Synthesis of quinolines by iron-catalyzed reaction of anilines with propane-1,3-diol

Article abstract of DOI:10.1134/S1070363215120105

Quinoline and its derivatives were synthesized by cyclocondensation of anilines with propane-1,3-diol in 57-96% yield in the presence of iron-containing catalysts in carbon tetrachloride.

Full text of DOI:10.1134/S1070363215120105

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 12, pp. 2725–2727. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © R.I. Khusnutdinov, A.R. Bayguzina, R.I. Aminov, 2015, published in Zhurnal Obshchei Khimii, 2015, Vol. 85, No. 12, pp. 1993–
1995.
Synthesis of Quinolines by Iron-Catalyzed Reaction
of Anilines with Propane-1,3-diol
R. I. Khusnutdinov, A. R. Bayguzina, and R. I. Aminov
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Russia
e-mail: khusnutdinovri47@gmail.com
Received June 18, 2015
Abstract—Quinoline and its derivatives were synthesized by cyclocondensation of anilines with propane-1,3-
diol in 57–96% yield in the presence of iron-containing catalysts in carbon tetrachloride.
Keywords: N-heterocyclization, aniline, propane-1,3-diol, carbon tetrachloride, quinolines
DOI: 10.1134/S1070363215120105
Quinoline and its derivatives are the most important
class of fused azaheterocycles widely used for the syn-
thesis of highly effective anti-malarial, anti-tuber-
culosis, anti-rheumatic, anesthetic, and anti-bacterial
drugs, as well as corrosion inhibitors, cyanine dyes,
extractants, and sorbents. Known methods of the quino-
lines synthesis are based on cyclocondensation of
anilines with oxygen-containing compounds like
glycerol, α,β-unsaturated aldehydes, β-diketones, and
β-ketoesters under the action of mineral acids [1–4].
tions the use of a hydrogen acceptor is not required;
the aromatization proceeds due to dehydrogenation
under the action of ruthenium catalyst. In spite of high
yields of quinolines, the main disadvantage of this
method is the use of expensive ruthenium catalysts.
In this work we developed a procedure for the
synthesis of quinolines based on the reaction of anilines
ХC6H4NH2 (X = H, o-CH3, m-CH3, p-CH3, o-C2H5,
o-Cl, m-Cl, p-Cl, p-OCH3, o-OH) with 1,3-propanediol
under the action of iron catalysts FeCl3·6H2O, FeCl3,
FeCl2·4H2O, Fe(C5H5)2, Fe(acac)3, Fe(OAc)2, Fe2(CO)9,
the best of which was FeCl3·6H2O.
Catalysis has opened new opportunities for the
preparation of quinolines in the absence of acids and
expanded significantly the range of C3-substrates used
to construct the quinoline ring applying aniline and its
derivatives.
The reaction of aniline 1a with propane-1,3-diol
afforded quinoline 2a. The reaction took place at 150°C
in CCl4 for 8 h at a molar ratio of FeCl3·6H2O : aniline :
CCl4 : 1,3-propanediol = 1 : 100 : 200 : 400. Substituted
anilines 1b–1j also reacted with 1,3-propanediol to
afford the corresponding quinoline derivatives 2b–2l in
57–96% yields. The yield of the target compounds did
not exceed 40–63% when using other iron catalysts
(Scheme 1).
Ruthenium compounds and complexes activated
with organophosphorus ligands are effective metal
complex catalysts for the synthesis of quinolines via
cyclocondensation of anilines with propane-1,3-diol
[5, 6]. Best results have been obtained when using
RuCl3·nH2O–PBu3 and RuCl3·nH2O–PEt3 catalyst sys-
tems while refluxing the reaction mixture in diglyme
for 5 h. It is interesting to note that under these condi-
According to the experimental data, the reactions
did not occur in the absence of CCl4. To clarify the
Scheme 1.
HO
HO
FeCl3 6H2O
+
X
X
CCl4, 150oС, 8 h
NH2
1а−1j
N
2а−2l
Х = H, o-CH3, m-CH3, p-CH3, o-C2H5, o-Cl, m-Cl, p-Cl, p-OCH3, o-OH.
2725

2726
KHUSNUTDINOV et al.
Scheme 2.
[Fe] − CCl4
− CHCl3
HO
HO
HO
HO
OH
O
OCl
O
− H2O
− HCl
5
3
4
Scheme 3.
data, concentration of HCl was 79 mg/mL. Taking into
account the known literature data [7–9], it was possible
to assume that the process began with the oxidation of
1,3-propanediol by CCl4 with sequential formation of
3-hydroxypropyl-1-hypochlorite 3 and 3-hydroxy-
propanal 4, which at dehydration gave acrolein 5
(Scheme 2).
O
O
− H2O
[Fe], PhNH2
[Fe], PhNH2
− H2O
− H2O
− H2O
In the next step 3-hydroxypropanal 4 and acrolein 5
react with aniline 1a to give the corresponding
intermediates A, B, and C that undergo heterocycliza-
tion, dehydration, and dehydrogenation to afford
quinoline 2a (Scheme 3).
OH
N
O
N
H
N
A
C
B
In summary, this study provided a convenient
approach to the synthesis of quinolines based on the
reaction of aniline and its derivatives with 1,3-
propanediol under the action of FeCl3·6H2O in the
presence of CCl4. The latter promotes the oxidation of
1,3-diol converting it into a carbonyl compound.
− H2O
− H2
− H2O
− H2
− H2
N
2а
EXPERIMENTAL
role of CCl4 in this reaction, we analyzed the reaction
mixture, which contained chloroform and propional-
dehyde (by GC and GC-MS data). Iodometric titration
allows to confirm the presence of hypochlorite
(0.6 mg/mL). According to mercurometric titration
1H and 13C NMR spectra of solutions in CDCl3
were recorded on a Bruker Avance-400 spectrometer
(400.13 and 100.62 MHz, respectively), internal
reference TMC. Mass spectra were obtained on a
Synthesis of quinolines by reacting of anilines with 1,3-diols under catalysis with FeCl3·6H2Oa
Aniline 1
H (1a)
Quinoline 2
Yield, %
96
Quinoline (2a)
o-CH3 (1b)
m-CH3 (1c)
p-CH3 (1d)
o-C2H5 (1e)
o-Cl (1f)
8-Methylquinoline (2b)
92
7-Methyl- (2c) and 5-methylquinoline (2d)
6-Methylquinoline (2e)
71
96
8-Ethylquinoline (2f)
88
8-Chloroquinoline (2g)
57
m-Cl (1g)
p-Cl (1h)
7-Chloro- (2h) and 5-chloroquinoline (2i)
6-Chloroquinoline (2j)
66
86
p-OCH3 (1i)
6-Methoxyquinoline (2k)
69
o-OH (1j)
8-Hydroxyquinoline (2l)
79
a Reaction conditions: 150°С, 8 h, FeCl3·6H2O : aniline : СCl4 : 1,3-diol = 1 : 100 : 200 : 400.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 12 2015

SYNTHESIS OF QUINOLINES BY IRON-CATALYZED REACTION
2727
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The solvents and reagents of analytically pure grade
were used for the synthesis.
General procedure for the preparation of quino-
lines 2a–2l. An ampule was charged with 0.02 mmol
of FeCl3·6H2O, 2 mmol of aniline, 4 mmol of carbon
tetrachloride, and 8 mmol 1,3-propanediol under
argon. The sealed ampule was placed into a pressure
reactor, which was hermetically closed and heated at
150°C for 8 h with continuous stirring. After the
reaction completion, the reactor was cooled to room
temperature, the ampule was opened, the reaction
mixture was poured in hydrochloric acid. The aqueous
layer was separated, neutralized with 10% sodium
hydroxide solution, and extracted with methylene
chloride. The organic layer was filtered, the solvent
was distilled off, and the residue was distilled in a
vacuum. Physicochemical characteristics and spectral
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