Reaction of primary amines with Pt/C catalyst in water under microwave irradiation: A convenient synthesis of secondary amines from primary amines

Article abstract of DOI:10.1016/j.tetlet.2005.12.075

Upon microwave irradiation in water, Pt/C converts primary amines into secondary amines in good yield via retro-reductive and reductive amination.

Full text of DOI:10.1016/j.tetlet.2005.12.075

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1437–1439
Reaction of primary amines with Pt/C catalyst in water
under microwave irradiation: a convenient synthesis
of secondary amines from primary amines
Akira Miyazawa,a,* Kaori Saitou,a Kan Tanaka,a Thomas M. Gadda,a Masashi Tashiro,a
¨
G. K. Surya Prakashb and George A. Olahb
aNational Institute of Advanced Industrial Science and Technology, AIST Central 5, Tsukuba, Ibaraki 305-8565, Japan
bLoker Hydrocarbon Research Institute, Department of Chemistry, University of Southern California, Los Angeles,
CA 90089-1661, USA
Received 24 October 2005; revised 8 December 2005; accepted 15 December 2005
Abstract—Upon microwave irradiation in water, Pt/C converts primary amines into secondary amines in good yield via retro-reduc-
tive and reductive amination.
Ó 2006 Elsevier Ltd. All rights reserved.
Recently, we reported that some amines can be directly
converted to ketones under microwave irradiation in the
presence of catalytic amount of Pd/C and water.1 In this
reaction, the products were strongly dependent on the
number of hydrogens on the a-carbon adjacent to nitro-
gen of starting amines. Amines having one hydrogen
atom on the a-carbon were converted to corresponding
ketones and amines having two hydrogen atoms on the
a-carbon were derived to secondary amines. As a further
extension of this method, we have developed a conve-
nient synthesis of secondary amines from primary
amines. Although many protocols for the preparation
of secondary amines from primary amines have been
reported, these require the use of organic solvents and
long reaction times.2
amine (2) was obtained along with butylidenebutyl-
amine (3) and tri-n-butylamine (4) (entries 1–3 and 5).
The conversions of 1 and yields of 2 were dependent
on the kind of metal catalyst used. The Pt/C catalyst
among them showed high conversion and selectivity
toward the desired secondary amine. In the case of Pt/C
catalyst used (entry 5), the temperature of ampoule sur-
face measured by infrared thermo detector rose to
158 °C upon continuous microwave irradiation at
50 W for 60 min. In order to compare conventional oil
bath heating, we examined the reaction using preheated
(158 °C) oil bath for 60 min (entry 7). The reaction pro-
ceeded to give 2 in high selectivity; however, the conver-
sion of the starting amine was low (30%) compared with
the reaction using microwave heating (76%, entry 5). It
is obvious that microwave heating showed the advan-
tage compared with conventional microwave heating.
The formation of 3 seemed to be due to lack of hydro-
gen for subsequent hydrogenation of 3 to form 2 (entries
1–7). It has been reported that a combination of alumi-
num powder and water can be used as a substitute for
hydrogen gas.3 Thus, we added a small amount of alu-
minum powder into the reaction. The addition of alumi-
num powder worked effectively and the reaction was
accelerated and selectively gave the desired 2 in good
yield (entry 8) and the reaction time was considerably
shortened compared with the reactions without alumi-
num powder (entries 4 and 6). It was found that the cat-
alyst combination of Pt/C and aluminum was effective
Table 1 lists the preliminary results of the reaction of
n-butylamines with four types of catalysts (Pd/C, Ru/C,
Rh/C, and Pt/C, 5 wt % of metal content). The reactions
were conducted in the presence of the catalysts in water
under microwave irradiation (2.45 GHz 50 W) using a
pressure resistant glass ampoule. When n-butylamine
(1) was reacted with the catalysts described above in
water under microwave irradiation, desired di-n-butyl-
Keywords: Microwave; Platinum supported on activated carbon;
Amination; Water; Reductive amination; retro-Reductive amination.
*
Corresponding author. Tel.: +81 29 861 9388; fax: +81 29 861
4566; e-mail: a.miyazawa@aist.go.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.12.075

1438
A. Miyazawa et al. / Tetrahedron Letters 47 (2006) 1437–1439
Table 1. The preliminary results of the reaction of n-butylamine
catalysts
NH2
N
3
N
N
water
microwave (50W)
H
1
3
4
2
b
b
Entry
Catalystsa
Time (min)
Conversion (%)
Relative yields (%)
2
3
4
1
2
3
4
Pd/C
Ru/C
Rh/C
Pt/C
Pt/C
Pt/C
Pt/C
Pt/C
60
60
60
15
60
15
60
15
20
41
40
29
76
4
39
60
34
81
94
48
92
93
44
36
57
19
3
52
8
0
17
4
9
Trace
3
Trace
Trace
7
5
6c
7c
8d
30
80
Conditions: n-butylamine (100 mg), catalysts (50 mg), water (2 ml), continuous microwave irradiation at 50 W.
a Metal (5 wt %) supported on activated carbon was used.
b Identification and quantification of the products were determined by GC and GC–MS analyses, and relative yields were based on peak area ratio.
c Preheated oil bath (158 °C) was used.
d Aluminum powder (30 mg) was used as an additive.
for selective transformation of 1 to 2 under microwave
a transient product in the middle of the reaction. These
results indicate that the formation of imine followed by
hydrolysis yielding carbonyl compound is a key step in
the case of latter substrates. Thus, water is not only a
solvent but also a mediator for promoting the reactions.
When D2O was used instead of H2O to the reaction
of neopentylamine, deuterated dineopentylamine was
obtained in 83% yield (Scheme 1).
irradiation in water.4
The reaction is generally applicable to other amines as
summarized in Table 2. Thus, n-pentylamine, n-hexyl-
amine, isobutylamine, and neopentylamine (bearing pri-
mary methylenes adjacent to amines) were converted to
corresponding secondary amines in good yields (entries
1–3 and 5). Tertiary amines were the main side products.
When amines having secondary alkyl group (sec-butyl-
amine, 3-pentylamine, cyclopentyl, and cyclohexylamine
(entries 4 and 6–8)) were reacted under similar condi-
tions, the selectivity to secondary amines was fairy low
and main products were ketones. However, the reactions
were quite fast. Furthermore, the reaction of benzyl-
amine under similar condition did not give the expected
dibenzylamine, only benzene and toluene were obtained
(entry 9). In this reaction, benzaldehyde was observed as
D
D
D
Pt/C, Al powder
NH2
N
D2O
D
D
microwave (50W)
83%
Scheme 1.
Table 2. Reaction of amines with Pt/C in water under microwave irradiation
Pt/C, Al powder
RNH2
R2NH
water
microwave (50W)
Entry
R
Time (min)
Conversiona (%)
Relative yielda (%)
Side products
R2NH
1
2
3
4
5
6
7
8
9
n-Pentyl
n-Hexyl
Isobutyl
sec-Butyl
neo-Pentyl
3-Pentyl
Cyclopentyl
Cyclohexyl
Benzyl
30
30
30
10
60
10
10
10
30
87
75
97
100
87
100
76
84
68
100
37
86
21
51
29
0
Tripentylamine (14)
Trihexylamine (26)
2-Butanone (58)
neo-Pentanenitrile (14)
3-Pentanone (71)
Cyclopentanone (32)
Cyclohexanone (67)
Benzene (46), toluene (53)
90
100
Conditions: amine (100 mg), Pt/C (50 mg), Al powder (30 mg), water (2 ml), continuous microwave irradiation at 50 W.
a Identification and quantification of the products were determined by GC and GC–MS analyses, and relative yields were based on peak area ratio.

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.