2
WANG ET AL.
methods have been developed, Gernigon et al have designed
and synthesized a series of ortho-iodo arylboronic acids from
the perspective of electronic effect and steric effect, and
5-methoxy-2-iodophenylboronic acid was demonstrated to
be the optimal catalyst. At room temperature, aryl carboxylic
acid, heterocyclic carboxylic acid and aliphatic carboxylic
acid coupled with secondary amines in a yield of 30-99%
after 2-48 h. Palmitic acid reacted with secondary amines
for 6 h at room temperature, and the yield of which was
95%.11 Tam et al have very recently found 2-furanylboronic
acid was excellent catalyst, which was easily accessible and
inexpensive compared with 5-methoxy-2-iodophenylboronic
acid. It was efficient for the direct amidation of aliphatic
carboxylic acids and aliphatic primary and secondary amines
at ambient temperature with the yield of 45-99% after
24 h.12 A synthetic boric acid derivative catalyst named
(2-(thiophen-2-ylmethyl)phenyl)boronic acid has been devel-
oped by Mohy El Dine et al, the catalyst was efficient for
aliphatic, aromatic, and heterocyclic carboxylic acids as well
as primary, secondary, aliphatic, and heterocyclic amine at
room temperature and a yield of 99% was achieved after
2-48 h.13 Other arylboronic acid compounds and their deriva-
tives such as 2-furanylboronic acid or borate esters were also
developed as a catalyst for the direct amidation in recent
years.12,14,15
2
EXPERIMENTAL
2.1 Materials
Oleic acid, AlCl3 (99%; Aladdin, Shanghai, China); ben-
zene, hydrochloric acid, ethylbenzene, toluene, sodium
hydroxide, ammonium chloride, ferric chloride, calcium
oxide, zinc oxide, boric acid, ethyl acetate, palmitic acid,
stearic acid, oleic acid, linoleic acid, linolenic acid, rici-
noleic acid (AR, Shanghai Lingfeng Chemical Reagent Co.,
Ltd, Shanghai, China); N,N-dimethyl-1,3-propanediamine
(99%, GC, Sigma, Shanghai, China), zirconium (IV) chlo-
ride, titanium tetrachloride, 3,4,5-trifluorophenylboronic acid
(98%; Macklin, Shanghai, China) were used without further
purification.
2.2 Synthesis of phenyl octadecanoic acid
Oleic acid (20.0 mL, 17.19 g) and benzene (100 mL) were
added to a 250 mL single-necked, round-bottomed flask, and
then AlCl3 (8.12 g) was slowly added to the mixture under
stirring. The flask was placed in an oil bath with the tem-
◦
perature set to 65 C and stirred for 5 h, it was allowed to
cool to the room temperature. To the above mixture 100 mL
dilute hydrochloric acid (1 mol/L) was added, the mixture
was stirred vigorously with a mechanical stirrer, and then
it was allowed to stand for a period of time and separate
into two layers. After the organic layer was washed with
deionized water, the benzene was removed by evaporating
under reduced pressure, and the light-yellow product was
obtained.
In addition to the above arylboronic acid-based catalysts,
it has been reported that transition metal complexes were
efficient as catalysts for the amidation reaction. Early in
1970, Wilson and Weingarten have reported the addition of
TiCl4 improved the yield of the formation of carboxamides
in THF. At room temperature, N-alkyl or N,N-dialkyl car-
boxamides were synthesized with the yield of 31-82% after
8 h-7 days, but it was confirmed aromatic amines were hard
to react with hindered acids.16 Lundberg and coworkers have
found several group IV metal complexes were active catalysts.
Titanium (IV) isopropoxide, zirconium complexes (ZrCl4 or
Cp2ZrCl2), and a hafnium complex [Hf(Cp)2Cl2] were all
developed to improve the yields of a range of amides under
mild conditions.17–19
2.3 Determination of the optimal catalyst for
the direct amidation of long-chain fatty acids
The synthesis of amides: To a 100 mL single-necked
round-bottomed flask, the phenyl octadecanoic acid (POA)
(5.0 mmol), 3,4,5-trifluorophenylboronic (0.50 mmol) or
other catalysts, toluene (25.0 mL) were added and then N,N-
dimethyl-1,3-propanediamine (DMPDA) (7.5 mmol) was
added at last. The reaction mixture was heated in an oil bath
Other types of catalysts including metal oxides (ZnO,
24
CeO2),20,21 silica gel,22 SBA-15,23 and FeCl3 were also
◦
reported in favor of amide formation in recent years.
Despite of availability of many reports regarding the
catalysts for the direct amidation, relatively few reports
mentioned about the catalysts for the direct amidation of
long-chain carboxylic acids. Since the long-chain fatty acid
amides are of great value and developing a simple opera-
tion and environmental-friendly synthetic method is may face
chanllenges.25,26
at 70-120 C with continuous stirring and refluxing for 4-12 h.
The product was obtained after the solvent was removed under
reduced pressure. POA was instead by palmitic acid, stearic
acid, oleic acid, linoleic acid, linolenic acid, or ricinoleic acid
to react with DMPDA in the above condition.
Detection of amides: To a glass test tube, 20.0 mg of
the above product and 1.00 mL of a methanol solution of
sulfuric acid (the volume fraction is 10%) were added, then
◦
The aim of this research is focused on the direct synthesis
of amides from various long-chain acids with an amine and
its kinetics.
the reaction proceeded in a water bath at 60 C for 1 h. After
cooled to the room temperature, the mixture was adjusted to
be alkaline by adding 4.0 mL 1.0 mol/L NaOH (aq). Then it