胺:一种具有独特稳定性和选择性的氨基保护组
Philipp Spieß1,2, Ana Sirvent1,3, Irmgard Tiefenbrunner1
1Institute of Organic Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.
Chemistry (Weinheim an der Bergstrasse, Germany)
|June 7, 2023
概括
引入氨基的Nms保护组,与有机合成中的传统tosiyl和nosyl组相比,提供更高的稳定性和更容易的裂变. 这种新方法提高了多步合成效率.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 保护群体保护群体
背景情况:
- 像p-toluenesulfonyl (tosyl) 和nitrobenzenesulfonyl (nosyl) 这样的硫保护基在有机合成期间对氨基的保护至关重要.
- 托西尔基具有很高的稳定性,但很难去除,使多步合成复杂化.
- 诺西尔基很容易分裂,但在各种反应条件下缺乏稳定性.
研究的目的:
- 开发一种新型的硫胺保护组,该组结合了tosiyl组的稳定性和nosyl组的易切割性.
- 解决当代有机合成中现有的硫烯保护基的局限性.
主要方法:
- 在新保护组的初始设计中,采用了in silico研究.
- 进行了实验调查,以评估Nms组的合并,强度和可分割性.
- 对传统的托西尔和鼻保护组进行了比较的案例研究.
主要成果:
- 新开发的Nms保护组与传统的tosyl和nosyl组相比,表现优越.
- 在广泛的反应条件下,Nms-amides表现出极好的强度和稳定性.
- 实现了Nms组的高效和简单的分裂,克服了托西胺的局限性.
结论:
- 保护Nms组代表了有机合成氨基保护策略的重大进步.
- 这个新组提供了平衡的稳定性和裂变性,提高了合成效率.
- 胺为复杂的合成路径提供了多功能和可靠的替代品.
相关概念视频
01:19Amines to Amides: Acylation of Amines
2.5K
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
2.5K
01:29Preparation of Amides
3.2K
Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
3.2K
01:22Preparation of 1° Amines: Azide Synthesis
4.0K
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
4.0K
01:19Structure of Amines
2.6K
The hybridized nitrogen atom in amines possesses a lone pair of electrons and is bound to three substituents with a bond angle of around 108°, which is less than the tetrahedral angle of 109.5°. However, the C–N–H bond angle is slightly larger at 112°, with a carbon–nitrogen bond length of 147 pm. This carbon–nitrogen bond length of of amines is longer than the carbon–oxygen bond of alcohols (143 pm) but shorter than alkanes’...
2.6K
01:07Acid Halides to Amides: Aminolysis
2.9K
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
2.9K
01:28Preparation of 1° Amines: Gabriel Synthesis
3.6K
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
3.6K