有機(jī)化學(xué)中的氧化反應(yīng)是指有機(jī)物分子中碳原子的氧化，可以根據(jù)氧化數(shù)確定。氧化數(shù)升高為氧化下降為還原，氧化還原總是同時(shí)進(jìn)行，但由于有機(jī)反應(yīng)中我們更多關(guān)注的是反應(yīng)底物，所以我們常常將底物中碳原子氧化數(shù)升高的反應(yīng)稱為氧化反應(yīng)。有機(jī)反應(yīng)中通常氧化反應(yīng)表現(xiàn)為分子中氧的增加或氫的減少。
六價(jià)鉻氧化劑
CrO3是一種深紅色極易吸潮的固體，可以溶于水和一些有機(jī)溶劑，如叔丁醇，吡啶，醋酸酐等等，但在有機(jī)溶中不穩(wěn)定易爆。其在水中的存在狀態(tài)為
一、瓊斯試劑（Jones Reagent）: CrO3/H2SO4/H2O/Acetone
主要活性成分為鉻酸，機(jī)理如下：
瓊斯試劑氧化伯醇時(shí)一般不會(huì)停留在醛這一步，將繼續(xù)氧化為酸，機(jī)理如下：
瓊斯試劑氧化的一般操作步驟：
A 0.15–0.40volume of H2SO4(c) isadded over one volume of a 1.5–4.5 M solution of CrO3in water. A fraction of the resulting redsolution is dropped over a 0.01–0.5 M stirred solution of the alcohol inacetone. The alcohol causes the reduction of the red Cr (VI) cations tochromium species with a greenish look. A complete oxidation of the alcohol in ashort time requires normally between 1.2 and 5.0 equiv. of CrO3. Whenthe 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 neutralizedby the addition of saturated aqueous NaHCO3 or diluted NaOH. The resulting mixture isextracted with an organic solvent, such as EtOAc, DCM or Et2O. Thecollected organic solutions are washed with brine, dried (Na2SO4 or MgSO4).
應(yīng)用實(shí)例：
二、沙瑞特試劑和柯林斯試劑（Sarett and CollinsReagents:）:CrO3·2Py
沙瑞特試劑為CrO3·2Py的吡啶溶液，柯林斯試劑為CrO3·2Py的二氯甲烷溶液，制備這兩種試劑時(shí)，應(yīng)當(dāng)是將三氧化鉻加入到吡啶中，這個(gè)過程中伴隨著大量的放熱，反加可能會(huì)發(fā)生爆炸，得到的試劑也極其易爆，并有很強(qiáng)的吸水性，因此做反應(yīng)時(shí)一般要求惰性氣體保護(hù)。此類氧化中，用的溶劑一般是二氯甲烷，最好不要用沒有文獻(xiàn)報(bào)道的其他溶劑（可能會(huì)爆炸）。反應(yīng)中常常會(huì)加入一些硅膠，這樣可以減少鉻酸鹽沉淀對(duì)產(chǎn)品的吸附導(dǎo)致的損失。另外醇的β位含有雜原子時(shí)，容易發(fā)生β消除的副反應(yīng)，加入乙酸酐可以有效阻止此副反應(yīng)的發(fā)生。
由于整個(gè)體系中是無水環(huán)境，因此此類試劑可以把伯醇氧化為醛時(shí)，不能形成縮醛，因此不會(huì)繼續(xù)氧化（機(jī)理見上方），可以停留在醛這一步。
氧化的一般操作步驟：
Oneequivalent of CrO3 is slowly added over a 0.2–2.0 M solution of2–2.03 equivalents of dry pyridine in dry DCM. Very often, ca. 2–7 g ofdry Celite per g of CrO3 are added-normally before the preparationof the CrO3·2Py complex-in order to avoid loss of product on thechromium precipitates during the work-up.
Veryfrequently,ca. 2–5 equivalents of acetic anhydride are added-normally after thepreparation of the CrO3·2Py complex-in order to facilitate a milderreaction, particularly in sugars and nucleosides. It is not common to add bothCelite and acetic anhydride in the same reaction.
Afterca. 15–20 min, a 0.02–0.70 M solution of the alcohol in dry DCM isslowly 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:
Thereaction mixture is filtered through a pad of silica, Florisil or Celite. Thefiltrate is washed with an organic solvent, like Et2O, EtOAc, orDCM. The collected organic phases may be optionally washed with diluted HCl,diluted aqueous base, brine or saturated CuSO4 solution. The resulting organic solutionis dried (Na2SO4 or MgSO4) and concentrated.
Work-up B:
Thereaction mixture is sequentially washed with NaOH (5%), HCl (5%), NaHCO3(5%) and brine. Adding some ether can help the fractioning. Optionally, theorganic phase can be subsequently filtered through Florisil. The resultingorganic solution is dried (Na2SO4 or MgSO4)and concentrated.
反應(yīng)實(shí)例
三、PDC（pyridinium dichromate）
將吡啶加入到三氧化鉻的水溶液中有亮黃色的PDC固體生成，PDC溶于有機(jī)溶劑，在空氣中溫度，易于儲(chǔ)存和操作。在二氯甲烷的懸浮溶液中可以將醇氧化為醛酮。PDC用DMF當(dāng)溶劑可以將伯醇氧化為酸。另外3?分子篩，HOAc，PPTS，PTFA，Ac2O可以加快PDC的氧化速度。
氧化的一般操作步驟：
Approximately,1.1–7 equivalents of solid PDC are added over a ca. 0.01–0.30 M solution of thealcohol in dry DCM. The resulting suspension is stirred at roomtemperature. Approximately, 0.5–4 g of activated MS-preferably finely ground 3?MS-per mmol of alcohol can be added in order to accelerate the oxidation. Thereaction can also be accelerated by the addition of ca. 0.9–4 equivalents of dryAcOH or 0.75–12 equivalents of acetic anhydride. The simultaneous use ofmolecular sieves and an organic acid has a synergistic accelerating effect. Theaddition of ca. 0.5–2.50 g of Celite or Florisil (magnesium silicate) per mmol of alcohol canfacilitate the work-up. Celite or Florisil can be added either at the beginningof the oxidation or ca. 30 min before the work-up. Two alternative work-ups canbe carried out.
Work-upA:
The most common workup. Et2Ois added and the precipitate is decanted and washed with ether. The collectedorganic phases are filtered through a pad of Celite, silica or Florisil.Alternatively, decanting the precipitate can be avoided and the mixture,resulting from the addition of ether, can be directly filtered through a pad ofsilica, Celite or Florisil. When the reaction is carried out under diluteconditions, the addition of diethyl ether can be avoided. The organic phase isconcentrated giving a residue that may need chromatographic purification. Whenthe reaction is
carried out in the presence of addedCelite or Florisil, a similar work-up is made in which the Celite or Florisilis filtered.
Work-upB:
Et2O is added and theresulting mixture is washed with aqueous phases. The aqueous phases used canbe: plain water, aqueous saturated NaHCO3 solution, diluted HCl or brine.The collected organic phases are dried (MgSO4 or Na2SO4)and concentrated, giving a residue that may need chromatographic purification.
注意事項(xiàng):
惰性氣體保護(hù)避免接觸空氣中的水。
可以用亞硫酸鈉快速淬滅反應(yīng)。
反應(yīng)應(yīng)用：
PCC（pyridinium chlorochromate）
將三氧化鉻（1eq）加入到6M鹽酸（1.1eq）中得到氯鉻酸溶液，0℃下加入吡啶（1eq）得到橙黃色的PCC固體，PDC溶于有機(jī)溶劑，在空氣中溫度，易于儲(chǔ)存和操作。在二氯甲烷的懸浮溶液中可以將醇氧化為醛酮。PDC用DMF當(dāng)溶劑可以將伯醇氧化為酸。另外3?分子篩，HOAc，PPTS，PTFA，Ac2O可以加快PCC的氧化速度。
氧化的一般操作步驟：
Approximately, 1.1–7 equiv., typically1.5 equiv. of solid PCC are added over a ca. 0.01–0.25 M solution of thestarting alcohol in dry DCM. The resulting mixture is stirred at roomtemperature. Very often, ca. 0.2–1.2 g of activated MS per mmol of alcohol areadded in order to accelerate the reaction. In order to moderate the acidity ofPCC, 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 oftenin a proportion of ca. 0.3–2 g of solid support per mmol of alcohol, in orderto facilitate the work-up. Occasionally alumina, working both as a solidsupport-used to facilitate the work-up and as an accelerant, mixed with PCC isadded, in a
proportion of ca. 0.4–1.5 g of aluminaper mmol of alcohol. Normally, PCC is deposited over the alumina. Occasionally,ca. 10–20 equivalents of acetic acid are added in order to accelerate thereaction.
Sometimes, the reaction flask issonicated with ultrasound in order to fragment the surface of the PCC particlesand, therefore, accelerate the reaction.
Although in PCC oxidations, it is verycommon to add simultaneously to the reaction an accelerant, a buffer and awork-up-facilitator; it is not common to employ simultaneously two materialsbelonging to the same kind, with the exception of the combination of the twoaccelerants molecular sieve and acetic acid, which are very often usedtogether.
Work-up:
When a TLC analysis shows that most ofthe starting alcohol is consumed,
the solids suspended in the reaction andthe 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 bydecantation. Other times, it is advisable to add some diethyl ether to thereaction mixture before the filtration, in order to promote the separation ofreduced chromium species in a granular form. Occasionally, the reaction mixtureis concentrated before the addition of diethyl ether. Finally, the collectedorganic phases are concentrated at the rotary evaporator, giving a crudealdehyde or ketone that may need some further purification.
注意事項(xiàng):
惰性氣體保護(hù)避免接觸空氣中的水。
可以用亞硫酸鈉快速淬滅反應(yīng)。
反應(yīng)應(yīng)用：
總結(jié)
1. 瓊斯試劑不要求無水環(huán)境，成本低，適用于大批量生產(chǎn)，但不能用于對(duì)酸敏感的反應(yīng)，也不能大量制備醛。
2. 柯林斯試劑成本低，但要求無水環(huán)境，選擇性不如PDC和PCC，但對(duì)于簡(jiǎn)單的制備醛酮的反應(yīng)能達(dá)到很好的效果。
3. PCC和PDC成本較高，但可以得到很好反應(yīng)結(jié)果。
參考文獻(xiàn)：common oxidation reagents, Yue Xu, Sundia Meditech
在由醇制備醛酮的過程中，由于鉻類氧化劑毒性較大，近年來發(fā)展了一類超價(jià)有機(jī)碘（V）氧化物。高價(jià)碘類氧化物有低毒，溫和和選擇性好等特點(diǎn)，其缺點(diǎn)就是有一定的爆炸性。比較常見的有DMP和IBX，其中IBX是制備DMP的一個(gè)前體，它的良性溶劑是DMSO。
