Amit K. Chaturvedi

Devdutt Chaturvedi

Nisha Mishra

Virendra Mishra

Organic Chemistry International

English

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.</jats:p

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Hindawi Publishing CorporationOrganic Chemistry InternationalVolume 2012, Article ID 208948, 4 pagesdoi:10.1155/2012/208948Research ArticleTriton-B-Catalyzed, Efficient,Solvent-Free Synthesis of BenzopyransDevdutt Chaturvedi,1 Amit K. Chaturvedi,2 Nisha Mishra,2 and Virendra Mishra21 Laboratory of Medicinal Chemistry, Amity Institute of Pharmacy, Amity University Uttar Pradesh,Lucknow Campus, Lucknow 226010, India2 Synthetic Research Laboratory, Department of Chemistry, B. S. A. College, Mathura 281004, IndiaCorrespondence should be addressed to Devdutt Chaturvedi, devduttchaturvedi@gmail.comReceived 5 June 2012; Accepted 16 August 2012Academic Editor: William N. SetzerCopyright © 2012 Devdutt Chaturvedi et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.A convenient and microwave-promoted novel protocol for the syntheses of diverse kinds of substituted benzopyrans from thecorresponding 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. Introduction2-H-1-benzopyrans, commonly known as 2H-benzopyransor 2H-chromenes, are an important structural motif presentin the varieties of biologically active natural, synthetic drugs,and lead molecules [1, 2]. Interesting chemistry have beenexploited to this structural unit for generating diverse seriesof compounds, which have displayed a wide spectrum ofpotential 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 synthesisof various kinds of dyes [13] and agrochemicals [14] is wellknown. Their major use in the development of diverse kindsof potassium channel openers has made further interest forbenzopyran chemistry [15]. Furthermore, benzopyran unithas been further explored, as a useful synthon for the genera-tion of diverse kinds of pharmaceutically important complexheterocycles of natural as well as synthetic molecules [16].Traditional syntheses of substituted benzopyrans involve thereaction of substituted hydroxyl acetophenones with ketocompounds using variety of strong bases [17]. Recently,their synthesis has been further achieved through diﬀerentkinds of starting materials using variety of metallic andnonmetallic 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 metallicsystem were also reported recently [23]. Most of thesemethods suﬀer from the limitations such as long-reactiontimes, use of expensive strongly basic reagents, tediouswork-up and low yields. Consequently, there is continuedinterest in developing new and convenient methods forthe synthesis of substituted benzopyrans using mild reac-tion conditions. Nowadays, microwave-assisted synthesis hasbecome as important tool for the synthesis of various kindof heterocycles [24]. In continuation of our work towardsvarious synthetic transformations employing Triton-B [25–29], we have invented a novel protocol for the synthesesof substituted benzopyrans using Triton-B under solvent-free conditions. Thus, in the present communication, wereport herein a novel microwave promoted, one-pot solvent-free protocol for the synthesis of substituted benzopyransthrough the direct reaction of corresponding substitutedacetophenones and keto compounds mediated by Triton-Bunder solvent-free conditions.2. Results and DiscussionInitially, the syntheses of various substituted benzopyranswere achieved from the corresponding hydroxy acetophe-nones and keto compounds using various kinds of solidsupport like neutral and basic alumina. Better yields of the2 Organic Chemistry InternationalTable 1: Conversion of substituted benzophenones into benzopyrans of general formula Ia.Product R1 R2 R3 R4 Time/min. Yieldsb/% Reference1 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 n-C2H5 CH3 5 92 [24]16 OH OCH3 n-C4H9 n-C4H9 5 83 [20–22]aAll the products were characterized by IR, NMR, and mass spectroscopic data.bIsolated yields.R1 R1R2 R2OOOOOH+R3R3R4 R4ITriton-B800 W, 5–8 min81–99%Scheme 1products were obtained in by using basic alumina as a solidsupport. Moreover, reaction was further carried out withoutusing solid support where minute amount of substitutedbenzopyrans was observed. Keeping the basic nature of ben-zyltrimethylammonium hydroxide (Triton-B), we have trieda reaction of hydroxyl acetophenone with a keto compound,where it was realized that there is complete transformationof the starting materials into desired substituted benzopyranderivative. A comparative study of use of various mild basesin caring out this synthetic reaction was studied where itwas further realized that best yields were obtained usingTriton-B. Moreover, the advantages associated with Triton-Binclude the easy removal from the reactionmixture by simplefiltration. Thus, various substituted hydroxyl compoundswere reacted with variety of keto compounds using Triton-B under microwave conditions to aﬀord the clean formationof the corresponding substituted benzopyrans in good toexcellent yields. Hence, it was concluded that reaction worksusing Triton-B under solvent-free conditions and completedin very short time (5–8min.) aﬀorded very excellent yields(81–99%) of the desired substituted benzopyrans. The resultswere summarizes in Table 1. It was further realized that theintroduction of electron releasing groups at para positionleads to increase in the yields, while electron withdrawinggroups do not have any eﬀect. The whole reaction conditionshave been shown in Scheme 1.In conclusion, we developed a convenient and eﬃcientprotocol for the one-pot, two-component coupling ofvarious substituted acetophenones with a variety of ketocompounds using basic resin. This method generates thecorresponding benzopyrans in good to excellent yields.Furthermore, this method exhibits substrate versatility, mildreaction conditions, and experimental convenience. Thissynthesis protocol developed is believed to oﬀer a moregeneral method for the formation of substituted benzopyransessential to numerous organic syntheses.3. ExperimentalChemicals were procured from Merck, Aldrich, and Flukachemical companies. Reactions were carried out underArgon. IR spectra 4000–200 cm−1 were recorded on BomemMB-104-FTIR spectrophotometer using neat technique,whereas NMRs were scanned on an AC-300F, NMR(300MHz) instrument using CDCl3 and TMS as internalstandard. Elemental analysis was conducted by means of aCarlo-Erba EA 1110-CNNO-S analyzer and agreed favorablywith calculated values.3.1. Typical Experimental Procedure. Substituted hydroxyacetophenone (0.01mol) was added to a mixture of corre-sponding ketone (0.01mol) and Triton-B (0.02mol). Thereactionmixture was irradiated undermicrowave at 800W ina sealed tube. The reaction mixture was extracted with ethylacetate thrice, and organic layer was concentrated to aﬀordthe desired substituted benzophenone derivative which wasrecrystallized 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 NMROrganic Chemistry International 3(300MHZ, 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 = 8.5Hz & 2.5Hz, 5-H); 13C NMR (75MHz, 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 = 2.5Hz, 8-H),6.56(1H, dd, J = 8.5Hz & 2.5Hz, 6-H), 7.83(1H, d, J= 8.5Hz,5-H); 13C NMR (50MHz, 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; 1HNMR (300MHz, CDCl3): 0.93(3H, t, J = 6.5Hz, CH3),1.40 (3H, s, CH3), 1.73 (2H, q, J = 6.5Hz, CH2), 2.73(2H,s, CH2), 6.53(1H, d, J = 2.5Hz, 8-H), 6.53(1H, dd, J1 =8.5Hz, J2= 2.5Hz, 6-H), 7.90(1H, d, J = 8.5Hz, 5-H); 13CNMR (75MHz, 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, MSat m/z (%): 206(22), 191(10), 177(52), 151(26), 137(100),136(20), 108(19), 81(8), 69(10), 53(11).AcknowledgmentsAuthor is thankful to Director General, Amity UniversityUttar Pradesh, Lucknow Campus, Lucknow, U. P., for hisconstant support and encouragement for research.Conflict of InterestsThe authors confirm that there is no conflict of interests withthe commercial identities used inside the paper.References[1] M. Curini, G. Cravotto, F. Epifano, and G. 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Triton-B-Catalyzed, Efficient, Solvent-Free Synthesis of Benzopyrans

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

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