LETTER
Carbamoyl Benzotriazoles via Curtius Rearrangement
C
Table 3 Synthesis of Ureas14 from Carbamoyl Benzotriazoles and Amines
Entry
Benzotriazole (R1)
Amine (R2)
4-MeC6H4
n-Bu
Time (h) Product
Mp (Lit. °C)
Yields (%)a
93.5
1
2
3
4
5
6
2a
2a
2h
3a
3a
3a
Ph
0.5
0.5
0.5
1
4a
4b
4c
4d
4e
4f
217–219 (219–220)15
133–135 (135)16
220–222 (219)17
58–59 (57–58)18
101–102 (103–104)19
–
Ph
94.3
4-MeC6H4CH=CH
MeCH2
4-MeC6H4
n-Bu
81.2
91.6
MeCH2
Bn
2
89.4
MeCH2
4-MeC6H4
12
n.r.b
a Isolated yield based on carbamoyl benzotriazoles.
b No reaction.
All the carbamoyl benzotriazoles synthesized here were Acknowledgment
crystalline solids and could be kept in open air at room
We are grateful to the National Natural Science Foundation of
China (No. 20802070) for financial support.
temperature for several months without any noticeable
changes, showing their good stability. Since N-acyl ben-
zotriazoles are good acylating agents, the carbamoyl ben-
zotriazoles, which contain the N-acyl benzotriazole
moiety, are thus promising stable isocyanate alternatives.
To demonstrate this point, a variety of amines were react-
ed with carbamoyl benzotriazoles (Scheme 3). It was
interesting to find that both N-phenylcarbamoyl benzotri-
azole and N-alkenylcarbamoyl benzotriazole could react
with aromatic amines with high efficiency to afford good
to excellent yields of the anticipated ureas (Table 3, en-
tries 1 and 3), however, N-alkylcarbamoyl benzotriazole
3a was unreactive to aromatic amine (Table 3, entry 6),
thus displaying less reactivity than its N-aryl counterparts
and N-alkylcarbamoyl azides.13 Nevertheless, 3a reacted
with aliphatic amines smoothly and the corresponding
ureas were prepared in excellent yields (Table 2, entries 4
and 5). The ability of N-alkylcarbamoyl benzotriazole to
distinguish between aliphatic and aromatic amines may be
useful in selective formation of a specific urea moiety
when a substrate with multiple amino groups is used.
References and Notes
(1) (a) Sunami, S.; Sagara, T.; Ohkubo, M.; Morishima, H.
Tetrahedron Lett. 1999, 40, 1721. (b) Sunami, S.; Ohkubo,
M. Tetrahedron 2009, 65, 638.
(2) Michael, T. M.; Swayze, E. E. Org. Lett. 2000, 2, 3309.
(3) (a) Affandi, H.; Bayquen, A. V.; Read, R. W. Tetrahedron
Lett. 1994, 35, 2729. (b) Marinescu, L.; Thinggaard, J.;
Thomsen, I. B.; Bols, M. J. Org. Chem. 2003, 68, 9453.
(c) Marinescu, L. G.; Pedersen, C. M.; Bols, M. Tetrahedron
2005, 61, 123. (d) Pedersen, C. M.; Marinescu, L. G.; Bols,
M. Org. Biomol. Chem. 2005, 3, 816. (e) Li, X.-Q.; Zhao,
X.-F.; Zhang, C. Synthesis 2008, 2589.
(4) Eduardo, G.-E.; Miryam, F.-S.; Luis, M. J. Org. Chem.
2008, 73, 2909.
(5) (a) Katritzky, A. R.; Yang, Z.; Cundy, D. J. Aldrichimica
Acta 1994, 27, 31. (b) Katritzky, A. R.; Lan, X.; Yang, J. Z.
Chem. Rev. 1998, 98, 409. (c) Katritzky, A. R.; Manju, K.;
Singh, S. K. Tetrahedron 2005, 61, 2555.
(6) (a) Katritzky, A. R.; Zhang, Y.; Singh, S. K. Synthesis 2003,
2795. (b) Katritzky, A. R.; He, H.-Y.; Suzuki, K. J. Org.
Chem. 2000, 65, 8210. (c) Katritzky, A. R.; Suzuki, K.;
Wang, Z. Synlett 2005, 1656.
N
H
N
N
(7) Staab, H. A.; Seel, G. Justus Liebigs Ann. Chem. 1958, 76,
H
N
R2
toluene
H
R2NH2
N
187.
+
N
R1
70–80 °C
(8) Henry, R. A.; Dehn, W. M. J. Am. Chem. Soc. 1949, 71, 229.
(9) Perry, C. J.; Holding, K.; Tyrrell, E. Synth. Commun. 2008,
38, 3354.
R1
O
O
4
2
(10) (a) Katritzky, A. R.; Widyan, K.; Kirichenko, K. J. Org.
Chem. 2007, 72, 5802. (b) Chuang, T.-H.; Wu, P.-L.
J. Chin. Chem. Soc. 2006, 53, 413.
Scheme 3
In conclusion, a variety of N-substituted carbamoyl ben-
zotriazoles were prepared by Curtius rearrangement via
trapping of isocyanates with benzotriazole in situ. The po-
tential of the carbamoyl benzotriazoles to act as stable iso-
cyanate alternatives has been demonstrated in part in the
synthesis of ureas.
(11) General Procedure for the Preparation of N-Aryl and
N-Alkenyl Carbamoyl Benzotriazoles 2a–k: To the aroyl
azide 1 (1 mmol) in toluene (3 mL), was added benzotriazole
(1.1 mmol, 0.31 g). The mixture was stirred at 70–80 °C for
the time indicated in Table 1 (reaction monitored by TLC).
After cooling, the crude product precipitated out and was
washed with cold EtOH to give pure N-aryl or N-alkenyl
carbamoyl benzotriazoles 2a–k.
(12) General Procedure for the Preparation of N-Alkyl-
carbamoyl Benzotriazoles 2l–o: To N-alkanoyl
benzotriazole 3 (1 mmol) in acetone (3 mL), was added a
fresh solution of NaN3 (3 mmol) dissolved in H2O (2 mL),
and FeCl3·6H2O (0.2 mmol, 54.1 mg). The mixture was
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