Synthetic Communicationsw, 36: 2543–2548, 2006 Copyright # Taylor & Francis Group, LLC ISSN 0039-7911 print/1532-2432 online DOI: 10.1080/00397910600781448
Facile and Efficient One-Pot Protocol for the Synthesis of Benzoxazole and Benzothiazole Derivatives using Molecular Iodine as Catalyst Firouz Matloubi Moghaddam, Ghasem Rezanejade Bardajee, Hossein Ismaili, and Seyedeh Maryam Dokht Taimoory Department of Chemistry, Sharif University of Technology, Tehran, Iran
Abstract: Rapid and efficient condensation reactions of 2-aminothiophenol and 2-aminophenol with various aldehydes were carried out using I2 in solvent-free conditions with or without microwave irradiation to afford the corresponding 2-substituted benzothiazole and benzoxazole derivatives in good to excellent yields. Keywords: Aldehydes, benzothiazole, benzoxazole, iodine, microwave, solvent free
Benzothiazoles and benzoxazoles are very important group of heterocyclic compounds that have many applications in both pharmaceutical and industrial research. They are widely found in bioorganic and medicinal chemistry with applications in drug discovery such as antitumour, anticonvulsant, and antiviral applications.[1 – 3] They have also found applications in industry as antioxidants, vulcanization accelerators, and as a dopant in a light-emitting organic electroluminescent device.[4,5] There are a few methods for the synthesis of title compounds. The important ones include the reaction of 2-aminothiophenol or 2-aminophenol with the substituted carboxylic acids or its derivatives in presence of polyphosphoric acid,[6] polyphosphate ester,[7] a mixture of methanesulfonic acid and phosphorous pentoxide,[8] or an ionic liquid;[9] palladium-catalyzed direct coupling of benzothiazoles or Received in Poland December 16, 2005 Address correspondence to Firouz Matloubi Moghaddam, Department of Chemistry, Sharif University of Technology, PO Box 11365-9516, Tehran, Iran. E-mail:
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benzoxazoles with aryl bromides;[10] reaction of copper(I) thiobenzoat and 2-iodoanilines;[11] palladium-catalyzed condensation of aryl halides whti 2-aminothiophenol or 2-aminophenol followed by dehydrative cyclization;[12] palladium-catalyzed cyclization of 2-bromophenylthioformamides;[13] and oxidative cyclization of phenolic Schiff bases using various oxidants such as [14a – d] PhI(OAc)2, Mn(OAc)3, ThþClO2 Microwave-assisted 4 , and Pb(OAc)4. reactions in solvent or solvent-free conditions have gained popularity because of rapid reaction rate, cleaner reactions, and ease of manipulation.[15] Recently, some methods use microwave heating for the synthesis of 2substituted benzothiazoles or benzoxazoles, such as condensation of aromatic or aliphatic aldehydes with 2-aminothiophenol on SiO2,[16] aromatic aldehydes with 2-aminothiophenol in the presence of nitrobenzene/SiO2 or nitrobenzene/montmorillonite K10,[17] carboxylic acids,[18] or acid chlorides[19] with 2-aminophenol. Molecular iodine has received considerable attention in organic synthesis as an inexpensive and easily available catalyst for effecting various organic transformations.[20a,b] We now report the synthesis of 2-substituted-benzothiazoles and benzoxazoles by condensation of 2-aminothiophenol and 2-aminophenol respectively with various aromatic aldehydes using molecular iodine as an efficient catalyst under solvent-free conditions with or without microwave irradiation in relatively short time, (Scheme 1 and Table 1). Our investigations showed that 2-aminothiophenol reacts smoothly with aromatic aldehydes in the presence of molecular iodine as a catalyst at room temperature and in solvent-free conditions at relatively short times, whereas the reaction of 2-aminophenol with aromatic aldehydes requires more vigorous conditions and is efficiently promoted with solvent-free microwave irradiation processes. The corresponding 2-substituted-benzothiazoles and benzoxazoles were obtained in high to excellent yields (Table 1). At first we focused on the reaction of 2-aminothiophenol and aromatic aldehydes. In a typical procedure, 2-aminothiophenol (1 mmol) with benzaldehyde (1 mmol) in the presence of a catalytic amount of molecular iodine (0.5 mmol) at room temperature afforded the desired 2-phenyl-benzothiazole in 92% yield (Entry 9, Table 1). The reaction then was applied to a variety of aromatic aldehydes (Scheme 1 and Table 1). Most of these reactions proceeded in relatively short times, and pure products were obtained by recrystallization or preparative thin layer chromatography (PTLC).
Scheme 1.
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Table 1. Synthesis of 2-substitued-benzoxazole and benzothiazoles catalyzed by molecular iodine under solvent-free condition with or without microwave irradiation Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Ar
T (min)
Yield (%)a
C6H5 4-CH3OC6H4 2-HOC6H4 4-BrC6H4 2-ClC6H4 4-ClC6H4 4-CH3C6H4 C6H5 C6H5 4-CH3OC6H4 2-HOC6H4 4-BrC6H4 2-ClC6H4 4-ClC6H4 4-CH3C6H4 C6H5
3b 4b 3b 3b 3b 3b 3b 4d 10c 20c 15c 10c 15c 10c 20c 10c
92 65 82 93 85 95 71 91 92 73 80 93 84 92 76 89
Mp/(lit.) (8C) (102)[14a] (101)[14a] (120– 121)[21] (154– 155)[22] (125.5)[23] (147)[14a] (113– 114)[14a] — 112– 113 (113) [16] 124– 125 (119– 121)[16] 128– 130 (127– 128)[16] 132 (132– 133)[24] 82 – 83 (84 – 85)[16] 120– 122 (119– 121)[16] 87 – 88 (85)[16] — 102– 104 103– 105 119– 121 156– 157 128– 129 147– 149 115– 116
a
All yields refer to isolated products, and the products were characterized by mp, IR, and1H NMR, and their physical data were similar to those reported in the literature. b The reaction was carried out using 2-aminophenol under microwave irradiation. c The reaction was carried out using 2-aminothiophenol at room temperature. d The reaction could also proceed without catalyst.[18,19]
Electron-donating substituents on the aromatic ring of aldehyde decrease the yield and increase the time of the reaction (Entries 10 and 15, Table 1). The substituents on the ortho position act in the same manner as electron-donating substituents (Entry 13, Table 1), whereas electron-donating ortho-substituents increase the yield (Entry 11, Table 1). We also prepared 2-substituted benzoxazoles under microwave-assisted, solvent-free conditions by the reaction of 2-aminophenol and aromatic aldehydes. The behavior of these reactions is similar to the reactions of 2-aminothiophenol and aldehydes (Entries 1– 8, Table 1). Also, the reaction of benzoic anhydride with 2-aminothiophenol or 2-aminophenol was investigated. 2-aminothiophenol reacts very efficiently with benzoic anhydride in the presence of molecular iodine at room temperature. The reactivity of 2-aminophenol is less than 2-aminothiophenol, and its reaction with benzoic anhydride promoted efficiently in microwave-assisted, solvent-free condition with I2 as a catalyst (Entries 8 and 16, Table 1). In conclusion, molecular iodine was found to be a mild and effective catalyst for the one-pot reactions of 2-aminothiophenol and 2-aminophenol with aromatic aldehydes to afford 2-substitued benzothiazole and benzoxazole derivatives in excellent yields. The use of this inexpensive and easily available
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catalyst under essentially neutral reaction and workup conditions and the cleaner reaction make this protocol practical and economically attractive. With regards to lower reactivity of 2-aminophenol relative to 2-aminothiophenol, the use of microwave irradiation introduced a new method for the synthesis of 2-substitued-benzoxazoles with a very safe, efficient, and cheap catalyst.
EXPERIMENTAL The compounds all gave satisfactory spectroscopic data. IR spectra were taken as thin films for liquid compounds and as KBr pellets for solids on a Nicolet spectrometer (Magna 550). A Bruker (DRX-500 Avance) NMR was used to record the 1H NMR spectra. All NMR spectra were determined in CDCl3 at ambient temperature. The microwave oven used for this work was ETHOSMR (800 W, 1308C) at 2450 MHz. Melting points were determined on a Buchi B540 apparatus.
General Procedure for the Synthesis of 2-Substitued Benzothiazole Compounds in Solvent-free Condition A mixture of 2-aminothiophenol (1 mmol), aromatic aldehyde (1 mmol), and a catalytic amount of molecular iodine (0.5 mmol) was stirred at room temperature for an appropriate time (see Table 1) as required for completion of the reaction, which was monitored by thin layer chromatography (TLC). The mixture was chromatographed over silica gel or PTLC using petroleum ether – ethyl acetate (4:1) to afford the pure product.
General Procedure for the Synthesis of 2-Substitued Benzoxazole Compounds in Microwave-Assisted, Solvent-Free Condition A mixture of 2-aminophenol (1 mmol), aromatic aldehyde (1 mmol), and catalytic amount of molecular iodine (0.5 mmol) was placed in a Teflonw flask (20 mL) and subjected to microwave irradiation for appropriate time (see Table 1). The reaction mixture was chromatographed over silica gel or PTLC using petroleum ether– ethyl acetate (4:1) to afford the pure product.
ACKNOWLEDGMENT We acknowledge the Islamic Development Bank (IDB) for granting the loan in 1993 for purchasing a 500-MHz Bruker NMR spectrometer.
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