Synthesis of Long Chain 2-Alkyl-1-(2-hydroxyethyl)-2-imidazolines under Microwave in Solvent-Free Conditions

Article abstract of DOI:10.1055/s-2003-41410

An efficient method for the synthesis of long chain 2-alkyl-1-(2-hydroxyethyl)-2-imidazolines, and their amide precursors, by condensing aminoethylethanolamine and several fatty acids under non-solvent microwave irradiation using CaO as support, is described. Products were obtained in good yields and high purity in a few minutes, in both multimode microwave and monomode microwave oven. Evidences of non-thermal microwave effects are given.

Full text of DOI:10.1055/s-2003-41410

LETTER
1847
Synthesis of Long Chain 2-Alkyl-1-(2-hydroxyethyl)-2-imidazolines under
Microwave in Solvent-Free Conditions
S
ynthesisof Lon
a
f
lkyl-1-(
a
2-hydroxye
e
thyl)-2-imi
l
dazolines Martínez-Palou,*a Gerardo de Paz,a Jesús Marín-Cruz,a Luis Gerardo Zepedab
a
Competencia de Química Aplicada. Programa de Ingeniería Molecular, Instituto Mexicano del Petróleo, Eje Central Lázaro Cárdenas
No. 152, San Bartolo Atepehuacan, 07730 México
Fax +525(3003)6239; E-mail: rpalou@imp.mx
b
Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. de Carpio y Plan de
Ayala, 11340 México
Received 24 July 2003
O
H
N
Abstract: An efficient method for the synthesis of long chain 2-
alkyl-1-(2-hydroxyethyl)-2-imidazolines, and their amide precur-
sors, by condensing aminoethylethanolamine and several fatty acids
under non-solvent microwave irradiation using CaO as support, is
described. Products were obtained in good yields and high purity in
a few minutes, in both multimode microwave and monomode
microwave oven. Evidences of non-thermal microwave effects are
given.
+
R
HO
NH2
- H2O
OH
4a, stearic acid
4b, palmitic acid
4c, myristic acid
4d, lauric acid
3
R
O
H
N
N
N
OH
Key words: microwave, solid-phase synthesis, cyclizations, imida-
zolines, amides
HO
N
R
- H2O
H
1a-1d
2a-2d
Scheme 1
Long chain 2-alkyl-1-(2-hydroxyethyl)-2-imidazolines
(1) and their amides precursors (2) are well known com-
pounds due to their industrial applications,1 particularly
are successfully as corrosion inhibitors in oilfield
applications.2 The general procedure to synthesize these
compounds involves dehydration between aminoethyl-
ethanolamine (3) and the fatty acids (i.e., tall-oil) at high
temperatures, under vacuum conditions in the cyclo-
dehydration step, and long reaction times (Scheme 1).3
During the last decade, several publications, reviews4 and
books5 have advocated the use of microwaves irradiation
in organic synthesis due to the generally short reaction
times, high yields and purity of the resulting products.
Specially dry reactions coupled with microwave have
received considerable interest,6 as a way of minimizing
safety problems.7 Recently the preparation of 1,3-azoles
under microwave in solvent-free conditions have been
described.8
Spectroscopic data (1H and C NMR, and IR) were also
13
compared.11
The reactions were performed within a short time, result-
ing products were obtained with high purity (>95%) and
yield greater than those obtained with other classical
procedures described in the literature.3
A comparison between thermal heating (TH), using a
thermostated oil bath, and MMW procedure for entry 2
(Table 1), with similar profile of raises in temperature and
reaction time is shown in Figure 1.12 An analysis by NMR
for the reaction mixture after 7.5 minutes of TH shows
that only the amine salt was formed. Then the reaction
mixture was heated 7.5 minutes more at 150 °C, at this
point only traces of the amide 2a were detected. These
results are evidence of the presence of non-thermal effects
during dielectric heating.4g
In this paper we report the efficient preparation of long
chain 2-alkyl-1-(2-hydroxyethyl)-2-imidazolines (1a–d),
and their amides precursors (2a–d), through the conden-
sation of aminoethylethanolamine (3) and several fatty ac-
ids (4a–d) in solvent-free conditions using CaO as
support; in both, domestic microwave (DMW) and mono-
mode microwave (MMW) ovens9 (Table 1).10
Reactions were monitored by GC-MS and compared with
the compounds obtained by traditional methods.
SYNLETT 2003, No. 12, pp 1847–1849
2
9
.0
9
.2
0
0
3
Advanced online publication: 28.08.2003
Figure 1 Temperature profile for the condensation of stearic acid
DOI: 10.1055/s-2003-41410; Art ID: S04103st.pdf
© Georg Thieme Verlag Stuttgart · New York
(4a) and 3 under TH and in MMW

1848
R. Martínez-Palou et al.
LETTER
Table 1 Amides 2a–d and Imidazolines 1a–d Synthesis under Microwave Conditionsa
Entry Fatty
DMW
MMW
CPe
Product
Acid
(R)
RTb
(min)
FTc
(°C)
Power
(W)
Yieldd
(%)
RTb
(min)
FTc
(°C)
Power
(W)
Yieldd
(%)
RTb
(h)
Yieldd
(%)
1
2
3
4
5
6
7
8
4a
(C17H35)
4.0
9.0
4.0
8.0
4.0
8.0
3.5
7.0
140
181
137
178
135
182
132
180
800
800
800
800
800
800
800
800
92
93
91
91
93
92
90
92
3.5
7.5
3.5
7.5
3.5
7.5
3.0
7.0
120
150
120
150
120
150
120
150
600
600
600
600
600
600
600
600
90
92
93
92
91
93
90
92
3.0
8.0
3.0
8.0
3.0
8.0
3.0
8.0
88
85
90
86
89
87
86
85
2a
1a
2b
1b
2c
1c
2d
1d
4a
(C17H35)
4b
(C15H31)
4b
(C15H31)
4c
(C13H27)
4c
(C13H27)
4d
(C11H23)
4d
(C11H23)
a All the reactions were performed with 5.0 mmol of 3 and 5.0 mmol of 4a–d.
b RT: reaction time.
c FT: final temperature.
d For isolated products.
e CP: classical procedure described in ref.3a
In summary, microwave irradiation in solvent-free
conditions provides an excellent methodology for the syn-
thesis of 2-alkyl-1-(2-hydroxyethyl)-2-imidazolines and
their amides precursors in only a few minutes and very
good yields. The procedure avoids the employment of re-
duced pressures and is carried out in an open vessel.
S.; Kobesheva, N. I.; Babynina, V. S.; Kataeva, V. A. Zh.
Prik. Khim. 1987, 60, 2732; Chem. Abstr. 1988, 109,
128898.
(4) (a) Strauss, C. R.; Trainor, R. W. Aust. J. Chem. 1995, 48,
1665. (b) Caddick, S. Tetrahedron 1995, 51, 10403.
(c) Galema, S. Chem. Soc. Rev. 1997, 26, 233. (d) Strauss,
C. R. Aust. J. Chem. 1999, 52, 86. (e) Romanova, N. N.;
Kudan, P. V.; Gravis, A. G.; Bundel Yu, G. Chem.
Heterocycl. Compd. 2000, 36, 1130. (f) Lidström, P.;
Tierney, J.; Wathey, B.; Westman, J. Tetrahedron 2001, 57,
9225. (g) Perreux, L.; Loupy, A. Tetrahedron 2001, 57,
9199.
The results show non-thermal effects involved in the reac-
tion rate increase for this procedure.
Acknowledgment
(5) (a) Hayes, B. L. Microwave Synthesis: Chemistry at the
Speed of Light; CEM Publishing: Matthews NC, 2002.
(b) Loupy, A. Microwave in Organic Synthesis; Wiley-
VCH: New York, 2002.
Authors wish to thank Instituto Mexicano del Petróleo for its finan-
cial support (Proyect D00328).
(6) (a) Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.;
Jacquault, P.; Mathé, D. Synthesis 1998, 1233. (b) Varma,
R. S. Green Chem. 1999, 43. (c) Varma, R. S. Pure Appl.
Chem. 2001, 73, 193.
References
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(e) McCullough, T. M. U.S. Pat. 5062992, 1991; Chem.
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(7) For microwave safety consideration see ref.5a, p. 175-179.
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659. (d) Brain, C.; Paul, J. M. Synlett 1999, 1642.
(e) Kerneur, G.; Lerestif, J. M.; Bazureau, J. P.; Hamelin, J.
Synthesis 1997, 287. (f) Marrero-Terrero, A. L.; Loupy, A.
Synlett 1996, 245. (g) Usyatinsky, A. Y.; Khmelnitsky, Y.
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Synlett 2003, No. 12, 1847–1849 © Thieme Stuttgart · New York

LETTER
Synthesis of Long Chain 2-Alkyl-1-(2-hydroxyethyl)-2-imidazolines
1849
(9) Microwave irradiations was carried out with a DMW
(Panasonic NM-5460A, 800 W, 2450 MHz) and a MMW
(MIC-I, 600 W, from SEV, México). For the reactions using
a DMW the final temperatures were measured directly,
immediately at the end of the reaction, with a contact
thermometer embedded in the reaction mixture. For a
comparison multimode vs monomode microwave oven see
ref.4b and ref.6a
(10) Typical Experimental Procedure: In an open Pyrex vessel
(100 mL, for DMW) or sealed tube (100 mL, for MMW)
were carefully mixed 0.52 g (5.0 mmol) of aminoethyl-
ethanolamine (3), 5.0 mmol of the corresponding fatty acid
(4a–d) and 2.5 g of CaO. The resulting mixture was
irradiated using the power and the reaction time showed in
Table 1. The reaction mixture was allowed to reach room
temperature, EtOAc (20 mL) was added and the mixture was
heated until boiling and filtered off while hot, and the
filtrated was concentrated under vacuum to dryness, yielding
the corresponding product as a white solid.
NMR (200 MHz, CDCl3): d = 0.86 (t, J = 6.0 Hz, 3 H), 1.23
(sa, 28 H), 1.45–1.63 (m, 2 H), 2.19 (t, J = 7.9 Hz, 2 H),
2.72–2.92 (m, 4 H), 3.39 (q, J = 6.0 Hz, 2 H), 3.70 (t, J = 5.0
Hz, 2 H), 4.10 (sa, 1 H). 13C NMR (50 MHz, CDCl3): d =
14.3, 22.8, 26.0, 29.4, 29.6, 29.7, 32.0, 36.8, 38.9, 48.6, 51.1,
60.4, 173.5.
2-Heptadecyl-1-(2-hydroxyethyl)-2-imidazoline (1a):
Recrystallization from EtOAc. Mp 62–63 °C (lit3a 63–65
°C). IR (KBr): 3310, 2917, 2849, 1602 cm–1 1H NMR (200
MHz, CDCl3): d = 0.86 (t, J = 6.0 Hz, 3 H), 1.23 (sa, 28 H),
1.45–1.65 (m, 2 H), 2.22 (t, J = 5.8 Hz, 2 H), 3.22 (t, J = 5.4
Hz, 2 H), 3.29–3.39 (m, 2 H), 3.61–3.71 (m, 4 H), 3.76 (sa,
1 H). 13C NMR (50 MHz, CDCl3): d = 14.3, 22.8, 26.6, 28.0,
29.5, 29.68, 29.72, 29.8, 49.4, 50.2, 51.6, 59.8, 168.0.
(12) The thermal heating reaction protocol was as in the case of
microwave methodology except that the glass tube
containing the reagents and a magnetic stirring bar, was
placed into a preheated oil bath at 150 ºC. The temperature
of each was measured for 5 s using a thermometer embedded
in the reaction mixture. The work-up procedure was as with
the microwave methodology.
(11) [2-(2-Hydroxyethylamino)ethyl]heptadecylamide (2a):
Recrystallization from EtOAc. Mp 102–103 °C (lit3a 103–
105 °C). IR (KBr): 3300–3270, 2920, 2850, 1641 cm–1. 1H
Synlett 2003, No. 12, 1847–1849 © Thieme Stuttgart · New York