黃美薇, 吳雙, 劉亦飛, 趙志剛

(1. 西南民族大學(xué)化學(xué)與環(huán)境保護工程學(xué)院, 四川 成都 610041; 2. 西南民族大學(xué)電氣信息工程學(xué)院, 四川 成都 610041)

新的金剛烷酰腙衍生物的微波合成及結(jié)構(gòu)表征

黃美薇1, 吳雙2, 劉亦飛1, 趙志剛1

(1. 西南民族大學(xué)化學(xué)與環(huán)境保護工程學(xué)院, 四川 成都 610041; 2. 西南民族大學(xué)電氣信息工程學(xué)院, 四川 成都 610041)

以1-金剛烷甲酸為起始原料, 利用微波輻射無溶劑法, 設(shè)計合成了9個金剛烷酰腙衍生物, 并利用1H NMR、ESI-MS、 IR和元素分析對其結(jié)構(gòu)進行了確認. 通過微波法和常規(guī)法的對比發(fā)現(xiàn), 使用微波法后, 反應(yīng)產(chǎn)率從70%～80%升高到90%～95% , 反應(yīng)時間從2.0～3.5 h縮短到1.0～3.0 min.

金剛烷; 酰腙; 微波合成

金剛烷有十分穩(wěn)定的籠狀結(jié)構(gòu). 具有高度對稱性, 良好的熱穩(wěn)定性、潤滑性、親油性和對光的穩(wěn)定性. 其衍生物在醫(yī)藥[1]、功能高分子材料[2]等領(lǐng)域具有重要應(yīng)用．酰腙類化合物在醫(yī)藥(如抗腫瘤[3-4]、抗病毒[5]、抗菌[6])、農(nóng)藥[7]、分析試劑[8]等方面有重要應(yīng)用. 金剛烷酰腙類化合物具有金剛烷和酰腙的雙重性能.

近幾年來微波合成法受到人們的廣泛關(guān)注, 微波合成法具有快速、高效、反應(yīng)條件溫和、環(huán)境友好等特點[9-10].本文采用微波輻射和傳統(tǒng)實驗的對照方法設(shè)計合成了一類新的金剛烷酰腙衍生物. 合成路線見圖1.

1 實驗部分

1.1 儀器與試劑

400 MHz核磁共振儀(Me4Si作內(nèi)標,CDCl3作溶劑,瓦利安公司); FINNIGAN-LCQDECA型質(zhì)譜儀(美國菲立根公司); IR-200 型紅外光譜儀(KBr壓片,美國利高麗公司); Vario Micro Cube 型元素分析儀(德國元素公司); WRS-1B型數(shù)字熔點儀; (上海申光儀器儀表有限公司); XH-100A商用微波爐反應(yīng)器(北京祥鵠科技發(fā)展有限公司). 所用試劑均為分析純. 中間體2、3參考文獻[11]的方法合成.

圖1 目標物的合成路線Scheme 1 The synthetic route of target compounds

1.2 目標物4a～4i 的合成通法

微波合成: 將1.5 mmol中間體3, 1.6 mmol 芳香醛, 1滴醋酸, 0.8 g 中性Al2O3, 混合均勻, 置于專用合成微波爐中, 并外接干燥管,于400 W微波輻射下反應(yīng)1.0～3.0 min(TLC監(jiān)測反應(yīng)進程), 反應(yīng)結(jié)束后用CH2Cl2提取(10 mL×3), 減壓蒸去溶劑后得粗品, 用無水乙醇-石油醚重結(jié)晶得到純品, 產(chǎn)率為90%～ 95%.

常規(guī)合成: 將1.5 mmol中間體3溶于5ml 甲醇, 再依次加入1.6 mmol 芳香醛, 1滴醋酸, 回流反應(yīng)2.0～3.5 h(TLC檢測反應(yīng)進程), 冷卻, 減壓蒸去溶劑后得粗品, 用無水乙醇-石油醚重結(jié)晶得純品.

化合物4a: 白色晶體, 收率91%, m. p. 300～301℃,1H NMR (CDCl3, 400MHz) δ∶ 8.99 (s, 1H, CONH); δ∶ 8.54 (s, 1H, N=CH); δ∶ 8.05 (d, J = 8.4 Hz, 1H, ArH); δ∶ 7.35 (s, 1H, ArH); δ∶ 7.25(s, 1H, ArH); 2.07～1.70 (m, 15H, Adamantryl-H). IR(KBr), ν, cm-1: 3166, 3029, 2900, 2850, 1652, 1588, 1541, 1472, 1867, 820. ESI-MS m/z (%): 725([2M+Na]+, 100). Ana1. Calcd.for C18H20Cl2N2O: C, 61.55; H, 5.74; N, 7.97. Found: C, 61.43; H, 5.77; N, 8.01.

化合物4b: 白色晶體, 收率91%, m. p. 252～253℃,1H NMR (CDCl3, 400MHz) δ: 8.91 (s, 1H, CONH); δ: 8.29 (s, 1H, N=CH); δ: 7.71 (s, 1H, ArH); δ: 7.58 (d, J = 7.8 Hz 1H, ArH); δ: 7.35～7.27 (m, 2H, ArH); 2.09～1.72 (m, 15H, Adamantryl-H). IR(KBr), ν, cm-1: 3180, 3024, 2902, 2850, 1652, 1557, 1471, 1451, 812, 728. ESI-MS m/z (%): 600([2M+Na]+, 100). Ana1. Calcd. for C18H21ClN2O: C, 68.24; H, 6.68; N, 8.84. Found: C, 67.99; H, 6.65; N, 8.85.

化合物4c: 白色晶體, 收率95%, m. p. 221～222℃, 1H NMR (CDCl3, 400MHz) δ: 8.76 (s, 1H, CONH); δ: 8.12(s, 1H, N=CH); δ: 7.66～7.62 (m, 2H, ArH); δ:7.45～7.38 (m, 2H, ArH); 2.01～1.67(m, 15H, Adamantryl-H). IR (KBr), ν, cm-1: 3238, 3059, 2903, 2849, 1652, 1605, 1489, 755, 692. ESI-MS m/z (%):655([2M+Na]+, 100). C18H21ClN2O: C, 68.24; H, 6.68; N, 8.84. Found: C, 68.80; H, 6.71; N, 8.87.

化合物4d: 白色晶體, 收率92%, m. p. 259～260℃,1H NMR (CDCl3, 400MHz) δ: 8.90 (s, 1H, CONH); δ: 8.43 (s, 1H, N=CH); δ: 7.79 (d, J = 9.0 Hz, 2H, ArH); 7.66(d, J = 8.0Hz,2H,ArH); δ: 2.01～1.72 (m,15H, Adamantryl-H).IR (KBr), ν,cm-1: 3358, 2905, 2850, 2223, 1675, 1652, 1544, 1517, 1500, 829. ESI-MS m/z (%): 638 ([2M+Na]+, 100). Ana1. Calcd.for: C19H21N3O: C, 74.27; H, 6.89; N, 9.92. Found: C, 74.20; H, 6.92; N, 9.95.

化合物4e: 白色晶體, 收率90%, m. p. 250～251℃,1H NMR (CDCl3, 400MHz) δ: 8.89 (s, 1H, CONH); δ: 8.77 (s, 1H, N=CH); δ: 8.61～8.60 (m, 1H, ArH); δ: 8.40 (s, 1H, ArH); δ: 8.19 (d, J = 7.2 Hz, 1H, ArH); δ: 2.10(s, 3H, CH3); δ: 1.98～1.74 (m, 15H, Adamantryl-H). IR(KBr), ν, cm-1: 3448, 3178, 2905, 1662, 1552, 1450, 810, 703.ESI-MS m/z(%): 645([2M+Na]+, 100). Ana1. Calcd. for C19H25N3O: C, 73.28; H, 8.09; N, 13.49. Found: C, 73.20; H, 8.12; N, 13.47.

化合物4f: 黃色晶體, 收率93%, m. p. 202～203℃,1H NMR (CDCl3, 400MHz) δ: 8.61 (s, 1H, CONH); δ: 8.07 (s, 1H, N=CH); δ: 7.60 (d, J = 8.8 Hz, 2H, ArH); δ: 6.68 (d, J = 8.8 Hz, 2H, ArH); δ: 3.00(s, 6H, CH3); δ: 2.07～1.71(m, 15H, Adamantryl-H). IR(KBr), ν, cm-1: 3222, 2902, 2847, 1639, 1603, 1552, 1521, 813. ESI-MS m/z(%): 674([2M+Na]+, 100). Ana1. for Calcd. C17H21N3O: C, 73.81; H, 8.36; N, 12.91. Found: C, 73.66; H, 8.39; N, 12.88.

化合物4g: 白色晶體, 收率92%, m. p. 218～219℃,1H NMR (DMSO, 400MHz) δ: 10.73 (s, 1H, OH); δ: 9.59 (s, 1H, CONH); δ: 8.29 (s, 1H, N=CH); δ: 7.30～7.20(m, 1 H, ArH); δ: 7.12 (d, J = 7.6 Hz, 1H, ArH); δ: 7.02 (d, J = 7.6 Hz, 1H, ArH); δ: 6.81～6.78(m, 1H, ArH); δ: 2.09～1.60(m, 15H, Adamantryl-H). IR(KBr), ν, cm-1: 3249, 3080,2849, 1652, 1578, 1538, 1452, 785. ESI-MS m/z(%): 620 ([2M+Na]+, 100). Ana1. Calcd. for C18H22N2O: C, 72.49; H, 7.43; N, 9.39. Found: C, 72.35; H, 7.40; N, 9.41.

化合物4h: 白色晶體, 收率92%, m. p. 225～226℃,1H NMR (CDCl3, 400MHz) δ∶ 8.71(s, 1H, CONH); δ∶ 8.34 (s, 1H, N=CH); δ∶ 7.48～7.44 (m, 2H, ArH); δ∶ 7.37～7.32(m, 1H, ArH); δ∶ 7.10～7.05 (m, 1H, ArH); δ∶ 2.10～1.72 (m, 15H, Adamantryl-H) . IR(KBr), ν, cm-1: 3181, 3019, 2901, 2852, 1651, 1490, 1449, 785, 685. ESI-MS m/z(%) :620([2M+ Na]+, 100). Ana1. Calcd. for C18H21FN2O: C,71.98; H,7.05; N, 9.33. Found: C, 71.87; H, 7.02; N, 9.31.

化合物4i: 黃色晶體, 收率94%, m. p. 292～293℃,1H NMR (CDCl3, 400MHz) δ: 9.06(s, 1H, CONH); δ: 8.71(s, 1H, N=CH); δ: 2.55(s, 3H, thiazole-H); δ: 2.04 (s, 3H, CH3); δ: 2.04～1.71(m, 15H, Adamantryl-H). IR(KBr), ν, cm-1: 3175, 2902, 2882, 2849, 1651, 1567, 953, 793. ESI-MS m/z(%): 630([2M+Na]+, 100). Ana1. Calcd.for C16H21N3OS: C, 63.33; H, 6.98; N, 13.85. Found: C, 63.20; H, 6.96; N, 13.83.

2 結(jié)果與討論

2.1 目標物4a ～ 4i合成方法比較

微波干法與常規(guī)法合成目標化合物的實驗結(jié)果見表1. 以中性Al2O3固體為載體, 在微波輻射無溶劑條件下,快速高效的合成了金剛烷酰腙類衍生物. 與傳統(tǒng)加熱合成方法相比, 微波輻射無溶劑法具有以下優(yōu)勢:

(1)反應(yīng)產(chǎn)率從常規(guī)方法的70%～80%, 提升到90%～95%.

(2)反應(yīng)時間從常規(guī)所需的2.0～3.5 h縮短到1.0～3.0 min, 反應(yīng)速度增大70～130倍不等.

(3)避免大量有機溶劑在反應(yīng)中的使用, 反應(yīng)更加“綠色”.

因此微波無溶劑法是一種快捷、高效、綠色的合成金剛烷酰腙類衍生物的方法.

表1 微波法與常規(guī)法合成目標物4a ～ 4i的比較Tab. 1 Synthetic comparison between microwave irradiation and conventional heation of compounds 4a ～ 4i

2.2 目標物4a～4i的結(jié)構(gòu)確認

在1H NMR譜圖中, δ 8.61～9.59 ppm 的單峰屬于酰腙結(jié)構(gòu)中CONH的質(zhì)子峰, δ 8.07～8.77 ppm 的單峰屬于酰腙結(jié)構(gòu)中N=CH的質(zhì)子峰, δ 1.60～2.09 ppm的多重峰為金剛烷上的質(zhì)子峰. 在IR譜圖中在1650 cm-1附近出現(xiàn)強吸收帶為酰腙羰基(C=O)的吸收峰. 從質(zhì)譜圖中可見, 所有的目標化合物均能給出分子離子峰, 其m/z與相應(yīng)分子式的分子量是一致的. 元素分析結(jié)果表明, 所有化合物的組成與其實驗式相符. 綜上所述化合物4a～4i所有光譜和元素分析數(shù)據(jù)與其結(jié)構(gòu)式相符合, 表明所有化合物均為目標化合物.

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Microwave-assisted synthesis and structural characterization of novel adamantaneacylhydrazone derivatives

HUANG Mei-wei1, WU Shuang2, LIU Yi-fei1, ZHAO Zhi-gang1
(1. School of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities,Chengdu 610041, P.R.C.; 2. School of Electrical and Information Engineering, Southwest University for Nationalities, Chengdu 610041, P. R.C.)

Nine novel adamantaneacylhydrazone derivatives were synthesized in the solvent-free condition under microwave irradiation by using 1-adamantanecarboxylic acid as starting material. Compared with a conventional method, the yield was increased from 70%～ 80% to 90%～95% and the reaction time was reduced from 2.0～ 3.5 h to 1.0～ 3.0 min. The structures of the new compounds are confirmed by1H NMR, ESI-MS spectra, IR and element analyses.

adamantane; acylhydrazone; microwave synthesis

O621.3

A

1003-4271(2014)05-0686-04

10.3969/j.issn.1003-4271.2014.05.09

2014-08-04

趙志剛(1963-), 男, 漢族, 四川合江人, 教授, 博士, 從事生物有機與微波化學(xué)研究.

四川省科技支撐計劃項目(No. 2012SZ0160)