Sulfide, dimethyl carboxylic acid reduction

Aldehydes are easily oxidized to carboxylic acids under conditions of ozonide hydroly SIS When one wishes to isolate the aldehyde itself a reducing agent such as zinc is included during the hydrolysis step Zinc reduces the ozonide and reacts with any oxi dants present (excess ozone and hydrogen peroxide) to prevent them from oxidizing any aldehyde formed An alternative more modem technique follows ozone treatment of the alkene m methanol with reduction by dimethyl sulfide (CH3SCH3)... 

The most common procedure is ozonolysis at -78 °C (P.S. Bailey, 1978) in methanol or methylene chloride in the presence of dimethyl sulfide or pyridine, which reduce the intermediate ozonides to aldehydes. Unsubstituted cydohexene derivatives give 1,6-dialdehydes, enol ethers or esters yield carboxylic acid derivatives. Oxygen-substituted C—C bonds in cyclohexene derivatives, which may also be obtained by Birch reduction of alkoxyarenes (see p. 103f.), are often more rapidly oxidized than non-substituted bonds (E.J. Corey, 1968 D G. Stork, 1968 A,B). Catechol derivatives may also be directly cleaved to afford conjugated hexa-dienedioic acid derivatives (R.B. Woodward, 1963). Highly regioselective cleavage of the more electron-rich double bond is achieved in the ozonization of dienes (W. KnOll, 1975). 

Both permanganate and ozonolysis break the carbon-carbon double bond and replace it with carbonyl (C=0) groups. In the permanganate cleavage, any aldehyde products are further oxidized to carboxylic acids. In the ozonolysis-reduction procedure, the aldehyde products are generated in the dimethyl sulfide reduction step (and not in the presence of ozone), and they are not oxidized. 

Reduction of carboxylic acids with borane-dimethyl sulfide generally proceeds rapidly In connection with reduction experiments with p-hydroxybenzoic acid, it was found that this compound gave only low yields of p-hydroxybenzyl alcohol when treated with borane-dimethyl sulfide according to the procedure described by Knstersson et al (1980) This is in accordance with studies of the... 

To ensure complete oxidation of aldehydes to carboxylic acids, Aulin-Erdtman and Tomita (1963) treated the ozonation products of lignin model compounds with hydrogen peroxide. Soteland (1971) applied hydrogen peroxide to a groundwood ozonation product and found that it degraded the components to unidentified volatile substances. To simplify the product mixture, reduction is sometimes used to stop further oxidation. Tanahashi et al. (1975) applied palladium-catalyzed hydrogenation, while Kondo et al. (1987) added dimethyl sulfide. 

There have been two major approaches towards achieving selective reduction of carboxylic acid derivatives to aldehydes (or derivatives) by hydrides. Firstly, hydride reagents themselves have been modified as, for example, sodium borohydride and sodium cyanoborohydride. Sometimes these modifications have led to finely tuned reducing agents, as with the dimethyl sulfide adduct of thexylbromoborane (see later). Secondly, the type of carboxylic acid derivative has been modified for the optimum yield of aldehyde. For example, amides have been made from an assortment of amines in efforts to maximize yields of aldehyde. Best yields of aldehydes are obtained usually by a combination of modified hydride reagent with a modified carboxylic acid derivative. 

Barton has devised such a pathway for converting carboxylic acids to hydroperoxides via A -hydroxypyridine-2-thione esters [16a,b] (Scheme 5). The yields of hydroperoxides are 45-89% [16]. Reduction of the crude products with trimethyl phosphite (rt) or dimethyl sulfide (80 °C) readily provides the corresponding alcohols. On the other hand, tosylation and ensuing Kornblum-De La Mare type fragmentation [17] leads to carbonyl compounds [16b] (Scheme 5). 

Fig. 8.3 Ozonolysis allows the cleavage of alkene double bonds. According to the Criegee mechanism the primary ozonide (POZ) is rapidly transformed into the more stable secondary ozonide (SOZ). Depending on the work-up, different products may be isolated. Oxidative work-up with hydrogen peroxide leads to carboxylic acids/ketones, while reductive work-up with either dimethyl sulfide or sodium borohydride gives aldehydes/ketones or alcohols, respectively...

An epimeric mixture of 2-cyanopyrrolidines resulted and upon separation of the desired isomer, the arabinitol derivative was produced by acid hydrolysis and borane-dimethyl sulfide reduction of the so-formed carboxylic acid7 ... 

---