The Milas hydroxylation is an

organic reaction Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical rea ...

converting an

alkene In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...

to a vicinal

diol A diol is a chemical compound containing two hydroxyl groups ( groups). An aliphatic diol is also called a glycol. This pairing of functional groups is pervasive, and many subcategories have been identified. The most common industrial diol is ...

, and was developed by Nicholas A. Milas in the 1930s. The cis-diol is formed by reaction of alkenes with

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3% ...

and either ultraviolet light or a catalytic

osmium tetroxide Osmium tetroxide (also osmium(VIII) oxide) is the chemical compound with the formula OsO4. The compound is noteworthy for its many uses, despite its toxicity and the rarity of osmium. It also has a number of unusual properties, one being that the ...

vanadium pentoxide Vanadium(V) oxide (''vanadia'') is the inorganic compound with the formula V2 O5. Commonly known as vanadium pentoxide, it is a brown/yellow solid, although when freshly precipitated from aqueous solution, its colour is deep orange. Because ...

, or

chromium trioxide Chromium trioxide (also known as chromium(VI) oxide or chromic anhydride) is an inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name. This compound is a dark-purple ...

. The reaction has been superseded in synthetic chemistry by the

Upjohn dihydroxylation The Upjohn dihydroxylation is an organic reaction which converts an alkene to a ''cis'' vicinal diol. It was developed by V. VanRheenen, R. C. Kelly and D. Y. Cha of the Upjohn Company in 1976. It is a catalytic system using ''N''-methylmorph ...

and later by the

Sharpless asymmetric dihydroxylation Sharpless asymmetric dihydroxylation (also called the Sharpless bishydroxylation) is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol. The reaction has been applied to alk ...

Mechanism

The proposed mechanism for the Milas hydroxylation involves the initial combination of hydrogen peroxide and the osmium tetroxide catalyst to form an intermediate, which then adds to the alkene, followed by a cleavage that forms the product and regenerates the OsO₄. Milas-Hydroxylierung RMV3

Limitations

One variation of the Milas hydroxylation (shown in the mechanism above) requires stoichiometric amounts of osmium tetroxide, which is toxic (highly volatile) and expensive. Furthermore, in Milas's own experiments his yields ranged from 37.6% to 60.2% for the cis-vicinal diol. Note that a vicinal diol is a molecule in which two hydroxy atoms are located on adjacent carbon atoms. Vicinal diols can be oxidized to aldehydes and ketones, rendering their synthesis useful. The catalyst, osmium tetroxide, also known as Merck osmic acid, dissolves readily in tertiary butyl alcohol which implies that the solution in which the reaction occurs is stable, unless isobutylene is already present. In the presence of isobutylene most of the osmium tetroxide is reduced to an insoluble black colloidal oxide. This colloidal oxide is a very active catalyst in decomposition of hydrogen peroxide. Thus, in aqueous solutions osmium tetroxide decomposes hydrogen peroxide, whereas an anhydrous tertiary butyl alcohol decomposes at a much slower rate. The Upjohn dihydroxylation and the Sharpless asymmetric dihydroxylation both result in cis-vicinal diols as well, and do not require the toxic, expensive catalyst.

Applications

In 1949, the Milas hydroxylation was applied to a study of the demethylation of N-Dimethyl-p-Amino-azobenzene, otherwise known as butter yellow. Hydrogen peroxide in tertiary butyl alcohol with osmium tetroxide as a catalyst (Milas reagents) was examined to determine the parallels of the reaction with butter yellow ''in vivo'' versus ''in vitro''. Previously it was discovered that the hydroxylation of butter yellow or its demethylated derivatives exist within rats, and thus rats were deemed suitable for the comparison. Absorption spectra were examined to confirm the results of the experiment, which found that the product of the Milas hydroxylation was one of the obtained products.

References

{{Reflist Organic oxidation reactions Name reactions