79

CHAPTER 5

SYNTHESIS OF 7-HYDROXY-4-METHYLCOUMARIN
OVER ZAPO-5 AND LEWIS ACID METAL
ION-EXCHANGED ZAPO-5 MOLECULAR SIEVES

5.1

INTRODUCTION

Coumarins are an important group of naturally occurring

compounds widely distributed in the plant kingdom. However, they have been
produced synthetically for many years for commercial use. Coumarin and its
derivatives have been studied for physiological activity. The coumarin
derivatives find their applications in pharmaceutical, fragrance, agrochemical
industries, optical brightening agent, dispersed fluorescent and anticoagulant
(Gunnewegh et al 1995). Among the various coumarin derivatives,
7-hydroxy-4-methylcoumarin is the most widely used one in fine chemical
industries. It is used as fluorescent brightener and as a standard for
fluorometric determination of enzymatic activity. It acts as a starting material
in the preparation of insecticide hymecromone. Pechmann reaction is the most
widely applied method for the preparation of substituted coumarins since it
proceeds from very simple starting materials and also offers good yield.

Mineral acids like H2SO4, HCl, H3PO4 and CF3COOH and Lewis
acids such as ZnCl2, FeCl3, SnCl4, TiCl4 and AlCl3 were used as catalysts in
the conventional methods of coumarin synthesis (Horning 1955). This route
causes formation of by-products, longer reaction time and corrosion
problems. For these reasons, there have been efforts to find alternative,

80

environmentally benign and heterogeneously catalysed synthetic routes.

The use of heterogeneous acid catalysts presumes advantages like ease of
operation

conditions,

reduced

equipment

corrosion

and

minimised

contamination of waste streams combined with reusability. Nafion-H, zeolites

, Amberlyst 15 and other solid acids have been employed for this purpose in
the Pechmann reaction (Hoefnagel et al 1995, Gunnewegh et al 1995 and
Li et al 1998).

Pechmann reaction of resorcinol and ethyl acetoacetate produced

7-hydroxy-4-methylcoumarin over regenerable H in toluene solvent
(Gunnewegh et al 1995). In the case of Amberlyst-15, special equipment for
accelerating

this

reaction

by

microwave

irradiation

was

used

(de la Hoz et al 1999). Potdar et al (2005) reported the synthesis of

7-hydroxy-4-methylcoumarin over neutral ionic liquids ([bmim] PF6/POCl3),
but it required the presence of POCl3 which is also a hazardous one.
Adopting the principles of green chemistry, we have established
dramatic improvement in the yield using solvent-free condition for
Knoevenagel and Pechmann reactions. Synthesis of coumarins directly
catalysed by Lewis acid ion-exchanged MeAPO-5 has not been reported so
far. In the present work we describe an eco-friendly procedure for the
synthesis of coumarins via Pechmann reaction catalysed by metal
ion-exchanged ZAPO-5. We report

the preparation of 7-hydroxy-

4-methylcoumarin using resorcinol and ethyl acetoacetate as the reactants

over ZAPO-5 and Lewis acid metal ion-exchanged ZAPO-5 in the liquid
phase.

The structure of 7-hydroxy-4-methylcoumarin

Figure 5.1.

is

shown

in

81

HO

O
C=O

CH3

Figure 5.1

5.2

Structure of 7-hydroxy-4-methylcoumarin

SYNTHESIS OF 7-HYDROXY-4-METHYLCOUMARIN
The liquid phase intermolecular condensation between resorcinol

and ethyl acetoacetate was carried over ZAPO-5 and La3+, Ce3+, In3+ and Ga3+
ion-exchanged ZAPO-5 catalysts. The reaction was carried out by changing
the reaction parameters viz., temperature, catalyst weight, feed ratio and
reaction time to obtain good yield at maximum conversion. The only product
obtained was 7-hydroxy-4-methylcoumarin.

5.2.1

Effect of Temperature

Intermolecular condensation of resorcinol and ethyl acetoacetate

was carried over ZAPO-5 and metal ion-exchanged ZAPO-5 catalysts in order
to correlate the effect of Lewis acid sites on resorcinol conversion and product
selectivity. The reaction was carried at 100, 125, 150 and 175 C in the liquid
phase. The feed ratio was kept at 1:3 (resorcinol: ethyl acetoacetate) and the
reaction was carried for 6 h in all the cases. The major product was found to
be 7-hydroxy-4-methylcoumarin. The results of resorcinol conversion,
selectivity and yield of products over all the catalysts are presented in
Table 5.1. The resorcinol conversion and selectivity to 7-hydroxy-4methylcoumarin increased with increase in temperature. The possible
pathways for the formation of coumarin derivative are illustrated in
Schemes 5.1 and 5.2. It is visualised as shown in the reaction Scheme 5.1 that

82

ethyl acetoacetate is activated by protonation at the ester carbonyl which

facilitates nucleophilic attack of resorcinol yielding the precursor of the final
product.

Table 5.1

Effect of temperature on resorcinol conversion, yield

and

selectivity of products over various catalysts

Selectivity
of
Resorcinol
7-hydroxyTemperature
Catalyst
conversion
o
( C)
4-methyl
(%)
coumarin
(%)
100
27.5
89.8
125
29.7
91.9
ZAPO-5
150
33.2
92.4
175
35.8
93.5
100
44.0
91.5
125
47.3
93.8
LaZAPO-5
150
51.8
94.4
175
53.7
95.3
100
47.8
92.8
125
52.3
94.6
CeZAPO-5
150
57.8
95.3
175
59.4
96.1
100
58.2
94.1
125
64.5
95.1
InZAPO-5
150
70.4
96.7
175
71.7
97.9
100
73.9
95.4
125
79.3
96.5
GaZAPO-5
150
89.4
97.6
175
91.2
98.5
Reaction conditions: Catalyst amount: 0.1 g; Time:
(Resorcinol: Ethyl acetoacetate)

Yield of
Yield of
7-hydroxyother
4-methyl
coumarin products
(%)
(%)
24.7
2.8
27.3
2.4
30.7
2.5
33.5
2.3
40.3
3.7
44.4
2.9
48.9
2.9
51.2
2.5
44.4
3.4
49.5
2.8
55.1
2.7
57.1
2.3
55.2
3.0
62.8
2.7
68.4
2.0
70.2
1.5
71.3
2.6
77.1
2.2
87.3
2.1
89.9
1.3
6 h; Feed ratio: 1:3

83

COOC2H5
OH

H2C
+

H
O

CH3

COOC2H5

2Zn

2Zn

H2C

COCH3

HO

OH
HO

C=O

HO

C=O

H2C
O=C

CH3

CH3

HO

HO

C-OH

HO

O
C O

MAPO-5
CH

C
HO

HO

HO

CH3

CH3

O
C=O

CH3

Scheme 5.1 Intermolecular

cyclisation

acetoacetate over ZAPO-5

of

resorcinol

and

ethyl

84
HO
COCH3

H3C

MO
MAPO-5

H2C
COOCH3CH2

OH

CH2
C

OCH2CH3

O
+

HO

O
HO

C=O

MO

CH
H

MO

C=O

OH

CH3

HO

CH3

HO

O
C O M=O

M=O
OH

CH3

HO

OH2

CH3

O
C=O

-H2O

CH3

Scheme 5.2 Intermolecular

cyclisation

of

resorcinol

and

ethyl acetoacetate over MO+.

The precursor undergoes enolisation and the enolised product is

also activated by protonation at the ester carbonyl. The resulting species
undergoes intermolecular cyclisation and subsequent dehydration to form the
product.

85

In the reaction Scheme 5.2, it is presumed that ethyl acetoacetate

co-ordinates to MO+. This is attacked by resorcinol yielding the precursor.
This precursor undergoes enolisation and rearrangement of electronic cloud to
form species that readily undergo intermolecular cyclisation. The conversion
of cyclised species into final product is also catalysed by MO+. Since the
precursor is not observed as product, cyclisation appears to be more rapid.
The conversion increased with increase in temperature over ZAPO-5.
The selectivity of product is above 90% at all temperatures. This revealed that
the intermediates formed immediately reacted further to form the final
product.

Comparison of the results of resorcinol conversion and product

yield revealed that ZAPO-5 is the least active among the catalysts. This
presumed that the reaction is largely controlled by Lewis acid sites.
LaZAPO-5 showed higher conversion of resorcinol and yield of 7-hydroxy-4methylcoumarin than ZAPO-5. Though LaZAPO-5 exhibited 48% reduction
of

strong

acid

sites,

the

enhanced

conversion

compared

to

ZAPO-5 clearly established the active role of LaO sites. These Lewis acid
ions like Bronsted acid sites also activate ester thus facilitating nucleophilic
reaction of ester with resorcinol as shown in the reaction Scheme 5.1.
Though they are lesser in number than the total number of strong Bronsted
acid sites, they may catalyse with higher activity. Co-ordination of both
reactants to LaO+ may be possible as it possesses higher co-ordination
capability than H+. The important observation is that ion-exchange of La3+
mainly occured on strong acid sites leaving weak acid sites unaffected as
discussed above. Hence, the metal ion dependent route may be more
pronounced than Bronsted acid sites dependent route.

The reaction over CeZAPO-5 exhibited nearly similar trend in

conversion and product yield as that of LaZAPO-5. However, there is further

86

enhancement in the conversion of resorcinol, yield and selectivity of

7-hydroxy-4-methylcoumarin over CeZAPO-5. Therefore Ce3+ may play
similar role as that of La3+. The high conversion and yield over CeZAPO-5
are due to more ion-exchange of Ce3+ (70%) than La3+ (48%) in ZAPO-5.
The results over In3+ and GaZAPO-5 exemplify higher conversion
than the previous catalysts. This is again due to more ion-exchange of
In3+ (90%) and Ga3+ (96%) than La3+ and Ce3+ in ZAPO-5. Hence it could be
concluded that MO+ sites (where M = La3+, Ce3+, In3+ and Ga3+) are more
active for intermolecular cyclisation of resorcinol and ethyl acetoacetate than
Bronsted acid sites. The yield of the product is also higher over GaZAPO-5
than other catalysts. Palaniappan and ChandraShekhar (2004) have reported
the synthesis of 7-hydroxy-4-methylcoumarin using polyaniline supported
sulphuric acid. They reported 74% yield of the product for a feed ratio of 1:2
(resorcinol: ethyl acetoacetate) at 170 C. The yield of the product in our
study is 17% higher than the already reported value although the catalyst
weight was 0.1 g less than the amount used by them. Hence ion-exchanged
ZAPO-5 is found to be better than others for this reaction. In addition, HY
and HZSM-5 zeolites have been used for the synthesis of 7-hydroxy-4methylcoumarin (Sabou et al 2005). The yield of the product with HY and
HZSM-5 was found to be 12% less than our report with ion-exchanged
ZAPO-5. Comparison of these results revealed that ion-exchanged ZAPO-5
with Lewis acid metal ion in the form MO+ species may catalyse this reaction
better than Bronsted acid sites.

5.2.2

Effect of Feed Ratio

The effect of feed ratio (resorcinol: ethyl acetoacetate) viz., 1:1, 1:3

and 1:5 on resorcinol conversion, product yield and selectivity was studied
over GaZAPO-5 at 160 C and the results are shown in Table 5.2 and

87

Figure 5.2. The conversion increased when the feed ratio increased from 1:1
to 1:3. This observation suggests enhanced adsorption and activation of ethyl
acetoacetate on the active sites of the catalyst. In order to facilitate
nucleophilic attack of resorcinol, ethyl acetoacetate should be first
chemisorbed on the active sites through the ester carbonyl group. This is the
prerequisite step for the subsequent intermolecular cyclisation. But the
conversion decreased with 1:5 feed ratio. There may be enhanced adsorption
of ethyl acetoacetate even at this feed ratio. But nucleophilic attack of
resorcinol on this could be suppressed due to the presence of excess free ethyl
acetoacetate. Although feed ratio changed the conversion, selectivity was not
much affected as all three feed ratios gave selectivity more than 90%.

Table 5.2

Effect of feed ratio on resorcinol conversion, product

selectivity and yield over GaZAPO-5

Resorcinol
Feed
ratio

conversion
(%)

Selectivity of

Yield of

Yield of

7-hydroxy-4methylcoumarin

7-hydroxy-4-

other

methylcoumarin

products

(%)

(%)

(%)

1:1

79.0

93.5

74.3

4.7

1:3

89.4

97.6

87.3

2.1

1:5

86.7

94.2

82.3

4.4

Reaction conditions: Temperature: 150 C; Catalyst amount: 0.1; Time: 6 h

88

120

Conversion
Selectivity
Yield

Distribution (%)

100

80

60

40

20

0
1:1

1:3

1:5

Feed ratio

Figure 5.2

Effect of feed ratio on resorcinol conversion, product

selectivity and yield of 7-hydroxy-4-methylcoumarin

5.2.3

Effect of Catalyst Loading

The effect of catalyst loading on resorcinol conversion and product

selectivity was studied using 0.05, 0.1 and 0.15 g catalyst with a constant feed
ratio of 1:3 at 150 C and the results are presented in Table 5.3.
The conversion increased with increase in the catalyst amount. Hence, it is
presumed that once the product formed it should be immediately desorbed
from the catalyst surface without allowing to chemisorb again. The selectivity
of 7-hydroxy-4-methylcoumarin also increased with increase in catalyst
amount from 0.05 to 0.15 g. Hence, the formation of intermediate and its
cyclisation to coumarin derivative require enough number of active sites to
increase resorcinol conversion as well as product selectivity. GaZAPO-5 with

89

more number of active sites is better than other catalysts. This study clearly
revealed that the reaction still depends on the number of active sites. Thus the
optimum amount of catalyst is found to be 0.1 g.

Table 5.3

Effect of catalyst amount on resorcinol conversion, product

selectivity and yield over GaZAPO-5

Catalyst

Resorcinol

amount

conversion

(g)

(%)

Selectivity of
7-hydroxy-4methylcoumarin

Yield of

Yield of

other
7-hydroxy-4methylcoumarin products

(%)

(%)

(%)

0.05

73.7

88.2

66.2

7.5

0.10

89.4

97.6

87.3

2.1

0.15

91.6

98.4

90.2

1.4

Reaction conditions: Temperature: 150 C; Time: 6 h; Feed ratio: 1:3

(Resorcinol: Ethyl acetoacetate)

5.2.4

Effect of Reaction Time

The sequential formation of intermediate and the product is evident

from the effect of reaction time on resorcinol conversion and product

selectivity as shown in Table 5.4. The selectivity to 7-hydroxy-4methylcoumarin increased with increase in the reaction time upto
8 h, beyond which the selectivity remained steady illustrating the attainment
of equilibrium. Since the selectivity of others also increased with increase in
time, they should include only the intermediates of 7-hydroxy-4methylcoumarin. This supported clearly the formation of intermediates first
and their cyclisation to coumarin derivative in a sequential manner.

90

Table 5.4

Effect of reaction time on resorcinol conversion, product

selectivity and yield over GaZAPO-5

Selectivity of
Time

Resorcinol

(h)

conversion (%)

7-hydroxy-4methylcoumarin
(%)

Yield of

Yield of

other
7-hydroxy-4methylcoumarin products
(%)
(%)

67.0

89.1

60.8

6.2

77.0

91.2

69.3

5.7

89.4

97.6

87.3

2.1

88.2

97.6

86.1

2.1

Reaction conditions: Temperature: 150 C; Catalyst amount: 0.1 g;

Feed ratio: 1:3 (Resorcinol: Ethyl acetoacetate)

5.3 CONCLUSION
The study concludes that ion-exchanged ZAPO-5 catalysts are
more active for intermolecular cyclisation of resorcinol and ethyl acetoacetate
in the synthesis of 7-hydroxy-4-methylcoumarin than the parent ZAPO-5.
The yield of the product is higher over ion-exchanged ZAPO-5 than those
catalysts already reported in the literature. The MO+ sites (where M = La3+,
Ce3+, In3+ or Ga3+) are found to be more active than Bronsted acid sites.
The formation of minimal amount of side product is an important observation
in this study. Thus, Lewis acid metal ion exchanged ZAPO-5 catalysts could
be an eco-friendly alternative for the industrial production of coumarin
derivatives from the appropriate precursors. Further, ZAPO-5 is suitable for
selective ion-exchange of Bronsted acid sites by trivalent metal ions.
Such ion-exchanged catalysts may find applications in the selective organic
transformations requiring only Lewis acid sites or weak Bronsted acid sites.