一种钯催化合成硒/硫化2-氨基联苯类化合物及构建含硒/硫八元环衍生物的方法

1.本发明涉及化合物合成技术领域，特别是涉及一种钯催化合成硒/硫化2-氨基联苯类化合物及构建含硒/硫八元环衍生物的方法。


背景技术：

2.c(sp2)-se键广泛存在于各种功能材料、荧光探针、候选药物和生物活性分子中。例如，芳基硒化物广泛存在于许多治疗癌症、sars-cov2和疼痛疾病的药物中。因此在过去的几十年中，对于c-se键的构建一直是化学工作者关注的重点。传统的c-se键的构建很大程度上依赖于金属硫醇盐与预官能化的芳基卤化物或芳基硼酸在直接交叉偶联反应。反应路线较长且反应条件苛刻导致官能团耐受性较差，产物的多样性极大的受到了限制。因此探索一条反应条件缓和，底物耐受性较好，反应步骤较短的新合成方法显得十分必要。
3.近年来，过渡金属催化的c-h键官能团化构建c-se具有原子和步骤经济性,已经成为生物活性分子合成或结构修饰的重要策略。在此背景下，过渡金属催化的直接邻位导向基团辅助的选择性c-h硒(硫)化反应已被逐渐开发。早在2012年，daugulis课题组利用双齿导向基团实现了铜促进苄胺衍生物惰性γ-c-h键硫化反应得到双硫化产物。随后，nishihara和li分别利用钯和铑催化剂分别成功地实现了芳基吡啶的直接c-h硫化反应。2014年，nishihara课题组通过使用吡啶酰胺二齿系统，在钯催化下萘的1位选择性c-h硫化反应。
4.尽管近年来过渡金属催化碳氢硒(硫)化反应取得了较大的进展，但是这些反应大都局限于导向基团邻位的c-h键官能团化，对于更具挑战性的2-氨基联苯远程δ位c-h硒(硫)化反应还尚未有报道。


技术实现要素：

5.本发明解决的主要技术问题是提供一种钯催化合成硒/硫化2-氨基联苯类化合物的方法及其八元环衍生物，通过发展一种条件缓和的过渡金属钯催化远端δ-c(sp2)-h反应方法构建合成硒/硫化2-氨基联苯化合物的新方法，首次实现了2-氨基联苯类化合物远端δ-c(sp2)-h选择性的硒(硫)化反应，并利用合成的硒/硫化2-氨基联苯类化合物生成了八元环衍生物。
6.为了解决上述的技术问题，本发明所采用的技术方案是：
7.一种构建八元环化合物b的方法，合成通式如下：
[0008][0009]
化合物b的合成步骤如下：
[0010]
将化合物a和碱混合，在空气下加入溶剂，加热反应，反应结束后添加水和二氯甲烷萃取，合并有机层，浓缩得到胺粗产品；将胺粗产品、催化剂和碱混合，在氮气保护下加入溶剂，加热反应，反应结束后添加饱和氯化胺和乙酸乙酯萃取，合并有机层，纯化得到化合物b；
[0011]
其中，化合物a中x＝se或s之一；
[0012]
ar选自苯基，卤代苯基；
[0013]
当x＝se时，化合物a的合成步骤如下：
[0014]
将2-氨基联苯底物和二芳基二硒醚混合，加入催化剂，氧化剂和添加剂混合，在氮气保护下加入溶剂，加热反应，反应结束后添加饱和氯化胺溶液和乙酸乙酯萃取，合并有机层，纯化得到硒化的2-氨基联苯化合物a；
[0015]
当x＝s时，化合物a的合成步骤如下：
[0016]
将2-氨基联苯类底物和二芳基二硫醚混合，加入催化剂、氧化剂和添加剂混合，在氮气保护下加入溶剂，加热反应，反应结束后添加饱和氯化胺溶液和乙酸乙酯萃取，合并有机层纯化得到硫化的2-氨基联苯类化合物a。
[0017]
进一步地，在化合物a的合成步骤中，当x＝se时，所述催化剂选自pd(tfa)2、pd(oac)2或pdcl2中的一种或几种；
[0018]
所述氧化剂选自agoac、agopiv、agno3、ag2o、ag2co3或phi(oac)2中的一种或几种；
[0019]
所述添加剂优选自tfa，pivoh，tfoh或1-admco2h中的一种或几种；
[0020]
所述溶剂选自phcf3、dmf、ch3cn或dce中的一种或几种；
[0021]
所述加热温度优选120℃；
[0022]
进一步地，所述催化剂优选为pd(tfa)2，所述氧化剂优选为agoac，所述溶剂优选为phcf3。
[0023]
进一步地，在化合物a的合成步骤中，当x＝s时，所述催化剂选自pd(tfa)2、pd(oac)2或pdcl2中的一种或几种，所述氧化剂选自agoac、ag2co3或agopiv中的一种或几种，所述添加剂选自naopiv、pivoh、tfoh、1-admco2h、hoac或naoac中的一种或几种，所述溶剂选自甲苯、dmf、phcf3或mesitylene的一种或几种，所述加热温度优选为140℃。
[0024]
进一步地，在化合物a的合成步骤中，当x＝se或s时，化合物a纯化均采用硅胶柱层析，洗脱剂比例均为石油醚：乙酸乙酯＝30：1～15：1。
[0025]
进一步地，在化合物b的合成中，所述溶剂选自乙二醇、丙三醇或1,2-丙二醇中一种或几种，所述碱选自碳酸铯、叔丁醇钠、碳酸钾或磷酸钾中的一种或几种；所述催化剂为cui；
[0026]
进一步地，所述溶剂优选为乙二醇，所述碱优选为碳酸铯。
[0027]
进一步地，在化合物b的合成中，纯化均采用硅胶柱层析，洗脱剂比例均为石油醚：乙酸乙酯＝80：1～40：1。
[0028]
进一步地，当x＝se时，所述化合物a包括以下化合物：
[0029][0030][0031]
其中，r1选自甲基，氟，溴；r2选自甲氧基，甲基，氟；r3选自氟，氯，溴；r4选自甲氧基，苯基；r5选自甲基，甲氧基，叔丁基，氟，氯，溴，苯基，三氟甲基；r6选自甲氧基，叔丁基；r7选自氢，甲基。
[0032]
进一步地，当x＝s时，所述化合物a包括以下化合物：
[0033][0034]
其中，r8选自甲氧基，甲基，氯，溴；r9选自甲基，氯。
[0035]
进一步地，化合物b包括以下化合物：
[0036][0037]
本发明的有益效果是：
[0038]
1.本发明提供了一条操作简单、条件缓和的2-氨基联苯类化合物硒/硫化反应的新方法，首次实现了2-氨基联苯类化合物远端δ-c(sp2)-h选择性的硒/硫化反应；并进一步通过分子内环合构建一系列含硒/硫八元环化合物，2-氨基联苯类底物和二芳基二硒(硫)醚类底物结构简单易制备，价格便宜，衍生范围广，该策略解决了传统反应条件苛刻，操作复杂，底物局限，步骤繁琐，底物的官能团不耐受等不足，极大的丰富了此类化合物的结构多样。
具体实施方式
[0039]
以下对本发明的技术方案进行清晰、完整地描述，显然，此处所描述的实施例仅是本发明中的一部分，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动的前提下所获得的所有其他实施例，都属于本发明的保护范围。
[0040]
本发明中用pa替代以方便书写。
[0041]
本发明中类似部分官能团显色为灰色的化合物结构，代表两种结构形式，一种为另一种为
[0042]
一、本发明中生成硒化的2-氨基联苯类化合物a的反应通式如下：
[0043][0044]
具体化合物a的合成参照如下实施例。
[0045]
实施例1
[0046]
合成本发明的硒化的2-氨基联苯类化合物3aa：
[0047][0048]
在封管中加入n-(3'-甲基-[1，1'-联苯]-2-基)吡啶甲酰胺(1a)(57.7mg,0.20mmol)，二苯基二硒醚(2a)(62.4mg,0.2mmol)，pd(tfa)2(3.3mg,0.01mmol),agoac(60.1mg,1.8mmol)在氮气保护下加入干燥三氟甲苯(2ml)，120℃反应12h得混合液体，反应结束后添加饱和氯化胺溶液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＝30/1，15/1)分离纯化得到3aa(82.8mg，93％)。
[0049][0050]
n-(5'-methyl-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3aa93％).1h nmr(600mhz,cdcl3)δ＝10.02(s,1h),8.58(dd,j＝8.3,1.2hz,1h),8.35
–
8.34(m,1h),8.24
–
8.22(m,1h),7.85
–
7.82(m,1h),7.46
–
7.43(m,1h),7.39
–
7.36(m,1h),7.36
–
7.35(m,1h),7.35
–
7.34(m,1h),7.28(d,j＝8.0hz,1h),7.20
–
7.17(m,2h),7.17
–
7.15(m,1h),7.14
–
7.12(m,2h),7.11
–
7.10(m,2h),2.34(s,3h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.2,148.0,139.3,137.5,135.2,134.5,134.5,132.7,132.1,131.8,130.5,130.3,130.3,130.0,129.2,129.0,127.7,126.2,123.9,122.4,120.5,21.1.hr-ms(esi)m/z calcd for:c
25h21
n2o
80
se

[m h]

445.0814,found 445.0818.
[0051]
实施例2
[0052]
根据前述合成通式的反应条件，改变2-氨基联苯类底物，可得以下硒化的2-氨基联苯化合物：
[0053][0054]
n-(5'-methoxy-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ba,92％).
[0055]1h nmr(600mhz,cdcl3)δ＝9.99(s,1h),8.58
–
8.56(m,1h),8.35
–
8.34(m,1h),8.22
–
8.20(m,1h),7.84
–
7.81(m,1h),7.47
–
7.46(m,1h),7.45
–
7.41(m,1h),7.37(ddd,j＝7.6,4.7,1.2hz,1h),7.27
–
7.26(m,1h),7.26
–
7.25(m,1h),7.16
–
7.14(m,1h),7.13(dd,j＝7.0,1.1hz,1h),7.12
–
7.09(m,1h),7.06
–
7.02(m,2h),6.92
–
6.88(m,2h),3.78(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,159.7,150.1,148.0,141.8,137.6,135.8,135.2,133.3,132.2,131.5,130.1,129.0,129.0,127.2,126.2,123.8,123.4,122.3,120.4,116.1,115.8,55.6.hr-ms(esi)m/z calcd for:c
25h21
n2o
280
se

[m h]

461.0763,found 461.0769.
[0056][0057]
n-(5'-(tert-butyl)-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ca,58％).
[0058]1h nmr(600mhz,cdcl3)δ＝9.99(s,1h),8.63(dd,j＝8.2,1.1hz,1h),8.29
–
8.28(m,1h),8.23
–
8.21(m,1h),7.84
–
7.81(m,1h),7.47
–
7.44(m,1h),7.37
–
7.34(m,3h),7.34
–
7.32(m,3h),7.30
–
7.28(m,1h),7.20
–
7.16(m,2h),7.12
–
7.08(m,2h),1.29(s,9h).
13
c nmr(150mhz,cdcl3)δ＝161.9,150.8,150.2,147.8,138.7,137.5,135.4,134.6,132.6,132.2,130.6,130.5,130.4,129.2,129.0,128.0,127.7,126.3,126.2,123.8,122.3,120.4,34.7,31.4.hr-ms(esi)m/z calcd for:c
28h27
n2o
80
se

[m h]

487.1283,found 487.1288.
[0059][0060]
n-(5'-fluoro-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3da,71％).
[0061]1h nmr(600mhz,cdcl3)δ＝9.95(s,1h),8.57(d,j＝8.2hz,1h),8.35(dd,j＝4.7,1.5hz,1h),8.23(d,j＝7.7hz,1h),7.86
–
7.83(m,1h),7.49
–
7.45(m,1h),7.41
–
7.38(m,1h),7.37
–
7.33(m,3h),7.22
–
7.18(m,1h),7.18
–
7.16(m,2h),7.14
–
7.11(m,2h),7.05(dd,j
＝9.0,2.8hz,1h),7.03
–
7.00(m,1h).
13
c nmr(150mhz,cdcl3)δ＝162.3(d,j＝249.2hz),161.9,150.0,148.0,141.3(d,j＝7.3hz),137.7,135.1,134.6,134.3(d,j＝7.8hz),131.0,130.0,129.5,129.4,129.0,129.0,128.0,126.4,124.1,122.4,120.8,118.1(d,j＝21.7hz),116.3(d,j＝21.2hz).
19
fnmr(565mhz,cdcl3)δ＝-114.85
–‑
114.89(m).hr-ms(esi)m/z calcd for:c
24h18
fn2o
80
se

[m h]

449.0563,found 449.0567.
[0062][0063]
n-(5'-chloro-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ea,86％).
[0064]1h nmr(600mhz,cdcl3)δ＝10.02(s,1h),8.58(d,j＝8.2hz,1h),8.39
–
8.37(m,1h),8.26
–
8.24(m,1h),7.88
–
7.85(m,1h),7.50
–
7.47(m,1h),7.42
–
7.40(m,3h),7.29(d,j＝2.3hz,1h),7.28
–
7.26(m,1h),7.23(dd,j＝8.5,2.3hz,1h),7.20
–
7.19(m,2h),7.19
–
7.17(m,3h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.0,148.0,140.2,137.6,135.4,135.1,133.4,133.0,132.7,130.8,130.6,130.1,129.6,129.5,129.2,129.1,128.4,126.4,124.2,122.4,120.9.hr-ms(esi)m/z calcd for:c
24h18
cln2o
80
se

[m h]

465.0267,found 465.0284.
[0065][0066]
n-(5'-bromo-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3fa,79％).
[0067]1h nmr(600mhz,cdcl3)δ＝10.04(s,1h),8.59(d,j＝8.2hz,1h),8.39
–
8.38(m,1h),8.25(d,j＝7.8hz,1h),7.87
–
7.84(m,1h),7.51
–
7.47(m,1h),7.45
–
7.43(m,1h),7.43
–
7.38(m,3h),7.38
–
7.35(m,1h),7.28
–
7.27(m,1h),7.20
–
7.18(m,4h),7.10(d,j＝8.7hz,1h).
13
cnmr(150mhz,cdcl3)δ＝162.0,150.0,148.0,140.3,137.6,135.5,135.1,134.2,133.6,132.7,132.0,130.4,130.1,129.6,129.5,128.9,128.5,126.3,124.2,122.3,120.8,120.8.hr-ms(esi)m/zcalcd for:c
24h18
brn2o
80
se

[m h]

508.9762,found 508.9760.
[0068][0069]
n-(6'-(phenylselanyl)-[1,1':3',1
”‑
terphenyl]-2-yl)picolinamide(3ga,
89％).
[0070]1h nmr(600mhz,cdcl3)δ＝10.16(s,1h),8.64(d,j＝8.2hz,1h),8.28
–
8.26(m,1h),8.23(d,j＝7.5hz,1h),7.84
–
7.81(m,1h),7.59
–
7.57(m,2h),7.55(d,j＝2.1hz,1h),7.51
–
7.48(m,2h),7.46
–
(m,2h),7.40
–
7.39(m,1h),7.37(s,1h),7.37
–
7.35(m,1h),7.34
–
7.32(m,1h),7.32
–
7.29(m,2h),7.27
–
7.24(m,1h),7.22
–
7.20(m,1h),7.20
–
7.17(m,2h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.2,148.0,140.2,139.0,137.6,135.3,135.3,133.8,132.2,131.6,130.4,129.6,129.5,129.4,129.3,129.0,129.0,128.2,127.7,127.6,127.0,126.2,124.0,122.3,120.6.hr-ms(esi)m/z calcd for:c
30h23
n2o
80
se

[m h]

507.0970,found 507.0977.
[0071][0072]
n-(2'-(phenylselanyl)-5'-(trifluoromethyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ha,48％).
[0073]1h nmr(600mhz,cdcl3)δ＝10.06(s,1h),8.64(d,j＝8.3hz,1h),8.33
–
8.32(m,1h),8.26
–
8.24(m,1h),7.87
–
7.84(m,1h),7.54
–
7.51(m,2h),7.52
–
7.49(m,2h),7.46
–
7.44(m,1h),7.39(ddd,j＝7.6,4.7,1.2hz,1h),7.38
–
7.35(m,1h),7.31
–
7.30(m,1h),7.29
–
7.27(m,2h),7.25
–
7.23(m,1h),7.21(d,j＝8.4hz,1h).
13
c nmr(150mhz,cdcl3)δ＝162.1,150.0,148.0,141.4,138.0,137.7,136.5,135.2,130.2,130.2,130.1,130.0,129.9,129.2,128.8(q,j＝32.9hz),127.9,127.5(q,j＝3.9hz),126.4,125.6(q,j＝3.7hz),124.4,124.2(q,j＝271.7hz),122.4,121.0.
19
f nmr(565mhz,cdcl3)δ＝-62.34.(s)hr-ms(esi)m/z calcd for:c
25h18
f3n2o
80
se

[m h]

499.0531,found 499.0533.
[0074][0075]
n-(4'-methoxy-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ia,93％).
[0076]1h nmr(600mhz,cdcl3)δ＝9.98(s,1h),8.57(d,j＝8.2hz,1h),8.36
–
8.33(m,1h),8.21(d,j＝8.0hz,1h),7.84
–
7.81(m,1h),7.47(d,j＝8.4hz,1h),7.46
–
7.42(m,1h),7.38
–
7.36(m,1h),7.27
–
7.25(m,2h),7.17
–
7.12(m,2h),7.12
–
7.09(m,1h),7.06
–
7.03(m,2h),6.92
–
6.88(m,2h),3.78(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,159.7,150.1,148.0,141.8,137.6,135.8,135.1,133.3,132.2,131.5,130.1,129.0,129.0,127.2,126.2,123.8,123.4,122.3,120.4,116.1,115.8,55.6.hr-ms(esi)m/z calcd for:c
25h21
n2o
280
se

[m h]

461.0763,found 461.0767.
[0077][0078]
n-(4'-(tert-butyl)-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ja,81％).
[0079]1h nmr(600mhz,cdcl3)δ＝9.98(s,1h),8.60(d,j＝8.2hz,1h),8.25
–
8.20(m,2h),7.84
–
7.81(m,1h),7.46
–
7.43(m,1h),7.40(d,j＝2.2hz,1h),7.37
–
7.35(m,4h),7.24
–
7.20(m,2h),7.20
–
7.13(m,2h),7.13
–
7.10(m,2h),1.27(s,9h).
13
c nmr(150mhz,cdcl3)δ＝161.8,152.1,150.2,147.7,137.6,136.2,135.5,134.7,133.8,131.8,130.6,130.3,130.2,129.6,129.2,129.0,127.8,126.2,124.5,123.8,122.3,120.1,34.9,31.3.hr-ms(esi)m/z calcd for:c
28h27
n2o
80
se

[m h]

487.1283,found 487.1296.
[0080][0081]
n-(2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ka,96％,mono:di＝4.1:1).
[0082]1h nmr(600mhz,cdcl3)δ＝10.00(s,1h),8.60(d,j＝8.3hz,1h),8.33
–
8.31(m,1h),8.23(d,j＝7.8hz,1h),7.85
–
7.82(m,1h),7.48
–
7.45(m,1h),7.42
–
7.40(m,2h),7.37(ddd,j＝7.5,4.8,1.2hz,1h),7.33
–
7.29(m,2h),7.29
–
7.26(m,2h),7.24
–
7.22(m,2h),7.19(dd,j＝7.4,1.2hz,1h),7.17
–
7.14(m,2h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.2,148.0,138.8,137.6,135.3,134.7,131.9,131.7,131.0,130.3,129.7,129.4,129.4,129.2,129.1,128.1,127.2,126.2,124.1,122.4,120.6.hr-ms(esi)m/z calcd for:c
24h19
n2o
80
se

[m h]

431.0657,found 431.0556.
[0083][0084]
n-(2',6'-bis(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ka',96％,mono:di＝4.1:1).
[0085]1h nmr(600mhz,cdcl3)δ＝10.04(s,1h),8.69(d,j＝8.2hz,1h),8.34
–
8.32(m,1h),8.26(d,j＝7.8hz,1h),7.87
–
7.85(m,1h),7.55
–
7.52(m,1h),7.43(d,j＝7.5hz,4h),7.41
–
7.39(m,1h),7.26
–
7.25(m,1h),7.25
–
7.23(m,3h),7.19
–
7.15(m,4h),7.03
–
7.02(m,3h).
13
cnmr(150mhz,cdcl3)δ＝161.9,150.3,147.9,137.6,137.3,136.8,135.7,135.2,130.6,130.1,130.0,129.8,129.6,129.5,128.8,128.4,126.2,124.4,122.4,120.6.hr-ms
(esi)m/z calcd for:c
30h23
n2o
80
se
2
[m h]

587.0135,found 587.0177.
[0086][0087]
n-(4'-methyl-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3la,91％,mono:di＝4.7:1).
[0088]1h nmr(600mhz,cdcl3)δ＝9.99(s,1h),8.57(dd,j＝8.2,1.1hz,1h),8.35
–
8.34(m,1h),8.23
–
8.22(m,1h),7.84
–
7.81(m,1h),7.45
–
7.43(m,1h),7.39
–
7.36(m,3h),7.22
–
7.20(m,1h),7.19
–
7.18(m,2h),7.17(s,1h),7.16
–
7.11(m,4h),2.32(s,3h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.2,148.0,139.0,137.5,136.2,135.4,134.8,133.9,132.8,132.0,130.8,130.5,130.1,129.3,128.9,128.3,127.8,126.2,124.0,122.4,120.5,21.3.hr-ms(esi)m/z calcd for:c
25h21
n2o
80
se

[m h]

445.0814,found 445.0818.
[0089][0090]
n-(4'-methyl-2',6'-bis(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3la',91％mono:di＝4.7:1).
[0091]1h nmr(600mhz,cdcl3)δ＝10.01(s,1h),8.66(d,j＝8.3hz,1h),8.35(s,1h),8.25(d,j＝7.9hz,1h),7.87
–
7.85(m,1h),7.52
–
7.49(m,1h),7.43
–
7.39(m,5h),7.24
–
7.17(m,3h),7.17
–
7.14(m,5h),6.91(s,2h),2.15(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,150.3,147.9,139.8,137.6,136.0,135.4,135.3,135.2,130.9,130.3,130.2,129.9,129.7,129.4,128.2,126.2,124.2,122.4,120.4,21.3.hr-ms(esi)m/z calcd for:c
31h25
n2o
80
se
2
[m h]

601.0292,found 601.0295.
[0092][0093]
n-(4'-chloro-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ma,94％,mono:di＝4.9:1).
[0094]1h nmr(600mhz,cdcl3)δ＝9.98(s,1h),8.57(d,j＝8.3hz,1h),8.39(d,j＝4.7hz,1h),8.24(d,j＝7.8hz,1h),7.87
–
7.84(m,1h),7.51
–
7.47(m,1h),7.45
–
7.43(m,2h),7.42
–
7.39(m,1h),7.33
–
7.27(m,2h),7.26
–
7.22(m,2h),7.21
–
7.19(m,3h),7.17(s,1h).
13
c nmr
(150mhz,cdcl3)δ＝162.0,150.0,148.1,137.6,137.1,136.7,135.8,135.2,135.0,131.9,130.7,130.3,129.7,129.7,129.5,128.8,128.5,127.1,126.4,124.3,122.4,121.0.hr-ms(esi)m/z calcd for:c
24h18
cln2o
80
se

[m h]

465.0267,found 465.0266.
[0095][0096]
n-(4'-chloro-2',6'-bis(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ma',94％,mono:di＝4.9:1).
[0097]1h nmr(600mhz,cdcl3)δ＝10.04(s,1h),8.69(dd,j＝8.3,1.1hz,1h),8.41
–
8.39(m,1h),8.28(d,j＝7.8hz,1h),7.90
–
7.87(m,1h),7.57
–
7.54(m,1h),7.46
–
7.44(m,4h),7.44
–
7.42(m,1h),7.33
–
7.30(m,2h),7.25
–
7.22(m,4h),7.22
–
7.20(m,2h),6.88(s,2h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.2,148.1,138.7,137.7,136.1,135.7,135.3,134.8,130.7,130.4,129.8,129.0,128.9,128.5,127.4,126.4,124.6,122.5,120.8.hr-ms(esi)m/z calcd for:c
30h22
cln2o
80
se
2
[m h]

620.9746,found 620.9748.
[0098][0099]
n-(4'-fluoro-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3na,94％,mono:di＝3.9:1).
[0100]1h nmr(600mhz,cdcl3)δ＝10.02(s,1h),8.59(d,j＝8.2hz,1h),8.39
–
8.37(m,1h),8.25(dd,j＝7.9,2.5hz,1h),7.88
–
7.85(m,1h),7.51
–
7.49(m,1h),7.47
–
7.46(m,2h),7.42
–
7.40(m,1h),7.34
–
7.31(m,1h),7.25
–
7.17(m,5h),7.00
–
6.97(m,1h),6.86(d,j＝9.4hz,1h).
13
c nmr(150mhz,cdcl3)δ＝163.0(d,j＝249.9hz),162.0,150.1,148.0,137.7,137.7,136.1,135.5,133.8(d,j＝3.2hz),132.2(d,j＝8.1hz),130.7,130.5,129.8,129.5,128.9,128.4,126.4,124.3,122.4,120.9,117.2(d,j＝23.9hz),113.8(d,j＝21.7hz).
19
f nmr(565mhz,cdcl3)δ＝-112.78
–‑
112.82(m).hr-ms(esi)m/z calcd for:c
24h18
fn2o
80
se

[m h]

449.0563,found 449.0568.
[0101][0102]
n-(4'-fluoro-2',6'-bis(phenylselanyl)-[1,1'-biphenyl]-2-yl)
picolinamide(3na',94％,mono:di＝3.9:1).
[0103]1h nmr(600mhz,cdcl3)δ＝10.07(s,1h),8.72(d,j＝7.9hz,1h),8.41
–
8.38(m,1h),8.29(d,j＝7.8hz,1h),7.90
–
7.87(m,1h),7.58
–
7.56(m,1h),7.48
–
7.46(m,4h),7.43(ddd,j＝7.6,4.7,1.2hz,1h),7.34
–
7.31(m,2h),7.26
–
7.24(m,3h),7.24(s,2h),7.23(d,j＝0.8hz,1h),6.59
–
6.58(m,2h).
13
c nmr(150mhz,cdcl3)δ＝163.2(d,j＝252.2hz),162.0,150.2,148.0,139.2(d,j＝7.2hz),137.7,136.4,135.6,131.8,131.0,130.4,129.8,129.1,128.8,128.4,126.4,124.5,122.5,120.8,114.4(d,j＝24.2hz).
19
f nmr(565mhz,cdcl3)δ＝-111.68
–‑
111.71(m).hr-ms(esi)m/z calcd for:c
30h22
fn2o
80
se
2
[m h]

605.0041,found 605.0049.
[0104][0105]
n-(2'-fluoro-6'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3oa,72％).
[0106]1h nmr(600mhz,cdcl3)δ＝10.00(s,1h),8.64(dd,j＝8.3,1.2hz,1h),8.33
–
8.32(m,1h),8.25
–
8.23(m,1h),7.86
–
7.83(m,1h),7.53
–
7.50(m,1h),7.45
–
7.43(m,2h),7.38(ddd,j＝7.6,4.7,1.2hz,1h),7.30
–
7.28(m,1h),7.27(d,j＝1.5hz,1h),7.25
–
7.23(m,1h),7.23
–
7.21(m,1h),7.21
–
7.18(m,2h),7.06
–
7.03(m,1h),7.00(dd,j＝8.0,1.1hz,1h).
13
c nmr(150mhz,cdcl3)δ＝161.9,160.3(d,j＝249.2hz),150.1,147.9,138.0,137.6,135.8,135.8,130.8,130.4(d,j＝8.5hz),129.9,129.6,128.9,128.6,126.5,126.3,125.5(d,j＝18.3hz),124.9,124.2,122.4,120.8,113.8(d,j＝22.5hz).
19
f nmr(565mhz,cdcl3)δ＝-111.29
–‑
111.32(m).hr-ms(esi)m/z calcd for:c
24h18
fn2o
80
se

[m h]

449.0563,found 449.0568.
[0107][0108]
n-(2'-methoxy-6'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3pa,47％).
[0109]1h nmr(600mhz,cdcl3)δ＝10.03(s,1h),8.64
–
8.61(m,1h),8.35
–
8.33(m,1h),8.25
–
8.23(m,1h),7.85
–
7.82(m,1h),7.50
–
7.47(m,1h),7.46
–
7.43(m,2h),7.37(ddd,j＝7.6,4.7,1.2hz,1h),7.29(dd,j＝7.6,1.7hz,1h),7.26
–
7.25(m,1h),7.24
–
7.21(m,2h),7.20
–
7.17(m,2h),6.88(d,j＝8.3hz,1h),6.80(d,j＝8.0hz,1h),3.70(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,157.6,150.4,147.9,137.5,137.2,135.8,135.7,131.0,130.0,129.6,129.4,129.2,128.3,127.9,126.4,126.1,124.1,123.2,122.3,120.5,109.0,56.0.hr-ms(esi)m/z calcd for:c
25h21
n2o
280
se

[m h]

461.0763,found 461.0763.
[0110][0111]
n-(2',4'-difluoro-6'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3qa,67％).
[0112]1h nmr(600mhz,cdcl3)δ＝10.01(s,1h),8.64(d,j＝8.3hz,1h),8.38(d,j＝4.8hz,1h),8.26(d,j＝7.7hz,1h),7.88
–
7.85(m,1h),7.55
–
7.53(m,1h),7.50
–
7.47(m,2h),7.41(ddd,j＝7.6,4.7,1.2hz,1h),7.38
–
7.34(m,1h),7.31
–
7.25(m,4h),6.80
–
6.76(m,1h),6.63
–
6.60(m,1h).
13
c nmr(150mhz,cdcl3)δ＝163.1(dd,j＝251.8,12.8hz),161.9,160.4(dd,j＝250.8,12.2hz),150.0,148.0,140.4(dd,j＝9.3,3.0hz),137.7,136.5,136.0,131.0,130.2,129.9,,129.3,127.6,126.4,124.4,123.9,122.4,121.0,120.8(d,j＝18.3hz),112.6(dd,j＝23.9,3.6hz),102.0(dd,j＝26.2 26.0hz).
19
f nmr(565mhz,cdcl3)δ＝-107.63
–‑
107.66(m),-109.02
–‑
109.06(m).hr-ms(esi)m/z calcd for:c
24h17
f2n2o
80
se

[m h]

467.0469,found 467.0472.
[0113][0114]
n-(3',5'-difluoro-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ra,68％).
[0115]1h nmr(600mhz,cdcl3)δ＝9.76(s,1h),8.51(d,j＝8.2hz,1h),8.37
–
8.34(m,1h),8.19(d,j＝7.8hz,1h),7.85
–
7.82(m,1h),7.45
–
7.42(m,1h),7.39(ddd,j＝7.5,4.8,1.2hz,1h),7.13
–
7.09(m,3h),7.04
–
7.03(m,1h),7.02
–
6.97(m,3h),6.93
–
6.91(m,2h).
13
c nmr(150mhz,cdcl3)δ＝163.6(dd,j＝247.8,13.1hz),163.5(dd,j＝252.2,13.0hz),161.7,149.8,148.0,146.2(dd,j＝10.1,2.8hz),137.6,135.1,132.0,130.9,130.8,129.9,129.4,128.9,127.1,126.4,123.9,122.3,120.6,114.8(dd,j＝22.4,4.5hz),114.6(dd,j＝21.3,3.7hz),104.3(dd,j＝29.4,25.4hz).
19
f nmr(565mhz,cdcl3)δ＝-92.03
–‑
92.07(m),-107.77
–‑
107.82(m).hr-ms(esi)m/z calcdfor:c
24h17
f2n2o
80
se

[m h]

467.0469,found 467.0475.
[0116][0117]
n-(2-(3-(phenylselanyl)thiophen-2-yl)phenyl)picolinamide(3sa,56％).
[0118]1h nmr(600mhz,cdcl3)δ＝10.18(s,1h),8.61
–
8.59(m,1h),8.41
–
8.40(m,1h),
8.24(d,j＝7.8hz,1h),7.86
–
7.83(m,1h),7.48
–
7.45(m,2h),7.40(ddd,j＝7.5,4.8,1.1hz,1h),7.29
–
7.27(m,3h),7.15
–
7.13(m,1h),7.11(d,j＝5.3hz,1h),7.10
–
7.07(m,1h),7.06
–
7.04(m,1h),7.04
–
7.02(m,1h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.0,148.1,138.6,137.6,136.5,133.2,132.4,131.9,131.3,130.0,129.0,127.2,127.1,126.3,125.2,124.1,123.8,122.4,120.6.hr-ms(esi)m/z calcd for:c
22h17
n2os
80
se

[m h]

437.0221,found 437.0225.
[0119][0120]
n-(2-(3-(phenylselanyl)pyridin-4-yl)phenyl)picolinamide(3ta,68％).
[0121]1h nmr(600mhz,cdcl3)δ＝9.87(s,1h),8.57
–
8.51(m,3h),8.38
–
8.36(m,1h),8.23(d,j＝7.5hz,1h),7.87
–
7.84(m,1h),7.52
–
7.49(m,1h),7.42
–
7.41(m,1h),7.39
–
7.38(m,2h),7.25
–
7.22(m,2h),7.22
–
7.20(m,1h),7.18
–
7.14(m,3h).
13
c nmr(150mhz,cdcl3)δ＝162.0,152.3,149.8,148.2,148.1,147.4,137.7,135.1,134.5,131.5,129.9,129.7,129.6,129.4,128.5,128.1,126.5,125.5,124.5,122.4,121.4.hr-ms(esi)m/z calcd for:c
23h18
n3o
80
se

[m h]

432.0610,found 432.0612.
[0122][0123]
n-(2-(3-(phenylselanyl)naphthalen-2-yl)phenyl)picolinamide(3ua,79％).
[0124]1h nmr(600mhz,cdcl3)δ＝10.07(s,1h),8.59(d,j＝8.3hz,1h),8.20(d,j＝7.8hz,1h),8.10
–
8.08(m,1h),7.80
–
7.77(m,4h),7.68(d,j＝6.9hz,1h),7.51
–
7.45(m,3h),7.42
–
7.41(m,2h),7.29
–
7.24(m,3h),7.20
–
7.16(m,3h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.1,147.9,137.5,136.8,135.7,135.2,133.8,132.5,132.5,131.7,130.8,130.7,130.1,129.8,129.4,129.2,128.2,128.0,127.1,126.8,126.3,126.1,124.0,122.3,120.8.hr-ms(esi)m/z calcd for:c
28h21
n2o
80
se

[m h]

481.0814,found 481.0817.
[0125][0126]
n-(4-chloro-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3va,81％,mono:di＝10.6:1).
[0127]1h nmr(600mhz,cdcl3)δ＝9.99(s,1h),8.71(d,j＝1.9hz,1h),8.32
–
8.31(m,1h),8.22(d,j＝7.7hz,1h),7.86
–
7.83(m,1h),7.40
–
7.38(m,2h),7.38
–
7.37(m,1h),7.35
–
7.32(m,2h),7.30
–
7.27(m,1h),7.25
–
7.22(m,2h),7.16
–
7.15(m,1h),7.15
–
7.14(m,1h),7.14(d,j＝1.9hz,1h),7.13(s,1h).
13
c nmr(150mhz,cdcl3)δ＝162.0,149.7,148.0,137.8,137.7,136.3,135.1,134.8,134.6,132.2,131.1,131.0,130.0,129.6,129.4,129.4,128.2,127.5,126.5,124.0,122.4,120.4.hr-ms(esi)m/z calcd for:c
24h18
cln2o
80
se

[m h]

465.0267,found 465.0269.
[0128][0129]
n-(4-chloro-2',6'-bis(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3va',81％mono:di＝10.6:1).
[0130]1h nmr(600mhz,cdcl3)δ＝10.01(s,1h),8.78(d,j＝2.1hz,1h),8.33
–
8.31(m,1h),8.25(d,j＝7.8hz,1h),7.90
–
7.87(m,1h),7.42
–
7.39(m,5h),7.26
–
7.23(m,2h),7.20
–
7.18(m,2h),7.18
–
7.15(m,3h),7.09(d,j＝8.1hz,1h),7.07
–
7.05(m,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,149.8,147.9,137.7,136.7,136.4,136.3,135.6,131.5,130.0,129.5,129.5,129.3,129.2,128.5,128.2,126.5,124.4,122.5,120.5.hr-ms(esi)m/z calcd for:c
30h22
cln2o
80
se
2
[m h]

620.9746,found 620.9740.
[0131][0132]
n-(5-chloro-2'-(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3wa,82％,mono:di＝8.1:1).
[0133]1h nmr(600mhz,cdcl3)δ＝9.97(s,1h),8.56(d,j＝9.1hz,1h),8.33
–
8.30(m,1h),8.21(d,j＝7.8hz,1h),7.85
–
7.82(m,1h),7.41(dd,j＝8.8,2.5hz,1h),7.39
–
7.35(m,4h),7.33(dd,j＝7.4,1.4hz,1h),7.30
–
7.28(m,1h),7.25
–
7.24(m,1h),7.24
–
7.21(m,1h),7.17
–
7.16(m,1h),7.16
–
7.13(m,2h).
13
c nmr(150mhz,cdcl3)δ＝162.0,149.8,148.0,137.7,137.6,135.1,135.1,134.3,134.0,133.3,132.3,130.9,130.1,129.5,129.4,129.0,128.9,128.2,127.5,126.4,122.4,121.7.hr-ms(esi)m/z calcd for:c
24h18
cln2o
80
se

[m h]

465.0267,found 465.0270.
[0134][0135]
n-(5-chloro-2',6'-bis(phenylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3wa',82％,mono:di＝8.1:1).
[0136]1h nmr(600mhz,cdcl3)δ＝9.99(s,1h),8.65(d,j＝8.9hz,1h),8.33
–
8.31(m,1h),8.24(d,j＝7.7hz,1h),7.88
–
7.86(m,1h),7.48
–
7.45(m,1h),7.42
–
7.39(m,5h),7.26
–
7.24(m,2h),7.19
–
7.15(m,4h),7.10
–
7.09(m,3h),7.07
–
7.05(m,1h).
13
c nmr(150mhz,cdcl3)δ＝161.9,149.8,147.9,137.7,136.7,136.4,136.3,135.6,135.6,131.5,130.0,129.5,129.3,129.2,128.5,128.2,126.5,124.4,122.5,120.5.hr-ms(esi)m/z calcd for:c
30h22
cln2o
80
se
2
[m h]

620.9746,found 620.9741.
[0137][0138]
n-(5'-methyl-2'-(o-tolylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3ab,77％).
[0139]1h nmr(600mhz,cdcl3)δ＝10.01(s,1h),8.60(d,j＝8.4hz,1h),8.33
–
8.32(m,1h),8.24
–
8.21(m,1h),7.85
–
7.82(m,1h),7.46
–
7.43(m,1h),7.38
–
7.34(m,2h),7.21
–
7.18(m,1h),7.18
–
7.15(m,1h),7.15
–
7.13(m,1h),7.13
–
7.11(m,2h),7.11
–
7.07(m,2h),6.93
–
6.90(m,1h),2.34(s,3h),2.16(s,3h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.2,147.9,141.5,139.0,137.5,137.1,135.9,135.3,132.0,131.8,130.8,130.2,130.2,130.2,130.1,130.0,129.0,128.4,126.6,126.2,124.0,122.3,120.5,22.5,21.1.hr-ms(esi)m/z calcd for:c
26h23
n2o
80
se

[m h]

459.0970,found 459.0973.
[0140][0141]
n-(2'-((2-fluorophenyl)selanyl)-5'-methyl-[1,1'-biphenyl]-2-yl)picolinamide(3ac,91％).
[0142]1h nmr(600mhz,cdcl3)δ＝9.99(s,1h),8.59(d,j＝8.2hz,1h),8.33(d,j＝4.6hz,1h),8.21(d,j＝7.7hz,1h),7.84
–
7.81(m,1h),7.46
–
7.42(m,1h),7.38
–
7.35(m,2h),7.21
–
7.17(m,2h),7.17
–
7.12(m,4h),6.92
–
6.90(m,1h),6.82
–
6.80(m,1h),2.36(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,161.8(d,j＝244.6hz),150.1,148.0,140.0,138.2,137.5,135.7,135.3,133.7,131.9,131.9,130.2,130.1,129.8(d,j＝7.7hz),129.0,128.1,
126.2,124.7(d,j＝3.8hz),123.9,122.3,120.4,117.7(d,j＝21.8hz),115.6(d,j＝23.3hz),21.1.
19
f nmr(565mhz,cdcl3)δ＝-102.50
–‑
102.55(m).hr-ms(esi)m/z calcd for:c
25h20
fn2o
80
se

[m h]

463.0719,found 463.0720.
[0143][0144]
n-(2'-((2-bromophenyl)selanyl)-5'-methyl-[1,1'-biphenyl]-2-yl)picolinamide(3ad,88％).
[0145]1h nmr(600mhz,cdcl3)δ＝9.98(s,1h),8.57(d,j＝8.2hz,1h),8.34(d,j＝4.9hz,1h),8.21(d,j＝7.7hz,1h),7.84
–
7.81(m,1h),7.49(d,j＝8.0hz,1h),7.41
–
7.36(m,3h),7.23(s,1h),7.20(d,j＝8.0hz,1h),7.16
–
7.15(m,1h),7.12
–
7.10(m,1h),7.07(d,j＝7.7hz,1h),6.94
–
6.92(m,1h),6.87
–
6.84(m,1h),2.39(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.8,150.1,147.9,141.3,139.1,137.6,135.6,135.2,135.2,133.3,132.8,132.2,132.1,130.4,130.1,129.0,128.3,128.1,127.6,126.2,126.0,123.8,122.3,120.4,21.2.hr-ms(esi)m/z calcd for:c
25h20
brn2o
80
se

[m h]

522.9919,found 522.9920.
[0146][0147]
n-(2'-((4-methoxyphenyl)selanyl)-5'-methyl-[1,1'-biphenyl]-2-yl)picolinamide(3ae,68％).1hnmr(600mhz,cdcl3)δ＝10.04(s,1h),8.61(d,j＝8.3hz,1h),8.34
–
8.32(m,1h),8.23(d,j＝7.8hz,1h),7.84
–
7.82(m,1h),7.48
–
7.45(m,1h),7.36(ddd,j＝7.6,4.7,1.2hz,1h),7.35
–
7.32(m,2h),7.23(dd,j＝7.5,1.7hz,1h),7.20
–
7.17(m,1h),7.12(d,j＝8.1hz,1h),7.08
–
7.07(m,1h),7.07
–
7.04(m,1h),6.71
–
6.69(m,2h),3.75(s,3h),2.31(s,3h).
13
c nmr(150mhz,cdcl3)δ＝162.0,159.9,150.3,147.9,138.1,137.5,137.4,136.7,135.3,132.0,131.7,131.6,131.0,130.3,129.9,129.0,126.2,124.0,122.3,120.5,119.6,115.0,55.3,21.0.hr-ms(esi)m/z calcd for:c
26h23
n2o
280
se

[m h]

475.0919,found 475.0925.
[0148][0149]
n-(5'-methyl-2'-(p-tolylselanyl)-[1,1'-biphenyl]-2-yl)picolinamide(3af,65％).
[0150]1h nmr(600mhz,cdcl3)δ＝10.03(s,1h),8.60(d,j＝8.3hz,1h),8.39
–
8.33(m,
1h),8.24
–
8.22(m,1h),7.85
–
7.82(m,1h),7.50
–
7.43(m,1h),7.37(ddd,j＝7.0,4.5,0.9hz,1h),7.31
–
7.27(m,2h),7.24
–
7.16(m,3h),7.14
–
7.06(m,2h),6.96
–
6.94(m,2h),2.32(s,3h),2.27(s,3h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.3,147.9,138.7,138.0,137.5,137.0,135.3,135.2,132.1,131.8,131.6,131.0,130.3,130.1,129.9,129.0,126.2,126.2,124.0,122.3,120.5,21.3,21.0.hr-ms(esi)m/z calcd for:c
26h23
n2o
80
se

[m h]

459.0970,found 459.0976.
[0151][0152]
n-(2'-((4-fluorophenyl)selanyl)-5'-methyl-[1,1'-biphenyl]-2-yl)picolinamide(3ag,52％).
[0153]1h nmr(600mhz,cdcl3)δ＝9.98(s,1h),8.59(d,j＝8.3hz,1h),8.32
–
8.31(m,1h),8.23(d,j＝7.8hz,1h),7.86
–
7.83(m,1h),7.46
–
7.44(m,1h),7.37(ddd,j＝7.6,4.7,1.2hz,1h),7.33
–
7.30(m,2h),7.24(d,j＝7.9hz,1h),7.16(s,1h),7.16
–
7.14(m,1h),7.12
–
7.10(m,2h),6.82
–
6.78(m,2h),2.34(s,3h).
13
c nmr(150mhz,cdcl3)δ＝162.8(d,j＝244.5hz),161.9,150.2,147.9,139.1,137.6,137.6,136.9(d,j＝8.0hz),135.2,132.3,131.9,131.9,130.5,130.2,130.0,129.0,126.2,124.8(d,j＝3.4hz),124.0,122.4,120.5,116.4(d,j＝21.6hz),21.1.
19
f nmr(565mhz,cdcl3)δ＝-113.54
–‑
113.58(m).hr-ms(esi)m/z calcd for:c
25h20
fn2o
80
se

[m h]

463.0719,found 463.0724.
[0154][0155]
n-(2'-((3-bromophenyl)selanyl)-5'-methyl-[1,1'-biphenyl]-2-yl)picolinamide(3ah,54％).
[0156]1h nmr(600mhz,cdcl3)δ＝9.98(s,1h),8.57(d,j＝8.3hz,1h),8.36(d,j＝3.4hz,1h),8.22(d,j＝7.8hz,1h),7.84
–
7.81(m,1h),7.45
–
7.41(m,2h),7.39
–
7.36(m,2h),7.26(d,j＝8.1hz,1h),7.22
–
7.20(d,j＝7.8hz,1h),7.16
–
7.12(m,4h),6.94
–
6.92(m,1h),2.36(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,150.1,148.1,139.9,138.3,137.6,136.3,135.2,133.5,132.7,132.5,132.1,131.9,130.6,130.4,130.2,130.2,129.3,129.0,126.3,123.9,122.9,122.3,120.4,21.1.hr-ms(esi)m/z calcd for:c
25h20
brn2o
80
se

[m h]

522.9919,found 522.9920.
[0157][0158]
n-(2'-((3-fluorophenyl)selanyl)-5'-methyl-[1,1'-biphenyl]-2-yl)picolinamide(3ai,77％).
[0159]1h nmr(600mhz,cdcl3)δ＝9.97(s,1h),8.56(d,j＝8.0hz,1h),8.37
–
8.35(m,1h),8.22(d,j＝7.8hz,1h),7.85
–
7.82(m,1h),7.45
–
7.42(m,1h),7.40
–
7.37(m,2h),7.17
–
7.13(m,4h),7.08
–
7.04(m,2h),7.04
–
7.01(m,1h),6.84
–
6.81(m,1h),2.37(s,3h).
13
c nmr(150mhz,cdcl3)δ＝162.8(d,j＝247.5hz),161.9,150.1,148.0,140.1,138.4,137.6,135.2,133.8,132.9(d,j＝6.8hz),132.1,132.0,130.3,130.2,130.2,129.2,129.1,129.0,126.3,123.9,122.3,120.5,120.3(d,j＝22.2hz),114.4(d,j＝21.3hz),21.2.
19
f nmr(565mhz,cdcl3)δ＝-111.93
–‑
111.97(m).hr-ms(esi)m/z calcd for:c
25h20
fn2o
80
se

[m h]

463.0719,found 463.0726.
[0160][0161]
n-(2'-((3-chlorophenyl)selanyl)-5'-methyl-[1,1'-biphenyl]-2-yl)picolinamide(3aj,76％).
[0162]1h nmr(600mhz,cdcl3)δ＝9.98(s,1h),8.57(d,j＝8.2hz,1h),8.36(d,j＝4.7hz,1h),8.22(d,j＝7.8hz,1h),7.84
–
7.81(m,1h),7.46
–
7.42(m,1h),7.38
–
7.36(m,2h),7.29
–
7.26(m,1h),7.17
–
7.13(m,5h),7.11(d,j＝8.1hz,1h),7.02
–
6.97(m,1h),2.36(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,150.1,148.1,139.9,138.3,137.6,135.2,134.7,133.6,133.4,132.5,132.0,131.9,131.9,130.2,130.2,130.1,129.3,129.0,127.7,126.3,123.9,122.3,120.4,21.1.hr-ms(esi)m/z calcd for:c
25h20
cln2o
80
se

[m h]

479.0424,found 479.0427.
[0163][0164]
n-(2'-((2-bromophenyl)selanyl)-5'-methoxy-[1,1'-biphenyl]-2-yl)picolinamide(3bd,86％).
[0165]1h nmr(600mhz,cdcl3)δ＝9.99(s,1h),8.58
–
8.55(m,1h),8.38
–
8.36(m,1h),8.22
–
8.19(m,1h),7.85
–
7.82(m,1h),7.67
–
7.64(m,1h),7.43
–
7.40(m,1h),7.38(dd,j＝7.4,4.1hz,1h),7.35
–
7.32(m,1h),7.14
–
7.13(m,1h),7.12
–
7.08(m,1h),7.01
–
6.98(m,
2h),6.92
–
6.88(m,2h),6.83
–
6.79(m,1h),3.82(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.8,160.6,150.0,148.0,143.9,138.7,137.6,136.2,135.1,132.7,132.2,131.8,129.9,129.1,127.5,127.5,126.3,124.6,123.8,122.3,121.4,120.4,116.5,116.2,55.7.hr-ms(esi)m/z calcd for:c
25h20
brn2o
280
se

[m h]

538.9868,found 538.9870.
[0166][0167]
n-(6'-((2-bromophenyl)selanyl)-[1,1':3',1
”‑
terphenyl]-2-yl)picolinamide(3gd,92％).
[0168]1h nmr(600mhz,cdcl3)δ＝10.13(s,1h),8.62(d,j＝7.2hz,1h),8.28
–
8.25(m,1h),8.22(d,j＝7.8hz,1h),7.84
–
7.81(m,1h),7.64(d,j＝2.1hz,1h),7.63
–
7.61(m,1h),7.61
–
7.59(m,2h),7.56(d,j＝8.2hz,1h),7.48
–
7.45(m,2h),7.42
–
7.40(m,2h),7.36
–
7.32(m,2h),7.27(dd,j＝7.6,1.6hz,1h),7.26
–
7.24(m,1h),7.18
–
7.16(m,1h),7.03
–
7.00(m,1h),6.95
–
6.92(m,1h).
13
c nmr(150mhz,cdcl3)δ＝161.9,150.0,148.0,141.4,140.9,140.0,137.6,135.3,134.9,134.5,134.2,133.1,131.6,130.2,129.9,129.3,129.0,129.0,128.8,128.0,127.9,127.8,127.1,127.1,126.3,124.0,122.3,120.5.hr-ms(esi)m/z calcd for:c
30h22
brn2o
80
se

[m h]

585.0075,found 585.0132.
[0169][0170]
n-(2'-((2-bromophenyl)selanyl)-4'-methoxy-[1,1'-biphenyl]-2-yl)picolinamide(3id,87％).1hnmr(600mhz,cdcl3)δ＝9.99(s,1h),8.56(dd,j＝8.3,1.1hz,1h),8.37
–
8.36(m,1h),8.21
–
8.20(m,1h),7.85
–
7.82(m,1h),7.65(dd,j＝8.1,0.9hz,1h),7.43
–
7.40(m,1h),7.38(ddd,j＝7.6,4.8,1.1hz,1h),7.34(dd,j＝7.8,1.4hz,1h),7.14
–
7.13(m,1h),7.11
–
7.08(m,1h),7.00
–
6.98(m,2h),6.92
–
6.88(m,2h),6.82
–
6.79(m,1h),3.82(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.8,160.6,150.0,148.0,143.9,138.7,137.6,136.2,135.1,132.7,132.2,131.8,129.9,129.1,127.5,127.5,126.3,124.6,123.8,122.3,121.4,120.4,116.5,116.2,55.7.hr-ms(esi)m/z calcd for:c
25h20
brn2o
280
se

[m h]

538.9868,found 538.9866.
[0171][0172]
n-(2-(3-((2-bromophenyl)selanyl)naphthalen-2-yl)phenyl)picolinamide(3ud,75％).
[0173]1h nmr(600mhz,cdcl3)δ＝10.04(s,1h),8.58(d,j＝7.3hz,1h),8.18(d,j＝6.9hz,1h),8.07
–
8.06(m,1h),8.02(s,1h),7.88(s,1h),7.84(dd,j＝6.4,3.2hz,1h),7.79
–
7.76(m,2h),7.55
–
7.51(m,2h),7.48
–
7.42(m,2h),7.29
–
7.24(m,1h),7.24
–
7.20(m,1h),7.18
–
7.12(m,2h),7.01
–
6.98(m,1h),6.92
–
6.89(m,1h).
13
c nmr(150mhz,cdcl3)δ＝161.9,150.0,147.9,137.9,137.5,135.6,134.4,134.1,133.9,133.1,133.0,131.6,130.5,130.2,129.2,128.7,128.1,127.8,127.4,127.0,127.0,126.9,126.1,123.9,122.3,120.6.hr-ms(esi)m/z calcd for:c
28h20
brn2o
80
se

[m h]

558.9919,found 558.9919.
[0174]
二、本发明中生成硫化的2-氨基联苯类化合物a的反应通式：
[0175][0176]
具体化合物a的合成参照如下实施例。
[0177]
实施例3
[0178]
合成本发明的硫化的化合物5aa：
[0179][0180]
在封管中加入n-(3'-甲基-[1，1'-联苯]-2-基)吡啶甲酰胺(1a)(57.7mg,0.20mmol)，二苯基二硫醚(2a)(43.7mg,0.2mmol)，pd(tfa)2(6.6mg,0.02mmol),agoac(66.8mg,2.0mmol)在氮气保护下加入干燥甲苯(2ml)，140℃反应24h得混合液体，反应结束后添加饱和氯化胺溶液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＝30/1，15/1)分离纯化得到5aa(56.3mg，71％)。
[0181][0182]
n-(5'-methyl-2'-(phenylthio)-[1,1'-biphenyl]-2-yl)picolinamide(5aa).
[0183]1h nmr(600mhz,cdcl3)δ＝10.02(s,1h),8.54(d,j＝8.1hz,1h),8.37(d,j＝4.6hz,1h),8.23(d,j＝7.6hz,1h),7.85
–
7.82(m,1h),7.43
–
7.40(m,1h),7.39
–
7.37(m,1h),7.27
–
7.25(m,1h),7.20
–
7.15(m,4h),7.14
–
7.12(m,2h),7.12
–
7.07(m,3h),2.36(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,150.2,147.9,138.8,137.6,137.6,135.5,135.3,133.3,132.1,131.8,131.8,131.4,130.4,129.9,129.0,128.8,127.1,126.2,124.0,122.4,120.6,21.1.hr-ms(esi)m/z calcd for:c
25h21
n2os

[m h]

397.1369,found 397.1372.
[0184]
实施例4
[0185]
根据前述合成通式的反应条件，改变2-氨基联苯类底物，可得以下硫化的2-氨基联苯化合物：
[0186][0187]
n-(5'-methoxy-2'-(phenylthio)-[1,1'-biphenyl]-2-yl)picolinamide(5ba,48％).
[0188]1h nmr(600mhz,cdcl3)δ＝9.98(s,1h),8.53
–
8.52(m,1h),8.38
–
8.37(m,1h),8.22
–
8.21(m,1h),7.85
–
7.82(m,1h),7.47(d,j＝8.7hz,1h),7.43
–
7.40(m,1h),7.40
–
7.37(m,1h),7.13
–
7.09(m,2h),7.07
–
7.05(m,2h),7.04
–
7.01(m,3h),6.97(dd,j＝8.7,2.9hz,1h),6.90(d,j＝2.8hz,1h),3.80(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,159.8,150.2,148.0,141.9,137.6,137.0,135.4,135.2,131.4,130.2,130.2,128.9,128.8,128.8,126.4,126.2,123.9,122.4,120.5,116.4,115.7,55.7.hr-ms(esi)m/z calcd for:c
25h21
n2o2s

[m h]

413.1318,found 413.1323.
[0189][0190]
n-(5'-chloro-2'-(phenylthio)-[1,1'-biphenyl]-2-yl)picolinamide(5ea,53％).
[0191]1h nmr(600mhz,cdcl3)δ＝10.02(s,1h),8.54(d,j＝8.2hz,1h),8.40(d,j＝4.4hz,1h),8.25
–
8.24(m,1h),7.87
–
7.84(m,1h),7.48
–
7.45(m,1h),7.41(ddd,j＝7.5,
4.7,1.2hz,1h),7.30(d,j＝2.3hz,1h),7.29
–
7.26(m,2h),7.26(s,1h),7.23
–
7.20(m,1h),7.20
–
7.16(m,4h),7.13(d,j＝8.4hz,1h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.1,148.0,139.3,137.7,136.8,135.2,133.6,133.2,132.6,131.2,131.1,130.2,129.9,129.5,129.4,129.1,128.1,126.4,124.3,122.5,121.0.hr-ms(esi)m/z calcd for:c
24h18
cln2os

[m h]

417.0823,found 417.0827.
[0192][0193]
n-(5'-bromo-2'-(phenylthio)-[1,1'-biphenyl]-2-yl)picolinamide(5fa,57％).
[0194]1h nmr(600mhz,cdcl3)δ＝10.04(s,1h),8.54(d,j＝8.3hz,1h),8.44
–
8.39(m,1h),8.25(d,j＝7.8hz,1h),7.87
–
7.85(m,1h),7.50
–
7.44(m,2h),7.43
–
7.40(m,2h),7.30
–
7.23(m,3h),7.22(d,j＝6.2hz,1h),7.20
–
7.18(m,4h),7.05
–
7.03(m,1h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.1,148.0,139.4,137.7,137.6,135.2,133.9,133.4,133.3,132.0,131.1,130.3,129.8,129.5,129.4,128.2,126.4,124.3,122.5,121.0,120.4.hr-ms(esi)m/z calcd for:c
24h18
brn2os

[m h]

461.0318,found 461.0316.
[0195][0196]
n-(4'-methoxy-2'-(phenylthio)-[1,1'-biphenyl]-2-yl)picolinamide(5ia,60％).
[0197]1h nmr(600mhz,cdcl3)δ＝9.98(s,1h),8.53
–
8.52(m,1h),8.38
–
8.37(m,1h),8.22(d,j＝7.8hz,1h),7.85
–
7.83(m,1h),7.47(d,j＝8.7hz,1h),7.43
–
7.40(m,1h),7.40
–
7.37(m,1h),7.14
–
7.10(m,2h),7.08
–
7.05(m,2h),7.04
–
7.01(m,3h),6.97(dd,j＝8.7,2.9hz,1h),6.90(d,j＝2.8hz,1h),3.80(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,159.8,150.1,148.0,141.8,137.6,137.0,135.4,135.2,131.4,130.2,128.9,128.8,128.8,126.4,126.3,126.3,123.9,122.4,120.5,116.4,115.7,55.7.hr-ms(esi)m/z calcd for:c
25h21
n2o2s

[m h]

413.1318,found413.1321.
[0198][0199]
n-(2-(3-(phenylthio)naphthalen-2-yl)phenyl)picolinamide(5ua,46％).
[0200]1h nmr(600mhz,cdcl3)δ＝10.07(s,1h),8.53(d,j＝8.3hz,1h),8.20(d,j＝7.8hz,1h),8.16
–
8.12(m,1h),7.80
–
7.77(m,3h),7.72
–
7.71(m,2h),7.50
–
7.45(m,3h),7.31
–
7.22(m,4h),7.21
–
7.13(m,4h).
13
c nmr(150mhz,cdcl3)δ＝162.1,150.1,147.9,137.5,136.2,135.7,135.6,134.2,133.6,133.0,132.4,131.0,130.8,130.7,129.3,129.2,129.1,128.0,127.8,127.2,126.9,126.4,126.1,124.1,122.3,120.9.hr-ms(esi)m/z calcd for:c
28h21
n2os

[m h]

433.1369,found433.1368.
[0201][0202]
n-(2'-((2-bromophenyl)thio)-5'-methyl-[1,1'-biphenyl]-2-yl)picolinamide(5ab,58％).
[0203]1h nmr(600mhz,cdcl3)δ＝9.98(s,1h),8.53(d,j＝7.3hz,1h),8.35
–
8.34(m,1h),8.21(d,j＝7.6hz,1h),7.84
–
7.81(m,1h),7.42
–
7.35(m,3h),7.32(d,j＝8.1hz,1h),7.24
–
7.18(m,2h),7.15(d,j＝7.4hz,1h),7.11
–
7.09(m,1h),7.05
–
6.99(m,1h),6.92
–
6.89(m,2h),2.38(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,150.2,148.0,140.0,138.6,137.7,137.6,135.3,133.4,133.1,132.4,132.0,131.3,131.0,130.2,130.2,128.9,127.9,127.6,126.2,125.1,123.9,122.4,120.5,21.2.hr-ms(esi)m/z calcd for:c
25h20
brn2os

[m h]

475.0474,found 475.0477.
[0204][0205]
n-(2'-((4-chlorophenyl)thio)-5'-methyl-[1,1'-biphenyl]-2-yl)picolinamide(5ac,73％).
[0206]1h nmr(600mhz,cdcl3)δ＝9.94(s,1h),8.54(d,j＝8.2hz,1h),8.34(d,j＝4.7hz,1h),8.22(d,j＝7.7hz,1h),7.86
–
7.83(m,1h),7.43
–
7.41(m,1h),7.40
–
7.38(m,1h),7.30(d,j＝8.0hz,1h),7.20(d,j＝8.2hz,1h),7.16(s,1h),7.13
–
7.11(m,2h),7.08
–
7.04(m,2h),7.04
–
6.98(m,2h),2.37(s,3h).
13
c nmr(150mhz,cdcl3)δ＝161.9,150.1,147.9,139.3,138.2,137.6,135.2,134.4,133.0,132.7,132.6,132.3,132.3,131.2,130.3,130.0,129.0,128.9,126.3,124.0,122.4,120.5,21.2.hr-ms(esi)m/z calcd for:c
25h20
cln2os

[m h]

431.0979,found 431.0988.
[0207]
[0208]
n-(5'-methyl-2'-(p-tolylthio)-[1,1'-biphenyl]-2-yl)picolinamide(5ad,73％).
[0209]1h nmr(600mhz,cdcl3)δ＝10.03(s,1h),8.55(d,j＝8.3hz,1h),8.37
–
8.36(m,1h),8.23(d,j＝7.7hz,1h),7.85
–
7.82(m,1h),7.45
–
7.42(m,1h),7.38(ddd,j＝7.6,4.7,1.2hz,1h),7.21
–
7.16(m,2h),7.15
–
7.14(m,1h),7.14
–
7.12(m,3h),7.10(s,1h),6.96
–
6.94(m,2h),2.34(s,3h),2.26(s,3h).
13
c nmr(150mhz,cdcl3)δ＝162.0,150.3,147.9,137.8,137.6,137.5,136.8,135.3,134.5,133.0,131.9,131.4,131.0,130.4,130.4,129.9,129.8,128.9,126.2,124.0,122.4,120.6,21.2,21.1.hr-ms(esi)m/z calcd for:c
26h23
n2os

[m h]

411.1526,found 411.1531.
[0210][0211]
n-(5'-methyl-2'-(thiophen-2-ylthio)-[1,1'-biphenyl]-2-yl)picolinamide(5ae,54％).
[0212]1h nmr(600mhz,cdcl3)δ＝10.09(s,1h),8.61(dd,j＝8.3,1.2hz,1h),8.36
–
8.35(m,1h),8.25
–
8.24(m,1h),7.85
–
7.83(m,1h),7.50
–
7.46(m,1h),7.39
–
7.36(m,1h),7.36(dd,j＝5.4,1.2hz,1h),7.27(dd,j＝7.6,1.7hz,1h),7.23
–
7.20(m,1h),7.14
–
7.12(m,1h),7.08
–
7.07(m,1h),7.03(d,j＝8.2hz,1h),7.01(dd,j＝3.6,1.3hz,1h),6.94(dd,j＝5.3,3.5hz,1h),2.33(s,3h).
13
c nmr(150mhz,cdcl3)δ＝162.1,150.2,148.1,137.5,136.5,136.3,135.9,135.6,135.5,131.7,131.3,131.0,130.6,130.5,129.9,129.1,127.9,127.8,126.2,124.2,122.3,120.7,21.0.hr-ms(esi)m/z calcd for:c
23h19
n2os
2
[m h]

403.0933,found 403.0936.
[0213]
三、应用前述制备的硒/硫化2-氨基联苯类化合物a合成八元环化合物b的反应通式如下：
[0214][0215]
实施例5
[0216]
硒化的八元环化合物2-methyl-10h-tribenzo[b,e,g][1,4]selenazocine(7a)的合成：
[0217][0218]
将0.1mmol硒化邻氨基联苯类底物(3ad)(52.2mg,0.1mmol)，氢氧化钠(60.0mg,1.5mmol)，1.5ml乙醇加到反应管中，置于80℃反应12h，反应结束后添加5ml水，用二氯甲烷萃取三次，合并有机层，无水na2so4干燥有机层，过滤，浓缩，得到胺的粗产物，将胺的粗产物、cui(9.5mg,0.05mmol)和cs2co3(65.2mg,0.2mmol)加到反应管中，在氮气保护下加入乙二醇(2ml)，125℃反应12h。反应结束后添加饱和氯化胺溶液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＝80/1，40/1)，分离纯化得到7a(16.2mg,48％)。
[0219][0220]
2-methyl-10h-tribenzo[b,e,g][1,4]selenazocine(7a，48％).
[0221]1h nmr(600mhz,d
6-dmso)δ＝7.68(d,j＝7.8hz,1h),7.43
–
7.40(m,1h),7.34(dd,j＝7.7,1.6hz,1h),7.33
–
7.30(m,2h),7.26(dd,j＝7.5,1.7hz,1h),7.19
–
7.15(m,2h),7.09
–
7.06(m,1h),7.01(s,1h),6.98(dd,j＝8.0,1.4hz,1h),6.71
–
6.68(m,1h),2.38(s,3h).
13
c nmr(150mhz,d
6-dmso)δ＝148.5,147.6,144.6,139.6,139.2,136.3,133.7,129.7,129.3,128.5,128.2,128.1,127.9,126.1,122.5,120.0,119.8,115.5,20.9.hr-ms(esi)m/z calcd for:c
19h16n80
se

[m h]

338.0442,found 338.0446.
[0222]
实施例6
[0223]
根据前述反应条件，更换硒化邻氨基联苯类底物，可得到各硒化2-氨基联苯类化合物：
[0224][0225]
2-methoxy-10h-tribenzo[b,e,g][1,4]selenazocine(7b,45％).
[0226]1h nmr(600mhz,d
6-dmso)δ＝7.72
–
7.68(m,1h),7.44
–
7.40(m,1h),7.34(dd,j＝7.7,1.5hz,1h),7.32(dd,j＝7.3,1.2hz,1h),7.30
–
7.28(m,1h),7.19
–
7.15(m,1h),7.10
–
7.05(m,1h),7.05
–
7.03(m,1h),7.01
–
7.00(m,1h),7.00
–
6.97(m,1h),6.93(dd,j＝8.5,3.0hz,1h),6.71
–
6.68(m,1h),3.81(s,3h).
13
c nmr(150mhz,d
6-dmso)δ＝160.4,149.2,148.4,144.5,139.2,137.6,133.5,129.4,128.6,128.1,127.8,126.1,120.0,119.9,
116.7,115.7,114.4,113.3,55.4.hr-ms(esi)m/z calcd for:c
19h16
no
80
se

[m h]

354.0392,found 354.0394.
[0227][0228]
2-phenyl-10h-tribenzo[b,e,g][1,4]selenazocine(7c,47％).
[0229]1h nmr(600mhz,d
6-dmso)δ＝7.89(d,j＝7.9hz,1h),7.75
–
7.74(m,2h),7.74
–
7.73(m,1h),7.65(dd,j＝8.0,2.2hz,1h),7.49
–
7.47(m,2h),7.46
–
7.44(m,1h),7.41
–
7.38(m,3h),7.36
–
7.34(m,1h),7.22
–
7.19(m,1h),7.12
–
7.07(m,2h),7.02(dd,j＝8.0,1.4hz,1h),6.74
–
6.71(m,1h).
13
c nmr(150mhz,d
6-dmso)δ＝148.4,148.3,144.5,141.7,139.3,139.2,137.1,133.7,129.5,129.1,128.6,128.3,128.0,127.2,127.0,127.0,126.2,125.6,124.9,120.1,120.0,115.4.hr-ms(esi)m/z calcd for:c
24h18n80
se

[m h]

400.0599,found 400.0591.
[0230][0231]
3-methoxy-10h-tribenzo[b,e,g][1,4]selenazocine(7d,46％).
[0232]1h nmr(600mhz,d
6-dmso)δ＝7.41(d,j＝8.3hz,1h),7.39(dd,j＝7.6,1.6hz,1h),7.38
–
7.34(m,2h),7.31
–
7.29(m,1h),7.25
–
7.22(m,1h),7.18
–
7.15(m,1h),7.12
–
7.09(m,1h),7.09
–
7.07(m,1h),7.06
–
7.04(m,1h),7.01
–
6.99(m,1h),6.72
–
6.69(m,1h),3.78(s,3h).
13
cnmr(150mhz,d
6-dmso)δ＝159.3,148.4,144.1,140.0,139.2,133.8,129.0,128.4,128.3,128.2,128.1,126.4,126.1,121.2,120.0,119.8,115.6,115.1,55.4.hr-ms(esi)m/z calcd for:c
19h16
no
80
se

[m h]

354.0392,found 354.0392.
[0233][0234]
5h-dibenzo[b,e]naphtho[2,3-g][1,4]selenazocine(7e,53％).
[0235]1h nmr(600mhz,d
6-dmso)δ＝8.47(s,1h),8.03
–
8.00(m,2h),7.98(dd,j＝8.2,1.2hz,1h),7.61
–
7.58(m,1h),7.56
–
7.53(m,1h),7.48
–
7.45(m,1h),7.43
–
7.40(m,2h),7.39
–
7.36(m,1h),7.19(d,j＝7.7hz,1h),7.10
–
7.08(m,1h),7.02(d,j＝7.1hz,1h),6.95(s,1h),6.76
–
6.73(m,1h).
13
c nmr(150mhz,d
6-dmso)δ＝148.6,144.7,144.4,139.6,
136.3,133.5,133.4,133.2,129.5,128.8,128.4,127.9,127.8,127.6,127.4,126.4,126.3,125.6,125.0,120.5,120.1,117.9.hr-ms(esi)m/z calcd for:c
22h16n80
se

[m h]

374.0442,found 374.0446.
[0236]
实施例7
[0237]
八元环硫化的化合物2-methyl-10h-tribenzo[b,e,g][1,4]thiazocine(7f)的合成：
[0238]
将0.1mmol硫化邻氨基联苯类底物(5ab)(47.5mg,0.1mmol)，氢氧化钠(60.0mg,1.5mmol)，1.5ml乙醇加到反应管中，置于80℃反应12h，反应结束后添加5ml水，用二氯甲烷萃取三次，合并有机层，无水na2so4干燥有机层，过滤，浓缩，得到胺的粗产物，将胺的粗产物、cui(19.5mg,0.10mmol)和cs2co3(65.2mg,0.2mmol)加到反应管中，在氮气保护下加入乙二醇(2ml)，140℃反应12h。反应结束后添加饱和氯化胺溶液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＝40/1)分离纯化得到7f(19.4mg,67％)。
[0239][0240]
2-methyl-10h-tribenzo[b,e,g][1,4]thiazocine(7f,67％).
[0241]
3-1
h nmr(600mhz,d
6-dmso)δ＝7.54(d,j＝7.8hz,1h),7.44
–
7.41(m,1h),7.33
–
7.28(m,3h),7.26(dd,j＝7.7,1.6hz,1h),7.23(dd,j＝7.5,1.7hz,1h),7.22
–
7.21(m,1h),7.18(dd,j＝7.8,1.2hz,1h),7.07
–
7.04(m,1h),6.93(dd,j＝8.1,1.4hz,1h),6.69
–
6.67(m,1h),2.37(s,3h).
13
c nmr(150mhz,d
6-dmso)δ＝148.3,147.3,141.8,139.7,139.5,135.3,133.2,129.8,129.4,128.5,128.4,128.2,127.4,125.9,125.8,119.1,118.9,118.3,20.9.hr-ms(esi)m/z calcd for:c
19h16
ns

[m h]

290.0998,found 290.1000.
[0242]
实施例8
[0243]
钯催化c-h硒化反应，反应条件：1a(0.20mmol),2a(1.0equiv,0.20mmol),pd(tfa)2(5.0mol％),氧化剂(1.8equiv),溶剂(2.0ml),120℃,12h,氮气保护。对反应中不同溶剂，氧化剂，添加剂进行探索实验，结果如表1所示：
[0244][0245]
表1对硒化反应中不同溶剂，氧化剂，添加剂进行探索实验
[0246][0247][0248]
备注：在前述反应条件的基础上，编号21中氧化剂agoac的用量改变为1.5equiv；编号22中温度改变为100℃；编号23中不使用催化剂。
[0249]
实验结果显示，优选溶剂为phcf3，优选氧化剂为agoac，优选添加剂为tfa，该实验条件下硒化邻氨基联苯类底物3aa的产率最优，为93％。
[0250]
实施例9
[0251]
钯催化c-h硫化反应，反应条件：1a(0.20mmol),2a'(1.0equiv,0.20mmol),pd(tfa)2(10mol％),氧化剂(2.0equiv),溶剂(2.0ml),添加剂(50mol％)，140℃,24h,氮气保护。对反应中不同溶剂，氧化剂，添加剂进行探索实验，结果如表2所示：
[0252][0253]
表2对硫化反应中不同溶剂，氧化剂，添加剂进行探索实验
[0254][0255][0256]
备注：在前述反应条件的基础上，编号25中pd(tfa)2的用量为7.5mol％；编号26中氧化剂agoac的用量变为1.8equiv；编号27中温度变为130℃。
[0257]
实验结果显示，优选溶剂为甲苯，优选氧化剂为agoac，优选添加剂为naopiv，该实验条件下硫化邻氨基联苯类底物5aa的产率最优，为73％。
[0258]
实施例10
[0259]
cui催化八元环化合物的实验条件探索：结果如表2所示：
[0260][0261]
表2cui催化八元环的实验条件探索
[0262][0263]
[0264]
实验结果显示：在加热温度为125℃，实验时间为12小时，催化剂使用量为0.5eq，以cs2co3为碱，乙二醇为溶剂，得到最优结果，八元环化合物产率为48％。