ALDEHYDES FROM PRIMARY ALCOHOLS BY OXIDATION

ALDEHYDES FROM PRIMARY ALCOHOLS BY OXIDATION WITH CHROMIUM TRIOXIDE 1-HEPTANAL, 52, 5 ALDEHYDES FROM sym-TRITHIANE n-PENTADECANAL, 51, 39 Aldehydes, acetylenic, 54, 45 Aldehydes, aromatic, 54, 45 Aldehydes, benzyl, 54, 45 Aldehydes, olefinic, 54, 45... 

ALDEHYDES FROM PRIMARY ALCOHOLS BY OXIDATION WITH CHROMIUM TRIOXIDE 1-HEPTANAL... 

Aldehydes, RCHO (Sec. 7.9) (Sec. 7.9) (Sec. 8.4) (Sec. 17.7, 19.2) (Sec. 19.2, 21.6) from disubstituted alkenes by ozonolysis from 1,2-diols by cleavage with sodium periodate from terminal alkynes by hydroboration followed by oxidation from primary alcohols by oxidation from esters by reduction with DIB AH [HA1(i-Bu)2]... 

The activation of DMSO by electrophilic reagents such as oxallyl chloride or trifluoroacetic anhydride (TFAA) (among many others) produces an oxidant capable of oxidizing primary alcohols to aldehydes in high yields. This oxidation is called the Swern oxidation and yields the aldehyde (oxidized product) by reductive elimination of dimethylsulfide (reduced product) and proceeds under mild, slightly basic conditions. It is a second widely used and effective oxidative method for the production of aldehydes from primary alcohols. 

A common step in the metabolism of alcohols is carried out by alcohol dehydrogenase enzymes that produce aldehydes from primary alcohols that have the -OH group on an end carbon and produce ketones from secondary alcohols that have the -OH group on a middle carbon, as shown by the examples in Reactions 7.3.6 and 7.3.7. As indicated by the double arrows in these reactions, the reactions are reversible and the aldehydes and ketones can be converted back to alcohols. The oxidation of aldehydes to carboxylic acids occurs readily (Reaction 7.3.8). This is an important detoxication process because aldehydes are lipid soluble and relatively toxic, whereas carboxylic acids are more water soluble and undergo phase n reactions leading to their elimination. 

Aldehydes can be obtained by the use of the general reaction, which in many cases serves as a method of preparation, of extracting two hydrogen atoms from a primary alcohol by oxidation. 

Aldehydes are obtained from primary alcohols by removing H2 in the presence of a copper chromite (CuO Cr203) catalyst. To do this, alcohol vapor at 250-300 °C is passed over hot CuO Cr203. One hydrogen molecule from each alcohol molecule is removed in the reaction. Thus, the alcohol is oxidized to an aldehyde. A hydrogen molecule can also be removed from low molar mass alcohols using just CuO as the catalyst. 

Another objection to the theory may be based on the experimental data existing on alcohol oxidation. According to Bone, alcohols should oxidize through a dihydroxy compound by the addition of an oxygen atom. The work of Wieland 5 and others has shown that the formation of aldehydes from primary alcohols may take place by dehydrogenation rather than further hydroxylation. Experimental evidence is lacking for the formation of the simple glycols by alcohol oxidation. 

It should be noted that A-bromo compounds can act as oxidizing agents e.g., A-bromo-acetamide and NBS oxidize secondary alcohols to ketones, and use of this has been made in steroid syntheses.355 Aldehydes, semiacetals, and finally esters are formed from primary alcohols by NBS, and disulfides from thiols (for references see Homer and Winkelmann354). Iodine is liberated from acidified KI solution, a reaction that can be utilized for quantitative determination of NBS and for detection of unchanged NBS in a reaction. 

Jones s oxidation is a powerful oxidizing medium for the conversion of alcohols to ketones. Unfortunately, this is such a powerful oxidizing medium that unwanted products are possible due to overoxidation. When a primary alcohol such as 1-pentanol (15) reacts with chromium trioxide and aqueous sulfuric acid, it follows the same mechanistic pathway as 9, with formation of chromate ester 16. However, experiments show that the yields of aldehyde from primary alcohols can be very low. 1-Propanol is oxidized to propanal, for example, in only 49% yield, and to obtain the product requires a short reaction time. Very often, a carboxylic acid is formed as a second product or even the major oxidation product rather than the aldehyde. It is known that aldehydes are easily oxidized to carboxyhc acids, even by oxygen in the air. If a sample of butanal were spilled, for example, it is rapidly oxidized to butanoic acid by air. This oxidation is easily detected as the sharp butanal smell is replaced by the pungent butanoic acid smell. Butanoic acid is found in rancid butter and in dirty feet, for example. 

Palladium nanoparticles stabilized with an amphiphilic resin catalyze the oxidation of alcohols by molecular oxygen in water. The corresponding products, aldehydes from primary alcohols and ketones from secondary alcohols, were... 

Acids can be produced by the oxidation of aldehydes or primary alcohols. For example, the souring of wine results from the oxidation of the ethyl alcohol in wine to acetic acid ... 

Primary alcohols are oxidized by chromic acid in sulfuric acid solution to aldehydes, but to stop the reaction at the aldehyde stage, it usually is necessary to remove the aldehyde from the reaction mixture as it forms. This can be done by distillation if the aldehyde is reasonably volatile ... 

A number of oxidants are able to selectively transform silyl ethers derived from primary alcohols into aldehydes in the presence of silyl ethers derived from secondary alcohols. This allows to perform selective oxidations, whereby persilylation of polyols is followed by the selective oxidation of primary silyl ethers, resulting in the formation of aldehydes possessing secondary alcohols protected as silyl ethers. As expected, the mild transformation of primary silyl ethers into aldehydes is only possible with silyl ethers that are not exceedingly robust, such as TMS, TES and TBS ethers. 

The Swern oxidation uses dimethyl sulfoxide (DMSO) as the oxidizing agent to convert alcohols to ketones and aldehydes. DMSO and oxalyl chloride are added to the alcohol at low temperature, followed by a hindered base such as triethylamine. The reactive species (CH3)2SC1, formed in the solution, is thought to act as the oxidant in the Swem oxidation. Secondary alcohols are oxidized to ketones, and primary alcohols are oxidized only as far as the aldehyde. The by-products of this reaction are all volatile and are easily separated from the organic products. 

Primary alcohols are oxidized either to aldehydes or to carboxylic addsl depending on the reagents chosen and on the conditions used. Probably tlM best method for preparing sn aldehyde from a primary alcohol on a laboratory scale (as opposed Co an industrial scaIo> is by use of pyrirhnii chlorochromale (PCC, C tNCrO CU in dichloromcthane solvent. 

The most common reagent for the oxidation of 1°- and 2°-alcohols is chromic acid (H2Cr04). It is difficult to stop the reaction at the aldehyde stage thus, primary alcohols are oxidized to carboxylic acids. In some cases, good yield of an aldehyde can be obtained by removing the aldehyde from the reaction mixture. 

Aldehydes are made by oxidation from primary alcohols, and ketones are made by the oxidation of secondary alcohols (Figure 7.2.4). 

Trialkyltin alkoxides prepared by evacuation of methanol from a mixture of an alcohol and trialkyltin methoxide are easily oxidized by bromine in the presence of trialkyltin alkoxide as HBr scavenger, producing the desired aldehyde and ketone efficiently [324]. This oxidation is more feasible on organotin alkoxides derived from secondary alcohols than those from primary alcohols, and enables regioselective oxidation of polyols [325]. The regioselectivity in oxidation of vicinal secondary alcohols was also examined [326], and the empirical informative results were invoked for access to namenamicin A-C disaccbarides (Scheme 12.177) [327]. 

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