July 2008
Notes
Chem. Pharm. Bull. 56(7) 1049—1051 (2008)
1049
Silica Supported Phosphomolybdic Acid: An Efficient Heterogeneous
1)
Catalyst for Friedlander Synthesis of Quinolines
Biswanath DAS,* Martha KRISHNAIAH, Keetha LAXMINARAYANA, and Duddukuri NANDANKUMAR
Organic Chemistry Division–I, Indian Institute of Chemical Technology; Hyderabad–500 007, India.
Received March 25, 2008; accepted April 17, 2008; published online April 25, 2008
Silica supported phosphomolybdic acid, an eco-friendly heterogeneous catalyst, has been found to be highly
efficient for Friedlander synthesis of quinolines in excellent yields. A variety of ketones afford the quinolines
smoothly. The catalyst can be easily recovered and reused.
Key words Friedlander synthesis; quinoline; silica supported phosphomolybdic acid; heterogeneous catalyst
Quinoline moiety is frequently found in natural products (81—95%) within 45—100 min. A cyclic 1,3-diketone such
2—4)
and bioactive compounds.
Various quinolines are known as dimedone (entry 3d, 3o) also underwent the conversion
to possess different important medicinal properties such as smoothly. The reaction is free of side products, which are
antimalarial, antibacterial and tyrosine kinase inhibiting ac- generally formed by self-condensation of ketones under basic
3
—5)
tivities.
Quinolines are also employed for the synthesis of conditions. The structures of the quinolines were established
1
nano- and meso-structures having enhanced electronic and from their spectral ( H-NMR and MS) data.
photonic properties.
synthesis of quinolines is the Friedlander annulation. This mental point of view as it works under heterogeneous condi-
6,7)
A straight-forward method for the
The catalyst, PMA·SiO is important from an environ-
2
8)
17)
reaction involves the base or acid catalyzed or thermal con- tions and possesses low toxicity and high stability. Its cat-
densation between a 2-aminoaryl ketone and an another car- alytic activity towards the synthesis of quinolines is impres-
bonyl compound having a reactive a-methylene group fol- sive. It was recovered from the reaction mixture and reused.
lowed by cyclodehydration. However, under thermal or base In absence of the catalyst or in the presence of only silica gel
catalysis conditions 2-aminobenzophenone could not react the reaction could not proceed while in the presence of only
with cyclohexanone and b-keto esters while under acid catal- PMA the yields were low.
ysis conditions side products were formed. Lewis acids such
In conclusion, we have developed an efficient general
as ZnCl , Bi(OTf) , Sc(OTf) , AuCl and ionic liquids have route for the synthesis of quinolines via Friedlander annula-
2
3
3
3
also recently been employed for the synthesis of quino- tion using PMA·SiO as a novel catalyst. The simple experi-
2
9—12)
lines.
However most of the methods suffer from harsh mental procedure, mild reaction conditions, excellent yields,
reaction conditions, prolonged reaction times, unsatisfactory rapid conversion and recovery of the catalyst are the notable
yields and tedious experimental procedure. In several cases advantages of the present protocol. The catalyst is highly
the recovery of the catalyst is also a problem. Here we report suitable for the preparation of diverse types of quinoline
a convenient and efficient method for the preparation of derivatives.
quinolines using silica supported phosphomolybdic acid
Experimental
(
PMA·SiO ) as a heterogeneous catalyst.
2
To a mixture of 2-aminoaryl ketone (1 mmol) and a-methylene carbonyl
compound (1.1 mmol) in EtOH (5 ml) PMA·SiO (10%, 100 mg) was
In recent years, heterogeneous catalysts have gained much
2
importance in organic synthesis due to eco-economic bene- added. The mixture was heated under reflux and the reaction was monitored
1
3—16)
fits. In connection with our work
on the applications of by TLC. After the completion the mixture was filtered and the catalyst was
recovered. The filtrate was concentrated under vacuum and the residue was
purified by column chromatography (silica gel, 5% EtOAc in hexane) to
obtain pure quinoline derivative.
The recovered catalyst was used consecutively three times to afford the
product without hampering its yield. As for an example, the reaction of
heterogeneous catalysts for the development of useful syn-
17)
thetic methodologies we have discovered that PMA·SiO2
is highly effective to catalyze the Friedlander synthesis of
quinolines (Chart 1).
A series of quinolines were prepared from various 2- 2-aminoacetophenone with ethyl acetoacetate in the presence of the catalyst
(
PMA·SiO ) afforded the corresponding quinoline (3a, Table 1, entry a) in
aminoaryl ketones (1) and a-methylene carbonyl compound
2) (Table 1). The 2-aminoaryl ketones used for the prepara-
tion of quinolines included both 2-amino acetophenone and
2
an yield of 88% while the same reaction using the recovered catalyst in con-
secutive three cycles furnished the products in the yields of 88, 87 and 87%.
(
1
The spectral ( H-NMR and MS) data of some representative quinolines
2
-aminobenzophenone while a-methylene carbonyl com- are given below.
1
pounds included 1,3- and 1,4-diketones, b-ketoesters and
cycloalkanones. The products were formed in high yields
Product 3b (Table 1): H-NMR (200 MHz, CDCl ): d 7.98 (2H, t, Jꢀ8.0
3
Hz), 7.68 (1H, t, Jꢀ8.0 Hz), 7.50 (1H, t, Jꢀ8.0 Hz), 3.98 (3H, s), 2.65 (3H,
s), 2.61 (3H, s); FAB-MS: m/z 238 [MꢁNa] .
Product 3g (Table 1): H-NMR (200 MHz, CDCl ): d 7.75 (1H, d, Jꢀ8.0
Hz), 7.57 (1H, t, Jꢀ8.0 Hz), 7.49 (1H, t, Jꢀ8.0 Hz), 7.21 (1H, d, Jꢀ8.0 Hz),
ꢁ
1
3
ꢁ
5.88 (2H, s), 1.97 (6H, s), 1.72 (3H, s); FAB-MS: m/z 236 [MꢁNa] .
1
Product 3h (Table 1): H-NMR (200 MHz, CDCl ): d 8.02 (1H, d, Jꢀ8.0
Hz), 7.71 (1H, t, Jꢀ8.0 Hz), 7.60—7.42 (5H, m), 7.40—7.29 (2H, m), 4.02
3
(
[
2H, q, Jꢀ7.0 Hz), 2.71 (3H, s), 0.94 (3H, t, Jꢀ7.0 Hz), FAB-MS: m/z 314
ꢁ
MꢁNa] .
1
Product 3l (Table 1): H-NMR (200 MHz, CDCl ): d 8.05 (1H, d, Jꢀ8.0
3
Chart 1
Hz), 7.66—7.29 (8H, m), 3.22 (2H, t, Jꢀ7.0 Hz), 2.90 (2H, t, Jꢀ7.0 Hz),
∗
© 2008 Pharmaceutical Society of Japan