CN114380712B - 一种α-氨基酰胺类化合物的合成方法 - Google Patents
一种α-氨基酰胺类化合物的合成方法 Download PDFInfo
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- CN114380712B CN114380712B CN202011131990.4A CN202011131990A CN114380712B CN 114380712 B CN114380712 B CN 114380712B CN 202011131990 A CN202011131990 A CN 202011131990A CN 114380712 B CN114380712 B CN 114380712B
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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Abstract
本发明涉及有机合成技术领域，特别涉及一种α‑氨基酰胺类化合物的合成方法。本发明开发了一种新的合成α‑氨基酰胺类化合物的方法，其由亚胺与异氰酸酯在光催化体系中反应生成α‑氨基酰胺类化合物，本发明的方法条件极度温和，无需采用极端温度，极端压力等苛刻条件；反应易于操作；所得产物产率很高；且所述有些实施例可以在无金属催化下进行，反应绿色环保且反应步骤简单，一步反应即可获得目标分子。
Description
技术领域
本发明涉及有机合成技术领域，特别涉及一种α-氨基酰胺类化合物的合成方法。
背景技术
酰胺类化合物是指氨或胺的氮原子上的氢被酰基取代后生成的化合物。多肽、蛋白质以及尼龙6、尼龙66、尼龙1010等合成纤维都是含有酰胺键的化合物。结构通式为生物体内常见的酰胺有谷氨酰胺(简写为GLn或Q)和天冬酰胺(简写为Asn或N)以及它们的衍生物。它们不仅是蛋白质的组成成分，而且在生命活动中起贮氮和供氮的作用，如合成嘌呤和嘧啶核苷酸中一部分氮均有谷氨酰胺提供，还常是糖蛋白中蛋白与碳水化合物之间联系的桥梁。
α-氨基酰胺广泛存在于天然产物和药物中，并已用作合成不同杂环的中间体。在生物化学领域，α-氨基酰胺结构作为多肽或者蛋白质结构单元，在多肽类，蛋白质与药物分子合成中具有广泛应用前景。
因此，关于α-氨基酰胺类化合物，开发一种简单高效、反应试剂价格低廉以及反应条件温和、化学选择性高的合成方法具有重要的意义和极高的实际应用价值。
在此之前关于α-氨基酰胺类化合物的合成已有一些报道。例如，2001年，Alper课题组利用钯催化的双碳氢加氢胺化反应，以芳基碘代物为底物实现了α-氨基酰胺的合成。但其使用的钯碳催化剂由于钯的颗粒细小，比表面积大，在空气中易与氧气发生氧化反应，放热，当热量累积到一定程度时就会发生钯颗粒和活性炭颗粒一起燃烧比较危险，且一氧化碳对人体组织细胞具有毒性作用对环境也不友好。
2009年Somfai课题组开发了一种通过修饰的Weinreb酰胺的碱基介导的重排成N，O-乙缩醛，从而直接地合成α-氨基酰胺的方法。同时该课题组对该反应进行了拓展研究，还实现了不带α-氨基的修饰的Weinreb酰胺可以与格式试剂进行α-芳基化反应。但该方法中运用到的格式试剂得严格防止与湿空气接触，否则会产生着火的危险。
2012年，Liu课题组通过对Ugi反应进行改造，实现了铜催化氧化Ugi型反应由N-烷基胺直接合成α-氨基酰胺。但该反应用到的TBHP即叔丁基过氧化氢与还原剂硫、磷等混合可爆，且需与有机物、还原剂等分开存放，运输过程中受热或撞击皆会引发爆炸的可能极其危险。
2013年，Reeves课题组以甲酰胺和N-叔丁烷-或N-2,4,6-三异丙基苯基亚磺酰基亚胺为原料，得到各种手性α-氨基酰胺产物。但该反应中用到的LDA即二异丙基氨基锂在使用时需要将其溶于极性非质子溶剂中，一般需要现配现用，故使用时不太方便。
发明内容
本发明旨在提供一种新的α-氨基酰胺类化合物的合成方法及应用。该方法利用亚胺与异氰酸酯类化合物作为原料通过可见光的介导进行还原偶联反应得到本发明目标产物。该方法反应条件温和，反应过程简单，易于操作。
为了实现上述目的，本发明具体采用如下技术方案：
一种α-氨基酰胺类化合物的合成方法，包括如下步骤：
采用式I所示的亚胺类化合物与式II所示的异氰酸酯类化合物在光源存在下，经光敏催化剂和胺类化合物作用反应生成α-氨基酰胺类化合物；
其中，R1，R2基团分别选自含有1-10个碳原子的饱和或不饱和的烷基、被取代基取代的含有1-10个碳原子的饱和或不饱和的烷基、芳基、取代芳基、杂芳基；
前述所述“被取代基取代的含有1-10个碳原子的饱和或不饱和的烷基”中的取代基选自苯基、吡啶基、取代苯基；
前述所述“取代芳基”，“取代苯基”中的取代基选自含有1-4个碳原子的饱和或不饱和的烷基、卤素基、三氟甲基、甲氧基；
所述的Ar1，Ar2分别选自苯基、取代苯基、吡啶基，所述取代苯基的取代基选自卤素基、含有1-10个碳原子的饱和或不饱和的烷基，Ar1，Ar2可连接成环，如化合物1o即为Ar1，Ar2连接成环。
前述所述胺类化合物选自甲胺类化合物、乙胺类化合物或芳基胺类化合物。
提到的“烷基”既包括支链烷基，也包括直链烷基，还包括成环的烷基，如环烷基、金刚烷基、烷基取代的环烷基等。不饱和烷基指的是含有双键或单键的烷基，如烯丙基等。
优选的，其中，R1，R2基团分别选自含有1-10个碳原子的饱和或不饱和的烷基、被取代基取代的含有1-10个碳原子的饱和烷基、苯基、取代苯基、吡啶基；
前述所述“被取代基取代的含有1-10个碳原子的饱和烷基”中的取代基选自苯基、吡啶基、取代苯基；
前述所述“取代苯基”中的取代基选自含有1-4个碳原子的饱和或不饱和的烷基、卤素基、三氟甲基、甲氧基。
优选的，式I所示的亚胺类化合物选自如下结构：
式II所示的异氰酸酯类化合物选自如下结构：
所述的胺类化合物选自二甲胺、二乙胺、三乙胺、己二胺、二异丙基甲胺、N，N-二异丙基乙胺、二环己基乙胺、N,N-二甲基苯胺、N,N-二环己基甲胺。
优选的，所述光源选自太阳光、LED光。
优选的，所述反应在有机溶剂中进行。
优选的，所述有机溶剂选自醇类、酯类、酰胺类、亚砜类、呋喃类、腈类化合物。
优选的，所述光敏催化剂选自如下结构：
优选的，所述反应于无水无氧条件下反应，反应温度为20～45℃。
优选的，所述光敏催化剂与式I所示的亚胺类化合物的摩尔比为0.5％～2％；所述式II所示异氰酸酯类化合物与式I所示的亚胺类化合物的摩尔比为2～4：1；所述胺类化合物与式I所示的亚胺类化合物的摩尔比为1～3：1。
优选的，所述光敏催化剂与式I所示的亚胺类化合物的摩尔比为0.5％；所述式II所示异氰酸酯类化合物与式I所示的亚胺类化合物的摩尔比为3：1；所述胺类化合物与式I所示的亚胺类化合物的摩尔比为2：1。
有益效果：
本发明由亚胺与异氰酸酯在光催化体系中反应生成α-氨基酰胺类化合物易于转化为苯并二氮类药物，开发了一种新的合成α-氨基酰胺类化合物的方法。本发明的方法条件极度温和，无需采用极端温度，极端压力等苛刻条件；反应易于操作；所得产物产率很高；且所述有些实施例可以在无金属催化下进行，反应绿色环保且反应步骤简单，一步反应即可获得目标分子且目标氨基酰胺类分子还可以进一步的衍生化得到苯并二氮类药物，该药物具有一定的药理活性，包括抗焦虑、抗晕厥以及镇静的作用，在最近的几十年里成为使用最频繁的药物之一。
附图说明
图1为实施例1中产物的1HNMR光谱分析图。
图2为实施例2中产物的1HNMR光谱分析图。
图3为实施例3中产物的1HNMR光谱分析图。
图4为实施例4中产物的1HNMR光谱分析图。
图5为实施例5中产物的1HNMR光谱分析图。
图6为实施例6中产物的1HNMR光谱分析图。
图7为实施例7中产物的1HNMR光谱分析图。
图8为实施例8中产物的1HNMR光谱分析图。
图9为实施例9中产物的1HNMR光谱分析图。
图10为实施例10中产物的1HNMR光谱分析图。
图11为实施例11中产物的1HNMR光谱分析图。
图12为实施例12中产物的1HNMR光谱分析图。
图13为实施例13中产物的1HNMR光谱分析图。
图14为实施例14中产物的1HNMR光谱分析图。
图15为实施例15中产物的1HNMR光谱分析图。
图16为实施例16中产物的1HNMR光谱分析图。
图17为实施例17中产物的1HNMR光谱分析图。
图18为实施例18中产物的1HNMR光谱分析图。
图19为实施例19中产物的1HNMR光谱分析图。
图20为实施例20中产物的1HNMR光谱分析图。
图21为实施例21中产物的1HNMR光谱分析图。
图22为实施例22中产物的1HNMR光谱分析图。
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。以下对至少一个示例性实施例的描述实际上仅仅是说明性的，决不作为对本发明及其应用或使用的任何限制。基于本发明中的实施例，本领域普通技术人员在没有作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。
需要注意的是，这里所使用的术语仅是为了描述具体实施方式，而非意图限制根据本申请的示例性实施方式。如在这里所使用的，除非上下文另外明确指出，否则单数形式也意图包括复数形式，此外，还应当理解的是，当在本说明书中使用术语“包含”和/或“包括”时，其指明存在特征、步骤、操作、器件、组件和/或它们的组合。
下面结合附图对本发明进行详细说明，以方便本领域技术人员理解本发明。
实施例中所使用的所有化学试剂除了亚胺是现场合成(合成方法均为现有技术)，
其他原料均购自市场。以下实施例中所使用的仪器包括400兆核磁波谱仪(JNM-ECZ400S)以及IS10 FT-IR红外光谱仪。
通过光氧化还原催化以亚胺和异氰酸酯为原料的α-氨基酰胺类化合物的合成
将亚胺(0.1mmol)，光催化剂(1-4毫克,0.5-2mmol％)，胺(0.2-0.4mmol,2-4eq)，异氰酸酯(0.2-0.4mmol,2-4eq)在无水无氧氛围下溶于有机溶剂中，室温下可见光照射搅拌反应12-36小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标α-氨基酰胺类化合物。
实施例1
按照典型实验过程，将N-苄基-1,1-二苯甲亚胺(1a:27.1毫克,0.10mmol)、异氰酸苄酯(37微升,0.3mmol)、有机催化剂1(0.5毫克,0.5mol％)、N,N-二异丙基乙胺(33微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(30.5毫克，收率75％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图1所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.32–7.24(m,5H),7.24–7.19(m,5H),7.19–7.16(m,3H),7.15–7.14(m,3H),6.98–6.89(m,4H),6.75(s,1H),4.68(t,J＝5.3Hz,1H),4.56(s,2H),4.34(d,J＝5.4Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ158.68,139.92,138.04,129.08,128.76,128.68,128.58,127.73,127.37,127.31,127.11,63.31,49.11,45.15ppm.IR(thin film):3053,1648,1516,1496,1454,1265,738,704cm-1；HRMS计算量：407.2123,实测量:407.2122
实施例2
按照典型实验过程，将N-(2-氯苯)-1,1-二苯甲亚胺(1b:30.6毫克,0.10mmol)、异氰酸苄酯(37微升,0.3mmol)、Ru-1(0.5毫克,0.5mol％)、二甲胺(10微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(34.8毫克，收率79％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图2所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.27–7.16(m,13H),7.15–7.11(m,1H),7.07–6.96(m,5H),6.76(s,1H),4.74(t,J＝4.8Hz,1H),4.66(s,2H),4.38(d,J＝5.5Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ158.42,139.49,139.28,134.68,129.16,128.92,128.64,128.58,128.21,127.69,127.38,127.20,126.64,63.37,46.40,45.09ppm.IR(thinfilm):3031,1650,1514,1454,1239,867,760,739,cm-1；HRMS计算量：441.1734,实测量：441.1730[M+H]+.
实施例3
按照典型实验过程，将N-(4-甲基苄基)-1,1-二苯甲亚胺(1c:28,5毫克,0.10mmol)，异氰酸苄酯(37微升,0.3mmol)，Ir-6(0.5毫克,0.5mol％)，N,N-二异丙基乙胺(50微升,0.3mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，20℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(37.9毫克，收率90％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图3所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.30–7.21(m,10H),7.19–7.16(m,3H),6.95(d,J＝7.9Hz,2H),6.93–6.89(m,2H),6.81(d,J＝7.6Hz,3H),4.69(t,J＝4.9Hz,1H),4.51(s,2H),4.32(d,J＝5.4Hz,2H),2.25(s,3H)ppm.13C NMR(101MHz,Chloroform-d)δ158.75,140.10,134.91,129.46,129.13,128.79,128.55,127.71,127.31,127.09,63.22,48.89,45.12,21.25ppm.IR(thin film):3442,3031,1647,1515,1257,801,765,714cm-1；HRMS calcd for C29H29N2O+421.2280,observed421.2276[M+H]+.
实施例4
按照典型实验过程，将N-(4-氯苯)-1,1-二苯甲亚胺(1d:30.6毫克,0.10mmol)、异氰酸苄酯(37微升,0.3mmol)、Ir-9(0.5毫克,0.5mol％)、二乙胺(21微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(35.3毫克，收率80％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图4所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.31–7.23(m,6H),7.23–7.14(m,7H),7.09(d,J＝8.4Hz,2H),6.95(dd,J＝7.3,2.0Hz,2H),6.85(d,J＝8.4Hz,2H),6.60(s,1H),4.65(t,J＝5.4Hz,1H),4.53(s,2H),4.34(d,J＝5.4Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ158.37,139.44,139.04,136.82,132.79,128.85,128.69,128.47,127.75,127.18,127.09,63.45,48.43,45.05ppm.IR(thin film):3447,1648,1516,1256,758,738,701,601cm-1；HRMS calcd for C28H26ClN2O+441.1734,observed441.1730[M+H]+.
实施例5
按照典型实验过程，将N-(2-溴苄)-1,1-二苯甲亚胺(1e:35.0毫克,0.10mmol)、异氰酸苄酯(37微升,0.3mmol)、Ir-8(0.5毫克,0.5mol％)、N,N-二异丙基乙胺(33微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(38.8毫克，收率80％)。产物结构如上所示，产物的1HNMR核磁分析谱图如图5所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.37–7.31(m,1H),7.29–7.16(m,13H),7.10–7.02(m,3H),7.01–6.94(m,2H),6.76(s,1H),4.68(t,J＝5.5Hz,1H),4.62(s,2H),4.40(d,J＝5.5Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ158.36,139.48,139.23,136.16,132.42,128.89,128.72,128.62,128.55,128.50,127.65,127.37,127.21,127.17,122.28,63.40,49.03,45.11ppm.IR(thin film):3446,3054,1649,1515,1265,777,738,705cm-1；HRMS calcd for C28H26BrN2O+485.1229,observed485.1226[M+H]+.
实施例6
按照典型实验过程，将N-(4-氟苄)-1,1-二苯甲亚胺(1f:28.9毫克,0.10mmol)、异氰酸苄酯(37微升,0.3mmol)、Ir-11(0.5毫克,0.5mol％)、三乙胺(28微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，30℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(39.1毫克，收率92％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图6所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.29–7.24(m,6H),7.23–7.14(m,7H),6.95(dd,J＝7.3,2.0Hz,2H),6.92–6.85(m,2H),6.81(t,J＝8.7Hz,2H),6.61(s,1H),4.65(t,J＝5.3Hz,1H),4.54(s,2H),4.35(d,J＝5.4Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ158.42,139.50,139.07,128.85,128.75,128.66,128.45,127.71,127.18,127.07,115.31,115.09,63.38,48.37,45.04ppm.IR(thin film):(thin film):3443,1645,1509,1239,818,747,739,728cm-1；HRMS calcd for C28H26FN2O+425.2029,observed425.2023[M+H]+.
实施例7
按照典型实验过程，将1,1-二苯-n-(4-(三氟甲基)苄基)甲亚胺(1g:33.9毫克,0.10mmol)、异氰酸苄酯(37微升,0.3mmol)、有机催化剂1(0.5毫克,0.5mol％)、N,N-二甲基苯胺(25微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(38.4毫克，收率81％)。产物结构如上所示，产物的1HNMR核磁分析谱图如图7所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.37(d,J＝8.1Hz,2H),7.31–7.22(m,6H),7.22–7.12(m,7H),7.02(d,J＝8.0Hz,2H),6.98–6.90(m,2H),6.56(s,1H),4.68(t,J＝5.3Hz,1H),4.62(s,2H),4.36(d,J＝5.4Hz,2H)ppm.13CNMR(101MHz,Chloroform-d)δ158.34,142.67,139.24,138.97,128.83,128.71,128.49,127.86,127.31,127.16,125.19,125.15,63.68,48.67,45.08ppm.IR(thin film):3443,3055,1640,1265,896,776,738,705cm-1；HRMS calcd for C29H26F3N2O+475.1997,observed475.1992[M+H]+.
实施例8
按照典型实验过程，以N-(4-(叔丁基)苄)-1,1-二苯甲亚胺(1h:32.7毫克,0.10mmol)、异氰酸苄酯(37微升,0.3mmol)、Ru-2(0.5毫克,0.5mol％)、N,N-二异丙基乙胺(17微升,0.1mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(37.5毫克，收率81％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图8所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.33–7.20(m,11H),7.19–7.12(m,5H),6.90(dd,J＝6.7,2.4Hz,2H),6.84(d,J＝8.6Hz,3H),4.69(t,J＝5.3Hz,1H),4.51(s,2H),4.33(d,J＝5.4Hz,2H),1.25(s,9H)ppm.13C NMR(101MHz,Chloroform-d)δ158.76,140.16,134.97,129.16,128.77,128.56,127.68,127.33,127.13,126.93,125.70,63.22,48.82,45.18,34.64,31.54ppm.IR(thin film):3443,3055,1644,1265,781,735,705,560cm-1；HRMS calcd for C32H35N2O+463.2749,observed463.2745[M+H]+.
实施例9
按照典型实验过程，以1,1-二苯-N-(2-吡啶基)甲亚胺(1i:27.2毫克,0.10mmol)、异氰酸苄酯(37微升,0.3mmol)、有机催化剂1(0.5毫克,0.5mol％)、N,N-二异丙基乙胺(33微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(35.9毫克，收率88％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图9所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ8.27(d,J＝4.2Hz,1H),7.84(s,1H),7.34–7.22(m,12H),7.22–7.16(m,4H),7.02(dd,J＝6.9,5.1Hz,1H),6.93(s,1H),5.89(d,J＝7.8Hz,1H),4.53(s,2H),4.50(d,J＝5.3Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ159.99,158.04,148.25,140.63,136.69,129.23,128.53,128.50,127.66,127.36,126.93,122.62,122.34,62.90,50.56,45.24ppm.IR(thin film):3440,3054,1637,1265,896,777,733,706cm-1；HRMS calcdforC27H26N3O+408.2076,observed408.2073[M+H]+.
实施例10
按照典型实验过程，将1,1-三苯甲亚胺(1j:25.7毫克,0.10mmol)，异氰酸苄酯(37微升,0.3mmol)，Ru-3(0.5毫克,0.5mol％)，N,N-二异丙基乙胺(33微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，35℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(27.5毫克，收率70％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图10所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.38–7.18(m,15H),7.18–7.11(m,4H),6.99–6.86(m,2H),4.61(t,J＝5.4Hz,1H),4.45(d,J＝5.8Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ157.39,140.11,139.32,130.87,129.47,129.33,128.53,128.04,128.00,127.23,127.11,64.49,44.80ppm.IR(thin film):3446,3054,1656,1507,1265,895,738,705,cm-1；HRMS calcd for C27H25N2O+393.1967,observed 393.1963[M+H]+.
实施例11
按照典型实验过程，将(Z)-N-苄基-1-苯基-1-(对甲苯)甲亚胺(1k:28.5m毫克,0.10mmol)、异氰酸苄酯(37微升,0.3mmol)，有机催化剂3(0.5毫克,0.5mol％)，N,N-二异丙基乙胺(33微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，35℃下太阳光照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(36.2毫克，收率86％)。产物结构如上所示，产物的1HNMR核磁分析谱图分别如图11所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.32–7.12(m,11H),7.08(s,4H),7.01–6.87(m,4H),6.65(s,1H),4.66(t,J＝5.1Hz,1H),4.56(d,J＝5.5Hz,2H),4.33(d,J＝4.8Hz,2H),2.30(s,3H)ppm.13C NMR(101MHz,Chloroform-d)δ158.63,140.00,138.17,137.38,136.74,129.39,128.95,128.91,128.67,128.60,128.49,127.59,127.27,127.24,127.18,127.04,63.08,49.11,45.06,21.21ppm.IR(thin film):3432,3054,1644,1265,896,777,737,705cm-1；HRMS calcd forC29H29N2O+421.2280,observed421.2278[M+H]+.
实施例12
按照典型实验过程，将N-苄基-1,1-双(4-氯苯基)甲亚胺(1l:34.0毫克,0.10mmol)，异氰酸苄酯(37微升,0.3mmol)，Ru-4(0.5毫克,0.5mol％)，N,N-二异丙基乙胺(33微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(38毫克，收率88％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图12所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.25(d,J＝8.4Hz,4H),7.23–7.15(m,6H),7.13(d,J＝8.6Hz,4H),6.95(dd,J＝6.9,1.9Hz,2H),6.91–6.89(m,2H),6.82(s,1H),4.69(t,J＝5.3Hz,1H),4.49(s,2H),4.34(d,J＝5.3Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ158.33,138.98,138.09,137.15,133.67,130.27,128.92,128.82,128.59,127.27,127.25,126.60,61.94,48.66,45.12ppm.IR(thin film):3446,1650,1492,1259,1092,765,716,524cm-1；HRMS calcd for C28H25Cl2N2O+475.1344,observed475.1342[M+H]+.
实施例13
按照典型实验过程，将(E)-N-苄基-1-(2-氟苯基)-1-苯基甲亚胺(1m:28.9毫克,0.10mmol)，异氰酸苄酯(37微升,0.3mmol)，有机催化剂1(0.5毫克,0.5mol％)，N,N-二异丙基乙胺(33微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，40℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(34毫克，收率80％)。产物结构如上所示，产物的1HNMR核磁分析谱图分别如图13所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.32–7.11(m,13H),7.07–7.02(m,1H),7.02–6.95(m,4H),6.95–6.90(m,2H),4.81–4.71(m,2H),4.42(d,J＝9.6Hz,1H),4.40–4.34(m,2H),4.32(d,J＝5.5Hz,0H)ppm.13C NMR(101MHz,Chloroform-d)δ158.47,139.07,137.81,130.34,130.31,129.80,129.72,128.78,128.55,128.15,127.74,127.27,127.20,127.12,126.78,124.24,124.21,57.70,57.67,49.08,45.07ppm.IR(thin film):3443,3055,1648,1516,1265,778,733,704cm-1；HRMS calcd for C28H26FN2O+425.2029,observed425.2023[M+H]+.
实施例14
按照典型实验过程，将(E)-N-苄基-1-苯基-1-(吡啶-2-基)甲亚胺(1n:27.2毫克,0.10mmol)，异氰酸苄酯(49微升,0.4mmol)，有机催化剂1(0.5毫克,0.5mol％)，N,N-二异丙基乙胺(33微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(35.9毫克，收率88％)。产物结构如上所示，产物的1HNMR核磁分析谱图如图14所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ8.55–8.40(m,1H),7.62(td,J＝7.7,1.8Hz,1H),7.31–7.22(m,3H),7.22–7.13(m,9H),7.11–7.08(m,3H),6.90(dd,J＝7.0,2.3Hz,2H),6.49(s,1H),5.99(s,1H),4.91(d,J＝16.4Hz,1H),4.63(d,J＝16.4Hz,1H),4.41–4.25(m,2H)ppm.13C NMR(101MHz,Chloroform-d)δ159.56,158.83,149.26,139.46,139.20,138.58,136.86,128.67,128.59,128.50,128.35,127.53,127.29,127.15,126.79,124.51,122.59,64.29,50.71,44.84ppm.IR(thinfilm):3442,3055,1637,1266,783,758,738,552cm-1；HRMS calcd for C27H26N3O+408.2076,observed408.2070[M+H]+.
实施例15
按照典型实验过程，将N-苯基-9-芴-亚胺(1o:25.5毫克,0.10mmol)、酸苄酯(37微升,0.3mmol)，有机催化剂2(2毫克,2mol％)，己二胺(26微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(35.1毫克，收率90％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图15所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.70–7.64(m,2H),7.57–7.50(m,2H),7.37–7.21(m,9H),7.06–6.95(m,4H),6.80(dd,J＝6.6,3.0Hz,2H),4.67(t,J＝5.7Hz,1H),4.52(d,J＝5.8Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ158.15,143.43,140.80,129.53,129.13,128.60,128.19,127.96,127.23,127.17,125.78,119.84,61.28,44.94ppm.IR(thin film):3442,1636,1508,1265,779,737,704,526cm-1；HRMS calcdfor C27H23N2O+391.1810,observed 391.1808[M+H]+.
实施例16
按照典型实验过程，将正丁基-1,1-二苯甲亚胺(1p:23.7毫克,0.10mmol)，异氰酸苄酯(37微升,0.3mmol)，Ru-31毫克,1mol％)，N,N-二异丙基乙胺(33微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，45℃下20W白色LED照射搅拌反应约12小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(32毫克，收率86％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图16所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.34–7.26(m,8H),7.21(d,J＝6.9Hz,5H),7.17(d,J＝7.0Hz,2H),6.58(s,1H),4.73(t,J＝5.3Hz,1H),4.43(d,J＝5.4Hz,2H),3.31–3.13(m,2H),1.13–0.92(m,4H),0.64(t,J＝7.2Hz,3H)ppm.13C NMR(101MHz,Chloroform-d)δ158.04,140.17,139.71,128.94,128.65,128.60,127.60,127.49,127.20,63.08,45.58,45.08,31.24,20.21,13.66ppm.IR(thin film):3440,3055,1640,1510,1265,781,735,704,cm-1；HRMS calcd for C25H29N2O+373.2280,observed 373.2278[M+H]+.
实施例17
按照典型实验过程，将N-烯丙基-1,1-二苯甲亚胺(1q:22.1毫克,0.10mmol)，异氰酸苄酯(37微升,0.3mmol)，有机催化剂1(0.5毫克,0.5mol％)，N,N-二异丙基乙胺(33微升,0.2mmol)在无水无氧的氛围下溶于N，N-二甲基甲酰胺(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(26.4毫克，收率74％)。产物结构如上所示，产物的1HNMR核磁分析谱图如图17所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.36–7.26(m,8H),7.26–7.17(m,7H),6.86(s,1H),5.32(ddt,J＝15.8,10.7,5.5Hz,1H),5.00(s,1H),4.94(d,J＝9.8Hz,2H),4.44(d,J＝5.4Hz,2H),3.89(d,J＝5.5Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ158.52,140.04,139.40,135.31,128.85,128.55,128.49,127.44,127.41,127.14,117.15,62.43,47.92,45.06ppm.IR(thin film):3443,3054,1643,1265,779,737,705,591cm-1；HRMS calcd for C24H25N2O+357.1967,observed357.1964[M+H]+.
实施例18
按照典型实验过程，将N-苄基-1,1-二苯甲亚胺(27.1毫克,0.10mmol)、叔丁基氰酸酯(2b:23微升,0.2mmol)、催化剂Ru-2(1毫克,1mol％)、二异丙基甲胺(31微升,0.2mmol)在无水无氧的氛围下溶于二甲亚砜(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(24.2毫克，收率65％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图18所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.34–7.27(m,5H),7.25–7.17(m,8H),7.04–6.96(m,2H),6.60(s,1H),4.50(s,2H),4.22(s,1H),1.10(s,9H)ppm.13CNMR(101MHz,Chloroform-d)δ140.22,129.00,128.71,128.64,127.60,127.40,62.75,50.95,49.36,29.26ppm.IR(thin film):3440,3055,1643,1265,896,746,733,706cm-1；HRMS calcd for C25H29N2O+373.2280,observed373.2279[M+H]+.
实施例19
按照典型实验过程，将N-苄基-1,1-二苯甲亚胺(27.1毫克,0.10mmol)，环戊基异氰酸酯(2c:23微升,0.2mmol)、催化剂Ir-12(1毫克,1mol％)、N,N-二环己基甲胺(42.8微升,0.2mmol)在无水无氧的氛围下溶于甲醇(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(29.6毫克，收率77％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图19所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.30(q,J＝6.0,5.3Hz,6H),7.24–7.15(m,7H),6.99(d,J＝6.6Hz,2H),6.63(s,1H),4.53(s,2H),4.22(d,J＝7.1Hz,1H),4.11–4.03(m,1H),1.75(dq,J＝12.9,6.4Hz,2H),1.48–1.35(m,2H),1.33–1.16(m,2H),1.04(dq,J＝12.7,6.3,5.9Hz,2H)ppm.13C NMR(101MHz,Chloroform-d)δ158.35,140.02,128.97,128.71,128.65,127.64,127.38,127.28,63.01,52.68,49.28,33.38,23.38ppm.IR(thin film):3442,1639,1516,1265,780,734,703,549,cm-1；HRMScalcd for C26H29N2O+385.2280,observed 385.2282[M+H]+.
实施例20
按照典型实验过程，将N-苄基-1,1-二苯甲亚胺(27.1毫克,0.10mmol)，异氰酸苯乙酯(2d:28微升,0.2mmol)、催化剂Ir-5(1毫克,1mol％)、N,N-二环己基甲胺(42.8微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(23.6毫克，收率56％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图20所示，产物的测试数据为：1H NMR(401MHz,Chloroform-d)δ7.26–7.24(m,6H),7.20–7.07(m,10H),6.97(d,J＝6.8Hz,2H),6.88–6.77(m,2H),6.68(s,1H),4.45(s,2H),4.33(s,1H),3.43(q,J＝6.0Hz,2H),2.62(t,J＝6.6Hz,2H)ppm；13C NMR(101MHz,Chloroform-d)δ158.69,139.87,139.23,137.84,129.00,128.77,128.61,128.48,127.57,127.15,126.83,126.29,63.12,48.90,42.13,36.20ppm.IR(thin film):3443,3054,1643,1265,896,746,734,705cm-1；HRMS calcd for C29H29N2O+421.2280,observed421.2281[M+H]+.
实施例21
按照典型实验过程，将N-苄基-1,1-二苯甲亚胺(27.1毫克,0.10mmol)，间甲苯异氰酸酯(2e:26微升,0.2mmol)、催化剂Ir-2(1毫克,1mol％)、N,N-二环己基甲胺(42.8微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(23.6毫克，收率56％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图21所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.38–7.27(m,10H),7.25–7.13(m,2H),7.08(dd,J＝7.6,2.1Hz,2H),7.06–6.99(m,2H),6.78(d,J＝7.5Hz,1H),6.71(d,J＝10.6Hz,2H),6.31(s,1H),4.68(s,2H),2.25(s,3H)ppm；13C NMR(101MHz,Chloroform-d)δ156.18,139.43,138.87,138.75,137.73,128.98,128.91,128.86,128.61,127.95,127.72,127.50,123.91,120.46,116.75,63.44,49.64,21.56ppm.IR(thin film):3423,3054,1662,1265,745,733,705,517cm-1；HRMS calcd for C28H27N2O+407.2123,observed 407.2118[M+H]+.
实施例22
按照典型实验过程，将N-苄基-1,1-二苯甲亚胺(27.1毫克,0.10mmol)，4-氟苯基异氰酸酯(2f:23微升,0.2mmol)、催化剂Ir-3(1毫克,1mol％)、N,N-二环己基甲胺(42.8微升,0.2mmol)在无水无氧的氛围下溶于乙腈(1毫升)中，25℃下20W白色LED照射搅拌反应约20小时。反应结束后用旋转蒸发仪除去挥发性溶剂，使用石油醚和乙酸乙酯作为洗脱剂通过柱层析法得到目标产物(29.1毫克，收率71％)。产物结构如上所示，产物的1H NMR核磁分析谱图如图22所示，产物的测试数据为：1H NMR(400MHz,Chloroform-d)δ7.38–7.29(m,6H),7.27–7.23(m,7H),7.07(dd,J＝7.2,2.1Hz,2H),6.98–6.91(m,2H),6.86(t,J＝8.7Hz,2H),6.66(s,1H),6.26(s,1H),4.67(s,2H)ppm；13C NMR(101MHz,Chloroform-d)δ159.41,157.01,155.59,138.66,136.96,134.24,128.28,128.25,127.36,127.15,126.85,120.96,120.89,114.83,114.61,62.76,48.98ppm.IR(thin film):3421,3054,1633,1509,1265,777,737,705cm-1；HRMS calcd forC27H24FN2O+411.1873,observed411.1875[M+H]+.
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对本发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。
Claims (9)
1.一种α-氨基酰胺类化合物的合成方法，其特征在于，包括如下步骤：
采用式I所示的亚胺类化合物与式II所示的异氰酸酯类化合物在光源存在下，经光敏催化剂和胺类化合物作用反应生成α-氨基酰胺类化合物；
其中，R1，R2基团分别选自含有1-10个碳原子的饱和烷基、被取代基取代的含有1-10个碳原子的饱和烷基、芳基、取代芳基、杂芳基；
前述所述“被取代基取代的含有1-10个碳原子的饱和烷基”中的取代基选自苯基、吡啶基、取代苯基；
前述所述“取代芳基”，“取代苯基”中的取代基选自含有1-4个碳原子的饱和烷基、卤素基、三氟甲基、甲氧基；
所述的Ar1，Ar2分别选自苯基、取代苯基、吡啶基，所述取代苯基的取代基选自卤素基、含有1-10个碳原子的饱和烷基，Ar1，Ar2可连接成环；
前述所述胺类化合物选自甲胺类化合物、乙胺类化合物或芳基胺类化合物；
所述光敏催化剂选自如下结构：
2.根据权利要求1所述的合成方法，其特征在于，其中，R1，R2基团分别选自含有1-10个碳原子的饱和烷基、被取代基取代的含有1-10个碳原子的饱和烷基、苯基、取代苯基、吡啶基；
前述所述“被取代基取代的含有1-10个碳原子的饱和烷基”中的取代基选自苯基、吡啶基、取代苯基；前述所述“取代苯基”中的取代基选自含有1-4个碳原子的饱和烷基、卤素基、三氟甲基、甲氧基。
3.根据权利要求1所述的合成方法，其特征在于，式I所示的亚胺类化合物选自如下结构：
式II所示的异氰酸酯类化合物选自如下结构：
所述的胺类化合物选自二甲胺、二乙胺、三乙胺、己二胺、二异丙基甲胺、N，N-二异丙基乙胺、二环己基乙胺、N,N-二甲基苯胺、N,N-二环己基甲胺。
4.根据权利要求1所述的合成方法，其特征在于，所述光源选自太阳光、LED光。
5.根据权利要求1所述的合成方法，其特征在于，所述反应在有机溶剂中进行。
6.根据权利要求5所述的合成方法，其特征在于，所述有机溶剂选自醇类、酯类、酰胺类、亚砜类、呋喃类、腈类化合物。
7.根据权利要求1所述的合成方法，其特征在于，所述反应于无水无氧条件下反应，反应温度为20～45℃。
8.根据权利要求1所述的合成方法，其特征在于，所述光敏催化剂与式I所示的亚胺类化合物的摩尔比为0.5％～2％；所述式II所示异氰酸酯类化合物与式I所示的亚胺类化合物的摩尔比为2～4：1；所述胺类化合物与式I所示的亚胺类化合物的摩尔比为1～3：1。
9.根据权利要求8所述的合成方法，其特征在于，所述光敏催化剂与式I所示的亚胺类化合物的摩尔比为0.5％；所述式II所示异氰酸酯类化合物与式I所示的亚胺类化合物的摩尔比为3：1；所述胺类化合物与式I所示的亚胺类化合物的摩尔比为2：1。
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