CN113214106A - 一种高效合成伯酰胺、n-甲基仲酰胺类化合物的方法 - Google Patents

一种高效合成伯酰胺、n-甲基仲酰胺类化合物的方法 Download PDF

Info

Publication number
CN113214106A
CN113214106A CN202110390372.XA CN202110390372A CN113214106A CN 113214106 A CN113214106 A CN 113214106A CN 202110390372 A CN202110390372 A CN 202110390372A CN 113214106 A CN113214106 A CN 113214106A
Authority
CN
China
Prior art keywords
methyl
primary amide
compound
amide
amide compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202110390372.XA
Other languages
English (en)
Other versions
CN113214106B (zh
Inventor
陈学年
郭宇
陈西孟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Henan Normal University
Original Assignee
Henan Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Henan Normal University filed Critical Henan Normal University
Priority to CN202110390372.XA priority Critical patent/CN113214106B/zh
Publication of CN113214106A publication Critical patent/CN113214106A/zh
Application granted granted Critical
Publication of CN113214106B publication Critical patent/CN113214106B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • 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
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

本发明公开了一种高效合成伯酰胺、N‑甲基仲酰胺类化合物的方法，其具体过程为：在无水无氧的条件下将金属胺硼烷MRNHBH3加入到装有无水THF的反应容器中，其中M=Na或K，R=H或Me，再加入酯类化合物R’CO2R’’，其中R’为烷基或芳基，R’’为烷基或芳基，于室温条件下搅拌反应并经后处理得到纯净的目标产物伯酰胺类化合物或N‑甲基仲酰胺类化合物。本发明操作简单，低毒无害，安全可靠，适合规模化生产。

Description

一种高效合成伯酰胺、N-甲基仲酰胺类化合物的方法
技术领域
本发明属于酰胺类化合物的合成技术领域，具体涉及一种高效合成伯酰胺、N-甲基仲酰胺类化合物的方法。
背景技术
酰胺键是一种典型的基本化学键，广泛存在于天然和人造产品中，如多肽蛋白质、农药、高分子材料和药物。目前最常见的合成酰胺键的方法几乎完全依赖于羧酸和胺的脱水，这个过程通常是需要催化剂先将羧酸转化为活化羧酸盐，因为羧酸的直接酰胺化是一个热力学上不利的过程。此外，酯是目标化合物中常见的合成中间体。在无催化剂、无任何添加物的条件下，酯与胺反应直接酰胺化是一个非常理想的方法。然而，由于反应条件苛刻，反应时间长，化学计量试剂或催化剂的使用限制了该方法的实际应用。
除了这些传统方法外，还开发了创新的酰胺合成的替代方法，包括新型的C-N连接方式：Staudinger连接、天然化学连接、化学选择性酰胺连接、硝基烷烃-胺偶联，叠氮炔偶联等，这些起始于不同的材料，如醇、醛或炔烃和腈。虽然这些替代酰胺形成的方法在许多应用中取得了显著成功，但由于大量使用超化学计量的偶联剂和添加剂，它们的效率受到了不利影响。因此，酰胺类化合物的合成方法一直被认为是有机化学面临的最大挑战。因此，设计一种简便新颖且绿色的方法高效合成酰胺是非常有必要的。
发明内容
本发明解决的技术问题是提供了一种操作简单、安全可靠且低毒无害的高效合成伯酰胺、N-甲基仲酰胺类化合物的方法。
本发明为解决上述技术问题采用如下技术方案，一种高效合成伯酰胺、N-甲基仲酰胺类化合物的方法，其特征在于具体过程为：在无水无氧的条件下将金属胺硼烷MRNHBH3加入到装有无水THF的反应容器中，其中M=Na或K，R=H或Me，再加入酯类化合物R’CO2R’’，其中R’为烷基或芳基，R’’为烷基或芳基，于室温条件下搅拌反应并经后处理得到纯净的目标产物伯酰胺类化合物或N-甲基仲酰胺类化合物。
本发明所述的高效合成伯酰胺、N-甲基仲酰胺类化合物的方法，其特征在于具体步骤为：将装有1.2mmol金属胺硼烷MRNHBH3的10mL烧瓶连接到Schlenk线上，再添加5mLTHF，然后添加0.5mmol底物酯类化合物R’CO2R’’，反应混合物在室温下搅拌反应，并通过1HNMR核磁共振光谱或TLC进行监测，5分钟后底物酯类化合物被消耗完，然后移走溶剂，接着，加入体积比为10:1的CH2Cl2与n-hexane的混合溶剂萃取NH3BH3，再在烧瓶中加入15mL水，搅拌15分钟后加入体积比为1:1的水和乙酸乙酯的混合溶剂萃取产物，重复7-8次，收集有机相并干燥即得到纯度高、收率高的伯酰胺类化合物或N-甲基仲酰胺类化合物。
本发明所述的高效合成伯酰胺、N-甲基仲酰胺类化合物的方法的反应方程式为：
Figure 3216DEST_PATH_IMAGE002
。
本发明与现有技术相比具有以下有益效果：本发明操作简单，低毒无害，安全可靠，适合规模化生产。
附图说明
图1是本发明实施例1制得苯甲酰胺在氘代乙腈中的1H NMR，由图可知制得的目标产物为纯净的苯甲酰胺(伯酰胺)。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例1
合成伯酰胺、N-甲基仲酰胺的方法以NaNH2BH3与苯甲酸甲酯的反应(目标产物是苯甲酰胺)为例。将一个含有0.0636g (1.20mmol) NaNH2BH3的10mL烧瓶连接到Schlenk线，然后依次添加5mL THF和0.5mmol苯甲酸甲酯。反应混合物在室温下搅拌，并通过1H NMR或TLC进行监测。苯甲酸甲酯被消耗完，反应完成仅需5分钟。反应后的主要产物Na[PhC(O)NHBH3]、NH3BH3和少量NaBH3NH2BH2NH2BH3可根据其溶解度的不同进行分离。首先，从反应混合物中泵出THF (可循环使用)，反应瓶中剩固体。NH3BH3可用溶剂为5mL CH2Cl2和0.5mL n-hexane (体积比为10:1) 从“固体混合物”中提取出来，并且可回收循环使用。然后，以1:1的比例加入水和乙酸乙酯的混合溶剂，提取NaBH3NH2BH2NH2BH3 (水相) 和苯甲酰胺 (Na[PhC(O)NHBH3]水解后的产物；乙酸乙酯相)。收集有机相，旋干得到纯苯甲酰胺，产率高达91%。同时，将底物苯甲酸甲酯换成其他的酯，例如，4-X1-苯甲酸甲酯 (X1 = Me, MeO, F,Cl, Br, I, CN, NO2, CF3 )、3-X2-苯甲酸甲酯 (X2 = Me，F)、2-X3-苯甲酸甲酯 (X3 = Me，F)、1-萘甲酸甲酯、2-萘甲酸甲酯、烟酸甲酯、2-噻吩甲酸甲酯、2-呋喃甲酸甲酯、环己甲酸甲酯、己酸甲酯、硬脂酸甲酯、戊内酯等，上述方法同样适用。
实施例2
合成伯酰胺、N-甲基仲酰胺的方法以NaMeNHBH3与底物苯甲酸甲酯的反应 (目标产物是N-甲基苯甲酰胺)为例。将一个含有0.0804g (1.20mmol) NaMeNHBH3的10mL烧瓶连接到Schlenk线，然后依次添加5mL THF和0.5mmol苯甲酸甲酯。反应混合物在室温下搅拌，并通过1H NMR或TLC进行监测。苯甲酸甲酯被消耗完，反应在5分钟内完成。该反应后的主要产物Na[PhC(O)NMeBH3]、MeNH2BH3和少量NaBH3NH(Me)BH2NH(Me)BH3，可根据其溶解度的不同进行分离。首先，从反应混合物中泵出THF (可循环使用)，反应瓶中剩固体。其中MeNH2BH3可用溶剂为5mL CH2Cl2和0.5mL n-hexane (体积比为10:1) 从“固体混合物”中提取出来，并且可回收循环使用。然后，以1:1的比例加入水和乙酸乙酯的混合溶剂，提取NaBH3NH(Me)BH2NH(Me)BH3 (水相) 和N-甲基苯甲酰胺 (Na[PhC(O)NMeBH3]水解后的产物；乙酸乙酯相）。收集有机相，旋干得到纯N-甲基苯甲酰胺，产率高达99%。上述方法适用于其他多样的底物酯类化合物，例如， 4-X1-苯甲酸甲酯(X1 = Me, MeO, F, Cl, Br, I, CN, NO2,CF3)、3-X2-苯甲酸甲酯 (X2 = Me，F)、2-X3-苯甲酸甲酯 (X3 = Me，F)、1-萘甲酸甲酯、2-萘甲酸甲酯、烟酸甲酯、2-噻吩甲酸甲酯、2-呋喃甲酸甲酯、环己甲酸甲酯、己酸甲酯、硬脂酸甲酯、戊内酯等。
以上实施例描述了本发明的基本原理、主要特征及优点，本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。

Claims (3)

1.一种高效合成伯酰胺、N-甲基仲酰胺类化合物的方法，其特征在于具体过程为：在无水无氧的条件下将金属胺硼烷MRNHBH3加入到装有无水THF的反应容器中，其中M=Na或K，R=H或Me，再加入酯类化合物R’CO2R’’，其中R’为烷基或芳基，R’’为烷基或芳基，于室温条件下搅拌反应并经后处理得到纯净的目标产物伯酰胺类化合物或N-甲基仲酰胺类化合物。
2. 根据权利要求1所述的高效合成伯酰胺、N-甲基仲酰胺类化合物的方法，其特征在于具体步骤为：将装有1.2mmol金属胺硼烷MRNHBH3的10mL烧瓶连接到Schlenk线上，再添加5mL THF，然后添加0.5mmol底物酯类化合物R’CO2R’’，反应混合物在室温下搅拌反应，并通过1H NMR核磁共振光谱或TLC进行监测，5分钟后底物酯类化合物被消耗完，然后移走溶剂，接着，加入体积比为10:1的CH2Cl2与n-hexane的混合溶剂萃取NH3BH3，再在烧瓶中加入15mL水，搅拌15分钟后加入体积比为1:1的水和乙酸乙酯的混合溶剂萃取产物，重复7-8次，收集有机相并干燥即得到纯度高、收率高的伯酰胺类化合物或N-甲基仲酰胺类化合物。
3.根据权利要求1或2所述的高效合成伯酰胺、N-甲基仲酰胺类化合物的方法，其特征在于：所述酯类化合物R’CO2R’’适用于多样的酯类化合物。
CN202110390372.XA 2021-06-22 2021-06-22 一种高效合成伯酰胺、n-甲基仲酰胺类化合物的方法 Active CN113214106B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110390372.XA CN113214106B (zh) 2021-06-22 2021-06-22 一种高效合成伯酰胺、n-甲基仲酰胺类化合物的方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110390372.XA CN113214106B (zh) 2021-06-22 2021-06-22 一种高效合成伯酰胺、n-甲基仲酰胺类化合物的方法

Publications (2)

Publication Number Publication Date
CN113214106A true CN113214106A (zh) 2021-08-06
CN113214106B CN113214106B (zh) 2023-05-09

Family

ID=77087161

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110390372.XA Active CN113214106B (zh) 2021-06-22 2021-06-22 一种高效合成伯酰胺、n-甲基仲酰胺类化合物的方法

Country Status (1)

Country Link
CN (1) CN113214106B (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114560785A (zh) * 2022-03-04 2022-05-31 郑州大学 一种伯酰胺类化合物的合成方法
CN115572212A (zh) * 2022-09-06 2023-01-06 周口师范学院 利用NaBH3NH2BH2NH2BH3高效还原羰基化合物的方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002032856A2 (en) * 2000-10-17 2002-04-25 E. I. Du Pont De Nemours And Company Insecticidal 1,8-naphthalenedicarboxamides
JP2003171355A (ja) * 2001-12-07 2003-06-20 Kao Corp アミノカルボン酸アミドの製造法
CN101081851A (zh) * 2006-05-30 2007-12-05 上海药明康德新药开发有限公司 一种α－氮杂螺环类药物模板的制备方法
US20100048866A1 (en) * 2008-08-22 2010-02-25 Raines Ronald T Water-soluble phosphinothiol reagents
WO2010054102A2 (en) * 2008-11-05 2010-05-14 Mpex Pharmaceuticals, Inc. Polybasic bacterial efflux pump inhibitors and therapeutic uses thereof
CN106349185A (zh) * 2016-08-26 2017-01-25 河北科技大学 一种氨基保护的3‑羟基金刚烷甘氨酸苯并噻唑‑2‑硫醇活性酯、其制备方法及应用

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002032856A2 (en) * 2000-10-17 2002-04-25 E. I. Du Pont De Nemours And Company Insecticidal 1,8-naphthalenedicarboxamides
JP2003171355A (ja) * 2001-12-07 2003-06-20 Kao Corp アミノカルボン酸アミドの製造法
CN101081851A (zh) * 2006-05-30 2007-12-05 上海药明康德新药开发有限公司 一种α－氮杂螺环类药物模板的制备方法
US20100048866A1 (en) * 2008-08-22 2010-02-25 Raines Ronald T Water-soluble phosphinothiol reagents
WO2010054102A2 (en) * 2008-11-05 2010-05-14 Mpex Pharmaceuticals, Inc. Polybasic bacterial efflux pump inhibitors and therapeutic uses thereof
CN106349185A (zh) * 2016-08-26 2017-01-25 河北科技大学 一种氨基保护的3‑羟基金刚烷甘氨酸苯并噻唑‑2‑硫醇活性酯、其制备方法及应用

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
JIN WANG等: "Hydroboration Reaction and Mechanism of Carboxylic Acids using NaNH2(BH3)2, a Hydroboration Reagent with Reducing Capability between NaBH4and LiAlH4" *
P. VEERARAGHAVAN RAMACHANDRAN等: "Amine-boranes as Dual-Purpose Reagents for Direct Amidation of Carboxylic Acids" *
XI-MENG CHEN: "Brønsted and Lewis Base Behavior of Sodium Amidotrihydridoborate (NaNH2BH3)" *
YU-QI MIAO: "Visible light-mediated synthesis of amides from carboxylic acids and amine-boranes†" *
李慧珍等: "RBH3中B-H键与酚类物质的反应研究" *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114560785A (zh) * 2022-03-04 2022-05-31 郑州大学 一种伯酰胺类化合物的合成方法
CN115572212A (zh) * 2022-09-06 2023-01-06 周口师范学院 利用NaBH3NH2BH2NH2BH3高效还原羰基化合物的方法

Also Published As

Publication number Publication date
CN113214106B (zh) 2023-05-09

Similar Documents

Publication Publication Date Title
CN113214106B (zh) 一种高效合成伯酰胺、n-甲基仲酰胺类化合物的方法
CN102344415A (zh) 阿奇沙坦中间体的制备方法
CN105153110A (zh) 一种阿托伐他汀钙手性中间体的合成方法
KR20010053294A (ko) 오르토-알킬화 벤조산 유도체의 제조방법
CN110577457A (zh) 一种铜催化的芳基硼酸与二氧化碳的羧化反应方法
CN111943929B (zh) 2,4-二氨基吡啶氮氧类催化剂及其在吖内酯醇解开环中的应用
CN112661584A (zh) 一种光催化n-烷基酰胺化合物的制备方法
CN101863829B (zh) 一种3-氟-4-氨基吡啶的合成方法
CN102049301B (zh) 一种高效离子液体交聚苯乙烯负载钯催化剂及其应用
CN105198768B (zh) 一种2‑氨基丁酰胺的合成方法
CN108623488B (zh) 一种氨甲苯酸的合成方法
CN107915653B (zh) 催化酯和胺进行反应制备酰胺的方法
US4351952A (en) Process for preparing phenyl pyruvic acids
CN106946724B (zh) 单胺基抑制剂类中间体2-乙酰氨基-2-苄基丙二酸单乙酯的合成方法
CN108727179B (zh) 一种α-烯丙基取代的α,β-不饱和酮、酯或腈化合物的合成方法
CN109796360B (zh) 一种3-氨基-2-萘甲酸类化合物的制备工艺
CN101239922A (zh) 一种适合工业生产的甘氨酸叔丁酯的生产工艺
JP2754763B2 (ja) カルボン酸エステルとホルムアミドの製造法
CN104496737A (zh) 一种合成α-胺甲酰基氟乙酸酯化合物的方法
CN114409602B (zh) 一种以草酰氯和格氏试剂为原料合成α-酮酸的方法
CN114635145B (zh) 一种酰亚胺衍生物的电化学制备方法
CN1137091C (zh) 甲氰菊酯的制备方法
CN111909057B (zh) 一种环戊烯基芳基酮肟类化合物的制备方法
CN116253659B (zh) 一种酰胺基烯胺类化合物及其制备方法与应用
US4981619A (en) Process for preparing alpha-hydroxy acids

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant