CN110272400B - 2-三氟甲基取代呋喃化合物及其衍生物的合成方法 - Google Patents
2-三氟甲基取代呋喃化合物及其衍生物的合成方法 Download PDFInfo
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- CN110272400B CN110272400B CN201910663244.0A CN201910663244A CN110272400B CN 110272400 B CN110272400 B CN 110272400B CN 201910663244 A CN201910663244 A CN 201910663244A CN 110272400 B CN110272400 B CN 110272400B
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
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Abstract
本发明公开了一种2‑三氟甲基取代呋喃化合物及其衍生物的合成方法,其是以碱为促进剂,苯甲酰乙腈衍生物为底物,3‑溴‑1,1,1‑三氟丙酮为氟化试剂,在溶剂中,经串联反应得到所述2‑三氟甲基取代呋喃化合物;再经脱水及氰的水解制得2‑三氟甲基取代呋喃衍生物。该反应采用一锅法合成,具有操作步骤简便、原料易制备,反应体系对官能团的普适性较高等优点。所得氟化呋喃化合物对松材线虫等具有很好的杀灭活性,在100 mg/L剂量下,对线虫的死亡率高达87%,可作为一种潜在的含氟杀虫剂。
Description
技术领域
本发明属于有机氟化学合成技术领域,具体涉及一种2-三氟甲基取代呋喃化合物及其衍生物的合成方法。
背景技术
将含氟基团引入到杂环分子中,能极大地改变分子内在的物理、化学性质以及生物性能,例如增强其分子的脂溶性、提高药物的生物利用度等,是药物化学结构改造的重要研究策略之一。其中,三氟甲基由于具有较强的吸电子性和极高的亲脂性,使研究如何高效、选择性地往杂环分子中引入三氟甲基成为有机合成氟化学的重要课题。呋喃类化合物作为一类五元杂环化合物,在杀虫、杀菌、抗癌上表现出较好的生物活性。往呋喃环上引入三氟甲基,有可能增强该类分子的生物活性,表现出和非氟有机杂环分子不同的特点,具有重要的理论研究意义和实际应用价值。
发明内容
本发明的目的在于提供一种2-三氟甲基取代呋喃化合物及其衍生物的合成方法,该方法步骤简便、原料易得,所得化合物有望作用潜在的含氟杀虫剂。
为实现上述目的,本发明采用如下技术方案:
一种2-三氟甲基取代呋喃化合物及其衍生物的合成方法,其是以碱为促进剂,苯甲酰乙腈衍生物为底物,3-溴-1,1,1-三氟丙酮为氟化试剂,经串联反应制得2-三氟甲基取代呋喃化合物;再经脱水及氰的水解制得2-三氟甲基取代呋喃衍生物;其反应式为:
其中,所述苯甲酰乙腈衍生物为下述式1-式26中的任意一种:
所述2-三氟甲基取代呋喃化合物的具体合成步骤如下:在氮气气氛中,向带有磁力搅拌装置的容器中加入苯甲酰乙腈衍生物、3-溴-1,1,1-三氟丙酮、碱以及溶剂,混合均匀后关好塞子,将其于60-80 ℃搅拌反应1-12小时后,用乙酸乙酯萃取3次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后旋蒸除去有机溶剂;得到的粗产物采用硅胶柱层析分离,以正戊烷-乙酸乙酯为洗脱剂进行洗脱,得到所述2-三氟甲基取代呋喃化合物;
其中所用碱为Na2CO3、NaOH、K2CO3、K3PO4、NEt3中的任意一种,优选为Na2CO3;所用溶剂为乙腈、1,4-二氧六环、甲醇中的任意一种,优选为1,4-二氧六环。
所述2-三氟甲基取代呋喃化合物的具体合成步骤如下:向带有磁力搅拌装置的容器中加入苯甲酰乙腈衍生物、3-溴-1,1,1-三氟丙酮、碱以及溶剂,混合均匀后关好塞子,将其于常温下搅拌反应1-12小时后,用乙醚萃取3次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后旋蒸除去有机溶剂;得到的粗产物采用硅胶柱层析分离,以正戊烷-乙酸乙酯为洗脱剂进行洗脱,得到所述2-三氟甲基取代呋喃化合物;
其中所所用碱为NaOAc;所用溶剂为乙腈、1,4-二氧六环、甲醇中的任意一种,优选为1,4-二氧六环。
上述操作中,所用苯甲酰乙腈衍生物、3-溴-1,1,1-三氟丙酮、碱及溶剂的摩尔比均为(0.1-1):(0.1-1):(0.1-1): (10-80)。
所述2-三氟甲基取代呋喃衍生物的具体合成步骤如下:向带有磁力搅拌装置的容器中加入5-羟基-2-苯基-5-(三氟甲基)-4,5-二氢呋喃-3-腈衍生物()、浓硫酸,混合均匀后关好塞子,将其于40-60 ℃下搅拌反应1-12小时后,用乙酸乙酯萃取3次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后旋蒸除去有机溶剂;得到的粗产物采用硅胶柱层析分离,以正戊烷-乙酸乙酯为洗脱剂进行洗脱,得到所述2-三氟甲基取代呋喃化合物。
上述操作中,所用5-羟基-2-苯基-5-(三氟甲基)-4,5-二氢呋喃-3-腈衍生物与浓硫酸的摩尔比为(0.1-1):(1-15)。
所得2-三氟甲基取代呋喃化合物及其衍生物对松材线虫等具有很好的杀灭活性,有望用于制备含氟杀虫剂。
本发明的有益效果在于:
(1)本发明以简单易得的苯甲酰乙腈衍生物、3-溴-1,1,1-三氟丙酮等为原料,以碱为促进剂,经串联反应合成2-三氟甲基取代呋喃化合物,并经进一步脱水及氰的水解制得2-三氟甲基取代呋喃衍生物,其官能团的适应性较好,且其操作简便,具有良好的工业应用前景。
(2)所得氟化呋喃化合物对松材线虫等具有很好的杀灭活性,在100 mg/L剂量下,对线虫的死亡率高达87%,可作为一种潜在的含氟杀虫剂。
附图说明
图1为实施例1制得的2-三氟甲基-4-苯甲酰基-5-氨基呋喃的单晶结构图。
图2为实施例20制得的5-羟基-2-苯基-5-(三氟甲基)-4,5-二氢呋喃-3-腈的单晶结构图。
图3为实施例47制得的2-(2-氯苯基)-5-(三氟甲基)呋喃-3-甲酰胺的单晶结构图。
具体实施方式
为了使本发明所述的内容更加便于理解,下面结合具体实施方式对本发明所述的技术方案做进一步的说明,但是本发明不仅限于此。
实施例1
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58 mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(苯基)甲酮(分离产率86%)。1H NMR (400MHz, CDCl3) δ 7.75 (d, J = 7.0 Hz, 2H), 7.53 (dt, J = 13.7, 6.7 Hz, 3H), 7.00(s, 1H), 6.79 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -64.1 (s, 3F). 13C NMR (101MHz, CDCl3) δ 189.3 (s), 164.2 (s), 139.1 (s), 131.7 (s), 130.7 (q, J = 44.0Hz), 128.6 (s), 127.9 (s), 119.1 (q, J = 265.6 Hz), 113.4 (dd, J = 5.8, 2.8Hz), 98.1 (s)。
实施例2
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 4-甲基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol氢氧化钠,最后加入58 mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(对甲苯基)甲酮(分离产率75%)。1HNMR (400 MHz, CDCl3) δ 7.67 (d, J = 7.4 Hz, 2H), 7.31 (d, J = 7.4 Hz, 2H),7.01 (s, 1H), 6.77 (s, 2H), 2.45 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -64.0 (s,3F). 13C NMR (101 MHz, CDCl3) δ 189.1 (s), 164.2 (s), 142.3 (s), 136.4 (s),130.5 (q, J = 44.0 Hz), 129.2 (s), 128.0 (s), 119.1 (q, J = 265.5 Hz), 113.5(dd, J = 5.9, 2.9 Hz), 98.1 (s), 21.5 (s)。
实施例3
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 4-叔丁基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol磷酸钾,最后加入58 mmol的1,4二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15mL水,用乙酸乙酯10mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(对叔丁基苯基)甲酮(分离产率74%)。 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.1 Hz, 2H), 7.54 (d, J = 7.1 Hz,2H), 7.05 (s, 1H), 6.70 (s, 2H), 1.39 (s, 9H). 19F NMR (376 MHz, CDCl3) δ -64.0 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 189.1 (s), 164.0 (s), 155.3 (s),136.4 (s), 130.6 (q, J = 44.0 Hz), 127.9 (s), 125.5 (s), 119.1 (q, J = 265.5Hz), 113.5 (q, J = 3.0 Hz), 98.2 (s), 35.0 (s), 31.2 (s)。
实施例4
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 2-甲氧基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58 mmol的1,4二氧六环,于60℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(2-甲氧基苯基)甲酮(分离产率45%)。1H NMR (400 MHz, CDCl3) δ 7.46 (t, J = 7.9 Hz, 1H), 7.38 (d, J = 7.5 Hz,1H), 7.04 (dd, J = 17.7, 8.0 Hz, 2H), 6.67 (s, 3H), 3.86 (s, 3H). 19F NMR (376MHz, CDCl3) δ -64.1 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 189.2 (s), 163.1 (s),156.4 (s), 131.9 (s), 130.5 (q, J = 44.0 Hz), 129.0 (s), 120.7 (s), 120.3(s), 119.1 (q, J = 265.6 Hz), 113.8 (dd, J = 6.0, 3.0 Hz), 111.5 (s), 100.1(s), 55.6 (s)。
实施例5
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 3-甲氧基苯甲酰乙腈、0.5 mmol3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入入58 mmol的1,4二氧六环,于80℃油浴条件下在密闭体系中搅拌反应3小时后冷却至室温,加入15 mL水,用乙酸乙酯10mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(甲氧基苯基)甲酮(分离产率53%). 1HNMR (400 MHz, CDCl3) δ 7.42 (t, J = 7.8 Hz, 1H), 7.32 (d, J = 7.5 Hz, 1H),7.27 (s, 1H), 7.11 (d, J = 8.1 Hz, 1H), 7.01 (s, 1H), 6.70 (s, 2H), 3.89 (s,3H). 19F NMR (376 MHz, CDCl3) δ -64.1 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 189.0(s), 164.1 (s), 159.7 (s), 140.4 (s), 130.7 (q, J = 43.9 Hz), 129.6 (s),120.3 (s), 119.1 (q, J = 267.6 Hz), 117.7 (s), 113.4 (dd, J = 6.0, 2.9 Hz),112.8 (s), 98.1 (s), 55.5 (s)。
实施例6
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 4-甲氧基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入60mmol的甲醇,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(4-甲氧基苯基)甲酮(分离产率48%). 1H NMR(400 MHz, CDCl3) δ 7.76 (d, J = 8.1 Hz, 2H), 7.33 – 6.89 (m, 3H), 6.79 (s,1H), 3.89 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -64.0 (s, 3F). 13C NMR (101 MHz,CDCl3) δ 188.1 (s), 164.2 (s), 162.5 (s), 131.7 (s), 130.5 (q, J = 44.0 Hz),130.1 (s), 119.2 (q, J = 265.5 Hz), 113.8 (s), 113.4 (dd, J = 5.8, 2.8 Hz),97.9 (s), 55.4 (s)。
实施例7
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 4-二甲基氨基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入60 mmol的乙腈,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(4-(二甲基氨基)苯基)甲酮(分离产率50%). 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.1 Hz, 2H), 7.09 (s, 1H), 6.75(d, J = 8.2 Hz, 2H), 6.63 (s, 2H), 3.09 (s, 6H). 19F NMR (376 MHz, CDCl3) δ -63.9 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 187.7 (s), 163.9 (s), 152.8 (s),130.21 (s), 130.2 (q, J = 43.8 Hz), 126.5 (s), 119.3 (q, J = 265.4 Hz), 113.7(dd, J = 5.8, 2.9 Hz), 111.0 (s), 98.0 (s)。
实施例8
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 4-氰基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(5:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(4-氰基苯基)甲酮(分离产率77%)。1H NMR (400 MHz, DMSO) δ 8.60 (s, 2H), 7.98 (d, J = 7.6 Hz, 2H), 7.87 (d, J =7.7 Hz, 2H), 7.29 (s, 1H). 19F NMR (376 MHz, DMSO) δ -62.6 (s, 3F). 13C NMR(101 MHz, DMSO) δ 185.9 (s), 165.6 (s), 143.3 (s), 133.1 (s), 129.0 (s),128.4 (q, J = 43.1 Hz), 119.8 (q, J = 264.7 Hz), 118.8 (s), 114.9 (dd, J =6.1, 2.9 Hz), 113.9 (s), 96.8 (s)。
实施例9
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol (2-氰基乙酰基)苯甲酸甲酯、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58 mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到4-(2-氨基-5-(三氟甲基)呋喃-3-羰基)苯甲酸甲酯酮(分离产率92%)。1H NMR (400 MHz, DMSO) δ 8.56 (s, 2H), 8.06 (s, 2H), 7.83 (d, J= 6.4 Hz, 2H), 7.28 (s, 1H), 3.90 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -64.1(s, 3F). 13C NMR (101 MHz, DMSO) δ 186.5 (s), 166.2 (s), 165.6 (s), 143.3 (s),132.1 (s), 129.8 (s), 128.5 (s), 128.3 (q, J = 42.6 Hz), 119.8 (q, J = 264.6Hz), 114.9 (s), 96.8 (s), 52.8 (s)。
实施例10
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 4-三氟甲基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58 mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(5:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(4-三氟甲基苯基)甲酮(分离产率90%)。 1H NMR (400 MHz, DMSO) δ 8.58 (s, 2H), 7.90 (d, J = 7.8 Hz, 2H),7.85 (d, J = 7.7 Hz, 2H), 7.30 (s, 1H). 19F NMR (376 MHz, DMSO) δ -61.6 (s,3F), -62.7 (s, 3F). 13C NMR (101 MHz, DMSO) δ 186.2 (s), 165.7 (s), 143.0 (s),131.4 (q, J = 32.0 Hz), 129.0 (s), 128.4 (q, J = 43.2 Hz), 125.9 (d, J = 3.6Hz), 124.4 (q, J = 272.4 Hz), 119.8 (q, J = 264.9 Hz), 114.8 (s), 96.7 (s)。
实施例11
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 4-三氟甲氧基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58 mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(4-三氟甲氧基苯基)甲酮(分离产率64%)。1H NMR (400 MHz, CDCl3) δ 7.82 (s, 2H), 7.36 (s, 2H), 6.98 (s, 1H),6.77 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -57.7 (s, 3F), -64.7 (s, 3F). 13C NMR(101 MHz, CDCl3) δ 187.6 (s), 164.3 (s), 151.5 (s), 137.4 (s), 131.0 (q, J =44.1 Hz), 129.7 (s), 120.7 (s), 120.4 (q, J = 258.4 Hz), 119.0 (q, J = 265.7Hz), 112.9 (dd, J = 6.0, 3.0 Hz), 97.9 (s)。
实施例12
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 3-氧代-3-(4-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)苯基)丙腈、0.5 mmol3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58 mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到(2-氨基-5-(三氟甲基)呋喃-3-基)(4-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷)-苯基)甲酮(分离产率76%)。 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.2 Hz, 2H), 7.71 (d, J = 7.3Hz, 2H), 6.95 (s, 1H), 6.77 (s, 2H), 1.39 (s, 12H). 19F NMR (376 MHz, CDCl3) δ-64.0 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 189.5 (s), 164.1 (s), 141.2 (s),134.9 (s), 130.8 (q, J = 44.3 Hz), 126.9 (s), 119.0 (q, J = 265.6 Hz), 113.3(dd, J = 5.8, 2.9 Hz), 98.3 (s), 84.2 (s), 24.9 (s)。
实施例13
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 4-氟苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(4-氟苯基)甲酮(分离产率88%)。1HNMR (400 MHz, CDCl3) δ 7.78 (dd, J = 8.4, 5.5 Hz, 2H), 7.19 (t, J = 8.5 Hz,2H), 6.97 (s, 1H), 6.70 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -64.1 (s, 3F), -107.2 – -107.4 (m). 13C NMR (101 MHz, CDCl3) δ 187.7 (s), 166.0 (s), 164.2(s), 163.5 (s), 135.3 (d, J = 3.1 Hz), 130.3 (q, J = 9.0 Hz), 119.0 (q, J =265.6 Hz), 115.7 (d, J = 21.8 Hz), 113.1 (dd, J = 6.0, 3.0 Hz), 97.9 (s)。
实施例14
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 2-氯苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(5:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(2-氯苯基)甲酮(分离产率72%)。 1HNMR (400 MHz, CDCl3) δ 7.48 (d, J = 7.7 Hz, 1H), 7.43 (d, J = 6.1 Hz, 1H),7.38 (dd, J = 13.8, 6.4 Hz, 2H), 6.79 (s, 2H), 6.60 (s, 1H). 19F NMR (376 MHz,CDCl3) δ -64.2 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 188.2 (s), 163.5 (s), 138.5(s), 131.1 (s), 131.0 (q, J = 44.2 Hz), 130.6 (s), 130.4 (s), 128.5 (s),126.9 (s), 118.9 (q, J = 265.6 Hz), 113.2 (dd, J = 6.0, 3.0 Hz), 99.3 (s)。
实施例15
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 4-氯苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(4-氯苯基)甲酮(分离产率85%)。1HNMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.1 Hz, 2H), 7.49 (d, J = 8.1 Hz, 2H),6.95 (s, 1H), 6.78 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -64.1 (s, 3F). 13C NMR(101 MHz, CDCl3) δ 187.8 (s), 164.3 (s), 137.9 (s), 137.3 (s), 130.9 (q, J =44.1 Hz), 129.3 (s), 128.9 (s), 119.0 (q, J = 265.6 Hz), 113.0 (q, J = 3.0Hz), 97.9 (s)。
实施例16
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 3-溴苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(3-溴苯基)甲酮(分离产率78%)。1HNMR (400 MHz, DMSO) δ 8.52 (s, 2H), 7.87 – 7.66 (m, 3H), 7.47 (t, J = 7.4 Hz,1H), 7.27 (s, 1H). 19F NMR (376 MHz, DMSO) δ -62.6 (s, 3F). 13C NMR (101 MHz,DMSO) δ 185.7 (s), 165.6 (s), 141.6 (s), 134.4 (s), 131.2 (s), 130.6 (s),128.3 (q, J = 44.0 Hz), 127.3 (s), 122.4 (s), 119.8 (q, J = 264.9 Hz), 114.8(s), 96.6 (s)。
实施例17
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 4-碘苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(4-碘苯基)甲酮(分离产率89%)。1HNMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.1 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H),6.94 (s, 1H), 6.83 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -64.1 (s, 3F). 13C NMR(101 MHz, CDCl3) δ 188.3 (s), 164.3 (s), 138.3 (s), 137.9 (s), 130.9 (q, J =44.2 Hz), 129.4 (s), 119.0 (q, J = 265.7 Hz), 113.0 (q, J = 3.0 Hz), 98.8(s), 97.8 (s)。
实施例18
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 3- ([1,1'-联苯] -4-基)-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58 mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到[1,1'-联苯] -4-基(2-氨基-5-(三氟甲基)呋喃-3-基)甲酮(分离产率85%)。1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.1 Hz, 2H),7.74 (d, J = 8.1 Hz, 2H), 7.67 (d, J = 7.6 Hz, 2H), 7.52 (t, J = 7.5 Hz,2H),7.45 (d, J = 7.3 Hz, 1H), 7.07 (s, 1H), 6.82 (s, 2H). 19F NMR (376 MHz, CDCl3)δ -64.0 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 188.9 (s), 164.3 (s), 144.6 (s),140.0 (s), 137.7 (s), 130.8 (q, J = 44.0 Hz), 129.1 (s), 129.0 (s), 128.5(s), 128.1 (s), 127.3 (s), 119.1 (q, J = 265.6 Hz), 113.4 (dd, J = 5.9, 2.9Hz), 98.2 (s)。
实施例19
氮气保护气氛下,在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5mmol 3-(萘-2-基)-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol碳酸钠,最后加入58 mmol的1,4-二氧六环,于80℃油浴条件下在密闭体系中搅拌反应12小时后冷却至室温,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-氨基-5-(三氟甲基)呋喃-3-(萘-2-基)甲酮(分离产率85%)。1H NMR (400 MHz, DMSO-d 6) δ 8.51 (s, 2H), 8.36 (s, 1H), 8.15 (d, J = 6.3Hz, 1H), 8.02 (dd, J = 14.3, 7.5 Hz, 2H), 7.82 (d, J = 7.6 Hz, 1H), 7.63 (s,2H), 7.44 (s, 1H). 19F NMR (376 MHz, DMSO-d 6) δ -62.4 (s, 3F). 13C NMR (101MHz, DMSO-d 6) δ 187.5 (s), 165.6 (s), 136.8 (s), 134.6 (s), 132.7 (s), 129.8(s), 128.7 (s), 128.3 (s), 128.1 (q, J = 43.0 Hz), 128.0 (s), 127.1 (s),125.0 (s), 119.9 (q, J = 264.9 Hz), 115.3 (d, J = 2.8 Hz), 96.9 (s)。
实施例20
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4-二氧六环,于常温下搅拌反应8小时后,加入15mL水,用乙醚10mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到5-羟基-2-苯基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率90%)。1H NMR (400 MHz, DMSO-d 6) δ 9.39 (s, 1H), 7.89 (d, J = 7.3Hz, 2H), 7.61 – 7.51 (m, 3H), 3.59 (d, J = 16.9 Hz, 1H), 3.19 (d, J = 16.9Hz, 1H). 19F NMR (376 MHz, DMSO-d 6) δ -84.4 (s, 3F). 13C NMR (101 MHz, DMSO-d 6)δ 164.1 (s), 132.5 (s), 129.6 (s), 127.1 (s), 127.0 (s), 122.3 (q, J = 284.2Hz), 116.4 (s), 104.8 (q, J = 34.2 Hz), 80.0 (s), 38.8 (s)。
实施例21
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 4-甲基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4-二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(4-甲基苯基)-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率78%)。1H NMR (400 MHz, CDCl3) δ 7.83 (d, J =7.4 Hz, 2H), 7.26 (d, J = 7.4 Hz, 2H), 4.84 (s, 1H), 3.45 (d, J = 16.5 Hz,1H), 3.13 (d, J = 16.5 Hz, 1H), 2.42 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -85.2(s, 3F). 13C NMR (101 MHz, CDCl3) δ 165.3 (s), 143.0 (s), 129.6 (s), 127.1(s), 123.8 (s), 121.5 (q, J = 283.6 Hz), 116.0 (s), 103.6 (q, J = 35.3 Hz),77.9 (s), 38.80 (s), 21.7 (s)。
实施例22
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 4-叔丁基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4-二氧六环,,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(4-叔丁基苯基)-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率80%)。1H NMR (400 MHz, CDCl3) δ 7.90 (d, J= 7.4 Hz, 2H), 7.49 (d, J = 7.4 Hz, 2H), 5.45 (s, 1H), 3.46 (d, J = 16.5 Hz,1H), 3.13 (d, J = 16.5 Hz, 1H), 1.35 (s, 9H). 19F NMR (376 MHz, CDCl3) δ -85.2(s, 3F). 13C NMR (101 MHz, CDCl3) δ 165.5 (s), 156.0 (s), 127.0 (s), 125.9(s), 123.9 (s), 121.7 (q, J = 283.8 Hz), 116.1 (s), 103.8 (q, J = 35.1 Hz),77.9 (s), 38.9 (s), 35.1 (s), 31.0 (s)。
实施例23
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 2-甲氧基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4-二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(4-二甲氨基苯基)-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率83%)。1H NMR (400 MHz, CDCl3) δ 7.58 (d, J= 7.5 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.01 (dd, J = 11.6, 8.2 Hz, 2H),4.59 – 4.31 (m, 1H), 3.95 (s, 3H), 3.49 (d, J = 16.6 Hz, 1H), 3.16 (d, J =16.5 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.2 (s, 3F). 13C NMR (101 MHz, CDCl3)δ 161.7 (s), 157.9 (s), 133.3 (s), 129.6 (s), 121.6 (q, J = 283.6 Hz), 120.4(s), 116.0 (s), 115.0 (s), 111.5 (s), 102.9 (q, J = 35.0 Hz), 83.2 (s), 54.9(s), 39.6 (s)。
实施例24
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 4-甲氧基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4-二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(4-甲氧基苯基)-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率85%)。1H NMR (400 MHz, CDCl3) δ 7.88 (d, J= 7.6 Hz, 2H), 6.93 (d, J = 7.6 Hz, 2H), 5.16 (s, 1H), 3.87 (s, 3H), 3.44 (d,J = 16.4 Hz, 1H), 3.11 (d, J = 16.4 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.1(s, 3F). 13C NMR (101 MHz, CDCl3) δ 129.1 (s), 121.6 (q, J = 283.7 Hz), 119.2(s), 116.3 (s), 114.3 (s), 103.6 (q, J = 35.2 Hz), 76.4 (s), 55.5 (s), 38.8(s)。
实施例25
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 4-二甲氨基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4-二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(4-二甲氨基苯基)-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率86%)。1H NMR (400 MHz, DMSO-d 6) δ 9.18(s, 1H), 7.73 (d, J = 5.3 Hz, 2H), 6.83 (d, J = 5.1 Hz, 2H), 3.50 (d, J =15.9 Hz, 1H), 3.06 (d, J = 26.0 Hz, 7H). 19F NMR (376 MHz, DMSO-d 6) δ -84.2(s, 3F). 13C NMR (101 MHz, DMSO-d 6) δ 164.8 (s), 152.7 (s), 128.4 (s), 122.4(q, J = 284.5 Hz), 117.7 (s), 113.4 (s), 111.9 (s), 104.1 (q, J = 33.9 Hz),73.8 (s), 38.6 (s)。
实施例26
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 4-氰基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4-二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(4-氰基苯基)-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率67%)。1H NMR (400 MHz, CDCl3) δ 8.07 (d, J =7.3 Hz, 2H), 7.77 (d, J = 7.2 Hz, 2H), 5.31 (s, 1H), 3.52 (d, J = 17.1 Hz,1H), 3.21 (d, J = 17.1 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.1 (s, 3F). 13CNMR (101 MHz, CDCl3) δ 162.4 (s), 132.6 (s), 130.6 (s), 127.6 (s), 121.4 (q,J = 283.8 Hz), 117.7 (s), 117.1 (s), 115.1 (s), 104.0 (q, J = 35.6 Hz), 82.7(s), 39.1 (s)。
实施例27
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 4-(2-氰基乙酰基)苯甲酸甲酯、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4-二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到4-(3-氰基-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-2-基)苯甲酸甲酯(分离产率75%)。1H NMR (400 MHz, CDCl3) δ8.05 (d, J = 7.9 Hz, 2H), 7.93 (d, J = 8.0 Hz, 2H), 5.88 (s, 1H), 3.98 (s,3H), 3.51 (d, J = 16.9 Hz, 1H), 3.19 (d, J = 16.9 Hz, 1H). 19F NMR (376 MHz,CDCl3) δ -85.0 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 166.7 (s), 163.3 (s), 132.6(s), 130.6 (s), 130.0 (s), 127.1 (s), 121.5 (d, J = 283.8 Hz), 115.2 (s),103.9 (q, J = 35.4 Hz), 81.5 (s), 52.8 (s), 39.2 (s)。
实施例28
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 3-(4-三氟甲基苯基)-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58mmol的1,4-二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到5-羟基-2-(4-三氟甲基苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率69%)。1H NMR (400 MHz, CDCl3)δ 8.03 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 8.2 Hz, 2H), 5.47 (s, 1H), 3.51 (d,J = 16.9 Hz, 1H), 3.19 (d, J = 16.9 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -63.4(s, 3F), -85.2 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 163.7 (s), 133.6 (q, J =33.0 Hz), 129.7 (s), 127.5 (s), 125.9 (dd, J = 7.4, 3.6 Hz), 123.3 (q, J =272.6 Hz), 121.4 (q, J = 283.7 Hz), 115.1 (s), 104.1 (q, J = 35.5 Hz), 81.1(s), 38.9 (s)。
实施例29
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 4-氟苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4-二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(4-氟苯基)-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率76%)。1H NMR (400 MHz, CDCl3) δ 8.13 – 7.85 (m,2H), 7.15 (t, J = 8.3 Hz, 2H), 5.22 (s, 1H), 3.47 (d, J = 16.6 Hz, 1H), 3.15(d, J = 16.6 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.2 (s, 3F), -105.2 – -105.4 (m). 13C NMR (101 MHz, CDCl3) δ 166.0 (s), 164.0 (s), 163.5 (s), 129.6(d, J = 9.0 Hz), 122.9 (s), 121.5 (q, J = 283.8 Hz), 116.2 (d, J = 22.2 Hz),103.8 (q, J = 35.3 Hz), 78.7 (s), 38.9 (s)。
实施例30
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 2-氯苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4-二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(2-氯苯基)-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率67%)。1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 7.6Hz, 1H), 7.49 (q, J = 7.8 Hz, 2H), 7.38 (t, J = 7.3 Hz, 1H), 4.35 (s, 1H),3.47 (d, J = 16.6 Hz, 1H), 3.17 (d, J = 16.6 Hz, 1H). 19F NMR (376 MHz, CDCl3)δ -85.3 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 165.0 (s), 133.4 (s), 132.7 (s),130.9 (s), 130.8 (s), 127.0 (s), 126.0 (s), 121.4 (q, J = 283.7 Hz), 114.1(s), 104.4 (q, J = 35.6 Hz), 85.3 (s), 38.3 (s)。
实施例31
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 3-(4-氯苯基)-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到5-羟基-2-(4-氯苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率60%)。1H NMR (400 MHz, CDCl3) δ 7.84 (d, J= 8.2 Hz, 2H), 7.40 (d, J = 8.2 Hz, 2H), 5.47 (s, 1H), 3.47 (d, J = 16.7 Hz,1H), 3.15 (d, J = 16.7 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.0 (s, 3F). 13CNMR (101 MHz, CDCl3) δ 164.3 (s), 138.5 (s), 129.2 (s), 128.4 (s), 124.9 (s),121.5 (q, J = 283.7 Hz), 115.5 (s), 103.9 (q, J = 35.4 Hz), 79.2 (s), 38.9(s)。
实施例32
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 3-(4-碘苯基)-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到5-羟基-2-(4-碘苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率67%)。1H NMR (400 MHz, CDCl3) δ 7.83 (s,2H), 7.67 (d, J = 5.1 Hz, 2H), 4.70 – 4.25 (m, 1H), 3.48 (d, J = 16.5 Hz,1H), 3.17 (d, J = 16.4 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.2 (s, 3F). 13CNMR (101 MHz, CDCl3) δ 163.9 (s), 138.2 (s), 128.3 (s), 125.9 (s), 121.74 (q,J = 283.2 Hz), 115.3 (s), 103.6 (q, J = 35.0 Hz), 99.3 (s), 80.0 (s), 38.9(s)。
实施例33
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 3-(3-碘-4-甲基苯基)-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58mmol的1,4二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到5-羟基-2-(3-碘-4-甲基苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率70%)。1H NMR (400 MHz,CDCl3) δ 8.27 (s, 1H), 7.92 (d, J= 7.9 Hz, 1H), 7.32 (dd, J = 13.4, 8.2 Hz,1H), 4.37 (d, J = 133.7 Hz, 1H), 3.48 (d, J = 16.7 Hz, 1H), 3.17 (d, J = 16.7Hz, 1H), 2.51 (s, 3H).19F NMR (376 MHz, CDCl3) δ -85.2 (s, 3F). 13C NMR (101MHz, CDCl3) δ 163.0 (s), 146.3 (s), 137.2 (s), 129.9 (s), 126.8 (s), 125.7(s), 121.4 (q, J = 283.6 Hz), 115.3 (s), 103.6 (q, J = 35.5 Hz), 101.1 (s),79.6 (s), 38.8 (s), 28.4 (s)。
实施例34
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 4-苯基苯甲酰乙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(4-联苯)-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率70%)。1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.7 Hz,2H), 7.70 (d, J = 7.7 Hz, 2H), 7.62 (d, J = 6.8 Hz, 2H), 7.49 (d, J = 6.8 Hz,2H), 7.44 (d, J = 6.7 Hz, 1H), 4.47 (s, 1H), 3.52 (d, J = 16.6 Hz, 1H), 3.21(d, J = 16.6 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.2 (s, 3F). 13C NMR (101MHz, CDCl3) δ 164.6 (s), 144.9 (s), 139.6 (s), 129.0 (s), 128.4 (s), 127.6(s), 127.5 (s), 127.2 (s), 125.3 (s), 121.5 (q, J = 283.9 Hz), 115.8 (s),103.5 (q, J = 34.7 Hz), 79.1 (s), 38.9 (s)。
实施例35
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 3-(萘-2-基)-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到5-羟基-2-(萘-2-基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率69%)。1H NMR (400 MHz, CDCl3) δ 8.41 (s,1H), 8.12 – 7.98 (m, 1H), 7.89 (dd, J = 10.7, 6.9 Hz, 3H), 7.58 (d, J = 0.6Hz, 2H), 4.73 (s, 1H), 3.55 (d, J = 16.0 Hz, 1H), 3.23 (d, J = 16.1 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.1 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 164.9 (s),134.7 (s), 132.5 (s), 129.1 (s), 128.8 (s), 128.4 (s), 128.2 (s), 127.8 (s),127.1 (s), 123.8 (s), 122.8 (s), 121.6 (q, J = 283.9 Hz), 115.9 (s), 103.6(q, J = 30.6 Hz), 79.3 (s), 39.1 (s)。
实施例36
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 3-(呋喃-2-基)-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到5-羟基-5-(三氟甲基)-4,5-二氢-[2-呋喃] -3-甲腈(分离产率61%)。 1H NMR (400 MHz, CDCl3) δ 7.63 (s, 1H),7.02 (s, 1H), 6.57 (s, 1H), 5.13 (s, 1H), 3.45 (d, J = 15.2 Hz, 1H), 3.15 (d,J = 15.1 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.1 (s, 3F). 13C NMR (101 MHz,CDCl3) δ 156.3 (s), 146.3 (s), 142.4 (s), 121.3 (q, J = 284.5 Hz), 115.2 (s),114.9 (s), 112.2 (s), 104.8 (q, J = 35.6 Hz), 77.1 (s), 38.2 (s)。
实施例37
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 3-(噻吩-2-基)-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到5-羟基-2-(噻吩-2-基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率82%)。1H NMR (400 MHz, CDCl3) δ 7.84 (s,1H), 7.58 (d, J = 4.3 Hz, 1H), 7.16 (d, J = 4.9 Hz, 1H), 4.59 (s, 1H), 3.47(d, J = 16.6 Hz, 1H), 3.16 (d, J = 16.6 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.1 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 160.4 (s), 130.9 (s), 128.5 (s),128.2 (s), 121.4 (q, J = 283.6 Hz), 115.4 (s), 104.3 (q, J = 35.4 Hz), 38.5(s)。
实施例38
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 3-(3-溴噻吩-2-基)-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58mmol的1,4二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(3-溴噻吩-2-基)-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率73%)。1H NMR (400 MHz, CDCl3)δ 7.52 (d, J = 1.4 Hz, 1H), 7.10 (s, 1H), 5.15 (s, 1H), 3.44 (d, J = 16.7 Hz,1H), 3.13 (d, J = 16.7 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -85.1 (s, 3F). 13CNMR (101 MHz, CDCl3) δ 159.1 (s), 132.6 (s), 130.4 (s), 123.5 (s), 121.3 (q,J = 283.7 Hz), 114.8 (s), 114.5 (s), 104.4 (q, J = 35.6 Hz), 82.7 (s), 38.6(s)。
实施例39
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 3-环己基-3-氧代丙腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-环己基-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率84%)。1H NMR (400 MHz, CDCl3) δ 5.56 (s, 1H),3.20 (d, J = 15.9 Hz, 1H), 2.90 (d, J = 16.0 Hz, 1H), 2.54 (t, J = 11.6 Hz,1H), 1.82 (d, J = 9.2 Hz, 4H), 1.72 (d, J = 11.6 Hz, 1H), 1.51 (dd, J = 24.5,12.0 Hz, 2H), 1.27 (tt, J = 24.3, 12.2 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ -85.7 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 176.4 (s), 121.5 (q, J = 283.9 Hz),114.9 (s), 104.3 (q, J = 35.0 Hz), 78.8 (s), 38.0 (s), 37.5 (s), 29.2 (d, J =1.3 Hz), 25.4 (s), 25.3 (s)。
实施例40
在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中,加入0.5 mmol 3-氧代-5-苯基戊腈、0.5 mmol 3-溴-1,1,1-三氟丙酮、0.5 mmol醋酸钠,最后加入58 mmol的1,4二氧六环,于常温下搅拌反应8小时后,加入15 mL水,用乙醚10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(10:1,v/v)为洗脱剂,通过硅胶柱层析分离得到5-羟基-2-苯乙基-5-(三氟甲基)-4,5-二氢呋喃-3-腈(分离产率65%)。1H NMR (400 MHz, CDCl3) δ 7.34 (t, J = 7.1 Hz,2H), 7.27 (d, J = 7.4 Hz, 1H), 7.22 (d, J = 7.2 Hz, 2H), 4.91 (s, 1H), 3.19(d, J = 16.1 Hz, 1H), 2.99 – 2.85 (m, 3H), 2.78 (t, J = 7.5 Hz, 2H). 19F NMR(376 MHz, CDCl3) δ -85.7 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 171.0 (s), 139.1(s), 128.7 (s), 128.4 (s), 126.7 (s), 121.4 (q, J = 283.7 Hz), 114.4 (s),104.5 (q, J = 35.2 Hz), 82.4 (s), 37.5 (s), 32.0 (s), 29.6 (s)。
实施例41
在一个置有聚四氟乙烯磁力搅拌子的25 mL圆底烧瓶中,加入0.5 mmol 2-苯基-5-羟基-5-(三氟甲基)-4,5-二氢呋喃-3-腈、135 μL浓硫酸,于50℃下搅拌反应4小时后,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-苯基-5-(三氟甲基)呋喃-3-甲酰胺(分离产率87%)。1H NMR (400MHz, DMSO-d 6) δ 7.93 (d, J = 7.8 Hz, 3H), 7.65 (s, 1H), 7.61 (s, 1H), 7.50(d, J = 6.2 Hz, 3H). 19F NMR (376 MHz, DMSO-d 6) δ -62.9 (s, 3F). 13C NMR (101MHz, DMSO-d 6) δ 163.8 (s), 155.9 (s), 138.5 (q, J = 42.6 Hz), 130.4 (s),129.0 (s), 128.7 (s), 128.2 (s), 119.4 (q, J = 266.9 Hz), 119.0 (s), 115.4(s)。
实施例42
在一个置有聚四氟乙烯磁力搅拌子的25 mL圆底烧瓶中,加入0.5 mmol 5-羟基-2-(4-甲基苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈、135 μL浓硫酸,于50℃下搅拌反应4小时后,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(对甲苯基)-5-(三氟甲基)呋喃-3-甲酰胺(分离产率84%)。1H NMR (400 MHz, DMSO-d 6) δ 7.98 – 7.69 (m, 3H), 7.62 (s, 1H), 7.55 (s,1H), 7.31 (d, J = 7.6 Hz, 2H), 2.37 (s, 1H). 19F NMR (376 MHz, DMSO-d 6) δ -62.9 (s, 3F). 13C NMR (101 MHz, DMSO-d 6) δ 163.9 (s), 156.2 (s), 140.3 (s),138.2 (q, J = 42.6 Hz), 129.5 (s), 128.1 (s), 126.0 (s), 119.4 (q, J = 266.8Hz), 118.4 (s), 115.4 (d, J = 2.6 Hz), 21.4 (s)。
实施例43
在一个置有聚四氟乙烯磁力搅拌子的25 mL圆底烧瓶中,加入0.5 mmol 5-羟基-2-(4-叔丁基苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈、135 μL浓硫酸,于50℃下搅拌反应4小时后,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(对叔丁基苯基)-5-(三氟甲基)呋喃-3-甲酰胺(分离产率82%)。1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.8 Hz, 2H), 7.54 (d, J = 7.9Hz, 2H), 7.20 (s, 1H), 5.94 (d, J = 69.8 Hz, 2H), 1.38 (s, 9H). 19F NMR (376MHz, CDCl3) δ -64.3 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 164.1 (s), 156.2 (d, J= 1.0 Hz), 154.2 (s), 140.7 (q, J = 43.4 Hz), 128.3 (s), 126.0 (s), 125.3(s), 118.8 (q, J = 267.4 Hz), 116.9 (s), 113.7 (dd, J = 5.4, 2.6 Hz), 35.0(s), 31.1 (s)。
实施例44
在一个置有聚四氟乙烯磁力搅拌子的25 mL圆底烧瓶中,加入0.5 mmol 5-羟基-2-(4-二甲氨基苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈、135 μL浓硫酸,于50℃下搅拌反应4小时后,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(对二甲氨基苯基)-5-(三氟甲基)呋喃-3-甲酰胺(分离产率73%)。1H NMR (400 MHz, DMSO-d 6) δ 7.96 (d, J = 2.3 Hz, 3H), 7.62 (dd,J = 37.9, 11.5 Hz, 2H), 6.87 (d, J = 2.1 Hz, 2H), 3.08 (d, J = 0.8 Hz, 6H).19F NMR (376 MHz, DMSO-d 6) δ -62.6 (s, 3F). 13C NMR (101 MHz, DMSO) δ 164.3(s), 157.7 (s), 151.5 (s), 136.9 (q, J = 42.5 Hz), 129.4 (s), 119.6 (q, J =266.4 Hz), 116.0 (s), 115.7 (s), 115.5 (s), 111.7 (s), 40.0 (s)。
实施例45
在一个置有聚四氟乙烯磁力搅拌子的25 mL圆底烧瓶中,加入0.5 mmol 5-羟基-2-(4-氰基苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈、135 μL浓硫酸,于50℃下搅拌反应4小时后,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(对-氰基苯基)-5-(三氟甲基)呋喃-3-甲酰胺(分离产率69%)。1H NMR (400 MHz, DMSO-d 6) δ 8.04 (t, J = 22.0 Hz, 1H), 7.67 (d, J = 11.2Hz, 1H), 7.51 (d, J = 0.8 Hz, 1H). 19F NMR (376 MHz, DMSO-d 6) δ -62.85 (s). 13CNMR (101 MHz, DMSO) δ 167.62 (s), 163.69 (s), 155.00 (s), 138.96 (d, J = 42.5Hz), 135.65 (s), 131.03 (s), 128.07 (s), 127.92 (s), 119.95 (s), 119.30 (d, J= 267.1 Hz), 115.54 (s)。
实施例46
在一个置有聚四氟乙烯磁力搅拌子的25 mL圆底烧瓶中,加入0.5 mmol 5-羟基-2-(4-氟苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈、135 μL浓硫酸,于50℃下搅拌反应4小时后,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(对-氟苯基)-5-(三氟甲基)呋喃-3-甲酰胺(分离产率71%)。1H NMR (400 MHz, DMSO-d 6) δ 8.07 – 7.97 (m, 2H), 7.94 (s, 1H), 7.66 (s,1H), 7.59 (s, 1H), 7.34 (t, J = 8.5 Hz, 2H). 19F NMR (376 MHz, DMSO-d 6) δ -62.9 (s, 3F), -110.10 – -110.56 (m). 13C NMR (101 MHz, DMSO-d 6) δ 164.6 (s),163.7 (s), 162.1 (s), 155.4 (s), 138.5 (q, J = 42.5 Hz), 130.8 (d, J = 8.7Hz), 125.3 (d, J = 3.1 Hz), 119.3 (q, J = 267.0 Hz), 118.7 (s), 115.3 (d, J =2.7 Hz)。
实施例47
在一个置有聚四氟乙烯磁力搅拌子的25 mL圆底烧瓶中,加入0.5 mmol 5-羟基-2-(2-氯苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈、135 μL浓硫酸,于50℃下搅拌反应4小时后,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(2-氯苯基)-5-(三氟甲基)呋喃-3-甲酰胺(分离产率82%)。1HNMR (400 MHz, DMSO-d 6) δ 7.79 (d, J = 21.8 Hz, 2H), 7.60 (s, 2H), 7.58 – 7.50(m, 1H), 7.48 (s, 2H). 19F NMR (376 MHz, DMSO-d 6) δ -63.1 (s, 3F). 13C NMR (101MHz, DMSO-d 6) δ 162.4 (s), 155.2 (d, J = 0.8 Hz), 139.6 (q, J = 42.7 Hz),133.6 (s), 133.1 (s), 132.3 (s), 130.0 (s), 128.5 (s), 127.4 (s), 121.2 (s),119.2 (q, J = 267.0 Hz), 113.7 (d, J = 2.6 Hz)。
实施例48
在一个置有聚四氟乙烯磁力搅拌子的25 mL圆底烧瓶中,加入0.5 mmol 5-羟基-2-(4-氯苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈、135 μL浓硫酸,于50℃下搅拌反应4小时后,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(4-氯苯基)-5-(三氟甲基)呋喃-3-甲酰胺(分离产率78%)。1H NMR (400 MHz, DMSO-d 6) δ 7.99 (d, J = 7.9 Hz, 3H), 7.65 (d, J = 15.1 Hz,2H), 7.55 (d, J = 8.0 Hz, 2H). 19F NMR (376 MHz, DMSO-d 6) δ -63.0 (s, 3F). 13CNMR (101 MHz, DMSO-d 6) δ 163.6 (s), 155.0 (d, J = 0.5 Hz), 138.8 (q, J = 42.6Hz), 135.2 (s), 130.0 (s), 129.0 (s), 127.5 (s), 119.3 (s), 119.3 (q, J =266.9 Hz), 115.4 (d, J = 2.2 Hz)。
实施例49
在一个置有聚四氟乙烯磁力搅拌子的25 mL圆底烧瓶中,加入0.5 mmol 5-羟基-2-(4-碘苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈、135 μL浓硫酸,于50℃下搅拌反应4小时后,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(4-碘苯基)-5-(三氟甲基)呋喃-3-甲酰胺(分离产率76%)。1HNMR (400 MHz, DMSO-d 6) δ 8.60 – 7.02 (m, 7H). 19F NMR (376 MHz, DMSO-d 6) δ -62.9 (s, 3F). 13C NMR (101 MHz, DMSO-d 6) δ 163.7 (s), 155.2 (s), 138.8 (q, J =42.7 Hz), 137.8 (s), 130.0 (s), 128.1 (s), 119.4 (s), 119.3 (q, J = 267.0Hz), 115.5 (d, J = 2.4 Hz), 97.6 (s)。
实施例50
在一个置有聚四氟乙烯磁力搅拌子的25 mL圆底烧瓶中,加入0.5 mmol 5-羟基-2-(3-碘-4-甲基苯基)-5-(三氟甲基)-4,5-二氢呋喃-3-腈、135 μL浓硫酸,于50℃下搅拌反应4小时后,加入15 mL水,用乙酸乙酯10 mL萃取三次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后,旋蒸除去有机溶剂;得到的粗产物以正戊烷和乙酸乙酯(2:1,v/v)为洗脱剂,通过硅胶柱层析分离得到2-(3-碘-4-甲基苯基)-5-(三氟甲基)呋喃-3-甲酰胺(分离产率66%)。1H NMR (400 MHz, DMSO-d 6) δ 8.48 (d, J = 0.6 Hz, 1H), 8.28 –7.81 (m, 2H), 7.68 (d, J = 1.4 Hz, 2H), 7.41 (dd, J = 53.9, 7.1 Hz, 1H), 3.45(s, 3H). 19F NMR (376 MHz, DMSO-d 6) δ -62.9 (s, 3F). 13C NMR (101 MHz, DMSO-d 6)δ 163.7 (s), 154.3 (s), 143.4 (s), 138.7 (q, J = 43.1 Hz), 137.8 (s), 130.2(s), 129.5 (s), 128.0 (d, J = 8.9 Hz), 119.3 (q, J = 267.0 Hz), 119.2 (s),115.4 (s), 101.4 (s), 27.9 (s)。
杀虫活性试验
实施例1:杀线虫的测定方法
将松材线虫从培养基中分离出来,浓度以200-300条/mL为宜。一般先吸取50 μL的线虫分离液,于显微镜下观察数其数量,50 μL中线虫数量控制在10-15条,若不是该浓度则做相应调整。
用20 mL乙酸乙酯,80 mL蒸馏水,100 μL曲拉通配成(2-氨基-5-(三氟甲基)呋喃-3-基)(对甲苯基)甲酮溶液后稀释待测液,再进一步稀释成5-6个梯度的不同浓度梯度的供试药液,备用。在96孔板的每孔中加入100 μL松材线虫悬浮液,再分别加入10 μL不同浓度的供试药液,每组3个重复。对照组则加10 μL空白溶液。封上封口膜,做好标记,将96孔板置于30℃恒温箱中。24 h后,在体视镜下对松材线虫的存活和死亡情况进行记录(线虫死亡、存活的判定方法:凡虫体呈波浪形、卷曲形、“S”形、螺旋形,在运动的均视为存活。凡虫体僵直呈针状或呈“J”形或“C”形或者虫体壁无折光性,且不运动的均视为死亡)。结果显示,对照组线虫基本能正常生长,在样品浓度为100 mg/L时,杀虫死亡率为87%。
实施例2:杀线虫的测定方法
将松材线虫从培养基中分离出来,浓度以200-300条/mL为宜。一般先吸取50μL的线虫分离液,于显微镜下观察数其数量,50μL中线虫数量控制在10-15条,若不是该浓度则做相应调整。
用20 mL乙酸乙酯,80 mL蒸馏水,100 μL曲拉通配成(2-氨基-5-(三氟甲基)呋喃-3-基)(2-甲氧苯基)甲酮溶液后稀释待测液,再进一步稀释成5-6个梯度的不同浓度梯度的供试药液,备用。在96孔板的每孔中加入100 μL松材线虫悬浮液,再分别加入10μl不同浓度的供试药液,每组3个重复。对照组则加10 μL空白溶液。封上封口膜,做好标记,将96孔板置于30℃恒温箱中。24 h后,在体视镜下对松材线虫的存活和死亡情况进行记录(线虫死亡、存活的判定方法:凡虫体呈波浪形、卷曲形、“S”形、螺旋形,在运动的均视为存活。凡虫体僵直呈针状或呈“J”形或“C”形或者虫体壁无折光性,且不运动的均视为死亡)。结果显示,对照组线虫基本能正常生长,在样品浓度为1g/L时,杀虫死亡率为100%。
以上所述仅为本发明的较佳实施例,凡依本发明申请专利范围所做的均等变化与修饰,皆应属本发明的涵盖范围。
Claims (3)
1. 一种2-三氟甲基取代呋喃化合物的合成方法,其特征在于:以碱为促进剂,苯甲酰乙腈衍生物为底物,3-溴-1,1,1-三氟丙酮为氟化试剂,经串联反应制得2-三氟甲基取代呋喃化合物;
其具体是在氮气气氛中,将苯甲酰乙腈衍生物、3-溴-1,1,1-三氟丙酮、碱以及溶剂混合均匀,置于60-80 ℃搅拌反应1-12小时后,用乙酸乙酯萃取3次,合并有机相,加饱和氯化钠溶液洗涤,经无水硫酸镁干燥后旋蒸除去有机溶剂,得到的粗产物采用硅胶柱层析分离,得到所述2-三氟甲基取代呋喃化合物;
其中所用碱为Na2CO3、K2CO3、NEt3中的任意一种;所用溶剂为乙腈、1,4-二氧六环、甲醇中的任意一种。
2. 根据权利要求1所述的2-三氟甲基取代呋喃化合物的合成方法,其特征在于:所用苯甲酰乙腈衍生物、3-溴-1,1,1-三氟丙酮、碱及溶剂的摩尔比为(0.1-1):(0.1-1):(0.1-1): (10-80)。
3.一种如权利要求1所述方法制备的2-三氟甲基取代呋喃化合物在制备杀虫剂中的应用。
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