CN109232416B - 一种合成4-三氟甲基-2-吡喃酮/吡啶酮化合物的方法 - Google Patents
一种合成4-三氟甲基-2-吡喃酮/吡啶酮化合物的方法 Download PDFInfo
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Abstract
本发明属于有机氟化学合成领域,具体涉及一种合成4‑三氟甲基‑2‑吡喃/吡啶酮化合物的方法。以有机碱小分子为催化剂,以1,3‑环己二酮及其类似物,以及三氟乙酰乙酸乙酯或醋酸铵为原料,在1,2‑二氯乙烷溶剂中,在120‑140℃下搅拌16‑48小时,反应结束后经柱层析纯化处理得到4‑三氟甲基‑2‑吡喃酮/吡啶酮化合物。本发明的合成方法使用非金属催化剂且催化剂价廉、易得、产率普遍较高、操作简便等优点,具有良好的应用前景。
Description
技术领域
本发明属于有机氟化学合成领域,具体涉及一种合成4-三氟甲基-2-吡喃/吡啶酮化合物的方法。
背景技术
2-吡喃酮化合物及其衍生物是一类重要的杂环化合物,具体广泛的生物活性,如抗真菌、抗生素、细胞毒性、神经毒性和植物毒性。2-吡喃酮也是一类重要的化学中间体,用于合成许多药物分子。由于氟原子具有模拟效应、电子效应、阻碍效应和渗透效应,将含氟基团引入到吡喃酮化合物及其衍生物上,有可能增强其生物活性,表现出和非氟分子不同的特点。目前文献报道的合成4-三氟甲基-2-吡喃酮的方法较少,需要多步反应,原料不易得。
本发明提供了一种简便的合成4-三氟甲基-2-吡喃酮/吡啶酮的方法,即利用有机碱小分子为催化剂,通过Pechmann类型的反应,制备一系列的4-三氟甲基-2-吡喃酮/吡啶酮化合物。该法具有原料简单、易得,催化剂廉价等优点。
发明内容
本发明的目的在于提供一种合成4-三氟甲基-2-吡喃酮/吡啶酮化合物的方法,该方法利用非金属催化剂及原料廉价易得,产率普遍较高,操作简便,具有良好的应用前景。
为实现上述目的,本发明采用如下技术方案:
一种合成4-三氟甲基-2-吡喃酮/吡啶酮化合物的方法,具体为:以有机碱小分子为催化剂,以1,3-环己二酮及其类似物,三氟乙酰乙酸乙酯或醋酸铵为原料,在溶剂中,反应制得4-三氟甲基-2-吡喃酮/吡啶酮化合物,反应流程示意图如图1所示;所述的4-三氟甲基-2-吡喃酮化合物的结构式为:; 所述的4-三氟甲基-2-吡啶酮化合物的结构式为:。
所述的有机碱小分子催化剂为2-二甲氨基吡啶、4-二甲氨基吡啶、三乙胺、吡啶和四氢吡咯中的任一种。
所述的溶剂为1,2-二氯乙烷、二乙二醇二甲醚、二甲基亚砜、N,N-二甲基甲酰胺、硝基苯、N-甲基吡咯烷酮中的任一种。
所述的1,3-环己二酮及其类似物为下述结构式1-式7的任意一种,如图2所示。合成4-三氟甲基-2-吡喃酮化合物的方法,优选的,有机碱小分子催化剂、1,3-环己二酮及其类似物、三氟乙酰乙酸乙酯以及溶剂的摩尔比为0.06-0.2:0.3-1: 0.45-1.5:12.7-42。
合成4-三氟甲基-2-吡啶酮化合物的方法,优选的,有机碱小分子催化剂、1,3-环己二酮及其类似物、三氟乙酰乙酸乙酯、醋酸铵以及溶剂的摩尔比为0.06-0.2:0.3-1:0.45-1.5:0.9-3:12.7-42。
合成4-三氟甲基-2-吡喃酮化合物的方法,具体步骤如下:在氮气气氛中,向带有磁力搅拌装置的容器中加入有机碱小分子催化剂、1,3-环己二酮及其类似物、三氟乙酰乙酸乙酯以及溶剂,混合均匀后关好塞子,将其放在120℃下继续搅拌16小时后,用100-200目硅胶过滤,二氯甲烷冲洗,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,然后旋蒸除去有机溶剂;得到的粗产物通过硅胶柱层析,以正戊烷和二氯甲烷为洗脱剂,得到4-三氟甲基-2-吡喃酮化合物。
合成4-三氟甲基-2-吡啶酮化合物的方法,具体步骤如下:在氮气气氛中,向带有磁力搅拌装置的容器中加入有机碱小分子催化剂、1,3-环己二酮及其类似物、三氟乙酰乙酸乙酯、醋酸铵以及溶剂,混合均匀后关好塞子,将其放在140℃下继续搅拌48小时后,用100-200目硅胶过滤,二氯甲烷冲洗,合并有机相,用饱和氯化钠溶液与乙酸乙酯萃取,然后旋蒸除去有机溶剂;得到的粗产物通过硅胶柱层析,以正戊烷和乙酸乙酯为洗脱剂,得到4-三氟甲基-2-吡啶酮化合物。
本发明的有益效果在于:
本发明以1,3-环己二酮及其类似物为底物,以三氟乙酰乙酸乙酯或醋酸铵为原料,以有机碱小分子为催化剂,一锅法合成4-三氟甲基-2-吡喃酮/吡啶酮化合物,得到普遍较高的产率,操作简便,具有良好的应用前景。
附图说明
图1 为本发明制备4-三氟甲基-2-吡喃酮/吡啶酮化合物的反应流程图;
图2为1,3-环己二酮及其类似物的结构式1-式7;
图3为实施例1制得的4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮的单晶结构图;
图4为实施例18制得的7-苯基-4-(三氟甲基)-7,8-二氢喹啉-2,5(1H,6H)-二酮的单晶结构图。
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5 mL反应管中,加入0.30mmol 1,3-环己二酮,1.0 mL 1,2-二氯乙烷,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和二氯甲烷洗脱,得到4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮(分离产率99%)。1H NMR (400 MHz, CDCl3) δ 6.67 (s, 1H), 2.94 (t, J = 6.2 Hz,2H), 2.62 (t, J = 6.3 Hz, 2H), 2.17 (dt, J = 12.0 Hz, J = 6.2 Hz, 2H). 19F NMR(376 MHz, CDCl3) δ -63.6 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 190.8 (s), 176.2(d, J = 1.3 Hz), 158.0 (s), 141.6 (q, J = 35.1 Hz), 120.8 (q, J = 275.1 Hz),115.0 (q, J = 7.3 Hz), 111.3 (s), 38.0 (s), 29.2 (s), 19.4 (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5 mL反应管中,加入0.30mmol 1,3-环己二酮,1.0 mL 二乙二醇二甲醚,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,二氯甲烷冲洗,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,然后旋蒸除去有机溶剂;得到的粗产物通过硅胶柱层析,以正戊烷和二氯甲烷为洗脱剂,以三氟甲氧基苯为内标,测得4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮氟谱产率66%。核磁谱图见实施例1。
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5 mL反应管中,加入0.30mmol 1,3-环己二酮,1.0 mL 硝基苯,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,二氯甲烷冲洗,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,然后旋蒸除去有机溶剂;得到的粗产物通过硅胶柱层析,以正戊烷和二氯甲烷为洗脱剂,以三氟甲氧基苯为内标,测得4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮氟谱产率73%。核磁谱图见实施例1。
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5 mL反应管中,加入0.30mmol 1,3-环己二酮,1.0 mL N,N-二甲基甲酰胺,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,二氯甲烷冲洗,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,然后旋蒸除去有机溶剂;得到的粗产物通过硅胶柱层析,以正戊烷和二氯甲烷为洗脱剂,以三氟甲氧基苯为内标,测得4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮氟谱产率53%。核磁谱图见实施例1。
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5 mL反应管中,加入0.30mmol 1,3-环己二酮,1.0 mL 1,2-二氯乙烷,0.060 mmol 吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,二氯甲烷冲洗,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,然后旋蒸除去有机溶剂;得到的粗产物通过硅胶柱层析,以正戊烷和二氯甲烷为洗脱剂,以三氟甲氧基苯为内标,测得4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮氟谱产率64%。核磁谱图见实施例1。
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5 mL反应管中,加入0.30mmol 1,3-环己二酮,1.0 mL 1,2-二氯乙烷,0.060 mmol 4-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,二氯甲烷冲洗,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,然后旋蒸除去有机溶剂;得到的粗产物通过硅胶柱层析,以正戊烷和二氯甲烷为洗脱剂,以三氟甲氧基苯为内标,测得4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮氟谱产率55%。核磁谱图见实施例1。
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5 mL反应管中,加入0.30mmol 1,3-环己二酮,1.0 mL 1,2-二氯乙烷,0.060 mmol 谷氨酸,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,二氯甲烷冲洗,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,然后旋蒸除去有机溶剂;得到的粗产物通过硅胶柱层析,以正戊烷和二氯甲烷为洗脱剂,以三氟甲氧基苯为内标,测得4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮氟谱产率29%。核磁谱图见实施例1。
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5 mL反应管中,加入0.30mmol 5,5’-二甲基-1,3-环己二酮,1.0 mL 1,2-二氯乙烷,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和二氯甲烷洗脱,得到7,7’-二甲基-4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮(分离产率99%)。1H NMR (400 MHz, CDCl3) δ 6.63 (s,1H), 2.78 (s, 2H), 2.47 (s, 2H), 1.14 (s, 6H). 19F NMR (376 MHz, CDCl3) δ -63.6 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 190.8 (s), 174.7 (s), 158.3 (s),141.4 (q, J = 35.4 Hz), 120.8 (q, J = 275.1 Hz), 114.8 (q, J = 7.4 Hz), 110.4(s), 51.9 (s), 42.7 (s), 31.7 (s), 27.9 (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5 mL反应管中,加入0.30mmol 5,5’-二甲基-1,3-环己二酮,1.0 mL 硝基苯,0.060 mmol 2-二甲氨基吡啶,0.45mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和二氯甲烷洗脱,以三氟甲氧基苯为内标,测得7,7’-二甲基-4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮氟谱产率75%。核磁谱图见实施例8。
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5 mL反应管中,加入0.30mmol 5,5’-二甲基-1,3-环己二酮,1.0 mL 二乙二醇二甲醚,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和二氯甲烷洗脱,以三氟甲氧基苯为内标,测得7,7’-二甲基-4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮氟谱产率87%。核磁谱图见实施例8。
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5 mL反应管中,加入0.30mmol 2H-吡喃-3,5(4H,6H)-二酮,1.0 mL 1,2-二氯乙烷,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和二氯甲烷洗脱,得到4-(三氟甲基)吡喃并[3,4-b]吡喃-2,5(6H,8H)-二酮(分离产率43%)。1H NMR (400 MHz, CDCl3) δ 6.75 (s, 1H), 4.73 (s,2H), 4.32 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -64.5 (s, 3F). 13C NMR (101 MHz,CDCl3) δ 186.2 (s), 173.1 (s), 156.5 (s), 140.7 (q, J = 36.4 Hz), 120.4 (q, J= 275.3 Hz), 115.6 (q, J = 7.1 Hz), 108.9 (s), 72.3 (s), 65.2 (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5 mL反应管中,加入0.30mmol 1,3-环戊二酮,1.0 mL 1,2-二氯乙烷,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和二氯甲烷洗脱,得到4-(三氟甲基)-6,7-二氢环戊[b]吡喃-1,5-二酮(分离产率84%)。1H NMR (400 MHz, CDCl3) δ 6.60 (s, 1H), 3.09 (t, J = 4.0 Hz, 2H),2.79 (t, J = 4.0 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -66.3 (s, 3F). 13C NMR(101 MHz, CDCl3) δ 194.2 (s), 187.4 (s), 158.9 (s), 139.5 (q, J = 37.2 Hz),120.1 (q, J = 275.1 Hz), 112.7 (s), 112.6 (q, J = 6.1 Hz), 34.36 (s), 26.29(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5 mL反应管中,加入0.30mmol 5-苯基-1,3-环己二酮,1.0 mL 1,2-二氯乙烷,0.060 mmol 2-二甲氨基吡啶,0.45mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和二氯甲烷洗脱,得到7-苯基-4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮(分离产率99%)。1H NMR (400 MHz, CDCl3) δ 7.42 (t, J = 7.1 Hz, 2H),7.35 (d, J = 7.0 Hz, 1H), 7.29 (d, J = 7.1 Hz, 2H), 6.71 (s, 1H), 3.55 (d, J= 5.8 Hz, 1H), 3.17 (d, J = 7.8 Hz, 2H), 3.02 – 2.60 (m, 2H). 19F NMR (376MHz, CDCl3) δ -63.5 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 190.0 (s), 175.2 (s),157.9 (s), 141.5 (q, J = 35.3 Hz), 140.7 (s), 129.2(s), 127.8 (s), 126.5 (s),120.9 (q, J = 275.2 Hz), 115.3 (q, J = 7.4 Hz), 111.1 (s), 45.1 (s), 37.4(s), 36.7 (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5 mL反应管中,加入0.30mmol 5-苯基-1,3-环己二酮,1.0 mL 1,2-二氯乙烷,0.060 mmol 三乙胺,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和二氯甲烷洗脱,以三氟甲氧基苯为内标,测得7-苯基-4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮氟谱产率85%。核磁谱图见实施例13。
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5 mL反应管中,加入0.30mmol 5-苯基-1,3-环己二酮,1.0 mL 1,2-二氯乙烷,0.060 mmol 吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴120℃条件下在密闭体系中搅拌反应16 h后冷却至室温,合并有机相,用饱和氯化铵溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和二氯甲烷洗脱,以三氟甲氧基苯为内标,测得7-苯基-4-(三氟甲基)-7,8-二氢-2H-苯并吡喃-2,5(6H)-二酮氟谱产率54%。核磁谱图见实施例13。
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5 mL反应管中,加入0.30mmol 1,3-环己二酮,0.90 mmol 醋酸铵,3.0 mL 1,2-二氯乙烷,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴140℃条件下在密闭体系中搅拌反应48 h后冷却至室温,合并有机相,用饱和氯化钠溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和乙酸乙酯洗脱,得到4-(三氟甲基)-7,8-二氢喹啉-2,5(1H,6H)-二酮(分离产率78%)。1H NMR (400 MHz, DMSO) δ 12.63 (br, 1H), 6.67 (s,1H), 2.87 (t, J = 5.5 Hz, 2H), 2.48 (t, J = 6.1 Hz, 2H), 2.12 – 1.82 (dt, J =12.0 Hz, J = 4.0 Hz, 2H). 19F NMR (376 MHz, DMSO) δ -61.2 (s, 3F). 13C NMR(101 MHz, DMSO) δ 191.6 (s), 161.5 (s), 161.0 (s), 138.6 (q, J = 33.0 Hz),122.6 (q, J = 274.6 Hz), 119.2 (q, J = 7.0 Hz), 109.3 (s), 38.6 (s), 28.2(s), 20.5 (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5 mL反应管中,加入0.30mmol 5-甲基-1,3-环己二酮,0.90 mmol 醋酸铵,3.0 mL 1,2-二氯乙烷,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴140℃条件下在密闭体系中搅拌反应48 h后冷却至室温,合并有机相,用饱和氯化钠溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和乙酸乙酯洗脱,得到7-甲基-4-(三氟甲基)-7,8-二氢喹啉-2,5(1H,6H)-二酮(分离产率91%)。1H NMR (400 MHz, DMSO) δ 12.65 (br,1H), 6.67 (s, 1H), 2.88 (d, J = 17.9 Hz, 1H), 2.64 (dd, J = 17.3, 9.3 Hz,1H), 2.48 (d, J = 12.0 Hz, 1H), 2.28 (d, J = 10.2 Hz, 2H), 1.04 (d, J = 4.5Hz, 3H). 19F NMR (376 MHz, DMSO) δ -61.2 (s, 3F). 13C NMR (101 MHz, DMSO) δ191.6 (s), 161.6 (s), 160.3 (s), 138.4 (q, J = 33.0 Hz), 122.6 (q, J = 274.5Hz), 119.1 (q, J = 7.5 Hz), 109.0 (s), 46.6 (s), 35.8 (s), 27.9 (s), 20.8(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5 mL反应管中,加入0.30mmol 5-苯基-1,3-环己二酮,1.5 mmol 醋酸铵,3.0 mL 1,2-二氯乙烷,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴140℃条件下在密闭体系中搅拌反应48 h后冷却至室温,合并有机相,用饱和氯化钠溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和乙酸乙酯洗脱,得到4-(三氟甲基)-6,7-二氢-1H-环戊[b]吡啶-2,5-二酮(分离产率50%)。1H NMR (400 MHz, DMSO) δ 13.07 (br, 1H),6.64 (s, 1H), 2.96 (t, J = 4.0 Hz, 2H), 2.58 (t, J = 4.0 Hz, 2H). 19F NMR (376MHz, DMSO) δ -63.9 (s, 3F). 13C NMR (101 MHz, DMSO) δ 196.5 (s), 172.3 (s),163.0 (s), 135.5 (q, J = 34.9 Hz), 123.2 (q, J = 275.7 Hz), 117.8 (q, J = 5.6Hz), 111.1 (s), 111.1 (s), 35.2 (s), 35.2 (s), 24.9 (s), 24.9 (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5 mL反应管中,加入0.30mmol 1,3-环戊二酮,1.5 mmol 醋酸铵,3.0 mL 1,2-二氯乙烷,0.060 mmol 2-二甲氨基吡啶,0.45 mmol三氟乙酰乙酸乙酯,油浴140℃条件下在密闭体系中搅拌反应48 h后冷却至室温,合并有机相,用饱和氯化钠溶液与乙酸乙酯萃取,旋蒸除去有机溶剂得到粗产物,粗产物通过硅胶柱层析,以正戊烷和乙酸乙酯洗脱,得到7-苯基-4-(三氟甲基)-7,8-二氢喹啉-2,5(1H,6H)-二酮(分离产率50%)。1H NMR (400 MHz, DMSO) δ 12.73 (br, 1H), 7.37(d, J = 1.5 Hz, 4H), 7.32 – 7.24 (m, 1H), 6.73 (s, 1H), 3.51 (t, J = 12.6 Hz,1H), 3.27 – 3.15 (m, 1H), 3.03 (d, J = 17.1 Hz, 1H), 2.90 (t, J = 16.0 Hz,1H), 2.64 (d, J = 15.1 Hz, 1H). 19F NMR (376 MHz, DMSO) δ -61.2 (s, 3F). 13CNMR (101 MHz, CDCl3) δ 190.5 (s), 161.2 (s), 159.7 (s), 142.5 (s), 138.0 (q,J = 33.3 Hz), 128.7 (s), 127.0 (s), 126.8 (s), 122.2 (q, J = 275.0 Hz), 118.9(q, J = 6.8 Hz), 108.5 (s), 45.1 (s), 37.5 (s), 34.9 (s).
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 (2)
1.一种合成4-三氟甲基-2-吡啶酮化合物的方法,其特征在于:以有机碱小分子为催化剂,以1,3-环己二酮及其类似物,以及三氟乙酰乙酸乙酯、醋酸铵为原料,在有机溶剂中,反应制得4-三氟甲基-2-吡啶酮化合物;有机碱小分子催化剂、1,3-环己二酮及其类似物、三氟乙酰乙酸乙酯、醋酸铵以及有机溶剂的摩尔比为0.06-0.2:0.3-1: 0.45-1.5:0.9-3:12.7-42;所述的有机碱小分子催化剂为2-二甲氨基吡啶、4-二甲氨基吡啶、三乙胺、吡啶和四氢吡咯中的任一种;所述的有机溶剂为1,2-二氯乙烷、二乙二醇二甲醚、二甲基亚砜、N,N-二甲基甲酰胺、硝基苯、N-甲基吡咯烷酮中的任一种;所述的1,3-环己二酮及其类似物为下述结构式1-式7的任意一种:
2.根据权利要求1所述的一种合成4-三氟甲基-2-吡啶酮化合物的方法,其特征在于:具体步骤如下:在氮气气氛中,向带有磁力搅拌装置的容器中加入有机碱小分子催化剂、1,3-环己二酮及其类似物、三氟乙酰乙酸乙酯、醋酸铵以及有机溶剂,混合均匀后关好塞子,将其放在140℃下继续搅拌48小时后,用100-200目硅胶过滤,二氯甲烷冲洗,合并有机相,用饱和氯化钠溶液与乙酸乙酯萃取,然后旋蒸除去有机溶剂;得到的粗产物通过硅胶柱层析,以正戊烷和乙酸乙酯为洗脱剂,得到4-三氟甲基-2-吡啶酮化合物。
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