Multivalent metal salts as versatile catalysts for the amidation of long-chain aliphatic acids with aliphatic amines

Article abstract of DOI:10.1055/s-2008-1067168

Multivalent metal salts, such as ferric chloride and sulfate, are active and versatile catalysts for the amidation of aliphatic fatty acids with long-chain aliphatic amines. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067168

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SHORT PAPER
Multivalent Metal Salts as Versatile Catalysts for the Amidation of
Long-Chain Aliphatic Acids with Aliphatic Amines
A
midationof Long
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cidswith
Ali
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mines erada, Noboru Ieda, Kenichi Komura, Yoshihiro Sugi*
Department of Materials Science and Technology, Faculty of Engineering, Gifu University, Gifu 501-1193, Japan
Fax +81(58)2932597; E-mail: ysugi@gifu-u.ac.jp
Received 18 February 2008; revised 22 April 2008
Figure 1 shows the performance of a range of metal chlor-
ide catalysts in the amidation of palmitic acid with decyl-
amine in refluxing mesitylene. The yield of palmitic acid
in the absence of catalyst was approximately 20% after 6
and 24 hours. All the multivalent metal salts examined
were active for the amidation, with the catalytic activity
over 6 hours decreasing in the order: FeCl3·6H2O > ZnCl2
Abstract: Multivalent metal salts, such as ferric chloride and sul-
fate, are active and versatile catalysts for the amidation of aliphatic
fatty acids with long-chain aliphatic amines.
Key words: multivalent metal salts, FeCl3·6H2O, amidation, long-
chain aliphatic acid, aliphatic amine
>
NiCl2·6H2O ≈ MnCl3·6H2O > CoCl2·6H2O >
N-Alkyl fatty acid amides, such as N-decylhexadecana-
mide, are important chemical substances for photographic
materials, polyolefin foaming materials, polymer stabiliz-
ers, photocurable developers and pigments.1 N-alkyl-
carboamides have been prepared by many classical
methods,2–5 such as the reaction of carboxylic acid esters
with amines, acid chlorides or anhydrides with amines,
and the direct reactions of acids with amines. In most of
the methods, a large excess of either the carboxylic acid or
the amine is essential in order to achieve high yields of
amides, and tedious work-up procedures are required to
obtain the reaction products. Since it is not practical to use
large amounts of condensing reagents in larger scale pro-
ductions, there is a need to develop new methods for en-
vironmentally friendly amidation processes.
CrCl3·6H2O > ZrOCl2·8H2O > CuCl2·4H2O > InCl3 >
AlCl3·6H2O >> none. FeCl3·6H2O was thus found to be
the most active among the multivalent metal chlorides.
Recently, Ishihara and Yamamoto have developed new
catalysts, such as N-alkyl-4-(borono)pyridinium salts,
3,5-bis(perfluorodecyl)phenylboronic acid, and 4,5,6,7-
tetrachlorobenzo[d][1,3,2]dioxaborol-2-ol, for the prepa-
ration of amides from equimolar mixtures of carboxylic
acids and amines.6,7 Some of these catalysts are highly ac-
tive and recyclable in fluorinated solvent.7 Catalysts de-
rived from boric acid, arylboronic acid and borane have
also been developed for the amidation of N-substituted
carboamides.8
We previously described the use of some highly catalyti-
cally active multivalent metal salts, such as zirconyl and
ferric salts, for the esterification of long-chain fatty acids
with long-chain aliphatic alcohols.8 Here, we describe
their application to the amidation of long-chain fatty acids
with long-chain aliphatic amines, and propose that a num-
ber of them, particularly ferric salts, are highly active and
versatile catalysts for amidation even when equimolar
amounts of acid and amine are present.
Figure 1 The amidation of palmitic acid with decylamine catalyzed
by multivalent metal chlorides. Reaction conditions: metal salt (0.12
mmol), palmitic acid (6.0 mmol), decylamine (6.0 mmol), mesitylene
(40 mL), reflux.
Table 1 summarizes the influence of a range of aromatic
hydrocarbon solvents on the amidation of palmitic acid
with decylamine catalyzed by FeCl3·6H2O under reflux.
The conversions of palmitic acid were less than 20% even
in mesitylene under reflux. The catalytic activity was
found to be dependent on the solvent: the reaction was en-
hanced with increasing reaction temperature in the order:
benzene << toluene < m-xylene << mesitylene.
SYNTHESIS 2008, No. 15, pp 2318–2320
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Advanced online publication: 08.07.2008
DOI: 10.1055/s-2008-1067168; Art ID: F04008SS
© Georg Thieme Verlag Stuttgart · New York

SHORT PAPER
Amidation of Long-Chain Aliphatic Acids with Aliphatic Amines
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Table 1 Influence of Solvent on the Amidation of Palmitic Acid
Table 3 Influence of Chain Length of Acid and Amine in the Ami-
dation Catalyzed by FeCl3·6H2Oa
with Decylamine Catalyzed by FeCl3·6H2Oa
Yield (%)
Acid
Amine
Yield (%)
No catalyst
6 h 24 h
0.0
0.7
18
23
FeCl3·6H2O
6 h 24 h
7.0
Palmitic acid
Palmitic acid
Palmitic acid
Palmitic acid
Palmitic acid
Palmitic acid
Octanoic acid
Decanoic acid
Dodecanoic acid
Myristic acid
Palmitic acid
Stearic acid
Octylamine
84
81
81
77
62
47
93
92
90
92
81
71
Solvent
Bp (°C)
80
Decylamine
Dodecylamine
Tetradecylamine
Hexadecylamine
Octadecylamine
Decylamine
Decylamine
Decylamine
Decylamine
Decylamine
Decylamine
Benzene
Toluene
0.5
3.2
24
78
90
94
110
48
60
81
m-Xylene
Mesitylene
140
20
24
160
a Reaction conditions: metal salt (0.12 mmol), palmitic acid (6.0
mmol), decylamine (6.0 mmol), solvent (40 mL), 6 h, reflux.
Table 2 summarizes the influence of metal salts on the
amidation of palmitic acid with decylamine. Metal sul-
fates, nitrates and acetates were active for the reaction as
well as chlorides, although the yields of the amides varied
with the salt used. These results show that the active cen-
ter for the amidation is on the metal cation and that the an-
ionic part did not significantly influence the catalysis.
a Reaction conditions: FeCl3·6H2O (0.12 mmol), acid (6.0 mmol),
amine (6.0 mmol), mesitylene (40 mL), 6 h, reflux.
Table 2 Influence of Metal Salts in the Amidation of Palmitic Acid
with Decylaminea
When the amidation was conducted in an autoclave at
160 °C under autogeneous pressure without removing wa-
ter, the yield of N-decylhexadecanamide from palmitic
acid and decylamine (63%) was slightly lower than that
observed using above method under atmospheric pressure
(81%). This means that the amidation occurs smoothly in
the presence of the small amounts of water formed by the
reaction. The addition of 3 Å molecular sieves enhanced
the amidation by removing water formed by the reaction
(yields were improved from 63% to 75%). Thus, the ami-
dation of palmitic acid with hexylamine and butylamine in
the presence of molecular sieves gave yields of 86% and
81%, respectively, at 160 °C after 6 hours under autoge-
neous pressure.
Yield (%)
2–
–
Metal salt
Fe3+
Cl–
81
27
37
51
65
75
76
SO4
77
42
51
62
52
75
73
NO3
68
33
52
67
62
72
55
AcO–
80
40
–
Al3+
In3+
ZrO2+
Co2+
79
71
50
79
Ni2+
Zn2+
a Reaction conditions: metal salt (0.12 mmol), palmitic acid (6.0
mmol), decylamine (6.0 mmol), mesitylene (40 mL), 6 h, reflux.
The presence of carboxyl groups is essential for the ami-
dation because the reaction did not occur between methyl
palmitate and decylamine. These results indicate that co-
operation between the carboxylic groups and the multiva-
lent salt is related to the extent of the amidation.
The influence of chain lengths of the acid and amine are
summarized in Table 3. The increase in chain length en-
hances the yield of the corresponding amide. Hexadecan-
amides from C8, C10, C12 and C14 amines were formed
in about 80% yield, however, those from C16 and C18
amines were obtained in lower yields. On the other hand,
decanamides from C8, C10 and C12 acids were obtained
in high yields of over 90%, whereas the yields obtained
from C16 and C18 acids were around 70–80%. These re-
sults indicate that FeCl3·6H2O is a versatile catalyst for the
amidation of long-chain aliphatic acids and amines.
The reaction mixture was yellow colored after the reaction
when FeCl3·6H2O was used as catalyst. This suggests that
the catalyst species are dispersed and stabilized as cationic
clusters or their agglomerated colloides formed by the hy-
drolysis of FeCl3·6H2O, although Tyndall phenomena
were not observed.10 Further investigation is necessary in
order to clarify the role of the catalytically active species
and the mechanism of the amidation.
In summary, multivalent metal halides, typically
FeCl3·6H2O, are versatile catalysts for the amidation of
long-chain aliphatic acids and amides under mild condi-
tions. Further aspects of the amidation catalyzed by mul-
The reactions were carried out under reflux using a Dean–
Stark trap to remove water as azeotropic mixtures. It is
thus difficult to apply this method to lower molecular
weight acids and amines due to their lower boiling points.
Synthesis 2008, No. 15, 2318–2320 © Thieme Stuttgart · New York

2320
Y. Terada et al.
SHORT PAPER
IR (KBr): 3315, 1637 cm–1.
tivalent metal salt hydrates will be discussed in the near
future.
1H NMR (500 MHz, CDCl3): d = 0.9 (6 H, br t), 1.3 (42 H, br t),
1.5–1.6 (4 H, m), 2.1 (2 H, t, J = 7.5, 8.3 Hz), 3.2 (2 H, dd, J = 6.9
Hz), 5.4 (1 H, br s).
13C NMR (125 MHz, CDCl3): d = 14.2, 22.7, 22.8, 26.0, 27.0, 29.3,
29.3, 29.4, 29.5, 29.5, 29.6, 29.7, 29.8, 29.9, 31.9, 32.0, 37.1, 39.6,
173.1.
Metal salts and all acids and amines used in this study were obtained
commercially and used without further purification. The product
yields were analyzed by gas chromatography using a Shimadzu Gas
Chromatograph 14A, Ultra-1 (25 m × 0.3 mm; 0.33 mm thick layer)
1
capillary column equipped with an FID. H and 13C NMR spectra
Anal. Calcd for C24H49NO: C, 79.36; H, 13.56; N, 3.31. Found: C,
79.36; H, 13.6; N, 3.31.
were recorded at 500 and 125 MHz, respectively, on a JEOL ECA-
500 NMR spectrometer. IR spectra were recorded on a Nexus 470
(Thermo Nicolet) FT-IR spectrometer using KBr discs. Elemental
analyses of all amides were performed at the Center for Organic
Elemental Microanalysis, Kyoto University.
Acknowledgment
Part of this work was financially supported by a Grant-in-Aid for
Scientific Research (B) 19310060, the Japan Society for the Promo-
tion of Science (JSPS).
Amidation of Long-Chain Carboxylic Acids with Amines; Gen-
eral Procedure
The amidation was carried out in a single-neck, round-bottom flask
(100 mL) equipped with a Teflon-coated magnetic stirring bar and
a Dean–Stark apparatus. Equimolar amounts of the substrates (long-
chain primary acid and amine; 6 mmol each) and FeCl3·6H2O (0.12
mmol) in solvent (benzene, toluene, m-xylene, mesitylene; 40 mL)
were charged into the flask and the mixture was heated to reflux
temperature with continuous removal of H2O generated from the re-
action. After 6 h or 24 h, the resulting reaction mixture was cooled
to r.t. and an aliquot of the reaction mixture was subjected to analy-
sis by GC in order to determine the conversion and product yield
(biphenyl as a standard). The solvent was removed in vacuo from
the reaction mixture and the amide product was extracted with
CHCl3. The amides were purified by column chromatography using
silica gel (0.063–0.2 mm; CHCl3–EtOAc, 10:1) to give the pure
product.
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N-Octylhexadecanamide
Mp 78–79 °C.
IR (KBr): 3318, 1637 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.9 (6 H, br t), 1.2 (34 H, br t),
1.5–1.6 (4 H, m), 2.1 (2 H, t, J = 7.4 Hz), 3.2 (2 H, dd, J = 6.9, 7.5
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29.6, 29.6, 29.7, 29.7, 29.8, 174.7.
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1.5–1.6 (4 H, m), 2.2 (2 H, t, J = 7.6 Hz), 3.2 (2 H, dd, J = 7.5, 7.6
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29.6, 29.6, 29.7, 29.7, 29.8, 32.0, 32.0, 37.1, 40.0, 173.1.
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Synthesis 2008, No. 15, 2318–2320 © Thieme Stuttgart · New York