アミン-アジド相互変換の化学:触媒性ダイアゾトランスファーと地域選択性アジド還元
Paul T Nyffeler1, Chang-Hsing Liang, Kathryn M Koeller
1Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Journal of the American Chemical Society
|September 5, 2002
まとめ
この研究は,新しい溶媒比率と亜鉛塩化物触媒を使用して,アミン合成のためのダイアゾトランスファー反応を強化しています. また,ポリアジド化合物の地域選択性アジド還元法が導入され,NMR分析による予測可能な制御が提供されています.
科学分野:
- 有機化学 オーガニック・ケミストリー
- 合成化学 合成化学とは
背景:
- アジドは有機合成において,特にアミンの生産のために,多用途の前駆体である.
- アジドを操作するための効率的で選択的な方法は,複雑な分子合成に不可欠です.
研究 の 目的:
- ダイアゾトランスファー反応の効率を改善し,反応時間を短縮します.
- 複数のアジド群を持つ化合物の地域選択性アジド還元の最初の例を達成するために.
- 地域選択性アジド減少とその予測可能性を支配する電子的要因を解明する.
主な方法:
- 特定の溶媒比率と亜鉛塩化物触媒を用いたダイアゾトランスファー反応条件の最適化.
- アジド還元のために低温でトリメチルフォスフィンを用いた改変されたスタウディンガー反応.
- 地域選択性の予測と分析のためのNMRスペクトロスコーピー.
主要な成果:
- ダイアゾトランスファー反応で>90%の変換を達成し,反応時間は大幅に短縮されました.
- ポリアジド化合物の減少において,良好な地域選択性と適度な収量を示した.
- 地域選択性を制御する電子的要因を特定し,NMR分析を通じて予測可能な結果を可能にしました.
結論:
- 改善されたダイアゾトランスファー反応は,アミン前駆体へのより効率的な経路を提供します.
- 地域選択的アジド還元は,ポリアジド分子の選択的機能化のための新しい方法を提供します.
- 両方の反応のメカニズムの仮説が提案され,将来の合成設計に役立つ.
関連する概念動画
01:22Preparation of 1° Amines: Azide Synthesis
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...
01:29Preparation of Amines: Reduction of Oximes and Nitro Compounds
Oximes can be reduced to primary amines using catalytic hydrogenation, hydride reduction, or sodium metal reduction. The reduction of aliphatic and aromatic nitro compounds to primary amines takes place by either catalytic hydrogenation or by using active metals like Fe, Zn, and Sn in the presence of an acid.
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
01:19Diazonium Group Substitution: –OH and –H
Nitrous acid, a weak acid, is prepared in situ via the reaction of sodium nitrite with a strong acid under cold conditions. This nitrous acid prepared in situ reacts with primary arylamines to form arenediazonium salts. Such reactions are known as diazotization reactions. As shown in Figure 1, the formation of arenediazonium salts begins with the decomposition of nitrous acid in an acidic solution to give nitrosonium ions.
01:11Aryldiazonium 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.
01:13Preparation of Amines: Reduction of Amides and Nitriles
Nitriles can be reduced to primary amines using reducing agents like lithium aluminum hydride or catalytic hydrogenation. The reduction introduces an amino group with an extra carbon in the skeleton. Nitriles are formed from the reaction between alkyl halides and sodium cyanide through the SN2 mechanism. Primary alkyl halides are the preferred substrates to prepare nitriles.
Amides can be reduced to primary, secondary, and tertiary amines using catalytic hydrogenation, active metals like Fe,...
Amides can be reduced to primary, secondary, and tertiary amines using catalytic hydrogenation, active metals like Fe,...
01:371° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO2 Mechanism
Nitrous acid is a relatively weak and unstable acid prepared in situ by the reaction of sodium nitrite and cold, dilute hydrochloric acid. In an acidic solution, the nitrous acid undergoes protonation when it loses water to form a nitrosonium ion—an electrophile. Nitrous acid reacts with primary amines to give diazonium salts. The reaction is called diazotization of primary amines.