通過DCC和DMSO氧化醇得到醛酮的反應(yīng)，也被稱為Pfitzner-Moffatt氧化。反應(yīng)中常常加入布朗斯特酸催化反應(yīng)反應(yīng)。與或所不同的是，活性因子分子體積較大而容易受到空間位阻的影響。利用到這一特點，反應(yīng)能夠選擇性氧化空間位阻較小的醇。另外，室溫條件下反應(yīng)能夠進行也是其一大優(yōu)點。作為副產(chǎn)物生成的尿素比較難除去，較容易發(fā)生副反應(yīng)硫醚化副反應(yīng)也是此反應(yīng)的一個不足之處。

副反應(yīng)中最常見的是甲硫甲基醚化（MTM化）。溫度高時反應(yīng)中的氯锍鹽發(fā)生異構(gòu)的產(chǎn)物與醇反應(yīng)，生成MTM保護產(chǎn)物。

反應(yīng)特點有：1、反應(yīng)條件溫和，不會過氧化，試劑易得，操作簡便；2、小試和放大反應(yīng)的產(chǎn)率都較高；3、很少有副反應(yīng)，有時會生成甲基甲硫基醚和β,γ不飽和羰基化合物的異構(gòu)化；4、反應(yīng)的官能團耐受度很好，但叔醇可能會發(fā)生消除；5、DCC是最常用的的活化試劑，反應(yīng)中一般會加過量（≥3eq）；6、DMSO要六倍當量以上，可以做溶劑，但加入一些惰性的混合溶劑（乙酸乙酯，苯）有利于產(chǎn)品的分離；7、要求溫和的酸催化條件，如正磷酸，二氯乙酸和吡啶的強酸鹽等等，酸一般加0.5eq產(chǎn)率最高，在強酸條件下，會阻止硫葉立德的生成，不能進行反應(yīng)或反應(yīng)很慢；8、反應(yīng)會生成二烷基脲，不容易除去，可也用一些水溶性的碳二酰亞胺試劑可以解決，如EDC，另外過量的DCC在處理時可以加入草酸除去。

反應(yīng)的常用操作步驟：

General procedure for oxidation ofalcohols by Pfitzner–Moffatt method

3 equiv. of a carbodiimide are addedover a solution of 1 equiv. of the alcohol and 0.5 equiv. of pyridiniumtrifluoroacetate in 0.6–40 mL of neat dry DMSO or a mixture of DMSO andbenzene, at room temperature. When most of the starting compound has beenconsumed, the work-up can be made according to the following alternatives:

Work-up A:

The solvent is removed at the rotaryevaporator, and the resulting residue is purified by chromatography. It can beadvisable to filter the precipitate of DCU-formed when DCC is used-beforeremoving the solvent. In order to avoid interferences from unreactedcarbodiimide, it can be advisable to transform it in the corresponding urea bycareful addition of oxalic acid-either solid or in a solution in methanol- tothe stirred reaction mixture. Addition of oxalic acid produces a copiousevolution of gas that signals the duration of the hydrolysis of thecarbodiimide.

Work-up B:

The reaction mixture is fractionedbetween water and an organic solvent, such as diethyl ether, ethyl acetate ordichloromethane. The organic phase is sequentially washed with water and withan aqueous solution of NaHCO3, dried with Na2SO4or MgSO4 and concentrated. When DCC is used, the resulting residuewill contain unreacted DCC and DCU that will need to be separated bychromatography.

反應(yīng)機理

包括以下幾步：1、DMSO被質(zhì)子化的二烷基碳二酰亞胺活化；2、醇的活化和烷氧基硫葉立德的生成；3、烷氧基硫葉立德的內(nèi)部重排生成相應(yīng)的醛酮和副產(chǎn)物二烷基脲。所有的活性DMSO 的氧化中，硫葉立德都是必要的中間體。

反應(yīng)實例

【J. Am. Chem. Soc.1992, 114, 1438-1449.】

【Liebigs Ann. Chem.1989, 939-943】

【J. Am. Chem. Soc. 1999, 121, 10270-10280】

【J. Chem. Soc., Perkin Trans. 11991, 1951-1958】

【J. Am. Chem. Soc. 2006, 128, 3926.】

【Synthesis 1987, 741-742】

【J. Med. Chem. 2005, 48, 3649-3653】

【J. Org. Chem.2011, 76, 2-12】

參考文獻

1. commonoxidation reagents, Yue Xu, Sundia Meditech

2. Strategic Applications of Named Reactions in Organic Synthesis, LászlóKürti and Barbara Czakó, Pfitzner-Moffatt oxidation, page 346-347.

3. 化學(xué)空間：普菲茨納-莫發(fā)特氧化反應(yīng) Pfitzner-Moffatt Oxidation

4. Name Reactions （A Collection of Detailed Reaction Mechanisms）, Jie Jack Li, Moffatt oxidation，page 411-412.