International Journal of ChemTech Research CODEN( USA): IJCRGG ISSN : 0974-4290 Vol.1, No.3 , pp 539-543, July-Sept 2009
I2-Al2O3: A suitable heterogeneous catalyst for the synthesis of flavones under microwave irradiation Swapnil R. Sarda1, Wamanrao N. Jadhav2 and Rajendra P. Pawar3*
1
Department of Chemistry, J. E. S. College, Jalna-431 203,(MS), India. 2 Organic Chemistry Synthesis Laboratory, Dnyanopasak College, Parbhani-431 401, (MS), India. 3 Department of Chemistry, Deogiri College, Aurangabad-431 005.(MS) India. *E-mail:
[email protected] Abstract: A simple method for the synthesis of flavones is reported using heterogeneous catalyst molecular iodine loaded neutral alumina under microwave irradiations. Key Words: Chalcones, flavones, molecular iodine, microwave irradiations etc.
Graphical abstract OH
OH Al2O3/NaOH +
ArCHO
R
MW
Ar R O
O 1(a-h)
3(a-h)
2(a-h) I2-Al2O3
MW
O
Ar
R O
4(a-h) R 4a =2-OH 4b =2-OH 4c =2-OH 4d =2-OH 4e =2-OH 4f ==2-OH 4g =2-OH 4h =2-OH,3-CH3
(Scheme-1)
Ar 4-Cl 4-OCH 3 4-CH3 Ar 4,5-OCH 3 4-NO 2 Furan ring Ar
Rajendra P. Pawar et al /Int.J. ChemTech Res.2009,1(3)
Introduction Environmental pressure to reduce waste and reuse materials has driven studies into ‘Green’ chemistry. Chemical and pharmaceutical industries are always under pressure to develop more environmentally friendly organic reaction methodologies using nonhazardous catalysis. Microwave irradiation is used for a variety of organic reactions due to short reaction time, cleaner reactions, easier work-up and better yield. Thus the microwave oven procedure is now well established in MORE chemistry [1]. More recently, the emphasis has shifted in favour of microwaves-assisted methods under solvent-free conditions, providing an opportunity to work in open vessels, thus avoiding the risk of the development of high pressure. Inorganic solid support organic transformations are gaining much attention due to simplified product isolation, mild reaction conditions, high selectivity etc. Solvent free microwave assisted chemical reactions in combination of solid supported reagents, were used to carry out a wide range of reaction in shorter time as compare to other conventional reaction methods [2]. The use of solvent free conditions with heterogeneous catalysts represents one of the more powerful green chemical procedures [3], Alumina is a particularly interesting metal oxide widely used industrially as filler, adsorbent, drying agent, catalyst, solid support and reagent [4]. In the continuation of our work [5-6] herein, we describe a simple and convenient method for the synthesis flavones using I2-Al2O3 catalyst under microwave irradiation in excellent yields. (Scheme-1) Inexpensive and nontoxic molecular iodine has received considerable attention in organic transformations, affording the corresponding products in excellent yields with high selectivity. I2-Al2O3 catalyzed synthesis of dihydropyrimidine under microwave irradiation has been recently reported [7]. The mild lewis acidity associated with iodine enhanced its usage in organic synthesis using stoichiometric levels to catalytic amounts. Owing to numerous advantages associated with this eco-friendly element, iodine has been explored as a powerful catalyst for various organic transformations [8], such as synthesis of benzothiophenes, bis-indoles, deprotection of acetals, transesterification, Michael addition, β-ketoenol ethers and multicomponent dihydropyrimidinone synthesis. Recently, we reported the use of iodine for the synthesis of tetrahydrobenzo [b] pyrans and imidazole [9]. Chalcones and its derivatives display many biological activities [10] and used as on starting materials in the synthesis of various heterocyclic compounds [11]. Flavones occupy a special place in the realm of natural and synthetic organic chemistry owing to their useful biological activities such as anti-inflammatory and antioxidant. Substituted flavones like amino flavones have been studied as tyrosine kinaes inhibitors and as antimitotic agents [12].
540 Various methods have been reported for the synthesis of flavones, includes Baker-Venkatraman rearrangement [13], HTIB (Koser’s reagent), FeCl3 [14], SeO2 [15], DMSO-I2 [16], Br2/CHCl3, NaOAc/AcOH, EtOH/HCl, clay [17], H2SO4, Palladium-Thiourea [18], Wells-Dawson heteropolyacid [19] had been reported. Recently we synthesized flavones by using EAN ionic liquid [5] under microwave irradiation and [bmim]BF4 ionic liquid at 100 OC temperature [6].
Experimental Materials and methods
Melting points were measured in open glass capillaries on a Perfit Electrothermal melting-point apparatus and are uncorrected. 1H NMR and 13C NMR spectra were recorded at room temperature on a 300 MHz. Varian Inova Spectrometer in CDCl3 using TMS as internal standard. A Samsung domestic microwave oven was used at 400W power level for all the experiments. The reactions were monitored by TLC using pre-coated plates (Merck). Column chromatography was performed using Acme silica gel (100–200 mesh). All reagents were obtained from commercial sources and used without further purification. Solvents for chromatography were distilled before use. The products were also characterized by comparison of their melting point with literature values. Synthesis of heterogeneous catalyst I2-Al2O3: Dissolve 2.538 g (10 mmol) iodine in minimum quantity of solvent dichloro methane. Adsorb this iodine solution on 25 g neutral alumina and stirred with glass rod. The mixture was air dried and stored in glass bottle until use. Synthesis of 1-phenyl-3-(4-chlorophenyl)-prop-2-en-1one Mixtures of 2-Hydroxy acetophenone (1mmol, 0.136 g, 1a) 4-chlorobenzaldehyde (1mmol, 0.140 g, 2a) and sodium hydroxide (2mmol, 0.08 g) were dissolved in minimum quantity of dichloromethane (2 mL). The solution was adsorbed on neutral alumina (1.5 g), airdried and irradiate in a microwave oven (400W) for appropriate time (4 to 5 min). After completion of reaction as monitored by TLC, the mixture was cooled, diluted with ethanol and filtered to separate insoluble Al2O3. The filtrate was poured on crushed ice and neutralized with dilute HCl. The isolated crude was purified by column chromatography using n-hexane: acetone (7:1) eluent to afford pure 1-phenyl-3-(4chlorophenyl)-prop-2-en-1-one (3a). The products were identified by comparison with standard physical and spectral data given in the literature (Table-1). Synthesis (4a)
of
2-(4-chlorophenyl)-4H-chromen-4-one
Rajendra P. Pawar et al /Int.J. ChemTech Res.2009,1(3) A mixture of 1-phenyl-3-(4-chlorophenyl)-prop2-en-1-one (1mmol, 0.258 g, 1a) and 0.25 g of I2-Al2O3 catalyst was irradiated in a microwave oven (400W) for appropriate time (3 to 5 min). After completion of reaction as monitored by TLC, the mixture was cooled, diluted with ethyl acetate and filtered to separate insoluble Al2O3. The filtrate was washed with a dilute solution of sodium thiosulfate to remove iodine and subsequently with water. After evaporation of ethyl acetate, the crude was purified by column chromatography hexane: ethyl acetate (9:1) eluent to afford pure 2-(4-chlorophenyl)-4H-chromen-4-one (4a). The products obtained were characterized by comparison of IR, 1H NMR and melting point with literature values (Table-1).
541 Spectral Analysis 2-(4-chlorophenyl)-4H-chromen-4-one (4a): 1H NMR (300 MHz, CDCl3) δ: 6.79 (s, 1H, pyrone ring), 7.05 (2H, dd, J=2.6 and 7.6 Hz, Ar-H), 7.32-7.48 (4H, m , Ar-H), 7.54 (2H, dd, J=7.8 and 2.6 Hz, Ar-H). 2-(4-methylphenyl)-4H-chromen-4-one (4b): 1H NMR (300 MHz, CDCl3) δ: 2.41 (3H, s, Ar-CH3), 6.61 (s, 1H, pyrone ring), 6.95 (2H, dd, J=2.6 and 7.6 Hz, Ar-H), 7.17-7.22 (4H, m , Ar-H), 7.48 (2H, dd, J=7.8 and 2.6 Hz, Ar-H). 2-(4-methoxylphenyl)-4H-chromen-4-one (4b): 1H NMR (300 MHz, CDCl3) δ: 3.85 (3H, s, Ar-OCH3), 6.76 (s, 1H, pyrone ring), 7.12 (2H, dd, J=2.6 and 7.6 Hz, ArH), 7.17-7.42 (4H, m , Ar-H), 7.48 (2H, dd, J=7.8 and 2.6 Hz, Ar-H).
Table-1: I2-Al2O3 catalyzed novel synthesis of flavones under microwave irradiation Entry
Chalcone (3a–h)
OH
a
Product (4a–h)
Cl
Cl O
O
Yield (%)a
M. P. (0C)b
4
90
187-188 (185-187)5
4.5
85
155-156 (155-156)5
4
88
78-80 (108-109)17
3.5
92
100 (97-98)19
5
80
160-162 (154)5
5
85
276-278 (277)5
3.5
90
130-132 (134-135)19
4
85
126-128 (122-124)19
O
OH
b
Time (min.)
OCH3
OCH3 O
O O
OH
c
O O
O
OH
d
O
O
O
OH
e
OCH3
O
OCH3 OCH3
OCH3
O
O
NO2
OH
f
NO 2
O
O
O
O
g
Cl
OH
O
h
OH
O Cl
O
O O
O
a
O
Isolated yield b Reported melting points
Rajendra P. Pawar et al /Int.J. ChemTech Res.2009,1(3)
Results and Discussion Synthesis of flavones using the heterogeneous catalyst I2-Al2O3 under microwave irradiation has been reported. Excellent yield was obtained in shorter reaction time (Scheme-1). As these reactions were carried out under microwave irradiation, it reduces the cost and time period of reaction. α-β-unsaturated carbonyl compounds were prepared by well-known Claisen-Schimdt condensation process using NaOH-Al2O3 under microwave irradiation. Most of the reaction was completed within 3-4 minutes giving 90-95% yield of products. For a synthesis of flavones, the 2-hydroxy chalcone and I2-Al2O3 was irradiated in a microwave oven for a specified time. After completion of reaction as monitored by TLC, aqueous work-up afforded pure flavones. Synthesis of flavones using molecular iodine catalyst was completed within 5-to7 min by dehydrogenative cyclisation of 2-hydroxy chalcone, afforded 80 to 95 % flavones (Table-1). However, in absence of iodine the reaction does not proceed even after long time (30 minutes). It indicates that the oxidation of 2-hydroxy chalcone into flavones is only due to molecular iodine and not because of air O2. The reactions can be faster, the reaching substantial completion in several minutes compared to hours in organic solvents. The result showed that efficiency and yield of the reaction is high as compared to other conventional methods. The use of 10-mol % of the catalyst was sufficient to promote the reaction; higher amount of the catalyst did not improve the yield of product. The reaction proceeds cleanly at 400 W and no undesirable side product were observed. At higher power level
542 decrease in yield were found due to product decomposition. Yields of all isolated product after purification found to be excellent as compare to the previously reported methods (Table-2). This method offers advantage in terms of simple procedure and workup, mild reaction condition and excellent yields. The 1HNMR spectra of flavones showed a singlet at 6.55-6.8 due to 1H of 3H i.e. pyrone ring, it is the characteristic singlet for flavones. The multiple at 7.1-7.9 is due to aromatic protons. Such observed 1 HNMR data and complete absence of a peak near 13 due to orthohydroxy group is in agreement with oxidation of chalcone in to flavones. Flavones do not give violet coloration with FeCl3 solution and pink coloration with conc. H2SO4 and Wilson test was negative.
Conclusions
In conclusion, we describe an efficient protocol for the dehydrogenativ cyclisation of 2-hydroxy chalcone to flavones in the presence I2-Al2O3 under microwave irradiation. Shorter reaction time, simple reaction conditions, and higher yield render this method superior.
Acknowledgements
The authors are thankful to the Principal Dr. P. L. More, Dnyanopasak College, Parbhani, and Principal Dr. R. S. Agrawal, J. E. S. College, Jalna, for encouragement during the process of carrying out this work. The authors are also thankful to University Grant Commission for funding under Minor Research Project to one of the author.
Table-2: synthesis of 1-(2-hydroxyphenyl)-3-p-tolylprop-2-en-1-one (4a) catalyzed by iodine under different condition Entry
Catalyst
1 I2 2 I2 3 I2 4 I2 5 Al2O3- I2 6 Al2O3- I2 a Isolated yield b Reported method
Solvent DMSO DMSO DMF Solvent free Solvent free Solvent free
Reaction conditionb Reflux18 MW19 Reflux MW 80 OC MW
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Time 5 hr. 10 min. 9 hr. 14 min. 7 hr. 4 min.
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