2564-83-2/TEMPO氧化醇到醛酮

Anelli在1987年報道了在二氯甲烷-水兩相溶劑中利用TEMPO（ca. 1% mol）， NaOCl，KBr 和NaHCO3將醇氧化為醛酮的反應(yīng)。

TEMPO氧化醇到醛酮

TEMPO = 四甲基哌啶氧化物。2,2,6,6-四甲基哌啶氧自由基是一種市售的很穩(wěn)定的氮氧自由基化合物，在此反應(yīng)中充當(dāng)催化劑。

反應(yīng)中加入碳酸氫鈉的作用是保持體系中的pH 在 8.6–9.5 ，因為市售的次氯酸鈉的pH=12.7，堿性太強影響反應(yīng)進行，當(dāng)反應(yīng)底物對堿敏感時可以用0.1 M HCl調(diào)節(jié)pH到6.5-7.5。

反應(yīng)中加入KBr的作用可能是會產(chǎn)生一些HOBr，加速反應(yīng)。反應(yīng)一般在0℃到室溫反應(yīng)，反應(yīng)速度很快（氧化到醛一般3min，氧化為酮7-10min）。

仲醇氧化到酮就會停止，但醛可能會繼續(xù)氧化生成羧酸，但反應(yīng)速度很慢，另外必須加入過量的次氯酸鈉才可以繼續(xù)氧化。具體內(nèi)容參考往期發(fā)布的：TEMPO氧化。

TEMPO氧化醇到醛酮

對于一些位阻較大的醇，反應(yīng)中加入季銨鹽作為相轉(zhuǎn)移催化劑，可以加速反應(yīng)。但是也會加快過氧化過程生成羧酸。

次氯酸鈉會產(chǎn)生HOCl，可以和烯烴等一些富電子的底物反應(yīng)。此過程可以通過TEMPO-PhI(OAc)2(Protocol of Piancatelli and Margarita)法解決。

TEMPO氧化醇到醛酮

【Jauch, J. Angew. Chem., Int. Ed.2000,39, 2764.】

操作步驟

General Procedure for Oxidation of Alcohols with TEMPO-NaOCl (Anelli’s Protocol)

A two phase system consisting of a ca. 0.2–2.9 M solution of 1 equiv. of the alcohol in DCM, containing ca. 0.2–5% mol, typically 1–2% mol—of TEMPO and a ca. 0.02–2.6 M solution of ca. 0.02–0.5 equiv., typically 0.1 equiv. of KBr or NaBr in water, is vigorously stirred over a water ice bath (0C) or an ice-salt bath (-10C).

Over this two phase system, ca. 1.09–1.4 equiv. of NaOCl in a fresh solution, prepared by adjusting a ca. 5–13% aqueous solution of NaOCl to a pH of 8.6–9.5 by addition of an aqueous solution of NaHCO3, are slowly added. When starting compound is consumed, the organic phase is separated and the aqueous phase is washed with DCM. The collected organic phases are washed with a Na2S2O3aqueous solution and water or brine.

后處理

Optionally, the collected organic phases may be washed with a solution of ca. 0.2–2.5 equivalents of KI in 10–20% hydrochloric acid, before washing with the sodium thiosulfate solution. Finally, the organic solution is dried (Na2SO4or MgSO4) and concentrated, giving a residue that may need further purification.

?General Procedure for Oxidation of Alcohols TEMPO-PhI(OAc)2(Protocol of Piancatelli and Margarita)

A ca. 0.04–1 M solution of the alcohol in DCM, containing 0.09–0.2 equiv., typically 0.1 equiv. of TEMPO and 1.1–5 equiv., typically 1.1 equiv. of PhI(OAc)2(BAIB), is stirred at room temperature till most of the starting alcohol is consumed. Then, some DCM may be optionally added in order to facilitate subsequent washings. The reaction mixture is washed with an aqueous Na2S2O3solution. Optionally, the organic phase can be washed with aqueous NaHCO3and brine. Finally, the organic solution is dried (Na2SO4) and concentrated, giving a residue that may need further purification.

此條件下反應(yīng)不要求無水，反應(yīng)時間2-12h。