Parikh–Doering氧化

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以二甲亞砜為氧化劑，固體三氧化硫-吡啶絡合物為活化劑，三乙胺為堿而將伯醇和仲醇轉化為相應的醛酮的反應，稱為Parikh–Doering氧化反應。此反應最早由Parikh和Doering在1967年報道【J. Am. Chem. Soc., 1967, 89, 5505】。在常溫條件下，DMSO 和 SO3-pyridine混合，和有機堿（如三乙胺和吡啶）反應生成的中間體可以快速氧化伯醇和仲醇生成醛或酮，且收率較高。可有效的將烯丙醇類化合物氧化為 a , ?-不飽和羰基化合物。還可以用來氧化生物堿類的醇化合物為酮類化合物。DMSO-SO3-pyridine試劑還用來氧化部分乙酰化的糖類化合物，得到新的不飽和的糖類化合物。【】【】

反應特點和注意事項：1、三氧化硫吡啶絡合物的量一般為3到3.3eq，三乙胺為6.5-16.5eq，反應溫度為0到10℃；2、二氯甲烷為常用的溶劑，有時也可以只加很少的二氯甲烷，而有時也會只加3eq DMSO，這樣有利于處理反應，四氫呋喃和氯仿也可作溶劑；3、反應通常是低于室溫反應的，冰浴甚至達到-12℃，而DMSO的凝固點是18℃，因此通常必須加入二氯甲烷；4、通常將三氧化硫吡啶固體加入到干燥的DMSO中，攪拌5到15分鐘，再加入到醇溶液中進行反應；5、此反應對水敏感；6、通常用DIPEA做堿而不是三乙胺，因為大位阻的堿可以減少一些活性醛酮的差向異構化；7、三氧化硫吡啶絡合物產生的副產物極易除去，后處理簡單，不易發生產生二甲硫醚的副反應；8、反應中保持較低的溫度，對產率有很大的影響。

反應機理

機理與swern氧化反應類似，二甲亞砜與三氧化硫在0°C或室溫下發生加成，并受到醇進攻，生成關鍵的烷氧基锍離子中間體，該中間體接下來被堿去質子化為相應的硫葉立德，然后硫葉立德經五元環過渡態、分解放出二甲硫醚，得到醛酮。

反應操作步驟

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.

反應實例

【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】

參考資料：

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. 維基百科（Parikh-Doering氧化反應）

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