Primary alcohol oxidations

Natural Product/Pharmaceutical Syntheses Involving Primary Alcohol Oxidations... 

A typical list of secondary carbohydrate oxidations is given in Table 2.3 bnt we start with primary alcohol oxidations in furanoses. Work on nncleosides and nncleotides is included in this section. 

P. L. Anelli, F. Montanan, S. Quid, Organic Syntheses CV8. 367. A number of other primary alcohol oxidations are reported. 

Primary alcohols oxidize to aldehydes, which, in turn, oxidize to carboxylic acids. Secondary alcohols oxidize to ketones. In each case, the reverse process is called re- duction... 

Nonblue. These include galactose oxidase (GO) and amine oxidases (e.g., plasma amine oxidase, diamine oxidase, lysyl oxidase), which produce dihydrogen peroxide by the two-electron reduction of 02 [33], For GO (stereospecific primary alcohol oxidation), spectroscopic studies by Whittaker [70,71] suggest that the two-electron oxidation carried out by a mononuclear copper center is aided by a stabilized ligand-protein radical (i.e., (L)Cu(I) + 02 —> (L +)Cu(lI) + H202), obviating the need to get to Cu(III) in the catalytic cycle. Protein x-ray structures [33,72] reveal a novel copper protein cofactor, which would seem... 

The nitroxyl-based systems are the most important and widely investigated homogeneous catalysts for the aerobic and non-aerobic oxidation of alcohols [9]. The different mechanisms with persistent (Scheme 1) and nonpersistent (Scheme 2) nitroxyl radicals is reflected in the selectivity of primary alcohol oxidation. Several... 

Chemoselective primary alcohol oxidation of the 1,5-diol 849 followed by in situ cyclization and lactol oxidation to afford 3,6-dihydropyran-2-one 850 is achieved using catalytic TEMPO in the presence of NCS (Equation 342) <20050L1853>. 

R—CH2 primary alcohol [oxidizing agent] —Tit R—C—H aldehyde [over-oxidation] [O] R—C—OH carboxylic acid... 

Among the aliphatic alcohols, oxidation of methanol has been studied most extensively [122-125]. At a platinum anode in acidic aqueous solutions, methanol oxidizes completely to CO2. Higher primary alcohols oxidize to aldehydes and acids under these conditions, though detailed mechanistic studies are lacking [126,127]. Anodic oxidation of secondary alcohols in aqueous acid leads to the corresponding ketones in high yield, but the reaction has received little attention over the years [126,128]. Indirect oxidation methods employing mediators are of considerable interest in this area and are treated elsewhere. 

Primary alcohols oxidize rapidly and efficiently to aldehydes. Aldehydes (from whatever source) oxidize very rapidly indeed to produce acids (eq. (22)), the likely final product ... 

Reaction of the C-0 and O-H Bonds Primary alcohols oxidize to carboxylic acids secondary alcohols oxidize to ketones with chromium trioxide or sodium dichromate. Tertiary alcohols do not oxidize under mild conditions. With pyridinium chlorochromate (PCC) the oxidation of primary alcohols can be stopped at aldehydes. 

Oxidation of Primary Alcohols Oxidation of Glycerol and Derivatives... 

The rate of oxidation using 1BX (5) has been determined to follow the trend primary alcohols oxidize faster than secondary alcohols which oxidize much faster than the benzylic moieties. 

The desired building block 204 was obtained by partial reduction of the triple bond in 218, followed by successive protection of the primary alcohol, oxidation of the secondary hydroxy group to the ketone, deprotection of the alcohol, Grignard reaction with vinylmagnesium bromide (65) and acetylation. The C2o-building block 204 was converted, with triphenylphosphine hydrobromide, into the phosphonium salt 219, reaction of which with the Cio-dialdehyde 45 gave C.p. 450 (203) Scheme 48). 

With some primary alcohols, it is possible to establish an equilibrium between the initially formed aldehyde and the precursor alcohol in which unreacted alcohol is converted to an hemiacetal (17), which can be further oxidized to an ester. This often accompanies the oxidation of lower molecular weight primary alcohols. Oxidation of 1-butanol to butyl butyrate with Cr(VI), for example, is an Organic Syntheses preparation. ... 

The most characteristic reactions of alcohols are their oxidation to aldehydes and ketones, which may undergo further oxidation, producing carboxylic acids. While primary alcohols oxidize to aldehyde, secondary alcohols produce ketones ... 

With both hemispheres 228 and 229 in hand, treatment of the TMS derivative of 228 with s-BuLi, followed by addition of 229 resulting in acylation and subsequent in situ hetero-Peterson olefination provided 227. Parikh-Doering oxidation, selective removal of the TMS and TES groups, followed by treatment with Sc(OTf)3 in benzene provided indole 243, assembling the AF ring system and installing the complete penitrem D carbon skeleton. Selective acylation, TIPS removal, selena-tion of the resulting primary alcohol, oxidative elimination and final hydrolytic removal of the acetate furnished (-)-penitrem D (226) (Scheme 43). 

Whatever its nature this electrochemlcally treated polymer has been shown to oxidize secondary alcohols to ketones in high yield (67). Since the reagent can be recycled by a continually applied current, the reaction proceeds catalytically. No supporting electrolyte is needed. Electrical efficiency is high. Primary alcohols oxidize more slowly to yield the carboxylic acid. The resin can be used many times without loss of reactivity. 

Aldehydes can be prepared by the oxidation of primary alcohols. Oxidizing agents such as pyridinium chlorochromate (PCC) or pyridinium dichromate (PDC) can be used for such conversions. 

The synthesis of 188 from epoxide 189 was done as shown in Scheme 25. Epoxide opening with a propargyl alane reagent [124], protection-deprotection of the alcohol functions, and Redal reduction led to the -allylic alcohol 194, also obtained by another route [116]. Asymmetric epoxidation-Redal epoxide opening [60-62] followed by silylation and debenzylation led to intermediate triol 195. Selective six-membered acetal formation and primary alcohol oxidation then furnished building block 188. 

Aristeromycin 5 -aldehyde has been prepared, and was shown to be a potent inhibitor of SAH hydrolase this study indicated that the fluoromethylene compounds (Vol. 26, p. 247), which are also inhibitors, do not act as precursors of the aldehyde. 2-Halo-derivatives 39 (X=F, Cl) of neplanocin A have been prepared, as have the equivalent structures lacking the CH2OH group and the analogue 40. Neplanocin analogues with the primary alcohol oxidized to the carboxylic acid level have also been made by oxidation, and aristeromycin and its cytosine analogue (carbodine) have been incorporated into a hammerhead ribozyme domain. ... 

Water is usually considered the most environmentally benign solvent however, the poor solubility of bulkier alcohols and molecular oxygen under ambient conditions has limited its application (in the absence of surfactants [25]). Pt nanoparticles supported on a water-soluble anion exchange resin exhibit excellent E-factors (12.8kilo waste per kilo product) in addition to very good activity and selectivity for alcohol oxidation [136]. Similarly, water has been used as solvent for, for example, benzyUc and primary alcohol oxidations over supported or stabilized Pd [137], Pt [138], and Au [139] clusters. 

With a different approach, the influence of bismuth on the electrocatalysis of glycerol was also investigated by Koper and co-workers [67]. They observed that a carbon supported platinum electrode in a bismuth-saturated solution is highly selective to the electro-oxidation of the secondary alcohol of the glycerol, leading to 100 % of dihydroxyacetone at a carefully chosen potential. Using a combinatiOTi of online HPLC and in situ FTIR, the authors have shown that bismuth not only blocks the pathway towards the primary alcohol oxidation but also provides a... 

With primary alcohols, oxidation can be stopped at the aldehyde stage by special reagents, such as pyridinium chlorochromate (PCC), shown in eq. 7.38. ... 

In the synthesis of methyl-2,3-0-isopropylidene-4-0-(methoxymethyl)-6-methylene-a-D-mannopyranoside (13), the hydroxyl groups of methyl-a-o-mannopyranosides are selectively protected 6-hydroxyl group as silyl ether 2,3-hydroxyl groups as acetonides and 4-hydroxyl group as methoxymethyle-ther. The silyl group at the C-6 position is then selectively cleaved to get primary alcohol. Oxidation of the alcohol to aldehyde followed by Wittig methylenation yields the desired olefin (13, Scheme 31.13). 

Primary alcohols afforded the corresjjonding carboxylic adds via further oxidation of the aldehyde intermediate for example, 1-hexanol afforded 1-hexanoic acid in 95% yield. It is important to note, however, thatthis was achieved without the requirement of one equivalent of base to neutralize the carboxylic acid product (which is the case with supported noble metal catalysts [5]). In contrast, when lmol% TEMPO (4 equivalents per Pd) was added the aldehyde was obtained in high yield for example, 1 -hexanol afforded 1 -hexanal in 97% yield. Some representative examples of primary alcohol oxidations using this system are shown in Table 5.9. The TEMPO was previously shown to suppress the autoxidation of aldehydes to the carboxyhc adds (see earlier). 

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