3
intermediate have taken place and the product 3 was formed
(For details of the mechanism, see the Supporting
Information).
In summary, we have developed
straightforward methodology for synthesizing
a
novel and
2-
1
dialkylamino-2-oxazolin-4-ones by one-pot reaction. Various
Vilsmeier salts and α-hydroxy amides derivatives were
investigated, and a series of corresponding products were
obtained in good yields and a certain degree of selectivity. It’s
worth mentioning that we obtained a pharmacologically active
compound 3a in 88% yield by this methodology, and the
pharmaceutical activity of products, analogous of 3a, are
being estimated in our laboratory.
We thank the financial support from the National Natural
Science Foundation of China (No. 51373067).
2c
References and Notes
1
2
M. S. von Wittenau, H. Els, J. Am. Chem. Soc. 1963, 85, 3425.
D. R. Witty, G. Walker, J. H. Bateson, P. J. O'Hanlon, D. S.
Eggleston, R. C. Haltiwanger, Tetrahedron Lett. 1996, 37, 3067.
R. B. Moffett, J. Heterocycl. Chem. 1980, 17, 753-758.
T. R. Herrin, J. M. Pauvlik, E. V. Schuber, A. O. Geiszler, J. Med.
Chem. 1975, 18, 1216.
3
4
5
6
7
M. R. Harnden, R. R. Rasmussen, J. Med. Chem. 1969, 12, 919.
M. R. Harnden, R. R. Rasmussen, J. Med. Chem. 1970, 13, 305.
J. P. Dirlam, D. A. Clark, S. J. Hecker, J. Org. Chem. 1986, 51,
4920.
3c
8
9
10
P. Kuś, P. G. Jones, R. Celiński, Z. Naturforsch. B. 2005, 60, 853.
J. C. Sheehan, P. T. Izzo, J. Am. Chem. Soc. 1949, 71, 4059.
A. J. Kassick, J. Jiang, J. Bunda, D. Wilson, J. Bao, H. Lu, P. Lin,
R. G. Ball, G. A. Doss, X. Tong, K.-L. C. Tsao, H. Wang, G.
Chicchi, B. Karanam, R. Tschirret-Guth, K. Samuel, D. F. Hora, S.
Kumar, M. Madeira, W. Eng, R. Hargreaves, M. Purcell, L. Gantert,
J. Cook, R. J. DeVita, S. G. Mills, J. Med. Chem. 2013, 56, 5940.
R. M. Rodehorst, T. H. Koch, J. Am. Chem. Soc. 1975, 97, 7298.
C.-M. Lee, B. W. Horrom, R. J. Michaels, R. M. Rasmussen, N. P.
Plotnikoff, J. Med. Chem. 1972, 15, 1252.
11
12
13
14
15
J. W. Clark-Lewis, Chem. Rev. 1958, 58, 63.
Cl
C.-M. Lee, N. Plotnikoff, J. Med. Chem. 1976, 19, 731.
A. Padwa, J. P. Snyder, E. A. Curtis, S. M. Sheehan, K. J.
Worsencroft, C. O. Kappe, J. Am. Chem. Soc. 2000, 122, 8155.
B. Ye, D. O. Arnaiz, Y.-L. Chou, B. D. Griedel, R. Karanjawala,
W. Lee, M. M. Morrissey, K. L. Sacchi, S. T. Sakata, K. J. Shaw, S.
C. Wu, Z. Zhao, M. Adler, S. Cheeseman, W. P. Dole, J. Ewing, R.
Fitch, D. Lentz, A. Liang, D. Light, J. Morser, J. Post, G.
Rumennik, B. Subramanyam, M. E. Sullivan, R. Vergona, J.
Walters, Y.-X. Wang, K. A. White, M. Whitlow, M. J. Kochanny, J.
Med. Chem. 2007, 50, 2967.
N
N
4
Cl
16
2e
5
6
17
18
19
20
F. Ramirez, C. D. Telefus, V. A. V. Prasad, Tetrahedron. 1975, 31,
2007.
C. F. Howell, N. Q. Quinones, R. A. Hardy, J. Org. Chem. 1962,
27, 1679.
C. F. Howell, N. Q. Quinones, R. A. Hardy, J. Org. Chem. 1962,
27, 1686.
C. F. Howell, W. Fulmor, N. Q. Quinones, R. A. Hardy, J. Org.
Chem. 1964, 29, 370.
21
22
23
24
H. Beyer, R. Spörl, Chem. Ber. 1966, 99, 2719.
W. Traube, R. Ascher, Eur. J. Inorg. Chem. 1913, 46, 2077.
Y. S. Rao, R. Filler, J. Chem. Soc. D. 1970, 1622.
V. V. Dabholkarl, Sagar D. Shah, V. M. Dave, Heterocyclic Lett.
2015, 5, 419.
a Reactions were conducted at 1 mmol scale in 10 ml of solvent. b Isolated
yield. cObtained double products.
25 D. Su, H. Duan, Z. Wei, J. Cao, D. Liang, Y. Lin, Tetrahedron Lett.
2013, 54, 6959.
26
C. Bosset, R. Coffinier, P. A. Peixoto, M. El Assal, K. Miqueu, J.
M. Sotiropoulos, L. Pouysegu, S. Quideau, Angew. Chem. Int. Ed.
2014, 53, 9860.
In our previous work, we have explored the possible
mechanism of the one-pot reaction. Under our optimized
conditions, 1 and 2a similarly experienced a nucleophilic
substitution process and generated a guanidine intermediate.
Subsequently, a intramolecular cyclization of the guanidine
27
28
M. Curini, F. Epifano, S. Genovese, M. C. Marcotullio, O. Rosati,
Org. Lett. 2005, 7, 1331.
E. J. Ebbers, G. J. A. Ariaans, A. Bruggink, B. Zwanenburg,
Tetrahedron: Asymmetry. 1999, 10, 3701.