Colloidal and Nanosized Catalysts in Organic Synthesis: XXIII. Reductive Amination of Carbonyl Compounds Catalyzed by Nickel Nanoparticles in a Plug-Flow Reactor

Article abstract of DOI:10.1134/S1070363219120016

Reductive amination of aldehydes and ketones with primary and secondary amines under catalysis with nickel nanoparticles supported on zeolite X, MgO, or activated carbon in the gas phase or in the gas-liquid system in a plug-flow reactor proceeds at atmospheric pressure of hydrogen with the formation of secondary or tertiary amines in high yield.

Full text of DOI:10.1134/S1070363219120016

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 12, pp. 2333–2340. © Pleiades Publishing, Ltd., 2019.
Russian Text © The Author(s), 2019, published in Zhurnal Obshchei Khimii, 2019, Vol. 89, No. 12, pp. 1807–1815.
Colloidal and Nanosized Catalysts in Organic Synthesis:
XXIII.1 Reductive Amination of Carbonyl Compounds
Catalyzed by Nickel Nanoparticles in a Plug-Flow Reactor
V. M. Mokhova,*, Yu. V. Popova, A. N. Paputinaa, D. N. Nebykova, and E. V. Shishkina
a Volgograd State Technical University, Volgograd, 400005 Russia
*e-mail: tons@vstu.ru
Received May 30, 2019; revised May 30, 2019; accepted June 6, 2019
Abstract—Reductive amination of aldehydes and ketones with primary and secondary amines under catalysis
with nickel nanoparticles supported on zeolite X, MgO, or activated carbon in the gas phase or in the gas-liquid
system in a plug-flow reactor proceeds at atmospheric pressure of hydrogen with the formation of secondary or
tertiary amines in high yield.
Keywords: catalysis, nanoparticles, nickel, hydrogenation, reductive amination, amines
DOI: 10.1134/S1070363219120016
Secondary and tertiary amines are widely used as
semi-products in the preparation of drugs, solvents, poly-
mers, dyes, and agricultural chemicals [2–5].
hydrogen catalyzed by copper chromite in a continuous
mode performed at 300°С has been accompanied by side
reactions of aniline C-alkylation [10]. Homogeneous
reductive amination of aldehydes and ketones catalyzed
by rhodium(I) complexes occurs at room temperature,
hydrogen pressure being 50 atm to yield a mixture of
the corresponding amine and the alcohol, a product of
the carbonyl compound reduction [11].
Reductive amination of carbonyl compounds is com-
monly widely applied methods of amines synthesis [6–8],
due to the possibility of preparation of a wide range of
amines bearing various alkyl groups (depending on the
precursor) and ease of the process. The synthesis occurs
via sequential condensation of the carbonyl compound
with the amine to give the imine (enamine) and hydro-
genation of the С=С or C=N multiple bonds in the inter-
mediates. Both stages often require prolonged duration,
and in certain cases periodic process using an autoclave
is exclusively possible. Continuous process of reductive
amination has been used mainly for the synthesis of low-
molecular primary amines from spatially non-hindered
aldehydes and ketones. The side reactions of sequential
alkylation of a secondary amine with a carbonyl com-
pound into the tertiary amine as well as hydrogenation
of a carbonyl compound into the alcohol reduces the
process selectivity.
Reductive amination of carbonyl compounds under
catalysis of various iridium complexes (30‒35°С, 5‒
60 atm of hydrogen, 12–13 h) has been studied [12, 13].
The yield of the amines was up to quantitative.
The reaction in the presence of copper immobilized at
different carriers has been performed in a periodic mode
(5‒24 h, 100‒130°С) under vigorous stirring and bubbling
with hydrogen (1 atm) [14]. Copper applied on silica or
its combinations with alumina or titania has exhibited
high activity. When alumina was used as the carrier, the
alcohols yield was up to 75%.
Reductive amination of aldehydes and ketones
catalyzed by supported cobalt oxide nanoparticles under
quasi-homogeneous periodic conditions (50 atm of hy-
drogen, 150°С, 15 h) [15] have resulted in the yield of
secondary or tertiary amines of 10 to 95%, depending on
the substrate. The catalyst has been regenerated at least
five times without any loss of activity.
Reductive amination of aldehydes or ketones cata-
lyzed by the Raney nickel is performed in an autoclave
at hydrogen pressure of 100‒150 atm and 100°С [9]. The
reaction between aniline and acetone in the presence of
1 For communication XXII, see [1].
2333

2334
MOKHOV et al.
Scheme 1.
R1
R2
O
Ni0
R3
R4
/NaX (MgO, ɋ)
+
+ H2
+ H
2O
HN
ꢀ
R1
R2
1 atm, 60–240°ɋ
N
R4
ꢂɚ–3r
R3
ꢀɚ–1j
ꢁɚ–2k
R1 = H, R2 = Et (1а), Pr (1b), i-Pr (1c), i-Bu (1d), CH3(CH2)5 (1e), CH3(CH2)6 (1f), Ph (1g); R1 = Me, R2 = Ph (1h), R1 = R2 =
Et (1i), R1‒R2 = (CH2)5 (1j); R3 = H, R4 = Bu (2а), i-Bu (2b), t-Bu (2c), CH3(CH2)5 (2d), Cy (2e), Ph (2f), PhCH2 (2g);
R3 = R4 = Bu (2h); R3‒R4 = (CH2)4 (2i), (CH2)5 (2j), (CH2)6 (2k); R1 = R3 = H, R2 = i-Pr, R4 = i-Bu (3а), CH3(CH2)5 (3b);
R1 = R3 = H, R4 = Ph, R2 = Et (3c), i-Pr (3d), i-Bu (3e); R1 = R3 = H, R2 = i-Pr, R4 = Cy (3f); R1 = R3 = H, R2 = Ph, R4 = Bu (3g);
R1 = H, R2 = CH3(CH2)6, R3 = R4 = Bu (3h), R2 = i-Pr, R3‒R4 = (CH2)4 (3i), R2 = Pr, R3‒R4 = (CH2)6 (3j), R2 = CH3(CH2)5, R3‒
R4 = (CH2)6 (3k); R1‒R2 = (CH2)5, R3 = H, R4 = Bu (3l), CH3(CH2)5 (3m), Ph (3n); R1‒R2 = Et, R3‒R4 = (CH2)5 (3o); R1‒R2 =
(CH2)5, R3‒R4 = (CH2)5 (3p); R1 = Me, R2 = Ph, R3 = H, R4 = i-Bu (3q), CH3(CH2)5 (3r).
Reductive amination of carbonyl compounds has been
performed by metal (palladium or platinum) nanoparticles
applied onto zeolites or alumina [16] in a continuous re-
actor (5 atm of hydrogen, 100°С, 7 h) [16]. The studied
catalysts have been found more active than the commer-
cial ones (Pt/C or Pd/Al2O3).
gen; in detail, the catalyst stability in the presence of reac-
tion water and the regularities of the reaction (Scheme 1)
selectivity were probed. The following substrates were
used: propionaldehyde, butyraldehyde, 2-methylpropio-
naldehyde, 3-methylbutyraldehyde, hexanal, heptanal,
benzaldehyde, diethyl ketone, cyclohexanone, and ace-
tophenone (carbonyl compounds); butylamine, isobutyl-
amine, tert-butylamine, hexylamine, cyclohexylamine,
aniline, pyrrolidine, piperidine, hexahydroazepine, and
dibutylamine (amines). Nickel nanoparticles were de-
posited onto the corresponding support (NaX zeolite,
bulk magnesia, or Norit RX 3 EXTRA activated carbon)
as described elsewhere [24, 25]; the Ni0/NaX, Ni0/MgO,
Ni0/С nanoparticles size was of 20‒100 nm.
A few reports have discussed reductive amination of
carbonyl compounds in a continuous mode. Benzylpi-
perazine derivatives have been obtained from substituted
benzaldehydes and piperazine in a continuous mode
using Pd/C, Pt/C, and Pd(OH)2/C [17–18]. The use of
gold nanoparticles (2‒3 nm) on titania for the catalysis
of amines alkylation in a flow system has been described
[19].Alcohols have been used as alkylating agents instead
of carbonyl compounds. The reaction in toluene (50 atm,
180‒200°С, 24 h) has yielded up to 92% of the amines.
The reaction between phenylethylamine and levulinic
acid in continuous mode (Fe/Ni catalyst, 150°С, hy-
drogen pressure 85 atm) has afforded the N-substituted
pyrrolidone with 91% yield [20].Acontinuous method of
reductive amination of ketones with ammonium formate
catalyzed by Pd/C has been described [21]. Commercial
Pd/C has been used for the catalysis of the reaction be-
tween amines and ketones supplied separately as 0.1 M
solutions in toluene (40‒140°С), the products yield has
been 63‒100% [22].
The reaction was performed under a stream of 5‒15-
fold excess of hydrogen at atmospheric pressure and
temperature 60‒240°C in a continuous reactor (a metal
tube with inner diameter 9 mm and heating zone height
100 mm put in an electric oven). The catalyst layer was
put in a middle part of the reactor, surrounded by inert
filler (quartz attachment).
The starting compounds 1a–1j and 2a–2k were
supplied to the reactor separately, without any solvent,
simultaneously with hydrogen (1 atm). The post-reaction
mixture composition was determined by means of mass
spectrometry. Majority of the products were identified by
comparison of their masses with the instrument internal
database, other products were identified by the molecular
ions and the characteristic decomposition.
When the Ni0/NaX catalyst was used [feeding rate
of carbonyl compounds and amines 0.9‒1.8 L/(kgcat h),
1a–1j to 2a–2k molar ratio (1‒1.5) : (1‒3), 5‒15-fold
excess of hydrogen, 60‒240°С], the yield of amines
3a–3r was 37‒97% depending on the substrate structure.
Development of available and highly active as well as
selective heterogeneous catalysts of reductive amination
has remained a topical issue. Hydrogenation of enamines
and imines catalyzed by nickel nanoparticles on zeolite
or activated carbon has been studied earlier [23].
Weinvestigatedthepossibilityofreductiveaminationof
aldehydes and ketones with primary and secondary amines
in continuous mode under atmospheric pressure of hydro-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

COLLOIDAL AND NANOSIZED CATALYSTS IN ORGANIC SYNTHESIS: XXIII.
2335
Intermediate imines and enamines were detected in the
reaction mixture during preparation of amines 3d, 3m,
3p; those intermediates disappeared upon the increase in
the hydrogen excess or temperature.
The increase in temperature above 200°С led to the
reduction of 5‒10% of the non-converted carbonyl com-
pounds into alcohols.At equimolar ratio of the substrates
and temperature decreased to 160‒180°С, the side reac-
tions were not observed, yet the conversion was typically
of 60‒80% and could be improved via heating above
200°С or decrease in the substrates feeding rate.
When the Ni0/NaX catalyst was used, the reaction
mixture practically did not contain the products of hydro-
genation of the aldehydes and ketones 1a–1j (the corre-
sponding alcohols): their content at reaction temperature
below 180°С did not exceed 1.5‒2%. It was shown that
the conversion of cyclohexanone into cyclohexanol under
the same conditions in the absence of an amine was of 2%,
whereas colloidal nickel is known to promote liquid-phase
hydrogenation of aliphatic ketones within 10‒12 h [24].
Hence, Ni0/NaX turned out to be a selective catalyst of
reductive amination of carbonyl compounds, and its use
would avoid the side hydrogenation reaction.
Reductive amination of aliphatic aldehydes with steri-
cally non-hindered amines occurred readily at tempera-
ture even below 100°С. The reaction of hexanal 1e with
hexahydroazepine 2k at 60°С with the Ni0/NaX catalyst
led to complete conversion of the substrates and almost
quantitative yield of compound 3k even at equimolar
ratio of the reactants 1d and 2k. When the reaction was
performed at 20 and 40°С, the yield of the secondary
amine 3k was of 70‒80%, the substrates conversion being
80‒90%. The intermediate enamine (3.5%) was detected
at 20°С along with compound 3k. Similar results were
revealed for the reaction of the С4‒С7 aldehydes with
cyclic secondary amines. The high yield of the reductive
amination products under mild conditions and their slight
dependence on temperature could be explained by high
catalyst activity as well as the increase in the duration of
its contact with liquid reactants.
Since the interaction of aliphatic aldehydes with pri-
mary and certain secondary amines occurs in the absence
of a catalyst, we also investigated the possibility of the
synthesis when carbonyl compounds and amines were
supplied to the reactor as equilibrium mixture with the
imine (enamine) and water. The yield and selectivity of
the process were found marginally different from those
obtained with separate supply of the reagents.
The support nature only slightly affected the catalytic
activity of nickel in the reaction of reductive amination,
whereas its influence on the reaction selectivity was
significant. When the Ni0/MgO catalyst was used for
reductive amination of 2-methylpropionaldehyde 1c
with hexylamine 2d, the secondary amide 3c was formed
along with N-isobutylaniline (yield 25%), the product of
dehydroaromatization of the hexyl group (Scheme 2).
Similarly, the interaction of cyclohexanone 1j with bu-
tylamine 2a gave N-butylaniline (yield 33%) as the side
product.
When the Ni0/MgO or Ni0/С catalyst was used, the
side reaction of carbonyl compounds reduction occurred
at lower temperature as compared to the Ni0/NaX one; that
resulted in the decrease in the selectivity of reductive ami-
nation. The Ni0/С catalyst revealed the best performance
in reductive amination of 2-methylpropionaldehyde
1c with tert-butylamine 2c. N-tert-Butylisobutylamine
3a was obtained with 48% yield, whereas the inter-
mediate imine was exclusively formed when using the
Ni0/NaX catalyst. The Ni0/С catalyst was more efficient
in reductive amination of ketones with secondary amines
at 120°С. The yield of N-cyclohexylpiperidine 3p upon
the interaction of cyclohexanone 1k with piperidine 2j
At high excess of primary amines 2a, 2b, 2d, 2e, 2g, a
competitive reaction of their disproportionation occurred,
leading to the formation of symmetric dialkylamines. That
reaction has been studied earlier using the same catalyst
[26]. For example, reductive amination of cyclohexanone
1j with butylamine 2a (molar ratio 1 : 3), N-butylcy-
clohexanamine was formed along with dibutylamine
(12 wt % in the products mixture, conversion of amine
2a 95%, selectivity with respect to dibutylamine 14%).
The use of secondary amines (morpholine, piperidine,
etc.) not prone to disproportionation allowed performing
the reaction at significant (3‒5-fold) excess of the amine,
the conversion of the carbonyl compound being complete
at 120‒160°С.
Amines 3b–3d, 3k were prepared using excess of the
carbonyl compound with respect to the amine. Reductive
amination of excess of propionaldehyde 1a with aniline
2f gave the secondary amine 3c along with the tertiary
one, N,N-dipropylaniline with yield 28%. The reaction
of aniline 2f with excess of 2-methylpropionaldehyde 1c
occurred selectively, and the fraction of the correspond-
ing tertiary amine in the products mixture was as low as
3 wt %.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

2336
MOKHOV et al.
Scheme 2.
H
(Ni0/MgO)
+
+
N
CHO
NH
NH2 + H2
56%
25%
O
H
N
H
N
(Ni0/MgO)
+
+
+ H2
NH2
33%
37%
was 73% as compared to 57% with the Ni0/NaX catalyst
under the same conditions. The Ni0/С catalyst was opera-
tive at even lower temperature. The yield of amine 3p at
80 and 60°С was 64 and 36%, respectively.
In summary, the use of the Ni0/NaX, Ni0/MgO, and
Ni0/С heterogeneous catalysts in the reaction of reductive
amination of carbonyl compounds afforded secondary
and tertiary amines with yield 37‒97% and selectivity
49‒100% at 60‒240°С and atmospheric pressure of hy-
drogen in continuous mode; the reaction water did not
affect the activity and stability of the catalysts.
the reactor, sandwiched between the pieces of inert filler
(quartz attachment). Liquid aldehyde (or ketone) and
amine were fed at certain ratio, and the desired hydrogen
feeding rate was set. Feeding rate of the liquid mixture
0.9‒1.8 L/(kgkat h). Hydrogen supply rate 250‒1500 L/
(kgcat h) (5‒15-fold molar excess).
N-tert-Butyl-2-methylpropane-1-amine (3a). Hy-
drogen [1500 L/(kgcat h)] and a mixture of 2-methyl-
propionaldehyde 1c and tert-butylamine 2c [1.8 L/(kgcat
h), molar ratio 1c : 2c = 1 : 2] was fed on 2 g of Ni0/C
at 160°С. Conversion of aldehyde 1c 48%. Selectivity
with respect to the product 3a 100%, yield 48%. Mass
spectrum, m/z (Irel, %): 130.8 (8.8) [M + 2]+, 129.8 (100)
[M + 1]+, 128.0 (4.2) [M ‒ 1]+, 115.0 (8.5), 114.0 (95.0),
85.8 (2.8), 58.0 (26.2), 57.0 (6.7), 56.0 (2.6), 54.9 (2.0),
42.0 (6.4), 41.0 (8.5).
EXPERIMENTAL
Chromato–mass spectral analysis was performed
using a Saturn 2100 T/GC3900 instrument (EI, 70 eV).
Catalyst preparation. The catalysts were prepared
via impregnation of a solid support (NaX zeolite, mag-
nesium oxide MgO, or Norit RX 3 EXTRA activated
carbon) with an aqueous solution of nickel(II) chloride
hexahydrate NiCl2·6H2O during 5‒6 h. The obtained
solid product was filtered off, washed with distilled water,
and treated with aqueous solution of sodium borohydride
NaBH4 at 20‒25°С during 20‒30 min. The size of nickel
particles on the support was of 70‒100 nm [23]. The
obtained moisty catalyst was charged to the reactor and
dried in a hydrogen stream at 120‒300°С just before the
reaction.
N-Isobutylhexane-1-amine (3b). a. Hydrogen
[750 L/(kgcat h)] and a mixture of 2-methylpropion-
aldehyde 1c [1.08 L/(kgcat h) and hexane-1-amine 2d
[0.72 L/(kgcat h), molar ratio 1c : 2d = 1.5 : 1] was fed
on 2 g of Ni0/NaX at 180°С. Conversion of amine 2d
100%. Selectivity with respect to the product 3b 55.8%,
yield 55.8%. Mass spectrum, m/z (Irel, %): 157.0 (9.8)
[M]+, 156.0 (100) [M ‒ 1]+, 154.1 (5.6), 112.9 (6.5), 112.0
(91.9), 83.0 (3.2), 70.0 (6.5), 68.0 (3.6), 57.0 (2.5), 56.0
(14.4), 54.9 (10.2), 53.0 (2.2), 43.9 (2.2), 43.0 (2.6), 42.0
(2.5), 41.0 (10.1). N-Hexyl-2-methylpropane-1-imine,
yield 12.9%. Mass spectrum, m/z (Irel, %): 157.0 (11)
[M + 2]+, 156.0 (100) [M + 1]+, 154.2 (4) [M ‒ 1]+, 112.1
(46), 84.2 (2), 70.0 (2), 56.0 (5), 55 (11), 43 (6), 42 (4),
41 (8). Dihexylamine, yield 22.3%. Mass spectrum, m/z
(Irel, %): 187.1 (8) [M + 2]+, 186.1 (50) [M + 1]+, 184.8 (4)
[M]+, 114.0 (60), 44.0 (100). N-Hexylhexane-1-imine,
yield 7.3%. Mass spectrum, m/z (Irel, %): 185.1 (13)
[M + 2]+, 184.1 (100) [M + 1]+, 182.2 (3) [M ‒ 1]+, 112.0
(37), 41.0 (4).
Reductive amination (general procedure). The reac-
tion was performed in a continuous reactor at atmospheric
pressure and temperature 60‒240°С. Depending on the
boiling point of the substrates, the reaction could occur
either in gas phase or in the gas‒liquid‒solid catalyst
system. The laboratory-scale reactor was manufactured
of a 12Х18Н10Т steel tube with inner diameter 9 mm and
the heating zone height 50 mm (electric oven heating).
The catalyst layer was positioned in the middle part of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

COLLOIDAL AND NANOSIZED CATALYSTS IN ORGANIC SYNTHESIS: XXIII.
2337
b. Hydrogen [1000 L/(kgcat h)] and a mixture of
2-methylpropionaldehyde 1c [1.08 L/(kgcat h)] and
hexane-1-amine 2d [0.72 L/(kgcat h), molar ratio 1c : 2d =
1.5 : 1] was fed on 4 g of Ni0/MgO at 200°С. Conversion
of amine 2d 100%. Selectivity with respect to the product
3b 56.3%, yield 56.3%. Mass spectrum, m/z (Irel, %):
157.0 (9.8) [M]+ 156.0 (100) [M ‒ 1]+, 154.1 (5.6), 112.9
(6.5), 112.0 (91.9), 83.0 (3.2), 70.0 (6.5), 68.0 (3.6), 57.0
(2.5), 56.0 (14.4), 54.9 (10.2), 53.0 (2.2), 43.9 (2.2), 43.0
(2.6), 42.0 (2.5), 41.0 (10.1). N-Isobutylhexane-1-imine.
Yield 19.7%. Mass spectrum, m/z (Irel, %): 156.0 (3.7)
[M + 1]+, 154.1 (1.2) [M ‒ 1]+, 144.4 (16.9), 142.8 (10.9),
112.0 (16.1), 100.8 (2.9), 74.0 (5.7), 72.9 (100), 70.8
(15.9), 57.0 (4.4), 56.0 (7.3), 54.9 (49.3), 45.0 (3.8), 43.0
(19.5), 41.0 (17.8). N-Isobutylaniline, yield 24.9%. Mass
spectrum, m/z (Irel, %): 150.9 (10.4) [M + 2]+, 150.0 (100)
[M + 1]+, 149.0 (48.5) [M]+, 148.1 (4.6) [M – 1], 107.1
(5.6), 106.2 (64.2), 79.1 (3.1), 77.0 (3.0).
on 4 g of Ni0/NaX at 160°С. Conversion of aldehyde 1d
89.7%. Selectivity with respect to the product 3e 100%,
yield 89.7%. Mass spectrum, m/z (Irel, %): 164.8 (1.2)
[M + 2]+, 163.9 (13.2) [M + 1]+, 163.0 (25.3) [M]+, 107.0
(7.2), 105.9 (100), 93.0 (4.1), 79.1 (9.8), 78.1 (3), 77.0
(13.2), 65.0 (3.4), 51.0 (5.8), 50.0 (3.4), 41.0 (3.5).
N-Isobutylcyclohexanamine (3f). a. Hydrogen [1500
L/(kgcat h)] and a mixture of 2-methylpropionaldehyde
1c and cyclohexylamine 2e [1.8 L/(kgcat h), molar ratio
1c : 2e = 1 : 1.5] was fed on 2 g of Ni0/NaX at 180°С.
Conversion of aldehyde 1c 99%. Selectivity with respect
to the product 3f 88.3%, yield 87.4%. Mass spectrum,
m/z (Irel, %): 156.9 (6) [M + 2]+, 156.0 (54.5) [M + 1]+,
154.1 (4) [M ‒ 1]+, 112.0 (100), 84.0 (13.6), 70.0 (14.5),
56.0 (13), 43.0 (18.5), 41.0 (21).
b. Hydrogen [500 L/(kgcat h)] and a mixture of cyclo-
hexanone 1j and isobutylamine 2b [0.9 L/(kgcat h), molar
ratio 1j : 2b = 1 : 3] was fed on 4 g of Ni0/MgO at 200°С.
Conversion of ketone 1j 88%. Selectivity with respect to
the product 3f 100%, yield 88%.
N-Propylaniline (3c). Hydrogen [1500 L/(kgcat h)]
and a mixture of propionaldehyde 1a and aniline 2f
[1.8 L/(kgcat h), molar ratio 1a : 2f = 1 : 1.5] was fed on
2 g of Ni0/NaX at 2000°С. Conversion of aldehyde 1a
99%. Selectivity with respect to the product 3c 57%,
yield 56.4%. Mass spectrum, m/z (Irel, %): 136.9 (3.5)
[M + 2]+, 136.0 (39.7) [M + 1]+, 134.8 (41.4) [M]+,
106.9 (7.5), 105.9 (100), 104.0 (4.1), 79.0 (14.1), 77.0
(19.1), 65.0 (3.6), 50.9 (9.4), 50.0 (6.1), 43.9 (1.4).
N,N-Dipropylaniline, yield 42.5%. Mass spectrum, m/z
(Irel, %): 178.9 (12.3) [M + 2]+, 177.9 (100) [M + 1]+,
177.2 (36.6) [M]+, 176.2 (5.0) [M ‒ 1]+, 107.0 (3.2), 106.1
(38.9), 104.0 (1.2), 77.0 (1.2).
N-Benzylbutane-1-amine (3g). Hydrogen
[1000 L/(kgcat h)] and a mixture of benzaldehyde 1g
[0.45 L/(kgcat h)] and 1-butylamine 2a [1.35 L/(kgcat h),
molar ratio 1g : 2a = 1 : 3] was fed on 2 g of Ni0/NaX
at 200°С. Conversion of aldehyde 1g 96.5%. Selectivity
with respect to the product 3g 88.1%, yield 85%. Mass
spectrum, m/e (Irel, %): 163.9 (9.4) [M + 1]+, 162.0 (3)
[M ‒ 1]+, 119.9 (44.4), 105.9 (11), 91.0 (100), 77.0 (3),
65.0 (11), 51 (3), 41 (3). N-Butylbenzylidenamine, yield
4.9%. Mass spectrum, m/z (Irel, %): 163.0 (5.7) [M + 2]+,
162.0 (40) [M + 1]+, 160.9 (9) [M]+, 160.0 (29) [M ‒ 1]+,
132.0 (32), 119.0 (13), 118.0 (88), 117.0 (10.4), 105.0
(11), 104.0 (28), 91.0 (100), 89.1 (13), 77.0 (12.3), 65.1
(13), 51 (12.6), 50.0 (10), 41 (9). N,N-Dibytulbenzyl-
amine, yield 6.5%. Mass spectrum, m/z (Irel, %): 221.2
(2) [M + 2]+, 220.1 (11.6) [M + 1]+, 219.1 (3) [M]+, 218.1
(13.7) [M ‒ 1]+, 177.0 (12), 176.0 (100), 142.1 (2), 134.1
(22), 91.1 (15), 65.0 (2), 41 (2).
N-Isobutylaniline (3d). a. Hydrogen [1500 L/(kgcat h)]
and a mixture of 2-methylpropionaldehyde 1c
[0.9 L/(kgcat h)] and aniline 2f [0.9 L/(kgcat h), molar ratio
1c : 2f = 1 : 1] was fed on 2 g of Ni0/NaX at 200°С. Con-
version of aldehyde 1c 95.7%. Selectivity with respect
to the product 3f 100%, yield 95.7%.Mass spectrum, m/z
(Irel, %): 150.9 (5) [M + 2]+, 150.0 (41) [M + 1]+, 149.0
(34) [M]+, 107.0 (8), 106.0 (100), 77.0 (11), 51.0 (6).
N,N-Dibutylheptane-1-amine (3h). Hydrogen
[200 L/(kgcat h)] and a mixture of heptanal 1f and di-
butylamine 2h [0.9 L/(kgcat h), molar ratio 1f : 2h =
1 : 2] was fed on 4 g of Ni0/NaX at 180°С. Conversion of
aldehyde 1f 100%. Selectivity with respect to the product
3h 80.9% yield. Mass spectrum, m/z (Irel, %): 229.1 (6.1)
[M + 2]+, 228.2 (40.2) [M + 1]+, 226.2 (11.8) [M ‒ 1]+,
185.1 (12.5), 184.2 (100), 183.2 (10.2), 143.2 (6.1), 144.2
(66.3), 140.2 (4.4), 101.1 (4.2), 100.0 (64.2), 98.2 (8.4),
58.1 (62.2), 57.2 (3.9).
b. Hydrogen [1500 L/(kgcat h)] and a mixture
of 2-methylpropionaldehyde 1c and aniline 2f
[1.8 L/(kgcat h), molar ratio 1c : 2f = 1 : 1.5] was fed on
2 g of Ni0/NaX at 180°С. Conversion of aldehyde 1c
89.3%. Selectivity with respect to the product 3d 100%,
yield 89.3%.
N-Isopentylaniline (3e). Hydrogen [500 L/(kgcat h)]
and a mixture of 3-methylbutyraldehyde 1d and aniline
2f [0.9 L/(kgcat h), molar ratio 1d : 2f = 1 : 1] was fed
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

2338
MOKHOV et al.
N-Isobutylpyrrolidine (3i). Hydrogen
N-Hexylcyclohexanamine (3m). Hydrogen
[750 L/(kgcat h)] and a mixture of cyclohexanone 1j and
hexylamine 2d [0.9 L/(kgcat h), molar ratio 1j : 2d =
1 : 1] was fed on 4 g of Ni0/NaX at 240°С. Conversion
of ketone 1j 100%. Selectivity with respect to the prod-
uct 3m 86%, yield 86%. Mass spectrum, m/z (Irel, %):
185.1 (12) [M + 2]+, 184.2 (100) [M + 1]+, 140.3 (4.2),
112.2 (9.7), 56 (1.8). Dihexylamine, yield 13.7%. Mass
spectrum, m/z (Irel, %): 187.1 (4.6) [M + 2]+, 186.1 (31.8)
[M + 1]+, 184.3 (2.5) [M ‒ 1]+, 115.0 (4.7), 114.1 (55.8),
56.0 (3.1), 55.1 (3.4), 45.1 (2.8), 44.2 (100), 43.2 (8.5),
42.2 (4.8), 41.1 (7.5).
[500 L/(kgcat h)] and a mixture of 2-methylpro-
pionaldehyde 1c [0.72 L/(kgcat h)] and pyrrolidine 2i
[1.08 L/(kgcat h), molar ratio 1c : 2i = 1 : 1.5] was fed
on 2 g of Ni0/NaX at 140°С. Conversion of aldehyde 1c
90.6%. Selectivity with respect to the product 3i 100%,
yield 90.6%. Mass spectrum, m/z (Irel, %): 129.0 (3)
[M + 2]+, 128.0 (37.6) [M + 1]+, 126.0 (11) [M ‒ 1]+,
112.0 (1), 84.9 (5), 84.0 (100), 83.0 (8).
N-Butylhexahydroazepine (3j). Hydrogen
[1500 L/(kgcat h)] and a mixture of butyraldehyde 1b
and hexahydroazepine 2k [1.8 L/(kgcat h), molar ratio
1b : 2k = 1.5 : 1] was fed on 2 g of Ni0/NaX at 180°С.
Conversion of amine 2k 93.8%. Selectivity with respect
to the product 3j 100%, yield 93.8%. Mass spectrum, m/z
(Irel, %): 157.0 (5) [M + 2]+, 156.0 (550) [M + 1]+, 154.2
(14.6) [M ‒ 1]+, 113.1 (9), 112.3 (100), 111.3 (17), 98.0
(1.5), 58.0 (45), 57.2 (5).
N - C y c l o h e x y l a n i l i n e ( 3 n ) . H y d r o g e n
[1500 L/(kgcat h)] and a mixture of cyclohexanone 1j
[0.9 L/(kgcat h)] and aniline 2f [0.9 L/(kgcat h), molar ratio
1j : 2f = 1 : 1] was fed on 2 g of Ni0/MgO at 200°С. Con-
version of ketone 1j 79%. Selectivity with respect to the
product 3n 88.5%, yield 70%. Mass spectrum, m/z (Irel,
%): 177.0 (3.8) [M + 2]+, 176.0 (33.8) [M + 1]+, 175.0
(67.1) [M]+, 146.0 (7.3), 133.0 (10.7), 132.0 (100), 130.1
(5.0), 119.1 (8.7), 118.0 (18.6), 117.1 (11.5), 106.1 (6.8),
104.0 (4.3), 93.1 (6.5), 91.1 (5.7), 77.0 (9.9), 65.0 (4.9),
51.0 (7.1), 50.0 (4.3). N-Phenylcyclohexanimine, yield
8.4%. Mass spectrum, m/z (Irel, %): 175.0 (8.1) [M + 2]+,
174.0 (64.9) [M + 1]+, 173.0 (100) [M], 172.2 (13.4),
144.1 (8.7), 131.0 (8.8), 130.1 (83.4), 117.1 (6.5), 77.0
(5.6), 51.0 (4.7), 50.0 (2.8).
N-Hexylhexahydroazepine (3k). Hydrogen
[1500 L/(kgcat h)] and a mixture of hexanal 1e
[0.9 L/(kgcat h)] and hexahydroazepine 2k
[0.9 L/(kgcat h), molar ratio 1e : 2k = 1 : 1] was fed on 4 g
of Ni0/NaX at 60°С. Conversion of amine 2k 84.4%.
Selectivity with respect to the product 3k 100%, yield
84.4%. Mass spectrum, m/z (Irel, %): 185.1 (1.6) [M + 2]+,
184.1 (10.7) [M + 1]+, 182.1 (3.8) [M ‒ 1]+, 113.0 (7.3),
112.0 (100), 84.1 (2.6), 58.2 (31.8), 44.2 (2.2), 42.0 (2.4).
N-(Pentan-3-yl)piperidine (3o). Hydrogen
[250 L/(kgcat h)] and a mixture of pentan-2-one 1i and
piperidine 2j [0.9 L/(kgcat h), molar ratio 1i : 2j = 1 : 3]
was fed on 4 g of Ni0/NaX at 200°С. Conversion of ke-
tone 1i 44.8%. Selectivity with respect to the product 3o
100%, yield 44.8%. Mass spectrum, m/z (Irel, %): 157.0
(1.1) [M + 2]+, 156.0 (8.7) [M + 1]+, 154.1 (3.2) [M ‒ 1]+,
127.0 (10.3), 126.1 (100), 124.2 (2.5), 110.1 (1.4), 98.2
(1.6), 70.1 (1.4), 42.0 (2.1).
N-Butylcyclohexanamine (3l). a. Hydrogen
[1000 L/(kgcat h)] and a mixture of cyclohexanone 1j
[0.72 L/(kgcat h)] and butylamine 2a [1.08 L/(kgcat h),
molar ratio 1j : 2a = 1 : 1.5] was fed on 4 g of Ni0/MgO
at 240°С. Conversion of ketone 1j 76.3%. Selectivity
with respect to the product 3l 48.8%, yield 37.3%. Mass
spectrum, m/z (Irel, %): 157.1 (5.6) [M + 2]+, 156.0 (43.3)
[M + 1]+, 154.8 (4.6) [M]+, 154.2 (3.3) [M – 1], 126.0
(3.9), 112.9 (10.1), 112.0 (100), 84.0 (3.5), 70.0 (7.6), 67.0
(3.8), 57.0 (4.7), 56.0 (12.6), 55.1 (6.3), 44.1 (5.7), 41.0
(7.7). N-Butylaniline, yield 33.4%. Mass spectrum, m/z
(Irel, %): 150.0 (8.1) [M + 1]+, 149.0 (23.7) [M]+, 148.1
(2.5) [M ‒ 1]+, 118.0 (2.8), 107.0 (6.8), 106.1 (100), 104.0
(2.7), 79.1 (10.9), 78.2 (3.1), 77.0 (15.9), 65.1 (3.9), 51.0
(5.9), 50.0 (3.4).
N-Cyclohexylpiperidine (3p). a. Hydrogen
[1500 L/(kgcat h)] and a mixture of cyclohexanone 1j and
piperidine 2j [0.9 L/(kgcat h), molar ratio 1j : 2j = 1 : 2]
was fed on 2 g of Ni0/C at 160°С. Conversion of ketone 1j
70.2%. Selectivity with respect to the product 3p 99.3%,
yield 69.7%. Mass spectrum, m/z (Irel, %): 169.0 (4.3)
[M + 2]+, 168.1 (35.3) [M + 1]+, 167.0 (13.3) [M]+, 166.2
(10.5) [M ‒ 1]+, 138.1 (2.5), 125.0 (9.8), 124.1 (100),
122.3 (2.0), 110.1 (3.5), 96.3 (4.6).
b. Hydrogen [1500 L/(kgcat h)] and a mixture of
butyraldehyde 1b and cyclohexylamine 2e [1.8 L/
(kgcat h), molar ratio 1b : 2e = 1 : 1] was fed on 2 g
of Ni0/NaX at 200°С. Conversion of aldehyde 1b
100%. Selectivity with respect to the product 3l 97%,
yield 97%.
b. Hydrogen [500 L/(kgcat h)] and a mixture of cy-
clohexanone 1j and piperidine 2j [0.9 L/(kgcat h), molar
ratio 1j : 2j = 1 : 2] was fed on 2 g of Ni0/NaX at 180°С.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

COLLOIDAL AND NANOSIZED CATALYSTS IN ORGANIC SYNTHESIS: XXIII.
2339
4. Ward, J. and Wohlgemuth, R., Curr. Org. Chem., 2010,
vol. 14, no. 17, p. 1914.
Conversion of ketone 1j 96.7%. Selectivity with respect
to the product 3p 98.5%, yield 95.2%. Mass spectrum, m/z
(Irel, %): 169.0 (4.3) [M + 2]+, 168.1 (35.3) [M + 1]+, 167.0
(13.3) [M]+, 166.2 (10.5) [M ‒ 1]+, 138.1 (2.5), 125.0
(9.8), 124.1 (100), 122.3 (2.0), 110.1 (3.5), 96.3 (4.6).
https://doi.org/10.2174/138527210792927546
5. Nador, F., Moglie, Y., Ciolino, A., Pierini, A., Dorn, V.,
Yus, M., Alonso, F., and Radivoy, G., Tetrahedron,
Lett., 2012, vol. 53, no. 25, p. 3156.
2-Methyl-N-(1-phenylethyl)propane-1-amine (3q).
Hydrogen [250 L/(kgcat h)] and a mixture of acetophenone
1h and isobutylamine 2b [0.9 L/(kgcat h), molar ratio
1h : 2b = 1 : 5] was fed on 2 g of Ni0/MgO at 180°С.
Conversion of ketone 1h 100%. Selectivity with respect
to the product 3q 42.4%, yield 42.4%. Mass spectrum,
m/z (Irel, %): 178.8 (9.6) [M + 2]+, 177.9 (87.4) [M + 1]+,
176.2 (3.5) [M ‒ 1]+, 162.0 (21.9), 133.9 (10.5), 105.9
(16.0), 105.0 (100), 104.2 (5.4), 103.1 (9.9), 79.1 (8.9),
77.0 (7.9), 51.0 (3.7), 41.0 (3.4). Ethylbenzene, yield
55.4%. Mass spectrum, m/z (Irel, %): 106.7 (2.9) [M +
1]+, 105.8 (33.1) [M]+, 105.0 (7.7) [M ‒ 1]+, 102.9 (3.7),
91.9 (6.6), 91.0 (100), 79.0 (3.0), 78.1 (3.0), 77.0 (4.5),
65.0 (11.4), 63.0 (3.8), 51.0 (5.9), 50.0 (4.4).
https://doi.org/10.1016/j.tetlet.2012.04.054
6. Menche, D., Bçhm, S., Li, J., Rudolph, S., and Zander, W.,
Tetrahedron, Lett., 2007, vol. 48, no. 3, p. 365.
https://doi.org/10.1016/j.tetlet.2006.11.082
7. Wang, C., Pettman, A., Basca, J., and Xiao, J., Angew.
Chem. Int. Ed., 2010, vol. 49, no. 41, p. 7548.
https://doi.org/10.1002/anie.201002944
8. Jung, Y.J., Bae, J.W., Park, E.S., Chang, Y.M.,
and Yoon, C.M., Tetrahedron, 2003, vol. 59, no. 51,
p. 10331.
https://doi.org/10.1016/j.tet.2003.09.054
9. Quintin, W.D. and Marcus, E., USA Patent 4190601,
1978.
10. Pillai, R.B.C., Proc. Indian Nat. Sci. Acad., 1995, vol. 61,
no. 2A, p. 97.
N-(1-Phenylethyl)hexane-1-amine (3r). Hydrogen
[750 L/(kgcat h)] and a mixture of acetophenone 1h and
hexylamine 2d [0.9 L/(kgcat h), molar ratio 1h : 2d =
1 : 1.5] was fed on 4 g of Ni0/NaX at 220°С. Conversion of
ketone 1h 92.1%. Selectivity with respect to the product
3r 80.4%, yield 74%. Mass spectrum, m/z (Irel, %): 206.8
(11.2) [M + 2]+, 205.8 (100) [M + 1]+, 204.2 (3.9) [M ‒
1]+, 191.1 (9.2), 190.2 (63.1), 134.0 (4.3), 120.0 (6.1),
106.0 (17.6), 105.1 (53.6), 103.2 (5.9), 79.0 (6.9), 77.9
(3.7), 77.0 (6.5), 51.2 (3.5), 41.1 (5.5). Dihexylamine,
yield 18.1%. Mass spectrum, m/z (Irel, %): 186.9 (8.1)
[M + 2]+, 186.0 (74.1) [M + 1]+, 184.5 (2.3) [M]+, 115.1
(4.1), 114.2 (29.6), 113.2 (6.6), 112.2 (2.6), 55.2 (2.8),
44.2 (100), 42.2 (4.6), 41.2 (6.6).
11. Tararov, V.I., Kadyrov, R., Riermeier, T.H., and Börner, A.,
Chem. Commun., 2000, no. 19, p. 1867.
https://doi.org/10.1039/B005777K
12. Huang, H., Zhao, Y., Yang, Y., Zhou, L., and Chang, M.,
Org. Lett., 2017, vol. 19, no. 8, p. 1942.
https://doi.org/10.1021/acs.orglett.7b00212
13. Li, C., Villa-Marcos, B., and Xiao, J., J. Am. Chem.
Soc., 2009, vol. 131, no. 20, p. 6967.
https://doi.org/10.1021/ja9021683
14. Santoro, F., Psaro, R., Ravasio, N., and Zaccheria, F.,
ChemCatChem., 2012, vol. 4, no. 9, p. 1249.
https://doi.org/10.1002/cctc.201200213
15. Pisiewicz, S., Stemmler, T., Surkus A.-E., Junge, K., and
Beller, M., ChemCatChem., 2015, vol. 7, no. 1, p. 62.
https://doi.org/10.1002/cctc.201402527
16. Domine, M.E., Hernández-Soto, M.C., Navarro, M.T., and
Pérez, Y., Catalysis Today, 2011, vol. 172, no. 1, p. 13.
https://doi.org/10.1016/j.cattod.2011.05.013
17. Liu, J., Fitzgeraldand, A.E., and Mani, N.S., Synthesis,
2012, vol. 44, no. 15, p. 2469.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
REFERENCES
1. Nebykov, D.N., Popov Yu.V., Mokhov, V.M., Latysho-
va, S.E., Shcherbakova, K.V., Nemtseva, N.V., and
Shishkin, E.V., Russ. J. Gen. Chem., 2019, vol. 89,
no. 10, p. 1985.
https://doi.org/10.1055/s-0032-1316550
18. Sharma, S.K., Lynch, J., Sobolewska, A.M., Plucinski, P.,
Watson, R.J., and Williams, J.J.M., Catal. Sci. Technol.,
2013, vol. 3, p. 85.
https://doi.org/10.1134/S1070363219100013
https://doi.org/10.1039/C2CY20431B
19. Zotova, N., Roberts, F.J., Kelsall, G.H., Jessiman, A.S.,
Hellgardt, K., and Hii, K.K., Green Chem., 2012,
vol. 14, p. 226.
2. Higassio, Y.S. and Shoji, T., Appl. Catal. (A), 2001,
vol. 221, nos. 1–2, p. 197.
https://doi.org/10.1016/s0926-860x(01)00815-8
https://doi.org/10.1039/C1GC16118K
20. Chieffi, G., Braun, M., and Esposito, D., ChemSusChem.,
2015, vol. 8, no. 21, p. 3590.
3. Rani,V.R.,Srinivas,N.,Kulkarni,S.J.,andRaghavan,K.V.,
J. Mol. Catal. (A), 2002, vol. 187, no. 2, p. 237.
https://doi.org/10.1016/s1381-1169(02)00208-x
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

2340
https://doi.org/10.1002/cssc.201500804
MOKHOV et al.
24. Popov, Yu.V., Mokhov, V.M., Nebykov, D.N., Shcherbako-
va, K.V., and Dontsova, A.A., Russ. J. Gen. Chem., 2018,
vol. 88, no. 1, p. 20.
21. Falus, P., Boros, Z., Hornyanszky, G., Nagy, J.,
Darvas, F., Urge, L., and Poppe, L., Tetrahedron Lett.,
2011, vol. 52, p. 1310.
https://doi.org/10.1134/S1070363218010048
25. Popov, Yu.V., Mokhov, V.M., Latyshova, S.E., Nebyk-
ov, D.N., Panov, A.O., and Pletneva, M.Yu., Russ. J.
Gen. Chem., 2017, vol. 87, no. 10, p. 2276.
https://doi.org/10.1016/j.tetlet.2011.01.062
22. Laroche, B., Ishitani, H., and Kobayashi Sh., Adv. Synth.
Catal., 2018, vol. 360, p. 4699.
https://doi.org/10.1002/adsc.201801457
https://doi.org/10.1134/S107036321710005X
26. Mokhov, V.M., Popov, Yu.V., and Nebykov, D.N., Russ.
J. Gen. Chem., 2014, vol. 84, no. 9, p. 1656.
23. Popov, Yu.V., Mokhov, V.M., Latyshova, S.E., Nebyk-
ov, D.N., Panov, A.O., and Davydova, T.M., Russ. J.
Gen. Chem., 2018, vol. 88, no. 10, p. 2035.
https://doi.org/10.1134/S1070363218100018
https://doi.org/10.1134/S1070363214090023
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019