Alcohols, primary trioxide complex

If homolytic reaction conditions (heat and nonpolar solvents) can be avoided and if the reaction is conducted in the presence of a weak base, lead tetraacetate is an efficient oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones. The yield of product is in many cases better than that obtained by oxidation with chromium trioxide. The reaction in pyridine is moderately slow the intial red pyridine complex turns to a yellow solution as the reaction progresses, the color change thus serving as an indicator. The method is surprisingly mild and free of side reactions. Thus 17a-ethinyl-17jS-hydroxy steroids are not attacked and 5a-hydroxy-3-ket-ones are not dehydrated. 

A recently discovered (2) oxidizing system promises to become very important for the oxidation of acid-sensitive compounds. The reagent is chromium trioxide-pyridine complex, which may be isolated after preparation and employed in nonaqueous solvents (usually methylene chloride). A remarkable feature of the reagent is that good yields of aldehydes are obtained by direct oxidation of primary alcohols. The preparation of the reagent and its use are given. 

Oxidation, of primary alcohols to aldehydes, 52, 5 of terminal olefins with chromyl chloride, 51, 6 of 2,4,4-trimethyl-1-pentene with chromyl chloride, 51, 4 with chromium trioxide-pyridine complex, 52, 5... 

A better reagent for oxidation of primary alcohols to aldehydes in good yield is pyridinium chlorochromate (PCC), a complex of chromium trioxide with pyridine and HCl. 

Cr03 2 Chromium trioxide-pyridine complex is used when nonacidic conditions are needed good for converting secondary alcohols to ketones or primary alcohols to aldehydes without overoxidation. 

A better reagent for the limited oxidation of primary alcohols to aldehydes is pyridinium chlorochromate (PCC), a complex of chromium trioxide with pyridine and HC1. PCC oxidizes most primary alcohols to aldehydes in excellent yields. Unlike most other oxidants, PCC is soluble in nonpolar solvents such as dichloromethane (CH2C12), which is an excellent solvent for most organic compounds. PCC can also serve as a mild reagent for oxidizing secondary alcohols to ketones. 

A complex of chromium trioxide with pyridine and HC1. PCC oxidizes primary alcohols to aldehydes without over-oxidizing them to carboxylic acids, (p. 471)... 

One of the best activators fw dimethyl sulfoxide is the complex of sulfur trioxide/pyiidine, which in the presence of triethylamine rapidly oxidizes primary and secondary alcrdmls to aldehydes and ketones in very good yields at ambient temperature. This reagent also allows the very useM crmversion of allylic alcohols to the corresponding a, unsaturated carbonyl compounds. A further advantage of this procedure over many of the others is the ease of woiit-up, especially over the dimethyl sulfoxide-dicy-clohexylcarbodiimide method. 

In contrast, the chemistry of the oxidation of a primary alcohol to an aldehyde differs sharply from the oxidation of an aldehyde to a carboxylic acid (case (b)). Advantage, in this case, must be taken of the difference in the mechanisms of these steps. Among the reagents which can effectively oxidize alcohols and remain rather inert toward aldehydes are pyridinium chlorochro-mate (a chromium trioxide-hydrogen chloride complex of pyridine) or dimethyl sulfoxide-Lewis acid. 

Oxidation. The chromium trioxide-pyridine complex is conveniently and safely prepared from the components in dichloromethane this solution readily oxidizes alcohols to give aldehydes or ketones. The complex has more vigorous oxidizing properties in acetic acid. " Primary and secondary alcohols are... 

In the first step of this reaction sequence, the primary alcohol 21 is oxidized to the corresponding aldehyde 38 in a Parikh-Doering oxidation which is related to the Swern oxidation. In general, this type of oxidation is conveniently carried out by addition of a solution of pyridine-SOs complex in DMSO to a mixture of the alcohol, DMSO and NEts. It can be assumed that dimethyl sulfoxide and sulfur trioxide react to form 0-dimethylsulfoxonium sulfate 40, which then further reacts with primary alcohol 39 to give 0-alkyl dimethylsulf-oxonium intermediate 41. Then, sulfonium salt 42 is formed and subsequently deprotonated by NEts to give sulfonium ylide 43. Finally, an intramolecular p-elimination occurs to provide the desired aldehyde 44 and dimethyl sulfide. 

Dimethyl sulfoxide-Sulfur trioxide [1, 309, before references]. The combination of DMSO and sulfur trioxide, in the form of the pyridine complex, in the presence of trimethylamine oxidizes primary and secondary alcohols in good yield to aldehydes and ketones, respectively.55 The reaction usually is complete within minutes and the products are isolated by acidification and precipitation with water. The reagent also oxidizes allylic alcohols to the corresponding a,fi-unsaturated carbonyl compounds. One advantage over the DMSO-DCC method is that the elaborate purification required when dicyclohexylurea is a product can be dispensed with. Testosterone, with a 17/3-hydroxyl group, was oxidized toA -androstene-3,17-dione very rapidly the 17-epimer required a period of 35 min. 

P. J. Garegg and B. Samuelsson, Oxidation of primary and secondary alcohols in partially protected sugars with the chromium trioxide-pyridine complex in the presence of acetic anhydride, Carbohydr. Res., 67 (1978) 267-270. 

A common way to change reaction conditions for the oxidation of alcohols is to modify the acid that is added to the medium. Indeed, chromium trioxide will have different oxidizing abilities in different acids. Since most organic compounds are insoluble in water, a cosolvent is usually required to dissolve not only the chromium reagent but also the alcohol substrate. This solvent must be resistant to oxidation, and acetic acid or acetone are commonly used. For the alcohol - carbonyl conversion several Cr(VI) reagents can be used, including chromium trioxide in water or aqueous acetic acid catalyzed by mineral acid, sodium dichromate in aqueous acetone catalyzed by mineral acid, sodium dichromate in acetic acid, the Cr03 pyridine complex, and err-butyl chromate.Both primary and secondary alcohols can be oxidized to the aldehyde or ketone, respectively. Aldehydes may be oxidized to the carboxylic acid under some conditions. 

B.i. Chromium Trioxide—Pyridine. In 1948, Sisler and co-workers isolated and characterized a stable complex from the reaction of chromium trioxide and pyridine. Sisler did not use this reagent for the oxidation of organic molecules but Sarett and co-workers recognized its utility in the synthesis of steroids. In this connection, alcohol 24 was oxidized to 26 in 89% yield. The reagent, which probably has the trigonal bipyramidal structure shown in 25, proved useful for the general oxidation of primary and secondary alcohols, even in the presence of double bonds and thioethers,. The oxidation usually requires pyridine as a solvent and... 

A modification was introduced by Collins et al., and when applied to the oxidation of alcohols it has come to be known as Collins oxidation. This modification was developed to circumvent the danger inherent in preparing the reagent, deal with the problem of poor yields in the oxidation of primary alcohols to aldehydes, and facilitate isolation of the carbonyl products. The Sisler-Sarett reagent formed by reaction of chromium trioxide and pyridine was first removed from the pyridine solvent and added to dichloromethane, and this mixture was then treated with the alcohol. The oxidation typically required a 5 1 or 6 1 ratio of complex/alcohol, and reaction occurred at ambient temperatures. Cyclohexanol was oxidized to... 

An insertion complex of chromium trioxide and graphite was also shown to have oxidizing properties (Lalancette et al., 1972). Primary alcohols were oxidized to aldehydes whereas secondary alcohols remained untouched. Recent results have suggested that the oxidizing ent is a surface deposit of CrsOg (Ebert et al., 1974). The complex is commercially available (Seloxcette, Alfa Division, Ventron Corp.). 

Olefinic aldehydes have been synthesized by a variety of methods including oxidation of the corresponding primary alcohols with the chromium trioxide-pyridine complex 195—197) or N-chlorosuccinimide-dimethyl sulfide complex 198), heating a primary alken-l-yl mesylate with dimethylsulfoxide 199), or by alkylation of the lithium salt of 5,6-dihydro-2,4,4,6-tetramethyl-l,3-(4H)-oxazine with an alkynyl iodide followed by sodium borohydride reduction and acid hydrolysis (200). 

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