Selectfluor promoted environmental-friendly synthesis of 2H-Chromen-2-ones derivatives under various reaction conditions

Article abstract of DOI:10.1007/BF03246215

A simple, clean and benign route to the synthesis of 2H-chromen-2-ones derivatives through one-pot condensation of β- ketoesters and substituted phenols in the presence of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2] octane bistetrafluoroborateis (SelectfluorF-TEDA-BF₄) as catalyst under solvent free reaction conditions was experimented. The application of ultrasonic irradiation improved the yields and reduced the reaction times. The use of selectfluor catalyst is feasible because of its stability, commercial value, easy handling, easy recovery and good activity. To extend our research, the ability of selectfluor for the synthesis of 2-aminochromene derivatives was also examined.

Full text of DOI:10.1007/BF03246215

J. Iran. Chem. Soc., Vol. 8, No. 1, March 2011, pp. 193-197.
JOURNAL OF THE
Iranian
Chemical Society
Selectfluor Promoted Environmental-Friendly Synthesis of 2H-Chromen-2-ones
Derivatives under Various Reaction Conditions
R. Ranjbar-Karimi*, S. Hashemi-Uderji and M. Mousavi
Department of Chemistry, Faculty of Science, Vali-e-Asr University, Rafsanjan, 77176 Islamic Republic of Iran
(
Received 6 March 2010, Accepted 24 June 2010)
A simple, clean and benign route to the synthesis of 2H-chromen-2-ones derivatives through one-pot condensation of β-
ketoesters and substituted phenols in the presence of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bistetrafluoro-
TM
borateis (Selectfluor F-TEDA-BF ) as catalyst under solvent free reaction conditions was experimented. The application of
4
ultrasonic irradiation improved the yields and reduced the reaction times. The use of selectfluor catalyst is feasible because of its
stability, commercial value, easy handling, easy recovery and good activity. To extend our research, the ability of selectfluor for
the synthesis of 2-aminochromene derivatives was also examined.
Keywords: Selectfluor, Solvent free, Phenol, β-Ketoesters, Chromen, Ultrasound
INTRODUCTION
CH Cl
2
N
1
-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane
+
-
(
BF )2
4
TM
N
+
bistetrafluoroborateis (Selectfluor F-TEDA-BF , Fig. 1) is
4
the most valuable reagent for electrophilic fluorination
reaction [1-4]. Recently, it has been used as a versatile
mediator or catalyst for various other functionalisations of
organic compounds. Its application for selective and effective
oxidation of alcohols [5], bromination [6], iodination [7],
nitration and thiocyanation of some organic compounds [8] is
reported.
Coumarins have attracted considerable interest because
they possess various biological activities such as antiviral [9],
antibacterial [10], antimicrobial [11], antiinflammatory [12],
anticancer [13] activity as well as inhibition of platelet
aggregation [14] and inhibition of steroid 5a-reductase [15].
Some coumarins have been used as photosensitizers [16],
fluorescent and laser dyes [17]. These compounds are also
F
Fig. 1
utilized in drug and pesticidal preparations [18]. Moreover,
these compounds can be used as fragrances, pharmaceuticals,
agrochemicals [19] and as antioxidants in lipid peroxidation
[20]. Application of coumarin derivatives for the synthesis of
some fused ring heterocyclic compounds is also reported
[21,22]. Several publications have described the preparation of
coumarin derivatives from the reaction of phenols with β-keto
esters in the presence of different catalysts such as ZrCl
ZnCl AlCl ZnCl /Al SO TBACl,
montmorillonite clay and Cu(ClO
of these methods suffer from one or more disadvantages such
4
,
,
2
,
3
,
2
2
O
3
,
H
2
4
,
P O
2
5
4
) [23-29]. However, some
2
*Corresponding author. E-mail: karimi_r110@yahoo.com

Ranjbar-Karimi et al.
OH
CN
CN
Selectfluor 10 mol%
H O-EtOH
O
R
NH2
CN
+
+
RCHO
2
R = 2,4-dichlorobenzaldehyde 93% Yield
R = 4-(dimethylamino)benzaldehyde 94% Yield
Scheme 1
as long reaction times, harsh reaction conditions, tedious
work-up procedure, use of highly flammable and expensive
reagents, formation of by-products, and low yields of the
desired products. Therefore, introduction of new methods and
catalysts for the preparation of coumarin is axiomatic.
Here, we would like to report the catalytic activity of
selectfluor reagent in the one-pot synthesis of 2H-chromen-2-
ones derivatives under stirring at room temperature or
ultrasonic irradiation conditions (Scheme 1). Also, the ability
of selectfluor for the synthesis of 2-aminochromene
derivatives is reported.
of substituted phenol (10 mmol) and metyl acetoacetate (15
mmol) and the reaction mixture was stirred at room
temperature for 80-90 min. After the completion of the
reaction (monitored by TLC), CH Cl was added after which
the reaction mixture was filtered. The solvent was evaporated
to obtain crude solid and recrystallized from ethanol to afford
pure product.
Method B. Selectfluor (10 mol%) was added to a mixture
of substituted phenol (10 mmol) and metyl acetoacetate (15
mmol) and the reaction mixture was irradiated with ultrasound
for 15-40 min. After the completion of the reaction (monitored
2
2
by TLC), CH
2
2
Cl was added following which the reaction
EXPERIMENTAL
mixture was filtered. The solvent was evaporated to obtain
crude solid and recrystallized from ethanol to afford pure
product.
Chemicals and Apparatus
All chemicals used in this research were purchased from
Merck and Aldrich Company. NMR spectra were recorded on
General Procedure for the Preparation of 2-
Aminochromene Derivatives
Selectfluor (10 mol%) was added to a mixture of
substituted aldehyde (1 mmol), malononitrile (1 mmol), α- or
1
a Bruker DRX300 spectrometer operating at 300 MHz for H
1
3
nuclei and 75 MHz for C nuclei with tetramethylsilane as the
internal standard. Mass spectra were recorded using a VG70-
SE spectrometer operating at nominal accelerating voltage of
β-naphthol (1 mmol) in H O-EtOH (10 ml, 1:1) solvent and
2
7
0 eV. Thin layer chromatography (TLC) was run on silica
the reaction mixture was stirred at room temperature for 90
min. After the completion of the reaction (monitored by TLC),
CH Cl was added and then the reaction mixture was filtered.
The solvent was evaporated to obtain crude solid and
recrystallized from ethanol to afford pure product.
percolated aluminium plates (Merck Kieselgel F254). Melting
points were determined on a Kofler hot-stage apparatus. A
multiwave ultrasonic generator (Bandlin Sonopuls Gerate-
Typ: UW 3200, Germany) equipped with a converter/
transducer and titanium oscillator (horn), 12.5 mm in
diameter, operating at 30 kHz with a maximum power output
of 780W, was used for the ultrasonic irradiation.
2
2
RESULTS AND DISCUSSION
The reaction between phenol and ethyl acetoacetate was
selected as the model reaction for optimization of various
parameters. The reaction was started with different amounts of
catalyst ranging from 5 to 30 mol% of selectfluor separately
General Procedure for the Preparation of 2H-
Chromen-2-ones Derivatives
Method A. Selectfluor (10 mol%) was added to a mixture
1
94

Selectfluor Promoted Environmental-Friendly Synthesis
(
Table 1).
The best results were obtained using 10 mol% of the
investigated. The synthesis of 4-methyl-2H-chromen-2-one
took place in the presence of 0, 5, 10, 15, 20 and 30 mol% of
selectfluor with and without ultrasound irradiation (Table 1).
In all the reactions, it was found that the use of ultrasound
radiations resulted in faster reaction and higher yields. A wide
range of substituted phenols was used to give maximum yields
(Table 2). All products have been described previously and are
fully characterized by NMR, IR and melting point by
catalyst. It was found that above and below 10 mol% of
selectfluor, the yield of the product decreased. In the absence
of the catalyst yield was found to be very low (Table 1). To
make it clean and green, the reaction was triggered under
solvent free reaction conditions.
The effect of ultrasound irradiation on this procedure was
Table 2. Effect of the Catalytic Amounts of Selectfluor with or Without Sonication for
Synthesis of 4-Methyl-2H-chromen-2-one at Room Tempratur
Entry
SF
Method A
Method B
(
mol%)
Time (min)
Yield (%)
Time (min)
Yield (%)
1
2
3
4
5
6
0
5
10
15
20
30
60
60
60
60
70
70
0
60
35
30
30
40
40
0
45
65
70
90
87
55
82
73
75
75
Table 2. Synthesis of Substituted 2H-Chromen-2-ones 3
Me
O
OH
O
O
Selectfluor
R1
+
rt, Solvent free
stiring or ))))
Me
OR2
O
R1
1
2
3
Entry
Phenol (1)
β-diketone (2)
Method A
Method B
3
3
a
Time (min)
90
Yield (%)
70
Time (min)
40
Yield (%)
82
b
OH
O
O
O
O
Me
Me
Me
OEt
HO
OH
O
3
3
c
85
80
75
80
20
15
92
95
OMe
OMe
OH
O
d
OH
OH
1
95

Ranjbar-Karimi et al.
Table 2. Continued
OH
O
O
3
e
85
79
15
94
Me
Me
OEt
HO
Me
OH
O
O
O
O
O
3
3
3
f
OH
90
73
80
83
30
25
20
90
91
92
OEt
g
h
MeO
OH
80
Me
Me
OEt
OH
O
85
OMe
MeO
EtO
3
3
i
j
OH
OH
O
O
O
O
90
80
82
30
35
90
90
Me
Me
OMe
90
OMe
EtO
R
CN
OH
CN
CN
Selectfluor 10 mol%
H O-EtOH
+
RCHO
+
2
O
NH2
R = 4-nitrobenzadehyde
92% Yilde
Scheme 2
comparison with the reported literature data.
chromenes in excellent yield (Scheme 2)
As part of our ongoing interest in the selectfluor catalyzed
reactions for various organic transformations, we examined
three-component one-pot synthesis of 2-aminochromene
derivatives by condensing malononitrile, α- or β-naphthol and
aromatic aldehydes in aqueous ethanol in the presence of
selectfluor as a heterogeneous and reusable catalyst. Treatment
of 4-(dimethylamino)benzaldehyde or 2,4-dichloro-benz-
aldehyde, malononitrile, and α-naphthol in the presence of
selectfluor in aqueous ethanol under refluxing conditions
resulted in the formation of 2-amino-2-chromene (Scheme 1).
Under similar reaction conditions, β-naphthol gave 2-amino-2-
CONCLUSIONS
Selectfluor is not only one of the most valuable reagents
for electrophilic fluorination but also can be used as a versatile
catalyst for environmental-friendly synthesis of 2H-chromen-
2-ones derivatives. Unlike some reported methods, this
method offers several noteworthy advantages including good
yields of products, easy work-up, in combination with
stability, non-toxicity, easy preparation and cheapness of the
catalyst. On the other hand, ultrasonic irradiation increased the
1
96

Selectfluor Promoted Environmental-Friendly Synthesis
catalytic activity and higher product yields were obtained.
[16] J.D. Hepworth, C.D. Gabbutt, B.M. Heron,
Comprehensive Heterocyclic Chemistry II, in: A.R.
Katritzky, C.W. Rees, E.F.V. Scriven (Eds.), Pyran and
Their Benzo Derivatives, Synthesis, Vol. 5, Pergamon
Press, 1996, p. 301.
ACKNOWLEDGEMENTS
The support of this work by Vali-e-Asr University (Grant
no. 2747) is gratefully acknowledged.
[17] G.R. Green, J.M. Evans, A.K. Vong, Comprehensive
Heterocyclic Chemistry II, in: A.R. Katritzky, C.W.
Rees, E.F.V. Scriven (Eds.), Pyran and Their Benzo
Derivatives, Synthesis, Vol. 5, Pergamon Press, 1996, p.
469.
REFERENCES
[
1] P. Kirsch (Ed.), Modern Fluoroorganic Chemistry,
Synthesis, Reactivity, Applications, Wiley, Weinheim,
[18] W.C. Meuly, Kirk-Othmer Encyclopedia of Chemical
th
2
004.
Technology, 3 ed., John Wiley & Sons, New York,
[
[
[
2] R.E. Banks, J. Fluorine Chem. 87 (1998) 1.
3] S. Rozen, Chem. Rev. 96 (1996) 1717.
4] R.P. Singh, J.M. Shreeve, Acc. Chem. Res. 37 (2004)
1979, p. 196.
[19] R. O’Kennedy, R.D. Thornes, Coumarins: Biology,
Applications and Mode of Action, Wiley & Sons,
Chichester, 1997.
[20] H.G. Raj, V.S. Parmar, S.C. Jain, S. Goel, H. Poonam,
S. Malhorta, A. Singh, C.E. Olsen, J. Wengel, Bioorg.
Med. Chem. 6 (1998) 2205.
3
1.
5] M. Zupan, J. Iskra, S. Stavber, Bull. Chem. Soc. Jpn. 68
1995) 1655.
[
(
[
[
6] C. Ye, J.M. Shreeve, J. Org. Chem. 69 (2004) 8561.
7] S. Stavber, M. Jereb, M. Zupan, Tetrahedron 59 (2003)
[21] V.S. Moskvina, V.P. Khilya, O.V. Turov, U.M. Groth,
Synthesis 8 (2009) 1279.
5
935.
[
[
8] R.G. Syvret, K.M. Butt, T.P. Nguyen, V.L. Bulleck,
R.D. Rieth, J. Org. Chem. 67 (2002) 4487.
9] D.E. Zembower, S. Liao, M.T. Flavin, Z.Q. Xu, T.L.
Stup, R.W. Buckheit, A. Khilevich, A.A. Mar, A.K.
Sheinkman, J. Med. Chem. 40 (1997) 1005.
10] A. Maxwell, Mol. Microbiol. 9 (1993) 681.
11] J.A. Maroliwala, B. Naik, K.R. Desai, Indian J.
Heterocycl Chem. 17 (2008) 363.
[22] J.F. Zhou, G.X. Gong, K.B. Shi, Y.L. Zhu, Monath.
Chem. 140 (2009) 651.
[23] H.V. Pechmann, C. Duisberg, Ber. Dtsch. Chem. Ges.
16 (1883) 2119.
[24] J.E.T. Corrie, J. Chem., Soc. Perkin Trans. I 7 (1990)
2151.
[25] A. Shockravi, M.M. Heravi, H. Valizadeh, Phosphor.
Sulphur 178 (2003) 2314.
[
[
[
[
[
[
12] P. Ronad, S. Dharbamalla, R. Hunshal, V. Maddi,
Archiv der Pharmazie 341 (2008) 696
13] C.J. Wang, Y.J. Hsieh, C.Y. Chu, Y.L. Lin, T.H. Tseng,
Cancer Lett. 183 (2002) 163.
14] G. Cravotto, G.M. Nano, G. Palmisano, S. Tagliapietra,
Tetrahedron: Asymmetry 12 (2001) 707.
15] G.J. Fan, W. Mar, M.K. Park, E.W. Choi, K. Kim, S.
Kim, Bioorg. Med. Chem. Lett. 11 (2001) 236.
[26] G. Smitha, C. Sanjeeva Reddy, Synth. Commun. 34
(2004) 3997.
[27] S. Setha, R. Phadke, Organic Reactions, Vol. 7, Wiley &
Sons, New York, 1953, pp. 1-58.
[28] T.S. Li, Z.H. Zhang, F. Yang, C.G. Fu, J. Chem. Res.
(S) 1 (1998) 38.
[29] S. Puri, B. Kaur, A. Parmar, H. Kumar, Ultrason.
Sonochem. 16 (2009) 705.
1
97