Communication
Green Chemistry
can provide beta-hydroxy acid 13. In the second possibility, the
Knoevenagel condensation of 12 and an aldehyde could occur
to provide benzylidene derivative 14 via the corresponding
alcohol 13. Decarboxylation of 14 and/or decarboxylation
assisted dehydration of alcohol 13 gave the thermodynamically
more stable trans-cinnamamides 15.
8 E. Yankep, Z. T. Fomum and E. Dagne, Phytochemisrry,
1997, 46, 591.
9 (a) Z.-H. Shi, N.-G. Li, Q.-P. Shi, H. Tang, Y.-P. Tang, W. Li,
L. Yin, J.-P. Yang and J.-A. Duan, Bioorg. Med. Chem. Lett.,
2013, 23, 1206; (b) T. Maki, K. Ishiharaa and H. Yamamoto,
Tetrahedron, 2007, 63, 8645; (c) Y. Saito, H. Ouchi and
H. Takahata, Tetrahedron, 2008, 64, 11129; (d) F. D. King
and S. Caddick, Tetrahedron, 2013, 69, 487; (e) G. Luo, L. Xu
and G. S. Poindexter, Tetrahedron Lett., 2002, 43, 8909;
(f) Z. Ruan, R. Michael Lawrence and C. B. Cooper,
Tetrahedron Lett., 2006, 47, 7649; (g) S. M. Potadar,
A. S. Mali, K. T. Waghmode and G. U. Chaturbhuj,
Tetrahedron Lett., 2018, 59, 4582; (h) N. Li, L. Wang,
L. Zhang, W. Zhao, J. Qiao, X. Xu and Z. Liang,
ChemCatChem, 2018, 10, 3532; (i) C. L. Allen,
A. R. Chhatwal and J. M. J. Williams, Chem. Commun.,
2012, 48, 666; ( j) L. Gu, J. Lim, J. L. Cheong and S. S. Lee,
Chem. Commun., 2014, 50, 7017; (k) E. Calcio Gaudino,
D. Carnaroglio, M. A. G. Nunes, L. Schmidt,
E. M. M. Flores, C. Deiana, Y. Sakhno, G. Martrac and
G. Cravotto, Catal. Sci. Technol., 2014, 4, 1395; (l) X. Chen,
B. Gao, Y. Su and H. Huanga, Adv. Synth. Catal., 2017, 359,
2535; (m) V. C. Agwada, J. Chem. Eng. Data, 1982, 27, 479;
(n) A. D. Kosal, E. E. Wilson and B. L. Ashfeld, Angew.
Chem., Int. Ed., 2012, 51, 12036; (o) A. Ojeda-Porras,
A. Hernandez-Santana and D. Gamba-Sanchez, Green
Chem., 2015, 17, 3157; (p) T. Maki, K. Ishihara and
H. Yamamoto, Org. Lett., 2005, 7, 5043; (q) N. D. Kokare,
R. R. Nagawade, V. P. Rane and D. B. Shinde, Synthesis,
2007, 0766.
Conclusions
We have developed an original three component reaction of
aldehydes, amines and Meldrum’s acid to obtain a wide
variety of cinnamamides and piper amides with very good
yields which are superior to those obtained using most of
the known methods. The reaction enables the synthesis of
cinnamamides without using coupling reagents, oxidants or
catalysts that produce undesired chemical wastes. The reaction
is highly atom economical producing CO2 and acetone as the
by-products. We believe that this method will find wide appli-
cations for the rapid synthesis of a library of medicinally
important cinnamamides/piper amides to facilitate the identi-
fication of the most potent molecule.
Conflicts of interest
A patent application has been filed on the synthesis of
cinnamamides and piper amides.
Notes and references
1 (a) P. De, M. Baltas and F. Bedos-Belval, Curr. Med. Chem., 10 (a) S. S. Kulkarni, X. Hu and R. Manetsch, Chem. Commun.,
2011, 18, 1672; (b) R. S. Dothager, K. S. Putt, B. J. Allen,
B. J. Leslie, V. Nesterenko and P. J. Hergenrother, J. Am.
Chem. Soc., 2005, 127, 8686; (c) R. Romagnoli, P. G. Baraldi,
M. K. Salvador, M. Chayah, M. E. Camacho, F. Prencipe,
E. Hamel, F. Consolaro, G. Basso and G. Viola, Eur. J. Med.
Chem., 2014, 81, 394.
2 B. C. Perez, C. Teixeira, I. S. Albuquerque, J. Gut,
P. J. Rosenthal, J. R. B. Gomes, M. Prudencio and
P. Gomes, J. Med. Chem., 2013, 56, 556.
3 F. Maiwald, D. Benítez, D. Charquero, M. A. Dar,
H. Erdmann, L. Preu, O. Koch, C. Holscher, N. Loaec,
L. Meijer, M. A. Comini and C. Kunick, Eur. J. Med. Chem.,
2014, 83, 274.
2013, 49, 1193; (b) S. E. Kim, H. Hahm, S. Kim, W. Jang,
B. Jeon, Y. Kim and M. Kim, Asian J. Org. Chem., 2016, 5,
222; (c) V. Prasad, R. R. Kale, B. B. Mishra, D. Kumar and
V. K. Tiwari, Org. Lett., 2012, 14, 2936; (d) R. E. Rodriguez-
Lugo, M. Trincado and H. Grutzmacher, ChemCatChem,
2013, 5, 1079; (e) H. Yao, Y. Tang and K. Yamamoto,
Tetrahedron Lett., 2012, 53, 5094; (f) B. Zhang, P. Feng,
Y. Cuia and N. Jiao, Chem. Commun., 2012, 48, 7280;
(g) M. Ji, S. Lima and H.-Y. Jang, RSC Adv., 2014, 4, 28225;
(h) S. De Sarkar and A. Studer, Org. Lett., 2010, 12, 992;
(i) N. Hazarika, G. Baishya and P. Phukan, Synthesis, 2015,
47, 2851; ( j) G. Singh, R. Dada and S. Yaragorla,
Tetrahedron Lett., 2016, 57, 4424; (k) T. K. Achara and
P. Mal, Adv. Synth. Catal., 2015, 357, 3977; (l) Y.-J. Wu,
H. He, L.-Q. Sun, A. L’Heureux, J. Chen, P. Dextraze,
J. E. Starrett Jr., C. G. Boissard, V. K. Gribkoff, J. Natale and
S. I. Dworetzky, J. Med. Chem., 2004, 47, 2887.
4 M. Sova, Med. Chem., 2012, 12, 749.
5 P. Phuwapraisirisan, T. Puksasook, J. Jong-aramruang and
U. Kokpol, Bioorg. Med. Chem. Lett., 2008, 18, 4956.
6 (a) B. Narasimhan, D. Belsare, D. Pharande, V. Mourya and
A. Dhake, Eur. J. Med. Chem., 2004, 39, 827; (b) S. Michalet, 11 (a) S. Kim, C. Lim, S. Lee, S. Lee, H. Cho, J.-Y. Lee,
G. Cartier, B. David, A.-M. Mariotte, M.-G. Dijoux-franca,
G. W. Kaatz, M. Stavri and S. Gibbons, Bioorg. Med. Chem.
Lett., 2007, 17, 1755.
7 (a) A. Gunia-Krzyzak, K. Panczyk, A. M. Waszkielewicz and
H. Marona, ChemMedChem, 2015, 10, 1302; (b) N. Gaikwad,
S. Nanduri and Y. V. Madhavi, Eur. J. Med. Chem., 2019,
181, 111561.
D. S. Shim, H. D. Park and S. Kim, ACS Comb. Sci., 2013,
15, 208; (b) V. Gandon, P. Bertus and J. Szymoniak,
Tetrahedron, 2000, 56, 4467; (c) E. Hernandez-Fernandez,
M. Fernandez-Zertuche, O. Garcia-Barradas, O. Munoz-
Muniz and M. Ordonez, Synlett, 2006, 440; (d) S. Ullah,
D. Kang, S. Lee, M. Ikram, C. Park, Y. Park, S. Yoon,
P. Chun and H. R. Moon, Eur. J. Med. Chem., 2019, 161, 78.
5806 | Green Chem., 2019, 21, 5803–5807
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