Reducing agents dimethyl sulfide

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)... 

Certain base adducts of borane, such as triethylamine borane [1722-26-5] (C2H )2N BH, dimethyl sulfide borane [13292-87-OJ, (CH2)2S BH, and tetrahydrofuran borane [14044-65-6] C HgO BH, are more easily and safely handled than B2H and are commercially available. These compounds find wide use as reducing agents and in hydroboration reactions (57). A wide variety of borane reducing agents and hydroborating agents is available from Aldrich Chemical Co., Milwaukee, Wisconsin. Base displacement reactions can be used to convert one adduct to another. The relative stabiUties of BH adducts as a function of Group 15 and 16 donor atoms are P > N and S > O. This order has sparked controversy because the trend opposes the normal order estabUshed by BF. In the case of anionic nucleophiles, base displacement leads to ionic hydroborate adducts (eqs. 20,21). 

To avoid further oxidation of the aldehyde by the byproduct H2C>2 formed, hydrolysis is usually carried out in the presence of mild reducing agents.584,592 Catalytic hydrogenation, Zn + CH3COOH, and Nal or KI are the most frequently used conventional reductants.582 584 592 Dimethyl sulfide,622 triphenyl phosphine,607 and thiourea,623 introduced later, are likewise effective and selective reducing agents. 

This solvent is fairly pure as received. The only impurities are water and traces of dimethyl sulfide. Dimethyl sulfide can be removed by a preliminary vacuum distillation, or by bubbling an inert gas through the solution for 10 to 20 min before use. The water content can be reduced to 10 ppm by sequential treatment with two batches of 3 A molecular sieves (activation of the sieve at 500°C for 16 h in an inert atmosphere has been advocated [62], but activation for 15 h at 300°C should suffice [52]). Calcium hydride and a number of other basic reagents have been advocated as drying agents, but in fact all of these are ineffective [32]. Tetrabutylammonium hexafluorophosphate exhibits good solubility in THF. 

Borane (as BH3 in tetrahydrofuran or dimethyl sulfide) is an even milder reducing agent than BH4G for the carbonyl group of aldehydes and ketones. This difference in reactivity can be used to advantage when selective reduction is necessary. For example, borohydride reduces a ketone carbonyl more rapidly than a carbon-carbon double bond, whereas borane reduces the carbon-carbon double bond more rapidly than carbonyl ... 

As cyano-substituted ozonides were easily reduced by triphenylphosphine, also p-tolyl sulfide can be used as a reducing agent and the corresponding sulfoxide could be isolated in quantitative yield. Alternatively, the 3-cyano-3-phenyl-ozonide 103 can oxidize 2,3-dimethyl-2-butene to the corresponding epoxide (Scheme 34). 

Ozonides are not very stable, and they are rarely isolated. In most cases, they are immediately reduced by a mild reducing agent such as zinc or (more recently) dimethyl sulfide. The products of this reduction are ketones and aldehydes. 

Because they are easily oxidized, sulfides are often used as mild reducing agents. For example, we have used dimethyl sulfide to reduce the potentially explosive ozonides that result from ozonolysis of alkenes (Section 8-15). 

The vacant orbital is able to accept a lone pair of electrons from a Lewis base to give a neutral species or can combine with a nucleophile to form a negatively charged tetrahedral anion. Thcj reducing agent boran e-dimethyl sulfide is an example of the Lewis acid behaviour while the borohy-j dride anion would be the result of the imaginary reaction of borane with a nucleophile hydride. The vacant orbital makes borane a target for nucleophiles. 

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. 

Ozonides are rarely isolated [75, 76, 77, 78, 79], These substances tend to decompose, sometimes violently, on heating and must, therefore, be handled with utmost safety precautions (safety goggles or face shield, protective shield, and work in the hood). In most instances, ozonides are worked up in the same solutions in which they have been prepared. Depending on the desired final products, ozonide cleavage is done by reductive or oxidative methods. Reductions of ozonides to aldehydes are performed by catalytic hydrogenation over palladium on carbon or other supports [80, 81, 82, S3], platinum oxide [84], or Raney nickel [S5] and often by reduction with zinc in acetic acid [72, 81, 86, 87], Other reducing agents are tri-phenylphosphine [SS], trimethyl phosphite [89], dimethyl sulfide (DMS) [90, 91, 92], and sodium iodide [93], Lithium aluminum hydride [94, 95] and sodium borohydride [95, 96] convert ozonides into alcohols. 

Polymer-supported chiral oxazoborolidines have also been used for the reduction of prochiral ketones. Enantiomeric excesses of 98% were obtained for the reduction of acetophenone using borane dimethyl sulfide as a stoichiometric reducing agent [77, 78]. 

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