English

• 氧杂蒽衍生物具有很好的生物活性, 如抗菌^[1]、抗病毒^[2]和抗癌^[3]等.同时, 在pH敏感型荧光材料^[4]、激光技术^[5]和染料^[6]等方面也有很好的应用.随着氧杂蒽在各领域上的广泛应用, 其在合成方面备受人们关注, 且在近几年出现了很多合成氧杂蒽的方法^[7~9].然而, 随着人们的环保意识的增强, “绿色化学”已成为化学研究的一个重要方向.因此, 寻求一种绿色高效的合成氧杂蒽的方法具有重要的意义.另一方面, 水作为一种廉价、环境友好和安全的反应介质更符合“绿色化学”理念.在最近的报道中水作为反应介质也经常被应用在有机反应中^{[10, 11]}.

  介孔材料的出现为催化合成领域提供了很好的前景, 其所具有的极大比表面积和特殊的微观结构, 赋予了介孔材料很多特殊的性能^[12].近年来, 介孔材料在有机催化方面有很好的应用, 如Michael加成^[13]、氧化反应^[14]、Suzuki偶联反应^[15]和串联反应^[16]等.本工作我们用席夫碱改性的介孔材料MCM-41与金属盐在水相中通过“一锅法”催化醛、5, 5-二甲基-1, 3-环己二酮和2-萘酚合成氧杂蒽衍生物.通过一系列的反应条件筛选, 在最佳反应条件下, 合成了一系列高产率的氧杂蒽衍生物.最后, 在最佳条件下成功考察了放大实验和催化剂循环再利用实验.此方法为合成氧杂蒽衍生物提供了一种更为简单绿色的合成方法.

  1.   结果与讨论

  1.1   反应条件的优化

  以苯甲醛(0.11 mmol)、5, 5-二甲基-1, 3-环己二酮(0.1 mmol)和2-萘酚(0.1 mmol)作为模板反应, 选择水(0.5 mL)作为溶剂, 考察了不同反应条件对“一锅法”合成氧杂蒽化合物的影响.我们发现无催化剂条件下, 反应无法得到目标产物(表 1, Entry 1);当加入SiO₂时也没有产物生成(表 1, Entry 2).然而, 当加入介孔分子筛MCM-41 (L1)时, 反应能顺利进行, 并得到25%的目标产物(表 1, Entry 3), 由Entries 2和3可以看出, MCM-41的特殊孔道结构有利于反应进行, 因为MCM-41的硅羟基成分在其孔道内部, 能够更好地对底物起到富集作用.当用有机官能团修饰的MCM-41 (L2~L4)时, 使得其孔道内活性位点增多, 从而增加了催化活性, 其中L3得到较好的产率(表 1, Entry 5).为了使反应有更好的效果, 我们又加入了不同的金属盐(5 mol%), 其中L3/Mn(OAc)₂的催化效果最好, 能够得到95%的产率(表 1, Entry 8);然而, 单纯用Mn(OAc)₂催化时, 产率只有42%(表 1, Entry 14).由此说明, 负载在MCM-41上的席夫碱与Mn²⁺配位大大增加了反应活性.接着对有机溶剂进行了考察, 结果发现质子溶剂乙醇和非质子溶剂二氯乙烷、四氢呋喃、1, 4-二氧六环和甲苯均不能使反应有利的进行(表 1, Entries 15~19);在温度和反应时间的考察中发现, 降低温度或缩短反应时间都不利于反应进行(表 1, Entries 20~21);当Mn(OAc)₂用量降到3 mol%或增加到10 mol%时, 产率都有明显的降低(表 1, Entry 22).最后, 对反应底物的配比进行了研究, 底物苯甲醛/5, 5-二甲基-1, 3-环己二酮/2-萘酚物质的量之比为1:1:1和1:1.2:1时, 其反应产率均低于1.1:1:1时的产率(表 1, Entry 23).综上所述, 反应的最优条件为:苯甲醛(0.11 mmol)、5, 5-二甲基-1, 3-环己二酮(0.1 mmol)、2-萘酚(0.1 mmol)和L3 (0.005 g)/Mn(OAc)₂ (5 mol%)在水(0.5 mL)中100 ℃回流反应6 h.另外, 在最优反应条件下进行了放大实验, 在20 mmol扩大量下进行克级反应时, 反应产率无明显下降(表 1, Entry 24).

  表 1

  

  表 1  优化反应条件^a

  Table 1.  Optimization of the reaction conditions

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  Entry	Catalyst	Solvent	Time/h	Temp./℃	Yieldb/%
  1	None	H2O	6	100	Trace
  2	SiO2	H2O	6	100	Trace
  3	L1	H2O	6	100	25
  4	L2	H2O	6	100	27
  5	L3	H2O	6	100	48
  6	L4	H2O	6	100	45
  7	L3/Co(OAc)2	H2O	6	100	66
  8	L3/Mn(OAc)2	H2O	6	100	95
  9	L3/Cu(OAc)2	H2O	6	100	64
  10	L3/Ni(OAc)2	H2O	6	100	63
  11	L3/Zn(OAc)2	H2O	6	100	70
  12	L3/Mn(ClO4)2	H2O	6	100	60
  13	L3/Co(ClO4)2	H2O	6	100	75
  14	Mn(OAc)2	H2O	6	100	42
  15	L3/Mn(OAc)2	EtOH	6	80	10
  16	L3/Mn(OAc)2	DCE	6	85	15
  17	L3/Mn(OAc)2	THF	6	70	NRc
  18	L3/Mn(OAc)2	Dioxane	6	105	NRc
  19	L3/Mn(OAc)2	Toluene	6	110	NRc
  20	L3/Mn(OAc)2	H2O	6	50/70/90	NR/55/76
  21	L3/Mn(OAc)2	H2O	4/6/8	100	77/95/94
  22	L3/Mn(OAc)2	H2O	6	100	65d/85e
  23	L3/Mn(OAc)2	H2O	6	100	85/80f
  24	L3/Mn(OAc)2	H2O	9	100	91g
  a Reaction conditions (unless noted otherwise): benzaldehyde (0.11 mmol), dimedone (0.10 mmol), 2-naphthol (0.10 mmol), ligand (0.0050 g) and metal salts (5 mol%) in solvent (0.5 mL) at reflux for 6 h. b Isolated yield. c Over 20 h. d Use 10 mol% Mn(OAc)2. e Use 3 mol% Mn(OAc)2. f The molar ratio of 1a/2/3 is 1:1:1 or 1:1.2:1. g The reaction was performed with benzaldehyde (22 mmol), dimedone (20 mmol), 2-naphthol (20 mmol), L3 (1 g)/Mn(OAc)2 (5 mol%) in H2O (100 mL) at reflux for 9 h.

  1.2   反应底物的普适性考察

  在最优条件下对反应底物进行普适性考察(表 2), 并得到相应的产物4a~4w.考察了含有不同取代基的芳香醛衍生物.反应都能顺利地进行(产率89%~96%) (表 2, Entries 1~17).然而, 芳醛带有吸电子基(F, Cl, Br, NO₂等)的产率高于带有给电子基(CH₃, CH₃O, HO等)的产率, 说明电子效应对反应有一定的影响.值得注意的是, 在芳醛邻位含有大的位阻基团(NO₂, Br等), 也能得到较好的产率(Entries 8, 9).稠环和杂环醛参与反应时, 反应也能得到很好的产率(表 2, Entries 18~20), 但要低于芳香醛的产率.另外, 我们也考察了正丙醛、正丁醛及环己基甲醛等脂肪醛, 也能得到中等偏上的产率(表 2, Entries 21~23).因此, 所得到的催化体系对各种醛类有很好的兼容性.

  表 2

  

  表 2  L3/Mn(OAc)₂催化合成氧杂蒽衍生物^a

  Table 2.  L3/Mn(OAc)₂ catalyzed synthesis of xanthene derivatives

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  Entry	R1	Product	Yieldb/%	m.p./℃		Ref.
  				Found	Reported
  1	C6H5	4a	95	151~152	147~149	[19]
  2	4-ClC6H4	4b	93	182~184	179~181	[19]
  3	4-FC6H4	4c	95	183~185	185~186	[21]
  4	4-BrC6H4	4d	92	187~188	187~189	[21]
  5	4-O2NC6H4	4e	94	176~178	175~177	[19]
  6	4-H3CC6H4	4f	92	173~175	172~174	[19]
  7	2-ClC6H4	4g	92	178~179	177~179	[19]
  8	2-BrC6H4	4h	90	173~175	171~172	[20]
  9	2-O2NC6H4	4i	94	225~227	221~223	[19]
  10	3-ClC6H4	4j	94	171~173	173~174	[21]
  11	3-H3CC6H4	4k	91	179~181	181~182	[20]
  12	3-H3COC6H4	4l	88	201~203	204~206	[22]
  13	2, 4-Cl2C6H3	4m	96	180~182	178~180	[19]
  14	2, 3-Cl2C6H3	4n	94	223~224	225~227	[20]
  15	2-HOC6H4	4o	90	221~223	223~224	[22]
  16	5-Br-2-HOC6H3	4p	92	280~282	266~268	[25]
  17	5-O2N-2-HOC6H3	4q	89	264~265	263~265	[25]
  18	1-Naphthyl	4r	92	194~196	191~193	[21]
  19	2-Naphthyl	4s	91	232~234	235~237	[21]
  20		4t	90	＞300	—	—
  21	n-Propyl	4u	88	Oil	Oil	[23]
  22	n-Butyl	4v	90	Oil	Oil	[24]
  23	Cyclohexyl	4w	87	Oil	Oil	[22]
  a Reaction conditions: aldehydes (0.11 mmol), dimedone (0.10 mmol), 2-naphthol (0.10 mmol) and L3 (0.005 g)/Mn(OAc)2 (5 mol%) in water at reflux for 6 h. b Isolated yield.

  1.3   催化剂的循环利用性

  均相催化剂的可循环利用性不仅是判定催化剂性能的重要指标, 而且是绿色化学的一个重要理念^[17].以L3/Mn(OAc)₂作为催化剂, 在最优条件下对模板反应进行催化循环利用实验.通过薄层色谱(TLC)跟踪, 待反应完成后加入乙酸乙酯(3 mL×3)萃取有机相, 水相部分通过离心分离出催化剂, 用乙醇洗涤干燥后直接用于下次催化反应.催化剂重复使用5次后, 反应依然能得到很好的催化效果(图 1).

  图 1

  

  图 1.  催化剂L3/Mn(OAc)₂的循环利用

  Figure 1.  Reusability of the catalyst L3/Mn(OAc)₂

  下载: 全尺寸图片 幻灯片

  而对于催化剂使用多次后反应产率的降低, 通过比表面积测试仪(BET)测试催化剂参与反应前后数据对比(表 3), 在反应前后比表面积明显降低, 因为催化剂相对较小的部分孔径被堵塞, 平均孔径变大.所以导致催化剂的催化效率降低.

  表 3

  

  表 3  催化剂L3/Mn(OAc)₂催化循环前后的BET测试

  Table 3.  BET test before and after the used catalyst L3/ Mn(OAc)₂

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  Entry	Catalyst	Surface area/ (m2•g－1)	Mean pore size/ nm
  1	L3+Mn(OAc)2	170.59049	3.61148
  2	Used L3/Mn(OAc)2	95.40932	4.08279

  1.4   反应机理

  根据文献[18]报道, 可能的反应机理如Scheme 1所示.首先, L3/Mn(OAc)₂活化醛1上的羰基形成1', 1'被亲核试剂2-萘酚(3)进攻, 通过亲核加成生成中间体Ⅰ, Ⅰ进一步转换为迈克受体Ⅱ. 5, 5-二甲基-1, 3-环己二酮(2)的烯醇式2'和中间体Ⅱ发生迈克加成得到Ⅲ, 由Ⅲ经分子内环化得到Ⅳ.最后, Ⅳ通过脱去一分子水得到产物4a.

  图式 1

  

  图式 1.  L3/Mn(OAc)₂催化合成氧杂蒽衍生物可能的机理

  Scheme 1.  Plausible reaction mechanism for synthesis of xanthene derivatives with L3/Mn(OAc)₂

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  2.   结论

  开发了一种简单、绿色、高效地合成氧杂蒽衍生物的方法.通过介孔分子筛MCM-41固载席夫碱和Mn(OAc)₂, 在水相中共催化以醛、5, 5-二甲基-1, 3-环己二酮和2-萘酚为底物合成氧杂蒽衍生物.反应具有操作简单、底物的普适性好及产率较高等优点.通过实验可以看出催化剂的特殊孔道结构有利于反应的进行.并且催化剂循环利用5次后, 依然得到高达82%的产率, 而且易于放大制备克级反应.综上可知, 此方法展现了很好的应用前景.

  3.   实验部分

  3.1   仪器与试剂

  核磁共振谱用Varian inova-400型核磁共振仪(CDCl₃为溶剂, 内标TMS); RV10型旋转蒸发仪; X-4数字显微熔点测试仪; ZF-2型紫外仪; BRUKER EQUINX55红外光谱仪; EX-1000 X射线衍射仪; S4700透射电镜扫描仪; SU8010扫描电子显微镜; Ultimate 3000/Q-Exactive质谱仪; 柱层层析硅胶(400目); GF₂₅₄高效薄层层析板.石油醚(b.p. 60~90 ℃)和乙酸乙酯为分析纯, 所有实验室药品均为市售分析纯试剂, 除苯甲醛经过重蒸处理外其他试剂均未进行纯化处理.

  3.2   目标化合物的合成

  以化合物4a的合成为例, 于反应管中加入苯甲醛(0.11 mmol)、5, 5-二甲基-1, 3-环己二酮(0.1 mmol)、2-萘酚(0.1 mmol)、介孔分子筛MCM-41固载席夫碱配体L3 (0.005 g)和Mn(OAc)₂ (5 mol%)、H₂O (0.5 mL), 在100 ℃回流反应6 h, TLC检测反应.待反应完毕, 加入乙酸乙酯(3 mL×3)萃取, 无水硫酸钠干燥, 减压浓缩得到粗品, 通过柱层析[V(乙酸乙酯):V(石油醚)＝1:50]分离纯化得到目标化合物4a.

  9, 9-二甲基-12-苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4a):白色固体, 产率95%. m.p. 151~152 ℃ (lit.^[19] m.p. 147~149 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.00 (d, J＝8.4 Hz, 1H), 7.82~7.73 (m, 2H), 7.46~7.30 (m, 5H), 7.21~7.13 (m, 2H), 7.09~7.01 (m, 1H), 5.71 (s, 1H), 2.57 (s, 2H), 2.28 (dd, J＝7.1, 16.3 Hz, 2H), 1.12 (s, 3H), 0.96 (s, 3H).

  9, 9-二甲基-12-对氯苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4b):白色固体, 产率93%. m.p. 182~184 ℃ (lit.^[19] m.p. 179~181 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.91 (d, J＝8.4 Hz, 1H), 7.82~7.76 (m, 2H), 7.47~7.42 (m, 1H), 7.41~7.36 (m, 1H), 7.33 (d, J＝8.9 Hz, 1H), 7.30~7.25 (m, 2H), 7.18~7.11 (m, 2H), 5.69 (s, 1H), 2.57 (s, 2H), 2.28 (dd, J＝8.5, 16.3 Hz, 2H), 1.13 (s, 3H), 0.97 (s, 3H).

  9, 9-二甲基-12-对氟苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4c):白色固体, 产率95%. m.p. 183~185 ℃ (lit.^[21] m.p. 185~186 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.95 (d, J＝8.5 Hz, 1H), 7.78 (t, J＝8.6 Hz, 2H), 7.47~7.36 (m, 2H), 7.36~7.30 (m, 3H), 6.91~6.84 (m, 2H), 5.72 (s, 1H), 2.57 (s, 2H), 2.29 (dd, J＝36.1, 16.3 Hz, 2H), 1.13 (s, 3H), 0.97 (s, 3H).

  9, 9-二甲基-12-对溴苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4d):白色固体, 产率92%. m.p. 187~188 ℃ (lit.^[21] m.p. 187~189 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.91 (d, J＝8.3 Hz, 1H), 7.82~7.74 (m, 2H), 7.47~7.36 (m, 2H), 7.35~7.27 (m, 3H), 7.25~7.19 (m, 2H), 5.68 (s, 1H), 2.57 (s, 2H), 2.28 (dd, J＝8.6, 16.5 Hz, 2H), 1.13 (s, 3H), 0.97 (s, 3H).

  9, 9-二甲基-12-对硝基苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4e):白色固体, 产率94%. m.p. 176~178 ℃ (lit.^[19] m.p. 175~177 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.07~8.00 (m, 2H), 7.86~7.79 (m, 3H), 7.54~7.49 (m, 2H), 7.48~7.38 (m, 2H), 7.36 (d, J＝9.0 Hz, 1H), 5.82 (s, 1H), 2.66~2.53 (m, 2H), 2.29 (dd, J＝35.9, 16.3 Hz, 2H), 1.14 (s, 3H), 0.95 (s, 3H).

  9, 9-二甲基-12-对甲基苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4f):白色固体, 产率92%. m.p. 173~175 ℃ (lit.^[19] m.p. 172~174 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.03 (d, J＝8.5 Hz, 1H), 7.82~7.72 (m, 2H), 7.47~7.41 (m, 1H), 7.40~7.31 (m, 2H), 7.30~7.22 (m, 2H), 6.99 (d, J＝7.9 Hz, 2H), 5.70 (s, 1H), 2.57 (s, 2H), 2.29 (dd, J＝36.1, 16.3 Hz, 2H), 2.21 (s, 3H), 1.12 (s, 3H), 0.99 (s, 3H).

  9, 9-二甲基-12-邻氯苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4g):白色固体, 产率92%. m.p. 178~179 ℃ (lit.^[19] m.p. 177~179 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (d, J＝8.5 Hz, 1H), 7.79~7.72 (m, 2H), 7.50~7.45 (m, 1H), 7.41~7.35 (m, 1H), 7.31~7.24 (m, 3H), 7.08~7.03 (m, 1H), 7.02~6.96 (m, 1H), 6.00 (s, 1H), 2.60 (d, J＝0.9 Hz, 2H), 2.27 (dd, J＝36.4, 16.3 Hz, 2H), 1.13 (s, 3H), 1.00 (s, 3H).

  9, 9-二甲基-12-邻溴苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4h):白色固体, 产率90%. m.p. 173~175 ℃ (lit.^[20] m.p. 171~172 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.38~8.27 (m, 1H), 7.79~7.73 (m, 2H), 7.53~7.45 (m, 2H), 7.42~7.35 (m, 1H), 7.32~7.18 (m, 2H), 7.12~7.05 (m, 1H), 6.93~6.87 (m, 1H), 5.97 (s, 1H), 2.61 (s, 2H), 2.28 (dd, J＝36.2, 16.2 Hz, 2H), 1.14 (s, 3H), 1.00 (s, 3H).

  9, 9-二甲基-12-邻硝基苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4i):黄色固体, 产率94%. m.p. 225~227 ℃ (lit.^[19] m.p. 221~223 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.56 (d, J＝8.5 Hz, 1H), 7.87~7.77 (m, 3H), 7.50~7.38 (m, 2H), 7.33 (d, J＝8.9 Hz, 1H), 7.28~7.15 (m, 2H), 7.06 (dd, J＝7.8, 1.5 Hz, 1H), 6.59 (s, 1H), 2.62~2.48 (m, 2H), 2.29~2.13 (m, 2H), 1.09 (s, 3H), 0.87 (s, 3H).

  9, 9-二甲基-12-间氯苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4j):白色固体, 产率94%. m.p. 171~173 ℃ (lit.^[21] m.p. 173~174 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.92 (d, J＝8.5 Hz, 1H), 7.81~7.75 (m, 2H), 7.48~7.42 (m, 1H), 7.41~7.36 (m, 1H), 7.33 (d, J＝8.9 Hz, 1H), 7.31~7.24 (m, 2H), 7.15~7.08 (m, 1H), 7.03~7.01 (m, 1H), 5.69 (s, 1H), 2.60~2.50 (m, 2H), 2.35~2.20 (m, 2H), 1.11 (s, 3H), 0.97 (s, 3H).

  9, 9-二甲基-12-间甲基苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4k):白色固体, 产率91%. m.p. 179~181 ℃ (lit.^[20] m.p. 181~182 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.07~8.02 (m, 1H), 7.81~7.74 (m, 2H), 7.47~7.42 (m, 1H), 7.41~7.32 (m, 2H), 7.19~7.13 (m, 2H), 7.07 (t, J＝7.6 Hz, 1H), 6.90~6.85 (m, 1H), 5.70 (s, 1H), 2.63~2.52 (m, 2H), 2.35~2.27 (m, 2H), 2.25 (s, 3H), 1.13 (s, 3H), 0.99 (s, 3H).

  9, 9-二甲基-12-间甲氧基苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4l):白色固体, 产率88%. m.p. 201~203 ℃ (lit.^[22] m.p. 204~206 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.02 (d, J＝8.3 Hz, 1H), 7.78 (dd, J＝12.6, 4.7 Hz, 2H), 7.47~7.42 (m, 1H), 7.41~7.35 (m, 1H), 7.33 (d, J＝8.9 Hz, 1H), 7.12~7.08 (m, 1H), 6.98~6.90 (m, 2H), 6.61 (dd, J＝8.2, 2.6 Hz, 1H), 5.71 (s, 1H), 3.72 (s, 3H), 2.57 (s, 2H), 2.37~2.23 (m, 2H), 1.12 (s, 3H), 0.99 (s, 3H).

  9, 9-二甲基-12-(2, 4-二氯苯基)-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4m):橙色固体, 产率96%. m.p. 180~182 ℃ (lit.^[19] m.p. 178~180 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.13 (d, J＝8.6 Hz, 1H), 7.81~7.75 (m, 2H), 7.52~7.46 (m, 1H), 7.43~7.38 (m, 1H), 7.31~7.27 (m, 2H), 7.25~7.19 (d, J＝8 Hz, 1H), 7.05 (dd, J＝8.4, 2.1 Hz, 1H), 5.95 (s, 1H), 2.68~2.55 (m, 2H), 2.28 (dd, J＝37.6, 16.3 Hz, 2H), 1.15 (s, 3H), 1.01 (s, 3H).

  9, 9-二甲基-12-(2, 3-二氯苯基)-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4n):白色固体, 产率94%. m.p. 223~224 ℃ (lit.^[20] m.p. 225~227 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.15 (d, J＝8.5 Hz, 1H), 7.80~7.74 (m, 2H), 7.52~7.47 (m, 1H), 7.42~7.37 (m, 1H), 7.30 (d, J＝8.9 Hz, 1H), 7.21~7.19 (m, 1H), 7.03~6.98 (m, 1H), 6.05 (s, 1H), 2.61 (s, 2H), 2.36~2.22 (m, 2H), 1.14 (s, 3H), 1.01 (s, 3H).

  9, 9-二甲基-12-邻羟基苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4o):白色固体, 产率90%. m.p. 221~223 ℃ (lit.^[22] m.p. 223~224 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 9.26 (s, 1H), 7.81~7.76 (m, 2H), 7.68 (d, J＝8.0 Hz, 1H), 7.43~7.37 (m, 2H), 7.35~7.32 (m, 1H), 7.03~6.98 (m, 2H), 6.65~6.59 (m, 2H), 5.77 (s, 1H), 2.61 (s, 2H), 2.45~2.32 (m, 2H), 1.15 (s, 3H), 1.00 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 200.61 (s), 166.80 (s), 152.84 (s), 147.81 (s), 132.68 (s), 131.51 (s), 131.08 (s), 129.08 (s), 128.73 (s), 128.21 (s), 127.87 (s), 127.51 (s), 125.24 (s), 123.44 (s), 121.51 (s), 118.81 (s), 117.46 (s), 116.54 (s), 113.90 (s), 50.24 (s), 41.58 (s), 32.40 (s), 29.03 (s), 27.99 (s), 27.24 (s).

  9, 9-二甲基-12-(2-羟基-5-溴)-苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4p):黄色固体, 产率92%. m.p. 280~282 ℃ (lit.^[25] m.p. 266~268 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 9.35 (s, 1H), 7.84~7.78 (m, 2H), 7.64~7.60 (m, 1H), 7.46~7.38 (m, 2H), 7.35 (d, J＝8.9 Hz, 1H), 7.10 (dd, J＝8.6, 2.5 Hz, 1H), 6.91 (d, J＝8.6 Hz, 1H), 6.66 (d, J＝2.4 Hz, 1H), 5.73 (s, 1H), 2.70~2.57 (m, 2H), 2.45~2.34 (m, 2H), 1.15 (s, 3H), 1.03 (s, 3H).

  9, 9-二甲基-12-(2-羟基-5-硝基)-苯基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4q):白色固体, 产率89%. m.p. 264~265 ℃ (lit.^[25] m.p. 263~265 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 10.43 (s, 1H), 7.92 (dd, J＝8.9, 2.8 Hz, 1H), 7.88~7.78 (m, 2H), 7.53~7.48 (m, 1H), 7.46 (d, J＝2.8 Hz, 1H), 7.44~7.37 (m, 3H), 7.09 (d, J＝8.9 Hz, 1H), 5.76 (s, 1H), 2.73~2.61 (m, 2H), 2.50~2.36 (m, 2H), 1.17 (s, 3H), 1.01 (s, 3H).

  9, 9-二甲基-12-(1-萘)-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4r):黄色固体, 产率92%. m.p. 194~196 ℃(lit.^[21] m.p. 191~193 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 9.23 (s, 1H), 7.93 (d, J＝8.3 Hz, 1H), 7.85~7.71 (m, 4H), 7.60 (d, J＝8.9 Hz, 1H), 7.57~7.51 (m, 1H), 7.43~7.21 (m, 5H), 6.47 (s, 1H), 2.63 (s, 2H), 2.25 (dd, J＝36.1, 16.4 Hz, 2H), 1.13 (s, 3H), 0.95 (s, 3H).

  9, 9-二甲基-12-(2-萘)-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4s):白色固体, 产率91%. m.p. 232~234 ℃(lit.^[21] m.p. 235~237 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.07 (d, J＝8.5 Hz, 1H), 7.85 (d, J＝1.4 Hz, 1H), 7.82~7.75 (m, 3H), 7.72~7.64 (m, 2H), 7.49 (dd, J＝8.5, 1.8 Hz, 1H), 7.45~7.33 (m, 5H), 5.91 (s, 1H), 2.60 (s, 2H), 2.28 (dd, J＝36.1, 16.4 Hz, 2H), 1.13 (s, 3H), 0.94 (s, 3H).

  9, 9-二甲基-12-(2-(5-(4-硝基苯基))呋喃)-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4t):红色固体, 产率90%. m.p.＞300 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.22 (d, J＝8.0 Hz, 1H), 8.17~8.10 (m, 2H), 7.86~7.78 (m, 2H), 7.60~7.51 (m, 3H), 7.48~7.43 (m, 1H), 7.33 (d, J＝8.9 Hz, 1H), 6.65 (d, J＝3.4 Hz, 1H), 6.21 (dd, J＝3.4, 0.5 Hz, 1H), 5.93 (s, 1H), 2.65 (s, 2H), 2.39 (s, 2H), 1.18 (s, 3H), 1.11 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 196.63 (s), 171.11 (s), 165.85 (s), 158.04 (s), 150.21 (s), 147.91 (s), 145.94 (s), 136.39 (s), 131.36 (s), 129.25 (s), 128.52 (s), 127.11 (s), 125.15 (s), 124.17 (s), 123.26 (d, J＝11.7 Hz), 117.19 (s), 114.56 (s), 110.48 (s), 110.02 (s), 109.20 (s), 60.36 (s), 50.82 (s), 41.48 (s), 32.30 (s), 29.40 (s), 28.46 (s), 27.11 (s), 21.02 (s), 14.17 (s); HRMS (ESI) calcd for C₂₉H₂₃NO₅ [M+Na]⁺ 488.14684, found 488.14633.

  9, 9-二甲基-12-乙基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4u)^[23]:黄色油状, 产率88%. ¹H NMR (400 MHz, CDCl₃) δ: 8.11 (d, J＝8.5 Hz, 1H), 7.86~7.79 (m, 1H), 7.70 (d, J＝8.9 Hz, 1H), 7.58~7.51 (m, 1H), 7.47~7.40 (m, 1H), 7.20 (d, J＝8.9 Hz, 1H), 4.73 (m, 1H), 2.60~2.47 (m, 2H), 2.42~2.31 (m, 2H), 1.82~1.70 (m, 2H), 1.19 (s, 3H), 1.15 (s, 3H), 0.79~0.67 (m, 3H).

  9, 9-二甲基-12-丙基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4v)^[24]:黄色油状, 产率90%. ¹H NMR (400 MHz, CDCl₃) δ: 8.09 (d, J＝8.5 Hz, 1H), 7.84~7.79 (m, 1H), 7.69 (d, J＝8.9 Hz, 1H), 7.56~7.50 (m, 1H), 7.46~7.40 (m, 1H), 7.19 (d, J＝8.9 Hz, 1H), 4.74 (t, J＝4.3 Hz, 1H), 2.60~2.48 (m, 2H), 2.41~2.31 (m, 2H), 1.90~1.81 (m, 2H), 1.31~1.22 (m, 2H), 1.20 (s, 3H), 1.15 (s, 3H), 0.61 (t, J＝7.5 Hz, 3H).

  9, 9-二甲基-12-环己基-8, 9, 10, 12-四氢-11H-苯并吡喃-11-酮(4w)^[22]:黄色油状, 产率87%. ¹H NMR (400 MHz, CDCl₃) δ: 8.12 (t, J＝7.7 Hz, 1H), 7.81 (t, J＝7.7 Hz, 1H), 7.73~7.67 (m, 1H), 7.57~7.49 (m, 1H), 7.46~7.40 (m, 1H), 7.25~7.19 (m, 1H), 5.21~4.62 (m, 1H), 2.64~2.48 (m, 2H), 2.43~2.26 (m, 2H), 2.00~1.38 (m, 8H), 1.26 (m, 3H), 1.14 (m, 3H), 1.00~0.84 (m, 3H).

  3.3   催化剂的合成及数据表征

  MCM-41介孔分子筛的改性参见文献[26].取MCM-41 (L1)介孔分子筛(Tansoole XF NANO, INC)与6 mL氨丙基三乙氧基硅烷在甲苯中N₂保护下反应得到改性分子筛(L2) 1.2 g, 干燥后取1 g改性分子筛(L2)加入到100 mL三颈瓶中, 然后加入5 mmol 2-苯基-1, 2, 3-三唑基或喹喔啉-2-甲醛, 在N₂环境下加入40 mL甲苯, 滴加0.4 mL Et₃N, 70 ℃回流搅拌反应24 h.溶液冷却至室温, 过滤, 将过滤后产物用乙醚和二氯甲烷分别洗涤3次, 产品烘干分别得灰白色粉末状固体L3和L4各1.1 g.

  辅助材料(Sopporting Information) 化合物4a~4w的核磁共振氢谱、碳谱图或质谱以及催化剂的数据表征.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

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• 

  图 1  催化剂L3/Mn(OAc)₂的循环利用

  Figure 1  Reusability of the catalyst L3/Mn(OAc)₂

  下载: 全尺寸图片 幻灯片
  

  图式 1  L3/Mn(OAc)₂催化合成氧杂蒽衍生物可能的机理

  Scheme 1  Plausible reaction mechanism for synthesis of xanthene derivatives with L3/Mn(OAc)₂

  下载: 全尺寸图片 幻灯片

  表 1  优化反应条件^a

  Table 1.  Optimization of the reaction conditions

  Entry	Catalyst	Solvent	Time/h	Temp./℃	Yieldb/%
  1	None	H2O	6	100	Trace
  2	SiO2	H2O	6	100	Trace
  3	L1	H2O	6	100	25
  4	L2	H2O	6	100	27
  5	L3	H2O	6	100	48
  6	L4	H2O	6	100	45
  7	L3/Co(OAc)2	H2O	6	100	66
  8	L3/Mn(OAc)2	H2O	6	100	95
  9	L3/Cu(OAc)2	H2O	6	100	64
  10	L3/Ni(OAc)2	H2O	6	100	63
  11	L3/Zn(OAc)2	H2O	6	100	70
  12	L3/Mn(ClO4)2	H2O	6	100	60
  13	L3/Co(ClO4)2	H2O	6	100	75
  14	Mn(OAc)2	H2O	6	100	42
  15	L3/Mn(OAc)2	EtOH	6	80	10
  16	L3/Mn(OAc)2	DCE	6	85	15
  17	L3/Mn(OAc)2	THF	6	70	NRc
  18	L3/Mn(OAc)2	Dioxane	6	105	NRc
  19	L3/Mn(OAc)2	Toluene	6	110	NRc
  20	L3/Mn(OAc)2	H2O	6	50/70/90	NR/55/76
  21	L3/Mn(OAc)2	H2O	4/6/8	100	77/95/94
  22	L3/Mn(OAc)2	H2O	6	100	65d/85e
  23	L3/Mn(OAc)2	H2O	6	100	85/80f
  24	L3/Mn(OAc)2	H2O	9	100	91g
  a Reaction conditions (unless noted otherwise): benzaldehyde (0.11 mmol), dimedone (0.10 mmol), 2-naphthol (0.10 mmol), ligand (0.0050 g) and metal salts (5 mol%) in solvent (0.5 mL) at reflux for 6 h. b Isolated yield. c Over 20 h. d Use 10 mol% Mn(OAc)2. e Use 3 mol% Mn(OAc)2. f The molar ratio of 1a/2/3 is 1:1:1 or 1:1.2:1. g The reaction was performed with benzaldehyde (22 mmol), dimedone (20 mmol), 2-naphthol (20 mmol), L3 (1 g)/Mn(OAc)2 (5 mol%) in H2O (100 mL) at reflux for 9 h.

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  表 2  L3/Mn(OAc)₂催化合成氧杂蒽衍生物^a

  Table 2.  L3/Mn(OAc)₂ catalyzed synthesis of xanthene derivatives

  Entry	R1	Product	Yieldb/%	m.p./℃		Ref.
  				Found	Reported
  1	C6H5	4a	95	151~152	147~149	[19]
  2	4-ClC6H4	4b	93	182~184	179~181	[19]
  3	4-FC6H4	4c	95	183~185	185~186	[21]
  4	4-BrC6H4	4d	92	187~188	187~189	[21]
  5	4-O2NC6H4	4e	94	176~178	175~177	[19]
  6	4-H3CC6H4	4f	92	173~175	172~174	[19]
  7	2-ClC6H4	4g	92	178~179	177~179	[19]
  8	2-BrC6H4	4h	90	173~175	171~172	[20]
  9	2-O2NC6H4	4i	94	225~227	221~223	[19]
  10	3-ClC6H4	4j	94	171~173	173~174	[21]
  11	3-H3CC6H4	4k	91	179~181	181~182	[20]
  12	3-H3COC6H4	4l	88	201~203	204~206	[22]
  13	2, 4-Cl2C6H3	4m	96	180~182	178~180	[19]
  14	2, 3-Cl2C6H3	4n	94	223~224	225~227	[20]
  15	2-HOC6H4	4o	90	221~223	223~224	[22]
  16	5-Br-2-HOC6H3	4p	92	280~282	266~268	[25]
  17	5-O2N-2-HOC6H3	4q	89	264~265	263~265	[25]
  18	1-Naphthyl	4r	92	194~196	191~193	[21]
  19	2-Naphthyl	4s	91	232~234	235~237	[21]
  20		4t	90	＞300	—	—
  21	n-Propyl	4u	88	Oil	Oil	[23]
  22	n-Butyl	4v	90	Oil	Oil	[24]
  23	Cyclohexyl	4w	87	Oil	Oil	[22]
  a Reaction conditions: aldehydes (0.11 mmol), dimedone (0.10 mmol), 2-naphthol (0.10 mmol) and L3 (0.005 g)/Mn(OAc)2 (5 mol%) in water at reflux for 6 h. b Isolated yield.

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  表 3  催化剂L3/Mn(OAc)₂催化循环前后的BET测试

  Table 3.  BET test before and after the used catalyst L3/ Mn(OAc)₂

  Entry	Catalyst	Surface area/ (m2•g－1)	Mean pore size/ nm
  1	L3+Mn(OAc)2	170.59049	3.61148
  2	Used L3/Mn(OAc)2	95.40932	4.08279

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