Parikh–Doering氧化

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以二甲亚砜为氧化剂，固体三氧化硫-吡啶络合物为活化剂，三乙胺为碱而将伯醇和仲醇转化为相应的醛酮的反应，称为Parikh–Doering氧化反应。此反应最早由Parikh和Doering在1967年报道【J. Am. Chem. Soc., 1967, 89, 5505】。在常温条件下，DMSO 和 SO3-pyridine混合，和有机碱（如三乙胺和吡啶）反应生成的中间体可以快速氧化伯醇和仲醇生成醛或酮，且收率较高。可有效的将烯丙醇类化合物氧化为 a , ß-不饱和羰基化合物。还可以用来氧化生物碱类的醇化合物为酮类化合物。DMSO-SO3-pyridine试剂还用来氧化部分乙酰化的糖类化合物，得到新的不饱和的糖类化合物。【】【】

反应特点和注意事项：1、三氧化硫吡啶络合物的量一般为3到3.3eq，三乙胺为6.5-16.5eq，反应温度为0到10℃；2、二氯甲烷为常用的溶剂，有时也可以只加很少的二氯甲烷，而有时也会只加3eq DMSO，这样有利于处理反应，四氢呋喃和氯仿也可作溶剂；3、反应通常是低于室温反应的，冰浴甚至达到-12℃，而DMSO的凝固点是18℃，因此通常必须加入二氯甲烷；4、通常将三氧化硫吡啶固体加入到干燥的DMSO中，搅拌5到15分钟，再加入到醇溶液中进行反应；5、此反应对水敏感；6、通常用DIPEA做碱而不是三乙胺，因为大位阻的碱可以减少一些活性醛酮的差向异构化；7、三氧化硫吡啶络合物产生的副产物极易除去，后处理简单，不易发生产生二甲硫醚的副反应；8、反应中保持较低的温度，对产率有很大的影响。

反应机理

机理与swern氧化反应类似，二甲亚砜与三氧化硫在0°C或室温下发生加成，并受到醇进攻，生成关键的烷氧基锍离子中间体，该中间体接下来被碱去质子化为相应的硫叶立德，然后硫叶立德经五元环过渡态、分解放出二甲硫醚，得到醛酮。

反应操作步骤

General Procedure for Parikh–Doering Oxidation:

Between 2 and 9, typically 2.9–3.3 equiv. of the SO3·Pycomplex in a ca. 190–400 mg/mL solution in dry DMSO are slowly added over ca.0.2–0.6 M solution of 1 equiv. of alcohol in dry DMSO, containing ca. 7–17equiv. of Et3N. When most of the starting compound is consumed,water is added. This may cause the precipitation of the product, particularlywhen no co-solvent has been added to the DMSO solution. In that case, the crudeproduct can be isolated by simple filtration, and the DMSO contaminant can bewashed away with water. If no precipitation occurs, an organic solvent, likeDCM, EtOAc or Et2O, is added and the organic phase is decanted andwashed with water. Optionally, the organic phase can also be washed with brine,a NaHCO3 aqueous solution and/or a NH4Cl aqueoussolution. Finally, the organic phase is dried with Na2SO4or MgSO4, and concentrated, leaving a residue that may need furtherpurification.

Normally, it takes between 10 min and 2 days,typically ca. 2 h.

反应实例

【Tetrahedron Letters, 1992, 33, 4179-4182】

【Tetrahedron Letters, 1988, 29, 643-646】

【Journal of Organic Chemistry 1990, 55(13), 4044-7】

In anhydrous dimethyl sulfoxide (75 ml)were dissolved, 1,2,3,4-tetramethoxy-5-methyl-6- (4-hydroxybutyl)benzene (14.2 g, 50 mmole) and triethylamine (56.0ml), and the solution was stirred at room temperature. A solution of sulfurtrioxide pyridine complex (31.8 g,200 mmole) in anhydrous dimethyl sulfoxide (75 ml) was added dropwise to thesolution over a 25-minute period, followed by stirring at room temperature for35 minutes. The reaction solution was poured into ice-water (300 g), and the product was extracted withisopropyl ether (500 ml). The isopropyl ether layer was washed with 10percentaqueous phosphoric acid solution and aqueous sodium chloride solution,successively, and dried (over MgSO4), and the solvent was distilled off. Theresidue was distilled under reduced pressure, thereby yielding1,2,3,4-tetramethoxy-5-methyl-6-(3-formylpropyl)-benzene (11.3 g, 80%, bp 137 to 140oC 0.7mmHg).

【US4393075】

【 J. Am. Chem. Soc. 1988, 110, 5201】

【J. Am. Chem. Soc. 1988, 110, 2919】

【 J. Am. Chem. Soc. 1988, 110, 3670】

To a solution of 10.2 g 1-tert-butyldiphenylsilyloxy-cis-2-butene-4-ol (31.2 mmol), 18.0 mL Et3N (129 mmol), and 20 mL DMSO in 200 mL CH2Cl2 at 0◦C, was added 9.75 g SO3-pyridine complex (61.3 mmol). The reaction was warmed to room temperature, stirred for 2 h then poured onto 200 mL water and extracted with 200 mL Et2O (three times). The combined organic layers were washed with 100 mL saturated aqueous NH4Cl, 50 mL 10% aq. CuSO4, 100 mL water (three times), and 100 mL brine; they were dried over Na2SO4. Concentration in vacuo gave an orange oil. 1H NMR analysis of the unpurified mixture showed a 2:1 mixture of the isomeric cis- and trans-aldehydes. The orange oil was allowed to stand at room temperature under high vacuum (<1 mmHg) for 24 h, whereupon complete isomerization to the trans-aldehyde was observed by TLC. The oil was then subjected to silica gel chromatography (20:1; hexanes/EtOAc) to give 6.35 g (2E)- 4-(2,2-dimethyl-1,1-diphenyl-1-silaprop-oxy)but-2-enal as a colorless solid, in a yield of 63%, Rf = 0.35 (4:1, hexanes/ EtOAc).

【J. Am. Chem. Soc., 2003, 125, 13531】

To a mixture of 80.68 g allyl alcohol (266.7 mmol) and 223 mL Et3N (1.60 mol) in 700 mL DMSO was added dropwise a solution of 127 g SO3·Py (798 mmol) in 500 mL DMSO over 10 min at room temperature. After being stirred at that temperature for 40 min, the reaction mixture was diluted with Et2O, and the resulting solution was poured into an ice-cold saturated NH4Cl solution. The mixture was extracted with Et2O (three times). The combined organic layers were washed with saturated NH4Cl solution (twice) and brine (twice), and dried over anhydrous Na2SO4. The solution was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel 1.0 kg, ether/hexane, 1:60–1:10) to give 74.41 g enone as a colorless oil, in a yield of 93%.

【J. Am. Chem. Soc., 2003, 125, 8798】

参考资料：

1.commonoxidation reagents, Yue Xu, Sundia Meditech

2. Strategic Applications of Named Reactions in Organic Synthesis, LászlóKürti and Barbara Czakó, Swernoxidation, page 450.

3. http://www.chem-station.com/cn/?p=1008

4. 维基百科（Parikh-Doering氧化反应）

5. Comprehensive Organic Name Reactions and Reagents, by Zerong Wang，2118-2120