Formation of secondary or tertiary aliphatic amines in aqueous media

Article abstract of DOI:10.1080/00397910802664269

Secondary and tertiary amines can be easily obtained from primary and secondary amines, respectively, in completely aqueous media, in the presence of a bicatalytic system formed of cheap commercial aluminum (Al) powder and 5% rhodium (Rh) or ruthenium (Ru) deposed on charcoal.

Full text of DOI:10.1080/00397910802664269

This article was downloaded by: [Duke University Libraries]
On: 19 June 2012, At: 05:31
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Formation of Secondary or
Tertiary Aliphatic Amines in
Aqueous Media
a
b
Alina Marieta Simion , Takashi Arimura , Akira
b
a
c
Miyazawa , Cristian Simion , G. K. Surya Prakash
c
b
,
a
George A. Olah & Masashi Tashiro
‘
Politehnica’ University of Bucharest, Faculty of
Applied Chemistry and Material Science, Organic
Chemistry Department, Bucharest, Romania
b
National Institute of Advanced Science and
Technology, Tsukuba, Ibaraki, Japan
c
Loker Hydrocarbon Research Institute, Department
of Chemistry, University of Southern California, Los
Angeles, California, USA
Available online: 14 Jul 2009
To cite this article: Alina Marieta Simion, Takashi Arimura, Akira Miyazawa, Cristian
Simion, G. K. Surya Prakash, George A. Olah & Masashi Tashiro (2009): Formation of
Secondary or Tertiary Aliphatic Amines in Aqueous Media, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
39:16, 2859-2865
To link to this article: http://dx.doi.org/10.1080/00397910802664269

PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

1
Synthetic Communications , 39: 2859–2865, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802664269
Formation of Secondary or Tertiary Aliphatic
Amines in Aqueous Media
1
Alina Marieta Simion, Takashi Arimura, Akira Miyazawa,
2
2
1
Cristian Simion, G. K. Surya Prakash, George A. Olah,
3
3
2
and Masashi Tashiro
Politehnica’ University of Bucharest, Faculty of Applied Chemistry and
1
‘
Material Science, Organic Chemistry Department, Bucharest, Romania
2
National Institute of Advanced Science and Technology,
Tsukuba, Ibaraki, Japan
3
Loker Hydrocarbon Research Institute, Department of Chemistry,
University of Southern California, Los Angeles, California, USA
Abstract: Secondary and tertiary amines can be easily obtained from primary
and secondary amines, respectively, in completely aqueous media, in the presence
of a bicatalytic system formed of cheap commercial aluminum (Al) powder and
5
% rhodium (Rh) or ruthenium (Ru) deposed on charcoal.
Keywords: Al powder, aqueous media, Rh=C, Ru=C, secondary amines, self-
alkylation
INTRODUCTION
Some of the most important classes of natural or biologically active
compounds are bearing secondary amino functions. Therefore, numerous
methods of synthesis have been developed over the years, with many
generations of chemists designing a large array of methodologies for
[1]
the formation of such moieties. The most convenient method seemed
Received October 13, 2008.
Address correspondence to Cristian Simion, Politehnica University of
Bucharest, Faculty of Applied Chemistry and Material Science, Organic
Chemistry Department, Spl. Independentei nr. 313, Bucharest 060042, Romania.
E-mail: c_simion@chim.upb.ro
2
859

2
860

Formation of Aliphatic Amines
2861
to be the treatment of a starting primary amine with a proper alkylating
agent (e.g., halide, alcohol, carbonyl compound) in the presence of a sui-
table catalyst and in a specific solvent. However, although possible, direct
alkylation processes using the same amine as reaction partner received
less attention from synthetic chemists. Thus, in the past decades, we
[2]
[3]
can only note the reports of Yoshimura et al. De Angelis et al. Kai
[
4]
[5]
[6]
et al. and Galen et al. along with our own results. A comparison
of these methods is presented in Table 1.
Most methods require high temperatures and long reaction times,
and catalysts are mainly based on platinum (Pt), palladium (Pd), rho-
dium (Rh), or ruthenium (Ru) (same metal-type complex catalysts are
[
7–12]
often used in the alkylation of primary amines with alcohols
). Yields
seem high, but large amounts of secondary products or reaction inter-
mediates are often recorded. Another important point is that very few
secondary amine preparations use water as reaction solvent. We report
our investigation of a simple, safe, and green self-alkylation process of
primary amines in completely aqueous media.
RESULTS AND DISCUSSION
Starting from our previous results, in which microwave irradiation
sufficed to activate a self-alkylation process of primary amines in aqu-
eous media and in the presence of a Pt=C þ aluminum (Al) powder cata-
lytic system, we decided to investigate the efficiency of a noble metal
catalyst for such a transformation when only heat is used as activator
[2]
and water as solvent. Yoshimura et al. used Pd (in the absence of
[6]
any solvent) and we previously tried Pt, but there are no literature
reports about the use of Ru=C or Rh=C in the synthesis of a secondary
amine in aqueous media. Kai et al. used a complex Ru halide and triphe-
[
4]
[5]
nylphosphine. Galen et al. although using Rh deposed on alumina,
started from nitriles and thus required gaseous hydrogen. Recently,
[8]
[7]
Hollman and coworkers used a complex Ru catalyst (Shvo’s catalyst )
in the alkylation of aniline with aliphatic amines, in tert-amylalcohol, in a
ꢀ
pressure tube, under an argon atmosphere at 150 C for 24 h.
In the first step, we studied the transformation of aliphatic primary
amines in the absence of microwave (MW) activation, with n-octyl amine
1
with previously obtained results.
a as the parent compound for these test runs for the sake of comparison
(See Scheme 1.)
[2,3,6]
Catalyst and temperature were very important: although Pt=C and
Pd=C offered only low to moderate yields of secondary amine, the best
catalysts proved to be Rh=C and Ru=C, especially when the reaction
ꢀ
was carried out in a sealed environment and temperature was 120 C

2862
A. M. Simion et al.
Scheme 1. Reaction of primary amines in water.
(Table 2). In this case, beside the main reaction product, which was the
secondary amine, and the main secondary reaction product, which was
the tertiary amine, the corresponding primary alcohol was also formed.
Meanwhile, no trace of imine was recorded.
As can be observed from Table 2, in all reactions carried out in open
tubes and boiling water (runs 1–4), the recovery of the starting amine was
almost complete, with no regard of the nature of the catalyst. When
ꢀ
working in a sealed tube (runs 5–8), the temperature rose to 120 C.
The best results were obtained using Rh=C and especially Ru=C as cata-
lysts (entries 7 and 8). Because no imine has been recorded (as in the pre-
viously mentioned processes, including our own), it appeared that in this
case, the reaction occurred through the intermediate formation of the
corresponding alcohol—it has been previously demonstrated that tertiary
amines can be obtained by the reaction of secondary amines with alcohol
[9,10]
in the presence of a Ru-based catalyst,
and mono-N-alkylation can
Table 2. Catalyst, time, and temperature influence on 1a transformation
b
Yield (%) after t h
t ¼ 1 h
t ¼ 2 h
t ¼ 3 h
Catalyst
a
Run (þAl)
Temp.
ꢀ
Tube
( C)
1
2
3
4
1
2
3
4
1
2
3
4
1
2
3
4
5
6
7
8
Pt=C
Open
Open
Open
Open
100 97 3 — — 97 3 — — 96 4 — —
100 98 2 — — 97 3 — — 96 4 — —
100 96 4 — — 95 5 — — 92 8 — —
Pd=C
Rh=C
Ru=C
Pt=C
Pd=C
Rh=C
Ru=C
100 93 6 —
1
87 12 —
1
80 19 —
1
Sealed 120 97 3 — — 96 4 — — 96 4 — —
Sealed 120 99 1 — — 98 2 — — 97 3 — —
Sealed 120 84 16 — — 71 29 — — 57 43 — —
Sealed 120 47 50 —
3
17 80 —
3
3 90
2
5
a
A mixture of 100 mg Al powder and 100 mg reduction catalyst (5% Met=C) in
mL water was added to 2 mmol of amine and stirred magnetically for 1 h. The
2
4
crude reaction mixture was extracted with diethyl ether. After drying on MgSO ,
the etheric extract was directly submitted to GC=MS analysis.
b
Established by GC=MS.

Formation of Aliphatic Amines
2863
Table 3. Secondary amine formation
a
Starting amine
Yield (%)
Catalyst
(þAl)
Run
R
1
R
2
Compound
1
2
3
4
1
2
3
4
5
6
7
8
9
0
1
2
3
4
n-C
7
H
13
–
n-C H –
H–
H–
H–
H–
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
1f
Rh=C
Ru=C
Rh=C
Ru=C
Rh=C
Ru=C
Rh=C
Ru=C
Rh=C
Ru=C
Rh=C
Ru=C
Rh=C
Ru=C
57
3
43
90
10
64
68
17
13
95
60
21
95
82
89
80
—
2
—
5
—
13
4
59
24
1
24
66
1
7
13
(CH
(CH
3
)
)
2
CH–
90
23
28
24
63
4
16
13
4
—
—
—
—
—
—
—
—
—
—
—
—
3
2
CH–
CH CH CH – CH3–
3
2
2
CH
(CH
3
CH
2
CH
C–
(CH ) C–
2
–
CH
3
–
3
)
3
H–
H–
3
3
CH
CH
3
CH
CH
–(CH ) –
2 5
–(CH ) –
–(CH
–(CH
2
–
–
CH
CH
3
–
–
1
1
1
1
1
3
2
3
1f
4
7
6
14
4
14
2
2
2
5
4
4
)
)
–
–
1g
1g
a
Established by GC=MS.
[
11]
[8,12]
occur using excess alcohol and a Rh- or Ru-based catalyst
at high
temperatures. When using only the noble metal catalyst deposed on
charcoal (without Al powder), no transformation occurred. Once the
most favorable reaction conditions were established (100 mg Al, 100 mg
ꢀ
Metal=C, 2 mL water, sealed tube, 120 C, and 3 h reaction time), the
reaction protocol was applied to other aliphatic amines (Table 3).
When considering the results obtained for compounds 1a–g, it is pos-
sible to note that when the primary amine has the structure RCH NH ,
2
2
the best catalyst is Ru=C, and when the formula is R CH–NH , the best
2
2
Table 4. Tertiary amine formation
a
Yield (%) after t time
2
f
3f
Entry
Catalyst (þAl)
1 h
2 h
3 h
7 h
1 h
2 h
3 h
7 h
1
2
Rh=C
Ru=C
91
88
84
79
82
71
32
37
9
10
15
18
17
26
68
58
a
Established by GC=MS.

2864
A. M. Simion et al.
Scheme 2. Amine transformations.
catalyst is Rh=C. Another important aspect is the absence of tertiary
amine at reaction times less than 3 h.
Having shown that primary amines transformed successfully to sec-
ondary amines in the presence of Rh=C or Ru=C and Al powder in an
aqueous system, we tried to apply the same process to the generation
of tertiary amines from secondary ones. We chose di-hexylamine 2f as
parent model (Table 4). In a sealed tube, the longer the reaction time
was, the greater the yields of tertiary amines were.
In every situation (1, 2, 3, or 7 h), small amounts of primary amines
were also detected by gas chromatography=mass spectroscopy (GC=MS).
Considering also the formation of secondary ammines from primary
ones, we may face two types of transformations (Scheme 2).
The rate of reaction (2) must be less than that of reaction (1), which
explains why no tertiary amine is formed when primary amines are sub-
mitted to the actual reaction conditions and why only traces of primary
amines are formed when secondary amines are introduced in the process.
Thus, both secondary and tertiary amines can be easily obtained in
an aqueous environment, in the presence of Al powder and Rh=C or
Ru=C, without the need for complex and expensive catalysts based on
the same metals. Secondary amines are formed starting from primary
amines in yields comparable to the previously reported ones, in shorter
reaction times and milder conditions. There are two other main advan-
tages of this process: the use of water as a solvent is cheap, harmless,
and safe, and most importantly there is no mixture of secondary and
tertiary amines formed, and thus the separation from the by-product
(the alcohol) is very easy to perform.
REFERENCES
1
2
. Salvatore, R. N.; Yoon, C. H.; Jung, K. W. Synthesis of secondary amines.
Tetrahedron 2001, 57, 7785–7811, and references cited therein.
. (a) Yoshimura, N.; Moritani, I.; Shimamura, T.; Murahashi, S.-I. Synthesis
of unsymmetrical secondary and tertiary amines from amines by palladium
catalyst. J. Am. Chem. Soc. 1973, 95, 3038–3039; (b) Murahashi, S.-I.;
Yoshimura, N.; Tsumiyama, T.; Kojima, T. Catalytic alkyl group exchange

Formation of Aliphatic Amines
2865
reaction of primary and secondary amines. J. Am. Chem. Soc. 1983, 105,
002–5011.
5
3
. De Angelis, F.; Grgurina, I.; Nicoletti, R. A convenient synthesis of second-
ary amines. Synthesis 1979, 70–71.
4
. Kai, B.-T.; Concilio, C.; Porzi, G. Cyclization of a,x-aliphatic diamines
and conversion of primary amines to symmetrical tertiary amines by a homo-
geneous ruthenium catalyst. J. Org. Chem. 1981, 46, 1759–1760.
. Galan, A.; de Mendoza, J.; Prados, P.; Rojo, J.; Echavarren, A. M. Synthesis
of secondary amines by rhodium-catalyzed hydrogenation of nitriles. J. Org.
Chem. 1991, 56, 452–454.
5
6
. Miyazawa, A.; Saitou, K.; Tanaka, K.; Gadda, T. M.; Tashiro, M.; Surya
Prakash, G. K.; Olah, G. A. Reaction of primary amines with Pt=C catalyst
in water under microwave irradiation: A convenient synthesis of secondary
amines from primary amines. Tetrahedron Lett. 2006, 47, 1437–1439.
5
5
7
. Prabhakaran, R. Shvo’s diruthenium complex [(g -C
m-H)(CO) Ru ]. Synlett 2004, 2048–2049.
4 4 4 4
Ph COHOCC Ph -g )
(
4
2
8
. (a) Hollmann, D.; B a¨ hn, S.; Tillack, A.; Beller, M. A general ruthenium-
catalyzed synthesis of aromatic amines. Angew. Chem., Int. Ed. Eng. 2007,
46 (43), 8291–8294; (b) Hollmann, D.; B a¨ hn, S.; Tillack, A.; Beller, M.
N-Dealkylation of aliphatic amines and selective synthesis of monoalkylated
aryl amines. Chem. Commun. 2008, 3199–3201; (c) Bahn, S.; Hollmann, D.;
Tillack, A.; Beller, M. Ruthenium-catalyzed synthesis of secondary alkyla-
mines: Selective alkylation with aliphatic amines. Adv. Synth. Catal. 2008,
350, 2099–2103; (d) Hollmann, D.; B a¨ hn, S.; Tillack, A.; Parton, R.; Altink,
R.; Beller, M. A novel salt-free ruthenium-catalyzed alkylation of aryl
amines. Tetrahedron Lett. 2008, 49, 5742–5745.
9
. Hamid, M. H. S. A.; Williams, J. M. J. Ruthenium-catalysed synthesis of
tertiary amines from alcohols. Tetrahedron Lett. 2007, 48, 8263–8265.
1
0. Tillack, A.; Hollmann, D.; Mevius, K.; Michalik, D.; Bahn, S.; Beller, M.
Salt-free synthesis of tertiary amines by ruthenium-catalyzed amination of
alcohols. Eur. J. Org. Chem. 2008, 4745–4750.
1
1. Baiker, A.; Kijenski, J. Catalytic synthesis of higher aliphatic amines from the
corresponding alcohols. Catal. Rev. Sci. Eng. 1985, 27, 653–697.
2. Watanabe, Y.; Tsuji, Y.; Ohusugi, Y. The ruthenium catalyzed N-alkylation
and N-heterocyclization of aniline using alcohols and aldehydes. Tetrahedron
Lett. 1981, 22, 2667–2670.
1