Organic Chemistry InternationalVolume 2012 (2012), Article ID 208948, 4 pagesdoi:10.1155/2012/208948

Research Article

Triton-B-Catalyzed, Efficient, Solvent-Free Synthesis of Benzopyrans

Devdutt Chaturvedi,¹ Amit K. Chaturvedi,² Nisha Mishra,² and Virendra Mishra²

¹Laboratory of Medicinal Chemistry, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Campus, Lucknow 226010, India²Synthetic Research Laboratory, Department of Chemistry, B. S. A. College, Mathura 281004, India

Received 5 June 2012; Accepted 16 August 2012

Academic Editor: William N. Setzer

Copyright © 2012 Devdutt Chaturvedi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

A convenient and microwave-promoted novel protocol for the syntheses of diverse kinds of substituted benzopyrans from the corresponding variety of substituted hydroxy acetophenones and keto compounds using benzyltrimethylammonium hydroxide (Triton-B) under solvent-free conditions has been developed. This protocol is mild and efficient than the other reported methods.

1. Introduction

2-H-1-benzopyrans, commonly known as 2H-benzopyrans or 2H-chromenes, are an important structural motif present in the varieties of biologically active natural, synthetic drugs, and lead molecules [1, 2]. Interesting chemistry have been exploited to this structural unit for generating diverse series of compounds, which have displayed a wide spectrum of potential biological activities such as anticancer [3, 4], antidiabetic [5, 6], anti-HIV [7], antiinflammatory [8], antimicrobial [9], antibacterial [10], antiarrhythmic [11], and antiestrogenic [12]. Moreover, their use in the synthesis of various kinds of dyes [13] and agrochemicals [14] is well known. Their major use in the development of diverse kinds of potassium channel openers has made further interest for benzopyran chemistry [15]. Furthermore, benzopyran unit has been further explored, as a useful synthon for the generation of diverse kinds of pharmaceutically important complex heterocycles of natural as well as synthetic molecules [16]. Traditional syntheses of substituted benzopyrans involve the reaction of substituted hydroxyl acetophenones with keto compounds using variety of strong bases [17]. Recently, their synthesis has been further achieved through different kinds of starting materials using variety of metallic and nonmetallic basic catalysts either by intramolecular cyclo-addition reactions [18, 19] or by condensation reactions [20–22] from the variety of the starting substrates. Furthermore, their solid phase syntheses using various kinds of metallic system were also reported recently [23]. Most of these methods suffer from the limitations such as long-reaction times, use of expensive strongly basic reagents, tedious work-up and low yields. Consequently, there is continued interest in developing new and convenient methods for the synthesis of substituted benzopyrans using mild reaction conditions. Nowadays, microwave-assisted synthesis has become as important tool for the synthesis of various kind of heterocycles [24]. In continuation of our work towards various synthetic transformations employing Triton-B [25–29], we have invented a novel protocol for the syntheses of substituted benzopyrans using Triton-B under solvent-free conditions. Thus, in the present communication, we report herein a novel microwave promoted, one-pot solvent-free protocol for the synthesis of substituted benzopyrans through the direct reaction of corresponding substituted acetophenones and keto compounds mediated by Triton-B under solvent-free conditions.

2. Results and Discussion

Initially, the syntheses of various substituted benzopyrans were achieved from the corresponding hydroxy acetophenones and keto compounds using various kinds of solid support like neutral and basic alumina. Better yields of the products were obtained in by using basic alumina as a solid support. Moreover, reaction was further carried out without using solid support where minute amount of substituted benzopyrans was observed. Keeping the basic nature of benzyltrimethylammonium hydroxide (Triton-B), we have tried a reaction of hydroxyl acetophenone with a keto compound, where it was realized that there is complete transformation of the starting materials into desired substituted benzopyran derivative. A comparative study of use of various mild bases in caring out this synthetic reaction was studied where it was further realized that best yields were obtained using Triton-B. Moreover, the advantages associated with Triton-B include the easy removal from the reaction mixture by simple filtration. Thus, various substituted hydroxyl compounds were reacted with variety of keto compounds using Triton-B under microwave conditions to afford the clean formation of the corresponding substituted benzopyrans in good to excellent yields. Hence, it was concluded that reaction works using Triton-B under solvent-free conditions and completed in very short time (5–8 min.) afforded very excellent yields (81–99%) of the desired substituted benzopyrans. The results were summarizes in Table 1. It was further realized that the introduction of electron releasing groups at para position leads to increase in the yields, while electron withdrawing groups do not have any effect. The whole reaction conditions have been shown in Scheme 1.

Table 1: Conversion of substituted benzophenones into benzopyrans of general formula I a.

Product
R¹
R²
R³
R⁴
Time/min.
Yieldsb/%
Reference

1
H
H
CH₃
CH₃
5
86
[18, 19]

2
H
OH
CH₃
CH₃
5
89
[18, 19]

3
H
OH
CH₃
C₂H₅
8
85
[20–22]

4
H
OH
R³ = R⁴ = Cyclopentyl
7
88
[23]

5
H
OH
R³ = R⁴ = Cyclohexyl
6
90
[24]

6
OH
H
CH₃
CH₃
10
81
[23]

7
OH
H
CH₃
C₂H₅
8
82
[23]

8
OH
H
R³ = R⁴ = Cyclopentyl
8
89
[24]

9
OH
H
R³ = R⁴ = Cyclohexyl
8
86
[25–29]

10
NO₂
H
CH₃
CH₃
8
85
[18, 19]

11
OCH₃
H
CH₃
CH₃
5
91
[23]

12
OCH₃
OH
CH₃
CH₃
5
92
[18, 19]

13
OCH₃
OCH₃
CH₃
C₂H₅
4
94
[24]

14
OCH₃
OCH₃
C₂H₅
C₂H₅
4
99
[25–29]

15
OCH₃
NO₂
-C₂H₅
CH₃
5
92
[24]

16
OH
OCH₃
-C₄H₉
-C₄H₉
5
83
[20–22]

aAll the products were characterized by IR, NMR, and mass spectroscopic data.

bIsolated yields.

Scheme 1

In conclusion, we developed a convenient and efficient protocol for the one-pot, two-component coupling of various substituted acetophenones with a variety of keto compounds using basic resin. This method generates the corresponding benzopyrans in good to excellent yields. Furthermore, this method exhibits substrate versatility, mild reaction conditions, and experimental convenience. This synthesis protocol developed is believed to offer a more general method for the formation of substituted benzopyrans essential to numerous organic syntheses.

3. Experimental

Chemicals were procured from Merck, Aldrich, and Fluka chemical companies. Reactions were carried out under Argon. IR spectra 4000–200 cm⁻¹ were recorded on Bomem MB-104-FTIR spectrophotometer using neat technique, whereas NMRs were scanned on an AC-300F, NMR (300 MHz) instrument using CDCl₃ and TMS as internal standard. Elemental analysis was conducted by means of a Carlo-Erba EA 1110-CNNO-S analyzer and agreed favorably with calculated values.

3.1. Typical Experimental Procedure

Substituted hydroxy acetophenone (0.01 mol) was added to a mixture of corresponding ketone (0.01 mol) and Triton-B (0.02 mol). The reaction mixture was irradiated under microwave at 800 W in a sealed tube. The reaction mixture was extracted with ethyl acetate thrice, and organic layer was concentrated to afford the desired substituted benzophenone derivative which was recrystallized with benzene/hexane.

3.2. 2,2-Dimethyl-Chroman-4-One (1)

Mp: 85–87°C; IR (KBr): 2978, 1690, 1604, 1573, 1456 cm⁻¹; ¹H NMR (300 MHZ, CDCl₃) δ: 1.48(6H, s, CH₃), 2.75(2H, s, CH₂), 6.90–7.28(1H, m, 6 & 8-H), 7.40–7.56(1H, m, 7-H), 7.91(1H, dd, J = 8.5 Hz & 2.5 Hz, 5-H); ¹³C NMR (75 MHz, CDCl₃): δ = 26.49, 48.74, 79.40, 118.18, 120.87, 126.36, 128.48, 136.00, 160.02, 192.12 ppm; MS: m/z (%): 176(100), 161(100), 121(100), 92(100), 63(87), 41(48).

3.3. 7-Hydroxy-2,2-Dimethyl-Chroman-4-One (2)

Mp: 168°C; IR (KBr): 3469, 1652, 1611, 1570, 1492, 1459, 1428, 1415 cm⁻¹; ¹H NMR (300MHZ, CDCl₃) δ: 1.43(6H, s, 2xCH₃), 2.63(2H, s, CH₂), 6.90(1H, d, J = 2.5 Hz, 8-H), 6.56(1H, dd, J = 8.5 Hz & 2.5 Hz, 6-H), 7.83(1H, d, J = 8.5 Hz,5-H); ¹³C NMR (50 MHz, CDCl₃): δ = 26.78, 48.55, 79.13, 103.44, 110.14, 114.0, 128.42, 163.12, 164.90, 192.89 ppm; MS: m/z (%): 192(51), 177(99), 137(100), 108(58), 80(22).

3.4. 2-Ethyl 7-Hydroxy-2-Methyl-Chroman-4-One (3)

Mp: 98°C; IR(KBr):3128, 2965, 1648, 1574, 1489, 1376 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): 0.93(3H, t, J = 6.5 Hz, CH₃), 1.40 (3H, s, CH₃), 1.73 (2H, q, J = 6.5 Hz, CH₂), 2.73(2H, s, CH₂), 6.53(1H, d, J = 2.5 Hz, 8-H), 6.53(1H, dd, = 8.5 Hz, = 2.5 Hz, 6-H), 7.90(1H, d, J = 8.5 Hz, 5-H); ¹³C NMR (75 MHz, CDCl₃): δ = 7.90, 23.44, 32.13, 46.69, 81.38, 103.65, 110.05, 113.30, 128.66, 162.00, 164.86,192.10, MS at m/z (%): 206(22), 191(10), 177(52), 151(26), 137(100), 136(20), 108(19), 81(8), 69(10), 53(11).

Acknowledgments

Author is thankful to Director General, Amity University Uttar Pradesh, Lucknow Campus, Lucknow, U. P., for his constant support and encouragement for research.

Conflict of Interests

The authors confirm that there is no conflict of interests with the commercial identities used inside the paper.

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