CN117229200A - 一种钌催化合成酰氧基化2-苯甲酰吡啶类化合物的方法 - Google Patents
一种钌催化合成酰氧基化2-苯甲酰吡啶类化合物的方法 Download PDFInfo
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Abstract
本发明公开了一种钌催化合成酰氧基化2‑苯甲酰吡啶类化合物的方法，涉及化合物合成技术领域，本发明使用2‑苯甲酰吡啶类化合物和羧酸钠化合物为底物，在钌催化剂的作用下，合成了酰氧基化2‑苯甲酰吡啶类化合物，本发明解决传统反应条件苛刻，操作复杂，底物局限，步骤繁琐等问题，极大的丰富了此类化合物的结构多样性。
Description
技术领域
本发明涉及有机合成领域，尤其涉及一种钌催化合成酰氧基化2-苯甲酰吡啶类化合物的方法。
背景技术
目前，过渡金属催化的C-H官能化反应被认为是从结构简单的化合物中合成有用和复杂分子的可靠策略之一。芳基酯类化合物普遍存在于天然产物、药品、生物活性化合物、香料中，这类化合物的传统合成方法依赖于芳香醇或芳基硅与羰基化合物的交叉偶联反应，反应条件苛刻导致官能团耐受性较差，产物的多样性受到了限制。人们也一直在探索构建C-O键的新方法，到目前为止，C-H键的酰氧基化是在有机化合物中引入氧官能团的最有效的策略之一。
各种过渡金属催化剂已被报道用于C-H酰氧基化反应。其中Ru(II)催化的C-H与羧酸的酰氧基化反应已被广泛研究，Jeganmohan分别于2013年和2014年报道了Ru(II)催化的乙酰苯胺和N-烷基苯甲酰胺与芳香族羧酸的C-H苯甲氧基化反应，Ackermann随后报道了Ru(II)催化的2-吡啶氧基芳烃与羧酸的C-H酰氧基化反应。此后，在Ru(II)催化的C-H酰氧基化反应中使用了各种底物，如咔唑，苯甲酰胺，吲哚啉，和偶氮芳烃等。
尽管近年来过渡金属催化的C-H酰氧基化反取得了较大进展，但是大都采用羧酸作为酰氧源，且底物的多样性受到了限制。酸类药物成钠盐由于优异溶解性、良好的药动学性质和化学稳定性而被广泛用于药物开发，因而开发一种以钠盐作为酰氧源的Ru(II)催化C-H键的酰氧基化反应具有重要意义，不仅能拓展芳香酯类化合物的多样性，还能应用于药物的“Late-Stage”，为药物的开发提供方法。
发明内容
本发明的目的是提供一种钌催化合成酰氧基化2-苯甲酰吡啶类化合物的方法，以2-苯甲酰吡啶类化合物、羧酸钠化合物为原料合成酰氧基化2-苯甲酰吡啶类化合物(式Ⅰ)。
本发明采用的技术方案是：
一种钌催化合成酰氧基化2-苯甲酰吡啶类化合物的方法，包括以下步骤：将2-苯甲酰吡啶类化合物、羧酸钠化合物、[RuCl2(p-cymene)]2、AgSbF6、Ag2CO3混合，在有机溶剂中反应12h～24h，反应完毕，使用水和乙酸乙酯进行萃取，合并有机层，干燥、过滤，浓缩，分离纯化得到式Ⅰ化合物，其反应通式如下：
R选自氢、C1-C30烷基、C3-C11环烷基、芳基、芳杂基、金刚烷基、C1-C30烯烃基、萜类基团、甾体基团；
每个R1独立的选自氢、C1-C5烷基、C1-C5烷氧基、芳基、卤素、酯基；两个相邻的R1可与他们相连的原子一起形成五至六元饱和或不饱和的芳环或芳杂环；
每个R2独立的选自氢、C1-C5烷基、卤素；两个相邻的R2可与他们相连的原子一起形成五至六元饱和或不饱和的芳环或芳杂环；
m、s分别独立的选自1、2或3。
在本发明中，2-苯甲酰吡啶类化合物、羧酸钠化合物、[RuCl2(p-cymene)]2、AgSbF6、Ag2CO3的添加顺序不限。
在一些实施方案中，先将2-苯甲酰吡啶类化合物、羧酸钠化合物混合后，再依次添加[RuCl2(p-cymene)]2、AgSbF6和Ag2CO3。
进一步地，2-苯甲酰吡啶类化合物与羧酸钠化合物的摩尔比为(0.1～0.5)：(0.2～1.0)。
在一些实施方案中，2-苯甲酰吡啶类化合物与羧酸钠化合物的摩尔比为0.2:0.4。
在一些实施方案中，2-苯甲酰吡啶类化合物与羧酸钠化合物的摩尔比为0.2:0.3。
进一步地，2-苯甲酰吡啶类化合物与AgSbF6的摩尔比为(0.1～0.5)：(0.04～0.1)。
进一步地，羧酸钠化合物与Ag2CO3的当量比为(1～2)：(1～2)，优选为1：1。
进一步地，羧酸钠化合物与[RuCl2(p-cymene)]2的摩尔比为(0.2～1.0)：(0.01～0.06)。
在本发明中，有机溶剂选自PhCF3、DMF、CH3CN或DCE中的一种或几种，优选为DCE。
在本发明中，水和乙酸乙酯的萃取次数为3～5次，优选为3次。
在本发明中，纯化均采用硅胶柱层析，洗脱剂比例均为石油醚：乙酸乙酯＝10：1～5：1。
在本发明中，反应的温度为100℃～150℃，优选为120℃。
在一些实施方案中，钌催化合成酰氧基化2-苯甲酰吡啶类化合物的反应通式如下：
本发明还提供了酰氧基化2-苯甲酰吡啶类化合物，其结构式通式如下：
进一步地，R选自氢、C1-C20烷基、C3-C6环烷基、芳基、芳杂基、金刚烷基、C1-C20烯烃基、萜类基团、甾体基团；每个R1独立的选自氢、C1-C5烷基、C1-C5烷氧基、芳基、卤素、酯基；两个相邻的R1可与他们相连的原子一起形成五至六元饱和或不饱和的芳环或芳杂环；每个R2独立的选自氢、C1-C3烷基、卤素；两个相邻的R2可与他们相连的原子一起形成五至六元饱和或不饱和的芳环或芳杂环；
更进一步地，m、s分别独立的选自1或2。
本发明中，酰氧基化2-苯甲酰吡啶类化合物选自如下化合物：
此处对制备得到的35个化合物根据不同类别进行编号，其编号为结构式后括号里的内容，此编号仅为方便后续说明。
除非另有说明，本发明所用的下列术语旨在具有下列定义。一个特定的术语在没有特别定义的情况下不应该被认为是不清楚的，而应该按照普通的含义去理解。
当任何变量(例如R1)在化合物的组成或结构中出现一次以上时，其在每一种情况下的定义都是独立的。因此，例如，如果一个基团被0-2个R1所取代，则所述基团可以任选地至多被两个R1所取代，并且每种情况下的R都有独立的选项。此外，取代基和/或其变体的组合只有在这样的组合会产生稳定的化合物的情况下才是被允许的。
前述芳基即具有共轭π电子系统的全碳单环或稠环多环芳族基团；芳基基团在一个或多个环中可具有6至10个碳原子。最常见的是，芳基基团在环中具有6个碳原子。例如，C6-C10芳基是含有6至10个碳原子的芳族基团，例如苯基或萘基。
本发明的有益效果：本发明使用2-苯甲酰吡啶类化合物和羧酸钠化合物为底物，其羧酸钠化合物具有良好的溶解性和稳定性，在钌催化剂的作用下，合成了酰氧基化的2-苯甲酰吡啶类化合物；本发明解决传统反应条件苛刻，操作复杂，底物局限，步骤繁琐等问题，极大的丰富了此类化合物的结构多样性。
本发明中的缩写具有如下意义：
PhCF3表示为三氟甲苯；
DMF表示为二甲基甲酰胺；
CH3CN表示为乙腈；
DCE表示为二氯乙烷。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。另外，如果没有明确说明，在下面的实施例中所采用的所有试剂均为市场上可以购得的，或者可以按照本文或已知的方法合成的，对于没有列出的反应条件，也均为本领域技术人员容易获得的。
本发明中生成酰氧基化2-苯甲酰吡啶类化合物(式Ⅰ)的反应通式如下：
具体式Ⅰ化合物的合成参照如下实施例。
实施例1合成本发明的酰氧基化2-苯甲酰吡啶类化合物：
(1)3-methyl-2-picolinoylphenyl pivalate(3aa):收率为83％
在反应管中加入2-(2-甲基苯甲酰基)吡啶(39.7mg，0.20mmol)，特戊酸钠(49.6mg，0.40mmol),[Ru(p-cymene)Cl2]2(6.1mg，0.01mmol),AgSbF6(27.4mg，0.08mmol)，Ag2CO3(110.3mg，0.4mmol)，加入干燥二氯乙烷(1mL)，120℃反应12h得混合液体，反应结束后添加水和乙酸乙酯萃取三次，合并有机层，无水Na2SO4干燥有机层，过滤，浓缩，硅胶柱层析(石油醚/乙酸乙酯＝10/1—5/1)分离纯化得到3aa(49.4mg,83％)。
1H NMR(600MHz,CDCl3)δ＝8.72–8.68(m,1H),8.11–8.10(m,1H),8.89–8.86(m,1H),7.47(ddd,J＝7.6,4.7,1.2Hz,1H),7.35–7.38(m,1H),7.14(d,J＝7.7Hz,1H),7.04(d,J＝8.2Hz,1H),2.24(s,3H),0.95(s,9H).13C NMR(150MHz,CDCl3)δ＝195.33,174.78,152.72,148.84,147.18,136.28,135.92,130.93,128.94,126.51,126.15,122.18,118.63,37.82,25.60,18.36.HR-MS(ESI)m/z calcd for:C18H19NO3Na+[M+Na]+320.1257,found320.1260.
实施例2
根据前述合成通式的反应条件，改变2-苯甲酰吡啶类化合物和羧酸钠化合物底物，可得以下酰氧基化2-苯甲酰吡啶类化合物：
(2)3-methyl-2-picolinoylphenyl acetate(3ab)：收率为67％
1H NMR(600MHz,CDCl3)δ＝8.71–8.67(m,1H),8.09(d,J＝7.8Hz,1H),7.92–7.88(m,1H),7.50–7.46(m,1H),7.40–7.37(m,1H),7.18–7.15(m,1H),7.07(d,J＝8.2Hz,1H),2.25(s,3H),1.82(s,3H).13C NMR(150MHz,CDCl3)δ＝164.5,158.1,150.4,148.0,137.4,133.8,133.2,131.2,129.5,129.3,128.2,127.4,126.3,126.0,122.3,109.6,55.7,39.7,29.4.HR-MS(ESI)m/z calcd for:C15H14NO3 +[M+H]+256.0968,found 256.0971.
(3)3-methyl-2-picolinoylphenyl butyrate(3ac):收率为78％
1H NMR(600MHz,CDCl3)δ＝8.72–8.64(m,1H),8.09(d,J＝7.2Hz,1H),7.90–7.88(m,1H),7.49–7.45(m,1H),7.40–7.35(m,1H),7.15(d,J＝7.6Hz,1H),7.07(d,J＝9.3Hz,1H),2.24(s,3H),2.04(t,J＝6.1Hz,2H),1.46–1.39(m,2H),0.79(t,J＝7.6Hz,3H).13C NMR(150MHz,CDCl3)δ＝196.51,171.13,154.10,149.94,148.10,137.63,137.09,131.93,130.22,127.86,127.17,123.09,120.06,35.81,19.59,18.04,13.56.HR-MS(ESI)m/zcalcd for:C17H18NO3 +[M+H]+284.1281,found284.1283.
(4)3-methyl-2-picolinoylphenyl hexanoate(3ad):收率为80％
1H NMR(600MHz,CDCl3)δ＝8.71–8.67(m,1H),8.09(d,J＝7.8Hz,1H),7.90–7.88(m,1H),7.50–7.45(m,1H),7.41–7.35(m,1H),7.15(d,J＝5.2Hz,1H),7.07(d,J＝5.6Hz,1H),2.25(s,3H),2.04(t,J＝7.3Hz,2H),1.40–1.34(m,2H),1.23–1.17(m,2H),1.17–1.11(m,2H),0.83(t,J＝7.9Hz,3H).13C NMR(150MHz,CDCl3)δ＝196.50,171.28,154.10,149.93,148.12,137.62,137.08,131.92,130.21,127.85,127.16,123.09,120.05,33.97,31.14,24.20,22.28,19.58,13.93.HR-MS(ESI)m/z calcd for:C19H22NO3 +[M+H]+312.1594,found 312.1599.
(5)3-methyl-2-picolinoylphenyl decanoate(3ae:)收率为79％
1H NMR(600MHz,CDCl3)δ＝7.82(d,J＝3.7Hz,1H),7.22(d,J＝7.8Hz,1H),7.04–7.00(m,1H),6.60(ddd,J＝7.7,4.7,1.3Hz,1H),6.52–6.49(m,1H),6.28(d,J＝7.7Hz,1H),6.20(d,J＝8.2Hz,1H),1.38(s,3H),1.19–1.16(m,2H),0.51–0.47(m,2H),0.44–0.38(m,4H),0.38–0.35(m,4H),0.31–0.27(m,4H),0.01(t,J＝7.1Hz,3H).13C NMR(150MHz,CDCl3)δ＝196.39,171.19,154.06,149.85,148.07,137.55,136.97,131.84,130.13,127.76,127.04,123.01,119.96,33.94,31.86,29.34,29.24,29.16,28.93,24.45,22.67,19.50,14.12.HR-MS(ESI)m/zcalcd for:C23H30NO3 +[M+H]+368.2220,found 368.2221.
(6)3-methyl-2-picolinoylphenyl heptadecanoate(3af):收率为65％
1H NMR(600MHz,CDCl3)δ＝8.69(d,J＝4.8Hz,1H),8.08(d,J＝7.8Hz,1H),7.91–7.86(m,1H),7.46(dd,1H),7.39–7.34(m,1H),7.15(d,J＝7.7Hz,1H),7.07(d,J＝8.2Hz,1H),2.24(s,3H),2.04(t,J＝7.6Hz,2H),1.38–1.34(m,2H),1.28–1.22(m,21H),1.17–1.12(m,4H),0.88(t,J＝6.9Hz,3H).13C NMR(150MHz,CDCl3)δ＝196.38,171.19,154.07,149.84,148.07,137.55,136.97,131.85,130.12,127.76,127.04,123.00,119.96,33.94,31.94,29.71,29.67,29.59,29.40,29.37,29.17,28.94,24.46,22.70,19.49,14.13.HR-MS(ESI)m/z calcd for:
C31H45NO3Na+[M+Na]+502.3291,found 502.3292.
(7)N-(5-fluoro-2-(phenylselanyl)phenethyl)picolinamide(3ag):收率为84％
1H NMR(600MHz,CDCl3)δ＝8.73–8.69(m,1H),8.09(d,J＝7.8Hz,1H),7.90–7.85(m,1H),7.47(ddd,J＝7.6,4.7,1.3Hz,1H),7.38–7.33(m,1H),7.13(d,J＝7.7Hz,1H),7.04(d,J＝8.2Hz,1H),2.24(s,3H),1.89–1.85(m,3H),1.65–1.61(m,3H),1.59–1.57(m,6H),1.55–1.51(m,3H).13C NMR(150MHz,CDCl3)δ＝196.40,174.96,153.92,149.98,148.34,137.43,136.98,131.96,130.06,127.56,127.18,123.42,119.81,40.84,38.25,36.32,27.75,19.48.HR-MS(ESI)m/z calcd for:C24H26NO3 +[M+H]+376.1907,found 376.1912.
(8)3-methyl-2-picolinoylphenyl cyclopropanecarboxylate(3ah):收率为71％
1H NMR(600MHz,CDCl3)δ＝8.71–8.67(m,1H),8.11–8.06(m,1H),7.92–7.86(m,1H),7.50–7.45(m,1H),7.39–7.34(m,1H),7.15(d,J＝8.1Hz,1H),7.07(d,J＝7.6Hz,1H),2.26(s,3H),1.37–1.31(m,1H),0.80–0.76(m,2H),0.72–0.66(m,2H).13C NMR(150MHz,CDCl3)δ＝196.37,172.25,154.09,149.81,148.08,137.65,136.96,131.74,130.16,127.78,127.01,123.03,119.98,19.49,12.58,8.78.HR-MS(ESI)m/z calcd for:C17H16NO3 +[M+H]+282.1125,found 282.1128.
(9)3-methyl-2-picolinoylphenyl cyclopentanecarboxylate(3ai):收率为81％
1H NMR(600MHz,CDCl3)δ＝8.72–8.67(m,1H),8.09(d,J＝7.6Hz,1H),7.91–7.86(m,1H),7.49–7.45(m,1H),7.40–7.34(m,1H),7.14(d,J＝6.7Hz,1H),7.06(d,J＝8.0Hz,1H),2.54–2.45(m,1H),2.24(s,3H),1.65–1.59(m,2H),1.55–1.47(m,4H),1.47–1.39(m,2H).13C NMR(150MHz,CDCl3)δ＝196.43,174.05,153.86,149.87,148.08,137.38,136.98,131.91,130.04,127.62,127.12,123.11,119.86,43.55,29.53,25.62,19.44.HR-MS(ESI)m/z calcd for:C19H20NO3 +[M+H]+310.1438,found 310.1440.
(10)3-methyl-2-picolinoylphenyl 4-methylbenzoate(3aj):收率为68％
1H NMR(600MHz,CDCl3)δ＝8.63–8.59(m,1H),8.00(d,J＝8.2Hz,1H),7.75–7.70(m,1H),7.56(dd,J＝8.1,2.7Hz,2H),7.45–7.40(m,1H),7.33–7.29(m,1H),7.23–7.19(m,2H),7.08(d,J＝7.9Hz,2H),2.35(s,3H),2.32(s,3H).13CNMR(150MHz,CDCl3)δ＝196.43,164.02,154.12,149.68,148.36,144.20,137.93,136.81,131.83,130.29,129.79,128.93,127.94,126.86,126.11,122.93,120.10,21.66,19.55.HR-MS(ESI)m/z calcd for:C21H17NO3Na+[M+Na]+354.1100,found354.1098.
(11)3-methyl-2-picolinoylphenyl 4-(tert-butyl)benzoate(3ak):收率为62％
1H NMR(600MHz,CDCl3)δ＝8.62(d,J＝4.4Hz,1H),8.01(d,J＝7.8Hz,1H),7.76–7.71(m,1H),7.64–7.60(m,2H),7.45–7.40(m,1H),7.33–7.29(m,3H),7.23–7.19(m,2H),2.31(s,3H),1.29(s,9H).13C NMR(150MHz,CDCl3)δ＝196.43,164.03,157.17,154.14,149.72,148.39,137.86,136.78,131.89,130.26,129.70,127.89,126.83,126.12,125.19,123.00,120.12,35.08,31.04,19.56.HR-MS(ESI)m/zcalcd for:C24H23NO3Na+[M+Na]+396.1570,found 396.1572.
(12)3-methyl-2-picolinoylphenyl benzoate(3al):收率为58％
1H NMR(600MHz,CDCl3)δ＝8.63–8.60(m,1H),8.02–7.99(m,1H),7.73–7.70(m,1H),7.68(dd,J＝8.3,1.4Hz,2H),7.50–7.46(m,1H),7.45–7.43(m,1H),7.31–7.27(m,3H),7.24–7.21(m,2H),2.33(s,3H).13C NMR(150MHz,CDCl3)δ＝196.35,163.98,154.11,149.69,148.34,138.02,136.84,133.37,131.82,130.33,129.75,128.90,128.22,128.06,126.88,122.95,120.08,19.56.HR-MS(ESI)m/z calcd for:C20H16NO3 +[M+H]+318.1125,found 318.1126.
(13)3-methyl-2-picolinoylphenyl 2,4,6-trimethylbenzoate(3am):收率为63％
1H NMR(600MHz,CDCl3)δ＝8.68–8.67(m,1H),8.06(d,J＝7.7Hz,1H),7.83–7.79(m,1H),7.44–7.40(m,2H),7.23(d,J＝8.2Hz,1H),7.18(d,J＝7.7Hz,1H),6.76(s,2H),2.23(s,3H),2.20(s,3H),2.18(s,6H).13C NMR(150MHz,CDCl3)δ＝196.51,167.83,153.63,149.89,147.82,139.84,137.11,136.90,135.88,132.72,129.99,129.34,128.50,127.67,127.18,123.24,119.74,21.10,19.81,19.51.HR-MS(ESI)m/z calcd for:C23H22NO3 +[M+H]+360.1594,found 360.1595.
(14)3-methyl-2-picolinoylphenyl 2-naphthoate(3an):收率为52％
1H NMR(600MHz,CDCl3)δ＝8.63(d,J＝4.7Hz,1H),8.18(s,1H),8.01(d,J＝7.8Hz,1H),7.80(dd,J＝22.1,8.2Hz,2H),7.75–7.70(m,2H),7.68–7.63(m,1H),7.59–7.55(m,1H),7.53–7.49(m,1H),7.48–7.44(m,1H),7.30–7.26(m,2H),7.24(d,J＝7.6Hz,1H),2.35(s,3H).13C NMR(150MHz,CDCl3)δ＝196.44,164.13,154.19,149.70,148.41,138.10,136.85,135.61,132.15,131.82,131.46,130.39,129.34,128.55,128.12,128.05,127.72,126.88,126.70,126.09,125.04,122.92,120.10,19.59.HR-MS(ESI)m/z calcd for:C24H18NO3 +[M+H]+368.1281,found 368.1283.
(15)3-methyl-2-picolinoylphenyl thiophene-2-carboxylate(3ao):收率为56％
1H NMR(600MHz,CDCl3)δ＝8.65–8.58(m,1H),8.05(d,J＝7.6Hz,1H),7.79–7.73(m,1H),7.53–7.50(m,1H),7.49–7.45(m,1H),7.45–7.40(m,1H),7.35–7.31(m,1H),7.23(dd,J＝18.1,8.0Hz,2H),6.99–6.95(m,1H),2.32(s,3H).13C NMR(150MHz,CDCl3)δ＝196.26,159.36,154.02,149.71,147.94,138.04,136.82,134.33,133.35,132.21,131.69,130.28,128.16,127.66,126.91,122.97,119.96,19.55.HR-MS(ESI)m/z calcd for:C18H13NO3SNa+[M+Na]+345.0508,found 346.0507.
(16)3-methyl-2-picolinoylphenyl cinnamate(3ap):收率为53％
1H NMR(600MHz,CDCl3)δ＝8.68(d,J＝4.7Hz,1H),8.07(d,J＝8.0Hz,1H),7.83–7.79(m,1H),7.43–7.39(m,3H),7.38–7.35(m,5H),7.18(dd,J＝13.1,8.0Hz,2H),6.15(d,J＝15.9Hz,1H),2.30(s,3H).13C NMR(150MHz,CDCl3)δ＝196.41,164.19,154.17,149.80,148.17,146.21,137.84,136.94,133.91,131.81,130.66,130.29,128.90,128.17,127.95,126.99,122.97,120.03,116.51,19.56,1.02.HR-MS(ESI)m/z calcd for:C22H18NO3 +[M+H]+344.1281,found 344.1282.
(17)3-methyl-2-picolinoylphenyl 2-(4-isobutylphenyl)propanoate(3aq):收率为80％
1H NMR(600MHz,CDCl3)δ＝8.66–8.59(m,1H),7.93(d,J＝7.7Hz,1H),7.84–7.78(m,1H),7.44–7.39(m,1H),7.36–7.30(m,1H),7.12(d,J＝7.6Hz,1H),7.01–6.97(m,5H),3.45–3.40(m,1H),2.42(d,J＝5.6Hz,2H),2.21(s,3H),1.85–1.79(m,1H),1.25(d,J＝6.2Hz,3H),0.89(d,J＝4.8Hz,6H).13C NMR(150MHz,CDCl3)δ＝196.23,172.06,153.71,149.69,147.97,140.52,137.31,136.80,136.58,131.88,129.94,129.29,127.67,127.10,126.98,122.97,119.61,45.03,44.95,30.17,22.40,19.37,18.20.HR-MS(ESI)m/z calcdfor:C26H28NO3 +[M+H]+402.2064,found402.2066.
(18)3-methyl-2-picolinoylphenyl 2-(4-benzoylphenyl)propanoate(3ar):收率为70％
1H NMR(600MHz,CDCl3)δ＝8.59–8.55(m,1H),7.91(d,J＝7.8Hz,1H),7.80–7.76(m,3H),7.66–7.63(m,1H),7.62–7.58(m,1H),7.51–7.47(m,3H),7.39–7.33(m,4H),7.13(d,J＝7.7Hz,1H),7.02(d,J＝8.3Hz,1H),3.55(q,J＝7.2Hz,1H),2.19(s,3H),1.33(d,J＝7.2Hz,3H).13C NMR(150MHz,CDCl3)δ＝196.29,196.12,171.45,153.54,149.70,147.77,139.65,137.81,137.42,137.38,136.93,132.55,131.90,131.46,130.06,129.97,129.25,129.06,128.62,128.37,127.85,127.12,122.88,119.52,45.20,19.37,18.15.HR-MS(ESI)m/z calcd for:C29H24NO4 +[M+H]+450.1700,found 450.1702.
(19)3-methyl-2-picolinoylphenyl 2-(6-methoxynaphthalen-2-yl)propanoate(3as):收率为60％
1H NMR(600MHz,CDCl3)δ＝8.45(d,J＝4.3Hz,1H),7.62–7.56(m,3H),7.45–7.41(m,1H),7.39(s,1H),7.34–7.30(m,1H),7.21(dd,J＝8.4,1.9Hz,1H),7.16–7.12(m,2H),7.12–7.08(m,2H),7.02(d,J＝8.3Hz,1H),3.93(s,3H),3.64(q,J＝7.1Hz,1H),2.16(s,3H),1.39(d,J＝7.1Hz,3H).13C NMR(150MHz,CDCl3)δ＝196.21,171.99,157.70,153.28,149.43,147.82,137.22,136.39,134.49,133.73,132.05,129.86,129.37,128.86,127.70,127.14,126.70,126.04,122.65,119.60,118.87,105.54,55.35,45.28,19.27,18.21.HR-MS(ESI)m/z calcd for:C27H24NO4 +[M+H]+426.1700,found 426.1700.
(20)3-methyl-2-picolinoylphenyl 2-(4-chlorophenyl)-3-methylbutanoate(3at):收率为82％
1H NMR(600MHz,CDCl3)δ＝8.49(ddd,J＝4.7,1.8,0.9Hz,1H),7.84–7.80(m,1H),7.75–7.72(m,1H),7.35–7.30(m,2H),7.13–7.09(m,3H),7.01–6.98(m,3H),2.99(d,J＝10.6Hz,1H),2.16(s,3H),0.95(d,J＝6.5Hz,3H),0.59(d,J＝6.7Hz,3H).13C NMR(150MHz,CDCl3)δ＝196.24,171.04,153.15,149.63,147.54,137.11,136.62,135.71,133.03,132.24,129.80,129.70,128.59,127.72,127.02,122.85,119.49,59.03,31.83,21.20,19.92,19.25.HR-MS(ESI)m/z calcd for:C24H22ClNO3Na+[M+Na]+430.1180,found430.1181.
(21)3-methyl-2-picolinoylphenyl 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoate(3au):收率为81％
1H NMR(600MHz,CDCl3)δ＝8.65(d,J＝4.7Hz,1H),8.04(d,J＝7.6Hz,1H),7.85–7.81(m,1H),7.43(ddd,J＝7.6,4.7,1.3Hz,1H),7.38–7.33(m,1H),7.16(d,J＝7.7Hz,1H),7.09(d,J＝8.6Hz,2H),6.97(d,J＝8.2Hz,1H),6.82–6.77(m,2H),2.86–2.81(m,1H),2.21(s,3H),1.95(dd,J＝10.7,7.4Hz,1H),1.79(dd,J＝7.9Hz,1H),1.33(d,J＝2.2Hz,6H).13CNMR(150MHz,CDCl3)δ＝196.11,171.69,154.65,153.57,149.85,147.66,137.44,136.97,132.03,130.08,129.60,128.53,127.99,127.27,123.14,119.34,119.19,79.16,60.88,34.83,25.84,24.95,19.47.HR-MS(ESI)m/z calcd for:C26H23Cl2NO4Na+[M+Na]+506.0896,found 506.0899.
(22)3-methyl-2-picolinoylphenyl 5-(2,5-dimethylphenoxy)pentanoate(3av):收率为83％
1H NMR(600MHz,CDCl3)δ＝8.70–8.67(m,1H),8.10–8.07(m,1H),7.82–7.78(m,1H),7.40(ddd,J＝7.6,4.7,1.2Hz,1H),7.38–7.34(m,1H),7.14(d,J＝7.8Hz,1H),7.03(d,J＝8.2Hz,1H),7.00(d,J＝7.4Hz,1H),6.66(d,J＝7.5Hz,1H),6.59–6.56(m,1H),3.80(t,J＝6.2Hz,2H),2.31(s,3H),2.22(s,3H),2.14(s,3H),0.97(s,6H).13C NMR(150MHz,CDCl3)δ＝196.36,175.22,156.89,153.65,149.89,148.11,137.21,136.96,136.46,132.06,130.31,129.95,127.53,127.22,123.56,123.23,120.71,119.61,111.90,67.73,42.23,36.64,24.56,21.41,19.38,15.78.HR-MS(ESI)m/z calcd for:C28H33NO4 +[M+H]+446.2326,found 446.2328.
(23)3-methyl-2-picolinoylphenyl(4S)-4-((8S,9R,10R,13S,14R,17S)-10,13-dimethyl-3,7,12-trioxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate(3aw):收率为68％
1H NMR(600MHz,CDCl3)δ＝8.70–8.67(m,1H),8.10–8.06(m,1H),7.92–7.89(m,1H),7.48(ddd,J＝7.6,4.7,1.3Hz,1H),7.39–7.36(m,1H),7.15(d,J＝7.7Hz,1H),7.06(d,J＝8.5Hz,1H),2.96–2.76(m,4H),2.37–2.31(m,3H),2.30–2.26(m,2H),2.24(s,3H),2.22–2.20(m,1H),2.16–2.11(m,3H),2.06–2.01(m,3H),1.98–1.95(m,1H),1.92–1.86(m,2H),1.83–1.79(m,1H),1.65–1.60(m,2H),1.40(s,3H),1.15–1.10(m,1H),1.05(s,3H),0.90–0.86(m,1H),0.70(d,J＝6.5Hz,3H).13C NMR(150MHz,CDCl3)δ＝164.4,150.1,148.2,140.1,137.4,132.0,131.0,129.1,126.5,126.1,125.9,122.2,38.1,37.7,33.9,31.0,24.6,23.0.HR-MS(ESI)m/z calcd for:C37H44NO6 +[M+H]+598.3163,found 598.3167.
(24)3-methyl-2-picolinoylphenyl(1R,4aR,4bR,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene-1-carboxylate(3ax):收率为59％
1H NMR(600MHz,CDCl3)δ＝δ8.67–8.65(m,1H),8.06(d,J＝7.9Hz,1H),7.82–7.79(m,1H),7.42(ddd,J＝7.5,4.7,1.2Hz,1H),7.35–7.31(m,1H),7.11(d,J＝7.8Hz,1H),6.99(d,J＝8.2Hz,1H),5.75(s,1H),5.28–5.24(m,1H),2.21(s,3H),2.12–1.95(m,3H),1.92–1.87(m,1H),1.74–1.68(m,3H),1.66–1.56(m,3H),1.49–1.40(m,3H),1.31–1.29(m,1H),1.15–1.11(m,1H),1.04(s,3H),1.03–1.01(m,6H),0.71(s,3H).13C NMR(150MHz,CDCl3)δ＝196.51,175.88,153.54,149.83,148.23,145.11,137.10,136.85,135.23,132.06,129.84,127.37,127.10,123.32,122.53,120.60,119.52,50.80,46.72,44.60,38.08,36.44,34.91,34.37,27.46,25.45,22.36,21.48,20.91,19.31,17.88,16.81,13.95.HR-MS(ESI)m/z calcd for:C33H40NO3 +[M+H]+498.3003,found 498.3005.
(25)3-methyl-2-picolinoylphenyl oleate(3ay):收率为63％
1H NMR(600MHz,CDCl3)δ＝8.68(d,J＝4.7Hz,1H),8.08(d,J＝7.8Hz,1H),7.90–7.86(m,1H),7.46(ddd,J＝7.6,4.7,1.3Hz,1H),7.40–7.35(m,1H),7.15(d,J＝7.7Hz,1H),7.07(d,J＝8.2Hz,1H),5.39–5.31(m,2H),2.24(s,3H),2.06–1.97(m,6H),1.37–1.26(m,18H),1.19–1.13(m,4H),0.88(t,J＝6.9Hz,3H).13C NMR(150MHz,CDCl3)δ＝196.43,171.22,154.15,149.91,148.14,137.62,137.03,131.92,130.18,130.12,129.79,127.82,127.10,123.07,120.03,33.99,31.98,29.85,29.78,29.76,29.73,29.60,29.40,29.15,29.11,28.98,27.31,27.24,24.51,22.76,19.56,14.19.HR-MS(ESI)m/z calcd for:C31H42NO3+[M+H]+478.3316,found 478.3316.
(26)3-methyl-2-picolinoylphenyl 2-propylpentanoate(3az):收率为70％
1H NMR(600MHz,CDCl3)δ＝8.64–8.61(m,1H),8.04–8.02(m,1H),7.82–7.78(m,1H),7.39(ddd,J＝7.6,4.7,1.3Hz,1H),7.30–7.26(m,1H),7.06(d,J＝7.7Hz,1H),7.00(d,J＝8.2Hz,1H),2.16–2.12(m,4H),1.32–1.26(m,2H),1.19–1.14(m,2H),1.09–1.03(m,4H),0.70(t,J＝7.3Hz,6H).13C NMR(150MHz,CDCl3)δ＝196.56,173.87,153.85,150.00,147.99,137.16,136.95,132.25,129.92,127.49,127.19,123.22,119.73,45.22,34.05,20.44,19.44,14.02.HR-MS(ESI)m/z calcd for:C21H26NO+[M+H]+340.1907,found340.1907.
(27)2-picolinoyl-[1,1'-biphenyl]-3-yl pivalate(3ba):收率为71％
1H NMR(600MHz,CDCl3)δ＝8.58(ddd,J＝4.7,1.7,0.9Hz,1H),7.91–7.86(m,1H),7.75–7.69(m,1H),7.55–7.51(m,1H),7.34–7.30(m,2H),7.24–7.21(m,3H),7.18–7.15(m,3H),1.03(s,9H).13C NMR(150MHz,CDCl3)δ＝195.78,176.00,154.14,149.44,148.44,142.48,139.67,136.60,131.71,130.14,128.98,128.14,127.39,127.09,126.68,122.97,121.35,38.91,26.71.HR-MS(ESI)m/z calcd for:C23H22NO3 +[M+H]+360.1594,found360.1595.
(28)3-chloro-2-picolinoylphenyl pivalate(3ca):收率为73％
1H NMR(600MHz,CDCl3)δ＝8.69(d,J＝3.8Hz,1H),8.18–8.14(m,1H),7.92–7.87(m,1H),7.49(ddd,J＝7.6,4.7,1.2Hz,1H),7.43–7.39(m,1H),7.32(dd,J＝8.1,1.0Hz,1H),7.18(dd,J＝8.2,1.0Hz,1H),1.01(s,9H).13C NMR(150MHz,CDCl3)δ＝192.82,175.51,152.95,149.83,148.93,137.01,131.97,131.67,130.46,127.47,126.67,123.15,121.08,38.95,26.64.R-MS(ESI)m/z calcd for:C17H17ClNO3 +[M+H]+318.0892,found 318.0893.
(29)1-picolinoylnaphthalen-2-yl pivalate(3da):收率为79％
1H NMR(600MHz,CDCl3)δ＝8.68–8.64(m,1H),8.18–8.13(m,1H),7.97(d,J＝8.9Hz,1H),7.91–7.87(m,2H),7.70(d,J＝8.0Hz,1H),7.50–7.44(m,3H),7.32(d,J＝8.9Hz,1H),0.98(s,9H).13C NMR(150MHz,CDCl3)δ＝195.86,175.94,154.12,149.93,146.41,137.02,131.54,131.44,131.03,128.34,127.39,127.37,127.27,125.89,124.91,123.56,121.20,38.91,26.62.HR-MS(ESI)m/z calcd for:C21H20NO3 +[M+H]+334.1438,found 334.1438.
(30)4-(tert-butyl)-2-picolinoylphenyl pivalate(3ea):收率为62％
1H NMR(600MHz,CDCl3)δ＝8.72–8.68(m,1H),8.08–8.04(m,1H),7.91–7.84(m,1H),7.64(d,J＝2.5Hz,1H),7.57(dd,J＝8.6,2.5Hz,1H),7.46(ddd,J＝7.6,4.7,1.2Hz,1H),7.08(d,J＝8.6Hz,1H),1.34(s,9H),0.98(s,9H).13C NMR(150MHz,CDCl3)δ＝194.56,176.15,154.57,149.27,148.34,147.00,136.92,130.44,129.73,127.65,126.67,123.87,121.97,38.86,34.62,31.30,26.61.HR-MS(ESI)m/z calcd for:C21H26NO3 +[M+H]+340.1907,found 340.1905.
(31)5-methoxy-2-picolinoyl-1,3-phenylene bis(2,2-dimethylpropanoate)(3fa):收率为61％
1H NMR(600MHz,CDCl3)δ＝8.70–8.67(m,1H),8.03(d,J＝7.7Hz,1H),7.86–7.82(m,1H),7.46–7.43(m,1H),6.63(s,2H),3.84(s,3H),1.03(s,18H).13C NMR(150MHz,CDCl3)δ＝191.09,175.65,161.55,154.08,150.53,149.64,136.84,126.88,123.38,117.82,106.10,55.84,38.97,26.68.HR-MS(ESI)m/z calcd for:C23H28NO6 +[M+H]+414.1911,found414.1913.
(32)3-methyl-2-(4-methylpicolinoyl)phenyl pivalate(3ga):收率为59％
1H NMR(600MHz,CDCl3)δ＝8.54(d,J＝4.9Hz,1H),7.93–7.89(m,1H),7.39–7.32(m,1H),7.29–7.27(m,1H),7.13(d,J＝7.6Hz,1H),7.03(d,J＝8.2Hz,1H),2.44(s,3H),2.23(s,3H),0.96(s,9H).13C NMR(150MHz,CDCl3)δ＝196.59,175.84,153.65,149.71,148.36,148.19,137.28,132.12,129.91,127.99,127.54,124.11,119.69,38.86,26.68,26.63,21.03,19.40.HR-MS(ESI)m/z calcd for:C19H22NO3+[M+H]+414.1911,found414.1913.
(33)2-(4-bromopicolinoyl)-3-methylphenyl pivalate(3ha):收率为70％
1H NMR(600MHz,CDCl3)δ＝8.49(d,J＝5.1Hz,1H),8.27(d,J＝1.8Hz,1H),7.63(dd,J＝5.1,1.9Hz,1H),7.39–7.36(m,1H),7.15–7.13(m,1H),7.04(d,J＝8.4Hz,1H),2.23(s,3H),0.99(s,9H).13C NMR(150MHz,CDCl3)δ＝195.14,175.75,154.75,150.51,148.31,137.39,133.98,131.27,130.31,130.22,127.60,126.42,119.67,38.88,26.64,19.43.HR-MS(ESI)m/z calcd for:C18H19BrNO3 +[M+H]+376.0543,found 376.0543.
(34)2-(isoquinoline-1-carbonyl)-3-methylphenyl pivalate(3ia):收率为73％
1H NMR(600MHz,CDCl3)δ＝9.09–9.04(m,1H),8.55(d,J＝5.5Hz,1H),7.92–7.89(m,1H),7.80(d,J＝5.5Hz,1H),7.77–7.73(m,2H),7.39–7.34(m,1H),7.16(d,J＝7.6Hz,1H),6.96(d,J＝8.1Hz,1H),2.32(s,3H),0.75(s,9H).13C NMR(150MHz,CDCl3)δ＝197.50,176.07,153.04,148.51,141.70,138.03,137.09,133.74,130.52,130.14,129.40,127.83,127.10,126.65,126.35,124.49,119.67,38.75,26.50,19.77.HR-MS(ESI)m/z calcd for:C22H22NO3 +[M+H]+348.1594,found 348.1594.
(35)3,5-dimethyl-2-picolinoylphenyl pivalate(3ka):收率为60％
1H NMR(600MHz,CDCl3)δ＝8.72–8.67(m,1H),8.09(d,J＝7.9Hz,1H),7.89–7.84(m,1H),7.45(ddd,J＝7.6,4.7,1.2Hz,1H),6.96(s,1H),6.84(s,1H),2.36(s,3H),2.21(s,3H),0.94(s,9H).13C NMR(150MHz,CDCl3)δ＝196.35,175.93,154.08,149.80,148.35,140.54,137.25,136.90,128.99,128.60,127.02,123.19,120.24,38.83,26.62,21.38,19.43.HR-MS(ESI)m/z calcd for:C19H22NO3+[M+H]+312.1594,found 312.1595。
Claims (10)
1.一种钌催化合成酰氧基化2-苯甲酰吡啶类化合物的方法，其特征在于，包括以下步骤：将2-苯甲酰吡啶类化合物、羧酸钠化合物、[RuCl2(p-cymene)]2、AgSbF6、Ag2CO3混合，在有机溶剂中反应12h～24h，反应完毕，使用水和乙酸乙酯进行萃取，合并有机层，干燥、过滤，浓缩，分离纯化得到式Ⅰ化合物，其反应通式如下：
R选自氢、C1-C30烷基、C3-C11环烷基、芳基、芳杂基、金刚烷基、C1-C30烯烃基、萜类基团、甾体基团；
每个R1独立的选自氢、C1-C5烷基、C1-C5烷氧基、芳基、卤素、酯基；两个相邻的R1可与他们相连的原子一起形成五至六元饱和或不饱和的芳环或芳杂环；
每个R2独立的选自氢、C1-C5烷基、卤素；两个相邻的R2可与他们相连的原子一起形成五至六元饱和或不饱和的芳环或芳杂环；
m、s分别独立的选自1、2或3。
2.根据权利要求1所述的方法，其特征在于，所述有机溶剂选自PhCF3、DMF、CH3CN或DCE中的一种或几种，优选为DCE。
3.根据权利要求1所述的方法，其特征在于，所述2-苯甲酰吡啶类化合物与羧酸钠化合物的摩尔比为0.1～0.5：0.2～1.0，优选为0.2：0.3～0.4。
4.根据权利要求1所述的方法，其特征在于，所述2-苯甲酰吡啶类化合物与AgSbF6的摩尔比为0.1～0.5：0.04～0.1。
5.根据权利要求1所述的方法，其特征在于，反应的温度为100℃～150℃，优选为120℃。
6.根据权利要求1所述的方法，其特征在于，所述羧酸钠化合物与Ag2CO3的当量比为1～2：1～2，优选为1：1。
7.根据权利要求1所述的方法，其特征在于，所述羧酸钠化合物与[RuCl2(p-cymene)]2的摩尔比为0.2～1.0：0.01～0.06。
8.权利要求1～7任意一项中所述的方法制备得到的化合物，其特征在于，其结构式通式如下：
9.根据权利要求8所述的化合物，其特征在于：
R选自氢、C1-C20烷基、C3-C6环烷基、芳基、芳杂基、金刚烷基、C1-C20烯烃基、萜类基团、甾体基团；
每个R1独立的选自氢、C1-C5烷基、C1-C5烷氧基、芳基、卤素、酯基；两个相邻的R1可与他们相连的原子一起形成五至六元饱和或不饱和的芳环或芳杂环；
每个R2独立的选自氢、C1-C3烷基、卤素；两个相邻的R2可与他们相连的原子一起形成五至六元饱和或不饱和的芳环或芳杂环；
m、s分别独立的选自1或2。
10.根据权利要求8所述的化合物，其特征在于，选自如下化合物：
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