Ketone and Aldehyde Reduction

Clemmensen reduction Aldehydes and ketones may generally be reduced to the corresponding hydrocarbons by healing with amalgamated zinc and hydrochloric acid. 

By application of the Clemmensen reduction,aldehydes and ketones 1 can be converted into the corresponding hydrocarbons 2. As the reducing agent zinc amalgam, together with concentrated hydrochloric acid or gaseous hydrogen chloride, is used. 

Upon one-electron reduction, aldehydes and ketones give anion radicals. It is the carbonyl group that serves as a reservoir for the unpaired electron Ketones yield pinacols exclusively. Thus, acetophenone forms 2,3-diphenylbutan-2,3-diol as a result of electrolysis at the potential of the first one-electron transfer wave (nonaqueous acetonitrile as a solvent, with tetraalkylammonium perchlorate as a supporting electrolyte) (van Tilborg Smit 1977). In contrast, calculations have shown that the spin densities on the carbonyl group and in the para position of the benzene ring are equal (Mendkovich et al. 1991). This means that one should wait for the formation of three types of dimer products, head-to-head, tail-to-tail, and head-to-tail cf. Section 3.2.1. For the anion radical of acetophenone, all three possible dimers are depicted in Scheme 5-10. 

Clemmensen reduction Aldehydes and ketones are reduced by heating with a solution of zinc metal in mercury (zinc amalgam) and hydrochloric acid. 

Reduction. Aldehydes and ketones are reduced electrochemically with A1 electrodes in refluxing ethanol (Nal as electrolyte). 

The reactivity of various functional groups toward 9-BBN thus is classified into five broad categories as (1) very rapid-reduction aldehyde and ketone (2) rapid reduction-reaction olefin, quinone, tertiary amide, acid anhydride, acid chloride, and lactone (3) slow-reduction ester, epoxide, and oxime (4) very slow-reduction carboxylic acid, sulfoxide, and azoxy and (5) inert (no reaction)... 

SchifT s bases A -Arylimides, Ar-N = CR2, prepared by reaction of aromatic amines with aliphatic or aromatic aldehydes and ketones. They are crystalline, weakly basic compounds which give hydrochlorides in non-aqueous solvents. With dilute aqueous acids the parent amine and carbonyl compounds are regenerated. Reduction with sodium and alcohol gives... 

NH2-C0-NH NH2,CH5N30. Colourless crystalline substance m.p. 96" C. Prepared by the electrolytic reduction of nitrourea in 20% sulphuric acid at 10 "C. Forms crystalline salts with acids. Reacts with aldehydes and ketones to give semicarbazones. Used for the isolation and identification of aldehydes and ketones. 

Aldehydes and ketones may be converted into the corresponding primary amines by reduction of their oximes or hydrazones (p. 93). A method of more limited application, known as the Leuckart Reaction, consists of heating the carbonyl compound with ammonium formate, whereby the formyLamino derivative is formed, and can be readily hydrolysed by acids to the amine. Thus acetophenone gives the i-phenylethylformamide, which without isolation can be hydrolysed to i-phenylethylamine. 

Clemmensen reduction of aldehydes and ketones. Upon reducing aldehydes or ketones with amalgamated zinc and concentrated hydrochloric acid, the main products are the hydrocarbons (>C=0 —> >CHj), but variable quantities of the secondary alcohols (in the case of ketones) and unsaturated substances are also formed. Examples are ... 

Wolff - Kishner reduction of aldehydes and ketones. Upon heating the hydrazoiie or semicarbazone of an aldehyde or ketone with potassium hydroxide or with sodium ethoxide solution (sealed tube), the corresponding hydrocarbon is obtained ... 

The condensation of aldehydes and ketones with succinic esters in the presence of sodium ethoxide is known as the Stobbe condensation. The reaction with sodium ethoxide is comparatively slow and a httlo reduction of the ketonic compound to the carbinol usually occurs a shorter reaction time and a better yield is generally obtained with the more powerful condensing agent potassium ieri.-butoxide or with sodium hydride. Thus benzophenone condenses with diethyl succinate in the presence of potassium [Pg.919]

The imides, primaiy and secondary nitro compounds, oximes and sulphon amides of Solubility Group III are weakly acidic nitrogen compounds they cannot be titrated satisfactorily with a standard alkaU nor do they exhibit the reactions characteristic of phenols. The neutral nitrogen compounds of Solubility Group VII include tertiary nitro compounds amides (simple and substituted) derivatives of aldehydes and ketones (hydrazones, semlcarb-azones, ete.) nitriles nitroso, azo, hydrazo and other Intermediate reduction products of aromatic nitro compounds. All the above nitrogen compounds, and also the sulphonamides of Solubility Group VII, respond, with few exceptions, to the same classification reactions (reduction and hydrolysis) and hence will be considered together. 

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

We will begin with the reduction of aldehydes and ketones... 

For most laboratory scale reductions of aldehydes and ketones catalytic hydro genation has been replaced by methods based on metal hydride reducing agents The two most common reagents are sodium borohydride and lithium aluminum hydride... 

The mechanism of lithium aluminum hydride reduction of aldehydes and ketones IS analogous to that of sodium borohydride except that the reduction and hydrolysis... 

Table 17 2 summarizes the reactions of aldehydes and ketones that you ve seen m ear her chapters All are valuable tools to the synthetic chemist Carbonyl groups provide access to hydrocarbons by Clemmensen or Wolff-Kishner reduction (Section 12 8) to alcohols by reduction (Section 15 2) or by reaction with Grignard or organolithmm reagents (Sections 14 6 and 14 7)... 

Converting aldehydes and ketones to cyanohydrins is of synthetic value for two reasons (1) a new carbon-carbon bond is formed and (2) the cyano group in the prod uct can be converted to a carboxylic acid function (CO2H) by hydrolysis (to be discussed in Section 19 12) or to an amine of the type CH2NH2 by reduction (to be discussed m Section 22 9)... 

Clemmensen reduction (Section 12 8) Method for reducing the carbonyl group of aldehydes and ketones to a methylene... 

Sodium cyanoborohydride is remarkably chemoselective. Reduction of aldehydes and ketones are, unlike those with NaBH pH-dependent, and practical reduction rates are achieved at pH 3 to 4. At pH 5—7, imines (>C=N—) are reduced more rapidly than carbonyls. This reactivity permits reductive amination of aldehydes and ketones under very mild conditions (42). 

By-Products. Almost all commercial manufacture of pyridine compounds involves the concomitant manufacture of various side products. Liquid- and vapor-phase synthesis of pyridines from ammonia and aldehydes or ketones produces pyridine or an alkylated pyridine as a primary product, as well as isomeric aLkylpyridines and higher substituted aLkylpyridines, along with their isomers. Furthermore, self-condensation of aldehydes and ketones can produce substituted ben2enes. Condensation of ammonia with the aldehydes can produce certain alkyl or unsaturated nitrile side products. Lasdy, self-condensation of the aldehydes and ketones, perhaps with reduction, can lead to alkanes and alkenes. 

Addition of sodium dithionite to formaldehyde yields the sodium salt of hydroxymethanesulfinic acid [79-25-4] H0CH2S02Na, which retains the useful reducing character of the sodium dithionite although somewhat attenuated in reactivity. The most important organic chemistry of sodium dithionite involves its use in reducing dyes, eg, anthraquinone vat dyes, sulfur dyes, and indigo, to their soluble leuco forms (see Dyes, anthraquinone). Dithionite can reduce various chromophores that are not reduced by sulfite. Dithionite can be used for the reduction of aldehydes and ketones to alcohols (348). Quantitative studies have been made of the reduction potential of dithionite as a function of pH and the concentration of other salts (349,350). 

The aromatic primary and secondary stibines are readily oxidized by air, but they are considerably more stable than their aHphatic counterparts. Diphenylstibine is a powerful reducing agent, reacting with many acids to Hberate hydrogen (79). It has also been used for the selective reduction of aldehydes and ketones to the corresponding alcohols (80). At low temperatures, diphenylstibine undergoes an addition reaction with ketene (81) ... 

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