Table of Contents
Organic Chemistry International
Volume 2014, Article ID 617153, 4 pages
http://dx.doi.org/10.1155/2014/617153
Research Article

An Efficient Method for Synthesis of N-tert-Butyl Amides Using Oxalic Acid Dihydrate in Solvent-Free Condition

1Department of Chemistry, Rasht Branch, Islamic Azad University, P.O. Box 41325-3516, Rasht, Iran
2Department of Chemistry, Science and Research Amol Branch, Islamic Azad University, P.O. Box 678, Amol, Iran

Received 7 January 2014; Revised 17 February 2014; Accepted 21 March 2014; Published 8 April 2014

Academic Editor: Ashraf Aly Shehata

Copyright © 2014 Masoud Mokhtary and Seyedeh Khadijeh Nasernezhad. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

An efficient method for the synthesis of N-tert-butyl amides by reaction of nitriles with tert-butyl acetate or tert-butanol is described using oxalic acid dihydrate in solvent-free condition. The result showed that tert-butyl acetate served as a relatively better source of tert-butyl carbocation than tert-butanol.

1. Introduction

Solvent-free reactions obviously reduce pollution and bring down handling costs due to simplification of experimental procedure, work-up technique, and saving energy. These would be especially important during industrial production [1]. The Ritter reaction makes possible the conversion of a group, capable of giving a relatively stable carbonium ion, to a substituted amide by reaction with a nitrile in the presence of a strong acid [2]. The classical Ritter reaction is the reaction of alkenes and tertiary or benzylic alcohols with nitriles in the presence of concentrated sulfuric acid [35]. Several modifications have been attempted to improve Ritter reaction conditions. However, as an alternative to sulfuric acid, other acid catalysts such as (CF3SO2)2O [6], BF3-Et2O [7], Fe3+-Montmorillonite [8], Mg(HSO4)2 [9], Bi(OTf)3 [10], CeCl37H2O/AcCl [11], P2O5/SiO2 [12], and Nafion [13] are employed in the classical Ritter reaction. Ritter reaction using tert-butyl acetate instead of alcohol was also reported to be catalyzed by sulfuric acid [14, 15], FeCl36H2O [16], ZnCl2-SiO2 [17], and I2 [18]. However, most of these methods suffer from at least one of the following disadvantages such as vigorous reaction conditions, high cost and toxicity of the reagent, tedious work-up procedures, and instability and hygroscopic nature of the reagent. Also, the use of tert-butanol can be complicated by the melting point (26°C) leading to a semisolid at room temperature. An attractive alternative is tert-butyl acetate due to its ease of handling (bp 97-98°C), availability as a common solvent, and low cost [15]. Recently, oxalic acid was efficiently used as catalyst in variety of chemical reactions like imino Diels-Alder reaction [19], Beckmann rearrangement [20], protection of carbonyl to thioacetal, and deprotection of thioacetal to carbonyl as well [21]. The conversion of a nitrile to the corresponding N-tert-butyl amide is a very important transformation in organic synthesis. The N-tert-butyl amides are pharmaceutically useful [22] and also serve as precursors to the corresponding amines. In connection of our research to develop application of oxalic acid dihydrate for oxygenation of sulfides to sufoxides in the presence of H2O2 [23], herein, we found thatoxalic acid dihydrate can be used for preparation of N-tert-butyl amide derivatives in good yields. This method often leads to the development of simple and ecofriendly protocols for preparation of N-tert-butyl amides via modified Ritter reaction. Amidation of tert-butyl acetate or tert-butanol with nitriles using oxalic acid dihydrate. where , .

2. Materials and Measurements

All chemicals were purchased from Merck chemical company. Melting points were recorded on an electrothermal melting point apparatus. The NMR spectra were recorded in CDCl3 with TMS as an internal standard on a Bruker advance DRX 400 MHz spectrometer. IR spectra were determined on a SP-1100, P-UV-Com instrument. Elemental analyses were performed using a CHN-O Rapid Heraeus elemental analyser (Wellesley, MA). Purity determination of the products was accomplished by TLC on silica gel polygram SIL G/UV 254 plates. Products were identified by comparison of the obtained FT-IR and 1H NMR spectra with those reported for authentic samples.

3. Experimental

3.1. General Procedure for the Amidation Reaction

A solution of 5 mmol nitrile in 5 mmol tert-butyl acetate or tert-butanol was prepared. 2.5 mmol oxalic acid dihydrate was added to the solution and the reaction mixture was stirred for 2–9 h under 70°C until TLC analysis showed that no nitrile remained. The solid residue was recrystallized from water to afford pure crystals of the proper amides in 42–94% yields.

3.2. Characterization Data
3.2.1. N-tert-Butyl-3-methylbenzamide (d)

M.p.: 96-97°C. IR (KBr)  : 3382, 2962, 1643, 1529, 1447, 748 cm−1. 1H NMR (400 MHz CDCl3) = 1.49 (s, 9H), 2.4 (s, 3H), 5.95 (br s, 1H), 7.28–7.56 (m, 4H) ppm. Anal. Calcd. For C12H17NO: C, 75.35; H, 8.91; N, 7.32. Found: C, 75.15; H, 8.71; N, 7.22.

3.2.2. N-tert-Butyl-4-hydroxybenzamide (e)

M.p.: 189–192°C. FT- IR (KBr): = 3274, 3068, 2969, 1639, 1548, 1307, 935 cm−1. 1H NMR (400 MHz, CDCl3) = 1.49 (s, 9H), 5.97 (br s, 1H), 6.84 (d, 2H), 7.59 (d, 2H) ppm. Anal. Calcd. For C11H15NO2: C, 68.36; H, 7.82; N, 7.25. Found: C, 67.85; H, 7.37; N, 6.92.

3.2.3. N1,N4-di-tert-Butylterephthalamide (f)

M.p.: 272–276°C. FT-IR (KBr): = 3301, 2969, 1639, 1546, 1324, 864 cm−1. 1H NMR (400 MHz, CDCl3) = 1.50 (s, 18H), 5.97 (br s, 2H), 7.77 (s, 4H) ppm. Anal. Calcd. For C16H24N2O2: C, 69.52; H, 10.13; N, 8.75. Found: C, 68.95; H, 9.47; N, 7.98.

3.2.4. N1,N3-di-tert-Butylisophthalamide (g)

M.p.: 204–207°C. IR (KBr) : 3272, 3068, 2969, 1639, 1548, 1307, 680 cm−1. 1H NMR (400 MHz CDCl3) = 1.49 (s, 18H), 6 (br s, 2H), 7.28–8.11 (m, 4H) ppm. Anal. Calcd. For C16H24N2O2: C, 69.52; H, 10.13; N, 8.75. Found: C, 68.87; H, 9.67; N, 8.18.

4. Results and Discussion

A variety of N-tert-butyl amides were prepared from tert-butyl acetate with nitriles in the presence of oxalic acid dihydrate in good yields. In order to show the merit of the catalyst for Ritter reactions, we have also studied the reaction of several aromatic nitriles with t-BuOH. The results were satisfactory and the aromatic nitriles proceeded well in good yields (Table 1, entries a–g′). Acrylonitrile and aliphatic nitriles were converted to the corresponding amides in moderate yields in both reaction conditions (Table 1, entries h–k′). It is worth mentioning that the corresponding amide in each case was isolated by simple crystallization from the crude product.

tab1
Table 1: Amidation of tert-butylacetate or tert-butanol with nitriles using oxalic acid dehydrate.

The formation of tert-butyl amides in good yields and shorter time as seen from Table 1 shows that tert-butyl acetate served as a relatively better source of tert-butyl carbocation. Greatly facilitated heterolytic cleavage of C–O bond of tert-butyl acetate by oxalic acid dihydrate is rationalized by the leaving group superiority of acetate over OH group.

5. Conclusions

In conclusion, we have developed a simple, inexpensive, and ecofriendly methodology for modified Ritter reaction that represents effective activity for the amidation of tert-butyl acetate and tert-butanol with nitriles. This method provides an easy access to a variety of tert-butyl amides.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Acknowledgment

The authors are grateful to Islamic Azad university of Rasht Branch for financial assistance of this work.

References

  1. K. Tanaka, Solvent-Free Organic Reaction, Wiley-VCH, Weinheim, Germany, 2003.
  2. J. J. Ritter and P. P. Minieri, “A new reaction of nitriles. I. Amides from alkenes and mononitriles,” Journal of the American Chemical Society, vol. 70, no. 12, pp. 4045–4048, 1948. View at Google Scholar · View at Scopus
  3. F. R. Benson and J. J. Ritter, “A new reaction of nitriles. III. Amides from dinitriles,” Journal of the American Chemical Society, vol. 71, no. 12, pp. 4128–4129, 1949. View at Google Scholar · View at Scopus
  4. C. L. Parris and R. M. Christenson, “The amidomethylation of aromatic compounds,” Journal of Organic Chemistry, vol. 25, no. 11, pp. 1888–1893, 1960. View at Google Scholar · View at Scopus
  5. B. A. Hathaway, “An investigation into the mechanism of the Ritter reaction,” Journal of Chemical Education, vol. 66, no. 9, p. 776, 1989. View at Publisher · View at Google Scholar
  6. A. G. Martínez, R. M. Alvarez, E. T. Vilar, A. G. Fraile, M. Hanack, and L. R. Subramanian, “An improved modification of Ritter reaction,” Tetrahedron Letters, vol. 30, no. 5, pp. 581–582, 1989. View at Google Scholar · View at Scopus
  7. H. Firouzabadi, A. R. Sardarian, and H. Badparva, “Highly selective amidation of benzylic alcohols with nitriles. A modified ritter reaction,” Synthetic Communications, vol. 24, no. 5, pp. 601–607, 1994. View at Google Scholar · View at Scopus
  8. M. M. Lakouraj, B. Movassagh, and J. Fasihi, “Fe3+-montmorillonite K10: an efficient catalyst for selective amidation of alcohols with nitriles under non-aqueous condition,” Synthetic Communications, vol. 30, no. 5, pp. 821–827, 2000. View at Google Scholar · View at Scopus
  9. P. Salehi, M. M. Khodaei, M. A. Zolfigol, and A. Keyvan, “Facile conversion of alcohols into N-substituted amides by magnesium hydrogensulfate under heterogeneous conditions,” Synthetic Communications, vol. 31, no. 13, pp. 1947–1951, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. E. Callens, A. J. Burton, and A. G. M. Barrett, “Synthesis of amides using the Ritter reaction with bismuth triflate catalysis,” Tetrahedron Letters, vol. 47, no. 49, pp. 8699–8701, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. J. S. Yadav, B. V. S. Reddy, G. G. K. S. N. Kumar, and G. M. Reddy, “CeCl3·7H2O/AcCl-catalyzed Prins-Ritter reaction sequence: a novel synthesis of 4-amido tetrahydropyran derivatives,” Tetrahedron Letters, vol. 48, no. 28, pp. 4903–4906, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. F. Tamaddon, M. Khoobi, and E. Keshavarz, “(P2O5/SiO2): a useful heterogeneous alternative for the Ritter reaction,” Tetrahedron Letters, vol. 48, no. 21, pp. 3643–3646, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. V. Polshettiwar and R. S. Varma, “Nafion-catalyzed microwave-assisted Ritter reaction: an atom-economic solvent-free synthesis of amides,” Tetrahedron Letters, vol. 49, no. 16, pp. 2661–2664, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. K. L. Reddy, “An efficient method for the conversion of aromatic and aliphatic nitriles to the corresponding N-tert-butyl amides: a modified Ritter reaction,” Tetrahedron Letters, vol. 44, no. 7, pp. 1453–1455, 2003. View at Publisher · View at Google Scholar · View at Scopus
  15. J. C. Baum, J. E. Milne, J. A. Murry, and O. R. Thiel, “An efficient and scalable ritter reaction for the synthesis of tert-butyl amides,” The Journal of Organic Chemistry, vol. 74, no. 5, pp. 2207–2209, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. B. Anxionnat, A. Guérinot, S. Reymond, and J. Cossy, “FeCl3-catalyzed Ritter reaction. Synthesis of amides,” Tetrahedron Letters, vol. 50, no. 26, pp. 3470–3473, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. F. Tamaddon and F. Tavakoli, “One-pot synthesis of N-tert-butyl amides from alcohols, ethers and esters using ZnCl2/SiO2 as a recyclable heterogeneous catalyst,” Journal of Molecular Catalysis A: Chemical, vol. 337, no. 1-2, pp. 52–55, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. P. Theerthagiri, A. Lalitha, and P. N. Arunachalam, “Iodine-catalyzed one-pot synthesis of amides from nitriles via Ritter reaction,” Tetrahedron Letters, vol. 51, no. 21, pp. 2813–2819, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. R. Nagarajan and P. T. Perumal, “Imino Diels-Alder reactions catalyzed by oxalic acid dihydrate. Synthesis of Tetrahydroquinoline derivatives,” Synthetic Communications, vol. 31, no. 11, pp. 1733–1736, 2001. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Chandrasekhar and K. Gopalaiah, “Ketones to amides via a formal Beckmann rearrangement in “one pot”: a solvent-free reaction promoted by anhydrous oxalic acid. Possible analogy with the Schmidt reaction,” Tetrahedron Letters, vol. 44, no. 40, pp. 7437–7439, 2003. View at Publisher · View at Google Scholar · View at Scopus
  21. H. Miyake, Y. Nakao, and M. Sasaki, “Oxalic acid-promoted preparation of dithioacetals from carbonyl compounds or acetals,” Chemistry Letters, vol. 36, no. 1, pp. 104–105, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. K. Ikeda, T. Tatsuno, N. Nishihara, T. Nagata, and H. Nishi, JP. Patent 90274 20000329, 2000.
  23. M. Mokhtary, M. Qandalee, and M. R. Niaki, “Highly efficient selective oxygenation of sulfides to sulfoxides by oxalic acid dihydrate in the presence of H2O2,” E-Journal of Chemistry, vol. 9, no. 2, pp. 863–868, 2012. View at Publisher · View at Google Scholar · View at Scopus