TEMPO was discovered by Lebedev and Kazarnowskii in 1960. It is prepared by oxidation of 2,2,6,6-tetramethylpiperidine.
Structure and bonding
According to X-ray crystallography, the N-O distance is 1.284 Å and the O is 0.1765 Å out of the C2N plane. The stability of this radical can be attributed to the delocalization of the radical to form a 2-center 3-electron N-O bond. The stability is reminiscent of the stability of nitric oxide and nitrogen dioxide. Additional stability is attributed to the steric protection provided by the four methyl groups adjacent to the aminoxyl group. These methyl groups serve as inert substituents, whereas any CH center adjacent to the aminoxyl would be subject to abstraction by the aminoxyl. Regardless of the reasons for the stability of the radical, the O–H bond in the hydrogenated derivative TEMPO–H is weak. With an O–H bond dissociation energy of about 70 kcal/mol, this bond is about 30% weaker than a typical O–H bond.
Application in organic synthesis
TEMPO is employed in organic synthesis as a catalyst for the oxidation of primary alcohols to aldehydes. The actual oxidant is the N-oxoammonium salt. In a catalytic cycle with sodium hypochlorite as the stoichiometric oxidant, hypochlorous acid generates the N-oxoammonium salt from TEMPO. One typical reaction example is the oxidation of --2-methyl-1-butanol to --2-methylbutanal: 4-Methoxyphenethyl alcohol is oxidized to the corresponding carboxylic acid in a system of catalytic TEMPO and sodium hypochlorite and a stoichiometric amount of sodium chlorite. TEMPO oxidations also exhibit chemoselectivity, being inert towards secondary alcohols, but the reagent will convert aldehydes to carboxylic acids. In cases where secondary oxidizing agents cause side reactions, it is possible to stoichiometrically convert TEMPO to the oxoammonium salt in a separate step. For example, in the oxidation of geraniol to geranial, 4-acetamido-TEMPO is first oxidized to the oxoammonium tetrafluoroborate. TEMPO can also be employed in nitroxide-mediated radical polymerization, a controlled free radical polymerization technique that allows better control over the final molecular weight distribution. The TEMPO free radical can be added to the end of a growing polymer chain, creating a "dormant" chain that stops polymerizing. However, the linkage between the polymer chain and TEMPO is weak, and can be broken upon heating, which then allows the polymerization to continue. Thus, the chemist can control the extent of polymerization and also synthesize narrowly distributed polymer chains.
Industrial applications and analogues
TEMPO is sufficiently inexpensive for use on a laboratory scale, however at an industrial scale its price is often prohibitive. Structurally related analogues do exist, which are largely based on 4-hydroxy-TEMPO. This is produced from acetone and ammonia, via triacetone amine, making it much less expensive. Other alternatives include polymer-supported TEMPO catalysts, which are economic due to their recyclability. Industrial-scale examples of TEMPO-like compounds include hindered amine light stabilizers and polymerisation inhibitors.
