ZrCl4-catalyzed Pechmann reaction: Synthesis of coumarins under solvent-free conditions

Article abstract of DOI:10.1081/SCC-200034821

Zirconium (IV) chloride is used as an efficient catalyst in the Pechmann condensation reaction of phenols with β-keto esters leading to the formation of coumarin derivatives in good yields under solvent-free conditions.

Full text of DOI:10.1081/SCC-200034821

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ZrCl4‐Catalyzed Pechmann
Reaction: Synthesis
of Coumarins Under
Solvent‐Free Conditions
G. Smitha a & Ch. Sanjeeva Reddy a
a Department of Chemistry, Kakatiya University,
Warangal, 506 009, India
Published online: 12 Jan 2011.
To cite this article: G. Smitha & Ch. Sanjeeva Reddy (2004): ZrCl4‐Catalyzed
Pechmann Reaction: Synthesis of Coumarins Under Solvent‐Free Conditions,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 34:21, 3997-4003
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 21, pp. 3997–4003, 2004
ZrCl4-Catalyzed Pechmann Reaction:
Synthesis of Coumarins Under Solvent-Free
Conditions
*
G. Smitha and Ch. Sanjeeva Reddy
Department of Chemistry, Kakatiya University, Warangal, India
ABSTRACT
Zirconium (IV) chloride is used as an efficient catalyst in the Pechmann
condensation reaction of phenols with b-keto esters leading to the
formation of coumarin derivatives in good yields under solvent-free
conditions.
Key Words: Phenol; Keto ester; Zirconium (IV) chloride; Pechmann
reaction; Coumarin.
Coumarin and its derivatives occur widely in nature, particularly in
plants; most of them show wide biological activities like anthelmintic,
*
Correspondence: Ch. Sanjeeva Reddy, Department of Chemistry, Kakatiya Univer-
sity, Warangal-506 009, India; E-mail: chsrkuc@yahoo.co.in.
3997
DOI: 10.1081/SCC-200034821
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3998
Smitha and Reddy
hypnotic, insecticidal, and anticoagulant properties.[1] They are widely used as
additives in food and cosmetics, agrochemicals, optical brightening agents,
dispersed fluoroscent and tunable dye lasers,[2] and also act as intermediates
for the synthesis of fluoro coumarins, chromenes, coumarones, 2-acyl
resorcinols, and others.[3] Many routes have been reported for the synthesis
of coumarins including the Perkin,[4] Pechmann,[5] Knoevenagel,[6] Refor-
matsky,[7] and the Wittig[8] reactions. The Pechmann reaction involves
the condensation of phenols with b-ketonic esters in the presence of
variety of acidic condensing agents such as sulfuric, hydrochloric, and
phosphoric acids, phosphorous pentoxide, trifluroacetic acid, and Lewis
[9]
acids such as ZnCl2, FeCl3, AlCl3 and exchange resins,[10] solid acid cata-
lysts[11] have also been used. Recently, there have been reports on the use of
microwaves,[12] ionic liquid as a Lewis acid catalyst and solvent,[13] Zn/I2,[14]
p-TsOH,[15] InCl3,[16] and Yb(OTf)3
as acid catalysts for the synthesis of
[17]
coumarins.
In connection with our work on catalytic applications of ZrCl4,[18] we
report herein a mild and convenient method for the synthesis of coumarins
under the Pechmann reaction conditions using ZrCl4 as an efficient catalyst
(Sch. 1).
Thus, treatment of resorcinol with ethyl acetoacetate in the presence of
2 mol% of ZrCl4 under solvent-free conditions at 708C for 8 min afforded
the 7-hydroxy-4-methyl coumarin in 95% yield (entry 1). In order to study
substituent effects, we have tested several combinations of phenol derivatives,
and b-keto esters were examined and the results are summarized in Table 1.
The condensation reaction with 4-chloro phenol failed to afford the corre-
sponding coumarin (entry 6). The electron donating group on phenol
promoted the reaction while the electron withdrawing group inhibited the
reaction. An alkyl group is not strong enough to furnish the activation
needed and thus gives a low yield. In contrast, electron-withdrawing groups
inhibit the reaction.
In summary, this paper describes a simple and efficient method for the
synthesis of coumarins via ZrCl4-catalyzed Pechmann condensation of
phenol and b-keto esters.
Scheme 1.

Synthesis of Coumarins Under Solvent-Free Conditions
3999
b

4000
Smitha and Reddy
b

Synthesis of Coumarins Under Solvent-Free Conditions
EXPERIMENTAL
4001
General Procedure for the Synthesis of Coumarins
A mixture of phenolic substrate (10 mmol) and keto ester (10 mmol) was
heated at 708C in the presence of zirconium (IV) chloride (46 mg, 2 mol%).
After completion of the reaction at the desired time as indicated in the
table, the reaction mixture was cooled to room temperature and poured onto
crushed ice (50 g). The solid product obtained was filtered off, washed
with ice-cold water, and recrystallized from hot ethanol to obtain the pure
1
product. All the products were characterized by IR, H NMR, and mass
spectroscopy and compared with the literature data for known products.
4-(Chloromethyl)-5, 7-dihydroxy-2H-chromen-2-one (entry 12):
White solid, m.p. 243–2458C; 1H NMR (DMSO-d6, 400 MHz): d 6.35
(s, 1H), 6.29 (s, 1H), 6.25 (s, 1H), 5.0 (s, 2H); 13C NMR (DMSO-d6,
400 MHz): d 162.0, 160.5, 157.6, 157.0, 152.5, 109.2, 100.2, 99.7, 95.3,
45.5; IR (Neat): 3159, 1654, 1601, 1374, 1170, 820 cm21; EIMS (m/z):
226 (Mþ); Anal. Calcd. for C10H7ClO4: C, 53.00; H, 3.11. Found C, 53.06;
H, 3.15.
Methyl 2-(5-7-dihydroxy-2-oxo-2H-chromen-4-yl)acetate (entry 13):
1
White crystalline solid, m.p. 234–2368C; H NMR (DMSO-d6, 400 MHz):
d 10.75 (s, 1H, OH), 10.37 (s, 1H, OH), 6.35 (s, 1H), 6.21 and 6.2 (2s, 2H),
5.98 (s, 1H), 3.88 (s, 2H), 3.6 (s, 3H); 13C NMR (DMSO-d6, 400 MHz): d
170.8, 161.7, 160.6, 157.6, 156.9, 150.5, 111.6, 102.0, 99.4, 95.1, 52.1,
41.3; IR (Neat): 3200, 1701, 1601, 1362, 1158, 825 cm21; EIMS (m/z):
250 (Mþ); Anal. Calcd. for C12H10O6: C, 57.60; H, 4.03. Found C, 57.62;
H, 4.07.
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Synthesis of Coumarins Under Solvent-Free Conditions
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Received in India July 7, 2004