CN115772177A - 一种螺吡喃类化合物的合成方法 - Google Patents
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Abstract
本发明提出了一种螺吡喃类化合物的合成方法,属于有机合成化学的技术领域,用以解决螺环类骨架合成困难、步骤复杂的技术问题。本发明在惰性氛围下将反应物噁嗪类化合物、1,4‑苯醌类化合物和催化剂、添加剂一起加入到溶剂当中进行反应,反应结束后制得螺吡喃类化合物。本发明开创性地选取简单易得的噁嗪类化合物和1,4‑苯醌类化合物作为反应物,在金属钌催化剂的作用下,通过[3+3]一步实现了新型含季碳中心螺[5.5]杂环骨架的构建,为复杂螺环的构建提供了一种简单有效的合成方法,并且该方法具有反应条件温和、操作简单、原子经济、步骤经济以及官能团耐受性强等特点。
Description
技术领域
本发明属于有机合成化学的技术领域,尤其涉及一种螺吡喃类化合物的合成方法。
背景技术
螺环化合物是一类具有重要应用价值和良好生物活性的化合物,在医药、农药、染料,催化等领域发挥着重要作用(Chem.Rev.2004,104,2751-2776;Chem.Rev.2007,107,1011-1065)。因此科学家们在螺环化合物的合成方法上进行了大量的探索,然而这些合成方法往往面临着原料合成复杂,步骤经济性差,条件苛刻等问题(ACS Catal.2013,3,540-553;Eur.J.Org.Chem.2017,5316-5342),以上问题极大的限制了该类化合物的使用,且目前螺环化合物研究多为构建螺碳骨架,而对于螺杂环骨架的合成研究较少。其中螺吡喃类化合物的构建方法更是极度匮乏,这主要因为很多螺吡喃类化合物的稳定性差,如何高效便捷地合成稳定的螺吡喃类化合物是合成螺杂环骨架的一个难点问题。我们之前报道过一例通过C-H键活化的方式构建螺吡喃类化合物(Chem.Commun.,2022,58,5144-5147),在金属Rh催化剂的作用下通过串联反应实现了螺吡喃类化合物的合成。对于此合成方法,所得的产物为双环产物,很难控制一次C-H键活化得到一次环化的螺吡喃产物,因此需要寻找经济效益更高、控制一次C-H键产物的方法。
另一方面,苯并噁嗪类衍生物作为一种广泛存在于玉米、小麦和黑麦等主要农作物中的内源性物质,在作物体内发挥着重要的作用,是作物抵抗微生物和病害侵染的主要活性成分,是作物防御系统的组成部分(Int.Rev.Cytol.,2000,198,319-346;Molecules,2017,22,1103)。基于多个课题组利用该类化合物对辣椒炭疽病菌、小麦纹枯病菌、稻瘟菌、纹枯病菌、赤星病菌、菌核病菌、灰霉病菌和赤霉病菌等致病菌展开了生物活性测定研究,研究结果表明该类化合物对多种致病菌展现出了一定的抑菌活性,因此开发基于苯并噁嗪类化合物的衍生物,对其进行结构改造,有望得到具有更高抑菌活性的苯并噁嗪类衍生物,对开发新型苯并噁嗪类杀菌剂,防治作物病害具有重要意义。
发明内容
针对螺环类骨架合成困难、步骤复杂的技术问题,本发明提出一种螺吡喃类化合物的合成方法,该方法具有反应条件温和、操作简单、原子经济、步骤经济以及官能团耐受性强等特点。
为了达到上述目的,本发明的技术方案是这样实现的:
一种螺吡喃类化合物的合成方法,噁嗪类化合物和1,4-苯醌类化合物作为原料,在催化剂的促进下合成了螺吡喃类化合物;反应式如下所示:
式中:R为H、Me、F、Cl、Br或t-Bu中的任意一种;R1为Me、Cl、t-Bu或Ph中的任意一种;Ar为Me、OMe、Cl、Br、Ph或CF3中的任意一种取代的苯环。
具体步骤为:在惰性氛围下将反应物噁嗪类化合物、1,4-苯醌类化合物和催化剂、添加剂一起加入到溶剂当中进行反应,反应结束后制得螺吡喃类化合物。
根据权利要求2所述的螺吡喃类化合物的合成方法,其特征在于,所述噁嗪类化合物、1,4-苯醌类化合物、催化剂和添加剂的摩尔比为1:(1.1-2.2):(0.1-0.2):(1.1-2.2)。
所述溶剂当中反应物的浓度为0.05M-0.1M。
所述添加剂为醋酸铜、醋酸钠、醋酸锂或碳酸氢钠中的任一种或两种以上。
所述催化剂由钌催化剂/铑催化剂和银盐组成,钌催化剂/铑催化剂和银盐的摩尔比为1:4。
所述钌催化剂为2二氯双(4-甲基异丙基苯基)钌([RuCl2(p-cymene)]2),所述铑催化剂为二氯(五甲基环戊二烯基)合铑(III)二聚体,所述银盐为六氟锑酸银(AgSbF6)。
所述溶剂1,2-二氯乙烷、二氯甲烷、乙二醇二甲醚或三氟甲苯中任意一种。
所述惰性氛围为氮气氛围。
所述反应的反应温度为30℃-80℃,反应时间为12h-24h。
苯并噁嗪在钌催化剂和六氟锑酸银的作用下生成环金属中间体A,1,4-苯醌插入生成中间体B,随后发生金属的脱除得到中间体C,羟基进攻生成螺环化合物D,该反应能有效地控制一次C-H键活化得到单次关环产物D。
本发明的有益效果:本发明开创性地选取简单易得的噁嗪类化合物和1,4-苯醌类化合物作为反应物,在金属钌催化剂的作用下,通过[3+3]一步实现了新型含季碳中心螺[5.5]杂环骨架的构建,为复杂螺环的构建提供了一种简单有效的合成方法,并且该方法具有反应条件温和、操作简单、原子经济、步骤经济以及官能团耐受性强等特点。所得产物有广阔的工业应用前景,通过在苯并噁唑嗪类类似物中引入螺吡喃类结构可作为杀菌剂应用,同时本发明为医药、天然产物合成以及发光材料等领域提供了一种新思路和新方法。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。
图1是化合物3aa的核磁1H谱图;图2是化合物3aa的核磁13C谱图。
图3是化合物3ba的核磁1H谱图;图4是化合物3ba的核磁13C谱图。
图5是化合物3ca的核磁1H谱图;图6是化合物3ca的核磁13C谱图。
图7是化合物3da的核磁1H谱图;图8是化合物3da的核磁13C谱图。
图9是化合物3ea的核磁1H谱图;图10是化合物3ea的核磁13C谱图。
图11是化合物3fa的核磁1H谱图;图12是化合物3fa的核磁13C谱图。
图13是化合物3ga的核磁1H谱图;图14是化合物3ga的核磁13C谱图。
图15是化合物3ha的核磁1H谱图;图16是化合物3ha的核磁13C谱图。
图17是化合物3ia的核磁1H谱图;图18是化合物3ia的核磁13C谱图。
图19是化合物3ja的核磁1H谱图;图20是化合物3ja的核磁13C谱图。
图21是化合物3ka的核磁1H谱图;图22是化合物3ka的核磁13C谱图。
图23是化合物3la的核磁1H谱图;图24是化合物3la的核磁13C谱图。
图25是化合物3ma的核磁1H谱图;图26是化合物3ma的核磁13C谱图。
图27是化合物3na的核磁1H谱图;图28是化合物3na的核磁13C谱图。
图29是化合物3ab的核磁1H谱图;图30是化合物3ab的核磁13C谱图。
图31是化合物3ac的核磁1H谱图;图32是化合物3ac的核磁13C谱图。
图33是化合物3ad的核磁1H谱图;图34是化合物3ad的核磁13C谱图。
图35是化合物3ad’的核磁1H谱图;图36是化合物3ad’的核磁13C谱图。
具体实施方式
下面将结合本发明实施例中的附图,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,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付出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
实施例1
氮气条件下,噁嗪化合物1a(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3aa),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,83%的产率,熔程:125–126℃.核磁谱图如图1和2所示,1H NMR(400MHz,CDCl3)δ7.73(d,J=7.8Hz,1H),7.54(dd,J=7.7,1.4Hz,1H),7.49(td,J=7.6,1.4Hz,1H),7.40(td,J=7.6,1.3Hz,1H),7.24(d,J=2.9Hz,1H),6.95–6.86(m,3H),6.81(td,J=7.6,1.6Hz,1H),6.75(td,2H),4.79(d,J=2.2Hz,1H),4.76(s,1H),4.40(dd,J=11.3,2.5Hz,1H),3.87(d,J=11.3Hz,1H).13C NMR(101MHz,CD3OD)δ153.50,146.33,144.41,133.72,133.41,132.21,130.62,129.50,126.56,123.50,123.40,122.76,119.99,119.95,117.86,116.97,116.64,110.11,84.82,68.62.HRMS:[M+H]+calculated forC20H16NO3 +:318.1125,found:318.1122.
实施例2
氮气条件下,噁嗪化合物1b(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),,Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物8-溴-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ba),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,73%的产率,熔程:133–134℃.核磁谱图如图3和4所示,1H NMR(400MHz,CDCl3)δ7.60(d,J=7.7Hz,1H),7.43(d,J=7.5Hz,2H),7.33(t,1H),7.15(d,J=2.9Hz,1H),7.02(d,J=7.8Hz,1H),6.83(d,J=8.6Hz,1H),6.75–6.60(m,3H),5.19(s,1H),4.92(s,1H),4.47(dd,J=11.3,2.4Hz,1H),3.86(d,J=11.3Hz,1H).13C NMR(101MHz,CDCl3)δ150.83,145.29,140.32,132.32,131.43,130.59,130.08,128.85,125.10,123.83,122.78,122.63,122.07,119.61,117.28,115.02,110.58,109.55,83.37,68.25.HRMS:[M+H]+calculated for C20H15BrNO3 +:396.0230,found:396.0222.
实施例3
氮气条件下,噁嗪化合物1c(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物7-氟-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ca),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,69%的产率,熔程:207-208℃.核磁谱图如图5和6所示,1HNMR(400MHz,CD3OD)δ7.74(d,J=7.8Hz,1H),7.51(d,J=7.7Hz,1H),7.44(t,J=7.6Hz,1H),7.36(t,J=7.5Hz,1H),7.23(d,J=2.9Hz,1H),6.86–6.65(m,3H),6.63–6.44(m,2H),4.28(d,J=11.1Hz,1H),3.73(d,J=11.2Hz,1H).13C NMR(101MHz,MeOD)δ157.70(d,J=234.7Hz),153.50,146.19,144.89(d,J=11.6Hz),133.45,132.14,130.65,129.74(d,J=2.5Hz),129.49,126.51,123.46,123.41,119.88,117.85,116.71(d,J=9.1Hz),110.14,108.61(d,J=22.7Hz),104.31(d,J=26.0Hz),84.46,68.70.HRMS:[M+H]+calculated forC20H15FNO3 +:336.1030,found:336.1028.
实施例4
氮气条件下,噁嗪化合物1d(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物7-甲基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3da),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,78%的产率,熔程:129–130℃.核磁谱图如图7和8所示,1HNMR(400MHz,DMSO-d6)δ9.21–9.14(m,1H),7.81(d,J=8.4Hz,1H),7.56–7.47(m,2H),7.42(td,J=7.4,1.2Hz,1H),7.27(q,J=2.6Hz,1H),7.21(t,J=1.9Hz,1H),6.77–6.72(m,1H),6.72–6.67(m,2H),6.64–6.58(m,2H),4.22(dt,J=11.2,2.1Hz,1H),3.75(dd,J=11.1,1.4Hz,1H),2.18(s,3H).13C NMR(101MHz,CD3OD)δ153.42,146.36,144.24,133.79,132.16,130.70,130.55,129.61,129.45,126.55,123.50,123.36,123.19,119.92,117.81,117.46,116.56,110.11,84.90,68.63,20.72.HRMS:[M+H]+calculated for C21H18NO3 +:332.1281,found:332.1282.
实施例5
氮气条件下,噁嗪化合物1e(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物6-氯-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ea),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,84%的产率,熔程:212–213℃.核磁谱图如图9和10所示,1HNMR(400MHz,DMSO-d6)δ9.21(s,1H),7.87–7.78(m,1H),7.69(d,J=2.0Hz,1H),7.56–7.47(m,2H),7.47–7.41(m,1H),7.27(d,J=2.7Hz,1H),6.84–6.78(m,2H),6.76(d,J=8.6Hz,1H),6.68(ddd,J=11.2,8.6,2.6Hz,2H),4.27(dd,J=11.3,2.0Hz,1H),3.83(d,J=11.3Hz,1H).13C NMR(101MHz,DMSO-d6)δ152.40,143.81,141.31,133.73,131.30,130.24,129.84,128.48,125.44,125.07,122.45,121.58,118.58,117.59,117.09,117.01,114.32,109.29,82.40,67.14.HRMS:[M+H]+calculated for C20H15ClNO3 +:352.0735,found:352.0740.
实施例6
氮气条件下,噁嗪化合物1f(0.20mmol),1,4-苯醌化合物2a(0.22mmol),[RuCl2(p-cymene)]2(噁嗪化合物的3mol%),AgSbF6(噁嗪化合物的12mol%),醋酸钠(0.22mmol)和溶剂二氯甲烷(3.0mL)加入到10mL密封管中,在50℃的反应模块中反应24h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物6-叔丁基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3fa),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,23%的产率,熔程:179–180℃.核磁谱图如图11和12所示,1H NMR(400MHz,CDCl3)δ7.74–7.63(m,1H),7.54(dd,J=7.6,1.4Hz,1H),7.46(td,J=7.6,1.4Hz,1H),7.38(td,J=7.5,1.3Hz,1H),7.22(d,J=2.9Hz,1H),6.91(d,J=8.6Hz,1H),6.89–6.80(m,2H),6.78(d,J=2.1Hz,1H),6.71(dd,J=8.7,2.9Hz,1H),4.82(d,J=6.7Hz,1H),4.77(d,J=2.4Hz,1H),4.36(dd,J=11.3,2.4Hz,1H),3.82(d,J=11.3Hz,1H),1.30(s,9H).13C NMR(101MHz,CDCl3)δ150.76,145.82,145.16,141.08,132.34,130.75,130.26,129.91,128.82,125.41,122.68,122.32,119.56,117.27,117.22,116.16,113.17,109.57,84.02,67.73,34.35,31.66.HRMS:[M+H]+calculated for C24H24NO3 +:374.1751,found:374.1753.
实施例7
氮气条件下,噁嗪化合物1g(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物5-氟-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ga),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,61%的产率,熔程:166–167℃.核磁谱图如图13和14所示,1HNMR(400MHz,CDCl3)δ7.69(dd,J=7.9,1.2Hz,1H),7.55(dd,J=7.6,1.4Hz,1H),7.47(td,J=7.6,1.5Hz,1H),7.39(td,J=7.5,1.3Hz,1H),7.22(d,J=2.9Hz,1H),6.89(d,J=8.6Hz,1H),6.76–6.68(m,4H),4.97(s,1H),4.85(s,1H),4.41(dd,J=11.4,2.5Hz,1H),3.85(d,J=11.4Hz,1H).13C NMR(101MHz,CDCl3)δ151.89(d,J=239.0Hz),150.86,150.71,145.50,144.71(d,J=5.4Hz),131.70,130.67,130.12,128.95,125.39,122.74,122.26,120.41(d,J=15.6Hz),119.45,118.73(d,J=9.0Hz),117.28,1112.13(d,J=2.8Hz),109.65,108.30(d,J=18.3Hz),82.74,67.81.HRMS:[M+H]+calculated for C20H15FNO3 +:336.1030,found:336.1027.
实施例8
氮气条件下,噁嗪化合物1h(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物6,8-二氯-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ha),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,37%的产率,熔程:125–126℃.核磁谱图如图15和16所示,1H NMR(400MHz,CDCl3)δ7.71(d,J=7.8Hz,1H),7.53–7.43(m,2H),7.39(t,J=7.4Hz,1H),7.22(d,J=2.9Hz,1H),6.95–6.83(m,2H),6.74(dd,J=8.7,2.9Hz,1H),6.64(d,J=2.5Hz,1H),4.94(d,J=2.3Hz,1H),4.73(s,1H),4.51(dd,J=11.4,2.4Hz,1H),3.88(d,J=11.4Hz,1H).13C NMR(101MHz,CDCl3)δ150.97,145.22,138.36,133.04,131.13,130.64,130.31,129.00,126.41,125.03,122.89,122.11,122.05,120.55,119.65,117.35,114.21,109.57,82.95,68.25.HRMS:[M+H]+calculated for C20H14Cl2NO3 +:386.0345,found:386.0345.
实施例9
氮气条件下,噁嗪化合物1i(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(4mol%),AgSbF6(16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物8'-苯基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ia),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,41%的产率,熔程:194–195℃.核磁谱图如图17和18所示,1H NMR(400MHz,CDCl3)δ7.8–7.7(m,2H),7.7(dd,J=8.2,1.8Hz,1H),7.7–7.6(m,2H),7.5–7.4(m,2H),7.4–7.4(m,1H),7.2(d,J=3.0Hz,1H),7.0–6.9(m,3H),6.8(td,J=7.6,1.7Hz,1H),6.8–6.7(m,2H),4.8(d,J=2.4Hz,1H),4.8(s,1H),4.4(dd,J=11.4,2.5Hz,1H),3.9(d,J=11.4Hz,1H).13CNMR(101MHz,CDCl3)δ150.71,145.60,143.33,141.59,139.99,132.54,130.94,129.53,128.97,128.36,127.84,126.93,123.85,123.13,121.94,120.25,119.39,117.11,116.63,115.94,109.40,83.72,67.69.HRMS[M+H]+calculated for C26H20NO3 +:394.1438,found:394.1447.
实施例10
氮气条件下,噁嗪化合物1j(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物8'-甲氧基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ja),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,68%的产率,熔程:220–221℃.核磁谱图如图19和20所示,1H NMR(400MHz,CD3OD)δ7.71(d,J=8.6Hz,1H),7.17(d,J=2.8Hz,1H),7.12(d,J=2.7Hz,1H),7.04(dd,J=8.6,2.7Hz,1H),6.85–6.80(m,2H),6.80–6.74(m,2H),6.72–6.66(m,1H),6.64(dd,J=8.6,2.8Hz,1H),4.27(d,J=11.2Hz,1H),3.85(s,3H),3.72(d,J=11.2Hz,1H).13C NMR(101MHz,CD3OD)δ161.65,153.49,145.57,144.45,135.33,133.38,125.06,124.95,123.72,122.74,120.05,119.72,116.96,116.72,116.66,116.32,111.71,109.59,84.78,68.40,55.92.HRMS[M+H]+calculated for C21H18NO4 +:348.1230,found:348.1230.
实施例11
氮气条件下,噁嗪化合物1k(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物9'-三氟甲基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ka),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,64%的产率,熔程:185–186℃.核磁谱图如图21和22所示,1H NMR(400MHz,CDCl3)δ7.92(s,1H),7.69–7.59(m,2H),7.24(d,J=2.9Hz,1H),6.94(d,J=8.5Hz,2H),6.91–6.81(m,2H),6.77(td,J=8.2,7.4,2.3Hz,2H),4.81(d,J=2.6Hz,1H),4.73(s,1H),4.39(dd,J=11.3,2.6Hz,1H),3.84(d,J=11.4Hz,1H).13C NMR(101MHz,CDCl3)δ151.04,145.73,143.34,135.34,132.21(q,J=32.5Hz),131.61,130.69,126.20,125.26(q,J=3.7Hz),122.57,122.30,121.00,120.66,119.77,119.62(q,J=3.8Hz),118.32,116.79,116.25,109.65,83.69,67.36.HRMS[M+H]+calculated for C21H15F3NO3 +:386.0999,found:368.1001.
实施例12
氮气条件下,噁嗪化合物1l(0.20mmol),1,4-苯醌化合物2a(0.3mmol),[RuCl2(p-cymene)]2(噁嗪化合物的2mol%),AgSbF6(噁嗪化合物的8mol%),醋酸锂(0.44mmol)和溶剂三氟甲苯(4.0mL)加入到10mL密封管中,在80℃的反应模块中反应12h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物9'-氯-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3la),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,29%的产率,熔程:123–124℃.核磁谱图如图23和24所示,1H NMR(400MHz,CDCl3)δ7.62(s,1H),7.43(d,J=8.2Hz,1H),7.31(d,J=8.0Hz,1H),7.13(s,1H),6.99–6.78(m,4H),6.78–6.59(m,2H),4.86(s,1H),4.80(s,1H),4.35(d,J=11.0Hz,1H),3.79(d,J=11.4Hz,1H).13C NMR(101MHz,CDCl3)δ150.90,145.90,143.36,136.21,132.52,130.84,130.44,128.64,127.02,122.81,122.18,121.09,120.52,119.70,118.07,116.77,116.12,109.60,83.63,67.58.HRMS[M+H]+calculated for C20H15ClNO3 +:352.0735,found:352.0736.
实施例13
氮气条件下,噁嗪化合物1m(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物9'-苯基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ma),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,65%的产率,熔程:159–160℃.核磁谱图如图25和26所示,1H NMR(400MHz,CDCl3)δ7.87(s,1H),7.62(d,J=6.9Hz,2H),7.57(t,2H),7.48(t,J=7.5Hz,2H),7.41(t,J=7.3Hz,1H),7.32–7.27(m,1H),6.96–6.89(m,2H),6.87(dd,J=7.6,1.6Hz,1H),6.81(td,J=7.6,1.6Hz,1H),6.78–6.69(m,2H),4.83(d,J=2.4Hz,1H),4.74(s,1H),4.42(dd,J=11.3,2.5Hz,1H),3.89(d,J=11.3Hz,1H).13C NMR(101MHz,CDCl3)δ150.81,145.95,143.47,143.01,140.49,131.09,129.12,128.08,127.59,127.35,125.88,122.25,122.09,121.50,120.34,119.63,117.37,116.77,116.00,109.59,83.71,67.83.(Two carbon is not visible due to overlapping peaks).HRMS[M+H]+calculated forC26H20NO3 +:394.1438,found:394.1438.
实施例14
氮气条件下,噁嗪化合物1n(0.20mmol),1,4-苯醌化合物2a(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物9'-甲基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3na),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,65%的产率,熔程:106–107℃.核磁谱图如图27和28所示,1H NMR(400MHz,CDCl3)δ7.48(d,J=1.7Hz,1H),7.38(d,J=7.8Hz,1H),7.22–7.14(m,2H),6.92(dd,J=7.9,1.5Hz,1H),6.89–6.83(m,2H),6.79(td,J=7.6,1.6Hz,1H),6.72(dd,J=7.6,1.6Hz,1H),6.68(dd,J=8.7,2.9Hz,1H),4.85(s,1H),4.78(d,J=2.4Hz,1H),4.36(dd,J=11.3,2.4Hz,1H),3.83(d,J=11.3Hz,1H),2.41(s,3H).13C NMR(101MHz,CDCl3)δ150.71,145.82,143.38,139.82,131.17,130.48,129.58,129.40,125.23,123.30,122.33,122.06,120.21,119.48,117.07,116.71,115.92,109.52,83.67,67.89,21.60.HRMS[M+H]+calculated for C21H18NO3 +:332.1281,found:332.1280.
实施例15
氮气条件下,噁嗪化合物1a(0.20mmol),1,4-苯醌化合物2b(0.44mmol),二氯(五甲基环戊二烯基)合铑(III)二聚体(4mol%),AgSbF6(16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物3',4'-二甲基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ab),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,45%的产率,熔程:185–186℃.核磁谱图如图29和30所示,1H NMR(400MHz,CDCl3)δ7.66(dd,J=7.8,1.2Hz,1H),7.51(dd,J=7.6,1.4Hz,1H),7.45(td,J=7.6,1.4Hz,1H),7.35(td,J=7.5,1.3Hz,1H),7.03(s,1H),6.95–6.84(m,2H),6.84–6.72(m,2H),4.77(d,J=2.5Hz,1H),4.52(s,1H),4.34(dd,J=11.1,2.5Hz,1H),3.85(d,J=11.2Hz,1H),2.18(s,3H),2.08(s,3H).13C NMR(101MHz,CDCl3)δ148.68,143.75,143.71,132.32,131.41,131.39,129.79,128.36,128.21,125.21,125.00,122.57,121.77,120.27,119.39,116.49,116.18,106.50,83.56,67.64,12.33,12.06.HRMS:[M+H]+calculated for C22H20NO3 +:346.1438,found:346.1441.
实施例16
氮气条件下,噁嗪化合物1a(0.20mmol),1,4-苯醌化合物2c(0.44mmol),[RuCl2(p-cymene)]2(噁嗪化合物的4mol%),AgSbF6(噁嗪化合物的16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物3'-甲氧基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ac),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。产物数据表征:白色固体,61%的产率,熔程:163–164℃.核磁谱图如图31和32所示,1H NMR(400MHz,CDCl3)δ7.62(dd,J=7.9,1.2Hz,1H),7.45(qd,J=7.7,1.4Hz,2H),7.34–7.27(m,2H),6.93(dd,J=7.8,1.5Hz,1H),6.88(td,J=7.5,1.6Hz,1H),6.80(td,J=7.6,1.7Hz,1H),6.74(dd,J=7.7,1.7Hz,1H),6.57(s,1H),5.35(s,1H),4.80(d,J=2.4Hz,1H),4.43(dd,J=11.2,2.3Hz,1H),3.86(d,J=11.3Hz,1H),3.84(s,3H).13C NMR(101MHz,CDCl3)δ148.09,145.64,143.41,141.08,131.16,131.02,130.87,129.96,127.70,125.16,122.08,122.05,120.21,116.72,115.95,113.86,108.29,101.67,83.90,67.83,56.20.HRMS[M+H]+calculated for C21H18NO4 +:348.1230,found:348.1230.
实施例17
氮气条件下,噁嗪化合物1a(0.20mmol),1,4-苯醌化合物2d(0.44mmol),[RuCl2(p-cymene)]2(4mol%),AgSbF6(16mol%),Cu(OAc)2(0.4mmol)和溶剂DCE(2.0mL)加入到10mL密封管中,在30℃的反应模块中反应16h,反应结束后减压除去溶剂,用硅胶柱分离得到目标产物4'-叔丁基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ad)和3'-叔丁基-2H,4H-螺环[苯并[b][1.4]噁嗪-3,6‘-苯并[c]色烯]-2’-醇(3ad’),所有洗脱剂为石油醚和乙酸乙酯和二氯甲烷按15:1:1的比例配制而成。3ad产物数据表征:白色固体,23%的产率,熔程:155-156℃.核磁谱图如图33和34所示,1H NMR(400MHz,CDCl3)δ7.70(d,J=7.8Hz,1H),7.54–7.43(m,2H),7.38(t,J=7.5Hz,1H),7.13(d,J=3.0Hz,1H),6.92–6.75(m,4H),6.70(dd,1H),4.78(d,1H),4.56(s,1H),4.48(dd,J=11.2,2.4Hz,1H),4.04(d,J=11.1Hz,1H),1.24(s,9H).13C NMR(101MHz,CDCl3)δ149.74,144.41,143.24,141.69,131.82,131.30,130.96,129.79,128.52,124.47,123.24,122.30,121.85,120.17,116.67,115.61,115.57,107.15,83.09,68.03,34.97,29.81.HRMS[M+H]+calculated for C24H24NO3 +:374.1751,found:374.1758.3ad’产物数据表征:白色固体,23%的产率,熔程:124–125℃.核磁谱图如图35和36所示,1HNMR(400MHz,CDCl3)δ7.65–7.58(m,1H),7.50(dd,J=7.7,1.4Hz,1H),7.43(td,J=7.6,1.4Hz,1H),7.34(td,J=7.5,1.2Hz,1H),7.02(s,1H),6.97–6.91(m,2H),6.89(td,J=7.5,1.5Hz,1H),6.81(td,J=7.6,1.6Hz,1H),6.75(dd,J=7.7,1.6Hz,1H),4.79(d,J=2.3Hz,1H),4.74(s,1H),4.42(dd,J=11.2,2.4Hz,1H),3.85(d,J=11.3Hz,1H),1.38(s,9H).13C NMR(101MHz,CDCl3)δ149.43,145.40,143.36,139.28,131.71,131.20,130.52,129.83,128.36,125.43,122.14,122.07,120.18,119.09,117.34,116.77,115.92,110.34,83.68,67.97,34.92,29.64.HRMS[M+H]+calculated for C24H24NO3 +:374.1751,found:374.1758.
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (10)
2.根据权利要求1所述的螺吡喃类化合物的合成方法,其特征在于,在惰性氛围下将反应物噁嗪类化合物、1,4-苯醌类化合物和催化剂、添加剂一起加入到溶剂当中进行反应,反应结束后制得螺吡喃类化合物。
3.根据权利要求2所述的螺吡喃类化合物的合成方法,其特征在于,具体步骤为:所述噁嗪类化合物、1,4-苯醌类化合物、催化剂和添加剂的摩尔比为1:(1.1-2.2):(0.1-0.2):(1.1-2.2)。
4.根据权利要求3所述的螺吡喃类化合物的合成方法,其特征在于:所述溶剂当中噁嗪类化合物的浓度为0.05M-0.1M。
5.根据权利要求4所述的螺吡喃类化合物的合成方法,其特征在于,所述添加剂为醋酸铜、醋酸钠、醋酸锂或碳酸氢钠中的任一种或两种以上。
6.根据权利要求2-5任一项所述的螺吡喃类化合物的合成方法,其特征在于,所述催化剂由钌催化剂/铑催化剂和银盐组成,钌催化剂/铑催化剂和银盐的摩尔比为1:4。
7.根据权利要求6所述的螺吡喃类化合物的合成方法,其特征在于,所述钌催化剂为2二氯双(4-甲基异丙基苯基)钌,所述铑催化剂为二氯(五甲基环戊二烯基)合铑(III)二聚体,所述银盐为六氟锑酸银。
8.根据权利要求7所述的螺吡喃类化合物的合成方法,其特征在于,所述溶剂1,2-二氯乙烷、二氯甲烷、乙二醇二甲醚或三氟甲苯中任意一种。
9.根据权利要求8所述的螺吡喃类化合物的合成方法,其特征在于,所述惰性氛围为氮气氛围。
10.根据权利要求6-9任一项所述的螺吡喃类化合物的合成方法,其特征在于,所述反应的反应温度为30℃-80℃,反应时间为12h-24h。
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Cited By (2)
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CN116768916A (zh) * | 2023-06-20 | 2023-09-19 | 河南农业大学 | 一种含螺吡喃结构的香豆素类化合物及其合成方法与应用 |
CN116768916B (zh) * | 2023-06-20 | 2024-04-26 | 河南农业大学 | 一种含螺吡喃结构的香豆素类化合物及其合成方法与应用 |
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