CN114805239A - 一种三氟甲硒基化试剂的制备方法及其应用 - Google Patents
一种三氟甲硒基化试剂的制备方法及其应用 Download PDFInfo
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- CN114805239A CN114805239A CN202210365956.6A CN202210365956A CN114805239A CN 114805239 A CN114805239 A CN 114805239A CN 202210365956 A CN202210365956 A CN 202210365956A CN 114805239 A CN114805239 A CN 114805239A
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- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B47/00—Formation or introduction of functional groups not provided for in groups C07B39/00 - C07B45/00
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- C07C391/00—Compounds containing selenium
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
- C07D209/28—1-(4-Chlorobenzoyl)-2-methyl-indolyl-3-acetic acid, substituted in position 5 by an oxygen or nitrogen atom; Esters thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D209/82—Carbazoles; Hydrogenated carbazoles
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
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- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/24—Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
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- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
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- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
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Abstract
本发明涉及化合物制备领域,特别涉及一种三氟甲硒基化试剂的制备方法及其应用,所述的三氟甲硒基化试剂结构式如式1所示,该化合物是将式1所示化合物2与三氟甲硒基氯反应获得的;所述的三氟甲硒基化试剂可与芳环类或者芳杂环类化合物进行反应得到含有三氟甲硒基的化合物。该试剂具有反应条件温和、转化率高、收率高、生产成本低、适用的底物范围广,适合于复杂的天然产物或对酸敏感的药物的三氟甲基硒化反应。
Description
技术领域
本发明化合物合成领域,特别涉及一种三氟甲硒基化试剂的制备方法及其应用。
背景技术
由于氟原子具有最强的电负性,同时其原子半径接近氢的原子半径。在分子中引入氟原子可以显著的改变分子的物理化学性质及生物活性。含氟化合物具有较高的亲脂性、代谢稳定性、膜通透性和生物活性。这使得含氟化合物广泛应用于医药、化工、材料以及农药等方面。三氟甲硒基是含氟官能团中一类重要的基团,它具有很强的电负性以及非常好的脂溶性(π=1.29,介于三氟甲硫基与三幅甲氧基之间),所以将三氟甲硒基引入到有机小分子中能够产生非常重要的作用。
目前,在有机分子中引入三氟甲硒基的方法主要分为两类:间接法和直接法。间接合成方法是指对含硒化合物实现硒原子上的三氟甲基化。由于该方法需要提前制备含硒反应物导致步骤较为繁琐,反应条件苛刻,效率低,适用范围窄,所以近些年来发展的大多是直接法,即直接向分子中引入三氟甲硒基。目前直接法有亲核、亲电和自由基三氟甲硒基化反应这三种反应类型。
亲核三氟甲硒基化试剂中,使用最广泛的CF3Se源是福州大学翁志强课题组发展的联吡啶三氟甲硒基亚铜配物([(bpy)CuSeCF3]2)和Yagupolskii课题组发展的[Me4N+][-SeCF3]。[(bpy)CuSeCF3]2是利用三氟甲基三甲基硅烷、单质硒、氟化钾、在碘化亚铜和联毗咤的作用下以中等收率得到的,该配合物实现了烷基芳基杂芳基卤代物、α-溴-α,β-不饱和羰基化合物、炔丙基氯和烯丙基溴化物、3-碘-2-吡啶酮、乙烯基卤化物、酰氯、端炔、α-溴酮、芳香和脂肪族α-重氮酯、2-(2,2-二溴酰)(硫代)酚/苯胺和二氟乙酸乙酯的三氟甲硒基化反应。虽然该配合物适应底物范围广且产率良好,但制备该配合物需要使用大量的金属和配体,并且很多反应都需要加热到较高温度(100度以上),反应16小时,因此其应用受到了很大的限制。[Me4N+][-SeCF3]是通过三氟甲基三甲基硅烷、单质硒、四甲基氟化铵制备得到的。[Me4N+][-SeCF3]是一种在室温下不挥发、空气稳定的固体,这使得它成为一种吸引合成化学家的三氟甲硒基试剂。近年来,随着[Me4N+][-SeCF3]在三氟甲基硒化反应中的广泛应用,它已成为目前最重要的三氟甲基硒化试剂之一。随着该方法的发展,它已应用于过渡金属催化、无过渡金属和光催化三氟甲硒基化反应。
与亲核三氟甲硒基化试剂相比,亲电三氟甲基硒化试剂由于缺乏易于获取的试剂和方法,应用相对有限。历史上,CF3SeCl和CF3SeSeCF3被用作亲电CF3Se源,但它们的低沸点、挥发性和毒性限制了它们的应用。2017年,Billard、Tlili等人开发了一种新的亲电三氟甲硒基化试剂—TsSeCF3,该试剂是由甲基苯磺酸钠(TsNa)与原位形成的CF3SeCl反应获得的。该试剂实现了硼酸、末端炔烃、富电子含氮杂环芳烃、末端炔烃的双功能化和烯酮的三氟甲硒基化反应,但是该试剂制备时需要-78℃的低温操作,对于环境要求较高,且经过试验后发现其亲电能力相对较弱。
因此能否提供一种更加合适的三氟甲硒基化试剂成为本领域亟待解决的问题。
发明内容
本发明针对现有技术存在的诸多问题,提供了一种三氟甲硒基化试剂的制备方法及其应用,所述的三氟甲硒基化试剂结构式如式1所示,该化合物是将式1所示化合物2与三氟甲硒基氯反应获得的;所述的三氟甲硒基化试剂可与芳环类或者芳杂环类化合物进行反应得到含有三氟甲硒基的化合物。该试剂具有反应条件温和、转化率高、收率高、生产成本低、适用的底物范围广,适合于复杂的天然产物或对酸敏感的药物的三氟甲基硒化反应,克服了现有技术中引入三氟甲硒基的方法反应条件苛刻、转化率低、收率低、生产成本高、适用的底物有限等缺陷。
本发明的具体技术方案如下:
发明人首先提供了一种化合物1,结构式如下所示:
上述化合物1的制备方法为:
在有机溶剂中,将化合物2与三氟甲硒基氯进行反应,即可得到化合物1,其反应反应方程式如下:
其中所述的有机溶剂为本领域中该类反应的常规有机溶剂,只要不与反应物或产物进行反应即可,更进一步优选为卤代烃类溶剂,特别是氯代烃类溶剂,最优选为二氯甲烷;
所述有机溶剂与化合物2的体积质量比为1mL/g—100mL/g;所述的化合物2与三氟甲硒基氯的摩尔比值为1—5;所述的反应的温度为10℃—100℃,所述的反应的时间为1min—12h,反应终点一般采用本领域中的常规测试方法(例如TLC、HPLC或NMR)进行监测,一般以TLC无原料点为反应的终点;
在上述反应参数的基础上,进一步优选为所述的氯代烃类溶剂与化合物2的体积质量比为1mL/g—50mL/g;所述的化合物2与所述的三氟甲硒基氯的摩尔比值为1—2;所述的反应的温度为10℃—80℃;所述的反应的时间为10min—3h;在上述反应条件下,最终的收率可以达到最佳,在综合收率和反应成本的情况下,做出了上述的优选条件。
上述反应中M可以是H、Na、K、Ag,其中Ag的效果最好,对应的,化合物1的制备方法为:在有机溶剂中,将糖精钠与硝酸银进行取代反应,得到所述的化合物2d,然后继续制备获得化合物1,其反应方程式如下:
所述的有机溶剂选择与上述选择相同,且所述的有机溶剂与糖精钠的体积质量比为1mL/g—100mL/g,所述的硝酸银与糖精钠的摩尔比值为1—20,所述的取代反应的温度为10℃—80℃,所述的取代反应的时间为1min—12h,反应终点一般采用本领域中的常规测试方法(例如TLC、HPLC或NMR)进行监测,一般以TLC无原料点为反应的终点。
优选的所述的有机溶剂与所述的糖精钠的体积质量比为1mL/g—20mL/g;所述的硝酸银与糖精钠的摩尔比值为1—2,所述的取代反应的温度为50℃—80℃,所述的取代反应的时间为5—30min。
上述的化合物1作为三氟甲硒基化试剂的应用,步骤为:化合物1与芳环类或者芳杂环类化合物在有机溶剂中进行反应得到含有三氟甲硒基的化合物;
更具体的为:
将化合物1与芳环类或者芳杂环类化合物3在有机溶剂中进行取代反应,得到化合物4,其反应方程式如下:
其中,所述芳环类或者芳杂环类化合物3为芳环类化合物时,R为烷基、烷氧基、硅氧基、羟基、羰基、醛基、酯基、卤素、酰胺、胺基中的任意一种;当取代基为多个时,所述的取代相同或不同;
所述芳环类或者芳杂环类化合物3为芳杂环类化合物时,R1为氢原子、烷基、羰基、磺酰基中的任意一种,R2为氢原子、烷基中的任意一种,X为O或者S,R3为烷基;当取代基为多个时,所述的取代相同或不同。
基于上述条件,所述的芳环类或者芳杂环类化合物3为如下任一化合物:
上述反应中,所述的有机溶剂为烃类溶剂、卤代烃类溶剂、醚类溶剂、腈类溶剂、酮类溶剂、酰胺类溶剂、醇类溶剂中的一种;所述的有机溶剂与所述的化合物3的体积质量比为1mL/g—200mL/g,所述的化合物1与所述的化合物3的摩尔比值为1—3,所述的取代反应的温度为0℃—100℃,所述的取代反应的时间为1min—12h;
优选的,所述的烃类溶剂为三氟甲苯;所述的卤代烃类溶剂为1,2-二氯乙烷;所述的醚类溶剂为四氢呋喃;所述的腈类溶剂为乙腈;所述的酮类溶剂为丙酮;所述的酰胺类溶剂为N,N-二甲基甲酰胺;所述的醇类溶剂为三氟乙醇和六氟异丙醇;
所述的有机溶剂与所述的化合物3的体积质量比为1mL/g—100mL/g;所述的化合物1与化合物3的摩尔比值为1—1.2;所述的取代反应的温度为0℃—80℃;所述的取代反应的时间为1h—12h。
对应的获得的化合物4可以是:
本发明与现有技术相比,具有以下有益效果:
提供了一个基于糖精骨架的全新的三氟甲硒基化试剂化合物1及其合成方法,本发明的化合物1可以与芳环类或者芳杂环类化合物进行反应,制得含有三氟甲硒基的化合物。本发明的三氟甲硒基化试剂1高效、反应条件温和、转化率高、收率高、生产成本低、适用的底物范围广,且适合于复杂的天然产物或对酸敏感的药物的三氟甲基硒化反应。
附图说明
图1为本发明实施例1所制备的化合物的核磁谱图;
图2为本发明实施例15所制备的化合物的核磁谱图;
图3为本发明实施例17所制备的化合物的核磁谱图;
图4为本发明实施例18所制备的化合物的核磁谱图;
图5为本发明实施例19所制备的化合物的核磁谱图;
图6为本发明实施例20所制备的化合物的核磁谱图;
图7为本发明实施例21所制备的化合物的核磁谱图;
图8为本发明实施例27所制备的化合物的核磁谱图;
图9为本发明实施例33所制备的化合物的核磁谱图;
图10为本发明实施例40所制备的化合物的核磁谱图。
具体实施方式
下面结合实施例来进一步说明本发明,有必要在此指出的是以下实施例不能理解为对本发明保护范围的限制,如果该领域的技术熟练人员根据上述本发明内容对本发明做出一些非本质的改进和调整,仍属于本发明保护范围。所述的室温是指环境温度,为10℃—35℃;本发明所用试剂和原料均市售可得。
实施例1
三氟甲硒基化试剂化合物1的合成方法,其反应方程式如下:
其具体步骤如下:
糖精银(2d)合成参考(Dolenc,D.Synlett 2000,4,544-546),将AgNO3(25.5g)溶于150mL水中,加热至80℃,将糖精钠(37.06g)溶于150mL水中,缓慢滴加至AgNO3溶液中,反应30分钟,将白色沉淀过滤,用水和丙酮洗,避光下自然风干得到糖精银2d(产率为98%)。
在反应管中抽真空,充氩气,加入BnSeCF3(7.17g)、SO2Cl2(2.91mL)、DCM(10mL),室温反应3h,加入糖精银2d(17.4g)、DCM(50mL),室温下反应2h,颜色由黄色变为无色,以TLC监测到原料反应完全为反应终点。将混合物过滤(DCM冲洗),旋干为固体,用戊烷洗,抽滤,得到化合物1(产率为82%)。试剂1室温下为白色固体,可溶于二氯甲烷,氯仿,二甲基亚砜等有机溶剂。
上述化合物1的核磁谱图如图1所示,m.p.46.3-46.6℃,1H NMR(400MHz,Chloroform-d)δ8.17(d,J=7.6Hz,1H),8.03(d,J=7.7Hz,1H),7.97(t,J=7.5Hz,1H),7.91(t,J=7.4Hz,1H);19F NMR(376MHz,Chloroform-d)δ-38.77(s,3F);13C NMR(101MHz,Chloroform-d)δ159.5,138.5,135.9,134.8,126.8,126.4,122.6(q,J=340.3Hz),121.9.HRMS-ESI(m/z)calcd for C8H5F3NO3SSe(M+H):331.9102,found:331.9102。
实施例2
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法:空气氛围下,在反应管中加入化合物1(0.1980g,0.6mmol,1.2eq.),加入三氟乙醇(2mL)、2-羟基-4-甲氧基苯甲醛(0.0761g,0.5mmol,1.0eq.),室温下反应过夜,TLC监测反应结束,用NaHCO3洗,DCM萃取,有机层用无水硫酸钠干燥,过滤、浓缩至干燥,柱层析(PE)得到产物化合物4,白色固体(产率为91%),其核磁谱图信息如下:
m.p.73.9—74.4℃,1H NMR(400MHz,Chloroform-d)δ11.68(s,1H),9.75(s,1H),7.90(s,1H),6.52(s,1H),3.96(s,3H);19F NMR(376MHz,Chloroform-d)δ-36.18(s,3F);13CNMR(101MHz,Chloroform-d)δ194.05,166.66,166.48,144.99,122.23(q,J=334.1Hz),115.80,103.25,99.94,56.77.HRMS-ESI(m/z)calcd for C9H8F3O3Se(M+H):300.9585,found:300.9577。
实施例3
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1085g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为69%。
其核磁谱图信息如下:
m.p.69.8—70.2℃,A:B=10:1,1H NMR(400MHz,Chloroform-d)δ6.91(d,J=2.4Hz,1H),6.45(d,J=2.4Hz,1H),3.86(s,3H),3.84(s,3H).6.77(s,0.2H),3.88(s,0.6H).(A:B=10:1);19F NMR(376MHz,Chloroform-d)δ-35.73(s,3F).-34.99.(A:B=10:1);13C NMR(126MHz,Chloroform-d)δ163.38,162.57,134.44,122.44(q,J=336.5Hz),110.39,98.27,56.50,55.76.161.53,127.16,122.44(q,J=336.5Hz),108.58,106.81,56.61.(A:B=10:1)HRMS-ESI(m/z)calcd for C9H9BrF3O2Se(M+H):364.8898,found:364.8898。
实施例4
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1001g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为96%。
其核磁谱图信息如下:
m.p.119.7—120.3℃,1H NMR(400MHz,Chloroform-d)δ8.55(d,J=9.0Hz,1H),8.43(d,J=1.6Hz,1H),8.18–8.08(m,2H),7.43(d,J=9.1Hz,1H),4.08(s,3H),2.72(s,3H);19F NMR(376MHz,Chloroform-d)δ-34.87(s,3F);13C NMR(101MHz,Chloroform-d)δ197.54,161.36,139.33,135.60,132.90,130.47,128.38,127.88,126.19,122.39(q,J=336.5Hz),113.60,107.33,56.95,26.71.HRMS-ESI(m/z)calcd for C14H12F3O2Se(M+H):348.9949,found:348.9933。
实施例5
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1246g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为81%。
其核磁谱图信息如下:
1H NMR(400MHz,Chloroform-d)δ7.31(s,1H),7.18(s,1H),5.56(s,1H),4.27(tdd,J=10.9,8.9,5.4Hz,2H),3.96(s,3H),3.93(s,3H),1.30(t,J=7.1Hz,3H);19F NMR(376MHz,Chloroform-d)δ-36.19(s,3F);13C NMR(101MHz,Chloroform-d)δ164.83,151.95,149.73,128.68,122.16(q,J=334.4Hz),121.23,115.76,114.55,111.14,63.62,56.32,56.26,43.48,13.90.HRMS-ESI(m/z)calcd for C14H14F3NNaO4Se(M+Na):419.9932,found:419.9925。
实施例6
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq),化合物3(0.1357g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为51%。。
其核磁谱图信息如下:
m.p.67.5—67.8℃,1H NMR(400MHz,Chloroform-d)δ7.58(s,1H),7.34(dt,J=13.9,4.6Hz,6H),6.91(d,J=8.4Hz,1H),5.14(s,2H),5.08(s,1H),4.33(d,J=5.9Hz,2H),3.88(s,3H);19F NMR(376MHz,Chloroform-d)δ-35.08(s,3F);13C NMR(101MHz,Chloroform-d)δ136.48,136.43,131.92,131.26,128.57,128.21,128.15,122.51(q,J=333.3Hz),111.46,66.94,56.24,44.13.HRMS-ESI(m/z)calcd for C17H16F3NNaO3Se(M+Na):442.0140,found:442.0129。
实施例7
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1436g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为72%。
其核磁谱图信息如下:
1H NMR(400MHz,Chloroform-d)δ7.91(d,J=2.1Hz,1H),7.53(dd,J=8.4,2.1Hz,1H),6.86(d,J=8.4Hz,1H),1.05(s,9H),0.28(s,6H);19F NMR(376MHz,Chloroform-d)δ-36.70(s,3F);13C NMR(101MHz,Chloroform-d)δ154.90,141.85,137.48,122.39(q,J=334.5Hz),120.73,116.16,114,26,25.61,18.35,-4.24.HRMS-ESI(m/z)calcd forC13H19BrF3OSeSi(M+H):434.9500,found:434.9500。
实施例8
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1448g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为87%。
其核磁谱图信息如下:
m.p.70.2—70.8℃,1H NMR(400MHz,DMSO-d6)δ11.07(s,1H),7.74(d,J=2.3Hz,1H),7.48(s,1H),7.37(dd,J=8.9,2.2Hz,1H),7.27(s,1H),6.82(d,J=8.9Hz,1H);19F NMR(376MHz,DMSO-d6)δ-36.41(s,3F);13C NMR(101MHz,Chloroform-d)δ149.58,149.43,142.56,136.20,131.01,128.56,128.49,126.63,126.61,122.30(q,J=334.1Hz),121.38,117.99,113.13.HRMS-ESI(m/z)calcd for C13H6Cl3F3NaO2Se(M+Na):458.8443,found:458.8443。
实施例9
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.0751g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为81%。
其核磁谱图信息如下:
m.p.79.7—80.0℃,1H NMR(400MHz,Chloroform-d)δ8.15(d,J=2.0Hz,1H),7.91(d,J=2.0Hz,1H),6.73(s,1H),2.57(s,3H),2.36(d,J=0.7Hz,3H);19F NMR(376MHz,Chloroform-d)δ-35.34(s,3F);13C NMR(101MHz,Chloroform-d)δ195.92,159.47,137.56,135.10,130.60,125.75,121.70(q,J=335.2Hz),108.70,26.30,16.87.HRMS-ESI(m/z)calcd for C10H10F3O2Se(M+H):298.9793,found:298.9780。
实施例10
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.0756g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为53%。
其核磁谱图信息如下:
m.p.153.4—153.9℃,1H NMR(400MHz,DMSO-d6)δ10.14(s,1H),9.86(s,1H),7.89(d,J=2.4Hz,1H),7.48(dd,J=8.8,2.6Hz,1H),6.93(d,J=8.8Hz,1H),2.00(s,3H);19FNMR(376MHz,DMSO-d6)δ-34.99(s,3F);13C NMR(101MHz,DMSO-d6)δ168.33,154.06,132.39,128.04,123.84,123.24(q,J=335.0Hz),116.17,109.38,24.23.HRMS-ESI(m/z)calcd forC9H9F3NO2Se(M+H):299.9745,found:299.9736。
实施例11
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.063g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为79%。
其核磁谱图信息如下:
1H NMR(400MHz,Chloroform-d)δ7.23(dd,J=7.3,3.0Hz,1H),7.03(dd,J=8.7,3.0Hz,1H),6.11(s,1H),2.31(s,3H);19F NMR(376MHz,Chloroform-d)δ-35.43(s,3F),-123.22(s,1F);13C NMR(101MHz,Chloroform-d)δ155.55(d,J=242.5Hz),151.94(d,J=2.3Hz),126.86(d,J=7.3Hz),121.98(d,J=22.6Hz),121.74(q,J=335.4Hz),121.46(d,J=23.4Hz),107.71(d,J=8.4Hz),17.08.HRMS-ESI(m/z)calcd for C8H7F4OSe(M+H):274.9593,found:274.9593。
实施例12
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.084g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为81%。
其核磁谱图信息如下:
m.p.87.8—88.4℃,1H NMR(400MHz,Chloroform-d)δ11.15(s,1H),8.22(s,1H),6.67(s,1H),6.54(s,1H),3.95(s,3H);19F NMR(376MHz,Chloroform-d)δ-36.47(s,3F);13CNMR(101MHz,Chloroform-d)δ169.43,166.45,162.78,141.87,121.59(q,J=335.7Hz),107.64,103.37,100.21,52.47.HRMS-ESI(m/z)calcd for C9H7F3NaO4Se(M+Na):338.9354,found:338.9354。
实施例13
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.0708g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为99%。
其核磁谱图信息如下:
m.p.59.0—59.6℃,1H NMR(400MHz,Chloroform-d)δ7.53(s,1H),7.33(s,1H),4.26(s,2H),2.20(s,3H);19F NMR(376MHz,Chloroform-d)δ-37.39(s,3F);13C NMR(101MHz,Chloroform-d)δ143.43,137.71,135.79,123.95,122.43(q,J=333.6Hz),118.89,108.85,17.72.HRMS-ESI(m/z)calcd for C8H8ClF3NSe(M+H):289.9457,found:289.9407。
实施例14
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.3034g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为66%,[A]:[B]=2:1,A和B为不同位置的同分异构体。
其核磁谱图信息如下:
m.p.73.1—73.4℃,1H NMR(400MHz,Chloroform-d)δ7.53(s,1H),6.80(d,J=3.1Hz,1H),3.82–3.67(m,2H),2.97–2.55(m,9H),2.42–2.06(m,11H),1.99–1.87(m,2H),1.87–1.09(m,52H),1.07–0.86(m,2H),0.79(s,5H).7.39(d,J=8.7Hz,0.5H),6.95(d,J=8.6Hz,0.5H);19F NMR(376MHz,Chloroform-d)δ-34.53,-35.94,-85.44,-118.16;13C NMR(101MHz,Chloroform-d)δ155.93,155.17,142.00,141.91,141.42,136.34,133.01,132.97,132.88,131.37,122.21(q,J=333.3Hz),122.06(q,J=333.7Hz),116.45,112.95,111.64,106.30,81.81,52.52,52.44,50.80,46.40,46.37,43.34,41.74,41.72,41.26,38.40,37.85,37.80,36.90,36.78,36.56,34.69,34.65,33.44,33.08,33.03,30.48,30.41,29.86,29.80,29.69,29.58,29.53,29.38,29.25,29.16,29.14,29.11,28.92,28.77,28.03,27.91,27.69,27.52,27.18,25.76,25.58,25.43,22.60,22.58,14.67,14.64,14.60,11.12.HRMS-ESI(m/z)calcd for C33H46F8NaO3SSe(M+Na):777.2097,found:777.2092。
实施例15
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1962g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为77%。
其核磁谱图信息如下:
m.p.189.1—189.6℃,1H NMR(400MHz,DMSO-d6)δ11.36(s,1H),8.23(d,J=9.1Hz,1H),7.67(d,J=9.2Hz,1H),7.24(s,1H),6.52(s,1H),5.43(s,2H),5.34(s,2H),3.63(dp,J=13.6,7.3Hz,2H),1.86(dp,J=14.0,7.2Hz,2H),1.34(t,J=7.4Hz,3H),0.87(t,J=7.3Hz,3H);19F NMR(376MHz,DMSO-d6)δ-35.75(s,3F);13C NMR(101MHz,DMSO-d6)δ173.00,161.13,157.17,150.48,149.07,146.38,145.83,145.21,136.76,132.41,130.66,123.10(q,J=337.7Hz),121.57,118.82,101.07,96.45,72.85,65.71,50.67,30.73,25.39,14.05,8.20.HRMS-ESI(m/z)calcd for C23H20F3N2O5Se(M+H):541.0484,found:541.0482。
实施例16
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1859g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为97%,[A]:[B]=3:2,A和B为不同位置的同分异构体。
其核磁谱图信息如下:
A:m.p.124.8—125.3℃,1H NMR(500MHz,Chloroform-d)δ7.71–7.67(m,2H),7.53–7.49(m,2H),7.32(s,1H),7.04(s,1H),3.95(s,3H),3.75(s,3H),3.71(s,2H),2.44(s,3H);19F NMR(471MHz,Chloroform-d)δ-35.97(s,3F);13C NMR(126MHz,Chloroform-d)δ171.10,168.01,155.45,139.80,137.64,133.21,132.56,131.20,130.73,129.28,123.11,122.44(q,J=334.8Hz),112.26,108.08,99.93,56.52,52.27,30.07,13.36.B:m.p.97.6—98.1℃,1H NMR(400MHz,Chloroform-d)δ7.73–7.65(m,2H),7.52–7.46(m,2H),7.27(d,J=8.6Hz,1H),6.80(d,J=9.1Hz,1H),4.11(s,2H),3.89(s,3H),3.72(s,3H),2.30(s,3H);19FNMR(376MHz,Chloroform-d)δ-35.91(s,3F);13C NMR(101MHz,Chloroform-d)δ171.86,168.07,157.29,139.83,138.50,133.58,133.01,131.81,131.37,129.31,122.19(q,J=335.2Hz),117.78,113.20,107.51,101.30,57.02,52.17,31.05,13.46.HRMS-ESI(m/z)calcd for C21H17ClF3NNaO4Se(M+Na):541.9856,found:541.9850。
实施例17
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.2072g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为96%。
其核磁谱图信息如下:
m.p.182.1—182.4℃,1H NMR(400MHz,Chloroform-d)δ7.09(s,1H),6.38(s,1H),6.16(s,1H),5.96(dd,J=5.5,1.2Hz,2H),5.66(d,J=6.0Hz,1H),4.84–4.72(m,1H),4.59(dd,J=8.7,6.6Hz,1H),4.08(t,J=9.4Hz,1H),3.93(s,3H),3.87(s,3H),3.65(s,3H),2.97–2.76(m,2H),2.61(d,J=6.3Hz,1H);19F NMR(376MHz,Chloroform-d)δ-36.48(s,3F);13C NMR(101MHz,Chloroform-d)δ174.31,155.28,155.44,147.98,147.65,141.60,140.71,132.81,131.37,123.13(q,J=334.6Hz),115.36,110.09,109.77,105.62,101.48,71.77,71.27,61.32,60.91,56.12,44.01,43.31,41.16.HRMS-ESI(m/z)calcd forC23H21F3NaO8Se(M+Na):585.0246,found:585.0246。
实施例18
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.2147g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为97%。
其核磁谱图信息如下:
m.p.54.4—54.9℃,1H NMR(500MHz,Chloroform-d)δ7.23–7.10(m,3H),7.00(t,J=8.6Hz,2H),6.30(s,1H),5.96(s,2H),4.45(d,J=12.1Hz,1H),4.30(s,1H),3.67(dd,J=9.1,2.5Hz,1H),3.62–3.46(m,1H),2.91(d,J=63.0Hz,3H),2.05(s,1H),1.90–1.80(m,1H),1.80–1.68(m,1H),1.53(s,9H);19F NMR(471MHz,Chloroform-d)δ-36.00(s,3F),-116.07(s,1F);13C NMR(126MHz,Chloroform-d)δ162.61,160.66,155.17,154.85,151.04,141.80,139.10,139.07,128.81,128.75,122.48(q,J=334.3Hz),117.13,115.65,115.48,101.96,101.77,95.55,79.74,42.04,33.91,28.51.HRMS-ESI(m/z)calcd forC25H27F4NNaO5Se(M+Na):600.0883,found:600.0873。
实施例19
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1551g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为99%。
其核磁谱图信息如下:
m.p.84.6—85.0℃,1H NMR(400MHz,Chloroform-d)δ7.59(d,J=1.9Hz,1H),7.47(dd,J=8.4,1.9Hz,1H),7.38(d,J=8.1Hz,2H),7.20(s,1H),7.07(t,J=8.1Hz,1H),6.48(d,J=8.4Hz,1H),3.80(s,2H),3.78(s,3H);19F NMR(376MHz,Chloroform-d)δ-36.82(s,3F);13C NMR(101MHz,Chloroform-d)δ172.22,145.08,139.89,137.33,136.52,130.50,129.01,125.33,124.25,122.52(q,J=333.5Hz),117.99,113.33,52.70,38.37.HRMS-ESI(m/z)calcd for C16H12Cl2F3NNaO2Se(M+Na):479.9255,found:479.9252。
实施例20
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.2468g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为61%。
其核磁谱图信息如下:
m.p.202.3—202.7℃,1H NMR(400MHz,Chloroform-d)δ9.81(s,1H),9.27(d,J=1.8Hz,1H),9.01(s,1H),8.80(dt,J=8.0,1.9Hz,1H),8.72(dd,J=4.8,1.6Hz,1H),8.59(d,J=5.2Hz,1H),7.91(d,J=8.2Hz,2H),7.64(s,1H),7.51(d,J=8.2Hz,2H),7.49–7.43(m,1H),7.29(d,J=5.2Hz,1H),7.22(s,1H),3.61(s,2H),2.56(s,8H),2.38(s,3H),2.35(s,3H);19F NMR(376MHz,Chloroform-d)δ-35.87(s,3F);13C NMR(101MHz,Chloroform-d)δ164.75,162.95,159.97,159.16,151.59,148.50,142.90,141.79,140.64,139.68,135.69,133.52,132.51,129.54,127.03,123.92,122.95,122.12(q,J=335.7Hz),111.42,109.23,104.90,62.44,55.01,52.88,45.84,17.45.HRMS-ESI(m/z)calcd for C30H31F3N7OSe(M+H):642.1702,found:642.1702。
实施例21
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例2,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1076g,0.5mmol,1.0eq.),其他条件与实施例2相同,最终产率为98%。
其核磁谱图信息如下:
m.p.190.9—191.3℃,1H NMR(400MHz,DMSO-d6)δ12.97(s,1H),8.23(s,2H),8.16(s,1H),7.02(d,J=3.3Hz,1H),6.42(d,J=3.2Hz,1H),4.77(s,2H);19F NMR(376MHz,DMSO-d6)δ-37.04(s,3F);13CNMR(101MHz,DMSO-d6)δ160.59,152.62,139.96,130.77,126.19,122.60(q,J=338.0Hz),110.12,37.19.HRMS-ESI(m/z)calcd for C11H9F3N5OSe(M+H):363.9919,found:363.9908。
实施例22
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法:空气氛围下,在反应管中加入试剂1(0.2376g,0.72mmol,1.2eq.),加入三氟乙醇(2mL)、2-萘酚(0.0865g,0.6mmol,1.0eq.),0℃下反应1h,TLC监测反应结束,用NaHCO3洗,DCM萃取,有机层用无水硫酸钠干燥,过滤、浓缩至干燥,柱层析(PE)得到白色固体,产率为93%。
其核磁谱图信息如下:
m.p.87.2—87.7℃,1H NMR(400MHz,Chloroform-d)δ8.30(d,J=8.5Hz,1H),7.93(d,J=8.9Hz,1H),7.80(d,J=8.1Hz,1H),7.60(ddd,J=8.4,6.9,1.3Hz,1H),7.41(ddd,J=8.0,7.0,1.1Hz,1H),7.33(d,J=8.9Hz,1H),6.83(s,1H);19F NMR(376MHz,Chloroform-d)δ-34.64(s,3F);13C NMR(101MHz,Chloroform-d)δ157.22,135.88,134.60,129.43,128.55,128.34,126.53,124.19,121.93(q,J=337.0Hz),116.79,103.71.HRMS-ESI(m/z)calcd for C11H7F3NaOSe(M+Na):314.9506,found:314.9506。
实施例23
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例22,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.0982g,0.5mmol,1.0eq.),其他条件与实施例22相同,最终产率为86%。
其核磁谱图信息如下:
1H NMR(400MHz,Chloroform-d)δ7.53(d,J=5.4Hz,1H),7.03(d,J=5.4Hz,1H),2.82–2.69(m,2H),1.64–1.56(m,2H),1.29(d,J=14.5Hz,10H),0.88(t,J=6.9Hz,3H);19FNMR(376MHz,Chloroform-d)δ-37.77(s,3F);13C NMR(101MHz,Chloroform-d)δ152.51,132.84,128.97,121.92(q,J=337.1Hz),111.58,31.89,30.76,30.11,29.41,29.38,29.24,22.70,14.13.HRMS-ESI(m/z)calcd for C13H19F3NaSSe(M+Na):367.0217,found:367.0217。
实施例24
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例22,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1362g,0.5mmol,1.0eq.),其他条件与实施例22相同,最终产率为86%,[A]:[B]=4:1,A和B为不同位置的同分异构体。
其核磁谱图信息如下:
m.p.83.4—84.1℃,1H NMR(400MHz,Chloroform-d)δ7.53(s,1H),6.82(s,1H),5.97(s,1H),3.74(t,J=8.5Hz,1H),2.87(dd,J=8.7,4.1Hz,2H),2.30(ddt,J=15.6,6.5,3.3Hz,2H),2.24–2.05(m,3H),2.03–1.81(m,3H),1.71(dtt,J=12.5,7.3,3.2Hz,2H),1.62–1.13(m,16H),0.79(s,4H).7.39(d,J=8.6Hz,0.25H),6.94(d,J=8.6Hz,0.25H),6.35(s,0.25H);19F NMR(376MHz,Chloroform-d)δ-34.39(s,3F).-36.03(s,3F);13C NMR(101MHz,Chloroform-d)δ154.91,143.55,135.85,134.12,130.80,122.00(q,J=335.1Hz),115.48,112.74,105.95,81.84,49.96,43.62,43.21,38.48,36.54,30.45,29.63,26.90,26.25,23.11,11.11.155.58,142.46,133.93,122.00(q,J=335.1Hz),110.86,44.21,38.02,36.66,31.84,30.51,27.36,26.50,23.07.HRMS-ESI(m/z)calcd forC19H24F3O2Se(M+H):421.0888,found:421.0888。
实施例25
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法:空气氛围下,在反应管中加入试剂1(0.1980g,0.72mmol,1.2eq.),加入三氟乙醇(2mL)、2,5-二甲氧基苯甲醛(0.0832g,0.6mmol,1.0eq.),80℃下反应过夜,TLC监测反应结束,用NaHCO3洗,DCM萃取,有机层用无水硫酸钠干燥,过滤、浓缩至干燥,柱层析(PE)得到白色固体,产率为89%。
其核磁谱图信息如下:
m.p.93.9—94.3℃,1H NMR(400MHz,DMSO-d6)δ10.33(s,1H),7.46(s,1H),7.35(s,1H),3.92(s,3H),3.87(s,3H);19F NMR(376MHz,Chloroform-d)δ-34.14(s,3F);13C NMR(101MHz,DMSO-d6)δ188.90,155.97,152.65,126.14,123.02(q,J=333.6Hz),121.73,120.55,109.37,57.15.HRMS-ESI(m/z)calcd for C10H10F3O3Se(M+H):314.9742,found:314.9733。
实施例26
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例25,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.0831g,0.5mmol,1.0eq.),其他条件与实施例25相同,最终产率为97%,A:B=5:4,A和B为不同位置的同分异构体。
其核磁谱图信息如下:
A:m.p.52.0—52.4℃,1H NMR(400MHz,Chloroform-d)δ10.41(s,1H),7.79(d,J=2.0Hz,1H),7.45(d,J=1.9Hz,1H),4.05(s,3H),3.94(s,3H);19F NMR(376MHz,Chloroform-d)δ-36.01(s,3F);13C NMR(101MHz,Chloroform-d)δ188.92,153.40,130.04,128.39,125.73,122.41(q,J=333.1Hz),62.40,56.36.B:1H NMR(400MHz,Chloroform-d)δ10.47(s,1H),7.40(d,J=8.8Hz,1H),7.18(d,J=8.8Hz,1H),4.02(s,3H),3.93(s,3H);19F NMR(376MHz,Chloroform-d)δ-36.79(s,3F);13C NMR(101MHz,Chloroform-d)δ190.99,154.33,151.48,128.05,124.87,124.84,123.52(q,J=337.1Hz),119.23,56.26.HRMS-ESI(m/z)calcd for C10H10F3O3Se(M+H):314.9742,found:314.9732。
实施例27
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例22,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1962g,0.5mmol,1.0eq.),其他条件与实施例25相同,最终产率为80%。
其核磁谱图信息如下:
m.p.181.2—181.9℃,1H NMR(400MHz,DMSO-d6)δ11.37(s,1H),8.98(s,1H),8.24(d,J=9.2Hz,1H),7.69(d,J=9.2Hz,1H),7.28(s,1H),6.51(s,1H),5.42(s,2H),5.30(s,2H),1.86(hept,J=7.0Hz,2H),0.88(t,J=7.3Hz,3H);19F NMR(376MHz,DMSO-d6)δ-34.89(s,3F);13C NMR(101MHz,DMSO-d6)δ172.99,160.29,157.12,150.28,145.57,144.10,134.89,132.60,131.69,130.13,123.20(q,J=335.5Hz),122.56,118.89,103.51,96.70,72.80,65.69,50.90,49.10,30.78,8.20.HRMS-ESI(m/z)calcd for C21H16F3N2O5Se(M+H):513.0171,found:513.0169。
实施例28
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法:空气氛围下,在反应管中加入试剂1(0.4950g,1.5mmol,2.5eq.),加入三氟乙醇(2mL)、2-萘酚(0.0865g,0.6mmol,1.0eq.),室温下反应过夜,TLC监测反应结束,用NaHCO3洗,DCM萃取,有机层用无水硫酸钠干燥,过滤、浓缩至干燥,柱层析(PE)得到淡黄色固体,产率为83%。
其核磁谱图信息如下:
m.p.89.2—89.7℃,1H NMR(400MHz,Chloroform-d)δ8.31(d,J=8.8Hz,1H),8.22(d,J=1.6Hz,1H),7.95(d,J=8.9Hz,1H),7.87(dd,J=8.8,1.6Hz,1H),7.41(d,J=8.9Hz,1H),6.95(s,1H);19F NMR(376MHz,Chloroform-d)δ-34.45(s,3F),-35.89(s,3F);13C NMR(101MHz,Chloroform-d)δ158.55,137.89,136.63,135.39,134.67,129.64,127.93,122.53(q,J=333.2Hz),121.78(q,J=336.9Hz),118.01,117.90,103.85.HRMS-ESI(m/z)calcdfor C12H7F6OSe2(M+H):440.8726,found:440.8726。
实施例29
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例28,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1432g,0.5mmol,1.0eq.),其他条件与实施例28相同,最终产率为86%。
其核磁谱图信息如下:
m.p.80.4—80.8℃,1H NMR(400MHz,Chloroform-d)δ8.34(d,J=1.6Hz,2H),8.03(d,J=9.0Hz,2H),7.60(dd,J=8.7,1.6Hz,2H),7.47(d,J=9.0Hz,2H),7.12(d,J=8.7Hz,2H),5.17(s,2H);19F NMR(376MHz,Chloroform-d)δ-35.91(s,6F);13CNMR(101MHz,Chloroform-d)δ154.25,138.07,134.80,133.93,132.00,129.76,125.35,122.02(q,J=334.2Hz),119.04,117.86,110.46.HRMS-ESI(m/z)calcd for C22H13F6O2Se2(M+H):582.9145,found:582.9145。
实施例30
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例28,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.0621g,0.5mmol,1.0eq.),其他条件与实施例28相同,最终产率为95%。
其核磁谱图信息如下:
m.p.71.0—72.0℃,1H NMR(400MHz,Chloroform-d)δ7.38(s,2H),2.99(s,3H);19FNMR(376MHz,Chloroform-d)δ-34.84(s,3F),-35.53(s,6F);13C NMR(101MHz,Chloroform-d)δ162.80,156.69,121.95(q,J=336.2Hz),121.79(q,J=336.4Hz),103.91,94.56,27.14.HRMS-ESI(m/z)calcd for C10H5F9NaO2Se3(M+Na):590.7534,found:590.7534。
实施例31
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例28,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.0606g,0.5mmol,1.0eq.),其他条件与实施例28相同,最终产率为90%。
其核磁谱图信息如下:
1H NMR(400MHz,Chloroform-d)δ7.96(s,1H),7.66(dd,J=8.3,1.8Hz,1H),7.16(d,J=8.3Hz,1H),2.78(s,6H);19F NMR(376MHz,Chloroform-d)δ-35.56(s,3F),-36.41(s,3F);13C NMR(101MHz,Chloroform-d)δ155.31,141.13,138.02,123.08(q,J=333.3Hz),122.40(q,J=333.3Hz),121.57,117.81,110.71,44.85.HRMS-ESI(m/z)calcd forC10H10F6NSe2(M+H):417.9042,found:417.9033.
实施例32
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例28,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.0836g,0.5mmol,1.0eq.),其他条件与实施例28相同,最终产率为79%。
其核磁谱图信息如下:
m.p.157.7—158.7℃,1H NMR(400MHz,Chloroform-d)δ8.53–8.46(m,2H),8.36(s,1H),7.83(dd,J=8.4,1.5Hz,2H),7.48(d,J=8.4Hz,2H);19F NMR(376MHz,Chloroform-d)δ-37.03(s,6F);13C NMR(101MHz,Chloroform-d)δ140.49,135.48,130.39,123.75,122.66(q,J=333.3Hz),112.78,111.90.HRMS-ESI(m/z)calcd for C14H8F6NSe2(M+H):463.8886,found:463.8886。
实施例33
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例28,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1106g,0.5mmol,1.0eq.),其他条件与实施例28相同,最终产率为91%。
其核磁谱图信息如下:
m.p.94.4—94.6℃,1H NMR(400MHz,Chloroform-d)δ6.84(s,1H),5.42(s,1H),5.02(dtd,J=8.9,5.5,3.8Hz,1H),4.24(qd,J=9.9,4.4Hz,2H),3.90–3.71(m,2H),2.98(s,3H),2.67(s,3H);19F NMR(376MHz,Chloroform-d)δ-35.13(s,3F),-35.59(s,3F);13CNMR(126MHz,Chloroform-d)δ160.52,159.44,152.80,150.67,122.72(q,J=334.5Hz),122.55(q,J=334.4Hz),118.60,112.28,111.79,73.66,68.71,42.68,27.11,26.06.HRMS-ESI(m/z)calcd for C14H13F6NNaO3Se2(M+Na):539.9022,found:539.9020。
实施例34
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法:空气氛围下,在反应管中加入试剂1(0.4125g,1.25mmol,2.5eq.),加入三氟乙醇(2mL)、5-甲基间苯二酚(0.0621g,0.5mmol,1.0eq.),0℃下反应1h,TLC监测反应结束,用NaHCO3洗,DCM萃取,有机层用无水硫酸钠干燥,过滤、浓缩至干燥,柱层析(PE)得到白色固体,产率为71%。
其核磁谱图信息如下:
m.p.57.9—58.5℃,1H NMR(400MHz,Chloroform-d)δ6.78(s,2H),6.75(s,1H),2.92(s,3H);19F NMR(376MHz,Chloroform-d)δ-35.73(s,6F);13C NMR(101MHz,Chloroform-d)δ161.80,152.32,121.79(q,J=336.6Hz),104.35,99.75,26.41.HRMS-ESI(m/z)calcd for C9H7F6O2Se2(M+H):420.8675,found:420.8675。
实施例35
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例34,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.0716g,0.5mmol,1.0eq.),其他条件与实施例34相同,最终产率为94%。
其核磁谱图信息如下:
m.p.99.4—99.9℃,1H NMR(400MHz,Chloroform-d)δ8.49(d,J=8.5Hz,1H),8.26(s,1H),7.86(d,J=8.4Hz,1H),7.70(ddd,J=8.3,6.9,1.1Hz,1H),7.58(ddd,J=8.2,6.9,1.2Hz,1H),5.46(s,2H);19F NMR(376MHz,Chloroform-d)δ-35.49(s,3F),-36.73(s,3F);13C NMR(126MHz,Chloroform-d)δ150.03,147.98,137.41,129.28,129.26,126.45,122.96,122.45(q,J=336.0Hz),122.39(q,J=336.0Hz),122.18,109.96,100.15.HRMS-ESI(m/z)calcd for C12H8F6NSe2(M+H):439.8886,found:439.8835。
实施例36
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法:空气氛围下,在反应管中加入试剂1(0.4125g,1.25mmol,2.5eq.),加入三氟乙醇(2mL)、1,4-二甲氧基苯(0.0691g,0.5mmol,1.0eq.),40℃下反应过夜,TLC监测反应结束,用NaHCO3洗,DCM萃取,有机层用无水硫酸钠干燥,过滤、浓缩至干燥,柱层析(PE)得到白色固体95%。
其核磁谱图信息如下:
m.p.107.1—107.5℃,1H NMR(400MHz,Chloroform-d)δ7.24(s,2H),3.87(s,6H);19F NMR(376MHz,Chloroform-d)δ-34.61(s,6F);13C NMR(101MHz,Chloroform-d)δ153.07,122.48(q,J=333.1Hz),118.67,115.76,56.91.HRMS-ESI(m/z)calcd forC10H8F6NaO2Se2(M+Na):456.8651,found:456.8645。
实施例37
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例36,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1477g,0.5mmol,1.0eq.),其他条件与实施例36相同,最终产率为38%。
其核磁谱图信息如下:
m.p.113.0—113.4℃,1H NMR(400MHz,Chloroform-d)δ7.56(s,2H),6.66(s,1H),5.05(d,J=7.5Hz,1H),4.57(d,J=6.1Hz,1H),3.72(s,3H),3.09(ddd,J=43.9,14.0,5.5Hz,2H),1.44(s,9H);19F NMR(376MHz,Chloroform-d)δ-35.09(s,6F);13CNMR(101MHz,Chloroform-d)δ171.60,156.66,154.90,142.68,130.48,122.02(q,J=334.4Hz),109.77,80.23,54.21,52.42,36.69,28.24.HRMS-ESI(m/z)calcd for C17H19F6NNaO5Se2(M+Na):613.9390,found:613.9390。
实施例38
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法:空气氛围下,在反应管中加入试剂1(0.4125g,1.25mmol,2.5eq.),加入三氟甲苯(2mL)、苯甲酰苯胺(0.0986g,0.5mmol,1.0eq.),80℃下反应过夜,TLC监测反应结束,用NaHCO3洗,DCM萃取,有机层用无水硫酸钠干燥,过滤、浓缩至干燥,柱层析(PE)得到白色固体,产率为66%。
其核磁谱图信息如下:
m.p.140.0—140.9,1H NMR(400MHz,Chloroform-d)δ9.13(s,1H),8.79(d,J=8.7Hz,1H),8.22(d,J=1.8Hz,1H),7.95(d,J=1.8Hz,3H),7.62(t,J=7.3Hz,1H),7.55(t,J=7.4Hz,2H);19F NMR(376MHz,Chloroform-d)δ-34.87(s,3F),-36.28(s,3F);13C NMR(101MHz,Chloroform-d)δ165.34,147.68,142.75,141.88,133.98,132.68,129.16,127.10,122.28(q,J=333.2Hz),121.89(q,J=335.1Hz),121.45,117.27,113.21.HRMS-ESI(m/z)calcd for C15H9F6NNaOSe2(M+Na):515.8811,found:515.8811。
实施例39
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法:空气氛围下,在反应管中加入试剂1(0.1980g,0.6mmol,1.2eq.),加入三氟乙醇(2mL)、化合物3(0.2073g,0.5mmol,1.0eq.),40℃下反应过夜,TLC监测反应结束,用NaHCO3洗,DCM萃取,有机层用无水硫酸钠干燥,过滤、浓缩至干燥,柱层析(PE)得到淡黄色粘稠液体,产率为94%。
其核磁谱图信息如下:
1H NMR(400MHz,Chloroform-d)δ7.54–7.44(m,3H),7.15(dd,J=8.4,2.1Hz,1H),7.11(d,J=8.3Hz,1H),6.80(d,J=8.4Hz,1H),4.95(dt,J=4.8,2.5Hz,1H),4.06(dd,J=10.2,4.8Hz,1H),4.02–3.88(m,5H),2.26–2.11(m,2H);19F NMR(376MHz,Chloroform-d)δ-34.92(s,3F);13C NMR(126MHz,Chloroform-d)δ155.64,140.60,139.52,137.62,136.94,134.24,132.21,131.80,131.35,122.55(q,J=333.4Hz),114.01,113.09,91.78,78.62,72.89,67.23,37.82,33.09.HRMS-ESI(m/z)calcd for C18H16ClF3IO2Se(M+H):562.8995,found:562.8995。
实施例40
化合物1作为三氟甲硒基化试剂制备化合物4的应用
所述的化合物3和4结构式顺次如下:
其制备方法参考实施例39,其中反应物用量修改为:化合物1(0.1980g,0.6mmol,1.2eq.),化合物3(0.1997g,0.5mmol,1.0eq.),其他条件与实施例39相同,最终产率为54%。
其核磁谱图信息如下:
m.p.130.9—131.4℃,1H NMR(400MHz,Chloroform-d)δ8.68(d,J=5.9Hz,1H),7.66(s,1H),7.31(d,J=10.6Hz,1H),6.92(d,J=11.0Hz,1H),4.56(dt,J=11.2,5.5Hz,1H),4.05(s,3H),4.01(s,3H),3.99(s,3H),3.70(s,3H),3.62–3.50(m,1H),2.32(t,J=7.9Hz,2H),1.99(s,3H),1.91(dt,J=11.7,6.3Hz,1H);19F NMR(376MHz,Chloroform-d)δ-35.05(s,3F);13C NMR(101MHz,Chloroform-d)δ179.56,170.50,164.45,156.06,154.24,152.28,145.84,140.12,136.22,135.90,129.98,129.75,122.13(q,J=334.5Hz),112.92,112.71,61.59,61.37,61.28,56.60,52.73,34.95,29.69,22.70.HRMS-ESI(m/z)calcd forC23H25F3NO6Se(M+H):548.0794,found:548.0786。
Claims (10)
3.根据权利要求2所述化合物1的制备方法,其特征在于:所述的卤代烃类溶剂为氯代烃类溶剂;所述的氯代烃类溶剂与化合物2的体积质量比为1mL/g—50mL/g;所述的化合物2与所述的三氟甲硒基氯的摩尔比值为1—2;所述的反应的温度为10℃—80℃;所述的反应的时间为10min—3h。
5.根据权利要求4所述的化合物1的制备方法,其特征在于:
所述的卤代烃类溶剂为氯代烃类溶剂;所述的有机溶剂与所述的糖精钠的体积质量比为1mL/g—20mL/g;所述的硝酸银与糖精钠的摩尔比值为1—2,所述的取代反应的温度为50℃—80℃,所述的取代反应的时间为5—30min。
6.权利要求1—5任一项所述的化合物1作为三氟甲硒基化试剂的应用,其特征在于:化合物1与芳环类或者芳杂环类化合物在有机溶剂中进行反应得到含有三氟甲硒基的化合物。
9.根据权利要求6所述的应用,其特征在于:所述的有机溶剂为烃类溶剂、卤代烃类溶剂、醚类溶剂、腈类溶剂、酮类溶剂、酰胺类溶剂、醇类溶剂中的一种;所述的有机溶剂与所述的化合物3的体积质量比为1mL/g—200mL/g,所述的化合物1与所述的化合物3的摩尔比值为1—3,所述的取代反应的温度为0℃—100℃,所述的取代反应的时间为1min—12h。
10.根据权利要求9所述的应用,其特征在于:所述的烃类溶剂为三氟甲苯;所述的卤代烃类溶剂为1,2-二氯乙烷;所述的醚类溶剂为四氢呋喃;所述的腈类溶剂为乙腈;所述的酮类溶剂为丙酮;所述的酰胺类溶剂为N,N-二甲基甲酰胺;所述的醇类溶剂为三氟乙醇和六氟异丙醇;
所述的有机溶剂与所述的化合物3的体积质量比为1mL/g—100mL/g;所述的化合物1与化合物3的摩尔比值为1—1.2;所述的取代反应的温度为0℃—80℃;所述的取代反应的时间为1h—12h。
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