• CHIRAGKUMAR J GOHIL Discipline of Pharmacy, Gujarat Technological University, Ahmedabad, Gujarat, India.
  • MALLESHAPPA N NOOLVI Department of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Surat, Gujarat, India.


Objective: Amide is one of the most important functional group presents in the chemicals, pharmaceuticals, and foods. Conventionally, it has been synthesized from the carboxylic acid and amines. This conventional reaction is lengthy and involves hazardous chemicals and solvents. Hence, it poses waste management, solvent removal, and environmental issues to the industries. To overcome this limitation, we have reported the green chemistry-based method for the synthesis of amide from carboxylic acid and urea.

Methods: In this reaction, we have used boric acid as a catalyst, it is a simple and readily available compound. It is simple, efficient, and solvent-free procedure which involves the trituration of the reactant mixture and subsequent, direct heating of the triturated mixture.

Results: The rate of reaction is very high and can synthesize the amide quickly.

Conclusion: Various amides were prepared in good yield by this technique.

Keywords: Carboxylic acid, Urea, Boric acid, Amides, Green chemistry, Solvent-free method, Trituration and direct heating


1. Valeur E, Bradley M. Amide bond formation: Beyond the myth of coupling reagents. Chem Soc Rev 2009;38:606-31.
2. Machetti F, Bucelli I, Indiani G, Kappe CO, Guarna A. Parallel synthesis of an amide library based on the 6,8-dioxa-3-azabicyclo[3.2.1] octane scaffold by direct aminolysis of methyl esters. J Comb Chem 2007;9:454-61.
3. Pattabiraman VR, Bode JW. Rethinking amide bond synthesis. Nature 2011;480:471-9.
4. Xiao F, Liu Y, Tang C, Deng GJ. Peroxide-mediated transition-metal-free direct amidation of alcohols with nitroarenes. Org Lett 2012;14:984-7.
5. Ghose AK, Viswanadhan VN, Wendoloski JJ. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem 1999;1:55-68.
6. Lanigan RM, Sheppard TD. Recent developments in amide synthesis:Direct amidation of carboxylic acids and transamidation reactions. Eur J Org Chem 2013;2013:7453-65.
7. Khalafi-Nezhad A, Mokhtari B, Soltani Rad MN. Direct preparation of primary amides from carboxylic acids and urea using imidazole under microwave irradiation. Tetrahedron Lett 2003;44:7325-8.
8. Leggio A, Belsito EL, De Luca G, Di Gioia ML, Leotta V, Romio E, et al. One-pot synthesis of amides from carboxylic acids activated using thionyl chloride. RSC Adv 2016;6:34468-75.
9. Swamy T, Raviteja P, Subba Reddy BV, Ravinder V. Efficient method for the synthesis of benzamides from benzoic acids and aryl isothiocyanates using K2HPO4. ChemistrySelect 2017;2:7612-4.
10. Crochet P, Cadierno V. Catalytic synthesis of amides via aldoximes rearrangement. Chem Commun 2015;51:7612-4.
11. Constable DJ, Dunn PJ, Hayler JD, Humphrey GR, Leazer JL Jr., Linderman RJ, et al. Key green chemistry research areas--a perspective from pharmaceutical manufacturers. Green Chem 2007;9:411-20.
12. Kidwai M. Dry media reactions. Pure Appl Chem 2001;73:147-51.
13. Ivankovi? A, Dronji? A, Bevanda AM, Tali? S. Review of 12 principles of green chemistry in practice. Int J Sustain Green Energy 2017;6:39-48.
14. Marvaniya HM, Modi KN, Sen DJ. Greener reactions under solvent free conditions. Int J Drug Dev Res 2011;3:42-51.
15. Mylavarapu RK, Kondaiah GC, Kolla N, Veeramalla R, Koilkonda P, Bhattacharya A, et al. Boric acid catalyzed amidation in the synthesis of active pharmaceutical ingredients. Org Process Res Dev 2007;11:1065-8.
16. Kamali M, Shockravi A, Doost MS, Hooshmand SE. One-pot, solvent-free synthesis via Biginelli reaction: Catalyst-free and new recyclable catalysts. Cogent Chem 2015;1:1081667.
17. Ge C, Li L, Zhang R, Wang R, Zhang X. Amidation of aromatic amine and benzoic acid under boric acid catalysis. Asian J Chem 2014;26:6805-7.
18. Tang T. Boric acid catalyzed amide formation from carboxylic acids and amines: N-benzyl-4-phenylbutyramide. Org Synth 2005;81:262-72.
19. Arce G, Carrau G, Bellomo A, Gonzalez D. Greener synthesis of an amide by direct reaction of an acid and amine under catalytic conditions. World J Chem Educ 2015;3:27-9.
20. Jursic BS, Zdravkovski ZA. Simple preparation of amides from acids and amines by heating of their mixture. Synth Commun 1993;23:2761-70.
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How to Cite
GOHIL, C. J., and M. N NOOLVI. “SOLVENT-FREE SYNTHESIS OF AMIDE: A NOVEL TECHNIQUE OF GREEN CHEMISTRY”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 14, no. 5, May 2021, pp. 99-102, doi:10.22159/ajpcr.2021.v14i5.40688.
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