CN107522648A - 一种3‑α‑二氟甲基‑α‑三氟甲基‑甲醇基吲哚及其衍生物的合成方法 - Google Patents
一种3‑α‑二氟甲基‑α‑三氟甲基‑甲醇基吲哚及其衍生物的合成方法 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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Abstract
本发明公开了一种3‑α‑二氟甲基‑α‑三氟甲基‑甲醇基吲哚及其衍生物的合成方法:以铜盐为催化剂,以吲哚、五氟丙烯氧基三甲基硅烷为原料,在溶剂中,80℃下搅拌1~24小时,反应结束后对反应液后处理得到3‑α‑二氟甲基‑α‑三氟甲基‑甲醇基吲哚化合物。然后将该产物与叔丁醇钾,在超干乙腈溶剂中在100℃反应16h,用乙酸乙酯萃取,柱色谱分离,得到二氟甲基二乙腈吲哚衍生物。本发明的合成方法具有反应条件温和、产率高、原料易得,操作简便,官能团普适性好等优点。
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3-α-二氟甲基-α-三氟甲基-甲醇基吲哚及其衍生物的合成方法。
背景技术
由于含氟基团的引入会极大的改变母体分子的新陈代谢稳定性、分子亲脂性和吸电子能力,有机含氟化合物在生物医药、农药和材料领域有非常关键的应用前景。因此,把含氟基团的直接引入到有机分子上,是研究新型生物活性分子的一种重要策略。其中,3-α-二氟甲基-α-三氟甲基-甲醇基化合物在生物活性分子和材料科学上已经展现出出乎意料的特效性,如在抗高血压药及抗炎药的研制中显示其特殊的生物活性(BE872311A4;US4381311A),在高分子材料引入此类基团在真空紫外敏感光致抗蚀剂有非常重要的效果(JP2003015298A)。而吲哚作为一种药物合成非常亲睐的母体,其在药物分子有着不可多得的生物活性。因此3-α-二氟甲基-α-三氟甲基-甲醇基吲哚及其衍生物具有重要的理论研究意义和实际应用价值。目前,通过一些廉价易得的原料,高效、简便地合成直接合成3-α-二氟甲基-α-三氟甲基-甲醇基化合物化合物的方法还未见报道。因此发明一种合成3-α-二氟甲基-α-三氟甲基-甲醇基吲哚及其衍生物的合成方法,为发展新型、高效、特效的药物分子提供了支撑和可能。
发明内容
本发明的目的在于提供一种3-α-二氟甲基-α-三氟甲基-甲醇基吲哚及其衍生物的合成方法,该法催化剂及原料廉价易得,产率普遍优秀,官能团的适应性很好,且其反应条件温和,操作简便,具有良好的工业应用前景。
为实现上述目的,本发明采用如下技术方案:
一种3-α-二氟甲基-α-三氟甲基-甲醇基吲哚的合成方法,以铜盐为催化剂,以吲哚、五氟丙烯氧基三甲基硅烷为原料,在溶剂中,反应制得3-α-二氟甲基-α-三氟甲基-甲醇基吲哚;所述吲哚的结构式为;所述的五氟丙烯氧基三甲基硅烷的结构式为:;所述的3-α-二氟甲基-α-三氟甲基-甲醇基吲哚化合物的结构式为:;化学反应式为:
。
所述的铜盐为氯化亚铜、溴化亚铜、碘化亚铜、氰化亚铜、硫氰酸亚铜中的一种。
所述的溶剂为1,2-二氯乙烷、二氯甲烷、乙腈和四氢呋喃中的一种。
所述吲哚的结构式为下述式1-式22中的任意一种:
所述铜盐、吲哚、五氟丙烯氧基三甲基硅烷以及溶剂的摩尔比为0.08-0.20:0.4-1:0.44-1.1:12.3-24.6。
优选的,铜盐、吲哚、五氟丙烯氧基三甲基硅烷以及溶剂的摩尔比为0.2:1:1.1:12.3。
如上所述的3-α-二氟甲基-α-三氟甲基-甲醇基吲哚的合成方法,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铜盐、吲哚、五氟丙烯氧基三甲基硅烷以及溶剂,混合均匀后关好塞子,将其放入80℃下继续搅拌1-24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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3-α-二氟甲基-α-三氟甲基-甲醇基吲哚产物。
接着将该3-α-二氟甲基-α-三氟甲基-甲醇基吲哚产物与叔丁醇钾,在超干乙腈溶剂中在100℃反应16h,用乙酸乙酯萃取,柱色谱分离,得到二氟甲基二乙腈吲哚衍生物:
本发明的有益效果在于:
本发明以廉价易得的吲哚、五氟丙烯氧基三甲基硅烷等为原料,以铜盐为催化剂,一步合成3-α-二氟甲基-α-三氟甲基-甲醇基吲哚产物,得到普遍优秀的产率,官能团的适应性很好,且其反应条件温和,操作简便,具有良好的工业应用前景。
附图说明
图1为实施例12制得的1,1,1,3,3-五氟-2-(5-苄氧基-1-甲基-1H-吲哚-3-基)丙烷-2-醇单晶结构示意图;
图2为实施例32制得的3-(二氟甲基)-3-(5-甲氧基-1-甲基-1H-吲哚-3-基)戊二腈单晶结构示意图。
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。
合成3-α-二氟甲基-α-三氟甲基-甲醇基吲哚化合物:
实施例1
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuI、0.4mmol N-甲基吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌16小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率90%)。 1H NMR(400 MHz, CDCl3) δ 7.97 (d, J = 8.1 Hz, 1H), 7.46 – 7.33 (m, 3H), 7.27 (t, J= 7.0 Hz, 1H), 6.31 (t, J = 54.6 Hz, 1H), 3.82 (s, 3H), 3.42 (s, 1H). 19F NMR(376 MHz, CDCl3) δ -76.4 (t, J = 8.7 Hz, 3F), -118.0 – -140.1 (m, 2F). 13C NMR(101 MHz, CDCl3) δ 137.1 (s), 128.7 (dt, J = 3.4, 1.8 Hz), 126.0 (s), 124.0(q, J = 285.6 Hz), 122.49 (s), 121.1 (d, J = 1.2 Hz), 120.5 (s), 113.6 (t, J= 251.4 Hz), 109.9 (s), 104.3 (s), 76.7 – 75.9 (m), 33.0 (s). IR (ATR):ν3582,3056, 2992, 2934, 2860, 1616, 1547, 1477, 1467, 1427, 1371, 1337, 1276, 1173,1137, 1084, 1032, 981, 907, 802, 727, 675, 528, 429 cm-1. GC-MS m/z 279 (M+).HRMS (EI) m/z: calcd. for C12H10NOF5: 279.0683; found: 279.0689。
实施例2
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuBr、0.4mmol N-甲基吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌16小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率96%)。
实施例3
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol N-甲基吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌16小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。
实施例4
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCN、 0.4mmol N-甲基吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌16小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率95%)。
实施例5
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuSCN、 0.4mmol N-甲基吲哚、0.44mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌16小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率98%)。
实施例6
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol N-甲基吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL二氯甲烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌16小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。
实施例7
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol N-甲基吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL四氢呋喃,混合均匀后关好塞子,将其放入80 ℃下继续搅拌16小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率40%)。
实施例8
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol 1,4-二甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1,4-二甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率95%)。1H NMR (400 MHz, CDCl3) δ 7.34 (s, 1H), 7.25 (d, J = 3.9 Hz, 2H), 7.16 –7.05 (m, 1H), 6.32 (t, J = 54.5 Hz, 1H), 3.83 (s, 3H), 3.23 (s, 1H), 2.81 (s,3H). 19F NMR (376 MHz, CDCl3) δ -74.6 (t, J = 9.5 Hz, 3F), -124.4 – -142.7 (m,2F). 13C NMR (101 MHz, CDCl3) δ 137.9 (s), 130.9 (s), 129.0 (dd, J = 4.7, 2.9Hz), 125.4 (s), 123.9 (s), 123.9 (q, J = 285.7 Hz), 122.6 (s), 114.0 (t, J =247.6 Hz), 107.6 (s), 104.4 (s), 76.5 – 75.5 (m), 33.4 (s), 23.4 (s). IR(ATR): ν 3475, 3138, 3042, 2924, 2851, 1651, 1609, 1567, 1497, 1459, 1421,1381, 1360, 1310, 1242, 1199, 1174, 1079, 1067, 1007, 962, 925, 867, 803,741, 718, 675, 632, 598, 537, 510, 458 cm-1. GC-MS m/z 293 (M+). HRMS (EI) m/z: calcd. for C13H12NOF5: 293.0839; found: 293.0830。
实施例9
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol 1,5-二甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1,5-二甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。1H NMR (400 MHz, CDCl3) δ 7.74 (s, 1H), 7.30 (d, J = 9.1 Hz, 2H), 7.19(d, J = 8.4 Hz, 1H), 6.29 (t, J = 54.6 Hz, 1H), 3.81 (s, 3H), 3.23 (s, 1H),2.55 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -76.4 (t, J = 8.7 Hz, 3F), -128.1 – -132.8 (m, 2F). 13C NMR (101 MHz, CDCl3) δ 135.5 (s), 129.9 (s), 128.6 (dt, J =3.5, 1.8 Hz), 126.2 (s), 124.2 (s), 124.0 (q, J = 286.2 Hz), 120.5 (s), 113.5(t, J = 250.8 Hz), 109.6 (s), 103.6 (s), 76.6 – 75.9 (m), 33.1 (s), 21.6 (s).IR (ATR): ν 3484, 3129, 3026, 2932, 2855, 1657, 1573, 1546, 1491, 1459, 1429,1378, 1304, 1262, 1234, 1212, 1192, 1168, 968, 919, 875, 836, 802, 792, 756,678, 638, 588, 532, 435 cm-1. GC-MS m/z 293 (M+). HRMS (EI) m/z: calcd. forC13H12NOF5: 293.0839; found: 293.0840。
实施例10
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol 1,7-二甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1,7-二甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.1 Hz, 1H), 7.24 (s, 1H), 7.10(t, J = 7.6 Hz, 1H), 7.03 (d, J = 7.1 Hz, 1H), 6.28 (t, J = 54.6 Hz, 1H),4.11 (s, 3H), 3.23 (s, 1H), 2.82 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -76.3 (t,J = 8.7 Hz, 3F), -128.1 – -132.7 (m, 2F). 13C NMR (101 MHz, CDCl3) δ 135.9(s), 130.3 (dt, J = 3.6, 1.8 Hz), 127.1 (s), 125.2 (s), 123.9 (q, J = 285.5Hz), 121.9 (s), 120.7 (s), 119.0 (s), 113.5 (t, J = 250.9 Hz), 103.8 (s),76.6 – 75.8 (m), 37.3 (s), 19.8 (s). IR (ATR): ν 3510, 3138, 3083, 2932,2852, 1670, 1581, 1496, 1458, 1411, 1361, 1328, 1283, 1213, 1160, 1082, 1047,987, 928, 872, 835, 788, 752, 731, 644, 634, 585, 521, 498 cm-1. GC-MS m/z 293(M+). HRMS (EI) m/z: calcd. for C13H12NOF5: 293.0839; found: 293.0844。
实施例11
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 5-甲氧基-1-甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(5-甲氧基-1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。1H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 1.6 Hz, 1H), 7.23 (s,1H), 7.16 (d, J = 8.9 Hz, 1H), 6.86 (dd, J = 8.9, 2.3 Hz, 1H), 3.80 (s, 3H),3.72 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -76.5 (t, J = 8.6 Hz, 3F), -122.1 – -138.7 (m, 2F). 13C NMR (101 MHz, CDCl3) δ 154.2 (s), 132.3 (s), 129.0 (s),126.9 (s), 124.3 (qd, J = 287.3, 3.4 Hz), 114.1 (t, J = 251.0 Hz), 112.4 (s),110.1 (s), 104.7 (s), 103.7 (s), 76.4 – 75.4 (m), 55.8 (s), 33.2 (s). IR(ATR): ν 3275, 3160, 2964, 2923, 2838, 1623, 1544, 1494, 1448, 1423, 1404,1373, 1264, 1224, 1169, 1071, 1049, 989, 940, 864, 842, 792, 732, 678, 650,623, 584, 484, 425 cm-1. GC-MS m/z 309 (M+). HRMS (EI) m/z: calcd. forC13H12NO2F5: 309.0788; found: 309.0785。
实施例12
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 5-苄氧基-1-甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(5-苄氧基-1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。1H NMR (400 MHz, CD3CN) δ 7.52 (d, J = 7.6 Hz, 2H), 7.42 (dd, J= 13.5, 5.8 Hz, 4H), 7.36 (t, J = 8.3 Hz, 2H), 7.01 (d, J = 9.0 Hz, 1H), 6.41(t, J = 54.1 Hz, 1H), 5.25 (s, 1H), 5.15 (s, 2H), 3.79 (s, 3H). 19F NMR (376MHz, CD3CN) δ -77.0 (t, J = 8.8 Hz, 3F), -126.5 – -140.3 (m, 2F). 13C NMR (101MHz, CD3CN) δ 153.2 (s), 137.9 (s), 132.6 (s), 129.6 (d, J = 1.7 Hz), 128.4(s), 127.8 (s), 127.7 (s), 126.5 (s), 124.5 (q, J = 286.3 Hz), 113.8 (t, J =248.9 Hz), 112.9 (s), 110.7 (s), 104.9 (s), 104.2 (d, J = 2.7 Hz), 76.6 –75.6 (m), 70.4 (s), 32.6 (s).IR (ATR): ν 3387, 3139, 3040, 2922, 2873, 1625,1579, 1491, 1455, 1427, 1385, 1358, 1335, 1302, 1243, 1224, 1098, 1014, 944,914, 852, 832, 815, 794, 763, 746, 696, 662, 609, 526, 495, 428 cm-1. LC-MS m/z 385 (M+). HRMS (EI) m/z: calcd. for C19H16NO2F5: 385.1101; found: 385.1094。
实施例13
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol 5-([1,1'-二苯基]-4-氧基)-1-甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(5-([1,1'-二苯基]-4-氧基)-1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。1H NMR (400 MHz, acetone-d 6) δ7.90 (d, J = 8.2 Hz, 2H), 7.80 (s, 1H), 7.76 (d, J = 7.9 Hz, 2H), 7.69 (d, J= 8.2 Hz, 2H), 7.53 (dd, J = 14.0, 8.2 Hz, 4H), 7.42 (t, J = 7.4 Hz, 1H),6.96 (dd, J = 9.0, 2.4 Hz, 1H), 6.67 (t, J = 54.0 Hz, 1H), 6.62 (s, 1H), 3.86(s, 3H). 19F NMR (376 MHz, acetone-d 6) δ -76.7 (t, J = 8.8 Hz, 3F), -127.2 – -142.7 (m, 2F). 13C NMR (101 MHz, acetone-d 6) δ 154.9 (s), 139.9 (s), 139.7(s), 138.3 (s), 131.4 (s), 129.0 (s), 128.3 (s), 128.0 (s), 127.7 (s), 126.9(s), 124.6 (q, J = 285.8 Hz), 124.5 (s), 114.0 (t, J = 249.6 Hz), 113.0 (s),111.4 (s), 108.3 (s), 104.0 (s), 100.0 (s), 76.5 – 75.8 (m), 55.1 (s). IR(ATR): ν 3351, 3147, 3037, 3001, 2950, 2849, 1702, 1619, 1589, 1548, 1481,1449, 1412, 1376, 1295, 1246, 1159, 1133, 1048, 1027, 940, 847, 823, 794,768, 724, 692, 675, 580, 524, 487, 431 cm-1. LC-MS m/z 447 (M+). HRMS (EI) m/z: calcd. for C24H18NO2F5: 447.1258; found: 447.1252。
实施例14
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 5-甲醛基-1-甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(5-甲醛基-1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率77%)。1H NMR (400 MHz, CD3CN) δ 10.04 (s, 1H), 8.46 (s, 1H), 7.82 (dd,J = 8.6, 1.2 Hz, 1H), 7.58 (d, J = 8.1 Hz, 2H), 6.43 (t, J = 54.0 Hz, 1H),5.47 (s, 1H), 3.88 (s, 3H). 19F NMR (376 MHz, CD3CN) δ -77.2 (t, J = 8.7 Hz,3F), -129.1 – -133.8 (m, 2F). 13C NMR (101 MHz, CD3CN) δ 192.5 (s), 140.2 (s),131.2 (dd, J = 3.9, 2.0 Hz), 129.9 (s), 126.7 (d, J = 1.1 Hz), 126.0 (s),124.2 (q, J = 285.8 Hz), 121.6 (s), 113.7 (t, J = 249.6 Hz), 110.9 (s), 106.7(d, J = 2.4 Hz), 76.7 – 75.5 (m), 32.9 (s). IR (ATR): ν 3304, 2953, 2921,2849, 1670, 1659, 1541, 1475, 1429, 1384, 1352, 1317, 1275, 1191, 1086, 1050,982, 937, 924, 828, 800, 780, 736, 722, 665, 629, 583, 556, 529, 498, 433 cm-1. GC-MS m/z 307 (M+). HRMS (EI) m/z: calcd. for C13H10NO2F5: 307.0632; found:307.0629。
实施例15
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 5-氰基-1-甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(5-氰基-1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率34%)。1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.38 (d, J = 5.8 Hz, 2H),7.31 (d, J = 8.6 Hz, 1H), 6.97 (s, 1H), 6.11 (t, J = 54.9 Hz, 1H), 3.76 (s,3H). 19F NMR (376 MHz, CDCl3) δ -76.7 (dd, J = 9.3, 7.4 Hz, 3F), -117.7 – -150.9 (m, 2F). 13C NMR (101 MHz, CDCl3) δ 138.4 (s), 130.9 (s), 128.0 (s),126.5 (s), 124.7 (s), 124.1 (qd, J = 286.8, 4.2 Hz), 120.6 (s), 113.8 (t, J =251.2 Hz), 110.5 (s), 106.6 (s), 103.0 (s), 75.7 (ddd, J = 29.5, 23.3, 6.1Hz), 33.3 (s). IR (ATR): ν 3403, 3125, 2982, 2923, 2850, 2221, 1615, 1542,1488, 1430, 1378, 1345, 1302, 1266, 1172, 1149, 1114, 1051, 1021, 1003, 935,816, 790, 759, 726, 676, 648, 621, 497, 425 cm-1. GC-MS m/z 303 (M+). HRMS(EI) m/z: calcd. for C13H9N2OF5: 303.0635; found: 303.0639。
实施例16
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 5-氟-1-甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(5-氟-1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.3 Hz, 1H), 7.35 (s, 1H),7.28 (dd, J = 8.6, 4.8 Hz, 1H), 7.06 (td, J = 9.0, 2.4 Hz, 1H), 6.21 (t, J =54.6 Hz, 1H), 3.83 (s, 3H), 3.19 (s, 1H). 19F NMR (376 MHz, CDCl3) δ -76.6 (t,J = 8.6 Hz, 3F), -123.3 (td, J = 9.7, 4.5 Hz, 1F), -126.1 – -137.3 (m, 2F).13C NMR (101 MHz, CDCl3) δ 159.4 (s), 157.0 (s), 133.7 (s), 129.9 (s), 126.3(d, J = 10.7 Hz), 123.8 (q, J = 285.4 Hz), 113.4 (t, J = 249.2 Hz), 110.8(dd, J = 62.3, 18.3 Hz), 106.3 (d, J = 25.2 Hz), 104.2 (d, J = 3.6 Hz), 76.4– 75.7 (m), 33.4 (s). IR (ATR): ν 3559, 3138, 2982, 2923, 2850, 1628, 1541,1489, 1457, 1430, 1397, 1341, 1300, 1251, 1175, 1077, 1024, 975, 931, 861,839, 825, 799, 760, 683, 672, 535, 470, 431 cm-1. GC-MS m/z 297 (M+). HRMS(EI) m/z: calcd. for C12H9NOF6: 297.0588; found: 297.0581。
实施例17
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol 6-氟-1-甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(6-氟-1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 8.9, 5.3 Hz, 1H), 7.31 (s,1H), 7.04 (dd, J = 9.5, 2.2 Hz, 1H), 6.97 (td, J = 9.2, 2.3 Hz, 1H), 6.22 (t,J = 54.6 Hz, 1H), 3.78 (s, 3H), 3.21 (s, 1H). 19F NMR (376 MHz, CDCl3) δ -76.6(t, J = 8.6 Hz, 3F), -119.6 (td, J = 9.5, 5.3 Hz, 1F), -125.8 – -135.6 (m,2F). 13C NMR (101 MHz, CDCl3) δ 161.2 (s), 158.8 (s), 137.2 (d, J = 11.9 Hz),129.0 – 128.8 (m), 123.8 (q, J = 286.8 Hz), 122.6 – 121.8 (m), 113.4 (t, J =250.4 Hz), 109.3 (d, J = 24.4 Hz), 104.6 (s), 96.0 (d, J = 26.1 Hz), 76.5 –75.7 (m), 33.2 (s). IR (ATR): ν 3568, 3497, 3144, 2987, 2921, 2851, 1624,1542, 1478, 1423, 1339, 1275, 1251, 1159, 1132, 1077, 1027, 983, 934, 887,837, 800, 762, 724, 697, 674, 494, 433 cm-1. GC-MS m/z 297 (M+). HRMS (EI) m/z: calcd. for C12H9NOF6: 297.0588; found: 297.0594。
实施例18
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 5-氯-1-甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(5-氯-1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率91%)。1H NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.34 (s, 1H), 7.25 (d, J =10.5 Hz, 2H), 6.21 (t, J = 54.6 Hz, 1H), 3.81 (s, 3H), 3.27 (s, 1H). 19F NMR(376 MHz, CDCl3) δ -76.6 (t, J = 8.6 Hz, 3F), -125.8 – -139.4 (m, 2F). 13C NMR(101 MHz, CDCl3) δ 135.5 (s), 129.7 (dt, J = 3.3, 1.8 Hz), 127.0 (s), 126.4(s), 123.8 (q, J = 286.2 Hz), 122.9 (s), 120.6 (d, J = 1.3 Hz), 113.4 (t, J =251.0 Hz), 110.8 (s), 103.9 (d, J = 1.6 Hz), 76.1 (ddd, J = 29.7, 23.1, 6.5Hz), 33.3 (s). IR (ATR): ν 3484, 3152, 3000, 2957, 2923, 2850, 1647, 1617,1542, 1478, 1431, 1381, 1336, 1298, 1257, 1185, 1085, 1024, 980, 967, 908,844, 799, 758, 724, 670, 527, 491, 421 cm-1. GC-MS m/z 313 (M+). HRMS (EI) m/z: calcd. for C12H9NOF5Cl: 313.0293; found: 313.0291。
实施例19
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 5-溴-1-甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(5-氯-1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.38 (d, J = 8.7 Hz, 1H),7.32 (s, 1H), 7.22 (d, J = 8.8 Hz, 1H), 6.21 (t, J = 54.6 Hz, 1H), 3.80 (s,3H), 3.19 (s, 1H). 19F NMR (376 MHz, CDCl3) δ -76.6 (t, J = 8.6 Hz, 3F), -124.8 – -135.3 (m, 2F). 13C NMR (101 MHz, CDCl3) δ 135.7 (s), 129.6 (s), 127.6(s), 125.4 (s), 123.7 (q, J = 286.2 Hz), 123.7 (s), 114.0 (s), 113.4 (t, J =251.1 Hz), 111.2 (s), 103.8 (s), 76.7 – 75.5 (m), 33.3 (s). IR (ATR): ν 3446,3152, 3026, 2923, 2855, 1615, 1541, 1429, 1384, 1335, 1299, 1272, 1170, 1082,1051, 979, 966, 895, 845, 797, 771, 723, 670, 594, 577, 489, 437 cm-1. GC-MSm/z 357 (M+). HRMS (EI) m/z: calcd. for C12H9NOF5Br: 356.9788; found: 356.9787。
实施例20
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol 1,2-二甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1,2-二甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.1 Hz, 1H), 7.34 (d, J = 8.1 Hz,1H), 7.25 (t, J = 7.6 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H), 6.79 (t, J = 54.2Hz, 1H), 3.70 (s, 3H), 3.32 (s, 1H), 2.66 (s, 3H). 19F NMR (376 MHz, CDCl3) δ-76.9 (dd, J = 10.8, 6.0 Hz, 3F), -123.7 – -138.0 (m, 2F). 13C NMR (101 MHz,CDCl3) δ 137.6 (s), 136.7 (s), 125.3 (s), 124.4 (q, J = 285.8 Hz), 121.3 (s),120.3 (s), 119.8 (s), 112.2 (t, J = 247.6 Hz), 109.4 (s), 101.4 (s), 78.8 –77.7 (m), 29.5 (s), 12.4 (s). IR (ATR): ν 3648, 3374, 3051, 2955, 2923, 2853,1635, 1613, 1540, 1475, 1407, 1377, 1360, 1324, 1250, 1219, 1161, 1139, 1113,1062, 970, 892, 805, 739, 725, 653, 561, 534, 430 cm-1. GC-MS m/z 293 (M+).HRMS (EI) m/z: calcd. for C13H12NOF5: 293.0839; found: 293.0850。
实施例21
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 2-苯基-1-甲基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(2-苯基-1-甲基-1H-吲哚-3-基)丙烷-2-醇(分离收率97%)。1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.1 Hz, 1H), 7.57 (dd, J =11.0, 4.1 Hz, 3H), 7.48 (d, J = 5.7 Hz, 1H), 7.44 (d, J = 10.0 Hz, 1H), 7.38(dd, J = 14.0, 7.1 Hz, 2H), 7.28 (t, J = 7.5 Hz, 1H), 5.96 (t, J = 54.3 Hz,1H), 3.44 (s, 3H), 3.12 (s, 1H). 19F NMR (376 MHz, CDCl3) δ -76.4 (dd, J =12.4, 4.1 Hz, 3F), -124.4 – -145.8 (m, 2F). 13C NMR (101 MHz, CDCl3) δ 139.1(s), 136.7 (s), 131.7 (s), 131.0 (d, J = 14.8 Hz), 129.8 (s), 128.7 (d, J =1.3 Hz), 126.0 (s), 123.9 (q, J = 287.4 Hz), 122.6 (s), 122.0 (t, J = 1.8Hz), 120.8 (s), 111.7 (t, J = 246.5 Hz), 109.7 (s), 103.9 (d, J = 3.9 Hz),77.8 (ddd, J = 24.3, 17.9, 5.0 Hz), 30.5 (s).IR (ATR): ν 3513, 3021, 2957,2924, 2855, 1726, 1605, 1542, 1467, 1443, 1433, 1382, 1344, 1258, 1224, 1199,1076, 1067, 957, 886, 849, 810, 756, 726, 702, 675, 637, 587, 553, 494, 442cm-1. GC-MS m/z 355 (M+). HRMS (EI) m/z: calcd. for C18H14NOF5: 355.0996; found:355.0999。
实施例22
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1H-吲哚-3-基)丙烷-2-醇(分离收率97%)。1H NMR (400 MHz,CDCl3) δ 8.39 (s, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.46 (dd, J = 8.5, 5.4 Hz,3H), 7.30 (t, J = 6.2 Hz, 2H), 7.23 (dt, J = 8.0, 3.9 Hz, 1H), 6.28 (t, J =54.6 Hz, 2H), 3.24 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -76.4 (t, J = 8.7 Hz,3F), -123.7 – -138.6 (m, 2F). 13C NMR (101 MHz, CDCl3) δ 136.1 (s), 125.3 (s),124.2 (dd, J = 4.9, 1.9 Hz), 123.9 (q, J = 286.8 Hz), 123.0 (s), 121.0 (dd, J= 2.6, 1.3 Hz), 120.9 (s), 113.4 (t, J = 251.4 Hz), 111.6 (s), 106.2 (d, J =1.6 Hz), 76.6 – 75.8 (m). IR (ATR): ν 3410, 3061, 2980, 2932, 2878, 1621,1543, 1492, 1459, 1422, 1385, 1340, 1275, 1246, 1174, 1079, 1014, 980, 919,893, 832, 802, 744, 727, 689, 629, 580, 523, 498, 426 cm-1. GC-MS m/z 265 (M+). HRMS (EI) m/z: calcd. for C11H8NOF5: 265.0526; found: 265.0533。
实施例23
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol 1-对甲苯基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-对甲苯基-1H-吲哚-3-基)丙烷-2-醇(分离收率88%)。1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.8 Hz, 1H), 7.58 (s, 1H), 7.54(d, J = 8.2 Hz, 1H), 7.42 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.33– 7.24 (m, 2H), 6.32 (t, J = 54.5 Hz, 1H), 3.35 (s, 1H), 2.49 (s, 3H). 19F NMR(376 MHz, CDCl3) δ -76.3 (t, J = 8.6 Hz, 3F), -119.7 – -141.7 (m, 2F). 13C NMR(101 MHz, CDCl3) δ 137.5 (s), 136.6 (s), 136.2 (s), 130.3 (s), 128.0 (d, J =2.8 Hz), 126.4 (s), 124.8 (s), 123.9 (q, J = 285.5 Hz), 123.1 (s), 121.3 (s),121.2 (s), 113.5 (t, J = 251.4 Hz), 111.1 (s), 106.4 (d, J = 1.7 Hz), 76.6 –75.9 (m), 21.1 (s). IR (ATR): ν 3579, 3141, 3040, 2926, 2857, 1651, 1609,1547, 1516, 1478, 1460, 1379, 1348, 1322, 1274, 1197, 1176, 1148, 1131, 1086,1020, 980, 948, 906, 821, 801, 729, 649, 591, 530, 483, 430 cm-1. LC-MS m/z355 (M+). HRMS (EI) m/z: calcd. for C18H14NOF5: 355.0996; found: 355.0992。
实施例24
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 1-对叔丁苯基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-叔丁苯基-1H-吲哚-3-基)丙烷-2-醇(分离收率99%)。1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.8 Hz, 1H), 7.59 (dd, J = 8.5,2.5 Hz, 4H), 7.47 (d, J = 8.5 Hz, 2H), 7.35 – 7.25 (m, 2H), 6.32 (t, J = 54.6Hz, 1H), 3.33 (s, 1H), 1.45 (s, 9H). 19F NMR (376 MHz, CDCl3) δ -76.3 (t, J =8.6 Hz, 3F), -125.1 – -135.0 (m, 2F). 13C NMR (101 MHz, CDCl3) δ 150.7 (s),136.6 (s), 136.2 (s), 128.0 (s), 126.7 (s), 126.5 (s), 124.5 (s), 123.9 (q, J= 285.8 Hz), 123.1 (s), 121.3 (s), 121.2 (s), 113.5 (t, J = 251.1 Hz), 111.2(s), 106.5 (s), 76.6 – 75.5 (m), 34.7 (s), 31.4 (s). IR (ATR): ν 3585, 3140,3051, 2964, 2906, 2870, 1680, 1608, 1547, 1517, 1478, 1460, 1366, 1323, 1271,1199, 1168 , 1087, 1018, 981, 950, 907, 841, 802, 730, 662, 594, 541, 429 cm-1. LC-MS m/z 397 (M+). HRMS (EI) m/z: calcd. for C21H20NOF5: 397.1465; found:397.1459。
实施例25
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、0.4mmol 1-4’-联苯基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-4’-联苯基-1H-吲哚-3-基)丙烷-2-醇(分离收率96%)。1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.9 Hz, 1H), 7.79 (d, J = 8.4Hz, 2H), 7.68 (d, J = 7.6 Hz, 2H), 7.65 – 7.60 (m, 4H), 7.53 (t, J = 7.5 Hz,2H), 7.44 (t, J = 7.4 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 7.29 (t, J = 7.4 Hz,1H), 6.33 (t, J = 54.5 Hz, 1H), 3.28 (s, 1H). 19F NMR (376 MHz, CDCl3) δ -76.3(t, J = 8.6 Hz, 3F), -121.1 – -135.9 (m, 2F). 13C NMR (101 MHz, CDCl3) δ 140.5(s), 140.0 (s), 137.9 (s), 136.5 (s), 129.0 (s), 128.4 (s), 127.8 (s), 127.8(s), 127.1 (s), 126.6 (s), 125.1 (s), 123.9 (q, J = 285.8 Hz), 123.3 (s),121.4 (s), 121.4 (s), 113.4 (t, J = 251.1 Hz), 111.1 (s), 106.9 (d, J = 1.5Hz), 76.7 – 75.9 (m). IR (ATR): ν 3538, 3459, 3144, 3035, 2998, 2849, 1644,1605, 1551, 1523, 1490, 1458, 1376, 1347, 1323, 1275, 1185, 1133, 1085, 1004,946, 910, 874, 846, 767, 756, 723, 691, 589, 524, 486, 432 cm-1. LC-MS m/z 417(M+). HRMS (EI) m/z: calcd. for C23H16NOF5: 417.1152; found: 417.1154。
实施例26
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 1-对甲氧苯基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-对甲氧苯基-1H-吲哚-3-基)丙烷-2-醇(分离收率96%)。1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.7 Hz, 1H), 7.55 (s, 1H),7.47 (d, J = 8.1 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.34 – 7.21 (m, 2H), 7.07(d, J = 8.8 Hz, 2H), 6.32 (t, J = 54.6 Hz, 1H), 3.92 (s, 3H), 3.42 (s, 1H).19F NMR (376 MHz, CDCl3) δ -76.3 (t, J = 8.6 Hz, 3F), -126.6 – -134.5 (m, 2F).13C NMR (101 MHz, CDCl3) δ 158.9 (s), 136.9 (s), 131.7 (s), 128.2 (s), 126.5(s), 126.2 (d, J = 3.6 Hz), 123.9 (q, J = 285.2 Hz), 123.0 (s), 121.2 (s),121.1 (s), 114.9 (s), 113.5 (t, J = 251.6 Hz), 110.9 (s), 76.6 – 75.9 (m),55.6 (s). IR (ATR): ν 3409, 3139, 3052, 2962, 2841, 1613, 1547, 1514, 1461,1460, 1275, 1164, 1148, 1131, 1107, 1031, 980, 946, 907, 836, 797, 741, 665,592, 518, 430 cm-1. LC-MS m/z 371 (M+). HRMS (EI) m/z: calcd. for C18H14NO2F5:371.0945; found: 371.0941。
实施例27
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 1-对溴苯基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-对溴苯基-1H-吲哚-3-基)丙烷-2-醇(分离收率84%)。1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.8 Hz, 1H), 7.70 (d, J = 8.6 Hz,2H), 7.56 (s, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 8.6 Hz, 2H), 7.30(td, J = 15.2, 7.4 Hz, 2H), 6.32 (t, J = 54.5 Hz, 1H), 3.34 (s, 1H). 19F NMR(376 MHz, CDCl3) δ -76.3 (t, J = 8.5 Hz, 3F), -127.2 – -137.7 (m, 2F). 13C NMR(101 MHz, CDCl3) δ 137.8 (s), 136.3 (s), 133.0 (s), 127.5 (dt, J = 3.3, 1.7Hz), 126.6 (s), 126.4 (s), 123.8 (q, J = 287.1 Hz), 123.5 (s), 121.6 (s),121.5 (d, J = 1.0 Hz), 121.0 (s), 113.4 (t, J = 251.4 Hz), 110.8 (s), 107.4(d, J = 1.8 Hz), 76.6 – 75.9 (m). IR (ATR): ν 3574, 3141, 3055, 2924, 2853,1653, 1611, 1590, 1550, 1492, 1458, 1377, 1346, 1318, 1273, 1228, 1175, 1070,1011, 981, 946, 906, 832, 802, 731, 650, 585, 530, 482, 429 cm-1. LC-MS m/z419 (M+). HRMS (EI) m/z: calcd. for C17H11NOF5Br: 418.9944; found: 418.9932。
实施例28
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.1 mmol CuCl、 0.4mmol 1-对硝基苯基-1H-吲哚、0.44 mmol五氟丙烯氧基三甲基硅烷以及4 mL 1,2-二氯乙烷,混合均匀后关好塞子,将其放入80 ℃下继续搅拌24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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1,1,1,3,3-五氟-2-(1-对硝基苯基-1H-吲哚-3-基)丙烷-2-醇(分离收率55%)。1H NMR (400 MHz, CDCl3) δ 8.43 (d, J = 8.6 Hz, 2H), 8.03 (d, J = 8.0Hz, 1H), 7.72 (d, J = 8.6 Hz, 2H), 7.65 (d, J = 9.7 Hz, 2H), 7.38 (t, J = 7.6Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 6.34 (t, J = 54.4 Hz, 1H), 3.54 (s, 1H).19F NMR (376 MHz, CDCl3) δ -76.3 (t, J = 8.5 Hz, 3F), -124.4 – -138.0 (m, 2F).13C NMR (101 MHz, CDCl3) δ 145.9 (s), 144.2 (s), 127.1 (dd, J = 3.1, 1.6 Hz),125.6 (s), 124.3 (s), 124.2 (s), 123.7 (q, J = 285.8 Hz), 123.1 (s), 122.4(s), 122.0 (s), 120.8 (s), 113.5 (t, J = 214.1 Hz), 110.8 (s), 109.3 (d, J =1.6 Hz), 76.6 – 75.8 (m). IR (ATR): ν 3593, 3141, 3087, 2926, 2852, 1608,1593, 1557, 1524, 1501, 1457, 1348, 1327, 1271, 1180, 1163, 1148, 1134, 1100,1065, 979, 947, 868, 803, 751, 723, 656, 584, 525, 481, 434 cm-1. LC-MS m/z386 (M+). HRMS (EI) m/z: calcd. for C17H11N2O3F5: 386.0690; found: 386.0689。
合成二氟甲基二乙腈吲哚衍生物
实施例29
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.2 mmol 1,1,1,3,3-五氟-2-(1-甲基-1H-吲哚-3-基)丙烷-2-醇、0.3 mmol 叔丁醇钾以及2 mL超干乙腈溶剂,混合均匀后关好塞子,将其放入100 ℃下继续搅拌16小时后,用乙酸乙酯萃取,加水洗涤三次,合并有机相,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3-(二氟甲基)-3-(1-甲基-1H-吲哚-3-基)戊二腈(分离收率74%)。 1HNMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 8.2 Hz, 1H),7.37 – 7.32 (m, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.16 (s, 1H), 6.26 (t, J =55.1 Hz, 1H), 3.85 (s, 3H), 3.34 – 3.22 (m, 4H). 19F NMR (376 MHz, CDCl3) δ -124.1 (d, J = 55.1 Hz, 2F). 13C NMR (101 MHz, CDCl3) δ 137.8 (s), 127.9 (s),124.7 (s), 122.8 (s), 120.5 (s), 119.6 (t, J = 2.5 Hz), 116.2 (t, J = 251.5Hz), 115.4 (s), 110.5 (s), 44.2 (t, J = 20.3 Hz), 33.2 (s), 22.4 (t, J = 4.0Hz). IR (ATR): ν 3384, 3125, 3056, 2925, 2853, 2252, 2191, 1733, 1635, 1595,1545, 1479, 1427, 1375, 1336, 1255, 1141, 1101, 1062, 907, 859, 841, 819,729, 649, 612, 572,550, 432 cm-1. GC-MS m/z 273 (M+)。
实施例30
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.2 mmol 1,1,1,3,3-五氟-2-(1,5-二甲基-1H-吲哚-3-基)丙烷-2-醇、0.3 mmol 叔丁醇钾以及2 mL超干乙腈溶剂,混合均匀后关好塞子,将其放入100 ℃下继续搅拌16小时后,用乙酸乙酯萃取,加水洗涤三次,合并有机相,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3-(二氟甲基)-3-(1,5-二甲基-1H-吲哚-3-基)戊二腈(分离收率96%)。1H NMR (400 MHz, CDCl3) δ 7.38 (s, 1H), 7.30 (d, J = 8.5 Hz, 1H), 7.17(d, J = 8.4 Hz, 1H), 7.11 (s, 1H), 6.27 (t, J = 55.1 Hz, 1H), 3.79 (s, 3H),3.34 – 3.20 (m, 4H), 2.52 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -124.1 (d, J =55.2 Hz, 2F). 13C NMR (101 MHz, CDCl3) δ 136.3 (s), 129.8 (s), 127.9 (s),124.9 (s), 124.4 (s), 119.2 (s), 116.2 (t, J = 251.4 Hz), 115.6 (s), 110.2(s), 106.8 (t, J = 2.7 Hz), 44.2 (t, J = 20.2 Hz), 33.2 (s), 22.3 (t, J = 3.9Hz), 21.7 (s). IR (ATR): ν 3128, 2924, 2855, 2253, 2191, 1734, 1574, 1544,1492, 1428, 1379, 1339, 1255, 1146, 1062, 1038, 906, 795, 727, 648, 605, 577,429 cm-1. GC-MS m/z 287 (M+)。
实施例31
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.2 mmol 1,1,1,3,3-五氟-2-(1,7-二甲基-1H-吲哚-3-基)丙烷-2-醇、0.3 mmol 叔丁醇钾以及2 mL超干乙腈溶剂,混合均匀后关好塞子,将其放入100 ℃下继续搅拌16小时后,用乙酸乙酯萃取,加水洗涤三次,合并有机相,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3-(二氟甲基)-3-(1,7-二甲基-1H-吲哚-3-基)戊二腈(分离收率94%)。1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 7.9 Hz, 1H), 7.07 (t, J = 7.6 Hz,1H), 7.02 (d, J = 7.7 Hz, 2H), 6.28 (t, J = 55.1 Hz, 1H), 4.11 (s, 3H), 3.33– 3.20 (m, 4H), 2.80 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -124.1 (d, J = 55.1Hz). 13C NMR (101 MHz, CDCl3) δ 136.6 (s), 129.6 (s), 125.7 (s), 125.5 (s),122.6 (s), 120.7 (s), 117.4 (s), 116.1 (t, J = 251.4 Hz), 115.5 (s), 107.0(s), 44.1 (t, J = 20.2 Hz), 22.2 (t, J = 3.9 Hz), 19.9 (s). IR (ATR): ν 3124,2960, 2926, 2854, 2252, 2191, 1973, 1733, 1634, 1601, 1583, 1551, 1494, 1460,1429, 1411, 1381, 1328, 1256, 1221, 1141, 1112, 1070, 1021, 978, 934, 909,880, 820, 780, 745, 701, 674, 648, 578, 550, 429 cm-1. GC-MS m/z 287 (M+)。
实施例32
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.2 mmol 1,1,1,3,3-五氟-2-(5-甲氧基-1-甲基-1H-吲哚-3-基)丙烷-2-醇、0.3 mmol 叔丁醇钾以及2 mL超干乙腈溶剂,混合均匀后关好塞子,将其放入100 ℃下继续搅拌16小时后,用乙酸乙酯萃取,加水洗涤三次,合并有机相,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3-(二氟甲基)-3-(5-甲氧基-1-甲基-1H-吲哚-3-基)戊二腈(分离收率92%)。1H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 8.9 Hz, 1H), 7.12 (s,1H), 7.05 (s, 1H), 7.01 (dd, J = 8.9, 1.8 Hz, 1H), 6.24 (t, J = 55.2 Hz, 1H),3.89 (s, 3H), 3.80 (s, 3H), 3.30 – 3.18 (m, 4H). 19F NMR (376 MHz, CDCl3) δ -123.9 (d, J = 55.2 Hz, 2F). 13C NMR (101 MHz, CDCl3) δ 154.5 (s), 133.2 (s),128.4 (s), 125.1 (s), 116.3 (t, J = 251.5 Hz), 115.5 (s), 112.3 (s), 111.1(s), 102.5 (t, J = 3.1 Hz), 56.1 (s), 44.1 (t, J = 20.3 Hz), 33.3 (s), 22.2(t, J = 4.0 Hz). IR (ATR): ν 3002, 2983, 2950, 2919, 2851, 2249, 1622, 1574,1543, 1493, 1427, 1361, 1291, 1258, 1223, 1182, 1136, 1123, 1071, 1035, 893,844, 821, 799, 776, 703, 683, 650, 555, 437 cm-1. GC-MS m/z 303 (M+)。
实施例33
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.2 mmol 1,1,1,3,3-五氟-2-(5-苄氧基-1-甲基-1H-吲哚-3-基)丙烷-2-醇、0.3 mmol 叔丁醇钾以及2 mL超干乙腈溶剂,混合均匀后关好塞子,将其放入100 ℃下继续搅拌16小时后,用乙酸乙酯萃取,加水洗涤三次,合并有机相,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3-(二氟甲基)-3-(5-苄氧基-1-甲基-1H-吲哚-3-基)戊二腈(分离收率94%)。 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 7.3 Hz, 2H), 7.43 (t,J = 7.3 Hz, 2H), 7.39 – 7.34 (m, 1H), 7.30 (d, J = 9.6 Hz, 1H), 7.10 (d, J =5.2 Hz, 3H), 6.20 (t, J = 55.2 Hz, 1H), 5.15 (s, 2H), 3.80 (s, 3H), 3.25 –3.13 (m, 4H). 19F NMR (376 MHz, CDCl3) δ -124.0 (d, J = 55.2 Hz, 2F). 13C NMR(101 MHz, CDCl3) δ 153.5 (s), 137.3 (s), 133.4 (s), 128.7 (s), 128.4 (s),128.0 (s), 127.6 (s), 125.0 (s), 116.2 (t, J = 251.6 Hz), 115.4 (s), 113.2(s), 111.1 (s), 106.8 (t, J = 2.5 Hz), 104.5 (t, J = 2.6 Hz), 71.4 (s), 44.1(t, J = 20.3 Hz), 33.3 (s), 22.2 (t, J = 3.9 Hz). IR (ATR): ν 2924, 2853,2252, 1623, 1572, 1542, 1480, 1455, 1427, 1383, 1342, 1299, 1259, 1221, 1202,1140, 1060, 1026, 906, 799, 730, 650, 611, 507, 433 cm-1. GC-MS m/z 379 (M+)。
实施例34
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.2 mmol 1,1,1,3,3-五氟-2-(5-氟-1-甲基-1H-吲哚-3-基)丙烷-2-醇、0.3 mmol 叔丁醇钾以及2 mL超干乙腈溶剂,混合均匀后关好塞子,将其放入100 ℃下继续搅拌16小时后,用乙酸乙酯萃取,加水洗涤三次,合并有机相,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3-(二氟甲基)-3-(5-氟-1-甲基-1H-吲哚-3-基)戊二腈(分离收率87%)。1H NMR (400 MHz, CDCl3) δ 7.33 (dd, J = 9.0, 4.4 Hz, 1H), 7.29 (t, J =4.7 Hz, 1H), 7.21 (s, 1H), 7.10 (td, J = 9.0, 2.1 Hz, 1H), 6.20 (t, J = 55.1Hz, 1H), 3.84 (s, 3H), 3.38 – 3.10 (m, 4H). 19F NMR (376 MHz, CDCl3) δ -122.5(td, J = 9.5, 4.4 Hz, 1F), -124.0 (d, J = 55.1 Hz, 2F). 13C NMR (101 MHz,CDCl3) δ 158.1 (d, J = 236.5 Hz), 134.5 (s), 129.5 (s), 124.9 (d, J = 9.7Hz), 116.2 (t, J = 251.5 Hz), 115.2 (s), 111.4 (d, J = 35.0 Hz), 111.3 (s),107.3 – 107.2 (m), 105.0 (dt, J = 25.1, 3.4 Hz), 44.1 (t, J = 20.5 Hz), 33.5(s), 22.4 (t, J = 4.0 Hz). IR (ATR): ν 3127, 2924, 2853, 2251, 2195, 1660,1627, 1575, 1544, 1490, 1428, 1385, 1342, 1248, 1216, 1190, 1130, 1060, 978,907, 878, 846, 798, 777, 732, 649, 607, 579, 468, 433 cm-1. GC-MS m/z 291 (M+)。
实施例35
在氮气气氛中,向带有磁力搅拌装置的25 mL玻璃反应器中加入0.2 mmol 1,1,1,3,3-五氟-2-(5-溴-1-甲基-1H-吲哚-3-基)丙烷-2-醇、0.3 mmol 叔丁醇钾以及2 mL超干乙腈溶剂,混合均匀后关好塞子,将其放入100 ℃下继续搅拌16小时后,用乙酸乙酯萃取,加水洗涤三次,合并有机相,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3-(二氟甲基)-3-(5-溴-1-甲基-1H-吲哚-3-基)戊二腈(分离收率54%)。1H NMR (400 MHz, CDCl3) δ 7.74 (s, 1H), 7.43 (d, J = 8.8 Hz, 1H), 7.28(d, J = 8.1 Hz, 1H), 7.17 (s, 1H), 6.21 (t, J = 55.1 Hz, 1H), 3.83 (s, 3H),3.35 – 3.15 (m, 4H). 19F NMR (376 MHz, CDCl3) δ -124.0 (d, J = 55.1 Hz, 2F).13C NMR (101 MHz, CDCl3) δ 136.5 (s), 129.2 (s), 126.3 (s), 125.9 (s), 122.2(t, J = 3.4 Hz), 116.0 (t, J = 251.5 Hz), 115.2 (s), 114.1 (s), 111.9 (s),106.9 (t, J = 2.3 Hz), 44.1 (t, J = 20.5 Hz), 33.4 (s), 22.5 (t, J = 3.9 Hz).IR (ATR): ν 3384, 3121, 3070, 2924, 2853, 2251, 2190, 1733, 1637, 1596, 1541,1477, 1425, 1378, 1335, 1254, 1144, 1071, 1056, 1038, 908, 866, 795, 733,700, 648, 423 cm-1. GC-MS m/z 351 (M+)。
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 (8)
1.一种3-α-二氟甲基-α-三氟甲基-甲醇基吲哚的合成方法,其特征在于:以铜盐为催化剂,以吲哚和五氟丙烯氧基三甲基硅烷为原料,在溶剂中反应制得3-α-二氟甲基-α-三氟甲基-甲醇基吲哚化合物;所述吲哚的结构式为;所述的五氟丙烯氧基三甲基硅烷的结构式为:;所述的3-α-二氟甲基-α-三氟甲基-甲醇基吲哚化合物的结构式为:。
2.一种3-α-二氟甲基-α-三氟甲基-甲醇基吲哚衍生物的合成方法,其特征在于:以铜盐为催化剂,以吲哚和五氟丙烯氧基三甲基硅烷为原料,在溶剂中反应制得3-α-二氟甲基-α-三氟甲基-甲醇基吲哚化合物;所述吲哚的结构式为;所述的五氟丙烯氧基三甲基硅烷的结构式为:;所述的3-α-二氟甲基-α-三氟甲基-甲醇基吲哚化合物的结构式为:;并以合成的3-α-二氟甲基-α-三氟甲基-甲醇基吲哚化合物为原料,在乙腈溶剂中,以叔丁醇钾为碱,合成二氟甲基二乙腈吲哚衍生物:。
3.根据权利要求1或2所述的合成方法,其特征在于:所述的铜盐为氯化亚铜、溴化亚铜、碘化亚铜、氰化亚铜和硫氰酸亚铜中的一种。
4.根据权利要求1或2所述的合成方法,其特征在于:所述的溶剂为1,2-二氯乙烷、二氯甲烷、乙腈和四氢呋喃中的一种。
5.根据权利要求1或2所述的合成方法,其特征在于:所述吲哚的结构式为下述式1-式22中的任意一种:
。
6.根据权利要求1或2所述的的合成方法,其特征在于:铜盐、吲哚、五氟丙烯氧基三甲基硅烷以及溶剂的摩尔比为0.08-0.20:0.4-1:0.44-1.1:12.3-24.6。
7.根据权利要求6所述的合成方法,其特征在于:铜盐、吲哚、五氟丙烯氧基三甲基硅烷以及溶剂的摩尔比为0.2:1:1.1:12.3。
8.根据权利要求1所述的3-α-二氟甲基-α-三氟甲基-甲醇基吲哚的合成方法,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铜盐、吲哚、五氟丙烯氧基三甲基硅烷以及溶剂,混合均匀后关好塞子,将其放入80℃下继续搅拌1-24小时后,用二氯甲烷萃取,加水洗涤三次,合并有机相,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3-α-二氟甲基-α-三氟甲基-甲醇基吲哚产物。
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