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CN115677529B - 一种一步高效制备酰腙的方法 - Google Patents

一种一步高效制备酰腙的方法 Download PDF

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CN115677529B
CN115677529B CN202211447232.2A CN202211447232A CN115677529B CN 115677529 B CN115677529 B CN 115677529B CN 202211447232 A CN202211447232 A CN 202211447232A CN 115677529 B CN115677529 B CN 115677529B
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CN115677529A (zh
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张国营
张国慧
杨伟
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Shanxi Institute of Coal Chemistry of CAS
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Abstract

本发明属于有机学合成技术领域，具体涉及一种一步高效制备酰腙的方法，其是以烯烃、肼、醛和一氧化碳为原料，在钯催化剂作用下发生羰基化反应，得到酰腙化合物。本发明所用反应原料廉价易得，通过插羰反应，仅一步即可高效得制备酰腙化合物，合成工艺简单，大大降低了合成成本，符合绿色化学的要求，可以实现克级规模实验，易于实现工业化。

Description

一种一步高效制备酰腙的方法
技术领域
本发明属于有机学合成技术领域，具体涉及一种一步高效制备酰腙的方法。
背景技术
酰腙化合物是一类重要的化合物，因其结构中含有酰腙官能团，可作为合成咪唑、四氮唑、喹唑啉酮、喹啉、喹诺酮以及其他杂环化合物的重要的中间体。酰腙化合物广泛存在于各种天然产物和医农药化学品中，通常表现出特殊价值的理化性质和重要的生物学活性。因此，关于该类化合物的合成，特别是发展一种简单的环境友好的合成路径，显得尤为重要。
酰腙化合物的合成方法有很多种，早期的制备方法一般都是通过多步反应实现的，反应效率不但低，产率较低，且会产生大量的副产物，同时操作复杂。为了解决此类反应带来的弊端，科学工作者们在反应体系中引入了过度金属催化剂，一步催化制备酰腙化合物，虽然实现了良好的催化性能以及底物适应性，但是还需要加入复杂的原料以及活性试剂，其不仅要求苛刻的反应条件，同时反应的效率大大降低，且会产生大量的副产物，不符合绿色合成化学的基本要求。
为了解决此类问题，需要开发一种新的合成方法：不加采用外加添加剂、的情况下，仅使用金属催化剂来促进廉价易得烯烃、肼、醛和一氧化碳直接反应制备酰腙化合物。目前，此类反应至目前为止还没有相关报道。
因此，发展一类绿色、快速、实用和方便的酰腙合成方法成为了亟待解决的问题，直接利用烯烃、肼、醛和一氧化碳羰基化反应，温和条件下高原子经济性制备底物适用性范围广泛的甲酰胺具有要的理论意义和广泛的应用前景。
发明内容
针对现有技术的不足，本发明提供了一种一步高效制备酰腙的方法。
为实现上述目的，本发明是通过以下技术方案来实现：
一种一步高效制备酰腙的方法，包括以下步骤：以烯烃、肼、醛和一氧化碳为原料，在钯催化剂作用下发生羰基化反应，得到酰腙化合物，其反应路线为：
其中，R1选自氢、脂肪类取代基团、取代芳基、萘基或噻吩基，R2选自脂肪类取代基团、取代芳基、萘基或噻吩基，R3选自取代芳基、萘基、蒽基或噻吩基。
进一步地，所述R1中脂肪类取代基团为环己基、环己烯基、乙腈基或1-12个碳的烷基，取代芳基为甲基芳基、叔丁基芳基、甲氧基芳基、苯基芳基、氟基芳基、氯基芳基、溴基芳基、三氟甲基芳基、硝基芳基、苯甲酸甲酯基或乙酰苯酯。
进一步地，所述R2中脂肪类取代基团为苄基或取代苄基，取代芳基为甲基芳基、叔丁基芳基、甲氧基芳基、苯基芳基、氟基芳基、氯基芳基、溴基芳基、三氟甲基芳基、硝基芳基、苯甲酸甲酯基或乙酰苯酯。
进一步地，所述R3中取代芳基为甲基芳基、叔丁基芳基、甲氧基芳基、苯基芳基、氟基芳基、氯基芳基、溴基芳基、三氟甲基芳基、三氟甲氧基芳基、羟基苯基、氰基苯基、硝基芳基、苯甲酸甲酯基或乙酰苯酯。
进一步地，所述催化剂为PdCl2、PdBr2、PdI2、Pd(OAc)2、Pd(TFA)2、PdCl2(CH3CN)2、PdBr2(CH3CN)2、PdCl2(COD)、PdBr2(COD)、PdCl2(PhCN)2、[PdCl(CH2＝CHCH2)]2、[PdCl(PhCH2＝CHCH2)]2、PdCl2(Ph3P)2、PdCl2[P(3,5-F2Ph)3]2、PdCl2(Xantphos)2中的一种或几种。
进一步地，所述催化剂为PdCl2、PdBr2、PdI2、Pd(OAc)2、Pd(TFA)2、PdCl2(CH3CN)2、PdBr2(CH3CN)2、PdCl2(COD)、PdBr2(COD)、PdCl2(PhCN)2、[PdCl(CH2＝CHCH2)]2、[PdCl(PhCH2＝CHCH2)]2中的一种或几种时，酰腙的制备方法中还包括加入配体，所述配体为P(3-FPh)3、P(2-FPh)3、P(3,5-F2Ph)3、P(3,5-Me2Ph)3、P(3,5-(MeO)2Ph)3、P(3,5-(CF3)2Ph)3、Xantphos中的一种或几种。
进一步地，所述催化剂的用量为肼摩尔量的0.1-10％。
进一步地，所述配体为P(3-FPh)3、P(2-FPh)3、P(3,5-F2Ph)3、P(3,5-Me2Ph)3、P(3,5-(MeO)2Ph)3、P(3,5-(CF3)2Ph)3、Xantphos中的一种或几种。
进一步地，所述溶剂为二氧六环、苯甲醚、二甲基醚、乙酸乙酯、乙腈、二氯甲烷、二氯乙烷或氯仿，优选二氯甲烷和苯甲醚。
进一步地，所述羰基化反应温度为40-140℃，时间为3-16小时。
与现有技术相比，本发明的有益效果如下：
1、本发明所用反应原料廉价易得，通过插羰反应，仅一步即可高效得制备酰腙化合物，合成工艺简单，大大降低了合成成本；
2、本发明可以实现高效合成各种取代基酰腙化合物；
3、本发明反应条件温和，产率高，底物适用性范围宽；
5、本发明反应原料清洁无毒，对环境污染小，原子经济性高；
6、本发明反应过程清洁，操作简单，更符合绿色化学的要求；
7、该反应转化效率较高，可以实现克级规模实验，易于实现工业化。
具体实施方式
为了便于理解本发明，下面将对本发明进行更全面的描述。但是，本发明可以以许多不同的形式来实现，并不限于本文所描述的实施例。相反地，提供这些实施例的目的是使对本发明的公开内容的理解更加透彻全面。
酰腙D1的制备
其合成路线如下：
实施例1
在手套箱里，往带有磁力搅拌子的干燥反应小瓶里加入苯乙烯A1(1.5mmol)、苯肼B1(1.0mmol)、苯甲醛C1(1.5mmol)、PdCl2[P(3,5-F2Ph)3]2(0.02mmol,2mol％)和二氯甲烷(2.0mL)，将反应小瓶放置于高压釜中，于高压釜中置换CO气体三次后，充入CO(2.5MPa)。反应搅拌均匀后，把高压釜放置于预先升温的油浴锅中，120℃下反应6h。停止反应，加入正十六烷作为内标，GC收率为96％。
1H NMR(400MHz,CDCl3)δ7.55–7.46(m,6H),7.45–7.40(m,1H),7.36–7.28(m,5H),7.23–7.17(m,1H),7.14(s,1H),7.07(d,J＝7.6Hz,2H),5.09(d,J＝7.2Hz,1H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,142.5,141.5,136.3,134.4,130.2,129.8,129.2,128.7,128.6,127.8,127.3,126.7,42.9,19.5ppm.MS(70eV):m/z(％)＝328[M]+,225,196,105.HRMS(ESI)calcd.for C22H21N2O[M+H]:329.1648,found:329.1645.
实施例2～7
与实施例1不同的是：催化剂替换为PdCl2[CH3CN]2，并加入配体(0.02mmol,2mol％)。具体数据如下表所示：
实施例8～9
与实施例4不同的是：催化剂的种类。具体数据如下表所示：
实施例10～14
与实施例1不同的是：PdCl2[P(3,5-F2Ph)3]2的用量。具体数据如下表所示：
实施例15～19
与实施例1不同的是：二氯甲烷的用量。具体数据如下表所示：
实施例20～25
与实施例1不同的是：溶剂的种类。具体数据如下表所示：
实施例26～32
与实施例1不同的是：苯乙烯A1的用量。具体数据如下表所示：
实施例33～39
与实施例1不同的是：苯肼B1的用量。具体数据如下表所示：
实施例40-46
与实施例1不同的是：苯甲醛C1的用量。具体数据如下表所示：
实施例47-50
与实施例4不同的是：充入CO气体的压强，具体数据如下表所示：
实施例51-55
与实施例4不同的是：反应时间。具体数据如下表所示：
实施例56-58
与实施例4不同的是：反应温度。具体数据如下表所示：
酰腙D2-D28的制备
实施例59-85
与实施例1不同的是：A1替换为A2、A3……A28。具体数据如下所示：
D2收率91％：1H NMR(400MHz,CDCl3)δ7.50(d,J＝6.4Hz,2H),7.47–7.43(m,2H),7.42–7.33(m,3H),7.32–7.27(m,3H),7.16–7.08(m,3H),7.05(d,J＝7.6Hz,2H),5.07(d,J＝7.2Hz,1H),2.25(s,3H),1.58(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ176.0,141.5,139.6,136.4,136.2,134.6,130.2,129.9,129.5,129.3,128.8,127.8,127.3,42.6,21.2,19.7ppm.MS(70eV):m/z(％)＝342[M]+(100),223,196,119.HRMS(ESI)calcd.forC23H23N2O[M+H]:343.1805,found:343.1806.
D3收率84％：1H NMR(400MHz,CDCl3)δ7.54–7.44(m,4H),7.43–7.37(m,1H),7.36–7.24(m,5H),7.22–7.16(m,1H),7.13(s,1H),7.06(d,J＝7.6Hz,2H),7.00(d,J＝7.2Hz,1H),5.03(d,J＝7.2Hz,1H),2.31(s,3H),1.58(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.9,142.5,141.5,138.2,136.4,134.5,130.2,129.9,129.3,128.7,127.5,127.3,124.9,43.1,21.6,19.6ppm.MS(70eV):m/z(％)＝342[M]+(100),196,119,91.HRMS(ESI)calcd.for C23H23N2O[M+H]:343.1805,found:343.1805.
D4收率73％：1H NMR(400MHz,CDCl3)δ7.53–7.45(m,2H),7.43–7.33(m,4H),7.29–7.24(m,3H),7.21–7.15(m,2H),7.14–7.07(m,4H),5.12(d,J＝6.8Hz,1H),2.56(s,3H),1.52(d,J＝6.8Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ176.3,142.0,141.4,136.5,135.1,134.4,130.5,130.3,129.8,129.3,128.6,127.4,126.6,126.2,39.7,19.8,18.5ppm.MS(70eV):m/z(％)＝342[M]+(100),196,119,91.HRMS(ESI)calcd.for C23H23N2O[M+H]:343.1805,found:343.1807.
D5收率90％：1H NMR(400MHz,CDCl3)δ7.49(d,J＝6.8Hz,2H),7.47–7.41(m,4H),7.37(d,J＝7.2Hz,1H),7.35–7.26(m,5H),7.14(s,1H),7.05(d,J＝7.6Hz,2H),5.12(d,J＝6.8Hz,1H),1.59(d,J＝7.2Hz,3H),1.27(s,9H)ppm.13CNMR(101MHz,CDCl3)δ176.1,149.44,141.5,139.3,136.4,134.6,130.2,129.9,129.3,128.8,127.5,127.4,125.6,42.2,34.5,31.6,19.6ppm.MS(70eV):m/z(％)＝384[M]+(100),252,196,105.HRMS(ESI)calcd.forC26H29N2O[M+H]:385.2274,found:385.2272.
D6收率70％：1H NMR(400MHz,CDCl3)δ7.50–7.32(m,6H),7.26–7.21(m,3H),7.17–7.05(m,4H),6.93–6.82(m,2H),5.43(d,J＝6.8Hz,1H),3.90(s,3H),1.52(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ176.7,156.2,140.8,136.5,134.8,131.7,130.2,129.7,129.3,128.6,127.7,127.4,127.2,120.9,110.4,55.4,36.6,18.3ppm.MS(70eV):m/z(％)＝358[M]+(100),196,135,105.HRMS(ESI)calcd.for C23H23N2O2[M+H]:359.1754,found:359.1753.
D7收率82％：1H NMR(400MHz,CDCl3)δ7.85–7.70(m,8H),7.69–7.62(m,2H),7.60–7.47(m,6H),7.47–7.42(m,1H),7.37(s,1H),7.27(d,J＝7.2Hz,2H),5.38(d,J＝6.8Hz,1H),1.87(d,J＝6.8Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,141.8,141.1,139.7,136.4,134.6,130.4,130.1,129.4,128.9,128.5,127.5,127.4,127.2,42.7,19.7ppm.MS(70eV):m/z(％)＝404[M]+(100),384,196,161.HRMS(ESI)calcd.for C28H25N2O[M+H]:405.1961,found:405.1959.
D8收率82％：1H NMR(400MHz,CDCl3)δ7.68–7.55(m,6H),7.54–7.49(m,1H),7.46–7.42(m,3H),7.32–7.28(m,1H),7.18(d,J＝7.6Hz,2H),7.10(t,J＝8.4Hz,2H),5.23(d,J＝5.2Hz,1H),1.79–1.65(m,3H)ppm.13C NMR(101MHz,CDCl3)δ175.6,163.0,160.6,141.8,138.2,136.2,134.4,130.3,130.0,129.5,129.4,129.2,128.9,127.3,115.6,115.4,42.1,19.6ppm.19F NMR(376MHz,CDCl3)δ-116.1.MS(70eV):m/z(％)＝346[M]+(100),243,196,123.HRMS(ESI)calcd.for C22H20FN2O[M+H]:347.1554,found:347.1555.
D9收率73％：1H NMR(400MHz,CDCl3)δ7.52–7.44(m,4H),7.42–7.36(m,1H),7.34–7.20(m,6H),7.17(s,1H),7.06(d,J＝7.6Hz,2H),7.89–7.83(m,1H),5.10(d,J＝7.2Hz,1H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.2,164.3,161.9,145.1,141.9,136.2,134.3,130.3,130.2,130.1,129.4,129.2,128.9,127.3,123.6,114.9,114.7,113.8,113.6,42.8,19.5ppm.19F NMR(376MHz,CDCl3)δ-112.8.MS(70eV):m/z(％)＝346[M]+(100),243,196,123.HRMS(ESI)calcd.for C22H20FN2O[M+H]:347.1554,found:347.1552.
D10收率67％：1H NMR(400MHz,CDCl3)δ7.50–7.37(m,6H),7.28–7.24(m,3H),7.16–7.01(m,6H),5.36(d,J＝6.8Hz,1H),1.65–1.49(m,3H)ppm.13CNMR(101MHz,CDCl3)δ175.3,161.3,158.9,141.9,136.2,134.3,130.3,129.9,129.4,129.3,128.7,128.4,128.3,128.2,127.4,124.6,124.5,115.6,115.4,36.0,18.5ppm. 19F NMR (376 MHz, CDCl3) δ -118.6. MS (70 eV): m/z (％) ＝ 346 [M]+ (100),243,196,123.HRMS(ESI)calcd.forC22H20FN2O[M+H]:347.1554,found:347.1555.
D11收率83％：1H NMR(400MHz,CDCl3)δ7.53–7.45(m,4H),7.42(d,J＝8.0Hz,3H),7.37–7.30(m,3H),7.26(d,J＝8.4Hz,2H),7.16(s,1H),7.06(d,J＝7.6Hz,2H),5.08(d,J＝7.2Hz,1H),1.57(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.3,141.9,141.0,136.1,134.3,132.5,130.3,130.0,129.4,129.3,129.2,128.8,127.3,42.3,19.5ppm.MS(70eV):m/z(％)＝362[M]+(100),230,105,77.HRMS(ESI)calcd.for C22H20ClN2O[M+H]:363.1258,found:363.1259.
D12收率74％：1H NMR(400MHz,CDCl3)δ7.54–7.43(m,5H),7.43–7.28(m,5H),7.22–7.13(m,3H),7.06(d,J＝7.6Hz,2H),5.03(d,J＝7.2Hz,1H),1.58(d,J＝7.2Hz,3H)ppm.13CNMR(101MHz,CDCl3)δ175.0,144.6,142.0,136.1,134.4,134.3,130.3,130.1,130.0,129.4,129.2,128.9,128.3,127.4,127.0,126.0,42.9,19.5ppm.MS(70eV):m/z(％)＝362[M]+(100),259,196,139.HRMS(ESI)calcd.for C22H20ClN2O[M+H]:363.1258,found:363.1258.
D13收率68％：1H NMR(400MHz,CDCl3)δ7.54–7.47(m,4H),7.45–7.37(m,3H),7.26(s,3H),7.20(t,J＝7.6Hz,1H),7.15–7.07(m,4H),5.42(d,J＝6.8Hz,1H),1.55(d,J＝6.8Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.4,142.0,140.8,136.2,134.2,133.3,130.3,129.9,129.7,129.4,129.2,128.6,127.9,127.8,127.5,127.4,40.6,17.9ppm.MS(70eV):m/z(％)＝362[M]+(100),224,196,139.HRMS(ESI)calcd.for C22H20ClN2O[M+H]:363.1259,found:363.1256.
D14收率80％：1H NMR(400MHz,CDCl3)δ7.58–7.51(m,4H),7.48–7.40(m,3H),7.40–7.32(m,5H),7.18(s,1H),7.09(d,J＝7.6Hz,2H),5.08(d,J＝7.2Hz,1H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.2,141.9,141.4,136.0,134.2,131.7,130.2,130.0,129.6,129.3,129.1,128.8,127.2 120.5,42.4,19.3ppm.MS(70eV):m/z(％)＝406[M]+(100),196,104,77.HRMS(ESI)calcd.for C22H20BrN2O[M+H]:407.0754,found:407.0754.
D15收率70％：1H NMR(400MHz,CDCl3)δ7.68(s,1H),7.52–7.44(m,4H),7.43–7.36(m,2H),7.35–7.27m,4H),7.17–7.10(m,2H),7.06(d,J＝7.6Hz,2H),5.00(d,J＝7.2Hz,1H),1.57(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.0,144.9,142.0,136.1,134.3,131.3,130.3,130.1,129.9,129.4,129.2,128.9,127.4,126.4,122.7,43.0,19.5ppm.MS(70eV):m/z(％)＝406[M]+(100),196,167,104.HRMS(ESI)calcd.forC22H20BrN2O[M+H]:407.0753,found:407.0750.
D16收率74％：1H NMR(400MHz,CDCl3)δ7.63–7.55(m,4H),7.53–7.47(m,4H),7.45–7.40(m,1H),7.37–7.29(m,3H),7.19(s,1H),7.08(d,J＝7.6Hz,2H),5.17(d,J＝7.2Hz,1H),1.62(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.0,146.5,142.2,136.0,134.2,130.3,130.1,129.4,129.1,128.8,128.3,127.3,125.6,42.9,19.4ppm.19F NMR(376MHz,CDCl3)δ-62.2.MS(70eV):m/z(％)＝396[M]+(100),293,196,173.HRMS(ESI)calcd.for C23H20F3N2O[M+H]:397.1522,found:397.1523.
D17收率43％：1H NMR(400MHz,CDCl3)δ8.19(d,J＝8.8Hz,2H),7.65(d,J＝8.8Hz,2H),7.57–7.44(m,5H),7.39–7.33(m,3H),7.26–7.16(m,2H),7.09(d,J＝7.6Hz,2H),5.19(d,J＝7.2Hz,1H),1.63(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ174.3,150.0,146.8,142.5,135.7,134.0,130.3,130.2,129.5,129.0,128.8,128.7,127.2,123.9,43.0,19.2ppm.MS(70eV):m/z(％)＝373[M]+(100),270,196,120.HRMS(ESI)calcd.forC22H20N3O3[M+H]:374.1499,found:374.1497.
D18收率81％：1H NMR(400MHz,CDCl3)δ8.02(d,J＝7.8Hz,2H),7.58(d,J＝7.8Hz,2H),7.51–7.44(m,4H),7.42–7.37(m,1H),7.34–7.27(m,3H),7.17(s,1H),7.08(d,J＝7.6Hz,2H),5.14(d,J＝7.2Hz,1H),3.80(s,3H),1.61(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ174.9,166.9,147.9,141.9,136.1,134.2,130.3,130.0,129.4,129.1,128.8,128.7,127.8,127.3,52.0,43.3,19.3ppm.MS(70eV):m/z(％)＝386[M]+(100),283,196,163.HRMS(ESI)calcd.for C24H23N2O3[M+H]:387.1703,found:387.1702.
D19收率76％：1H NMR(400MHz,CDCl3)δ7.57–7.43(m,6H),7.43–7.37(m,1H),7.36–7.28(m,3H),7.17(s,1H),7.11–7.02(m,4H),5.13(d,J＝7.2Hz,1H),2.20(s,3H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.5,169.5,149.5,141.8,139.8,136.2,134.4,130.2,129.9,129.3,129.2,128.9,128.8,127.3,121.6,42.1,21.2,19.5ppm.MS(70eV):m/z(％)＝386[M]+(100),196,121,77.HRMS(ESI)calcd.for C24H23N2O3[M+H]:387.1703,found:387.1703.
D20收率88％：1H NMR(400MHz,CDCl3)δ8.00(s,1H),7.89–7.81(m,3H),7.71(d,J＝8.4Hz,1H),7.65–7.51(m,4H),7.51–7.43(m,3H),7.42–7.34(m,3H),7.18(s,1H),7.13(d,J＝7.6Hz,2H),5.30(d,J＝7.2Hz,1H),1.74(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.7,141.6,140.0,136.3,134.4,133.8,132.5,130.2,129.8,129.3,129.2,128.7,128.3,127.8,127.7,127.3,126.5,126.3,126.0,125.5,43.2,19.5ppm.MS(70eV):m/z(％)＝378[M]+(100),258,196,155.HRMS(ESI)calcd.for C26H23N2O[M+H]:379.1805,found:379.1801.
D21收率72％：1H NMR(400MHz,CDCl3)δ8.40(d,J＝8.8Hz,1H),7.79(d,J＝8.0Hz,1H),7.67–7.55(m,3H),7.49–7.30(m,5H),7.11–7.03(m,3H),7.00(s,1H),6.99–6.87(m,4H),5.72(d,J＝7.2Hz,1H),1.69(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ176.4,141.5,140.0,136.4,134.4,134.2,131.4,130.4,129.7,129.4,129.3,128.5,127.3,126.4,126.1,125.8,123.8,123.6,39.4,19.1ppm.MS(70eV):m/z(％)＝378[M]+(100),196,155,77.HRMS(ESI)calcd.for C26H23N2O[M+H]:379.1805,found:379.1802.
D22收率34％：1H NMR(400MHz,CDCl3)δ7.64–7.59(m,2H),7.55–7.49(m,2H),7.47–7.43(m,1H),7.39–7.36(d,J＝5.0Hz,3H),7.25(d,J＝2.8Hz,2H),7.18–7.06(m,4H),6.96–6.93(m,1H),5.46(d,J＝6.8Hz,1H),1.70(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ174.8,144.5,141.8,136.0,134.2,130.2,130.0,129.3,129.1,128.8,127.4,126.6,124.5,124.1,37.6,19.5ppm.MS(70eV):m/z(％)＝334[M]+(100),196,111,77.HRMS(ESI)calcd.for C20H19N2OS[M+H]:335.1212,found:335.1209.
D23收率80％，1H NMR(400MHz,CDCl3)δ7.60–7.52(m,4H),7.47–7.43(m,1H),7.37–7.34(m,3H),7.22(s,1H),7.15(d,J＝7.6Hz,2H),3.87–3.63(m,1H),1.93(d,J＝12.4Hz,1H),1.88–1.56(m,6H),1.30–1.22(m,7H)ppm.13C NMR(101MHz,CDCl3)δ178.6,140.9,136.6,134.6,130.2,129.7,129.3,129.1,128.8,127.1,41.3,41.1,31.8,29.9,26.6,26.5,14.4ppm.MS(70eV):m/z(％)＝334[M]+(100),196,111,69.HRMS(ESI)calcd.forC22H27N2O[M+H]:335.2117,found:335.2116.
D24收率75％，1H NMR(400MHz,CDCl3)δ7.60–7.51(m,4H),7.49–7.43(m,1H),7.40–7.32(m,3H),7.26–7.22(m,1H),7.21–7.11(m,2H),5.68(d,J＝14.4Hz,2H),3.87(d,J＝17.6Hz,1H),2.44–1.63(m,7H),1.35–1.20(m,3H)ppm.13C NMR(101MHz,CDCl3)δ178.3,178.2,141.2,141.2,136.5,134.6,130.2,129.8,129.3,129.2,128.8,127.2,126.9,126.6,126.4,41.2,40.2,37.1,36.8,30.0,28.8,27.8,25.8,25.5,25.4,14.3ppm.MS(70eV):m/z(％)＝332[M]+(100),252,196,109.HRMS(ESI)calcd.for C22H25N2O[M+H]:333.1961,found:333.1959.
D25收率64％，1H NMR(400MHz,CDCl3)δ7.61–7.51(m,4H),7.50–7.44(m,1H),7.40–7.33(m,3H),7.31(s,1H),7.16(d,J＝7.6Hz,2H),4.17–4.09(m,1H),2.83–2.75(m,1H),2.67–2.59(m,1H),1.52(d,J＝7.2Hz,3H)ppm.13CNMR(101MHz,CDCl3)δ174.7,142.8,135.5,133.9,130.4,130.3,129.6,129.1,128.9,127.4,118.9,34.5,21.1,17.3ppm.MS(70eV):m/z(％)＝291[M]+(100),196,167,77.HRMS(ESI)calcd.for C18H18N3O[M+H]:292.1444,found:292.1443.
D26收率63％，1H NMR(400MHz,CDCl3)δ7.61–7.50(m,4H),7.47–7.42(m,1H),7.39–7.30(m,3H),7.25–7.22(m,1H),7.15(d,J＝7.6Hz,2H),3.86(d,J＝6.8Hz,1H),1.92–1.83(m,1H),1.58–1.23(m,8H),0.91(t,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ178.7,141.1,136.5,134.6,130.2,129.8,129.3,129.1,128.7,127.2,36.3,33.7,29.8,22.9,17.3,14.2,12.2ppm.MS(70eV):m/z(％)＝308[M]+(100),196,85,43.HRMS(ESI)calcd.forC20H25N2O[M+H]:309.1961,found:309.1961.
D27收率67％，1H NMR(400MHz,CDCl3)δ7.59–7.51(m,4H),7.47–7.42(m,1H),7.36–7.33(m,3H),7.24(s,1H),7.14(d,J＝7.6Hz,2H),3.86(d,J＝6.6Hz,1H),1.93–1.85(m,1H),1.42–1.21(m,12H),0.87(t,J＝6.6Hz,3H)ppm.13CNMR(101MHz,CDCl3)δ178.7,141.1,136.5,134.6,130.2,129.7,129.3,129.1,128.7,127.2,36.2,34.1,31.9,29.5,27.5,22.7,17.3,14.1ppm.MS(70eV):m/z(％)＝336[M]+(100),196,149,57.HRMS(ESI)calcd.for C22H29N2O[M+H]:337.2274,found:337.2272.
D28收率70％，1H NMR(400MHz,CDCl3)δ7.58–7.50(m,4H),7.46–7.41(m,1H),7.36–7.32(m,3H),7.24(s,1H),7.14(d,J＝7.6Hz,2H),3.87(d,J＝6.6Hz,1H),1.52–1.09(m,17H),0.86(t,J＝6.8Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ178.7,141.1,136.5,134.6,130.2,129.8,129.3,129.1,128.7,127.2,36.2,34.1,31.9,29.9,29.7,29.4,27.6,22.8,17.3,14.2ppm.MS(70eV):m/z(％)＝364[M]+(100),196,149,85.HRMS(ESI)calcd.forC24H33N2O[M+H]:365.2587,found:365.2582.
酰腙D29-D54的制备
实施例86-111
与实施例1不同的是：C1替换为C29、C30……C54。具体数据如下所示：
D29收率92％：1H NMR(400MHz,CDCl3)δ7.53–7.46(m,4H),7.45–7.39(m,3H),7.31(t,J＝7.6Hz,2H),7.24–7.19(m,1H),7.19–7.14(m,2H),7.12(s,1H),7.08(d,J＝7.6Hz,2H),5.09(d,J＝7.2Hz,1H),2.35(s,3H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.7,142.5,141.6,140.0,136.3,131.7,130.1,129.5,129.2,129.1,128.6,127.8,127.2,126.6,42.9,21.5,19.4ppm.MS(70eV):m/z(％)＝342[M]+(100),225,210,105.HRMS(ESI)calcd.for C23H23N2O[M+H]:343.1805,found:343.1803.
D30收率83％：1H NMR(400MHz,CDCl3)δ7.52–7.42(m,4H),7.39–7.34(m,1H),7.32–7.27(m,4H),7.21–7.14(m,2H),7.12–7.08(m,2H),7.04(d,J＝7.6Hz,2H),5.08(d,J＝7.2Hz,1H),2.30(s,3H),1.59(d,J＝7.2Hz,3H)ppm.13CNMR(101MHz,CDCl3)δ175.8,142.7,141.8,138.4,136.4,134.5,130.7,130.3,129.3,128.7,128.1,127.9,126.8,124.5,43.1,21.5,19.7ppm.MS(70eV):m/z(％)＝342[M]+(100),210,105,77.HRMS(ESI)calcd.forC23H23N2O[M+H]:343.1805,found:343.1804.
D31收率80％：1H NMR(400MHz,CDCl3)δ7.80–7.64(m,1H),7.57–7.38(m,6H),7.32(t,J＝7.6Hz,2H),7.26–7.19(m,3H),7.13–7.07(m,3H),5.09(d,J＝6.8Hz,1H),2.14(s,3H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,142.4,140.5,136.9,136.4,132.3,130.8,130.2,129.5,129.2,129.1,128.6,127.8,126.6,126.5,126.2,42.8,19.6,19.4ppm.MS(70eV):m/z(％)＝342[M]+(100),225,210,105.HRMS(ESI)calcd.forC23H23N2O[M+H]:343.1805,found:343.1803.
D32收率81％：1H NMR(400MHz,CDCl3)δ7.76(s,1H),7.70–7.63(m,4H),7.57(t,J＝7.6Hz,1H),7.48(t,J＝7.6Hz,2H),7.40–7.32(m,3H),6.99(s,2H),5.29(d,J＝6.8Hz,1H),2.40(d,J＝6.8Hz,9H),1.81(d,J＝7.2Hz,3H)ppm.13CNMR(101MHz,CDCl3)δ175.9,143.1,142.4,138.8,137.5,136.8,130.4,129.7,129.5,129.3,128.7,128.5,128.0,126.8,42.4,21.3,20.1ppm.MS(70eV):m/z(％)＝370[M]+(100),225,105,93.HRMS(ESI)calcd.forC25H27N2O[M+H]:371.2118,found:371.2117.
D33收率87％：1H NMR(400MHz,CDCl3)δ7.54–7.41(m,7H),7.37(d,J＝8.4Hz,2H),7.32(t,J＝7.6Hz,2H),7.24–7.18(m,1H),7.14(s,1H),7.07(d,J＝7.6Hz,2H),5.09(d,J＝7.2Hz,1H),1.59(d,J＝7.2Hz,3H),1.32(s,9H)ppm.13CNMR(101MHz,CDCl3)δ175.7,153.2,142.5,141.5,136.4,131.7,130.1,129.2,129.1,128.6,127.8,127.0,126.6,125.7,42.8,34.9,31.2,19.4ppm.MS(70eV):m/z(％)＝384[M]+(100),252,195,105.HRMS(ESI)calcd.for C26H29N2O[M+H]:385.2274,found:385.2272.
D34收率83％：1H NMR(400MHz,CDCl3)δ7.59–7.47(m,8H),7.43(t,J＝7.6Hz,2H),7.38–7.33(m,3H),7.32–7.24(m,3H),7.19–7.13(m,2H),7.04(d,J＝7.6Hz,2H),5.11(d,J＝7.2Hz,1H),1.61(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,142.7,142.6,141.2,140.4,136.4,133.6,130.3,129.4,129.3,129.1,128.8,128.0,127.9,127.5,127.2,126.9,43.2,19.8ppm.MS(70eV):m/z(％)＝404[M]+(100),281,207,105.HRMS(ESI)calcd.for C28H25N2O[M+H]:405.1961,found:405.1958.
D35收率90％：1H NMR(400MHz,CDCl3)δ7.52–7.41(m,6H),7.39–7.33(m,1H),7.29(t,J＝7.6Hz,2H),7.19–7.14(m,1H),7.10(s,1H),7.05(d,J＝7.6Hz,2H),6.84(d,J＝8.8Hz,2H),5.09(d,J＝7.2Hz,1H),3.72(s,3H),1.58(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.6,161.1,142.7,141.5,136.5,130.2,129.3,129.2,128.8,128.7,127.9,127.2,126.7,114.3,55.4,43.0,19.6ppm.MS(70eV):m/z(％)＝358[M]+(100),226,182,105.HRMS(ESI)calcd.for C23H23N2O2[M+H]:359.1754,found:359.1750.
D36收率81％：1H NMR(400MHz,CDCl3)δ7.47(t,J＝7.6Hz,4H),7.42–7.37(m,1H),7.30(t,J＝7.6Hz,2H),7.23–7.17(m,2H),7.15–7.10(m,2H),7.07(d,J＝7.6Hz,2H),7.00(d,J＝7.6Hz,1H),6.89–6.83(m,1H),5.07(d,J＝7.2Hz,1H),3.79(s,3H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.7,160.0,142.6,141.4,136.3,135.8,130.2,129.8,129.3,129.2,128.7,127.7,126.7,120.5,116.3,111.2,55.4,43.2,19.7ppm.MS(70eV):m/z(％)＝358[M]+(100),226,105,77.HRMS(ESI)calcd.for C23H23N2O2[M+H]:359.1754,found:359.1751.
D37收率73％：1H NMR(400MHz,CDCl3)δ7.79(d,J＝7.6Hz,1H),7.49(s,1H),7.39–7.32(m,4H),7.28–7.23(m,1H),7.21–7.13(m,3H),7.08–7.04(m,1H),6.96(d,J＝7.6Hz,2H),6.87(t,J＝7.6Hz,1H),6.64(d,J＝8.4Hz,1H),4.99(d,J＝7.2Hz,1H),3.44(s,3H),1.48(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ174.6,156.9,141.5,136.7,135.4,130.0,128.9,128.0,127.9,127.5,126.7,125.5,125.0,121.8,119.7,109.9,54.2,41.8,18.4ppm.MS(70eV):m/z(％)＝358[M]+(100),226,210,105.HRMS(ESI)calcd.forC23H23N2O2[M+H]:359.1754,found:359.1753.
D38收率88％：1H NMR(400MHz,CDCl3)δ7.58–7.39(m,7H),7.32(t,J＝7.5Hz,2H),7.23–7.17(m,4.3Hz,1H),7.13–6.97(m,5H),5.04(d,J＝7.2Hz,1H),1.58(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.6,164.9,162.4,142.5,140.2,136.2,130.7,130.2,129.3,19.1,129.0,128.9,128.6,127.7,126.7,115.9,115.7,43.0,19.5ppm.19F NMR(376MHz,CDCl3)δ-110.4.MS(70eV):m/z(％)＝346[M]+(100),214,105,77.HRMS(ESI)calcd.for C22H20FN2O[M+H]:347.1554,found:347.1551.
D39收率71％：1H NMR(400MHz,CDCl3)δ7.51–7.45(m,4H),7.43–7.37(m,1H),7.34–7.23(m,4H),7.23–7.15(m,2H),7.11–7.02(m,3H),7.01–6.95(m,1H),5.03(d,J＝6.8Hz,1H),1.58(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,164.3,161.9,142.5,140.1,136.9,136.8,136.1,130.3,129.4,129.1,128.7,127.7,126.8,123.6,123.5,116.9,116.6,113.3,113.1,43.2,19.6ppm.19FNMR(376MHz,CDCl3)δ-112.4.MS(70eV):m/z(％)＝346[M]+(100),214,105,77.HRMS(ESI)calcd.for C22H20FN2O[M+H]:347.1554,found:347.1549.
D40收率62％：1H NMR(400MHz,CDCl3)δ7.87(s,1H),7.53–7.39(m,5H),7.37(d,J＝7.6Hz,1H),7.35–7.27(m,2H),7.26–7.11(m,3H),7.06(d,J＝7.5Hz,2H),6.95–6.88(m,1H),5.09(s,1H),1.69–1.53(m,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,162.7,160.2,142.5,136.1,134.8,131.4,131.3,130.3,129.4,129.1,128.7,127.8,126.8,124.5,122.4,122.3,116.0,115.8,43.1,19.7ppm.19FNMR(376MHz,CDCl3)δ-120.5.MS(70eV):m/z(％)＝346[M]+(100),214,105,77.HRMS(ESI)calcd.for C22H20FN2O[M+H]:347.1554,found:347.1550.
D41收率86％：1H NMR(400MHz,CDCl3)δ7.54–7.37(m,7H),7.52–7.40(m,4H),7.22–7.17(m,1H),7.09–7.04(m,3H),5.08(d,J＝6.8Hz,1H),1.58(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.7,142.4,140.1,136.1,135.6,133.0,130.2,129.4,129.1,129.0,128.7,128.4,127.7,126.7,43.1,19.6ppm.MS(70eV):m/z(％)＝362[M]+(100),230,105,77.HRMS(ESI)calcd.for C22H20ClN2O[M+H]:363.1258,found:363.1254.
D42收率62％：1H NMR(400MHz,CDCl3)δ7.91(d,J＝7.6Hz,1H),7.59(s,1H),7.51–7.45(m,4H),7.40(t,J＝7.6Hz,1H),7.34–7.27(m,2H),7.27–7.23(m,1H),7.23–7.16(m,3H),7.09(d,J＝7.6Hz,2H),5.05(d,J＝6.8Hz,1H),1.60(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,142.5,138.3,136.2,134.4,131.9,130.7,130.3,129.9,129.5,129.0,128.8,127.8,127.1,126.8,43.2,19.7ppm.MS(70eV):m/z(％)＝362[M]+(100),224,105,77.HRMS(ESI)calcd.for C22H20ClN2O[M+H]:363.1258,found:363.1256.
D43收率82％：1H NMR(400MHz,CDCl3)δ7.47–7.35(m,7H),7.34–7.25(m,4H),7.16(t,J＝7.6Hz,1H),7.06–7.01(m,3H),5.03(d,J＝7.2Hz,1H),1.58(d,J＝7.2Hz,3H)ppm.13CNMR(101MHz,CDCl3)δ175.7,142.6,140.1,136.2,133.5,132.0,130.3,129.4,129.2,128.8,128.7,127.7,126.8,124.0,43.2,19.7ppm.MS(70eV):m/z(％)＝406[M]+(100),274,194,105.HRMS(ESI)calcd.for C22H20BrN2O[M+H]:407.0753,found:407.0751.
D44收率73％：1H NMR(400MHz,CDCl3)δ7.87(d,J＝7.6Hz,1H),7.56–7.49(m,3H),7.48–7.40(m,4H),7.33(t,J＝7.6Hz,3H),7.24–7.19(m,1H),7.18–7.13(m,1H),7.10(d,J＝7.6Hz,2H),5.03(d,J＝6.8Hz,1H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.7,142.4,140.8,136.1,133.3,133.1,130.9,130.3,129.4,128.9,128.7,127.7,127.6,127.4,126.7,124.5,43.1,19.6ppm.MS(70eV):m/z(％)＝406[M]+(100),274,225,195.HRMS(ESI)calcd.for C22H20BrN2O[M+H]:407.0753,found:407.0750.
D45收率80％：1H NMR(400MHz,CDCl3)δ7.47(t,J＝7.6Hz,4H),7.41–7.37(m,1H),7.30(t,J＝7.6Hz,2H),7.21–7.15(m,2H),7.10–7.05(m,3H),6.82–6.75(m,2H),6.36(s,1H),5.04(d,J＝7.2Hz,1H),3.88(s,3H),1.58(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.6,147.9,147.2,142.9,142.1,136.4,130.2,129.2,128.7,127.6,126.8,126.7,122.5,114.6,108.1,56.0,43.3,19.7ppm.MS(70eV):m/z(％)＝374[M]+(100),281,242,207.HRMS(ESI)calcd.for C23H23N2O3[M+H]:375.1703,found:375.1701.
D46收率73％：1H NMR(400MHz,CDCl3)δ11.86–10.26(m,1H),7.55–7.40(m,5H),7.35–7.25(m,2H),7.23–7.15(m,3H),7.13(s,1H),6.96(d,J＝8.0Hz,2H),6.84(d,J＝7.6Hz,1H),6.74(t,J＝7.2Hz,1H),4.67–3.58(m,1H),1.57(s,3H)ppm.13C NMR(101MHz,CDCl3)δ174.2,157.4,146.2,141.0,135.3,131.6,130.5,129.7,129.4,129.0,127.5,127.1,127.1,119.6,117.6,116.8,112.5,43.5,20.5ppm.MS(70eV):m/z(％)＝344[M]+(100),281,212,105.HRMS(ESI)calcd.for C22H21N2O2[M+H]:345.1597,found:345.1595.
D47收率87％：1H NMR(400MHz,CDCl3)δ7.52(t,J＝8.8Hz,4H),7.46(d,J＝7.2Hz,3H),7.33(t,J＝7.6Hz,2H),7.25–7.17(m,3H),7.14–7.05(m,3H),5.03(d,J＝6.8Hz,1H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.7,150.0,142.4,139.7,136.1,133.1,130.2,129.3,129.1,128.7,128.6,127.6,126.7,121.7,121.0,119.1,43.1,19.5ppm.19F NMR(376MHz,CDCl3)δ-57.7.MS(70eV):m/z(％)＝412[M]+(100),280,105,77.HRMS(ESI)calcd.for C23H20F3N2O2[M+H]:413.1471,found:413.1467.
D48收率83％：1H NMR(400MHz,CDCl3)δ7.60(s,4H),7.56–7.51(m,2H),7.49–7.44(m,3H),7.33(t,J＝7.6Hz,2H),7.25–7.20(m,1H),7.15(s,1H),7.09(d,J＝7.6Hz,2H),5.03(d,J＝6.8Hz,1H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,142.3,139.5,137.8,136.0,131.4,131.0,130.3,129.5,129.0,128.7,127.6,127.3,126.7,125.6,125.3,122.6,43.2,19.5ppm.19F NMR(376MHz,CDCl3)δ-62.7.MS(70eV):m/z(％)＝396[M]+(100),264,105,77.HRMS(ESI)calcd.for C23H20F3N2O[M+H]:397.1522,found:397.1518.
D49收率82％：1H NMR(400MHz,CDCl3)δ7.61–7.55(m,4H),7.52–7.40(m,5H),7.34–7.26(m,2H),7.22–7.17(m,1H),7.11(s,1H),7.07(d,J＝7.6Hz,2H),5.03(d,J＝6.8Hz,1H),1.58(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,142.3,139.1,138.7,135.8,132.5,130.4,129.6,129.0,128.8,127.6,126.9,118.7,112.7,43.3,19.7ppm.MS(70eV):m/z(％)＝353[M]+(100),221,105,77.HRMS(ESI)calcd.for C23H20N3O[M+H]:354.1600,found:354.1595.
D50收率90％：1H NMR(400MHz,CDCl3)δ8.00(d,J＝8.4Hz,2H),7.54(d,J＝8.4Hz,2H),7.49–7.43(m,4H),7.40–7.35(m,1H),7.31–7.26(m,2H),7.18–7.14(m,2H),7.05(d,J＝7.6Hz,2H),5.06(d,J＝6.8Hz,1H),3.82(s,3H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ177.6,175.8,166.5,142.4,140.5,140.1,138.7,136.0,130.9,130.3,130.0,129.5,129.1,128.8,128.7,127.7,127.1,126.8,52.2,45.3,43.2,19.7,18.5ppm.MS(70eV):m/z(％)＝386[M]+(100),254,105,77.HRMS(ESI)calcd.for C24H23N2O3[M+H]:387.1703,found:387.1700.
D51收率92％：1H NMR(400MHz,CDCl3)δ7.93(d,J＝8.4Hz,1H),7.86–7.79(m,2H),7.75–7.71(m,1H),7.66(s,1H),7.55–7.50(m,4H),7.49–7.40(m,3H),7.36–7.29(m,3H),7.22–7.18(m,1H),7.12(d,J＝7.6Hz,2H),5.14(d,J＝7.2Hz,1H),1.62(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,142.5,141.6,136.3,134.1,133.2,132.2,130.2,129.2,129.1,128.7,128.6,128.2,127.9,127.8,127.0,126.7,126.6,122.8,43.0,19.5ppm.MS(70eV):m/z(％)＝378[M]+(100),246,207,153.HRMS(ESI)calcd.for C26H23N2O[M+H]:379.1805,found:379.1802.
D52收率81％：1H NMR(400MHz,CDCl3)δ8.15(d,J＝7.2Hz,1H),7.84(s,1H),7.73(d,J＝8.4Hz,2H),7.67(d,J＝7.2Hz,1H),7.54(d,J＝7.2Hz,2H),7.47(t,J＝7.6Hz,2H),7.42–7.34(m,4H),7.30(t,J＝7.6Hz,2H),7.19–7.12(m,3H),5.15(d,J＝6.8Hz,1H),1.64(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.9,142.6,141.3,136.5,134.0,130.9,130.6,130.5,130.0,129.5,129.0,128.9,128.0,127.2,127.1,126.9,126.3,125.5,123.8,43.2,20.1ppm.MS(70eV):m/z(％)＝378[M]+(100),246,153,105.HRMS(ESI)calcd.for C26H23N2O[M+H]:379.1805,found:379.1802.
D53收率77％：1H NMR(400MHz,CDCl3)δ8.36(s,1H),8.25(s,1H),7.98(d,J＝8.4Hz,2H),7.92(d,J＝8.0Hz,2H),7.61(t,J＝7.6Hz,2H),7.50(d,J＝7.6Hz,1H),7.47–7.40(m,5H),7.39–7.31(m,5H),7.27(d,J＝7.2Hz,1H),5.08(d,J＝7.2Hz,1H),1.58(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ176.1,142.4,141.2,136.6,131.3,130.6,130.0,129.6,129.4,129.2,129.1,129.0,128.9,128.8,128.0,127.8,126.8,126.0,125.4,124.8,119.8,47.9,42.6,20.1,18.7ppm.MS(70eV):m/z(％)＝428[M]+(100),378,246,105.HRMS(ESI)calcd.forC30H25N2O[M+H]:429.1961,found:429.1966.
D54收率41％：1H NMR(400MHz,CDCl3)δ7.57–7.46(m,4H),7.45–7.40(m,1H),7.34–7.28(m,3H),7.27–7.18(m,2H),7.05(d,J＝7.6Hz,2H),6.94(d,J＝3.4Hz,2H),4.99(d,J＝7.2Hz,1H),1.56(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.4,142.3,139.8,136.1,135.9,130.2,129.6,129.3,129.1,128.6,128.0,127.7,127.4,126.6,42.8,19.3ppm.MS(70eV):m/z(％)＝334[M]+(100),202,105,77.HRMS(ESI)calcd.for C20H19N2OS[M+H]:335.1212,found:335.1212.
酰腙D55-D68的制备
实施例112-125
与实施例1不同的是：B1替换为B55、B56……B68。具体数据如下所示：
D55收率91％：1H NMR(400MHz,CDCl3)δ7.48(d,J＝7.2Hz,4H),7.31–7.22(m,7H),7.17–7.11(m,2H),6.92(d,J＝7.6Hz,2H),5.09(d,J＝7.2Hz,1H),2.33(s,3H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,142.7,141.5,139.3,134.6,133.6,131.0,129.9,129.0,128.8,128.7,127.9,127.3,126.8,43.1,21.5,19.7ppm.MS(70eV):m/z(％)＝342[M]+(100),210,105,77.HRMS(ESI)calcd.for C23H23N2O[M+H]:343.1805,found:343.1806.
D56收率80％：1H NMR(400MHz,CDCl3)δ7.49(d,J＝6.8Hz,4H),7.37–7.25(m,6H),7.21–7.13(m,3H),6.87–6.83(m,2H),5.09(d,J＝6.8Hz,1H),2.32(s,3H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.8,142.6,141.6,140.3,136.2,134.6,130.2,130.2,129.9,129.7,128.8,128.7,127.9,127.3,126.7,126.1,43.0,21.5,19.6ppm.MS(70eV):m/z(％)＝342[M]+(100),210,105,77.HRMS(ESI)calcd.for C23H23N2O[M+H]:343.1805,found:343.1805.
D57收率51％：1H NMR(400MHz,CDCl3)δ7.47–7.34(m,4H),7.28–7.10(m,8H),7.10–7.03(m,1H),7.01–6.97(m,1H),6.89(s,1H),6.75(d,J＝7.6Hz,1H),5.02(d,J＝7.2Hz,1H),2.00(s,1H),1.54(s,2H),1.53–1.47(m,3H)ppm.13C NMR(101MHz,CDCl3)δ175.5,175.2,142.5,142.2,140.8,137.3,136.8,135.2,134.9,134.6,131.6,131.5,129.9,129.7,129.4,129.2,128.8,128.7,128.6,128.1,127.9,127.8,127.7,127.3,126.8,42.8,19.5,19.2,17.6,16.9ppm.MS(70eV):m/z(％)＝342[M]+(100),239,210,105.HRMS(ESI)calcd.for C23H23N2O[M+H]:343.1805,found:343.1804.
D58收率92％：1H NMR(400MHz,CDCl3)δ7.49(d,J＝7.2Hz,4H),7.32–7.23(m,7H),7.18–7.12(m,2H),6.95(d,J＝8.0Hz,2H),5.09(d,J＝7.2Hz,1H),2.65(q,J＝7.6Hz,2H),1.59(d,J＝7.2Hz,3H),1.23(t,J＝7.6Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.9,145.4,142.7,141.5,134.6,133.7,129.8,129.7,129.0,128.8,128.7,127.9,127.3,126.7,43.0,28.8,19.7,15.5ppm.MS(70eV):m/z(％)＝356[M]+(100),253,224,105.HRMS(ESI)calcd.for C24H25N2O[M+H]:357.1961,found:357.1962.
D59收率78％：1H NMR(400MHz,CDCl3)δ7.43–7.38(m,2H),7.37–7.28(m,3H),7.25–7.15(m,5H),7.10–6.97(m,3H),6.76–6.67(m,2H),4.94(d,J＝4.8Hz,1H),1.48(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.7,164.8,162.3,142.2,141.9,137.8,137.7,134.2,131.5,131.4,130.1,128.8,127.8,127.4,126.8,125.2,125.1,116.9,116.7,116.5,43.0,19.5ppm.19F NMR(376MHz,CDCl3)δ-110.0.MS(70eV):m/z(％)＝346[M]+(100),214,105,77.HRMS(ESI)calcd.for C22H20FN2O[M+H]:347.1554,found:347.1552.
D60收率42％：1H NMR(400MHz,CDCl3)δ7.56–7.52(m,2H),7.46(d,J＝7.2Hz,2H),7.44–7.25(m,6H),7.23–7.14(m,2H),7.11–6.97(m,2H),5.06(d,J＝7.2Hz,1H),1.61(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.4,160.5,160.3,160.2,158.0,157.9,157.8,157.7,141.9,141.0,133.9,131.6,131.5,131.4,130.1,128.7,128.5,127.8,127.5,126.7,112.7,112.6,112.5,112.4,112.3,43.2,19.4ppm.19F NMR(376MHz,CDCl3)δ-115.5,-115.9.MS(70eV):m/z(％)＝364[M]+(100),232,209,105.HRMS(ESI)calcd.forC22H19F2N2O[M+H]:365.1459,found:365.1459.
D61收率83％：1H NMR(400MHz,CDCl3)δ7.53–7.48(m,3H),7.44(d,J＝6.8Hz,2H),7.34–7.27(m,6H),7.23(s,1H),7.19–7.14(t,J＝7.4Hz,1H),7.11(s,1H),6.99(d,J＝8.0Hz,1H),5.02(d,J＝5.6Hz,1H),1.56(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.7,142.2,142.0,138.2,137.6,134.2,132.6,132.4,131.4,130.5,130.1,128.8,128.1,127.8,127.4,126.8,126.4,123.6,122.3,115.5,111.4,43.0,19.5ppm.MS(70eV):m/z(％)＝406[M]+(100),274,105,77.HRMS(ESI)calcd.for C22H20BrN2O[M+H]:407.0753,found:407.0753.
D62收率40％：1H NMR(400MHz,CDCl3)δ7.76(dd,J＝8.0,1.6Hz,1H),7.68(dd,J＝8.0,1.2Hz,1H),7.60–7.54(m,2H),7.53–7.47(m,2H),7.48–7.39(m,1H),7.40–7.28(m,5H),7.27–7.16(m,2H),7.05(dd,J＝7.6,1.6Hz,1H),6.99(d,J＝3.2Hz,1H),5.30–4.94(m,1H),1.62(d,J＝7.2,3H)ppm.13C NMR(101MHz,CDCl3)δ175.3,175.1,142.1,141.4,141.0,135.7,135.4,134.3,134.1,133.9,131.4,131.3,130.9,129.9,129.2,129.1,128.7,128.6,128.3,127.9,127.3,126.7,123.9,123.7,42.7,19.4,19.1ppm.MS(70eV):m/z(％)＝406[M]+(100),274,194,105.HRMS(ESI)calcd.for C22H20BrN2O[M+H]:407.0753,found:407.0751.
D63收率84％：1H NMR(400MHz,CDCl3)δ7.56–7.52(m,2H),7.47(d,J＝7.2Hz,2H),7.38–7.25(m,7H),7.20–7.13(m,2H),7.09(d,J＝8.8Hz,2H),5.07(d,J＝6.4Hz,1H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.9,149.4,142.3,141.8,134.7,134.2,131.0,130.1,128.8,127.8,127.4,126.8,122.6,43.0,19.5ppm.19F NMR(376MHz,CDCl3)δ-57.7.MS(70eV):m/z(％)＝412[M]+(100),280,105,77.HRMS(ESI)calcd.for C23H20F3N2O2[M+H]:413.1471,found:413.1470.
D64收率80％：1H NMR(400MHz,CDCl3)δ7.75(d,J＝8.4Hz,2H),7.56–
7.52(m,2H),7.47(d,J＝7.6Hz,2H),7.40–7.25(m,5H),7.23–7.16(m,3H),7.13(s,1H),5.06(d,J＝5.6Hz,1H),1.59(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ175.7,142.1,139.8,134.1,131.5,131.1,130.2,130.0,128.9,128.8,127.8,127.4,126.9,125.2,122.5,43.1,19.5ppm.19F NMR(376MHz,CDCl3)δ-62.6.MS(70eV):m/z(％)＝396[M]+(100),264,105,77.HRMS(ESI)calcd.for C23H20F3N2O[M+H]:397.1522,found:397.1518.
D65收率43％：1H NMR(400MHz,CDCl3)δ7.88(dd,J＝26.0,8.0Hz,2H),
7.60–7.54(m,3H),7.52–7.43(m,3H),7.42–7.34(m,3H),7.33–7.24(m,4H),7.19–7.12(m,1H),6.94(s,1H),6.81(d,J＝8.4Hz,1H),5.32–5.21(m,1H),1.66(t,J＝8.0Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ176.1,175.9,142.5,142.3,141.8,134.8,134.5,134.4,133.1,132.8,130.0,129.9,129.8,128.8,128.7,128.6,128.2,128.0,127.8,127.7,127.5,127.3,127.0,126.8,126.7,126.0,125.9,122.6,122.3,43.2,43.1,19.6,19.3ppm.MS(70eV):m/z(％)＝378[M]+(100),246,142,105.HRMS(ESI)calcd.for C26H23N2O[M+H]:379.1805,found:379.1805.
D66收率82％：1H NMR(400MHz,CDCl3)δ7.96(d,J＝8.8Hz,1H),7.89(d,J＝7.6Hz,1H),7.83(d,J＝7.6Hz,1H),7.62(s,1H),7.60–7.41(m,6H),7.41–7.25(m,5H),7.24–7.17(m,2H),7.12(d,J＝8.4Hz,1H),5.15(d,J＝6.8Hz,1H),1.63(d,J＝6.8Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ176.0,142.5,141.8,134.4,133.9,133.6,133.3,130.3,129.8,128.7,128.3,127.9,127.3,127.2,126.7,126.2,43.0,19.5ppm.MS(70eV):m/z(％)＝378[M]+(100),246,105,77.HRMS(ESI)calcd.for C26H23N2O[M+H]:379.1805,found:379.1804.
D67收率73％：1H NMR(400MHz,CDCl3)δ7.54–7.51(m,3H),7.49–7.43(m,2H),7.36–7.26(m,5H),7.24–7.13(m,4H),7.00(d,J＝6.8Hz,2H),5.30(d,J＝16.4Hz,1H),5.17–5.06(m,2H),1.61(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ176.2,142.3,139.9,135.2,134.8,129.7,128.9,128.7,128.6,127.9,127.3,127.2,126.8,126.3,44.8,42.4,19.5ppm.MS(70eV):m/z(％)＝342[M]+(100),238,196,182.HRMS(ESI)calcd.for C23H23N2O[M+H]:343.1805,found:343.1805.
D68收率71％：1H NMR(400MHz,CDCl3)δ7.57–7.53(m,3H),7.50–7.41(m,3H),7.36–7.27(m,5H),7.22–7.16(m,2H),6.94(d,J＝8.8Hz,2H),6.75(d,J＝8.8Hz,2H),5.24(d,J＝16.4Hz,1H),5.13–5.04(m,2H),3.71(s,3H),1.60(d,J＝7.2Hz,3H)ppm.13C NMR(101MHz,CDCl3)δ176.2,158.8,142.3,139.8,134.8,129.6,128.9,128.7,128.6,127.9,127.6,127.1,126.7,126.3,114.3,114.1,55.3,44.2,42.3,19.4ppm.MS(70eV):m/z(％)＝372[M]+(100),268,136,121.HRMS(ESI)calcd.for C24H25N2O2[M+H]:373.1911,found:373.1912.

Claims (3)

1.一种一步高效制备酰腙的方法，其特征在于：以烯烃、肼、醛和一氧化碳为原料，在钯催化剂作用下发生羰基化反应，得到酰腙化合物，其反应路线为：
所述催化剂为PdCl2、PdBr2、PdI2、Pd(OAc)2、Pd(TFA)2、PdCl2(CH3CN)2、PdBr2(CH3CN)2、PdCl2(COD)、PdBr2(COD)、PdCl2(PhCN)2、[PdCl(CH2＝CHCH2)]2、[PdCl(PhCH2＝CHCH2)]2、PdCl2(Ph3P)2、PdCl2[P(3,5-F2Ph)3]2、PdCl2(Xantphos)2中的一种或几种；其中，所述催化剂为PdCl2、PdBr2、PdI2、Pd(OAc)2、Pd(TFA)2、PdCl2(CH3CN)2、PdBr2(CH3CN)2、PdCl2(COD)、PdBr2(COD)、PdCl2(PhCN)2、[PdCl(CH2＝CHCH2)]2、[PdCl(PhCH2＝CHCH2)]2中的一种或几种时，酰腙的制备方法中还包括加入配体，所述配体为P(3-FPh)3、P(2-FPh)3、P(3,5-F2Ph)3、P(3,5-Me2Ph)3、P(3,5-(MeO)2Ph)3、P(3,5-(CF3)2Ph)3、Xantphos中的一种或几种；
所述溶剂为石油醚、二氧六环、苯甲醚、二甲基醚、三甲苯、硝基苯、甲苯、三乙胺、吡啶、特戊醇、乙酸乙酯、正己烷、乙腈、二氯甲烷、二氯乙烷或氯仿；
所述D为如下结构中的一种：
2.根据权利要求1所述的一种一步高效制备酰腙的方法，其特征在于：所述催化剂的用量为肼摩尔量的0.1-10％。
3.根据权利要求1所述的一种一步高效制备酰腙的方法，其特征在于：所述羰基化反应温度为40-140℃，时间为3-16小时。
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