Chromium Reagents (Chromate)

All forms of Cr(VI) are powerful oxidizing agents, and oxidize any CH bonds on a carbon with an oxygen as far as possible without breaking any carbon-carbon bonds; for example, secondary alcohols are converted to ketones, and aldehydes to carboxylic acids. The most common reagents are: H₂CrO₄; K₂Cr₂O₇ + H₂SO₄; CrO₃ + H₂SO₄; they are approximately equivalent. They oxidize the activated CH bonds next to an aromatic ring, the "benzyl" hydrogens, so completely that they usually convert any alkyl benzene to a benzoic acid. Cr(VI) reagents are so powerful that they can also oxidize alkenes and alkynes, breaking the carbon-carbon bond as ozone does, but this reaction is not synthetically useful.

In non-aqueous solutions, oxidation by Cr(VI) does not go to completion (the intermediate partially oxidized material containing Cr must be hydrolyzed for oxidation to continue); thus, under these conditions, primary alcohols may be oxidized to aldehydes without forming carboxylic acid. The most common reagents for this partial oxidation are: PCC, or pyridinium chlorochromate (formed by dissolving CrO₃ and HCl in pyridine); Collins reagent (CrO₃ in CH₂Cl₂); chromyl chloride (CrO₂Cl₂).

Some of the oxidizing reagents containing Cr(VI) are listed below:

Sarett reagent: CrO₃.2C₅H₅N     (where C₅H₅N = pyridine): The highly exothermic reaction of chromium trioxide when added to an excess of pyridine leads to the formation the CrO₃ • 2 Py complex (Sarett Reagent). Compared to the Jones Reagent, Sarett Reagent allows the oxidation of various primary alcohols to aldehydes due to the non-aqueous conditions (see  Jones Oxidation for an explanation). Unfortunately, the complex is highly hygroscopic and the preparation of the reagent is not without risk because the solvent occasionally catches fire during preparation. In addition, the use of pyridine as solvent does not permit the oxidation of base-sensitive substrates.

The reagent is named after the American chemist Lewis Hastings Sarett (1917– 1999).

Collins reagent: CrO₃.2C₅H₅N diluted in CH₂Cl₂ : A solution of CrO₃ • 2 Py (Sarett Reagent) in methylene chloride is called the "Collins Reagent". One advantage over the Sarett Reagent is that the addition of one equivalent chromium trioxide to a stirred solution of two equivalents of pyridine in methylene chloride allows the convenient and safe preparation of the oxidant. In addition, the use of methylene chloride as solvent and stoichiometric amounts of pyridine makes the Collins Reagent less basic than the Sarett Reagent. Thus, most acid and base-sensitive substrates can be oxidized with Collins Reagent, unlike both the Sarett and Jones Reagent.

As the Collins Reagent does not contain water (compared to the Jones Reagent) and is not as hygroscopic as is the Sarett Reagent, the oxidant is especially useful for the oxidation of primary alcohols to aldehydes where traces of water can lead to overoxidation.

This complex is both difficult and dangerous to prepare, as it is very hygroscopic and can inflame during preparation. It is typically used in a sixfold excess in order to complete the reaction. Nowadays, PCC or PDC oxidation have largely supplanted Collins oxidation for these very reasons.

Cornforth reagent: CrO₃/ Pyridine / H₂O: The Cornforth reagent or pyridinium dichromate (PDC) is a pyridinium salt of dichromate with the chemical formula [C₅H₅NH]2[Cr₂O₇]. This compound is named after the Australian-British chemist Sir John Warcup Cornforth (born. 1917) who introduced it in 1962. The Cornforth reagent is a strong oxidizing agent which can convert primary and secondary alcohols to aldehydes and ketones respectively. In its chemical structure and functions it is closely related to other compounds made from hexavalent chromium oxide, such as pyridinium chlorochromate and Collins reagent. Because of their toxicity, these reagents are rarely used nowadays.

The Cornforth reagent is prepared by slow addition of a concentrated aqueous solution of chromium trioxide to pyridine. The reaction may cause explosion, which is avoided by thoroughly dissolving the trioxide in water and cooling the solution by ice. The product is filtered, washed with acetone and dried, yielding an orange powder. The powder is stable in air, not particularly hygroscopic and has an almost neutral pH that facilitates its handling; it is only slightly acidic owing to the presence of pyridinium cations. The Cornforth reagent is readily soluble in water, dimethylformamide and dimethyl sulfoxide (DMSO). It is poorly soluble in acetone and chlorinated organic solvents, such as dichloromethane, and forms suspensions.

The oxidation is usually carried out at ambient conditions, in nearly neutral pH conditions, in dimethylformamide or dichloromethane or their mixture. The choice of solvent or their ratio affects the reaction rate; in particular, higher content of dimethylformamide results in stronger oxidation. The slow oxidation rate for some alcohols can be accelerated by the addition of molecular sieves, organic acids or acetic anhydride or of their combinations. The acceleration by molecular sieves works best when their pore diameter is about 0.3 nm, and it is apparently unrelated to their water absorption capability. Among organic acids, acetic acid, pyridinium trifluoroacetate or pyridinium tosylate can be added, the first one being most efficient and easiest to remove. The achieved acceleration is remarkable, but the reaction inevitably turns from neutral (pH) to acidic. Comparable acceleration is achieved with acetic anhydride, which is used in sugar and nucleoside chemistry. Reaction acceleration depends not only on the additives but also on their form, so all reagents are preferred dry and freshly prepared, and PDC and molecular sieves should be finely ground. The disadvantange of the accelerators is that they may simultaneously promote several oxidation routes thereby reducing the selectivity of the reaction.

Fieser reagent: CrO₃ in acetic acid: Fieser's reagent is a mixture of chromium trioxide in acetic acid.

Jones reagent: CrO₃ + H₂SO₄ : The Jones Reagent is a solution of chromium trioxide in diluted sulfuric acid that can be used safely for oxidations of organic substrates in acetone. The reagent can also be prepared from sodium dichromate and potassium dichromate. Jones Reagent is especially suitable for the oxidation of secondary alcohols to ketones and of primary alcohols to carboxylic acids and in a few cases to aldehydes (Jones Oxidation). Some alternative chromium reagents allow the selective preparation of aldehydes, such as PCC and PDC.

Although the reagent is very acidic, the substrate in acetone is essentially titrated with the oxidant solution and only very acid-sensitive groups are incompatible. For example esters, even tert-butyl esters, remain unchanged. The concentration of sulfuric acid can be decreased to minimize side reactions, although the oxidation power increases too.

Depending on the reaction conditions, the aldehydes may then be converted to carboxylic acids. For oxidations to the aldehydes and ketones, two equivalents of chromic acid oxidize three equivalents of the alcohol:

2 HCrO₄^– + 3 RR'C(OH)H + 8 H⁺ + 4 H₂O → 2 [Cr(H₂O)₆]³⁺ + 3 RR'CO

For oxidation of primary alcohols to carboxylic acids, one equivalent of Jones reagent is required for each substrate. The aldehyde is an intermediate.

4 HCrO₄^– + 3 RCH₂OH + 16 H⁺ + 11 H₂O → 4 [Cr(H₂O)₆]³⁺ + 3 RCOOH

The inorganic products are green, characteristic of chromium(III) aquo complexes.  Although the reagent is very acidic, the substrate in acetone is essentially titrated with the oxidant solution and only very acid-sensitive groups are incompatible. For example esters, even tert-butyl esters, remain unchanged. The concentration of sulfuric acid can be decreased to minimize side reactions, although the oxidation power increases too.

Thiele reagent: CrO₃ + acetic anhydride + H₂SO₄

Corey-Suggs reagent (Pyridinium Chlorochromate (PCC) in CH₂Cl₂): [C₅H₅NH]+[CrO₃Cl]^-

Corey-Schmidt reagent (Pyridinium Dichromate (PDC) in CH₂Cl₂ or DMF):(C₅H₅NH)₂Cr₂O₇

Brown-Garg H2CrO4/(ether or benzene)/water

Kiliani Reagent H2CrO4 /H2SO4/ water/ acetic acid

Chromic anhydride CrO3/ water/ acetic acid

Snatze Reagent CrO3/ DMF

CrO3/ acetic anhydride/ acetic acid

CrO3 /HMPT

All the above reagents can be used with co-catalysts like mercuric acetate, ceric ammonium nitrate, manganous nitrate, oxalic acid and special effects come with controlled amounts of water in the reagent.

ATTENTION: Cr(VI) reagents have been shown to be carcinogenic, upon ingestion either through the stomach or the lungs. Not many years ago chromic acid solutions were the way to clean glassware (they remove organic compounds very well and leave the glass sparkling). They have been shown to leave traces of Cr(VI) on the glass, which can be death to a Grignard reagent, for example. The cancer-causing properties have resulted in strict regulations for disposal (you can't!), and thus these reagents are no longer used routinely. Interestingly, the chromate (CrO4-) looks like sulfate to cells, and is readily incorporated. Once in the cell, it oxidizes something and is converted to Cr(III); the Cr(III) looks a lot like Zn(II) and other biologically important ions. It is the Cr(III) that actually causes the damage that leads to cancer but the Cr(III) itself cannot get into the cells - it has to enter as Cr(VI).