Colloid and nanodimensional catalysts in organic synthesis: III. Alkylation of amines with primary alcohols catalyzed by colloidal nickel and cobalt

Article abstract of DOI:10.1134/S1070363214050065

Alkylation of primary amines with primary alcohols has been performed under catalysis by colloidal nickel and cobalt particles. The synthesis of the catalyst and alkylation of amines have been carried out in a one-pot mode. The alkylation at 160-180°C in 6-12 h yields 55-90% of secondary amines.

Full text of DOI:10.1134/S1070363214050065

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 5, pp. 826–830. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © Yu.V. Popov, V.M. Mokhov, N.A. Tankabekyan, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 5, pp. 733–737.
Colloid and Nanodimensional Catalysts in Organic Synthesis:
III.1 Alkylation of Amines with Primary Alcohols
Catalyzed by Colloidal Nickel and Cobalt
Yu. V. Popov, V. M. Mokhov, and N. A. Tankabekyan
Volgograd State Technical University, pr. Lenina 28, Volgograd, 400005 Russia
e-mail: xseoz@yandex.ru
Received July 29, 2013
Abstract—Alkylation of primary amines with primary alcohols has been performed under catalysis by
colloidal nickel and cobalt particles. The synthesis of the catalyst and alkylation of amines have been carried
out in a one-pot mode. The alkylation at 160–180°C in 6–12 h yields 55–90% of secondary amines.
Keywords: alkylation, catalyst, nanoparticles, amines, alcohols
DOI: 10.1134/S1070363214050065
Amines are generally alkylated with alkyl halides at
elevated temperature [2]. However, this method is not
free from some disadvantages related to low acces-
sibility and toxicity of many alkyl halides and the
necessity of utilizing hydrogen halides formed during
the process. Alkylation of amines with alcohols in the
presence of conventional catalysts, such as aluminum
oxide or mixed metal oxides, requires fairly harsh
conditions, including the use of gaseous hydrogen
under high pressure and elevated temperature (as a
rule, not lower than 200°C) [3, 4]. Moreover, this
reaction leads to the formation of mixtures of
secondary and tertiary amines at different ratios.
Alkylation of amines with alcohols under catalysis by
ruthenium [5, 6] and iridium complexes [7, 8] has been
reported. However, the use of these procedures is
limited due to complexity of preparation of the catalysts
and their high cost. Alkylation of amines in the
presence of accessible nickel powder or Raney nickel
requires considerable amounts of the catalyst [9].
particles [11]. Among more accessible and less
expensive catalysts, copper–nickel particles stabilized
by barium stearate were used to catalyze amine
alkylation at temperatures exceeding 210°C [12].
Supported iron nanoparticles showed high efficiency in
the alkylation of amines with alcohols under micro-
wave irradiation [13]. Alonso et al. [14] reported on
the alkylation of aniline derivative with various
alcohols in the presence of nickel nanoparticles to
obtain secondary amines.
The available published data suggest importance of
studies directed toward search for accessible catalytic
systems that could ensure synthesis of secondary
amines via alkylation of primary amines with alcohols
under as mild conditions as possible.
As catalysts we tried ultrafine cobalt and nickel
particles. Colloidal solutions of these metals were
prepared according to known procedures. Nickel
nanoparticles capable of forming a homogeneous
colloidal solution were obtained by reduction of nickel
salts with hydrazine hydrate in aqueous–alcoholic
medium [15, 16]; the size of the metal particles was
less than 20 nm. We were the first to accomplish direct
alkylation of amines Ia–Ie with alcohols IIa–IIc in the
presence of colloidal cobalt or nickel particles without
their stabilization in the reaction mixture. We thus
obtained the corresponding secondary amines in 55–
87% yield (see Scheme 1).
Kwon et al. [10] described alkylation of amines
over palladium nanoparticles under mild conditions,
which afforded 75–90% of secondary amines. Kegnaes
et al. [11] reported on the synthesis of imines by
oxidative cross-coupling of amines with alcohols
catalyzed by titanium dioxide-supported gold nano-
1
For communication II, see [1].
826

COLLOID AND NANODIMENSIONAL CATALYSTS IN ORGANIC SYNTHESIS: III.
827
Scheme 1.
Ni0 (Co0)
RNH2 + R1OH
Iа_Ie IIа_IIc
RNHR' + H2O
IIIа_IIIg
160_180oC
R = Ph, R' = PhCH2 (Iа, IIа, IIIа), C6H13 (IIb, IIIb), C8H17 (IIc, IIIc);
R = PhCH2, R' = PhCH2 (Ib, IIId);
N
, R' = C6H13 (Id, IIIf), R =
R =
, R' = C6H13 (Ic, IIIe);
, R' = PhCH2 (Ie, IIIg).
R =
CH2
Scheme 2.
M0
+
H2(ads.)
R'
HO
R'
R'
O
N
RNH2
R
+
+
H2O
O
R'
R
H
R'
N
H2(ads.)
+
N
R'
R
Our experiments showed that the reaction requires
heating to 160°C and above; therefore, the developed
liquid-phase procedure is applicable to high-boiling
alcohols and amines.
methylene group attached to nitrogen resonated at δ
2.8–3.0 ppm. The properties of previously described
compounds were consistent with published data.
In keeping with published data [17, 18], a probable
reaction mechanism may be illustrated by the Scheme 2.
Nickel nanoparticles showed a higher catalytic
activity than cobalt nanoparticles in the alkylation of
amines with primary alcohols. In order to increase the
selectivity and the yield of secondary amines it was
necessary to use 1.5–2 equiv of alcohol with respect to
the amine; the reactions with equimolar amounts of the
reactants were characterized by incomplete conversion,
and by-products (including imines) were formed. In
the presence of a large excess of alkali the yields of
tertiary amines were insignificant.
Alcohol is oxidized to the corresponding aldehyde
on the catalyst surface, and the aldehyde reacts with
amine to give Schiff base which is reduced to
secondary amine with adsorbed hydrogen. Analogous
mechanism for the catalysis by metal complexes is
referred to as “borrowing hydrogen methodology” or
“hydrogen autotransfer” [17, 18]. The proposed
mechanism is confirmed by the 1H NMR spectra of the
reaction mixture obtained with a small excess of
alcohol, which contained a signal at δ ~6.0 ppm due to
the CH=N proton in intermediate imine.
The yields of secondary amines IIIa–IIIg depended
on the amount of the catalyst. It was necessary to use
at least 10 wt % of the catalyst to ensure efficient
alkylation, and the best yields of secondary amines in
the shortest time were obtained when the amount of
the catalyst was 25–30 wt % with respect to primary
amine. The process is accompanied by agglomeration
of the catalyst particles, which leads to reduction of
their specific surface area and hence catalytic activity,
so that considerable amounts of the catalyst are
required.
According to the GC/MS data, the alkylation
catalyzed by colloidal cobalt particles was accom-
panied by disproportionation of amines. With a view to
verify this reaction path, we successfully accomplished
disproportionation of benzylamine in the absence of
alcohol (Scheme 3). The reaction was carried out at
130°C and higher temperature (2–4 h), and the yield of
dibenzylamine (IIIg) was 67%. Likewise, amine IIIg
was obtained in 78% yield when 18 mol % of nickel
nanoparticles was used as catalyst. These data indicate
that colloidal nickel particles are more efficient than
Raney nickel in disproportionation of amines.
Analogous reaction with Raney nickel requires 80–
The structure of secondary amines IIIa–IIIg was
1
1
confirmed by H NMR and GC/MS data. Their H
NMR spectra contained signals from protons in the
benzene ring and alkyl group, and protons in the
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828
POPOV et al.
Scheme 3.
Ni0 (Co0)
_NH3
2
CH2NH2
CH2NHCH2
Ib
IIId
400 mol % of the catalyst and prolonged (up to 15 h)
heating, and the yield of secondary amines amounts to
67–88% [17].
EXPERIMENTAL
1
The H NMR spectra were recorded on a Varian
Mercury-300 spectrometer (300 MHz) from solutions
in carbon tetrachloride using hexamethyldisiloxane or
tetramethylsilane as internal reference. Gas chromato-
graphic–mass spectrometric analyses were obtained on
a Varian Saturn 2100 T/GC3900 instrument.
Our results suggest the possibility for cross-
coupling of amines catalyzed by metal nanoparticles
[18]. The mechanism of this reaction is likely to be
similar to the mechanism of amine alkylation with
alcohols, i.e., it involves elimination of hydrogen on
the metal surface with formation of imine.
Colloidal nickel and cobalt particles were prepared
by reduction of nickel(II) and cobalt(II) chlorides or
nitrates with hydrazine hydrate in aqueous isopropyl
alcohol according to the procedures described in [15,
16]. Insofar as all reactions were carried out at 130–
190°C, the corresponding amine and alcohol were
commonly added to a colloidal metal solution, and
aqueous isopropyl alcohol was then distilled off.
We tried to perform cross-disproportionation of
primary and secondary amines. Shimizu et al. [19]
previously reported on analogous reaction catalyzed by
alumina-supported palladium nanoparticles, which
ensured a yield of up to 88%. The reactivity of amines
is largely determined by their structure and stability of
intermediate Schiff bases. The conversion of 1-
adamantylmethanamine or 2-(1-adamantyl)ethanamine
in 6 h at 160°C was insignificant. By GC/MS we
detected only ~2% of the corresponding secondary
amines. Cross-coupling of 2-(1-adamantyl)ethanamine
with 3 equiv of piperazine was also inefficient. The
yield of expected N-[2-(1-adamantyl)ethyl]piperazine
was about 1%, and the yield of the primary amine
disproportionation product was 2%. Taking into
account that the data in [19] were obtained with
benzylamine and its derivatives, we can conclude that
these amines are considerably more prone to
disproportionation than other primary alkylamines.
N-Benzylaniline (IIIa). a. A mixture of 10.8 g
(0.1 mol) of benzyl alcohol, 15 g (0.161 mol) of
aniline, and 3 g of colloidal nickel particles was heated
for 6 h at 183–184°C. When the reaction was com-
plete, the mixture was filtered from the settled catalyst.
The product was isolated by distillation. Yield 7.7 g
(0.042 mol, 76.5%), bp 306–307°C; published data
1
[19]: bp 306–307°C. H NMR spectrum, δ, ppm: 3.60
s (1H, NH), 3.86 s (2H, CH2), 6.74–7.07 m (10H,
C6H5).
b. Likewise, from 6 g (0.055 mol) of benzyl alcohol
and 2.8 g (0.03 mol) of aniline using 1.8 g of colloidal
cobalt particles (183–184°C, 8 h) we obtained 4 g
(0.022 mol, 72%) of compound IIIa (isolated by
vacuum distillation).
In summary, we have developed a convenient
liquid-phase procedure for the alkylation of primary
amines with primary alcohols in the presence of
colloidal cobalt and nickel nanoparticles whose con-
siderable specific surface area allows the use of
smaller amount of the catalyst. Colloidal metal par-
ticles are readily available via reduction of their water-
soluble salts, and no stabilization of nanoparticles in
the reaction mixture is necessary. Further improvement
of the proposed method with a view to increase the
yield of secondary amines and reduce the catalyst
consumption is challenging.
N-Hexylaniline (IIIb). A mixture of 30.6 g (0.3 mol)
of hexan-1-ol, 14 g (0.15 mol) of aniline, and 4 g of
colloidal nickel was heated for 6 h at the boiling point.
The product was isolated as described above for IIIa.
Yield 23.1 g (0.13 mol, 87%), bp 169–171°C
(20 mmHg). 1H NMR spectrum, δ, ppm (J, Hz): 0.83 t
(3H, CH3, J = 12.9), 1.20 m (6H, CH2), 1.37 q (2H,
CH2, J = 19.5), 2.85 t (2H, CH2N, J = 14.7), 3.32 s
(1H, NH), 6.32–6.99 m (5H, C6H5). Mass spectrum
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COLLOID AND NANODIMENSIONAL CATALYSTS IN ORGANIC SYNTHESIS: III.
829
(EI, 70 eV), m/z (Irel, %): 177 (100) [M]+, 106 [M –
C5H11] (61). Found, %: C 81.36; H 10.75; N 7.89.
C12H19N. Calculated, %: C 81.30; H 10.80; N 7.90.
J = 14.0), 3.87 s (1H, NH), 6.28–7.56 m (6H, C10H7).
Found, %: C 84.60; H 9.29; N 6.11. C16H21N.
Calculated, %: C 84.53; H 9.31; N 6.16.
N-Octylaniline (IIIc). A mixture of 17.2 g
(0.132 mol) of octan-1-ol, 7.5 g (0.081 mol) of aniline,
and 0.6 g of colloidal nickel particles was heated for
10 h at 185–195°C. When the reaction was complete,
the mixture was filtered from the settled catalyst. The
product was isolated by vacuum distillation. Yield 11.4 g
N-Hexylquinolin-8-amine (IIIf). A mixture of
10.2 g (0.1 mol) of hexan-1-ol, 7.2 g (0.05 mol) of
quinolin-8-amine, and 3 g of nickel nanoparticles was
heated for 10 h at 160–180°C. When the reaction was
complete, the mixture was filtered from the catalyst,
and the product was isolated by vacuum distillation.
Yield 6.8 g (0.03 mol, 60%), bp 221–224°C (10 mmHg).
1H NMR spectrum, δ, ppm (J, Hz): 0.86 t (3H, CH3,
J = 13.8), 1.190–1.430 m (6H, CH2), 1.64 m (2H,
CH2), 3.12 t (2H, CH2N, J = 14.0), 4.33 s (1H, NH),
6.39–8.66 m (6H, C9H6N). Found, %: C 78.97; H 8.81;
N 12.22. C15H20N2. Calculated, %: C 78.90; H 8.83; N
12.27.
1
(0.055 mol, 68.5%), bp 180°C (20 mmHg). H NMR
spectrum, δ, ppm (J, Hz): 0.87 t (3H, CH3, J 12.4),
1.25 m (10H, CH2), 1.51 q (2H, CH2, J = 18.9), 2.98 t
(2H, CH2N, J = 14.1), 3.39 s (1H, NH), 6.38–7.02 m
(5H, C6H5). Mass spectrum (EI, 70 eV), m/z (Irel, %):
205 (100) [M]+, 106 [M – C7H15]+ (34). Found, %: C
81.86; H 11.31; N 6.83. C14H23N. Calculated, %: C
81.89; H 11.29; N 6.82.
N-Benzyladamantan-1-ylmethanamine (IIIg). A
mixture of 5.4 g (0.05 mol) of benzyl alcohol, 3.3 g
(0.02 mol) of adamantan-1-ylmethanamine, and 0.5 g
of colloidal nickel was heated for 8 h at 160–180°C.
The product was isolated by vacuum distillation. Yield
6.8 g (0.011 mol, 55%), bp 233–236°C (10 mmHg). 1H
NMR spectrum, δ, ppm (J, Hz): 1.34–2.20 m (16H,
C10H15, NH), 2.56 d (2H, CH2, J = 14.2), 3.74 d (2H,
CH2, J = 13.9), 6.85–7.30 m (5H, C6H5). Found, %: C
84.70; H 9.83; N 5.47. C18H25N. Calculated, %: C
84.65; H 9.87; N 5.48.
Dibenzylamine (IIId). a. A mixture of 6 g
(0.056 mol) of benzyl alcohol, 4.4 g (0.041 mol) of
benzylamine, and 0.8 g of colloidal cobalt particles
was heated for 5 h at 185–190°C. When the reaction
was complete, the mixture was filtered from the
catalyst, and the product was isolated by vacuum
distillation. Yield 5.7 g (0.029 mol, 71%), bp 159–162°C
(10 mmHg), nD20 1.5742; published data: bp 160–163°C
(10 mmHg) [19], nD20 = 1.5745 [20].
b. A mixture of 5 g (0.047 mol) of benzylamine and
0.4 g of colloidal cobalt particles was heated for 4 h at
140–145°C. When the reaction was complete, the
mixture was filtered from the catalyst, and the product
was isolated by vacuum distillation. Yield 3.1 g
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