco-friendly protocols for amide bond formation.In particular, the direct coupling of an amine with a carboxylic acid results in an acid-base reaction to form a stable salt following which the amide bond formation has to fight against adverse thermodynamics as the equilibrium lies on the side of hydrolysis rather than synthesis (Scheme 1).Herein, azeotropic removal of water accumulated in the solution has been attempted 2 for accomplishing an effective synthesis of amides. Alternatively, molecular sieves are added to the solution to trap the water and expedite the reaction.On the other hand, the direct coupling of amines with carboxylic acids has been assisted by coupling reagents 3 (Scheme 2). Apparently, use of excess of coupling reagents and their corrosive nature is hazardous to the environment.Further, other approaches like aminocarbonylation 4 of aryl halides with amines and catalysis 5 in amide bond formation in solvent medium are with limitations such as loading of metal carbonyls/catalyst for large scale preparation and difficulties in reactivation/reusability of deactivated catalyst which may preclude the scope of their applicability. The polarity of the substrates and reagents puts restriction to the number of useful solvents. Further, solvents employed may either enhance or retard the rate of the reaction performed in view of differing interacti...

Effect of Microwave Cure on the Thermo-Mechanical Properties of Tung Oil-Based/Carbon Nanotube Composites

“…Microwave reactions have been used to speed-up and simplify reactions by removing the need for a solvent [31]. For example, amides have been synthesized with the Aza-Wittig reaction under microwaves in the absence of a solvent [31].…”

“…For example, amides have been synthesized with the Aza-Wittig reaction under microwaves in the absence of a solvent [31]. The conducting behavior of CNTs can be utilized for the fabrication of electrochemical sensors [32].…”

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