A. Miyazawa et al. / Tetrahedron Letters 47 (2006) 1437–1439
1439
RCH2NH2
5
-H2
RCH-NH2
RCH2NH2
RCH=NH
RCH2NHCH2R
NH3
+
+
NHCH2R
5
6
7
8
Scheme 2.
In summary, we have demonstrated the convenient syn-
thesis of secondary amines from primary amines with a
catalytic amount of Pt/C and aluminum powder in
water under microwave irradiation conditions. The pres-
ently developed method should be very useful since the
reaction proceeds very rapidly and shows high second-
ary amine selectivity. Further investigations into the
application of the methodology to other substrates are
in progress in our laboratories.
RCH2NH2
RCH2NHCH2R
Pt/C
[Pt/C][H2]
RCHO
RCH=NH
H2O
RCH=NCH2R
H2O
RCH2NH2
NH3
References and notes
Scheme 3.
1. Miyazawa, A.; Tanaka, K.; Sakakura, T.; Tashiro, M.;
Tashiro, H.; Prakash, G. K. S.; Olah, G. A. Chem.
Commun. 2005, 2104–2106.
In the literature, some have proposed aminal (7) as an
intermediate formed by the reaction of amine (5) and
imine (6) generated by the dehydrogenation of 5 in
organic solvent or under neat conditions (Scheme 2).2
On the other hand, the reactions using water as a solvent
seem to proceed via different intermediates. Scheme 3
depicts a plausible reaction pathway of Pt/C catalyzed
reaction of primary amine to secondary amine in water
under microwave irradiation. Oxidative removal of
dihydrogen, which is initially formed in situ in the reac-
tion of starting alkylamine with Pt/C, produces an
imine. The imine is hydrolyzed to afford an aldehyde
derivative as an intermediate and ammonia. The alde-
hyde immediately reacts with starting amine to give
alkylidenealkylamine. The Pt/C-dihydrogen species
hydrogenates the alkylidenealkylamine to give a second-
ary amine and regenerate fresh Pt/C catalyst. Thus addi-
tion of aluminum helps to produce additional
dihydrogen for the hydrogenation reaction. As shown
in Scheme 3, the first part of the reaction (from primary
amine to aldehyde) is retro-reductive amination (oxida-
tive deamination) and the second part of the reaction
(from aldehyde to secondary amine) is reductive amina-
tion.5 Thus, in this unique reaction contrasting processes
(retro-reductive and reductive amination) seem to occur
concurrently in one pot.
2. (a) Kindler, K. Liebigs Ann. Chem. 1931, 485, 113–126; (b)
Kindler, K.; Melamed, G.; Matthies, D. Liebigs Ann. Chem.
1961, 644, 23–30; (c) Yoshimura, N.; Moritani, I.; Shi-
mamura, T.; Murahashi, S.-I. J. Am. Chem. Soc. 1973, 95,
3038–3039; (d) De Angelis, F.; Grgurina, I.; Nicoletti, R.
Synthesis 1979, 70–71; (e) Khai, B.-T.; Concilio, C.; Porzi,
G. J. Organomet. Chem. 1981, 208, 249–251; (f) Khai, B.-T.;
Concilio, C.; Porzi, G. J. Org. Chem. 1981, 46, 1759–1760;
(g) Arcelli, A.; Khai, B.-T.; Porzi, G. J. Organomet. Chem.
1982, 235, 93–96; (h) Tsuji, Y.; Shida, J.; Takeuchi, R.;
Watanabe, Y. Chem. Lett. 1984, 889–890; (i) Doctorovich,
F.; Trapani, C. Tetrahedron Lett. 1999, 40, 4635–4638.
3. Tyman, J. H. P. J. Appl. Chem. 1970, 20, 179–182.
4. The typical experimental procedure is as follows (i.e., Table
1 entry 8): A mixture of 100 mg (1.37 mmol) of n-
butylamine, 50 mg of 5 wt % of Pt/C, 30 mg (1.1 mmol)
of aluminum powder, and 2 ml of water in a pressure
resistant glass ampoule equipped with rubber septum and
aluminum cap is introduced into the cavity of microwave
apparatus (CEM Discover, 2.45 GHz, CEM corporation,
NC USA). The reaction mixture was irradiated by micro-
wave (50 W) continuously for 15 min. The reaction vessel
was cooled in an ice-water bath and the organic materials
were extracted with ether. The ether fraction was analyzed
by GC (FID detector) and GC–MS for identification and
quantification of products.
5. Emerson, W. S. Org. React. 1948, 4, 174–255.