TEMPO -mediated oxidation

NaHCOg, CHgClg TEMPO = tetramethyl pentahydropyridine oxide  

Yamaguchi, M. Miyazawa, T. Takata, T. Endo, T. Pure Appl. Chem. 1990, 62, 217. 

This method has been used to introduce carboxyl groups onto the surface of M FC from wood and sugar beet pulp, BC microfibrUs and nanocrystals based on cotton, sugar beet pulp and tunicin [50, 58,59,61,71]. Using C NMR spectroscopy, Isogai and Kato [61] showed that only small amounts of the hydroxyls in the MFC surface were oxidized. Montanari et al. [50] found that TEMPO-mediated carboxylation resulted in DS = 0.23 for sugar beet nanocrystals and 0.15 for cotton nanocrystals ( C NMR and conductometric titration). The crystals formed electrostatically stabilized suspensions in water. Habibi et al. [59] have reported similar results with tunicin cellulose. 

The bonding of P EG was confirmed by gravimetry, IR and conductometric titration of carboxyl groups. Freeze-dried nanocrystals could be redispersed in water or organic solvents and showed strongly increased stability towards flocculation with polyelectrolyte. 

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Scheme 11.12 TEMPO mediated oxidation of primary alcohols. (After [95]).

Lemoine, S. Thomazeau, C. Joannard, D. et al. Sucrose tricarboxylate by sonocata-lyzed TEMPO-mediated oxidation, Carbohydr. Res., 2000, 326, 176-184. 

Ru/SILIA CAT TEMPO-MEDIATED OXIDATION OF ALKENES TO a-HYDROXYACIDS... 

Table 6.3 Silia Cat TEMPO-mediated oxidation of vie diols to a-hydroxy acids.

Nevertheless, Celia et al. have proved that employing MCPBA as secondary oxidant in TEMPO-mediated oxidations may have a number of advantages when a one-pot oxidation of an alcohol with a concurrent alkene epoxidation or a Baeyer-Villiger oxidation is desired.6 The use of MCPBA as a secondary oxidant in TEMPO-mediated alcohol oxidations was recently reviewed.7... 

Anelli s protocol for the TEMPO-mediated oxidation of alcohols... 

Anelli s TEMPO-mediated oxidation can be accelerated by the addition of a quaternary ammonium salt, like Aliquat 336, acting as a phase transfer catalyst. This can be advisable in the oxidation of hindered secondary alcohols but can encourage the over-oxidation of primary alcohols to carboxylic acids.16... 

One important limitation of TEMPO-mediated oxidations, under Anelli s conditions, originates from competing reactions produced by HOC1, generated in situ from NaOCl. This problem can be solved by the use of [bis(acetoxy)iodo]benzene (BAIB) as a secondary oxidant following the protocol of Piancatelli and Margarita27 which has proved to be particularly efficient in difficult substrates,34 and it is a highly recommended alternative to Anelli s procedure when oxidations with oxoammonium salts are desired. 

The use of [bis(acetoxy)iodo]benzene as secondary oxidant in TEMPO-mediated oxidations was first reported in 1997 by Piancatelli, Margarita el al.21 In the foundational paper, it was stated that the reaction ... can be performed in an open flask without any particular precautions, e.g. inert atmosphere or dry solvents. .. . In fact, not following these particular precautions could be mandatory, as Mickel et al.35 found that, in the oxidation of a difficult substrate on a big scale, results were not reproducible unless 0.1 equivalents of water are added to the reaction mixture. One advantage of the employment of [bis(acetoxy)iodo]benzene is that, iodobenzene, a rather inert side compound, is generated, which needs not be removed before performing many subsequent reactions. 

TEMPO-mediated oxidations can be performed under almost neutral conditions. Therefore, acid- and base-sensitive functionalities and protecting groups can remain unchanged during TEMPO-mediated oxidations. 

Although TEMPO-mediated oxidations under Anelli s protocol are routinely performed at a slightly basic pH of 8.6 9.8,10 obtained by buffering the bleach solution with NaHCX>3, sometimes, in order to avoid base-induced side reactions, it is advisable to adjust the pH at 6.5-7.5 by adding an acid.13 A proper adjustment of the pH for example allows to obtain carbonyl compounds without a-epimerization in difficult substrates in which other common oxidants fail.42... 

The most serious limitation of TEMPO-mediated oxidations under Anelli s conditions is posed by the presence of HOC1—generated in situ— as a secondary oxidant, a quite reactive chemical that adds to olefins and produces electrophilic chlorination in many electron-rich substrates. 

In variance with Anelli s conditions, TEMPO-mediated-oxidations—under the protocol of ... 

Sulfides are transformed very easily into sulfoxides during TEMPO-mediated oxidations. It is even possible to oxidize sulfides without affecting alcohols in the same molecule.48... 

Lactols are easily transformed into lactones in TEMPO-mediated oxidations.49 When the oxidation of a diol leads to a hydroxyaldehyde that is able to equilibrate with a hemiacetal, the latter is further oxidized to a lactone.50 Interestingly, as TEMPO-mediated oxidations can be very selective in favouring oxidations of less hindered alcohols, lactone formation from diols can be very regioselective.500... 

For a detailed account of TEMPO-mediated oxidations see chapter 5. 

Among common alcohol oxidants, TEMPO-mediated oxidations have been the subject of a close scrutiny, aimed at finding optimum conditions for the selective oxidation of primary alcohols. In fact, TEMPO-mediated oxidations, that is oxidations in which an oxoammonium salt acts as a primary oxidant, have a great tendency to operate quicker with primary alcohols, regardless of the secondary oxidant employed and the exact experimental conditions. 

When a TEMPO-mediated oxidation of an 1,4- or 1,5-diol leads to an hydroxyaldehyde able to equilibrate with a lactol, the lactol is normally further oxidized to a lactone.7... 

A scant look at the facts might suggest that the selective oxidation of primary alcohols in TEMPO-mediated oxidations can be explained solely on steric grounds. Things are not so simple, as it was found8 that the primary oxidants, that is oxoammonium salts, when used stoichiometrically, react quicker with primary alcohols when present as oxoammonium chlorides, while the reverse selectivity, that is selective oxidation of secondary alcohols, is observed when oxoammonium bromides are employed. 

Other TEMPO-mediated oxidations reported to possess selectivity for the oxidation of primary alcohols versus secondary ones, include oxidations involving Q1CI2/O2,15 NaBr02,16 NCS17 and trichloroisocyanuric acid18 as secondary oxidants. 

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