CN108840806B - 一种苯甲酰胺类化合物的制备方法 - Google Patents

一种苯甲酰胺类化合物的制备方法 Download PDF

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CN108840806B
CN108840806B CN201810653261.1A CN201810653261A CN108840806B CN 108840806 B CN108840806 B CN 108840806B CN 201810653261 A CN201810653261 A CN 201810653261A CN 108840806 B CN108840806 B CN 108840806B
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benzamide
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CN108840806A (zh
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张辰
郑佳垚
崔冬梅
汪涛
施宇龙
刘登辉
班孟涛
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Zhejiang University ZJU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/06—Preparation of carboxylic acid amides from nitriles by transformation of cyano groups into carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B43/00—Formation or introduction of functional groups containing nitrogen
    • C07B43/06—Formation or introduction of functional groups containing nitrogen of amide groups
    • 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
    • C07D213/04—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 having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—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 having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom

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Abstract

本发明提供一种苯甲酰胺类化合物的制备方法，将氨基化合物与苯乙氰混合加入溶剂中，在铜催化剂作用下，在80～120℃温度下搅拌反应15‑30小时，反应结束后，反应液后处理制得苯甲酰胺类化合物。本发明提供的制备方法，设计合理，该工艺反应条件温和，原料易得，操作方便，有着广泛的工业应用前景。为新药筛选及开发奠定了基础，具有较好的实用价值。

Description

一种苯甲酰胺类化合物的制备方法
技术领域
本发明属于制药领域，涉及一种苯甲酰胺类化合物的制备方法。
背景技术
酰胺类化合物不仅是重要的有机合成中间体，也广泛应用于医药、农药及材料的合成中。因此研究开发该类化合物的制备方法具有一定的应用价值。
发明内容
本发明提供一种苯甲酰胺类化合物的制备方法，所述的苯甲酰胺类化合物的结构通式如式(II)所示，通过以下技术方案实现：
Figure BDA0001704685640000011
式(II)中R为C4～C10芳基；优选为苯基或芳杂环；其中芳杂环优选为吡啶或嘧啶。
具体制备方法如下：
将式(I)所示的氨基化合物与苯乙氰混合加入溶剂中，在铜催化剂作用下，在80～120℃温度下搅拌反应15～30小时，反应结束后，反应液后处理制得式(II)所示的苯甲酰胺类化合物。
式(I)所示的氨基化合物与苯乙氰、金属铜催化剂的量比为1：1.0～10.0：0.1～0.4。
式(I)结构式为：
R-NH2 (1)
其中R的定义同通式(II)相同。
所述的溶剂为芳烃类；优选为取代苯类，优选为二氯苯或氯苯。所述溶剂的体积用量通常以氨基化合物的质量计为2～10mL/mmol。
所述金属铜催化剂为一价铜化合物；优选为溴化亚铜或氯化亚铜。
本发明所述制备方法中，所述后处理可采用如下方法：反应结束后，加水，用二氯甲烷萃取萃取，合并有机层，用无水硫酸钠干燥，过滤，浓缩滤液，柱层析(石油醚：乙酸乙酯＝10：1，V:V)，收集洗脱液，减压蒸馏，残渣干燥后经核磁共振检测确定为目标化合物(II)。
本发明开发了一种苯甲酰胺类化合物的制备方法，设计合理，该工艺反应条件温和，原料易得，操作方便，有着广泛的工业应用前景。为新药筛选及开发奠定了基础，具有较好的实用价值。
具体实施方式
下面将通过实施例对本发明作进一步的说明，但本发明的保护范围不限于此。
实施例1化合物(II-1)的制备:
将苯胺(118.8mg,1.28mmol)，苯乙腈(748.5mg,6.39mmol)，CuCl(24.2mg,0.24mmol)在氯苯(2.0mL)中混合，在120℃条件下反应，反应15h，反应结束后，加水50mL，用二氯甲烷萃取(20mL×3)，合并有机层，用无水硫酸钠干燥，过滤，浓缩，柱层析(洗脱剂为石油醚：乙酸乙酯＝10：1，V：V)，收集Rf值0.3～0.35的洗脱液(TLC监测，展开剂同洗脱剂)，减压蒸馏除去溶剂，干燥得目标化合物(II-1)150.1mg，收率60％。1H NMR(500MHz,CDCl3):δ7.91(s,1H),7.89-7.87(m,2H),7.67-7.65(m,2H),7.58-7.55(m,1H),7.51-7.48(m,2H),7.40-7.37(m,2H),7.19-7.16(m,1H)。
Figure BDA0001704685640000021
实施例2：
将氯化亚铜改为溴化亚铜(79mg，0.5mmol)，苯乙腈改为(1.5g,12.8mmol)，时间改为30h，其他操作同实施例1，得量137.6mg，收率55％。
实施例3：
将氯苯改为二氯苯(13mL)，苯乙腈改为(150mg,1.28mmol)，温度改为80℃，其他操作同实施例1，得量50mg，收率20％。
实施例4：
将苯胺改为2-氨基吡啶(119.4mg,1.27mmol)，其他操作同实施例1，目标化合物(II-2)186.8mg，收率75％。1H NMR(500MHz,CDCl3):δ9.03(s,1H),8.43-8.41(m,1H),8.22-8.20(m,1H),7.95-7.94(m,2H),7.78-7.75(m,1H),7.59-7.55(m,1H),7.51-7.48(m,2H),7.07-7.04(m,1H)。
Figure BDA0001704685640000022
实施例5：
将苯胺改为2-氨基嘧啶(120.5mg,1.27mmol)，CuCl改为(12.8mg,0.13mmol)，其他操作同实施例1，目标化合物(II-3)68.1mg，收率28％。1H NMR(500MHz,CDCl3):δ8.87(s,1H),8.66(d,J＝4.9Hz,2H),7.96-7.94(m,2H),7.61-7.57(m,1H),7.53-7.50(m,2H),7.07(t,J＝4.9Hz,1H)。
Figure BDA0001704685640000023

Claims (2)

1.一种苯甲酰胺类化合物的制备方法，所述苯甲酰胺类化合物的结构通式如下：
Figure DEST_PATH_IMAGE002
其中R为苯基或吡啶或嘧啶；
其特征在于，通过以下制备步骤实现：将式(I)所示的氨基化合物与苯乙氰混合加入溶剂中，在铜催化剂作用下，在80～120℃温度下搅拌反应15~30小时，反应结束后，反应液后处理制得式（II）所示的苯甲酰胺类化合物；其中式(I)所示的氨基化合物与苯乙氰、铜催化剂的量比为1：1.0~10.0：0.1~0.4；
式(I)结构式为：
Figure DEST_PATH_IMAGE004
其中R的定义同式（II）；
所述溶剂为二氯苯或氯苯，所述溶剂的体积用量以氨基化合物的质量计为2~10 mL/mmol；所述铜催化剂为溴化亚铜或氯化亚铜。
2.根据权利要求1所述的一种苯甲酰胺类化合物的制备方法，其特征在于，所述后处理采用如下方法：反应结束后，加水，用二氯甲烷萃取，合并有机层，用无水硫酸钠干燥，过滤，浓缩滤液，柱层析，其中石油醚：乙酸乙酯的体积比为10：1，收集洗脱液，减压蒸馏，残渣干燥后经核磁共振检测确定为目标化合物（II）。
CN201810653261.1A 2018-06-22 2018-06-22 一种苯甲酰胺类化合物的制备方法 Expired - Fee Related CN108840806B (zh)

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