A new method for synthesis of N,N-diethyl-m-methylbenzamide
Keywords:
m -Toluic acid, N, N-diethyl-m-toluamide, ingredient, insects repellent.Abstract
Introduction: N, N-diethyl-m-methylbenzamide or N, N-diethyl-m-toluamide (DEET), is well known as an insect repellent. In addition, it is used to improve the dermal and transdermal delivery of many drugs.Objectives: To present a feasible procedure to synthesize DEET from m-toluic acid and diethylamine.
Methods: The m-toluic acid was activated with 1,1'-carbonyl-diimidazole, to obtain the intermediate product 1- (m-toluoyl) imidazole that continues to react with diethylamine, to produce DEET. In this way, the factors affecting the synthesis of N, N-diethyl-m-toluamide are improved.
Results: DEET was obtained through an optimal procedure. The by-products of the reaction are soluble in water; they are easily removed by the liquid-liquid extraction method with water and dichloromethane. Most of the DEET obtained has high purity. The yields were 94 to 95 %.
Conclusions: An improved route has been provided for a simple and efficient synthesis of DEET from m-toluic acid and diethylamine in the presence of 1,1'-carbonyl-diimidazole. The synthesis procedure was carried out in one-pot, and the isolation of DEET was achieved by liquid-liquid extraction. The total procedure time was significantly reduced. This synthesis method is easily scalable and industrially feasible.
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References
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3. Warren J, Westphal D, Zoubek S. Pfizer Inc. Process for the production of amides. Wipo Patent WO 2002036559. 2002 Sep 6. Available from: https://patents.google.com/patent/WO2002036559A3/en?oq=WO+2002036559
4. Khalafi-Nezhad A, Parhami A, Soltani R, Navid M, Zarea A. Efficient method for the direct preparation of amides from carboxylic acids using tosyl chloride under solvent-free conditions, Tetrahedron Letters. 2005 [access: 10/03/2020]; 46(40): 6879-82. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0040403905017399
5. Krull M, Morschhaeuser R, Lerch A, Ritter H, Schmitz S. Clariant International Ltd. Process for the preparation of tertiary amides of alkylphenylcarboxylic acids. Germany Patent DE 102006047620. 2008 Nov 27. Available from: https://patents.google.com/patent/DE102006047620B4/en?oq=DE+102006047620
6. Zhang F. Tianjin Chemical Reagent Research Institute. Method for preparing of N,N-diethyl-m-methylbenzoyl amide, Chinese Patent CN 101,914,034. 2010 Dec 15. Available from: https://patents.google.com/patent/CN101914034A/en?oq=CN+101%2c914%2c034
7. Croud VB, Maltas PJ, McCallien DWJ. Johnson Matthey Public Limited Company. Identifiable chemical product, Wipo Patent WO 2016185177. 2016 Nov 24. Available from: https://patents.google.com/patent/WO2016185177A1/en?oq=WO+2016185177
8. Peter KH, Edward G, Neeland. A Modified Synthesis of Insect Repellent DEET. Journal of Chemical Education. 1998 [access: 22/12/2019]; 75(10): 1267-1268. Available from: https://pubs.acs.org/doi/10.1021/ed075p1267
9. Zhuang Z, Zhi-Peng H, Liao, Wei-Wei. Asymmetric Synthesis of Functionalized Dihydronaphthoquinones Containing Quaternary Carbon Centers via a Metal-Free Catalytic Intramolecular Acylcyanation of Activated Alkenes. Organic Letters. 2014 [access: 08/01/2020]; 16(12): 3380-3. Available from: https://pubs.acs.org/doi/abs/10.1021/ol501427h
10. Habeck JC, Diop L, Dickman M. Synthesis of N,N-Diethyl-3-methylbenzamide (DEET): Two Ways to the Same Goal. Journal of Chemical Education. 2010 [access: 03/03/2020]; 87(5): 528-9. Available from: https://pubs.acs.org/doi/10.1021/ed800169h
11. Xie S, Lin H, Liu D, Shi C, Li L, Shen B, Zhang L. Guangzhou Liby Enterprise Group Co Ltd. A kind of mite-assistant fabricses care composition. Chinese Patent CN 104988725. 2015 Oct 21. Available from: https://patents.google.com/patent/CN104988725B/en?oq=CN+104988725
12. Ellis LC, Kise MA. Virginia Chemicals Inc. Process for the manufacture of N,N-diethyl-m-toluamide by aqueous caustic procedure. United State Patent US 3,870,756. 1975 Mar 11. Available from: https://patents.google.com/patent/US3870756A/en
13. Nery MS, Ribeiro RP, Lopes CC, Lopes RSC. Niobium pentachloride promoted conversion of carboxylic acids to carboxamides: Synthesis of the 4-aryl-1,2,3,4-tetrahydroisoquinoline alkaloid structures. Synthesis. 2003 [access: 05/03/2020]; 2: 272-6. Available from: https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2003-36823
14. Chaysripongkul S, Pluempanupat W, Jang DO, Chavasiri W. Application of Cl3CCONH2/PPh3 towards the synthesis of bioactive amides. Bulletin of the Korean Chemical Society. 2009 [access: 08/03/2020]; 30(9): 2066-70. Available from: https://koreascience.or.kr/article/JAKO200902727494345.page
Published
2021-12-03
How to Cite
1.
Thinh PD, Chau PD, Anh DD, Quyet DB, Duong VB. A new method for synthesis of N,N-diethyl-m-methylbenzamide. Rev Cubana Med Milit [Internet]. 2021 Dec. 3 [cited 2025 Mar. 13];50(4):e02101523. Available from: https://revmedmilitar.sld.cu/index.php/mil/article/view/1523
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