Aldehydes using TEMPO

Table 2 Ruthenium/2,2, 6,6 -tetramethylpiperidinyl-W-oxyl (TEMPO) catalysed oxidation of primary and secondary alcohols to the corresponding aldehyde using molecular oxygen. 15 mmol substrate, 30 ml chlorobenzene, RuCl2(PPh3)3/TEMPO ratio of 1/3, 10 ml mur1 02/N2 (8/92 v/v), P=10 bar, T=100 °C...

A copper catalysed click (azide-alkyne cycloaddition) reaction has been used to prepare a fluorous-tagged TEMPO catalyst (Figure 7.20). TEMPO is a stable organic free radical that can be used in a range of processes. In this case, its use in metal-free catalytic oxidation of primary alcohols to aldehydes using bleach as the terminal oxidant was demonstrated. The modified TEMPO can be sequestered at the end of the reaction on silica gel 60 and then released using ethyl acetate for reuse in further reactions in this way the TEMPO was used four times with no loss in activity. 

The order of firstly reducing an ester or an acid to the corresponding alcohol and then reoxidizing it to an aldehyde is quite typical in organic synthesis, as it is often impossible to control the reduction step to stop at the aldehyde stage. There are, however, several possibilities to selectively oxidize an alcohol to an aldehyde, some of which are presented in this chapter, namely oxidations using TEMPO, IBX and DMP. ... 

An efficient and mild procedure has been described for the oxidation of different types of alcohols to carbonyl compounds using TEMPO as the catalyst and (dichloroiodo)benzene as a stoichiometric oxidant at 50 °C in chloroform solution in the presence of pyridine [157]. Under these conditions, 1,2-diols are oxidized to p-hydroxyketones or p-diketones depending upon the amount of PhICh used. Interestingly, a competitive study has shown that this system preferentially oxidizes aliphatic secondary alcohols over aliphatic primary alcohols [157], while the PhI(OAc)2-TEMPO system selectively converts primary alcohols into the corresponding aldehydes in the presence of secondary alcohols. 

On the basis of these mechanistic insights, the authors developed the a-amino-xylation reaction using TEMPO and a synergistic combination of copper and chiral imidazolidinones [61 ]. A radical cation similar to IV has also been proposed by Jang and co-workers [62] for the organocatalytic a-oxidation of aldehydes using anodic oxidation. 

Table 5.3 Ruthenium-TEMPO-catalyzed oxidation of primary and secondary alcohols to the corresponding aldehyde using molecular oxygen. ...

Cooperative catalysis using chiral imidazolidinones and metal catalysts is not restricted to carbon electrophiles. In 2012, the MacMillan group [50] disclosed a general approach to undertake enantioselective -oxidation of aldehydes with TEMPO by combining organocatalysis with copper catalysis (Scheme 26.5b). 

The resurgence of interest in NHC as catalysts in the last 6 years led several chemists to reinvestigate external oxidants for the azolium-catalyzed esterification of aldehydes. Using cyanide, which shares many similarities to azolium salts in its reactions with aldehyde, Corey had shown in 1968 that the combination of an aldehyde and sodium cyanide in the presence of Mn02 and an alcohol led to esters. Scheldt executed this work with triazolium carbene as a promoter, leading to similar results (Scheme 14.9). Other oxidants including TEMPO radicals (2,2,6,6-tetramethylpiperidine 1-oxyl) and azobenzene" were also found suitable for NHC-catalyzed oxidative esterifications. 

The method uses a simple electrode made of a thin film of sol-gel organosilica doped with nitroxyl radicals deposited on the surface of an indium tin oxide (ITO) electrode. Thus, whereas in water benzyl alcohol is rapidly oxidized to benzoic acid, the use of the hydrophobic sol-gel molecular electrode TEMPO DE affords benzaldehyde only (Figure 1.9), with an unprecedented purity, which is highly desirable for the fragrance and pharmaceutical industries where this aromatic aldehyde is employed in large amounts. 

Synthesis of aldehydes from alcohols is an important transformation in several applications. In small scale oxidations still chromic acid is being used as a stoichiometric oxidant of alcohols, which leads to a large amount of toxic waste and it is also expensive. Catalytic routes have been reported using palladium catalyst [18], or TEMPO (see also Figure 15.13) as a radical catalyst for the oxidation of alcohols [19], or combinations of TEMPO and copper [20] related work is mentioned in the references of these articles. The mechanism of... 

Some successful attempts to immobilize catalysts for the oxidation of alcohols to carbonyl compounds involve the attachment of TEMPO-derivatives to a solid phase. Bolm et al. were the first to immobilize l-hydroxy-2,2,6,6-tetramethylpiperi-dine to modified silica gel (SG-TMP-OH) (11) and applied in the oxidation of multifunctional alcohols [68]. Other groups further investigated the use of polymer-supported TEMPO [69]. This system allowed the oxidation of alcohols to aldehydes and ketones, respectively, using bleach to regenerate the immobilized ni-troxyl radical (Scheme 4.6). 

The oxidation of alcohols to aldehydes and ketones using catalytic amounts of TEMPO and controlled potential electrolysis has been reported, including the observation of a special selectivity for primary alcohols in the presence of secondary alcohols (equation 20) °. The oxidation of secondary alcohol is much slower than that of primary alcohols. This method is especially effective for oxidation of the primary alcohol group in carbohydrates (equations 21 and 22) . ... 

NaClO, or else in the two-phase system but with a quaternary ammonium (viz. AUquat) ion as a phase-transfer catalyst, overoxidation to the corresponding carboxylic acid is obtained (entry 4). Therefore, by proper choice of the experimental conditions, a synthetically useful distinction in products formation can be made for the oxidation of primary alcohols, even though we are far from a satisfactory understanding of the reason behind this different behaviour. In fact TEMPO, as a well-known inhibitor of free-radical processes is allegedly responsible for the lack of overoxidation of an aldehyde to carboxylic acid (entry 3) this notwithstanding, TEMPO is also present under those conditions where the overoxidation does occur (eutry 4). Moreover, a commou teuet is that the formation of the hydrated form of an aldehyde (in water solution) prevents further oxidation to the carboxylic acid however, both entries 3 and 4 refer to water-organic solutions, and their... 

The most profitable is certainly the use of laccase (Lc) with TEMPO. It enables the almost quantitative conversion of primary benzylic and allylic alcohols to aldehydes without overoxidation under mild conditions (Table 14, entries 1 and 2), that is, 25 °C and pH = 4.5 in the presence of atmospheric O2, for a reaction time of 24 h. The successful enzyme is the one obtained from the fungus Trametes villosa. 

Primary and secondary alcohols were selectively oxidized to the corresponding aldehydes and ketones, respectively, by using Oxone in the presence of a catalytic amount of TEMPO (2,2,6,6-tetramethyl-l-oxypiperidinyl). This reaction has been proved to be a highly selective and efficient oxidation reaction, where a catalytic amount of TEMPO plays an important role. Thus TBDMS protected benzyl alcohols were oxidized selectively to benzaldehydes in 81% yield, without affecting the TBDMS moiety. 

An obvious test of such a mechanism is use of standard free-radical traps (p-benzoquinone, TEMPO) indeed they block the reaction which, to us, also indicates that the reaction is not exclusively interfacial, but occurs also in the solution. We believe that the role of the nickel (II) centers is joint coordination of the sacrificial aldehyde and of dioxygen in the initiation step. 

The application of ionic liquids as a reaction medium for the copper-catalyzed aerobic oxidation of primary alcohols was reported recently by various groups, in attempts to recycle the relatively expensive oxidant TEMPO [150,151]. A TEMPO/CuCl-based system was employed using [bmim]PF6 (bmim = l-butyl-3-methylimodazolium) as the ionic liquid. At 65 °C a variety of allylic, benzylic, aliphatic primary and secondary alcohols were converted to the respective aldehydes or ketones, with good selectiv-ities [150]. A three-component catalytic system comprised of Cu(C104)2, dimethylaminopyridine (DMAP) and acetamido-TEMPO in the ionic liquid [bmpy]Pp6 (bmpy = l-butyl-4-methylpyridinium) was also applied for the oxidation of benzylic and allylic alcohols as well as selected primary alcohols. Possible recycling of the catalyst system for up to five runs was demonstrated, albeit with significant loss of activity and yields. No reactivity was observed with 1-phenylethanol and cyclohexanol [151]. 

The initial study on the MeO-TEMPO / Mg(N03)2 / NBS triple catalyst system in the oxidation of 1 indicated the necessity of all three components the TEMPO based catalyst, the nitrate source (MNT) and the bromine source (NBS). A large number of metal nitrates and nitrites were screened initially and the highest activity and aldehyde selectivity under comparable reaction conditions were recorded using Mg(N03)2 as the nitrate component. A number of organic and inorganic bromides soluble in HOAc were also screened and high reaction rates were found when NBS was used as the bromide source. The effect of the concentration of the individual components of the new triple catalyst system on the reaction rate, on the conversion of 1 and on the selectivity to 2 over 60 min reaction time is shown in Figure 1. 

One of the most efficient methods for oxidation of primary alcohols to either aldehydes or carboxylic acids is the one, commonly known as the Anelli oxidation. This reaction is carried out in a two-phase (CH2Cl2/aq.buffer) system utilizing TEMPO/NaBr as a catalyst and NaOCl as the terminal oxidant The new system described here is an extension of the Anelli oxidation, but surprisingly, does not require the use of any organic solvents and replaces the KBr co-catalyst with the more benign, Na2B40y (Borax). The use of the new cocatalyst reduces the volume of the buffer solution and eliminates completely the need of a reaction solvent. The new system was successfully applied in the industrial synthesis of the 3,3-Dimethylbutanal, which is a key intermediate in the preparation of the new artificial sweetener Neotame. 

Here we report on a new TEMPO based catalyst system for the oxidation of primary and secondary alcohols selectively to aldehydes and ketones using NaOCl as a terminal oxidant. 

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