获得N-单甲基化 (Thio) 碳酸盐,甲基胺,胺和相关衍生物
Filip G Zivkovic1, Fritz Bahns1, Che-Ming Hsu1
1Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074, Aachen, Germany.
Angewandte Chemie (International ed. in English)
|May 1, 2025
概括
研究人员开发了一种新方法来合成化有机化合物,如碳酸盐和胺. 这种方法利用了新的化构建块,提供了一条通往重要化学结构的多功能途径.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 化学 的化学
背景情况:
- 化有机化合物在制药和材料科学中至关重要.
- 对N-化化合物的一般合成方法仍然有限.
- N-CH2F和N-CHRF部分是有价值的,但具有挑战性.
研究的目的:
- 建立第一个对含有N-CH2F和N-CHRF化合物的通用合成接入.
- 引入N-CH2F和N-CHRF碳醇化物作为多功能合成中间体.
- 开发一种高效的方法,从常见的前体中合成这些构件.
主要方法:
- 使用N-CH2F和N-CHRF碳基化物作为关键构建块.
- 开发了这些化中间体的单步合成方法.
- 使用易于获得的胺或胺素作为起始材料.
主要成果:
- 实现了对N-CH2F和N-CHRF碳酸盐,硫酸盐,胺和胺的首次通用合成访问.
- 证明了N-CH2F和N-CHRF碳酸的高效,单步合成.
- 展示了这些构建块在构建各种化化合物的多功能性.
结论:
- 开发的合成策略为获取有价值的N-化有机分子提供了广泛适用的方法.
- N-CH2F和N-CHRF碳醇化物是有机合成的高效和多功能构建块.
- 这项工作显著推进了用于化学的合成工具包.
相关概念视频
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Carboxylic acids react with diazomethane in an ether solvent via alkylation at the carboxylate oxygen atom to give methyl esters of the corresponding acid with excellent yields.
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The IUPAC and common names of amides are derived from the parent carboxylic acid, by replacing the suffix “oic acid” and “ic acid,” respectively, with “amide.” In the following example, the IUPAC name ethanamide is derived from ethanoic acid, and the common name, acetamide, is obtained from acetic acid.
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Preparation of Amides
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Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
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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.
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Structure of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the...
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
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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...
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Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction...
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