之醇氧化到醛酮
有机反应中通常氧化反应表现为分子中氧的增加或氢的减少。醇（包括伯，仲，叔醇）的氧化反应是有机合成中经常用到的反应之一。醇用不同的氧化条件可以得到醛，酮或酸。下面就伯，仲醇氧化成醛酮做总结；主要可以通过：铬化合物，锰化合物，碘，钌化合物及DMSO氧化等。
氧化反应之- 醇氧化成醛酮 | 铬（VI） | 琼斯试剂 （Jones Reagent）: CrO3/H2SO4/H2O/Acetone | 易成酸 |
沙瑞特试剂 (Sarett Reagent) CrO3·2Py的吡啶溶液； 柯林斯试剂( CollinsReagents) CrO3·2Py的二氯甲烷溶液 | 易吸潮，不稳定；需要无水条件反应 | ||
PCC(CrO3/HCl/Py) | 弥补collins 缺点 | ||
PDC(CrO3/Acetone/Py) | 中性条件反应 | ||
锰 | 高锰酸钾(KMnO4) | 易成酸（杂） | |
二氧化锰（MnO2） | 选择性好 | ||
活性DMSO | Pfizner-Moffatt氧化 | DCC/毒性大，不易除去 | |
Albright-Goldmannyang氧化 | （Ac)2O/代替DCC缺点 | ||
Parrikh-Doering氧化 | SO3-Py/反应迅速 | ||
Swern氧化 | （COCl)2/低温，副反应少 | ||
碘 | IBX(DMP) | ||
钌（Ru） | TPAP | ||
Oppenauer/ TEMPO oxidation | |||
一：铬的化合物
氧化醇的铬化合物主要是六价铬化合物，包括氧化铬（CrO3,铬酐），氧化铬-吡啶配位化合物（Collins reagent）, 氯铬酸吡啶鎓盐（PCC）等。这些试剂都需在酸性条件下反应，他们是使醇氧化成醛酮最普通方法。
CrO3是一种深红色极易吸潮的固体，可以溶于水和一些有机溶剂，如叔丁醇，吡啶，醋酸酐等等，但在有机溶中不稳定易爆。其在水中的存在状态为。
醇的铬酸氧化机理：醇和铬酸作用首先形成铬酸酯，随后酯发生断裂生成醛酮。
1.琼斯试剂（Jones Reagent）: CrO3/H2SO4/H2O/Acetone
琼斯试剂氧化伯醇时一般不会停留在醛这一步，将继续氧化为酸，机理如下：
Jones试剂，其制备方法是将26.72g CrO3 溶于23mL 浓硫酸中，加水稀释到100mL。
琼斯试剂氧化的一般操作步骤：
A 0.15–0.40 volume of H2SO4(c) is added over one volume of a 1.5–4.5 M solution of CrO3 in water. A fraction of the resulting red solution is dropped over a 0.01–0.5 M stirred solution of the alcohol in acetone. The alcohol causes the reduction of the red Cr (VI) cations to chromium species with a greenish look. A complete oxidation of the alcohol in a short time requires normally between 1.2 and 5.0 equiv. of CrO3. When the reaction is finished, the oxidant is quenched by the addition of 0.1–0.4volumes of 2-propanol. If so desired, the reaction mixture can be neutralized by the addition of saturated aqueous NaHCO3 or diluted NaOH. The resulting mixture is extracted with an organic solvent, such as EtOAc, DCM or Et2O. The collected organic solutions are washed with brine, dried (Na2SO4 or MgSO4).
2.柯林斯试剂（Collins Reagents:）:CrO3·2Py
沙瑞特试剂为CrO3·2Py的吡啶溶液；
柯林斯试剂为CrO3·2Py的二氯甲烷溶液。制备这两种试剂时，应当是将三氧化铬加入到吡啶中，这个过程中伴随着大量的放热，反加可能会发生爆炸，得到的试剂也极其易爆，并有很强的吸水性，因此做反应时一般要求惰性气体保护。此类氧化中，用的溶剂一般是二氯甲烷，最好不要用没有文献报道的其他溶剂（可能会爆炸）。反应中常常会加入一些硅胶，这样可以减少铬酸盐沉淀对产品的吸附导致的损失。另外醇的β位含有杂原子时，容易发生β消除的副反应，加入乙酸酐可以有效阻止此副反应的发生。
由于整个体系中是无水环境，因此此类试剂可以把伯醇氧化为醛时，不能形成缩醛，因此不会继续氧化，可以停留在醛这一步。
但是Collins试剂存在较大的缺点：易吸潮，很不稳定，需在无水条件下反应。为使反应完全及加快，需要过量的试剂。配置时容易着火。
氧化的一般操作步骤：
One equivalent of CrO3 is slowly added over a 0.2–2.0 M solution of 2–2.03 equivalents of dry pyridine in dry DCM. Very often, ca. 2–7 g of dry Celite per g of CrO3 are added-normally before the preparation of the CrO3·2Py complex-in order to avoid loss of product on the chromium precipitates during the work-up.
Very frequently, ca. 2–5 equivalents of acetic anhydride are added-normally after the preparation of the CrO3·2Py complex-in order to facilitate a milder reaction, particularly in sugars and nucleosides. It is not common to add both Celite and acetic anhydride in the same reaction.
After ca. 15–20 min, a 0.02–0.70 M solution of the alcohol in dry DCM is slowly added. Normally, between 4 and 10 equivalents of the CrO3·2Pycomplex are used per equivalent of alcohol. When most of the starting alcoholis consumed, two alternative work-ups can be carried out.
Work-up A:
The reaction mixture is filtered through a pad of silica, Florisil or Celite. The filtrate is washed with an organic solvent, like Et2O, EtOAc, or DCM. The collected organic phases may be optionally washed with diluted HCl, diluted aqueous base, and brine or saturated CuSO4 solution. The resulting organic solution is dried (Na2SO4 or MgSO4) and concentrated.
Work-up B:
The reaction mixture is sequentially washed with NaOH (5%), HCl (5%), NaHCO3 (5%) and brine. Adding some ether can help the fractioning. Optionally, the organic phase can be subsequently filtered through Florisil. The result in gorganic solution is dried (Na2SO4 or MgSO4) and concentrated.
3.PCC（pyridinium chlorochromate）
PCC法基本弥补了Collins法的所有缺点；成为目前最为广泛的醇氧化成醛酮的方法。
制备方法：将三氧化铬（1eq）加入到6M盐酸（1.1eq）中得到氯铬酸溶液，0℃下分批加入吡啶（1eq）后过滤得到橙黄色的PCC固体，易于储存和操作。
氧化的一般操作步骤：
Approximately, 1.1–7 equiv., typically1.5 equiv. of solid PCC is added over a ca. 0.01–0.25 M solution of the starting alcohol in dry DCM. The resulting mixture is stirred at room temperature. Very often, ca. 0.2–1.2 g of activated MS per mmol of alcohol are added in order to accelerate the reaction. In order to moderate the acidity of PCC, it is very common to add ca. 0.3–1 equivalents of NaOAc. A solid support, such as silica gel, Celite, Florisil or magnesium sulfate, is added, very often in a proportion of ca. 0.3–2 g of solid support per mmol of alcohol, in order to facilitate the work-up. Occasionally alumina, working both as a solid support-used to facilitate the work-up and as an accelerant, mixed with PCC is added, in a proportion of ca. 0.4–1.5 g of alumina per mmol of alcohol. Normally, PCC is deposited over the alumina. Occasionally, ca. 10–20 equivalents of acetic acid are added in order to accelerate the reaction.
Sometimes, the reaction flask is sonicated with ultrasound in order to fragment the surface of the PCC particle sand, therefore, accelerate the reaction.
Although in PCC oxidations, it is very common to add simultaneously to the reaction an accelerant, a buffer and a work-up-facilitator; it is not common to employ simultaneously two materials belonging to the same kind, with the exception of the combination of the two accelerants molecular sieve and acetic acid, which are very often used together.
Work-up:
When a TLC analysis shows that most of the starting alcohol is consumed, the solids suspended in the reaction and the chromium species are removed by filtration through a pad of Florisil1,silica gel, alumina or Celite, and the pad is washed with an organic solvent, such as ether, DCM, or EtOAc. Sometimes, the solids can be removed by decantation. Other times, it is advisable to add some diethyl ether to the reaction mixture before the filtration, in order to promote the separation of reduced chromium species in a granular form. Occasionally, the reaction mixture is c
