Rapid and Efficient Synthesis of N-alkylbenzamides Under Microwave
Letters in Organic Chemistry, 2013, Vol. 10, No. 2
129
Melting points were taken on a Stuart SMP10 apparatus
REFERENCES
1
13
and were uncorrected. H and C spectra were recorded at
00.13 and 100.62 MHz (Bruker AVANCE II 400). Chemi-
[1]
Buffer, C.R. Microwave Cooking and Processing: engineering
fundamentals for the food scientist, 1st ed.; Springler: New York,
1993.
4
1
cal shifts were relative to the signal of solvent, ꢀ = 2.55 ( H),
1
3
[
2]
Gedye, R.; Smith, F.; Westaway, K.; Ali, H.; Baldisera, L.; La-
berge, L.; Rousell, J. The Use of Microwave Ovens for Rapid Or-
ganic Synthesis. Tetrahedron Lett., 1986, 27, 279-282.
Tierney, J.P.; Lidström, P. Microwave assisted organic synthesis,
1st ed.; Wiley & Sons: New York, 2005.
Polshettiwar, V.; Varma, R.S. Microwave-Assisted Organic Syn-
thesis and Transformations using Benign Reaction Media. Acc.
Chem. Res., 2008, 41(5), 629-639.
ꢀ
= 39.6 ( C).
N-Butylbenzamide: mp = 40-42°C (Lit. 40-41 [24]); IR
-
1
[
3]
4]
(
1
8
film, cm ) 3313, 3062, 2954, 2927, 2869, 1636, 1578,
1
544, 1488, 1305, 697; H NMR (400 MHz, DMSO-d6) ꢀ
.58 (br. s, 1H, NH), ꢀ 7.98 (d, 2H, ArH), ꢀ 7.53 (t, 1H,
[
ArH), ꢀ 7.48 (t, 2H, ArH), ꢀ 3.37 (q, 2H, NCH
2
), 1.62-1.32
); C NMR (100 MHz,
DMSO-d6) ꢀ 13.8, 19.9, 31.5, 39.1, 127.3, 128.2, 131.0,
1
3
(
m, 4H, CH
2
), ꢀ 0.93 (t, 3H, CH
3
[5]
Cappe, O.C. Controlled Microwave Heating in Modern Organic
Synthesis. Angew. Chem. Int. Ed., 2004, 43, 6250-6284.
Varma, R.S. Solvent-free organic syntheses. using supported rea-
gents and microwave irradiation. Green Chem., 1999, 1, 43-55.
Roberts, B. A.; Strauss, C.R. Toward Rapid, “Green”, Predictable
Microwave-Assisted Synthesis. Acc. Chem. Res., 2005, 38(8), 653-
[
[
6]
7]
1
35.0, 166.5.
N-Hexylbenzamide: mp = 43-44°C (Lit. 42-44 [25]); IR
-
1
(
1
8
film, cm ) 3318, 3061, 2951, 2923, 2854, 1640, 1576,
6
61.
1
545, 1488, 1307, 695; H NMR (400 MHz, DMSO-d6) ꢀ
.51 (br. s, 1H, NH), ꢀ 7.92 (d, 2H, ArH), ꢀ 7.54 (m, 1H,
[
8]
Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.; Jacquault, P.;
Mathé, D. New solvent-free organic synthesis using focused mi-
crowaves. Synthesis, 1998, 9, 1213-1234.
ArH), ꢀ 7.48 (m, 2H, ArH), ꢀ 3.31 (q, 2H, NCH
m, 8H, CH ), ꢀ 0.89 (t, 3H, CH
2 3
2
), 1.61-1.23
); C NMR (100 MHz,
DMSO-d6) ꢀ 13.9, 22.1, 26.3, 29.2, 31.2, 39.3, 127.2, 128.2,
1
3
[9]
Smith, M.B.; March, J. March’s Advanced Organic Chemistry.
Reactions, Mechanisms and Structure, 5th ed.; Wiley & Sons: New
York, 2001.
(
1
30.9, 134.8, 166.2.
[10]
Montalbetti, A.G.N.C.; Falque, V. Amide bond formation and
peptide coupling. Tetrahedron, 2005, 61, 10827-10852.
Perreux, L.; Loupy, A.; Volatron, F. Solvent-free preparation of
amides from acids and primary amines under microwave irradia-
tion. Tetrahedron, 2002, 58(11), 2155-2162.
Gelens, E.; Smeets, L.; Sliedregt, L.A.J.M.; Steen, B.J.; Kruse,
C.G.; Leurs, R.; Orru R.V.A. An atom efficient and solvent-free
synthesis of structurally diverse amides using microwaves. Tetra-
hedron Lett., 2005, 46(21), 3751-3754.
N-Octylbenzamide: mp = 40-41°C (Lit. 39-41 [11]); IR
[
11]
12]
-
1
(
film, cm ) 3337, 3063, 2953, 2917, 2845, 1633, 1534,
1
1
466, 714, 691; H NMR (400 MHz, DMSO-d6) ꢀ 8.49 (br.
[
s, 1H, NH), ꢀ 7.89 (d, 2H, ArH), ꢀ 7.57 - 7.47 (m, 3H, ArH),
ꢀ
3
2
1
3.30 (q, 2H, NCH
2
), 1.61-1.22 (m, 12H, CH
2
), ꢀ 0.89 (t,
1
3
H, CH
3
); C NMR (100 MHz, DMSO-d6) ꢀ 14.0, 22.2,
6.6, 28.8, 28.9, 29.2, 31.3, 39.3, 127.2, 128.2, 131.0, 134.8,
66.1.
[13]
Goretzki, C.; Krlej, A.; Steffens, C.; Ritter, H. Green Polymer
Chemistry: Microwave Assisted Single-Step Synthesis of Various
(Meth)acrylamides and Poly(meth). Macromol. Rapid Commun.,
N-Decylbenzamide: mp = 55°C; (Lit. 56-57 [26]); IR
2004, 25, 513-516.
-
1
[
14]
Li, X.; Wang, Y.; Wang, J. Microwave-Assisted Synthesis of Am-
ides from Various Amines and Benzoyl Chloride under Solvent-
Free Conditions: A Rapid and Effecient Method For Selective Pro-
tection Of Diverse Amines. Russ. J. Org. Chem., 2008, 44, 358-361
Wang X.-J.; Yang, Q.; Liu, F.; You, Q.-D. Microwave-assisted
synthesis of amide under solvent-free conditions. Synth. Commun.,
(
film, cm ) 3341, 2953, 2917, 2845, 1629, 1532, 1465, 714,
1
6
ꢀ
ꢀ
3
2
1
91; H NMR (400 MHz, DMSO-d6) ꢀ 8.48 (br. s, 1H, NH),
7.89 (d, 2H, ArH), ꢀ 7.54 (t, 1H, ArH), ꢀ 7.48 (t, 2H, ArH),
3.29 (q, 2H, NCH
2
), 1.61-1.20 (m, 16H, CH
2
), ꢀ 0.88 (t,
[15]
1
3
H, CH
3
); C NMR (100 MHz, DMSO-d6) ꢀ 14.0, 22.2,
2
008, 38, 1028-1035.
6.6, 28.8, 28.9, 29.0, 29.1, 29.2, 31.4, 39.3, 127.2, 128.2,
30.9, 134.8, 166.1.
[
16]
17]
Vazquéz-Tato, M.P. Microwave-Mediated Synthesis of Amides.
Synlett, 1993, 7, 506.
Ruault, P.; Pilard, J.F.; Touaux, B.; Texier-Boullet, F.; Hamelin, J.
Bentonite K10 Clay, an Efficient Catalyst for the Formation of Ni-
trogen Derivatives. Synlett, 1994, 104(6), 935.
Baldwin, B.W.; Hirose, T.; Wang, Z.-H. Improved microwave oven
synthesis of amides and imides promoted by imidazole; convenient
transport agent preparation. Chem. Commun., 1996, 23, 2669-2670.
Hajipour, A.R.; Ghasemi, M. A Rapid and Convenient Synthesis of
Amides from Aromatic Acids and Aliphatic Amines in Dry Media
under Microwave Irradiation. Indian J. Chem. B, 2001, 40B, 504-
507.
Chandrasekhar, S.; Takhi, M.; Uma, G. Solvent Free N-Alkyl and
N-Arylimides Preparation from Anhydrides Catalyzed by TaCl5-
Silica gel. Tetrahedron Lett., 1997, 38, 8089-8092.
[
CONCLUSIONS
[
18]
19]
In summary, these studies should not only enable an ex-
tension of applicability of the microwave heating, but also
introduce environmentally friendlier methods in amide bond
synthesis. A rapid microwave inducted procedure for the
preparation of primary aliphatic amides under solvent-free
conditions was introduced. With the use of acidic conditions
amides were formed in excellent yields (97 - 99%).
[
[20]
[21]
[22]
[23]
[24]
[25]
Mohan, K.V.V.K.; Narender, N.; Kulkarni, S.J. Zeolite catalyzed
acylation of alcohols and amines with acetic acid under microwave
irradiation. Green Chem., 2006, 8, 368-372.
Comerford, W. J.; Clark, H. J.; Macquarrie J. D.; Breeden, W. S.
Clean, reusable and low cost heterogeneous catalyst for amide syn-
thesis. Chem. Commun., 2009, 18, 2562-2564.
Nüchter, M.; Ondruschka, B.; Bonrath, W.; Gum, A. Microwave
assisted synthesis – a critical technology overview. Green Chem.,
2004, 6, 128-141.
Kim, B. R.; Lee, H. -G.; Kang, S. -B.; Sung, G. H.; Kim, J. -J.;
Park, J. K.; Lee, S. -G.; Yoon, Y. -J. tert-Butoxide-Assisted Amida-
tion of Esters under Green Conditions. Synthesis, 2012, 1, 42-50.
Ohshima, T.; Iwasaki, T.; Maegawa, Y.; Yoshiyama, A.; Mashima,
A. Enzyme-Like Chemoselective Acylation of Alcohols in the
CONFLICT OF INTEREST
The author(s) confirm that this article content has no con-
flict of interest.
ACKNOWLEDGEMENTS
We gratefully acknowledge Prof. Dr. Antonín Lyꢁka for
NMR spectra measurement and to RNDr. Radek Fajgar,
CSc. for IR spectra measurement. This work was supported
by the PdF UHK Specific Research Grant No. 2108/01450.