苏苏基-米亚乌拉合亚碳酸盐,碳酸盐和硫酸盐的合
Kyle W Quasdorf1, Michelle Riener, Krastina V Petrova
1Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
Journal of the American Chemical Society
|November 26, 2009
概括
这项研究引入了第一个苏苏基-米亚乌拉交叉合反应,用于碳酸盐,碳酸盐和硫酸盐. 这种新的方法有效地从简单的衍生物中合成多替代芳香化合物,包括抗炎药物flurbiprofen.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 药用化学 医学化学
背景情况:
- 木-米拉交叉合是有机合成中的一个重要反应.
- 碳酸,碳酸盐和硫酸盐是常见的功能组.
- 多重置换芳香化合物的高效合成对于药物发现至关重要.
研究的目的:
- 开发了第一个使用碳酸盐,碳酸盐和硫酸盐的苏子基-米亚乌拉交叉合反应.
- 建立一种通用的方法来获取多替代芳香化合物.
- 通过合成flurbiprofen来证明这种方法的实用性.
主要方法:
- 开发新型反应条件,用于木-米亚乌拉交叉合.
- 使用碳酸盐,碳酸盐和硫酸盐作为合伙伴.
- 应用开发的方法来合成flurbiprofen.
主要成果:
- 首次成功实施了 Suzuki-Miyaura 与碳酸盐,碳酸盐和硫酸盐的交叉合.
- 展示了一条通往多替代芳香化合物的强大途径.
- 实现了抗炎药物flurbiprofen的简洁合成.
结论:
- 开发的木-米亚乌拉交叉合方法在合成有机化学方面取得了重大进展.
- 这种方法为功能化芳香化合物提供了一个简单的方法.
- 比的合成突出了这种新反应的实际应用.
相关概念视频
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the para position.
Electrophilic Aromatic Substitution: Sulfonation of Benzene
Sulfonation of benzene is a reaction wherein benzene is treated with fuming sulfuric acid at room temperature to produce benzenesulfonic acid. Fuming sulfuric acid is a mixture of sulfur trioxide and concentrated sulfuric acid.
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...
Preparation and Reactions of Sulfides
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
Amines to Amides: Acylation of Amines
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 amide...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
Nucleophilic Aromatic Substitution: Elimination–Addition
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is confirmed through isotopic...

