LETTER
Regioselective 1,4- or 1,2-Addition of Amines
3045
Table 3 Reactions of Aliphatic Amines with N-Cinnamoylbenzo-
triazoles
References
(
1) For reviews, see: (a) Xu, L. W.; Xia, C. G.; Wu, H.; Yang,
L.; Zhou, W.; Zhang, Y. Chin. J. Org. Chem. 2005, 25, 167.
(b) Romanova, N. N.; Gravis, A. G.; Bundel, Y. G. Usp.
Khim. 1996, 65, 1170; Chem. Abstr. 1998, 128, 179940.
Entry Alkyl amines 6 Ar¢ of 2
Products Reaction Yield
(%)a
time
1
5a
5b
5c
5d
5d
5e
5f
6 h
91
(2) (a) Bartoli, G.; Bosco, M.; Eurico, M.; Petrini, M.; Sambri,
NH2
3
H C
L.; Torregiani, E. J. Org. Chem. 2001, 66, 9052.
(b) Shaikh, N. S.; Deshpande, V. H.; Bedekar, A. V.
2
d
Tetrahedron 2001, 57, 9045. (c) Varala, R.; Alam, M. M.;
Adapa, S. R. Synlett 2003, 720. (d) Yadav, J. S.; Reddy, B.
V. S.; Asak, A. K.; Narsaiah, A. V. Chem. Lett. 2003, 32,
988. (e) Kawatsura, M.; Hartwig, J. F. Organometallics
2001, 20, 1960. (f) Azizi, N.; Saidi, M. R. Tetrahedron
2
3
4
5
6
7
8
9
2.5 h
1.5
86
91
NH2
Cl
2
e
n-C H NH
3
7
2
2
H3CO
2004, 60, 383.
(
3) (a) Inaba, T.; Okada, H.; Suzuki, R. Eur. Pat. 775688, 1997;
Chem. Abstr. 1997, 127, 81161. (b) Moghaddam, F. M.;
Mohammadi, M.; Hosseinnia, A. Synth. Commun. 2000, 30,
2
g
n-C H NH
10 min 95
30 minb 95
10 minb 95
4
9
Cl
643. (c) Um, I.-H.; Lee, J.-S.; Yuk, S.-M. J. Org. Chem.
2
e
1998, 63, 9152. (d) Makara, G. M.; Ma, Y. Tetrahedron
Lett. 2001, 42, 4123. (e) Tye, H. Tetrahedron Lett. 2002, 43,
n-C H NH
4
9
2
2
Cl
9421. (f) D’Angelo, J.; Maddaluno, J. J. Am. Chem. Soc.
1986, 10, 8112. (g) Enders, D.; Müller, S. F.; Raabe, G.
2
e
Angew. Chem. Int. Ed. 1999, 38, 195. (h) Gandelman, M.;
Jacobsen, E. N. Angew. Chem. Int. Ed. 2005, 44, 2393.
n-C H NH
3
7
O2N
(
i) Fadini, L.; Togni, A. Chem. Commun. 2003, 30. (j) Li,
2
2
2
f
K.; Hii, K. K. Chem. Commun. 2003, 1132. (k) Ahn, K. H.;
Lee, S. J. Tetrahedron Lett. 1994, 35, 1875.
3 h
3 h
3 h
88
83
80
NH
NH
(
4) (a) Pfau, M. Bull. Soc. Chim. Fr. 1967, 1117. (b) Kinas, R.;
Pankiewicz, K.; Stec, W. J.; Farmer, P. B.; Forster, A. B.;
Jarman, M. J. Org. Chem. 1977, 42, 1650.
a
a
5g
5h
(
(
5) Jenner, G. Tetrahedron Lett. 1995, 36, 233.
O
6) (a) Katritzky, A. R.; Lan, X.; Yang, J. Z.; Denisko, O. V.
Chem. Rev. 1998, 98, 409. (b) Katritzky, A. R.; Manju, K.;
Singh, S. K.; Meher, N. K. Tetrahedron 2005, 61, 2555.
(C H ) NH
2
5 2
Cl
(
1
c) Katritzky, A. R.; Suzuki, K.; Wang, Z. Synlett 2005,
656. (d) Katritzky, A. R.; Yang, Z.; Cundy, D. J.
2
e
Aldrichimica Acta 1994, 27, 31. (e) Katritzky, A. R.; Lan,
X. Chem. Soc. Rev. 1994, 23, 363. (f) Katritzky, A. R.; Lan,
X.; Fan, W. Q. Synthesis 1994, 445. (g) Katritzky, A. R.;
Rachwal, S.; Hitchings, G. J. Tetrahedron 1991, 47, 2683.
7) (a) Katritzky, A. R.; Wang, M.; Zhang, S. ARKIVOC 2001,
a
Isolated yields based on N-cinnamoylbenzotriazoles.
b
The run was carried out at r.t.
(
such as aliphatic amines have a higher affinity to hard acid
positions (i.e. the carboxyl end of N-cinnamoylbenzo-
triazole).
(ix), 19. (b) Wang, X. X.; Yu, H. P.; Xu, P. F.; Zheng, R. W.
J. Chem. Res., Synop. 2005, 595.
(
(
8) Katritzky, A. R.; He, H. Y.; Suzuki, K. J. Org. Chem. 2000,
6
5, 8210.
9) (a) Heininger, S. A. J. Org. Chem. 1957, 22, 1213.
b) Zhong, W. H.; Zhang, Y. M. Chin. J. Org. Chem. 2000,
0, 747. (c) Toh, T. P.; Wei, L. L. Synlett 1998, 975.
In conclusion, N-cinnamoylbenzotriazoles are good
Michael acceptors as well as effective acylating agents de-
pending on the structures of reacting amine partners. With
aromatic amines, Michael additions predominate and b-
amino N-acylbenzotriazoles were obtained in good yields;
with o-phenylenediamine, Michael addition followed by
acylation afforded 1,3,4,5-tetrahydro-4-aryl-1,5-benzo-
diazepine-2-ones in satisfactory yields. For aliphatic
amines, excellent yields of cinnamides could be pre-
pared. This good control of regioselectivity is extremely
valuable in organic synthesis. The reaction between other
nucleophiles and N-cinnamoylbenzotriazoles are now
underway in our laboratory.
(
2
(
(
d) Basu, B.; Das, P.; Hossain, I. Synlett 2004, 2630.
e) Zhuang, W.; Hazell, R. G.; Jorgensen, K. A. Chem.
Commun. 2001, 1240. (f) Matsubara, S.; Yoshioka, M.;
Utimoto, K. Chem. Lett. 1994, 827.
(
(
(
10) Herpin, T. F.; Kirk, K. G. V.; Salvino, J. M.; Yu, S. T.;
Labaudinière, R. F. J. Comb. Chem. 2000, 2, 513.
11) Nallini, A.; Saraboji, K.; Ponnuswamy, M. N.; Venkatraj,
M.; Jeyaraman, R. Cryst. Res. Technol. 2005, 40, 622.
12) Dubey, P. K.; Kumar, R.; Kumar, C. R.; Grossert, J. S.;
Hooper, D. L. Synth. Commun. 2001, 31, 3439.
1
5
(13) Typical Experimental Procedure.
A mixture of aromatic or aliphatic amine (1.1 mmol),
N-cinnamoybenzotriazole (1 mmol) and Et N (1 mL) was
refluxed in dry THF (10 mL) for the indicated time
3
Acknowledgment
(
monitored by TLC). Removal of THF and Et N under
3
We are grateful to the Education Foundation of Zhejiang Province
reduced pressure afforded a residue, which was separated by
preparative TLC on silica gel with EtOAc and cyclohexane
(
Project No.20040847) for financial support.
(
1:6) as eluent to afford b-amino N-acylbenzotriazoles.
Alternatively, Et O was added to the reaction mixture,
2
Synlett 2005, No. 20, 3042–3046 © Thieme Stuttgart · New York