Solvent-free synthesis of 4-aryl-3,4-dihydrobenzopyran-2-ones via [3+3] cyclocoupling of phenols with cinnamic acid catalyzed by molecular iodine

Article abstract of DOI:10.1016/j.tetlet.2012.06.069

Molecular iodine was used as a catalyst in the [3+3] cyclocoupling of phenols and cinnamic acids which proceeds via a tandem esterification- hydroarylation process at 120-130 °C under solvent-free conditions. Substituted 4-aryl-3,4-dihydrobenzopyran-2-one

Full text of DOI:10.1016/j.tetlet.2012.06.069

Tetrahedron Letters 53 (2012) 4469–4472
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Tetrahedron Letters
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Solvent-free synthesis of 4-aryl-3,4-dihydrobenzopyran-2-ones via [3+3]
cyclocoupling of phenols with cinnamic acid catalyzed by molecular iodine
⇑
Durga P. Kamat, Santosh G. Tilve , Vijayendra P. Kamat
Department of Chemistry, Goa University, Taleigao Plateau, Goa 403 206, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Molecular iodine was used as a catalyst in the [3+3] cyclocoupling of phenols and cinnamic acids which
proceeds via a tandem esterification–hydroarylation process at 120–130 °C under solvent-free condi-
tions. Substituted 4-aryl-3,4-dihydrobenzopyran-2-ones were obtained in good yields.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 10 March 2012
Revised 13 June 2012
Accepted 15 June 2012
Available online 19 June 2012
Keywords:
3,4-Dihydrobenzopyran-2-one
Iodine
Solvent-free
Phenol
Cinnamic acid
Molecular iodine has received considerable attention in the last
few years as an inexpensive, non-toxic, readily available catalyst
for various organic transformations.1 Iodine has high tolerance to
air as well as moisture making it an ideal catalyst. It can be easily
removed from the reaction mixture by washing with reducing
agents. Recently use of iodine as a reagent and catalyst is
reviewed2 for transformation of molecules containing oxygen
functional groups. As a continuation of our interest3 in application
of iodine in the synthesis of heterocycles, we herein report the syn-
thesis of 4-aryl-3,4-dihydrobenzopyran-2-ones via the [3+3] cyclo-
coupling of phenols with cinnamic acids using molecular iodine as
a catalyst (Scheme 1).
3,4-Dihydrobenzopyran-2-ones or dihydrocoumarins are well
known for fragrance in cosmetics,4 food flavouring,5 and perfumery
industries.6 4-Aryl-3,4-dihydrocoumarins are naturally occurring
compounds7 which exhibit some interesting biological activities
such as aldose reductase inhibition,8 antiherpetic,9 protein
kinases,10 and are important synthetic intermediates for pharma-
ceutical compounds. It has been recently reported that 4-aryl-
3,4-dihydrocoumarins serve as starting materials for the synthesis
of N-diaryl (aryl) substituted amides which possess antiarrhythmic
properties.11
arylonitrile,14 reaction of Fischer carbene complexes with ketene
acetals,15 p-TSA mediated hydroarylation of cinnamic acids with
anisoles or phenols,16 AlCl3 mediated C–C coupling reaction be-
tween hydroxyketene s,s-acetals and arenes,17 [4+2] cycloaddition
reaction of o-quinone methides with silyl ketene acetals,18
biotransformation of coumarins by microorganisms,19 microwave
assisted synthesis from phenols and cinnamoyl chloride in the pres-
ence of montmorillonite K-10 catalyst,20 microwave assisted sol-
vent-free synthesis from phenols and cinnamic acid using silica
supported Wells-Dawson heteropolyacid as catalyst,21 and recently
the p-TSA mediated synthesis from aryl cinnamic esters.22
For initial studies b-naphthol and cinnamic acid were chosen as
substrates. First the cyclocoupling reactions were studied in differ-
ent solvents such as ethyl alcohol, methyl alcohol, chloroform,
dichloromethane, acetonitrile, dioxane, and water at room temper-
ature using 20 mol % of iodine. Having seen no formation of any
products the reaction masses were subjected to reflux conditions
(Table 1).
In case of ethyl alcohol only 10% of the desired product was
formed after 24 h of refluxing along with a large percentage of
ethyl cinnamate. Refluxing the reaction mixture in xylene could
The conventional methods for the synthesis of dihydrocouma-
rins include, the hydroarylation of cinnamic acids with phenols in
strong acidic media,12 the catalytic hydrogenation of coumarins,13
Lewis acid promoted reaction of activated phenols with
O
HO
OH
O
O
20 mol% I2
R
R
+
120-130 oC, neat
Ar
Ar
⇑
Corresponding author. Tel.: +91 832 6519317; fax: +91 832 2452886.
E-mail address: stilve@unigoa.ac.in (S.G. Tilve).
Scheme 1. Reaction of phenol with cinnamic acid.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.069

4470
D. P. Kamat et al. / Tetrahedron Letters 53 (2012) 4469–4472
Table 1
Table 2
Screening of solvents in refluxing conditions using b-naphthol and cinnamic acid
Optimization of iodine concentration
Solvent
Time (h)
Yield (%)
Entry
Iodine (mol %)
Time (h)
Yield (%)
Methanol
24
24
24
24
24
24
24
24
24
5
30
0
1
2
3
4
5
6
7
8
0
1
5
10
15
20
25
30
24
24
8
8
3
1
1
1
0
0
Chloroform
Acetonitrile
1,2-Dichloroethane
Ethanol
1,4-Dioxane
Water
Toluene
Acetic acid
Xylene
25
30
10
10
10
20
30
70
30
30
50
70
80
78
70
1,2-Dichlorobenzene
5
Table 3
Reaction of various phenols with cinnamic acids under optimized reaction conditions23
Entry
Substituted
Product
Time (h)
Yielda (%)
1a
3a
Ph
O
OH
1
1
80
O
1b
3b
OH
O
O
2
3
1.5
78
83
Ph
O
1c
3c
OH
O
1
Ph
1d
3d
OH
O
O
4
5
6
3
4
5
60
83
65
Ph
1e
1f
3e
3f
OH
O
O
Ph
OH
O
O
Ph
1g
1h
3g
3h
O
O
OH
7
8
2
2
85
85
Ph
O
O
OH
Ph

D. P. Kamat et al. / Tetrahedron Letters 53 (2012) 4469–4472
4471
Table 3 (continued)
Entry
Substituted
Product
Time (h)
Yielda (%)
1i
3i
O
OH
O
9
2
77
60
HO
HO
Ph
1j
3j
O
O
OH
10
4
4
Ph
O
1k
1l
3k
OH
O
11
65
Ph
3l
OH
O
O
12
13
3
70
78
Cl
Cl
Ph
3mb
3n
1c
OHb
O
O
1.5
C6H4 ( 4-OMe)
1m
OH
O
Ph
14
15
24
24
20
30
O
O
O2N
O2N
3o
1n
O
Ph
O2N
OH
O2N
1o
3p
OH
O
Ph
16
24
50
O
F
F
a
Isolated % yield after column chromatography.
In this case p-methoxy cinnamic acid was used.
b
account for 70% of the product formation in 5 h. However the reac-
tion in refluxing 1,2-dichlorobenzene resulted only in 30% forma-
tion of the product in 5 h.
phenols also gave the dihydrocoumarins in moderate to good
yields (3d–3f). Parent phenol gave 60% yield of product (3j) in
4 h, while a-naphthol gave product (3k) in 65% yield. Phenol with
Encouraged by these results, we thought of carrying out the
reaction under solvent-free conditions. The reactions were studied
at different temperature conditions. Formation of the product was
observed in the range of 80–130 °C. As the reaction was complete
within one hour without solvent at 120–130 °C, this condition was
selected for further studies. Lower temperatures (80–100 °C)
prolonged the reaction time. For standardizing the catalyst amount
we used different catalyst loadings (Table 2). Higher catalyst load-
ing could not enhance the reaction rates or increase the yields
evidently.
However when less than 20 mol % of iodine was used prolonged
reaction time was needed. No product was formed in the absence
of catalyst.
After optimization of reaction conditions the reaction was
explored for substrate scope (Table 3).23 Several phenols having
electron donating groups were rapidly converted into
dihydrocoumarins with good yields. The ortho substituted methyl
electron withdrawing chloro group at para position gave the prod-
uct (3l) in good yield (70%). Strong electron withdrawing nitro
groups at para and meta positions did not yield the dihydrocouma-
rins but resulted in the formation of the corresponding nitro phe-
nyl cinnamates after 24 h in low yields.
Similarly p-fluorophenol resulted in the formation of ester 3p in
50% yield. The reaction was also performed with p-methoxy substi-
tuted cinnamic acid, which on reaction with p-cresol gave the cor-
responding dihydrocoumarin (3m).
The formation of dihydrocoumarins has been accounted for in
two different pathways (Scheme 2), either via transesterification
followed by hydroarylation (path A, Scheme 2) or via hydroaryla-
tion followed by lactonization (path B, Scheme 2). In the case of
reaction of phenols with cinnamic acid using p-toluenesulfonic
acid,16 dihydrocoumarin formation occurs via transesterification
followed by intramolecular hydroarylation (path A, Scheme 2),
while phenols react with benzylidine malonates in the presence

4472
D. P. Kamat et al. / Tetrahedron Letters 53 (2012) 4469–4472
is that it provides an efficient, cost-effective, easy to handle, and
O
OH
environmentally benign route, with the use of iodine as a mild and
safer catalyst. The reaction is important from the green chemistry
point of view also because hydroarylation exhibits perfect atom
economy.
Path
A
Path
B
OH
+
Acknowledgment
HO
O
D.P.K is thankful to UGC for the award of Junior Research
Fellowship.
O
HO
O
Supplementary data
( 4 )
( 5 )
Supplementary data associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.tetlet.2012. 06.069.
hydroarylation
lactonisation
3a
References and notes
Scheme 2. Possible pathways leading to the formation of dihydrocoumarin (3a).
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O+
Ph
O
O
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I
H
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Scheme 3. The probable mechanism.
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12c
of a catalytic amount of TiCl4
to give dihydrocoumarin via
hydroarylation followed by lactonization. (path B, Scheme 2).
To study the mechanism in the present case, (E)-2-naphthyl cin-
namate (4) was subjected to the standardized reaction condition.
The dihydrocoumarin (3a) was obtained along with trace amounts
of cinnamic acid and b-naphthol. Similarly, methyl ether of b-
naphthol was heated with cinnamic acid in the presence of
20 mol % of iodine at 120–160 °C for 3 h to evaluate the possibility
of direct hydroarylation. However, we did not observe any change
in the reaction mass. Thus, in the present case most likely, transe-
sterification takes place first followed by hydroarylation (path A,
Scheme 2). The probable mechanism of iodine catalyzed cyclocou-
pling is depicted in Scheme 3.
14. (a) Johnson, K. M. Tetrahedron 1968, 24, 5595; (b) Fillion, E.; Dumas, A. M.;
Kuropatwa, B. A.; Malhotra, N. R.; Sitler, T. C. J. Org. Chem. 2006, 71, 409.
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23. General procedure for the synthesis of dihydrocoumarins: Iodine (0.13 mmol) was
added into a mixture of phenol (0.69 mmol) and cinnamic acid (0.69 mmol)
under an air atmosphere and the mixture was neat heated at 120–130 °C for a
period of time (1–4 h). Following completion of the reaction as monitored by
TLC, the reaction mixture was cooled, diluted with ethyl acetate, washed with
aqueous sodium thiosulphate solution and dried over anhydrous sodium
sulphate. The solvent was removed under vacuum to provide the crude
products. Further purification was done by column chromatography on silica
gel with hexanes/ethyl acetate (4:1) as an eluent.
Inconclusion, wehavedevelopeda simple, convenient, metaland
solvent-free process for the one pot synthesis of 4-aryl-3,4-
dihydrocoumarins by using inexpensive and readily available start-
ing materials, in good yields. The main feature of the present method