Microwave-assisted direct transformation of amines to ketones using water as an oxygen source

Article abstract of DOI:10.1039/b500541h

Retro-reductive animations, direct transformations of amines to ketones, were catalyzed by Pd/C in water under microwave irradiation. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b500541h

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Microwave-assisted direct transformation of amines to ketones using
water as an oxygen source
Akira Miyazawa,*a Kan Tanaka,a Toshiyasu Sakakura,a Masashi Tashiro,a Hideki Tashiro,b
G. K. Surya Prakashb and George. A. Olahb
Received (in Cambridge, UK) 13th January 2005, Accepted 22nd February 2005
First published as an Advance Article on the web 9th March 2005
DOI: 10.1039/b500541h
completion of the reactions, litmus paper indicated that the
resulting aqueous solution was alkaline with a smell of ammonia.
The reaction strongly depended on the structure of the butyl
groups, especially the number of hydrogens on the carbon adjacent
to the nitrogen. sec-Butylamine was completely converted to
2-butanone within 1 h (entry 4). The reactions of n-butyl and
isobutylamines under the similar conditions were slower and
afforded (butylidene)butylamines (3) and dibutylamines (4) along
with a small amount of the desired aldehyde (entries 1–3). For tert-
butylamine, the reaction did not proceed and the starting amine
was quantitatively recovered (entry 8). Other heating methods
were investigated. The reaction of sec-butylamine using a pre-
heated oil bath at 170 uC for 1 h gave the desired 2-butanone in
29% yield without by-products (entry 5), but a longer reaction time
increased the amount of di-sec-butylamine (entry 6), which was
presumably formed by the reductive amination of 2-butanone with
sec-butylamine. The reaction under reflux conditions with
microwave irradiation (50 W for 2.5 h) is apparently too slow
for practical purposes. Thus, microwave irradiation in a sealed
vessel effectively enhances the selectivity and accelerates the
reaction in the direct conversion of sec-butylamine to 2-butanone.
The reaction is generally applicable to other primary and
secondary amines as summarized in Table 2. Thus, isopropyl-
amine, diisopropylamine and di-sec-butylamine, meso–DL mixture,
were directly converted to the corresponding ketones, acetone and
2-butanone (entries 1–3), within 1 h in excellent yields. When
1-amino-1-phenylethane and diphenylmethylamine were reacted
under the same conditions, both amines were completely
consumed within 10 min to afford the desired acetophenone and
benzophenone in 69% and 56% yields, respectively, but the
undesired hydrogenolysis products, ethylbenzene and diphenyl-
methane, were formed in 31% and 44% yields (entries 4–5).
Scheme 2 depicts a plausible reaction pathway. Oxidative
removal of dihydrogen,16 which is initially formed in situ in the
reaction between the starting amine and Pd/C, produces an imine.
The imine is hydrolyzed to give desired carbonyl compounds and
ammonia. As for benzylic amines, the Pd/C–dihydrogen species
causes hydrogenolysis as a side reaction, which increases the yield
of hydrocarbon products (Table 2. entries 4–5). For alkylamines,
the Pd/C–dihydrogen species releases dihydrogen to regenerate the
starting Pd/C catalyst.
Retro-reductive aminations, direct transformations of amines to
ketones, were catalyzed by Pd/C in water under microwave
irradiation.
Utilization of water as a chemical reagent and an alternative to
organic solvents is an essential aspect of Green Chemistry.1 We
have found that some amines can be directly and rapidly converted
to the corresponding ketones in good yields. This process is the
first example of an efficient retro-reductive amination reaction2
(Scheme 1).
Although the selective chemical transformation of an amine to a
ketone is a relatively common biological process,3 chemical
conversions of amines to ketones are rather limited.4 Some metal
oxidizing reagents such as KMnO4,5 K2FeO4,6 Pb(OAc)4,7 NiO2,8
and HgO–I29 have been used to convert amines to ketones through
imines. However these processes require stoichiometric or larger
amounts of poisonous late transition metals. Using a strong base
such as n-butyllithium10 or DBU11 to generate imines from amines
and subsequent hydrolysis to obtain ketones has been reported.
This two-step process needs dry conditions and the total yields of
ketones from amines were fairly low.
In the last two decades, microwave-assisted organic synthesis
has been an attractive tool for enhancing the selectivities and rates
of chemical reactions.12 Microwave irradiation has also been used
in the selective regeneration of carbonyl compounds from amine
derivatives such as oximes,13 hydrazones14 and semicarbazones15
in good yields. Herein we report the direct transformation of
amines to ketones with water, catalyzed by Pd/C, under microwave
irradiation.
Table 1 lists the preliminary results with several types of
butylamines. The reactions were conducted in the presence of Pd/C
and water, under continuous microwave irradiation (2.45 GHz,
50 W), in a pressure resistant glass ampoule. Within 5 min of
microwave irradiation, the temperature of the ampoule surface
rose to 170 uC, measured by an infrared thermo detector, and the
inside pressure of the ampoule was raised to 10.0 bar. Upon
In summary, we have demonstrated the direct transformation of
mono- or di-sec-alkylamines to the corresponding ketones with a
catalytic amount of Pd/C in water under microwave irradiation
conditions. The presently developed method should be very useful
since the reaction proceeds smoothly without an oxidant based on
Scheme 1
*a.miyazawa@aist.go.jp
2104 | Chem. Commun., 2005, 2104–2106
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Table 1 Preliminary results of the direct conversion of butylamines into carbonyl compoundsa
Relative yieldb (%)
Entry
R1
R2
R3
Method
Time (h)
Conversionb (%)
2
3
4
1
2
3
4
5
6
7
8
a
n-Pr
i-Pr
i-Pr
Me
Me
Me
Me
Me
H
H
H
Et
Et
Et
Et
Me
H
H
H
H
H
H
H
Me
MWc
1
1
5
1
1
9
2.5
1
16
20
32
100
29
76
13
0
0
20
Trace
Quant.
Quant.
59
53
80
50
0
0
Trace
0
0
47
0
50
0
0
41
0
MWc
MWc
MWc
170 uCd
170 uCd
Refluxe
MWc
Quant.
0
0
b
Conditions; [amine]/[Pd/C] 5 2 (mg/mg), 2 ml of water used. Determined by GC and GC-MS. Using pressure resistant glass ampoule with
c
d
microwave irradiation (50 W). Using a pre-heated oil bath. Refluxing with microwave irradiation (50 W).
e
Table 2 Reaction of mono- and di-sec-alkylamines with Pd/C in
water under microwave irradiationa
methodology to other substrates are underway and will be
published elsewhere.{
Time Conversionb
Entry Compounds (min) (%)
Productsb (relative yield, %)
Akira Miyazawa,*a Kan Tanaka,a Toshiyasu Sakakura,a
Masashi Tashiro,a Hideki Tashiro,b G. K. Surya Prakashb and
George. A. Olahb
1
60
60
100
100
aNational Institute of Advanced Industrial Science and Technology
(AIST), AIST Central 5, Tsukuba, Ibaraki, 305-8565, Japan.
E-mail: a.miyazawa@aist.go.jp; Fax: +81 29 861 4566;
Tel: +81 29 861 9388
2
bLoker Hydrocarbon Research Institute, Department of Chemistry,
University of Southern California, Los Angeles, California 90089-1661
3
60
100
Notes and references
{ The typical experimental procedure was as follows (i.e. Table 1 entry 4): a
mixture of 100 mg (1.4 mmol) of sec-butylamine, 50 mg of 5 wt% Pd/C
(1.7 mol%) and 2 ml of water in a pressure resistant glass ampoule
equipped with rubber septum and an aluminium cap, was introduced into
the cavity of microwave apparatus (CEM Discover, 2.45 GHz, CEM
Corporation, NC, USA). The reaction mixture was irradiated by
microwave (50 W) continuously for 1 h. The reaction vessel was cooled
in an ice–water bath and the organic products were extracted with ether.
The ether fraction was analyzed by GC (FID detector) and GC-MS for
identification and quantification of the products.
4
5
5
100
100
10
a
b
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Conditions; [amine]/[Pd/C] 5 2 (mg/mg), 2 ml of water used.
Determined by GC and GC-MS.
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Scheme 2
poisonous heavy metals and volatile organic solvents. Moreover, it
has a high selectivity and a faster rate. Further investigations
into detailed reaction mechanisms, and application of the
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