Ketone reduction, chemical reaction

The ability to protect an aldehyde in the presence of a ketone allows chemical reactions of the ketone group without competitive reactions that would occur in the original unprotected compound. For example, the Wolff-Kishner reduction converts the carbonyl group to a methylene group. 

During electrochemical reduction of aldehydes and ketones other chemical reactions take place in addition to protonation in the region in the vicinity of the electrode. Thus, with aromatic aldehydes and ketones in sufficiently acidic solutions at the potentials of the first reduction wave the free radicals dimerize to pinacols immediately after the electron transfer, and under conditions where the electrode process proper is reversible the dimerization affects the... 

Two classes of charged radicals derived from ketones have been well studied. Ketyls are radical anions formed by one-electron reduction of carbonyl compounds. The formation of the benzophenone radical anion by reduction with sodium metal is an example. This radical anion is deep blue in color and is veiy reactive toward both oxygen and protons. Many detailed studies on the structure and spectral properties of this and related radical anions have been carried out. A common chemical reaction of the ketyl radicals is coupling to form a diamagnetic dianion. This occurs reversibly for simple aromatic ketyls. The dimerization is promoted by protonation of one or both of the ketyls because the electrostatic repulsion is then removed. The coupling process leads to reductive dimerization of carbonyl compounds, a reaction that will be discussed in detail in Section 5.5.3 of Part B. 

The principles outlined above are, of course, important in electro-synthetic reactions. The pH of the electrolysis medium, however, also affects the occurrence and rate of proton transfers which follow the primary electron transfer and hence determine the stability of electrode intermediates to chemical reactions of further oxidation or reduction. These factors are well illustrated by the reduction at a mercury cathode of aryl alkyl ketones (Zuman et al., 1968). In acidic solution the ketone is protonated and reduces readily to a radical which may be reduced further only at more negative potentials. 

The hydrogen transfer reaction (HTR), a chemical redox process in which a substrate is reduced by an hydrogen donor, is generally catalysed by an organometallic complex [72]. Isopropanol is often used for this purpose since it can also act as the reaction solvent. Moreover the oxidation product, acetone, is easily removed from the reaction media (Scheme 14). The use of chiral ligands in the catalyst complex affords enantioselective ketone reductions [73, 74]. 

The asymmetric formation of industrially useful diaryl methanols can be realized through either the addition of aryl nucleophiles to aromatic aldehydes or the reduction of diaryl ketones. The latter route is frequently the more desirable, as the starting materials are often inexpensive and readily available and nonselective background reactions are not as common. For good enantioselectivity, chemical catalysts of diaryl ketone reductions require large steric or electronic differentiation between the two aryl components of the substrate and, as a result, have substantially limited applicability. In contrast, recent work has shown commercially available ketoreductase enzymes to have excellent results with a much broader range of substrates in reactions that are very easy to operate (Figure 9.6). ... 

Because carbohydrates are so frequently used as substrates in kinetic studies of enzymes and metabolic pathways, we refer the reader to the following topics in Ro-byt s excellent account of chemical reactions used to modify carbohydrates formation of carbohydrate esters, pp. 77-81 sulfonic acid esters, pp. 81-83 ethers [methyl, p. 83 trityl, pp. 83-84 benzyl, pp. 84-85 trialkyl silyl, p. 85] acetals and ketals, pp. 85-92 modifications at C-1 [reduction of aldehydes and ketones, pp. 92-93 reduction of thioacetals, p. 93 oxidation, pp. 93-94 chain elongation, pp. 94-98 chain length reduction, pp. 98-99 substitution at the reducing carbon atom, pp. 99-103 formation of gycosides, pp. 103-105 formation of glycosidic linkages between monosaccharide residues, 105-108] modifications at C-2, pp. 108-113 modifications at C-3, pp. 113-120 modifications at C-4, pp. 121-124 modifications at C-5, pp. 125-128 modifications at C-6 in hexopy-ranoses, pp. 128-134. 

The electrochemical reduction of acid chlorides takes a very different course when carried out in an undivided cell equipped with nickel cathode and anode79. The product is a symmetrical ketone (57) 57 is formed by a complex sequence involving both electrodes (Scheme 12). This is really a chemical reaction induced by a highly reactive form of nickel produced by dissolution of the anode and plated onto the cathode. We have already encountered similar chemistry involving highly reactive zinc (Section V.A.l). 

The simplest method for generation of a ketyl anion is via direct reduction (chemically of electrochemically) of an aldehyde or ketone (Figure 1, reaction 1). Historically, it was via direct reduction of a ketone with an alkali metal that ketyl anions were first discovered. 

Other examples have been provided by the anodically initiated isomerization of several decarbene metal carbonyl couples [197]. Electrochemical induction of chemical reactions can also be successfully used for conversion of alcoolates into ketones with simultaneous reduction of aromatic halides [198], the tetramerization of aziridines [199], or ligand substitution [200] in organometallic compounds. A useful review on this subject was published [201]. 

The scheme was verified usii chronopotentiometric and potentio-static methods (Alberts and Shain, 1963). A similar scheme was considered for the reduction of o- and p-nitrophenols and nitroanilines but the theoretical treatment is more involved owing to the irreversibility of the first four-electron reduction step. Similarly also a chemical reaction is interposed between the first and second electrode process in the reductions of a-substituted ketones of the type RCO.CHg—X (for X=NR2, NR, SR, SRf, OR, PRJ and halogen) and in the reductions of a,)9-unsaturated ketones. In both these systems enolate is a primary electro-inactive reduction product that must be first transformed into the electro-active keto-form. The rate of this transformation, which is acid-base catalysed, limits the wave-height of the more negative wave of the saturated ketone. Similarly it was explained why the more negative wave observed on curves of benzil is smaller than expected for the given concentration of benzoin. 

Use of imines as synthetic intermediates has been limited to mainly two processes reduction to amines, and as precursors to azaallyl anions for reaction with a variety of electrophiles (equation 36). The former transformation can often provide the best access to highly substituted amines and the latter represents one of the highest yield methods for carbon-carbon bond formation a to the carbonyl group of an aldehyde or ketone. Thus, the following sections will deal not only with imines but also with the properties and chemical reactions of the derived anions. Several reviews are available (in addition to those that cover both enamine and imine anion chemistry) as the result of recently uncovered methods for asymmetric induction through reactions of the anions. > ... 

The possibility that ultrasound can be involved chemically in an intended electrochemical system is not without precedent at Wesleyan University. In earlier work involving the electroreduction of a,a -dibromo ketones at a mercury cathode, ultrasound was employed just for stirring [201,202]. It was then realized that although the dihaloketone was stable to mercury (without electrolysis) over weeks in silent conditions, the ultrasonic irradiation, which tended to produce a range of finely divided mercury droplets above the pool, induced sonochemical reduction on the metal [203]. The authors later deduced experimental conditions using either electrochemistry or chemical reaction on ultrasonically dispersed mercury that could select from the range of possible products [204]. 

The amine 2 is made by a chemical reaction - the reductive amination of ketone 1. The starting material 1 and the reagents are all achiral so the product 2, though chiral, must be racemic. Reaction with one enantiomer of tartaric acid 3 forms the amine salt 4, or rather the amine salts 4a and 4b. Examine these structures carefully. The stereochemistry of tartaric acid 3 is the same for both salts but the stereochemistry of the amine 2 is different so these salts 4a and 4b are diastereoisomers. They have different physical properties the useful distinction, discovered by trial and error, is that 4b crystallises preferentially from a solution in methanol leaving 4a behind in solution. Neutralisation of 4b with NaOH gives the free amine (S) -2, insoluble in water and essentially optically pure. 

Nevertheless, it must be pointed out that the formation of such transient species has never been spectroscopically observed. Native CDs are effective inverse phase-transfer catalysts for the deoxygenation of allylic alcohols, epoxydation,or oxidation " of olefins, reduction of a,/ -unsaturated acids,a-keto ester,conjugated dienes,or aryl alkyl ketones.Interestingly, chemically modified CDs like the partially 0-methylated CDs show a better catalytic activity than native CDs in numerous reactions such as the Wacker oxidation,hydrogenation of aldehydes,Suzuki cross-coupling reaction, hydroformylation, " or hydrocarboxylation of olefins. Methylated /3-CDs were also used successfully to perform substrate-selective reactions in a two-phase system. 

The limited quantities of teloidine so far available have precluded an investigation of its structure. However, from the marked similarity of its chemical reactions with those of tropine and oscine and from the association of meteloidine with atropine and 1-scopolamine in Datura meteloides, teloidine was considered to be one of the stereoisomers of the trihydroxytropane, XCI. This has been confirmed by synthesis. Teloidinone, the Cj-ketone of teloidine, has been synthesized (3) (mesotartaric aldehyde, methylamine, and acetonedicarboxylic acid) under physiological conditions. Teloidine and an isomer were formed in the reduction of this ketone. 

Steric Effects.—The consequences upon chemical reaction of non-bonded interactions between enantiomeric pairs of molecules have been discussed an antipodal interaction effect was observed in a reductive camphor dimerization and in a camphor reduction. The full paper on the correlation of the rates of chromic acid oxidation of secondary alcohols to ketones with the strain change in going from the alcohol to the carbonyl product has now appeared. It is concluded that the properties of the product are reflected in the transition state for the oxidation. High yields of hindered carbonyls are available from the corresponding alcohols by reaction with DMSO and trifluoroacetic anhydride (TFAA) indeed, the more hindered the alcohol, the higher the yield of carbonyl compound reported Since the DMSO-TFAA reaction occurs instantaneously at low temperatures (<—50°C), it is possible to oxidize alcohols that form stable sulphonium salts only at low temperature. Thus, ( )-isoborneol reacts at room temperature to give camphene, the product of solvolysis of the sulphonium salt the oxidation product, ( + )-camphor, was obtained by the addition of base at low temperature. 

The case of dimerization following electron transfer, e.g., in ketone reduction and reduction of some RMesN" salts, is a special case of a chemical reaction following charge transfer (e and f above). This type of situation has been dealt with specially in papers by Koutecky and Hanus, " Saveant and Vianello, " and by Olmstead, Hamilton, and Nicholson. 

Benzene was introduced in Chapter 5 (Section 5.10). Chapter 21 will discuss many benzene derivatives, along with the chemical reactions that are characteristic of these compounds. In the context of dissolving metal reductions of aldehydes, ketones, and alkynes, however, one reaction of benzene must be introduced. When benzene (65) is treated with sodium metal in a mixture of liquid ammonia and ethanol, the product is 1,4-cyclohexadiene 66. Note that the nonconjugated diene is formed. The reaction follows a similar mechanism to that presented for alkynes. Initial electron transfer from sodium metal to benzene leads to radical anion 67. Resonance delocalization as shown shordd favor the resonance contributor 67B due to charge separation. 

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