高 潔, 劉 碩, 周紅英, 朱婉莉, 劉 璐, 應(yīng)安國(guó),4*

(1.臺(tái)州學(xué)院 醫(yī)藥化工學(xué)院，浙江 臺(tái)州 318000； 2.天津大學(xué) 化工學(xué)院，天津 300072；3.浙江建業(yè)化工股份有限公司，浙江 杭州 311604； 4.臺(tái)州學(xué)院 應(yīng)用化學(xué)研究所，浙江 臺(tái)州 318000)

一種四氫苯并吡喃及其衍生物的水相合成

高 潔1, 劉 碩2, 周紅英3, 朱婉莉1, 劉 璐1, 應(yīng)安國(guó)1,4*

(1.臺(tái)州學(xué)院 醫(yī)藥化工學(xué)院，浙江 臺(tái)州 318000； 2.天津大學(xué) 化工學(xué)院，天津 300072；
3.浙江建業(yè)化工股份有限公司，浙江 杭州 311604； 4.臺(tái)州學(xué)院 應(yīng)用化學(xué)研究所，浙江 臺(tái)州 318000)

制備了一種以三乙烯二胺(DABCO)為基礎(chǔ)的離子液體；在水溶劑中，以該離子液體為催化劑催化三組分一鍋法制備四氫苯并吡喃的反應(yīng)，得到2-氨基-3-氰基-4-芳基-7,7-二甲基-5-氧代-4H-5,6,7,8-四氫苯并[b]吡喃；考察了反應(yīng)時(shí)間、催化劑用量、催化劑加入時(shí)間、反應(yīng)溫度對(duì)反應(yīng)收率的影響，確定了最優(yōu)反應(yīng)條件；由不同的芳香醛和活性亞甲基化合物制備了一系列四氫苯并吡喃衍生物，并討論了可能的反應(yīng)機(jī)理. 結(jié)果表明，所選用的合成反應(yīng)條件溫和、時(shí)間短、收率高、后處理簡(jiǎn)單，且催化劑重復(fù)使用4次催化效果變化不大；就反應(yīng)機(jī)理而言，所用催化劑具有雙重催化活性.

三乙烯二胺；離子液體；四氫苯并吡喃；衍生物；水相合成

四氫苯并[b]吡喃衍生物在醫(yī)藥領(lǐng)域是一類非常重要的有機(jī)雜環(huán)化合物. 這些化合物具有多種生物活性和藥理活性，廣泛用于抗凝劑，利尿劑，解痙藥，抗癌藥和抗過(guò)敏藥[1]. 此外，它們可以用作認(rèn)知增強(qiáng)劑，治療神經(jīng)退化性疾病，包括老年癡呆癥，肌萎縮性脊髓側(cè)索硬化癥，亨廷頓氏病，帕金森病，艾滋相關(guān)的癡呆，唐氏綜合癥，以及精神分裂癥和肌陣攣[2-3]. 一些2-氨基-四氫苯并[b]吡喃可以作為光敏材料[4]. 因此，這類化合物的合成引起了人們極大的興趣.

四氫苯并[b]吡喃的合成通常需要強(qiáng)堿，強(qiáng)酸和較高的溫度，并用到揮發(fā)性有機(jī)溶劑[5-9]. 因此這些反應(yīng)都具有反應(yīng)條件苛刻，時(shí)間長(zhǎng)，收率低，需要有機(jī)溶劑等缺點(diǎn).

隨著人們對(duì)人類生存環(huán)境的日益重視，綠色合成逐漸成為科學(xué)家的研究重點(diǎn)，提倡在有機(jī)合成過(guò)程中采用無(wú)毒溶劑(如水)和催化劑，或無(wú)溶劑條件，實(shí)現(xiàn)綠色全合成. 靳通收等[10]報(bào)道了以十二烷基苯磺酸為催化劑，水中一鍋法制備四氫苯并[b]吡喃的反應(yīng)，收率較高. 史達(dá)清等[11]使用三乙基芐基氯化銨為催化劑，水中一鍋法制備四氫苯并[b]吡喃. 張慧等[12]以碳酸鉀為堿，無(wú)溶劑研磨條件下制備四氫苯并[b]吡喃. 以上催化體系，反應(yīng)時(shí)間大部分偏長(zhǎng)，適用范圍窄. 離子液體因其熔點(diǎn)低、蒸汽壓可忽略、液程寬、溶解性強(qiáng)、熱穩(wěn)定性高、對(duì)環(huán)境無(wú)污染等優(yōu)點(diǎn)，逐漸被人們應(yīng)用于有機(jī)合成中. BALALAIE等[13]合成了氫氧化四甲基銨鹽離子液體，在水中催化一鍋法合成四氫苯并[b]吡喃的反應(yīng)；KOLEKAR等[14]利用4-氨基吡啶與3-氯-1,2-丙二醇合成了一系列離子液體，催化芳香醛、丙二腈、雙甲酮合成四氫苯并[b]吡喃的反應(yīng). 相比之前的反應(yīng)體系，這些反應(yīng)體系有了較大提升. 但是，由于該反應(yīng)體系研究較少，開(kāi)發(fā)更高效、新穎的催化劑還是很有必要的.

DABCO(三乙烯二胺)是一種有機(jī)堿，WANG等[15]報(bào)道了以DABCO為基礎(chǔ)的一系列離子液體用于催化Knoevenagel縮合反應(yīng). 而KOLEKAR等[14]利用4-氨基吡啶與3-氯-1,2-丙二醇合成了一系列離子液體. 受上述兩方法的啟發(fā)，我們以DABCO和3-氯-1,2-丙二醇為原料，制備含DABCO的離子液體. 本文報(bào)道了以離子液體[DABCO][CF3SO3]為催化劑在水相介質(zhì)中一鍋法催化芳醛，丙二腈和雙甲酮三組分反應(yīng)合成四氫苯并[b]吡喃的反應(yīng).

1 實(shí)驗(yàn)部分

1.1 儀器與試劑

Bruker 400核磁共振儀；Carlo Erba 1160元素分析儀；HK-2A型超級(jí)恒溫水??；Mettler Doledo 電子天平. 實(shí)驗(yàn)所用試劑全為阿拉丁公司所購(gòu)買(mǎi)，純度為分析純.

1.2 離子液體[DABCO][CF3SO3]的制備

向100 mL 圓底燒瓶中加入10.15 g (90.5 mmol) 三乙烯二胺 (DABCO)和10 g(7.57 mL，90.5 mmol)3-氯-1,2-丙二醇, 加入50 mL乙醇. 在磁力攪拌下，溫度設(shè)置為80 ℃ , 加熱回流反應(yīng)24 h. 旋蒸得到[DABCO][Cl]. 取3 g(13.4 mmol) [DABCO][Cl]與2.53 g (13.4 mmol)CF3SO3K于15 mL甲醇中，65 ℃下，加熱回流反應(yīng)8 h，真空旋蒸得到淡黃色液體，即為離子液體[DABCO][CF3SO3]. 具體合成路線見(jiàn)圖1.

圖1 離子液體[DABCO][CF3SO3]的合成路線Fig.1 Synthesis route of [DABCO][CF3SO3]

1.3 三組分一鍋法制備四氫苯并吡喃及其衍生物

三組分一鍋法制備四氫苯并吡喃及其衍生物的反應(yīng)方程式如圖2.

圖2 三組分一鍋法制備四氫苯并吡喃及其衍生物Fig.2 One-pot three-component synthesis of tetrahydrobenzo[b]pyran

以2-氨基-3-氰基-4-芳基-7,7-二甲基-5-氧代-4H-5,6,7,8-四氫苯并[b]吡喃的合成為例，取雙甲酮0.5 g，苯甲醛0.36 mL，丙二腈0.23 mL加入 50 mL 圓底燒瓶中，加入離子液體0.06 g，60 ℃攪拌. 用TLC監(jiān)測(cè)反應(yīng)進(jìn)行程度(展開(kāi)劑，石油醚與乙酸乙酯體積比1∶1). 反應(yīng)結(jié)束后用乙酸乙酯萃取，收集有機(jī)相，旋干乙酸乙酯，用乙醇重結(jié)晶，抽濾、旋干得到黃色固體0.97 g，收率93%.1H NMR (400 MHz, CDCl3)δ: 7.24～7.31(m, 5H, Ph), 4.56(s, 2H, NH2), 4.43(s, 1H, CH), 2.48(s, 2H, CH2), 1.61(s, 2H, CH2), 1.13(s, 3H, CH3), 1.06(s, 3H, CH3)；MSm/z=294.1; Anal. Calcd for C18H18N2O2(%): C 73.45，H 6.16，N 9.52，O 10.87；found： C 73.41，H 6.23，N 9.44，O 10.92.

1.4 產(chǎn)物的結(jié)構(gòu)表征數(shù)據(jù)

2-Amino-7,7-dimethyl-4-(4-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile：黃色固體1.14 g，產(chǎn)率94%.1H NMR (400 MHz, CDCl3)δ: 8.19(d,J= 8.8 Hz, 2H, Ph), 7.44(d,J=8.4 Hz, 2H, Ph), 4.69(s, 2H, NH2), 4.54(s, 1H, CH), 2.51(s, 2H, CH2), 2.24～2.27(m, 2H, CH2), 1.15(s, 3H, CH3), 1.06(s, 3H, CH3)；MSm/z=339.1; Anal Calcd for C18H17N3O4(%): C 63.71，H 5.23，N 12.38，O 18.86；found: C 63.51，H 5.23，N 12.28，O 18.98.

2-Amino-7,7-dimethyl-4-(3-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile：黃色固體1.15 g，產(chǎn)率95%.1H NMR (400 MHz, CDCl3)δ: 8.10(d,J=8.4 Hz, 1H, Ph), 8.06(s, 1H, Ph), 7.70(d,J=8.4 Hz, 1H, Ph), 7.49～7.53(m, 1H, Ph), 4.74(s, 2H, NH2), 4.55(s, 1H, CH), 2.47～2.57(m, 2H, CH2), 2.20～2.30(m, 2H, CH2), 1.15(s, 3H, CH3), 1.07(s, 3H, CH3)；MSm/z=339.1;Anal Calcd for C18H17N3O4(%): C 63.71，H 5.23，N 12.38，O 18.86；found: C 63.58，H 5.21，N 12.25，O 18.96.

2-Amino-4-(2-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile：黃色固體1.09 g，產(chǎn)率93%.1H NMR (400 MHz, CDCl3)δ: 7.34(d,J=7.6 Hz, 1H, Ph), 7.21～7.23(m, 2H, Ph), 7.14～7.18(m, 1H, Ph), 4.87(s, 1H, CH), 4.64(s, 2H, NH2), 2.47(s, 2H, CH2), 2.18～2.28(m, 2H, CH2), 1.14(s, 3H, CH3), 1.09(s, 3H, CH3)；MSm/z=328.1;Anal Calcd for C18H17ClN2O2(%): C 65.75，H 5.21，Cl 10.78，N 8.52，O 9.73；found: C 65.71，H 5.29，Cl 10.73，N 8.48，O 9.81.

2-Amino-4-(3-methoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile：白色固體1.03 g，產(chǎn)率90%.1H NMR (400 MHz, CDCl3)δ: 7.21～7.25(m, 1H, Ph), 6.84(d,J=7.6 Hz, 1H, Ph), 6.75～6.79(m, 2H, Ph), 4.61(s, 2H, NH2), 4.39(s, 1H, CH), 3.81(s, 3H, OCH3), 2.47(s, 2H, CH2), 2.25(d,J=2.4Hz, 2H, CH2), 1.13(s, 3H, CH3), 1.07(s, 3H, CH3)，MSm/z=324.1;Anal Calcd for C19H20N2O3(%): C 70.35，H 6.21，N 8.64，O 14.80；found: C 70.25，H 6.29，N 8.57，O 14.89.

2-Amino-4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile：白色固體1.02 g，產(chǎn)率89%.1H NMR (400 MHz, CDCl3)δ: 7.17(d,J=8.4 Hz, 2H, Ph), 6.84(d,J=8.4 Hz, 2H, Ph), 4.53(s, 2H, NH2), 4.38(s, 1H, CH), 3.79(s, 3H, OCH3), 2.46(s, 2H, CH2), 2.23(d,J=5.2Hz, 2H, CH2), 1.13(s, 3H, CH3), 1.06(s, 3H, CH3)，MSm/z=324.1;Anal Calcd for C19H20N2O3(%): C 70.35，H 6.21，N 8.64，O 14.80；found: C 70.21，H 6.30，N 8.53，O 14.96.

2-Amino-4-(2-methoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile：白色固體0.99 g，產(chǎn)率86%.1H NMR (400 MHz, CDCl3)δ: 7.18～7.22(m, 1H, Ph), 7.11～7.13(m, 1H, Ph), 6.87～6.91(m, 2H, Ph), 4.73(s, 1H, CH), 4.46(s, 2H, NH2), 3.86(s, 3H, OCH3), 2.46(s, 2H, CH2), 2.23(d,J=8.4Hz, 2H, CH2), 1.14(s, 3H, CH3), 1.07(s, 3H, CH3)，MSm/z=324.1;Anal Calcd for C19H20N2O3(%): C 70.35，H 6.21，N 8.64，O 14.80；found: C 70.26，H 6.29，N 8.59，O 14.86.

2-Amino-4-(4-hydroxy-3,5-dimethoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile：黃色固體1.06 g，產(chǎn)率80%.1H NMR (400 MHz, CDCl3)δ: 6.46(s, 2H, Ph), 5.47(s, 1H, CH), 4.62(s, 2H, NH2), 4.34(s, 1H, OH), 3.88(s, 6H, OCH3), 2.43～2.53(m, 2H, CH2), 2.22～2.31(m, 2H, CH2), 1.14(s, 3H, CH3), 1.09(s, 3H, CH3). MSm/z=370.1；;Anal Calcd for C20H22N2O5(%): C 64.85，H 5.99，N 7.56，O 21.60；found: C 64.76，H 6.11，N 7.46，O 21.67.

2-Amino-7,7-dimethyl-5-oxo-4-(thiophen-2-yl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile：黃色固體0.88 g，產(chǎn)率82%.1H NMR (400 MHz, CDCl3)δ: 7.15(d,J=4.4 Hz, 1H, Ph), 7.01(d,J=3.2 Hz, 1H, Ph), 6.91～6.93(m, 1H, Ph), 4.80(s, 1H, CH), 4.63(s, 2H, NH2), 2.45(s, 2H, CH2), 2.30(s, 2H, CH2), 1.14(s, 3H, CH3), 1.09(s, 3H, CH3)，MSm/z=300.1；Anal Calcd for C16H16N2O2S(%): C 63.98，H 5.37，N 9.33，O 10.65，S 10.67；found: C 63.87，H 5.49，N 9.29，O 10.62，S 10.72.

2-Amino-7,7-dimethyl-4-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile：黃色固體1.02 g，產(chǎn)率83%.1H NMR (400 MHz, CDCl3)δ: 8.40(d,J=8.4 Hz, 1H, Ph), 7.85(d,J=8.0 Hz, 1H, Ph), 7.74(d,J=8.0 Hz, 1H, Ph), 7.59～7.61(m, 1H, Ph), 7.57(s, 1H, Ph), 7.48～7.52(m, 1H, Ph), 7.25～7.43(m, 1H, Ph), 5.23(s, 1H, CH), 4.53(s, 2H, NH2), 2.53～2.60(m, 2H, CH2), 2.17～2.28(m, 2H, CH2), 1.15(s, 3H, CH3), 1.09(s, 3H, CH3)，MSm/z=344.1，Anal Calcd for C22H20N2O2(%): C 76.73，H 5.85，N 8.13，O 9.29；found: C 76.67，H 5.93，N 8.06，O 9.34.

2-Amino-4-(1H-indol-3-yl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile：黃色固體0.93 g，產(chǎn)率78%.1H NMR (400 MHz, CDCl3)δ: 8.10(s, 1H, NH), 7.40(d,J=8.0 Hz, 1H, Ph), 7.35(d,J=8.0 Hz, 1H, Ph), 7.21(s, 1H, Ph), 7.14～7.18(m, 1H, Ph), 7.05～7.09(m, 1H, Ph), 4.75(s, 1H, CH), 4.54(s, 2H, NH2), 2.43～2.55(m, 2H, CH2), 2,15～2,25(m, 2H, CH2), 1.12(s, 3H, CH3), 0.97(s, 3H, CH3)，MSm/z=333.1; Anal Calcd for C20H19N3O2(%): C 72.06，H 5.74，N 12.60，O 9.60；found: C 72.00，H 5.83，N 12.53，O 9.64.

Ethyl 2-amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carboxylate：黃色固體1.08 g，產(chǎn)率89%.1H NMR (400 MHz, CDCl3)δ: 7.27～7.29(m, 2H, Ph), 7.20～7.24(m, 2H, Ph), 7.10～7.14(m, 1H, Ph), 6.18(m, 2H, NH2), 4.72(s, 1H, CH), 3.99～4.09(m, 2H, CH2), 2.45(s, 2H, CH2), 2.16～2.27(m, 2H, CH3), 1.16～1.20(m, 3H, CH3), 1.12(s, 3H, CH3), 0.99(s, 3H, CH3)；MSm/z=341.1; Anal Calcd for C20H23NO4(%): C 70.36，H 6.79，N 4.10，O 18.75；found: C 70.27，H 6.87，N 4.05，O 18.81.

Ethyl 2-amino-4-(4-fluorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carboxylate：黃色固體1.17 g，產(chǎn)率91%.1H NMR (400 MHz, CDCl3)δ: 7.22～7.26(m, 2H, Ph), 6.88～6.93(m, 2H, Ph), 6.19(s, 2H, NH2), 4.70(s, 1H, CH), 4.03～4.08(m, 2H, CH2), 2.44(s, 2H, CH2), 2.16～2.27(m, 2H, CH2), 1.15～1.19(m, 3H, CH3), 1.12(s, 3H, CH3), 0.99(s, 3H, CH3)；MSm/z=359.1; Anal Calcd for C20H22FNO4(%): C 66.83，H 6.17，F(xiàn) 5.29，N 3.90，O 17.81；found: C 66,76，H 6.25，F(xiàn) 5.31，N 3.82，O 17.86.

2 結(jié)果與討論

2.1 反應(yīng)條件優(yōu)化

2.1.1 催化劑用量對(duì)反應(yīng)的影響

以苯甲醛為底物，離子液體[DABCO][CF3SO3]為催化劑，反應(yīng)在60℃下進(jìn)行，只改變催化劑的用量，由此考察了催化劑的用量對(duì)反應(yīng)時(shí)間以及產(chǎn)率的影響，結(jié)果見(jiàn)表1.

表1 催化劑用量對(duì)反應(yīng)時(shí)間和產(chǎn)率的影響Table 1 Effects of the amount of catalyst on reaction yields

上表的實(shí)驗(yàn)結(jié)果表明，催化劑的用量對(duì)反應(yīng)是有影響的. 在沒(méi)有催化劑存在時(shí)，反應(yīng)可以進(jìn)行，但是沒(méi)有得到多組分縮合產(chǎn)物. 當(dāng)催化劑用量為1.0%(物質(zhì)的量分?jǐn)?shù)，下同)時(shí)，產(chǎn)率為53%，反應(yīng)時(shí)間為120 min；當(dāng)催化劑用量為2.0%時(shí)，產(chǎn)率為71%，反應(yīng)時(shí)間為105 min；當(dāng)催化劑用量為5%時(shí)，產(chǎn)率達(dá)到93%，且反應(yīng)時(shí)間縮短為30 min；當(dāng)催化劑用量為8%時(shí)，產(chǎn)率為92%，反應(yīng)時(shí)間為30 min；當(dāng)催化劑用量為10%時(shí)，產(chǎn)率為93%，反應(yīng)時(shí)間為30 min. 由上述實(shí)驗(yàn)結(jié)果我們可以知道，催化劑對(duì)反應(yīng)的產(chǎn)率和時(shí)間都有影響，但催化劑的用量也有一個(gè)最適值，由實(shí)驗(yàn)可得，催化劑用量為5%較合適，此時(shí)產(chǎn)率最高，反應(yīng)時(shí)間也最短.

2.1.2 溫度對(duì)反應(yīng)的影響

以苯甲醛作為底物，離子液體[DABCO][CF3SO3]為催化劑，催化劑用量為5 mol%，只改變反應(yīng)的溫度，由此考察了反應(yīng)溫度對(duì)反應(yīng)時(shí)間和產(chǎn)率的影響，結(jié)果見(jiàn)表2.

表2 反應(yīng)溫度對(duì)反應(yīng)時(shí)間和產(chǎn)率的影響Table 2 Effects of reaction temperature on reaction yields

實(shí)驗(yàn)結(jié)果表明，溫度對(duì)反應(yīng)有影響. 當(dāng)溫度為60 ℃時(shí)，產(chǎn)率最高為93%，且反應(yīng)時(shí)間也相對(duì)較短；而當(dāng)溫度繼續(xù)升高或降低時(shí)，反應(yīng)產(chǎn)率并沒(méi)有提高，反應(yīng)時(shí)間也沒(méi)有相應(yīng)縮短. 由此，本實(shí)驗(yàn)的最佳溫度為60 ℃.

3.1.3 反應(yīng)時(shí)間對(duì)反應(yīng)的影響

以苯甲醛為底物，離子液體[DABCO][CF3SO3]為催化劑，反應(yīng)在60 ℃下進(jìn)行，催化劑用量為5%，控制反應(yīng)時(shí)間，由此考察反應(yīng)時(shí)間對(duì)產(chǎn)率的影響. 結(jié)果見(jiàn)圖3.

反應(yīng)時(shí)間過(guò)短，反應(yīng)不完全；在一定范圍內(nèi)，反應(yīng)時(shí)間越長(zhǎng)，反應(yīng)越完全，收率越高. 由圖3可知，當(dāng)反應(yīng)時(shí)間在30 min之前時(shí)，隨著時(shí)間的增加，反應(yīng)產(chǎn)率逐漸的提高，但繼續(xù)延長(zhǎng)反應(yīng)時(shí)間，產(chǎn)率基本不變.

最終我們得到的以苯甲醛為底物進(jìn)行反應(yīng)的最佳反應(yīng)條件為：催化劑用量5%(物質(zhì)的量分?jǐn)?shù))，反應(yīng)溫度為60 ℃，反應(yīng)時(shí)間為30 min.

3.2 [DABCO][CF3SO3]一鍋法制備四氫苯并吡喃及其衍生物

各種芳香醛與丙二腈、雙甲酮的三組分一鍋法反應(yīng)結(jié)果見(jiàn)表3. 由表可知，帶有不同取代基的芳香醛都能在離子液體[DABCO][CF3SO3]的催化下，在60℃下與丙二腈，雙甲酮等活性亞甲基化合物發(fā)生反應(yīng)，反應(yīng)時(shí)間短，產(chǎn)率高. 芳香醛的取代基不同會(huì)影響反應(yīng)時(shí)間和收率. 帶有吸電子基的芳香醛如硝基，氯(表3，序號(hào)2-4)比帶給電子基的芳香醛如甲氧基(表3，序號(hào)5-7)反應(yīng)效果更好. 這是由于芳香醛上取代基團(tuán)對(duì)羰基碳正電性的影響所致，具有更強(qiáng)羰基碳正電性的醛所需的時(shí)間更短，產(chǎn)率更高. 當(dāng)苯環(huán)上有多基團(tuán)取代(表3，序號(hào)8)時(shí)，由于存在空間位阻，所需的反應(yīng)時(shí)間更長(zhǎng)，產(chǎn)率相對(duì)較低. 作者也嘗試了雜原子取代的芳香醛，如2-噻吩醛，1-萘醛，吲哚-3-甲醛(表3，序號(hào)9-11)，反應(yīng)仍很迅速，產(chǎn)率也可以達(dá)到80%左右. 將丙二腈替換為活性相對(duì)較差的氰乙酸乙酯，反應(yīng)產(chǎn)率可達(dá)到85%以上(表3，序號(hào)12，13).

表3 一鍋法制備四氫苯并吡喃及其衍生物Table 3 One-pot synthesis of various 4H-benzo[b]pyran derivatives via a three-component condensation in aqueous media

3.3 催化劑循環(huán)使用性能

以苯甲醛為底物，離子液體[DABCO][CF3SO3]為催化劑，反應(yīng)在60℃下進(jìn)行，初始催化劑用量為5%，由此考察催化劑的重復(fù)使用性能. 反應(yīng)結(jié)束后，過(guò)濾析出固體產(chǎn)物，產(chǎn)物用適量乙醇重結(jié)晶. 由于該離子液體不溶于乙酸乙酯，只需要將濾液通過(guò)簡(jiǎn)單的乙酸乙酯萃取分離，然后通過(guò)真空干燥除水即可直接用于催化下次反應(yīng). 催化劑重復(fù)使用結(jié)果見(jiàn)圖4. 結(jié)果表明，催化劑重復(fù)使用4次以后仍保持較好的活性.

圖3 反應(yīng)時(shí)間對(duì)反應(yīng)產(chǎn)率的影響Fig.3 Effects of the reaction time on reaction yields

圖4 催化劑循環(huán)使用性能Fig.4 The resuabilities of the catalyst

3.4 催化劑的催化機(jī)理

可能的反應(yīng)機(jī)理(見(jiàn)圖5)：[DABCO][CF3SO3]中未與3-氯-1,2-丙二醇連接的氮原子顯堿性，可以?shī)Z去丙二腈活性亞甲基的氫原子；該分子中的羥基可與芳香醛的羰基形成氫鍵，使羰基碳的電正性更強(qiáng)，容易受到碳負(fù)離子進(jìn)攻. 通過(guò)Knoevenagel縮合反應(yīng)，得到中間體A. 同時(shí)，[DABCO][CF3SO3]中未與3-氯-1,2-丙二醇連接的氮原子也可以?shī)Z去雙甲酮活性亞甲基的氫原子，形成的碳負(fù)離子與A進(jìn)行加成反應(yīng)，得到中間體B，B經(jīng)過(guò)烯醇化、環(huán)合、互變異構(gòu)等過(guò)程得到目標(biāo)產(chǎn)物.

圖5 [DABCO][CF3SO3]的催化機(jī)理Fig.5 Catalytic mechanism of [DABCO][CF3SO3]

結(jié)論：[DABCO][CF3SO3]是一種環(huán)保，簡(jiǎn)單易得，催化效率高，使用安全的離子液體催化劑. 能夠催化以水為溶劑的三組分一鍋法制備四氫苯并吡喃及其衍生物的反應(yīng). 與文獻(xiàn)相比，該方法具有反應(yīng)條件溫和，反應(yīng)時(shí)間短，反應(yīng)覆蓋率大，產(chǎn)率高(80%～95%)，同時(shí)催化劑制作簡(jiǎn)便，且重復(fù)使用率高，反應(yīng)后處理方便等優(yōu)點(diǎn)，為四氫苯并吡喃的制備提供了一種有效，環(huán)保的合成方法，在精細(xì)化學(xué)品合成方面有一定的工業(yè)化應(yīng)用潛力.

[1]BONSIGNORE L, LOY G, SECCI D, et al. Synthesis and pharmacological activity of 2-oxo-(2H) 1-benzopyran-3-carboxamide derivatives [J]. Eur J Med Chem, 1993, 28(6): 517-520.

[2]CHINIGO G M, PAIGE M, GRINDROD S, et al. Asymmetric synthesis of 2,3-dihydro-2-arylquinazolin-4-ones: methodology and application to a potent fluorescent tubulin inhibitor with anticancer activity [J]. J Med Chem, 2008, 51: 4620-4631.

[3]COHEN E, KLARBERG B, VAUGHAN J R. Quinazolinone sulfonamides. A new class of diuretic agents [J]. J Am Chem Soc, 1960, 82: 2731-2735.

[4]ARMETSO D, HORSPOOL W M, MARTIN N, et al. Synthesis of cyclobutenes by the novel photochemical ring contraction of 4-substituted, 2-amino-3, 5-dicyano-6-phenyl-4H-pyrans [J]. J Org Chem, 1989, 54(13): 3069-3072.

[5]WANG Xiangshan, SHI Daqing, TU Shujiang, et al. A convenient synthesis of 5-oxo-5,6,7,8-tetrahydro-4H-benzo-[b]pyran derivatives catalyzed by KF-alumina [J]. Synth Commun, 2003, 33: 119-126.

[6]BALALAIE S, BARARJANIAN M, AMANI A M, et al. (S)-Proline as a neutral and efficient catalyst for the one-pot synthesis of tetrahydrobenzo[b]pyran derivatives in aqueous media [J]. Synlett, 2006, 2: 263-266.

[7]SINGH K, SINGH J, SINGH H. A synthetic entry into fused pyran derivatives through carbon transfer reactions of 1,3-oxazinanes and oxazolidines with carbon nucleophiles [J]. Tetrahedron, 1996, 52(45): 14273-14280.

[8]PORE D M, UNDALE K A, DONGARE B B, et al. Potassium phosphate catalyzed a rapid three-component synthesis of tetrahydrobenzo[b]pyran at ambient temperature [J]. Catal Lett, 2009,132: 104-108.

[9]SEIFI M, SHEIBANI H. High surface area MgO as a highly effective heterogeneous base catalyst for three-component synthesis of tetrahydrobenzopyran and 3,4-dihydropyrano[c]chromene derivatives in aqueous media [J]. Catal Lett, 2008, 126(3/4): 275-279.

[10]靳通收，王愛(ài)卿，張建設(shè)，等. 水中“一鍋法”合成2-氨基-3-氰基-4-芳基-7, 7-二甲基-5-氧代-4H-5, 6, 7, 8-四氫苯并[b]吡喃[J]. 有機(jī)化學(xué), 2004, 24(12): 1598-1600.

[11]史達(dá)清，張 姝，莊啟亞. 水介質(zhì)中2-氨基-4-芳基-7,7-二甲基-5-氧代-4 H-5,6,7,8-四氫苯并[b]吡喃-3-羧酸酯的有效合成[J]. 有機(jī)化學(xué), 2005,25(12): 1570-1574.

[12]張 慧，曹衛(wèi)國(guó)，任仲皎. 無(wú)溶劑研磨條件下四氫苯并毗喃衍生物的一鍋法合成[J]. 有機(jī)化學(xué), 2006, 26(8): 1018-1021.

[13]BALALAIE S, SHEIKH-AHMADI M, BARARJANIAN M. Tetra-methyl ammonium hydroxide: An efficient and versatile catalyst for the one-pot synthesis of tetrahydrobenzo[b]pyran derivatives in aqueous media [J]. Catal Commun, 2007, 8: 1724-1728.

[14]SALVI P P, MANDHARE A M, SARTAPE A S, et al. An efficient protocol for synthesis of tetrahydrobenzo[b]pyrans using amino functionalized ionic liquid [J]. C R Chimie, 2011, 14: 878-882.

[15]XU Dazhen, LIU Yingjun, SHI Sen, et al. A simple, efficient and green procedure for Knoevenagel condensation catalyzed by [C4dabco][BF4]ionic liquid in water [J]. Green Chem, 2010, 12(3): 514-517.

[16]SHAABANI A, SAMADI S, RAHMATI A. One-pot, three-component condensation reaction in water. An efficient and improved procedure for the synthesis of pyran annulated heterocyclic systems [J]. Synth Commun, 2007, 37(3): 491-499.

[17]XU Jiangcheng, LI Wanmei, ZHENG Hui, et al. One-pot synthesis of tetrahydrochromene derivatives catalyzed by lipase [J]. Tetrahedron, 2011, 67(49): 9582-9587.

[18]ZHI Huizhen, LV Chunxu, ZHANG Qiang, et al. A new PEG-1000-based dicationic ionic liquid exhibiting temperature-dependent phase behavior with toluene and its application in one-pot synthesis of benzofurans [J]. Chem Commun, 2009, 20: 2878-2880.

[19]MOSADDEGH E, HASSANKHANI A, MANSOURI G. An efficient, simple and green Zn(Phen)2Cl2complex catalyzed synthesis of 4-H-benzo[b]pyrans in water at ambient temperature [J]. E-J Chem, 2011, 8(2): 529-534.

[20]PATRA A, MAHAPATRA T. Synthesis of tetrahydrobenzo[b]pyran derivatives catalysed by Aliquat 336 in water under microwave irradiation [J]. J Chem Res, 2010, 34(12): 689-693.

[21]HASANINEJAD A, SHEKOUHY M, GOLZAR N, et al. Silica bondedn-propyl-4-aza-1-azoniabicyclo[2.2.2]octane chloride (SB-DABCO):a highly efficient, reusable and new heterogeneous catalyst for the synthesis of 4H-benzo[b]pyran derivatives [J]. Appl Catal A: Gen, 2011, 402(1/2): 11-22.

[22]GAO S, TSAI C H, TSENG C, et al. Fluoride ion catalyzed multicomponent reactions for efficient synthesis of 4H-chromene and N-arylquinoline derivatives in aqueous media [J]. Tetrahedron, 2008, 64(38): 9143-9149.

[23]KHAN A T, LAL M, ALI S, et al. One-pot three-component reaction for the synthesis of pyran annulated heterocyclic compounds using DMAP as a catalyst [J]. Tetrahedron Lett, 2011, 52(41): 5327-5332.

[24]FAN Xuesen; HU Xueyuan, ZHANG Xinying, et al. Ionic liquid-promoted Knoevenagel and Michael reactions [J]. Aust J Chem, 2004, 57(11): 1067-1071.

Abstract: A novel naphthalene-based fluorescent Hg2+sensor was designed and synthesized. The selective recongnition ability of as-synthesized Hg2+sensor towards Hg2+, Li+, Na+, K+, Zn2+, Co2+, Ni2+, Cu2+, Fe2+, Mn2+, Cr3+and Fe3+was evaluated by fluorescent spectra titration experiments. Results indicate that as-synthesized Hg2+sensor exhibits good selectivity towards Hg2+over Li+, Na+, K+, Zn2+, Co2+, Ni2+, Cu2+, Fe2+, Mn2+, Cr3+and Fe3+in H2O-DMSO with a buffered pH value of 7. 4. The fluorescent sensor and Hg2+form a 1∶1 complex, thereby leading to fluorescent quenching with a binding constant of (9.07 ± 0.41) × 104.

Keywords: fluorescence; chemical sensor; Hg2+; design; synthesis

Synthesisofatetrahydrobenzo-pyrananditsderivatives
inaqueousmedium

GAO Jie1, LIU Shuo2, ZHOU Hongying3, ZHU Wanli1, LIU Lu1, YING Anguo1,4*

(1.SchoolofPharmaceuticalandChemicalEngineering,TaizhouUniversity,Taizhou318000,Zhejiang,China;
2.SchoolofChemicalEngineeringandTechnology,TianjinUniversity,Tianjin300072,China;
3.ZhejiangJianyeOrganicChemicalCompanyLtd.,Hangzhou311604,Zhejiang,China;
4.InstituteofAppliedChemistry,TaizhouUniversity,Taizhou318000,Zhejiang,China)

1,4-diazabicyclo[2.2.2]octane (denoted as DABCO) based ionic liquid was synthesized. As-obtained DABCO-based ionic liquid was adopted as a catalyst to catalyze the one-pot three-component condensation reaction for synthesizing 4H-benzo[b]pyran derivatives in aqueous media affording target compound 2-amino-3-cyano-4-aryl-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran. The effects of reaction time, catalyst dosage, catalyst-adding time, and reaction temperature on the yield were investigated, and the optimal reaction condition was established. Moreover, various aromatic aldehydes and active methylene compounds were adopted as starting materials to synthesize a series of tetrahydrobenzo-pyran compounds, and possible reaction mechanisms were discussed. Results indicate that as-established synthesis route has the advantages of mild reaction condition, short reaction time, high yield and easy post-treatment, while the catalyst retains nearly unchanged activity after 4 times of recycle. In terms of the reaction mechanisms, as-prepared DABCO-based ionic liquid catalyst exhibits dual catalytic activity.

DABCO; ionic liquid; 4H-benzo[b]pyran; derivative; aqueous phase synthesis

DesignandsynthesisofanewfluorescentHg2+sensor

ZU Fuli, LI Qian, SONG Pan, WANG Chenjuan, XU Kuoxi*

(CollegeofChemistryandChemicalEngineering,HenanUniversity,Kaifeng475004,Henan,China)

O 621.25DocumentcodeAArticleID1008-1011(2014)03-0254-06

2013-12-26.

國(guó)家自然科學(xué)基金項(xiàng)目(No. 21106090)，浙江省低碳脂肪胺工程技術(shù)研究中心開(kāi)放基金項(xiàng)目(2012E10033)，臺(tái)州學(xué)院校立學(xué)生科研項(xiàng)目(13XS26).

高 潔(1992-)，女，本科生，研究方向?yàn)樗幬锖铣?*

，E-mail: agying@tzc.edu.cn, yinganguo@163.com.

O 626.31

A

1008-1011(2014)03-0247-07