Synthesis of Tetrahydrobenzo[b]pyran Derivatives Using H
2WO
4/ Fe
3O
4Magnetic Nanocatalyst
Forough. Sepehr
1, Sadegh. Allameh
2*, Abolghasem. Davoodnia
31
M.Sc,
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran.2,3
PhD,
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran.E- mail: [email protected]
*Corresponding Author
ABSTRACT
Nowaday, the application of environmentally friendly catalysts has been interested in the synthesis of many heterocyclic compounds. Using these catalysts, reactions can be performed in a very short time and satisfactory efficiency. In addition, there are fewer recovery, separation and environmental problems in these catalysts. In this study, a number of tetrahydrobenzo[b]pyran derivatives with antifungal, antibacterial properties, etc have been synthesized using aromatic aldehydes, malononitrile and dimedone in the presence of H2WO4/ Fe3O4 magetic catalyst.
ArCHO
O O
H2WO4/Fe3O4
H2O +
O O
CN
NH2 Ar
CN CN
+
. Figure 1
Keywords
Dimedone, Malononitrile, Tetrahydrobenzo[b]pyran, H2WO4/ Fe3O4
Introduction
Catalysts are the keys to chemical modifications, most industrial syntheses and almost all biological reactions require catalysts. During the last decades, an increasing interest has been paid to the application of heterogeneous reusable catalysts in organic synthesis owing their easy work-up, easy filtration and minimization of cost and waste generation [1].
Despite the importance of catalysts in the synthesis of various materials in industry and the laboratory, the mechanism of many catalytic reactions is still not known and most researchers have reached a suitable catalyst through trial and error. The catalyst awakens the dormant affinity of the reactant, but can not be effective in impossible reactions. The presence of a catalyst in an equilibrium reaction does not change the equilibrium constant, but increases the rate of equilibrium[2].
Catalysts can be in the form of ions, atoms, molecules or larger sets. Catalysts are divided into homogeneous, heterogeneous, and enzymatic according to their function, but nanocatalysts should also be considered as a separate group [3].
In chemistry, reactions with more than two starting materials in a container are called Multi Component Reactions (MCRs). Multi component reactions allow the creation of several bonds in a single operation and are known as an efficient and powerful tool for the synthesis of complex organic molecules. Also, this manner is very fast and impressive without the isolation of any intermediate. Multi component reactions have emerged as valuable tools for the preparation of structurally diverse chemical libraries of drug-like heterocyclic compounds.
Water is one of the greenest solvents in terms of price, availability, safety and environmental damage, but due to the low solubility of most organic compounds in water and the high reactivity of water with some organic metal compounds, use of water as a solvent before 1980s were limited to hydrolysis reactions only. Chemical conversions in aqueous solvents are not new to organic chemists and have attracted their attention for many years. At present, most multi component reactions are performed either solvent-free or in aqueous medium. The occurrence of multicomponent
reactions in nature is so common that some believe that the adenine molecule is produced from the concentration of five moles of hydrogen cyanide that was once abundant in the Earth's atmosphere [4].
Pyran is six-membered heterocycles consisting of one oxygen atom. These heterocycles can be divided into 3 main categories; Pyrilium salts, 2H-pyrane and 4H-pyran [5].
Pyran derivatives are interested increasingly because of the wide role in biological activities [6]. These compounds are abundant in nature [7]. Benzo[b]pyran is an important group of derivatives of pyran, many of which in nature are the basic substance of color and odor of plant species [8,9]. According to some reports, pyran derivatives have antimicrobial activities [10], growth stimulating [11], antifungal [12], antitumor activities [13], Hypotensive effects [14] Platelet antiaggregating, local anaesthetic [15-17] and Anti depressant effects [18]. Due to the importance of pyran in terms of chemical and medicinal properties, their synthesis and study have been of great importance.
Experimental
The reagents and solvents used in this study were purchased from Floca Switzerland and Merck Germany and used without further modification and purification. Melting points were recorded on a Stuart SMP3 melting point apparatus.
IR spectra were recorded on a Tensor 27 Bruker spectrophotometer using KBr disks. The 1HNMR spectra were obtained on Bruker 300 spectrometer using TMS as an internal standard. All products were known by spectral data and comparision of their melting points with those of authentic sample.
Preparation of H2WO4/Fe3O4 Magnetic Nanocatalyst
One of the important points in the synthesis of nanocatalysts is the correct weighting of the initial powders. To prepare the nanocatalyst, a mixture of FeCl2.4H2O(1.58 g), deionized distilled water (30 ml), NH4OH(25%, 10 ml) stirred vigorously for 15 minutes at room temperature. Then 100 ml of Ca(NO3)2.4H2O (0.5M), (NH4)2HPO4 (3M) with pH=11 and added to the previous solution. The resulting milky solution was heated at 90°C for 2 hours. The dark brown precipitate washed with deionized distilled water and first dried at room temperature and then the sample was dried at 300 °C for 3 hours. Then, Fe2O3 (1 g) and H2WO4 (2 g) were added slowly to the powder obtained from the previous steps at room temperature and stirring vigorously for 6 hours. The resulting nanoparticles were separated by an external magnet and washed with diethyl ether and dried at room temperature.
Optimization of Synthesis Conditions
Initially, in order to optimize the reaction conditions, a mixture of benzaldehyde (1 mmol), malononitrile (1 mmol) and dimedone (1 mmol) was selected as the model reaction and the best results were obtained under solvent-free conditions at 110°C in the presence of H2WO4/ Fe3O4 (0.5 g) magnetic nanocatalysts. After optimizing the reaction conditions, the synthesis of different tetrahydrobenzo[b]pyran derivatives under optimal conditions was investigated.
General procedure for synthesis of tetrahydrobenzo[b]pyrans
To prepare tetrahydrobenzo[b]pyran by a simple three-component reaction a mixture of an aromatic aldehyde 1 a-g (1 mmol), dimedone (1 mmol), malononitrile (1 mmol) in the presence of H2WO4/Fe3O4 catalyst (0.05 g) was stirred in an oil bath at 110°C for 15-35 min under solvent- free conditions. The reaction was monitored using thin- layer chromatography (TLC). After completion the reaction, the mixture cooled to room temperature and the precipitate was recrystallized from ethanol to obtain the product.
ArCHO
O O
H2WO4/Fe3O4 +
O
CN Ar
CN +
1e Ar = 4-OH-C6H4 4e Ar = 4-OH-C6H4
1f Ar = 3-NO2-C6H4 4f Ar = 3-NO2-C6H4
1g Ar = C6H5 4g Ar = C6H5
Since the catalyst is insoluble in ethanol, the reaction mixture was crystallized by ethanol. After a simple filtering, the catalyst remained on filter paper. The catalyst is dried in a vacuum oven and can be reused in model reaction. The results of the first and subsequent experiments were almost consistent in yields (82, 80 and 77%).
Results
Proposed Mechanism
Ar H
O
C
C N
N
+ -H2O
H
Ar
CN
C N
+
O O
O O4WH2
O Ar O
CN
O NH
O Ar
CN
NH2
(I)
H2WO4
H
Figure 3
According to the proposed mechanism, the aldehyde is first activated by the H2WO4 (tungstic acid) and ready for nucleophilic attack by malonontitrile and creation an intermediate I molecule which then reacts with the catalyst- activated dimedone, and finally reacts by transferring hydrogen from the carbon to the nitrogen atom of the product.
Spectral data of tetrahydrobenzo[b]pyran derivatives
O O
CN
NH2 Me
Figure 4 2-amino-3-cyano-4-(4-methylphenyl)-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran
1H-NMR (300 MHZ, CDCl3) δ: 1.07 (S, 3H, CH3), 1.14 (S, 3H, CH3), 2.24 (d, 2H, CH2), 2.32 (S, 3H, CH3), 2.48 (S, 2H, CH2), 4.39 (S, 1H, CH), 4.54 (S, 2H, NH2), 7.10- 7.16 (M, 4H, arom-H) ppm.
IR (KBr disk) ν: 3383, 3320 (N-H), 2193 (CN), 1654 (C=O), 1512, 1606 (C=C) cm-1.
O O
CN
NH2 OMe
Figure 5 2-amino-3-cyano-4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran
1H-NMR (300 MHZ, CDCl3) δ: 1.06 (S, 3H, CH3), 1.13 (S, 3H, CH3), 2.24 (d, 2H, CH2), 2.46 (S, 2H, CH2), 3.79 (S, 3H, OMe), 4.38 (S, 1H, CH), 4.58 (S, 2H, NH2), 6.38-7.19 (m, 4H, arom-H) ppm.
IR (KBr disk) ν: 3375, 3319 (N-H), 2192 (CN), 1655(C=O), 1509, 1606 (C=C) cm-1.
O O
CN
NH2 NO2
Figure 6 2-amino-3-cyano-4-(4-nitrophenyl)-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran IR (KBr disk) ν: 3333 (N-H), 2193 (CN), 1663 (C=O), 1599 (C=C), 1347, 1519 (C=C) cm-1.
O O
CN
NH2 Cl
Figure 7 2-amino-3-cyano-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran
O O
CN
NH2
OH
Figure 8 2-amino-3-cyano-4-(4-hydroxyphenyl)-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran IR (KBr disk) ν: 3282 (OH), 225 (CN), 1655 (C=O), 1446,1511 (C=C) cm-1.
O O
CN
NH2 NO2
Figure 9 2-amino-3-cyano-4-(3-nitrophenyl)-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran IR (KBr disk) ν: 3428 (N-H), 2194 (CN), 1665 (C=O), 1530, 1599 (C=C) cm-1.
O O
CN
NH2
Figure 10 2-amino-3-cyano-4-(phenyl)-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran IR (KBr disk) ν: 3395, 3324 (N-H), 2198 (CN), 1660 (C=O), 1606 (C=C) cm-1 (Table 1).
Table 1: Melting point, time and yield of tetrahydrobenzo[b]pyrans
Row Ar Time(Min) Yield)%( Determined
Melting Point (°C)
Reported Melting Point [19] (°C)
1 4-MeC6H4 35 85 215-218 218-224
2 4-OMeC6H4 25 85 204-205 200-202
3 4-NO2C6H4 20 83 180-182 169-171
4 4-ClC6H4 30 80 217-219 216-219
5 4-OHC6H4 25 93 216-218 212-215
6 3-NO2C6H4 15 90 210-212 200-204
7 C6H4 25 85 236-238 234-238
Conclusion
In conclusion, a simple and convenient method for the synthesis of benzo[b]pyran derivatives using magnetic nanocatalyst H2WO4/ Fe3O4, was reported. The catalyst showed high catalytic activity in the synthesis of tetrahydrobenzo[b]pyrans. Some attractive features of this method are high yields, short reaction times and recyclability and reusability of the catalyst.
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