Colloid and nanosized catalysts in organic synthesis: XIII. Synthesis of 2-R-2-imidazolines catalyzed by copper and iron oxide nanoparticles

Article abstract of DOI:10.1134/S1070363216020122

The reaction of carboxylic acids with ethylenediamine catalyzed by copper or iron oxide nanoparticles proceeds at 80°C with azeotropic water distilling off during 2-8 h to form 2-R-2-imidazolines. Acyl and diacyl derivatives of ethylenediamine are formed in the reaction as side products.

Full text of DOI:10.1134/S1070363216020122

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 2, pp. 281–285. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © Yu.V. Popov, V.M. Mokhov, I.I. Kalitina, 2016, published in Zhurnal Obshchei Khimii, 2016, Vol. 86, No. 2, pp. 253–257.
Colloid and Nanosized Catalysts in Organic Synthesis:
XIII.1 Synthesis of 2-R-2-Imidazolines Catalyzed
by Copper and Iron Oxide Nanoparticles
Yu. V. Popov, V. M. Mokhov, and I. I. Kalitina
Volgograd State Technical University, pr. Lenina 28, Volgograd, 400131 Russia
e-mail: tons@vstu.ru
Received July 9, 2015
Abstract—The reaction of carboxylic acids with ethylenediamine catalyzed by copper or iron oxide
nanoparticles proceeds at 80°C with azeotropic water distilling off during 2–8 h to form 2-R-2-imidazolines.
Acyl and diacyl derivatives of ethylenediamine are formed in the reaction as side products.
Keywords: catalysis, nanoparticles, copper, Fe3O4, ethylenediamine, imidazoline
DOI: 10.1134/S1070363216020122
2-Alkyl substituted imidazolines have been used as
corrosion inhibitors [2, 3], components of detergents
[4], additives for lubricating oil [5], components of
nonpolar solvents for hydrophobization of wood,
concrete, metal, and tissue softeners and antistatic agents
[6]. Furthermore, 2-imidazolines have been widely
used in pharmaceutical industry. In particularly, well
known drugs such as Naphthyzin [2-(1-naphthyl-
methyl)-2-imidazoline nitrate], Galazolin, Clophelin,
and some others contain imidazoline fragment in their
structure [7].
obtained via the reaction of the saturated acids or their
esters with 1,2-diamines or polyethylene-polyamines
[16]. The reaction has been performed without any
catalyst at evelated temperature (120–220°C) at
equimolar ratio of the reagents. It has been shown that
the yield of side products increases with the increase of
the alkyl chain of the carboxylic acid. In particular, in
the case of acetic acid yield of the high-boiling side
products was of about 33%, but it increased to 92% in
the case of myristic acid; yield of the target
imidazolines do not exceed 30% [16]. Later it has been
shown that non-catalytic synthesis provides a number
of compounds besides imidazolines, such as amine
soaps, amidoamines, and diamides [17]. Formation of
amidoamines and diamines started at 120–180°C;
further increase of temperature promotes cyclization of
amidoamines to form imidazolines. Diamides are not
involved in any further conversions. To reduce the
fraction of diamines in the prepared product, a large
excess of ethylenediamine has been applied, β-
oxyethylethylenediamine or polyethylene-polyamine
have been alternatively used as starting materials [17].
The main drawbacks of the catalyst-free synthesis are
high temperature of the process and formation of the
side products.
A number of methods for preparation of imida-
zolines have been developed [8–15]. The main
approach towards their preparation is the reaction of
nitriles of with ethylenediamine monohydrochloride or
other salts at high temperature [8, 9] or under
microwave irradiation [10]. In addition, imidazolines
can be obtained starting from carboxylic acids esters or
amides [11, 12], aldehydes [13], imidates [14], and
other compounds [8, 15]. A significant limitation of
these methods is a requirement to use the carboxylic
acids derivatives rather than better available carboxylic
acids.
However, the methods of preparation of imida-
zolines from aliphatic carboxylic acids and ethylene-
diamine have been also reported. For example,
nitrogen-containing heterocyclic derivatives have been
When esters have been used instead of the acids at
the ester : ethylenediamine molar ratio of 1:3 and 100–
250°C, yield of imidazolines has reached 85%, the
reaction duration being of 12–20 h [18]. High reaction
1
For communication XII, see [1].
281

282
POPOV et al.
Scheme 1.
N
Cu0, benzene
RCOOH + H2NCH2CH2NH2
+ 2H2O
R
80oC
N
H
3а_3c
1а_1c
2
R = Me (a), i-Pr (b), i-Bu (c).
temperature, its long duration, and the multi-stage
character (the synthesis proceeds via initial mono-
amide formation followed by its cyclization to give 2-
alkyl-2-imidazoline) are among the disadvantages of
this method.
thesis. However, data on the synthesis of 2-alkyl-2-
imidazolines catalyzed by metal nanoparticles have
been absent.
The procedure for direct amidation of carboxylic
acids with amines and transamidation of carboxamides
under catalysis with copper nanoparticles has been
earlier described [22]. In this work we investigated the
possibility to apply this catalyst in condensation of
carboxylic acids with ethylenediamine as a novel
approach towards synthesis of imidazolines.
Over the recent years, significant efforts have been
concentrated on preparation of novel derivatives of 2-
imidazoline [19–21]. For example, the reaction of
ethylenediamine with carboxylic acids at 120–140°C
in toluene or in bulk has led to the formation of
amides; their heating under argon at 180–220°C has
resulted in the cyclization affording 2-alkylimidazo-
lines in 70–75% yield [19]. Moderate yield of the
target compounds can be explained by the formation of
1,2-disubstituted amides along with the mono-
substituted acid amides as a result of rapid reaction
between ethylenediamine and the acids; 1,2-disub-
stituted amides undergo cyclization at 180–220°C to
form 3-amidoalkylimidazolines.
We performed the synthesis of 2-alkyl-2-imida-
zolines via reaction of carboxylic acids with ethylene-
diamine in the presence of neutral colloidal copper
catalyst for the first time. Acetic acid 1a, 2-
methylpropionic acid 1b, and isovaleric acid 1c were
used as the starting materials. The reactions were
performed in benzene at 80°C using the acid and
ethelenediamine in the molar ratio of 1 : 1–1.2 in the
presence of copper nanoparticles, upon distilling off
water as azeotropic mixture with benzene. Yield of 2-
alkyl-2-imidazolines 3a–3c was of 70–88% (Scheme 1).
Another procedure for imidazolines preparation
utilizes cation exchange resin KU-2 as a catalyst; this
allows for the mild reaction conditions, but the yield of
the products was as low as 65–75% [20].
Gas chromatography–mass spectrometry analysis
data showed that two side products were also formed:
monoacylethylenediamines (8–15 wt %) and N,N′-
diacylethylenediamines (5–12 wt %). It was found that
addition of fresh portions of the catalyst to the reaction
mixture enhanced the water release, thus confirming
the catalytic action of colloidal copper.
2-Imidazolines can be also prepared from technical
grade stearin, soy-bean fatty acids, and flax oil as well
as bisimidazolines of the fatty acid dimers, via
condensation of the corresponding fatty acids with
diethylenetriamines [17], however the process requires
high-temperature heating.
The effect of carboxylic acid structure on the
reaction outcome was discovered: the linear acids
reacted with ethylenediamine faster than their
branched analogs. It should be noted that the reaction
of ethylenediamine with 1-adamantanecarboxylic acid
and 1-naphthylacetic acid did not proceed under the
studied conditions [22], that could be explained by the
steric effect hindering the interaction of the C=O bond
with surface of large copper nanoparticles (70 nm).
To sum up, the simplest (and, at the same time, the
least suitable) method for 2-imidazolines preparation is
heating of an organic acid and diamine in the presence
of acidic agent. To increase the process efficiency, the
attempts to use of orthophosphoric and hydrochloric
acids as catalysts have been made. The acid presence
blocks one of ethylenediamine amine groups, and the
yield of diamides has been decreased [21].
Nowadays, the application of the catalysts based on
nanoparticles or their colloidal solutions is of great
interest, enhancing the possibilities of organic syn-
Formation of imidazolines in the neutral medium at
relatively low temperature is interesting in view of
elucidation of the possible reaction mechanism.
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COLLOID AND NANOSIZED CATALYSTS IN ORGANIC SYNTHESIS: XIII.
283
Scheme 2.
R
O
M0
O M0
R
OH
OH
NHCH2CH2NH2
O M0
R
NH
OH
R
H2NCH2CH2NH2
−M0
OH
NH2
OH
M0
N
M0
O
NH
OH
R
−M0
−H2O
−H2O
R
NHCH2CH2NH2
NH
R
NH
Scheme 3.
N
Fe3O4, benzene
80oC
RCOOH + H2NCH2CH2NH2
1а, 1d_1g
R
+ 2H2O
CH2−
N
H
2
3а, 3d_3g
R = Me (1а, 3а), Pr (1d, 3d), i-Bu (1c, 3c),
(1e, 3e),
(1f, 3f).
O
Presumably, the mechanism of catalysis in imidazo-
lines synthesis is similar to that in the carboxylic acids
amidation [22] (Scheme 2).
catalyst from the reaction mixture and the possibility
of its recovery, owing to the ferromagnetic (or
paramagnetic) properties.
Fe3O4 nanoparticles were prepared via gel
precipitation in the course of ammonia solution
addition to the solution of a mixture of Fe2+ and Fe3+
salts. Aqueous colloid solution was used in the further
synthesis without isolation of the nanoparticles. When
mixing the catalyst with ethylenediamine, a stable
solution was formed, probably stabilized by the
diamine. Moreover, the use of diamine excess
prevented the undesired reaction of the catalyst
particles with carboxylic acids.
The catalytic effect of copper nanoparticles could
be explained by appearance of significant fraction of
metal atoms (M0) with lower coordination number at
the edges or apexes of the crystal, increasing the ability
of those sites to coordinate at polar groups of organic
molecules. Based on the reference data [23], it might
be supposed that the catalyst coordination occurred
through the oxygen of carbonyl fragment of the acid.
At the second step, the coordination of the carbonyl
oxygen with the nanoparticle surface occurred, accom-
panied by attack of the amino group of monoamide at
the carbonyl carbon atom followed by the ring closure.
Acetic, butyric, isovaleric, 2-furoic, and 1-naphthyl-
acetic acids were used as the starting materials
(Scheme 3).
It was supposed that enhancement of the nano-
catalyst acidic properties accelerated the reaction and
increased the yield of the target imidazolines. Of a
number of the opportunities, we selected nanosized
iron oxide Fe3O4 to be used as the catalyst; the
methods of its preparation have been described in Ref.
[24]. Our choice was based on the easy removal of the
It was found that the reaction catalyzed by the iron
oxide proceeded faster than that catalyzed by copper
nanoparticles. Moreover, even acids 1e and 1f (inert in
the latter case) participated in the reaction with
ethylenediamine catalyzed by the iron oxide. Water
was distilled off in the form of the azeotrope with
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284
POPOV et al.
benzene. The yield of imidazolines reached 70%. The
GC–MS data revealed the formation of mono- and
diacyl derivatives of ethylenediamine as side products
in the reaction.
40–43°C (mp 42°C [25]). Mass spectrum, m/e (Irel, %):
112.0 (33) [M]+, 97.0(80), 83.0 (58), 41.0 (100).
2-Isobutyl-2-imidazoline (3c) was prepared
similarly by procedure a from ethylenediamine (12 g,
0.2 mol) and isovaleric acid (20.4 g, 0.2 mol); the
reaction duration was 7 h. Yield 17.6 g (0.14 mol,
70%), bp 167–170°С (30 mmHg). Mass spectrum, m/e
(Irel, %): 128.0 (8.0) [М + 1], 127.0 (100) [М]+, 97.1
(64.0), 82.0 (12), 41.0 (25).
All the prepared compounds were isolated by
vacuum distillation. The structure of the obtained
imidazolines 3a–3f was confirmed by means of mass
spectrometry data. The spectral characteristics of the
compounds matched the reference data.
In summary, a suitable preparative method for the
synthesis of imidazolines in high yield under mild
conditions of catalysis with copper or iron oxides
nanoparticles was elaborated.
b. Similarly, by method b from ethylenediamine
(7.1 g, 0.12 mol) and isovaleric acid (8 g, 0.078 mol);
the reaction duration was 4 h. Yield 6.9 g (0.055 mol,
70%).
2-Propyl-2-imidazoline (3d) was prepared similarly
to method b from ethylenediamine (7.2 g, 0.12 mol)
and butyric acid (7 g, 0.08 mol); the reaction duration
was 4 h. Yield 6.2 g (0.056 mol, 70%), bp 145–150°С
(30 mmHg), mp 40–43°C (mp 42°C [25]). Mass
spectrum, m/e (Irel, %): 112.0 (33) [M]+, 97.0 (80), 83.0
(58), 41.0 (100).
EXPERIMENTAL
GC–MS analysis was performed using a Saturn
2100 T/GC3900 (EI, 70 eV) instrument. Copper nano-
particles were prepared by as described in [22].
Synthesis of Fe3O4 nanoparticles. A solution of
FeSO4·7H2O (7 g, 0.0583 mol) and FeCl3·6H2O (5 g,
0.0292 mol) in 40 mL of distilled water was stirred
during 60 min, and then aqueous 10% ammonia
solution was added to slightly basic pH. The obtained
colloidal solution was used as the catalyst without
isolation of the nanoparticles.
2-(2-Furyl)-2-imidazoline (3e) was prepared similarly
to method b from ethylenediamine (5.6 g, 0.094 mol)
and 2-furoic acid (7 g, 0.063 mol); the reaction
duration was 3 h. Yield 3.43 g (0.025 mol, 40%), bp
168–170°С (30 mmHg) (decomp.). Mass spectrum,
m/e (Irel, %): 136.9 (80.3) [М + 1], 135.0 (79.9) [М –
1], 107.0 (100), 79.0 (72), 52.0 (38).
2-Methyl-2-imidazoline (3a). a. A mixture of ethylene-
diamine (12 g, 0.2 mol), acetic acid (12 g, 0.2 mol),
15 mL of benzene, and 0.1 g of copper nanoparticles
was refluxed during 5 h with water distillation off
(7.2 mL, 0.4 mol). After the reaction was complete, the
solvent was distilled off, and the residue was distilled
in vacuum. Yield 12.6 g (0.15 mol, 74%), bp 110–114°С
(100 mmHg), mp 86–88°C {bp 144°C (140 mmHg),
mp 87°C [25]}. Mass spectrum, m/e (Irel, %): 85.0
(100) [M + 1], 83 (25), 55.0 (49), 42.0 (22).
2-(Naphthylmethyl)-2-imidazoline (3f) was prepared
similarly to method b from ethylenediamine (3.4 g,
0.057 mol) and 1-naphthylacetic acid (7 g, 0.038 mol);
the reaction duration was 4 h. Yield 2.4 g (0.0114 mol,
30%), bp 308–310°С (30 mmHg) (decomp.), mp 117–
119°С {bp 230°C (10 mmHg), mp 119°С [26]}. Mass
spectrum, m/e (Irel, %): 211.0 (8.0) [М + 1], 210.0 (35)
[М]+, 209.0 (100) [М – 1], 141.0 (22), 115.0 (15).
ACKNOWLEDGMENTS
b. A mixture of ethylenediamine (10.5 g, 0.18 mol),
acetic acid (7 g, 0.12 mol), 15 mL of benzene, and
1 mL of aqueous 50% suspension of nanosized iron
oxide Fe3O4 was refluxed during 3 h with water
distillation off (4.7 mL, 0.26 mol). After the reaction
was complete, the solvent was removed, and the
residue was distilled in vacuum. Yield 8.3 g (0.1 mol,
85%).
The work was financially supported by the Ministry
of Education and Science of the Russian Federation in
the frame of the basic part of the governmental
contract no. 2014/16 (project no. 2679) and the
Program of Strategic Development of Volgograd State
Technical University for 2010–2015.
REFERENCES
2-Isopropyl-2-imidazoline (3b) was prepared similarly
by procedure a from ethylenediamine (9.6 g, 0.16 mol)
and 2-methylbutanoic acid (13.2 g, 0.15 mol). Yield
14.8 g (0.132 mol, 88%), bp 150°С (30 mmHg), mp
1. Mokhov, V.M., Popov, Yu.V., and Shcherbakova, K.V.,
Russ. J. Gen. Chem., 2016, vol. 86, no. 2, p. 273. DOI:
10.1134/S1070363216020110.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 2 2016

COLLOID AND NANOSIZED CATALYSTS IN ORGANIC SYNTHESIS: XIII.
285
2. Frolov, V.I., Tr. Ros. Gos. Univ. Nefti i Gaza, 2009,
Henichart, J.-P., Heterocycles, 2006, vol. 68, p. 1149.
no. 2, p. 165.
DOI: 10.3987/COM-06-10708.
3. Kuznetsov, S.A., Belyaeva, N.A., and Kol’tsov, N.I.,
15. Liua, H., and Du, D.-M., Adv. Synth. Catal., 2009,
Khim. i Tekhnol. Topliv i Masel, 2009, no. 3, p. 48.
vol. 351, p. 489. DOI: 10.1002/adsc.200800797.
4. Peregudova, A.S., Kruzhilin, A.A., Perelygina, I.E.,
Falaleev, A.V., and Stolpovskaya, N.V., Sorbts.
Khromatograf. Protsessy, 2015, vol. 15, no. 3, p. 464.
5. Kuznetsov, S.A., and Kol’tsov, N.I., Russ. J. Appl.
Chem., 2010, vol. 83, no. 11, p. 1993. DOI: 10.1134/
S1070427210110194.
16. Riebsomer, J.L., J. Am. Chem. Soc., 1948, vol. 70, no. 4,
p. l629. DOI: 10.1021/ja01184a095.
17. Chebaksarov, A.I., Chebaksarova, L.V., and Pak, Kh.S.,
RF Patent 2487122, 2013.
18. Verolainen, N.V., Petrova, V.E., and Temnikova, S.A.,
Vestn. TvGU. Khimiya, 2014, vol. 8, no. 1, p. 36.
6. Khimicheskaya entsiklopediya (Chemical Encyclo-
pedia), Knunyants, I.L., Ed., Moscow: Sovetskaya
Entsiclopediya, 1990, vol. 2, p. 413.
19. Zagidullin, R.N., Rakhmankulov, D.L., Rysaev, U.Sh.,
Rysaev, D.U., Kozyreva, Yu.P., and Mazitova, I.Sh.,
Bash. Khim. Zh., 2007, vol. 14, no. 4, p. 21.
7. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Kharkov: Torsing, 1998.
8. Crouch, R.D., Tetrahedron, 2009, vol. 65, no. 12,
20. Isagulyants, V.I., Bova, R.S., and Belov, P.S., Author’s
Certificate no. 189437, 1967; Byull. Izobret., 1966,
no. 24.
p. 2387. DOI: 10.1016/j.tet.2008.12.022.
9. Ferm, R.J., and Riebsomer, J.L., Chem. Rev., 1954,
21. Baganz, Н., Domaschke, L., and Fock, J., Chem. Ber.,
1962, vol. 95, no. 7, p. 1832. DOI: 10.1002/
cber.19620950740.
vol. 54, p. 593. DOI: 10.1021/cr60170a002.
10. de la Hoz, A., Diaz-Ortiz, A., Mateo, M.d.C., Moral, M.,
Moreno, A., Elguero, J., Foces-Foces, C., Rodriguez, M.L.,
and Sanchez-Migallon, A., Tetrahedron, 2006, vol. 62,
no. 26, p. 5868. DOI: 10.1016/j.tet.2006.04.020.
22. Mokhov, V.M., Popov, Yu.V., and Budko, I.I., Russ. J.
Gen. Chem., 2015, vol. 85, no. 4, p. 820. DOI: 10.1134/
S1070363215040088.
23. Xie, Y.-X., Song, R.-J., Liu, Y., Liu, Y.-Y., Xiang, J.-N.,
Li, J.-H., Adv. Synth. Catal., 2013, vol. 355, p. 3387.
DOI: 10.1002/adsc.201300630.
11. Sperber, N., and Fricano, R., J. Am. Chem. Soc., 1953,
vol. 75, no. 12, p. 2986. DOI: 10.1021/ja01108a058.
12. Hill, A.J., and Aspinall, S.R., J. Am. Chem. Soc., 1939,
24. Mahdavi, M., Ahmad, M.B., Haron, M.J., Namvar, F.,
and Nadi, B., Molecules, 2013, vol. 18, p. 7533. DOI:
10.3390/molecules 18077533.
vol. 61, no. 4, p. 822. DOI: 10.1021/ja01873a015.
13. Fujioka, H., Murai, K., Ohba, Y., Hiramatsu, A., and
Kita, Y., Tetrahedron Lett., 2005, vol. 46, no. 13,
p. 2197. DOI: 10.1016/j.tetlet.2005.02.025.
25. Alfa Aesar, Research Chemicals, Metals and Materials,
2006–2007.
14. Lauwagie, S., Millet, R., Pommery, J., Depreux, P., and
26. Carlsson, S., US Patent 2441867, 1948.
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