LETTER
Reactions of Amines with Trichloroisocyanuric Acid
2183
(14) Bachmann, W. E.; Cava, M. P.; Dreiding, A. S. J. Am. Chem.
Soc. 1954, 76, 5554.
(15) Probably owing to the formation of insoluble salts formed by
TEA and the formed trihydroxytriazine.
In conclusion, this work has shown an easy transforma-
tion of amines and a-aminoacids through reaction with
TCCA: in all cases the yields are practically quantitative
and the products recovered in pure form from the reaction
mixture.21 This method is characterized by mild reaction
conditions, non-toxic by-products and easy reaction
work-up, making it ideal for both laboratory and large
scale.
(16) The presence of the compounds in the reaction mixture was
evidenced by 1H NMR analysis.
(17) (a) Schönberg, A.; Moubacher, R. Chem. Rev. 1952, 50,
261. (b) Clarke, T. G.; Hampson, N. A.; Lee, J. B.; Morley,
J. R.; Scanlon, B. J. Chem. Soc. C 1970, 815; and references
therein.
(18) Rozen, S.; Bar-Haim, A.; Mishani, E. J. Org. Chem. 1994,
59, 1208; and references therein.
Acknowledgment
(19) (a) Friedman, A. H.; Morgulis, S. J. Am. Chem. Soc. 1936,
58, 909. (b) McGregor, W. H.; Carpenter, F. H.
The University of Sassari (Fondi ex-60%) has financially supported
this work.
Biochemistry 1962, 1, 53. (c) Gowda, B. T.; Mahadevappa,
D. S. J. Chem. Soc., Perkin Trans. 2 1983, 323.
(d) Hiremath, R. C.; Mayanna, S. M.; Venkatasubramanian,
N. J. Chem. Soc., Perkin Trans. 2 1987, 1569. (e) Takeda,
T.; Yamauchi, S.; Fujiwara, T. Synthesis 1996, 600.
(20) Casanova, J. Jr.; Werner, N. D.; Schuster, R. E. J. Org.
Chem. 1966, 31, 3473.
(21) All solvents and reagents were used as obtained from
commercial source. Standard 1H NMR and 13C NMR were
recorded from CDCl3 solutions at 300 MHz and 75.4 MHz.
Mass spectra were recorded at 70 eV with a direct probe for
sample introduction. When possible, compounds were
identified by comparison with authentic samples. All runs
were conducted at least in duplicate.
References
(1) Tilstam, U.; Weinmann, H. Org. Process Res. Dev. 2002, 6,
384.
(2) Ura, Y.; Sakata, G. Ullmann’s Encyclopedia of Industrial
Chemistry, 6th ed.; Wiley-VCH: Weinheim, 2001.
(3) Ziegler, K.; Spath, A.; Schaaf, E.; Schumann, W.;
Winkelmann, E. Anal. Chem. 1942, 551, 80.
(4) Newkome, G. R.; Kiefer, G. E.; Xia, Y. J.; Gupta, V. K.
Synthesis 1984, 676.
(5) (a) Firouzabadi, H.; Iranpoor, N.; Hazarkhani, H. Synlett
2001, 1641. (b) Zolfigol, M. A.; Choghamarani, A. G.;
Hazarkhani, H. Synlett 2002, 1002. (c) Zolfigol, M. A.;
Madrakian, E.; Ghaemi, E.; Mallakpour, S. Synlett 2003,
1633. (d) Zolfigol, M. A.; Ghaemi, E.; Madrakian, E. Synlett
2003, 191. (e) Zolfigol, M. A.; Madrakian, E.; Ghaemi, E.;
Mallakpour, S. Synlett 2003, 2222. (f) Mendonça, G. F.;
Sanseverino, A. M.; de Mattos, M. C. S. Synthesis 2003, 45.
(6) (a) Falorni, M.; Porcheddu, A.; Taddei, M. Tetrahedron Lett.
1999, 40, 4395. (b) Falorni, M.; Giacomelli, G.; Porcheddu,
A.; Taddei, M. J. Org. Chem. 1999, 64, 8962. (c) Falchi,
A.; Giacomelli, G.; Porcheddu, A.; Taddei, M. Synlett 2000,
275. (d) De Luca, L.; Giacomelli, G.; Taddei, M. J. Org.
Chem. 2001, 66, 2534. (e) De Luca, L.; Giacomelli, G.;
Porcheddu, A. Org. Lett. 2001, 3, 1519. (f) De Luca, L.;
Giacomelli, G.; Porcheddu, A. Org. Lett. 2002, 4, 553.
(g) De Luca, L.; Giacomelli, G.; Porcheddu, A. J. Org.
Chem. 2002, 67, 5152. (h) De Luca, L.; Giacomelli, G.;
Porcheddu, A. J. Org. Chem. 2002, 67, 6272.
(i) Giacomelli, G.; Porcheddu, A.; Salaris, M. Org. Lett.
2003, 5, 2715.
(7) De Luca, L.; Giacomelli, G.; Porcheddu, A. Org. Lett. 2001,
3, 3041.
(8) De Luca, L.; Giacomelli, G.; Masala, S.; Porcheddu, A. J.
Org. Chem. 2003, 68, 4999.
(9) Chen, F.; Kuang, Y.; Dai, H.; Lu, L.; Huo, M. Synthesis
2003, 2629.
(10) These results are obviously inconsistent with those
published (ref.9). We have repeated the experiments with
other substrates, such as those reported in Table 1, following
the reported procedure and always no traces of nitriles were
detected. We have no explanation for this disagreement: in
our opinion, this might perhaps depend on the distillation
procedure adopted from the above-cited authors that should
have caused hydrochloride elimination from the substrate.
(11) Wright, G. F. J. Am. Chem. Soc. 1948, 70, 1958.
(12) The reaction is not chemoselective: a mixture of primary and
secondary amines yielded a mixture of chloroamines when
reacted with 1 equiv of TCCA.
General Preparation of N,N-Dichloroamines. The
procedure for the chlorination of benzylamine (Table 1, run
3) is representative for all cases. Benzylamine (2.00 g, 19
mmol) was dissolved in CH2Cl2 (80 mL) and treated with
TCCA (4.64 g, 19 mmol) at 0 °C. After the addition, the
mixture was warmed to r.t. and stirred for the required time
until completion. After 1 h, TLC analysis showed the
complete absence of the amine, the reaction mixture was
filtered on Celite and the solvent evaporated to yield N,N-
dichlorobenzylamine(3) that was isolated without further
purification (oil, 3.2 g, 98%). 1H NMR: d = 7.39 (s, 5 H),
4.68 (s, 2 H). 13C NMR: d = 135.1, 130.3, 129.5, 128.8, 79.1.
MS: m/e (relative intensity): 179 (1), 177 (3), 176 (1), 175
(4), 112 (2), 106 (3), 105 (14), 104 (23), 103 (4), 92 (91), 91
(100), 79 (1), 78 (4), 77 (15), 76 (3), 65 (9), 63 (2), 51 (9).
General Procedure for the Preparation of Nitriles and N-
Chloroimines from N,N-Dichloroamine. The reported
procedure is representative: N,N-dichlorocyclohexanamine
(2, 1.00 g, 6 mmol) was dissolved in CH2Cl2 (20 mL) and
treated with TEA (2.56 mL, 18 mmol) at 25 °C. After 2 h,
TLC analysis showed the complete absence of the N,N-
dichloroamine. Then the reaction mixture was washed with
H2O (15 mL), with HCl 0.5 N (10 mL), dried on Na2SO4,
filtered on Celite and concentrated in vacuo to yield N-
chlorocyclohexanimine (18, oil, 0.61 g, 77%). 1H NMR: d =
2.60–0.95 (br m, 10 H). 13C NMR: d = 182.8, 36.9, 32.7,
26.9, 25.9, 25.1.
General One-Pot Procedure. The reported procedure is
representative: Benzylamine (1.00 g, 9.5 mmol) was
dissolved in DMF (10 mL) and treated with TEA (4 mL, 28.5
mmol), and with TCCA (2.32 g, 9.5 mmol) at 25 °C. After 4
h, the reaction mixture was quenched with H2O (20 mL), and
then it was extracted twice with Et2O (15 mL). The organic
layers were washed with H2O (10 mL), then with HCl 0.5 N
(10 mL), were dried (Na2SO4), and the solvent was
evaporated to yield benzonitrile (19, 1.1 g, 95%).
General One-Pot Procedure for the Preparation of
Nitriles from a-Aminoacids. The reported procedure is
(13) Tilstam, U.; Harre, M.; Heckrodt, T.; Weinmann, H.
Tetrahedron Lett. 2001, 42, 5385.
Synlett 2004, No. 12, 2180–2184 © Thieme Stuttgart · New York