Primary alcohol oxidations acetic anhydride

By a suitable choice of activating reagents, primary and secondary alcohols can be selectively oxidized to carbonyl compounds in good yields at room temperatures. Typical activating reagents ate acetic anhydride, sulfur trioxide—pyridine, dicyclohexyl catbodiimide, and phosphorus pentoxide (40). 

Knoevenagel reaction. Hydrogenation of the double bond, desilylation and oxidation of the released primary alcohol group to the aldehydic function with PCC in dichloromethane in the presence of molecular sieves, gives the branched chain L-riho-hepturonic acid derivative 31. Treatment with acetic anhydride and pyridine results in cyclization, and acetylation of the resulting alcohol affords the acetate 32 in 69% yield. 

In general reaction of an alcohol with the appropriate anhydride or acid chloride in pyridine at 0-20 JC is sufficient. In the case of tertiary alcohols, acylation is very slow in which case a catalytic amount of 4-dimethylaminopyridine (DMAP) can be added to speed up the reaction by a factor of 10,000. Reaction of polyols with acyl chlorides (1.2 equiv) in the presence of hindered bases (2.0equiv) such as 2,4,6-collidine, diisopropylethylamine or 1,2,2,6,6-penta-methylpiperidine in dichloromethane at -78 °C leads to selective acylation of a primary alcohol. Primary alcohols can also be acylated selectively with isopro-penyl acetate or acetic anhydride in the presence of a catalytic amount of 1,3-dichlorotetrabutyldistannoxane 325.1 [Scheme 4.325].602 The catalyst 325.1 is available commercially or can be easily prepared by simply mixing dibutyltin oxide and dibutyldichlorostannane. No aqueous workup is necessary since the catalyst can be removed by simple chromatography. 

Oxidation of alcohols. The reactivity of PDC is increased by acetic anhydride. Primary and secondary alcohols are oxidized efficiently with 0.6-0.7 equiv of PDC and 3 equiv. of Ac.O in CfLCl, at 40°. Addition of DMF in the oxidation of primary alcohols retards further oxidation to the carboxylic acid. Acid-sensitive groups are stable to the conditions. 

Oxidation of alcohols.1 The reactivity of PDC is increased by acetic anhydride. Primary and secondary alcohols are oxidized efficiently with 0.6-0.7 equiv. of PDC and... 

PDC with acetic anhydride gives a strong but mild, neutral oxidant It is normally used in dichloromethane at room temperature. Under these conditions secondary alcohols are oxidized to ketones in high yield with 0.6 equiv. of PDC and 3 equiv. of acetic anhydride. With only slightly more PDC (0.7 equiv.) primary alcohols are rapidly and selectively oxidized to aldehydes. (The extra oxidant serves to increase... 

Methylthiomethyl ethers (6, 109-110). Alcohols can be converted into these ethers in 40-95% yield by reaction with DMSO, acetic anhydride, and acetic acid at room temperature. (Higher temperatures favor oxidation of the alcohol to the ketone.) This reaction is applicable to primary, secondary, tertiary, and hindered alcohols. 

Oxidations by chlorine are limited to only few types of compounds. In organic solvents and pyridine [681] or hexamethylphosphoramide (HMPA) [682] as cosolvents, primary alcohols are oxidized to aldehydes and secondary alcohols to ketones [681, 682]. Secondary alcohols are oxidized in preference to primary alcohols [681]. Many oxidations with chlorine are carried out in aqueous media and involve sulfur-containing compounds. Mercaptans [683], alkyl thiolcarboxylates [683], thiocyanates [684], isothioureas [684], disulfides [655], and sulfinic acids [656] are transformed into sulfonyl chlorides. The chlorination of dimethyl disulfide in acetic anhydride yields methanesulfinyl chloride [657]. 

The oxidation of diols having alcoholic groups of the same nature, for example, both alcoholic groups are primary, secondary, allylic, or benzylic, is usually carried out at both groups to yield dialdehydes [832] or diketones [552], Such reactions are achieved by chromium trioxide [582], barium manganate [832], dimethyl sulfoxide activated with acetic anhydride [1013], and others (equations 284 and 285). 

Another chromium(VI) oxidant for the preparation of uronic acids is PDC [28]. The oxidation is carried out in an aprotic solvent like dimethylformamide (DMF) or dichloromethane. Acetals and sulfides are stable under these conditions [59]. Although PDC is also used for oxidation of primary alcohols to aldehydes, use of a larger excess and/or a longer reaction time will give the carboxylic acid [60]. PDC can be further activated by addition of acetic anhydride which will shorten the reaction time [61]. If tert-butanol is added to the reaction, the terf-butyl ester can be obtained directly as shown by the conversion of 15 into 16 (O Scheme 5) [62]. Presumably, the intermediate aldehyde forms a hemiacetal with terf-butanol which is then further oxidized to the ester. 

S-, N-Protective derivatives. The reagent reacts under mild acid catalysis with primary and secondary alcohols, and with phenols, to form tetrahydropyranyl ethers, which are stable to bases, to RMgX, to L1AIH4, to acetic anhydride in pyridine, and to oxidation. When synthetic operations at another site in the molecule have... 

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 few years later the Swem laboratory then developed an activator which they claimed to be the most successful in activating dimethyl sulfoxide toward oxidation, namely, oxalyl chloride. Since oxalyl chloride reacted violently and exothermically with dimethyl sulfoxide, successful activation required the use of low temperatures to form the initial intermediate.6 Swem et al. reported the oxidation of long chain primary alcohols to aldehydes which was previously unsuccessful by first converting to the sulfonate ester (either mesylate or tosylate) and then employing the dimethyl sulfoxide-acetic anhydride procedure. They found that long-chain saturated, unsaturated, acetylenic and steroidal alcohols could all be oxidised with dimethyl sulfoxide-oxalyl chloride in high yields under mild conditions. 

In modern organic synthesis Dess-Martin periodinane (DMP, structure 800 in Scheme 3.316) has emerged as the reagent of choice for the oxidation of primary and secondary alcohols to the respective carbonyl compounds. DMP is commercially available or can be conveniently prepared by the reaction of IBX with acetic anhydride (Section 2.2.3.2) [1211]. The synthetic applications of DMP have been summarized in several overviews [1102,1104,1212,1213]. 

This reaction was first reported by Albright and Goldman from the American Cyanamid Company in 1965. It is a mild conversion of primary and secondary alcohols into corresponding aldehydes and ketones using the mixture of dimethyl sulfoxide and acetic anhydride as the oxidant. This reaction is particularly useful for the oxidation of the steri-cally hindered hydroxyl groups. In general, the oxidation is carried out by allowing a mixture of 1 mmol primary or secondary alcohol, 3 mL DMSO, and 2 mL (20 mmol excess) acetic anhydride to stand at room temperature for 18-24 h. ... 

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