2
Tetrahedron
electron-withdrawing groups (Table 1, entries 3, 4 and 5) were
vacuum and was utilized over five runs in the N–H insertion of
aniline with the conversion and selectivity being unchanged.
In summary, the N–H insertion of amines with ethyl
diazoacetate, using the ionic liquid [Hmim][BF4] as catalyst, has
several advantages: (1) the ionic liquid is a strong Brønsted acid,
and shows superior catalytic activity, (2) the preparation of
[Hmim][BF4] is very simple, (3) [Hmim][BF4] can be reused
after removal of water, (4) the reactions occur under solvent-free
conditions, (5) the products can be isolated conveniently in high
yields and purity, and (6) the yields are generally high for both
secondary and primary amines.
found to be less active and gave the corresponding single
insertion products in good yields but only after longer reaction
times. Bulky amines, such as dibenzylamine also afforded the
corresponding product (Table 1, entry 6). Reaction between p-
bromoaniline and one equivalent of EDA (Table 1, entry 7), also
afforded the single insertion product selectively. The insertion of
EDA into the N–H bonds of benzamide and indole was not
successful (Table 1, entries 8 and 9). Even though, in the method
for the preparation of the ionic liquid (see above), it seems
unlikely that trace metals could be incorporated, one cannot
totally rule out the possibility, since in other instances „metal-
free‟ procedures have been shown to rely on traces of metal.
Acknowledgments
We are thankful to Tarbiat Modares University for partial
support of this work
R1
R2
R1
R2
NH
[Hmim][BF ]
+
(10 mol%)
4
N2
COOEt
N
COOEt
Supplementary data
_
Characterization of compounds and analytical data (IR, MS,
+
NH
1
[Hmim][BF4] :
BF4
1H NMR and 13C NMR) for new compounds. Copies of H NMR
N
and 13C NMR spectra.
Scheme 1. N–H insertion reaction of amines using
References and notes
[Hmim][BF4] as the catalyst
1. (a) Bashford, K. E.; Cooper, A. L.; Kane, P. D.; Moody, C. J.; Muthusamy,
S.; Swann, E. J. Chem. Soc., Perkin Trans. 1 2002, 1672; (b) Yamazaki, K.;
Kondo, Y. Chem. Commun. 2002, 210; (c) Taylor, E. C.; Davies, H. M. L. J.
Table 1. N–H insertion reactions of amines with ethyl
diazoacetate (EDA) using [Hmim][BF ]
4
Org. Chem. 1984, 49, 113.
Entry
1
Amine
Amine/EDA ratio
1:1
Ref.
16
Time (h)
1
Yield (%)
2. Yates, P. J. Am. Chem. Soc. 1952, 74, 5376.
NH2
NH2
3. (a) Saegusa, T.; Ito, Y.; Kobayashi, S.; Hirota, K.; Shimizu, T. Tetrahedron
Lett. 1966, 7, 6131; (b) Nicoud, J. F.; Kagan, H. B. Tetrahedron Lett. 1971,
12, 2065.
4. Paulissen, R.; Hayez, E.; Hubert, A. J.; Teyssie, P. Tetrahedron Lett. 1974,
15, 607.
5. Osipov, S. N.; Sewald, N.; Kolomiets, A. F.; Fokin, A. V.; Berger, K.
Tetrahedron Lett. 1996, 37, 615.
6. (a) Galardon, E.; Maux, P. L.; Simonneaux, G. J. Chem. Soc., Perkin
Trans. 1 1997, 2455; (b) Zotto, A. L.; Baratta, W.; Rigo, P. J. Chem. Soc.,
Perkin Trans. 1 1999, 3079; (c) Galardon, E.; Maux P. L.; Simonneaux, G.
Tetrahedron 2000, 56, 615.
7. Morilla, M. E.; Diaz-Requejo, M. M.; Belderrain, T. R.; Nicasio, M. C.;
Trofimenko, S.; Perez, P. J. Chem. Commun. 2002, 2998.
8. Kantam, M. L.; Soumi, L.; Jagjit, Y.; Shailendra, J. Tetrahedron Lett.
2009, 50, 4467.
9. Bachmann, S.; Fielenbach, D.; Jorgensen, K. A. Org. Biomol. Chem. 2004,
2, 3044.
10. Kantam, M. L.; Neelima, B.; Venkat Reddy, C. J. Mol. Catal. A: Chem.
2006, 256, 269.
94 (45:55)a
95b
92c
2
3
4
1:2
1.5
2
16
NH2
-
1:1.2
NO2
NH2
1:1.2
94c
2
16
O2N
NH2
F
O
1:1
1:1
90c
94c
2
2
-
5
6
NO2
NH
Ph
Ph
17
16
-
11. Wasserscheid, P.; Welton, T. Ionic Liquids in Synthesis; Wiley-VCH:
Weinheim, 2007.
NH2
1:1
94c
-
0.5
-
12. (a) Litschauer, M.; Neouze, M. A. J. Mater. Chem. 2008, 18, 640; (b)
Lee, S. G. Chem. Commun. 2006, 1049; (c) Wang, Z.; Zhang, Q.; Kuehner,
D.; Ivaska, A.; Niu, L. Green Chem. 2008, 10, 907; (d) Jiang, Y. Y.; Wang,
G. N.; Zhou, Z.; Wu, Y. T.; Geng, J.; Zhang. Z. B. Chem. Commun. 2008,
505; (e) Zhao, G.; Jiang, T.; Gao, H.; Han, B.; Huang, J.; Sun, D. Green
Chem. 2004, 6, 57; (f) Li, X.; Geng, W.; Zhou, J.; Luo, W.; Wang, F.; Wang,
L.; Tsang, S. C. New J. Chem. 2007, 31, 2088; (g) Holbrey, J. D.; Turner, M.
B.; Reichert, W. M.; Rogers, R. D. Green Chem. 2003, 5, 731.
13. (a) Kalhor, H. R.; Kamizi, M.; Akbari, J.; Heydari, A. Biomacromolecules
2009, 10, 2468; (b) Akbari, J.; Heydari, A. Tetrahedron Lett. 2009, 50, 4236;
(c) Akbari, J.; Hekmati, M.; Sheykhan, M.; Heydari, A. Arkivoc 2009, (xi),
123; (d) Akbari, J.; Heydari, A.; Kalhor, H. R.; Azizian Kohan, S. J. Comb.
Chem. 2010, 12, 137; (e) Dabirmanesh, B.; Daneshjou, S.; Akhavan Sepahi,
A.; Ranjbar, B.; Khavari-Nejad, R. A.; Gill, P.; Heydari, A.; Khajeh, K. Int. J.
Biol. Mac. 2011, 48, 93; (f) Akbari, N.; Daneshjoo, S.; Akbari, J.; Khajeh, K.
Appl. Biochem. Biotechnol. 2011, 165, 785; (g) Mirkhani S. A.; Vossoughi,
M.; Pazuki, G. R.; Safekordi, A. A.; Heydari, A.; Akbari, J.; Yavari, M. J.
Chem. Thermodyn. 2011, 43, 1530; (h) Dabirmanesh, B.; Khajeh, K.; Akbari,
J.; Falahati, H.; Daneshjoo, S.; Heydari, A. J. Mol. Liq. 2011, 161, 139; (i)
Heydari, H.; Akbari, J.; Curr. Nanoscience, 2012, 8, 398; (j) Noori, A. R.;
7
Br
O
NH2
1:1.5
1:1.5
8
9
-
-
-
N
H
a Ratio of the single insertion to the double insertion product given in
parentheses.
b Only the double insertion product was isolated.
c Only the single insertion product was isolated.
The ionic liquid [Hmim][BF4] could be easily recycled. After
completion of the reactions, water and dichloromethane were
added to the container and the mixture was decanted. The ionic
liquid was separated from the aqueous phase by drying under