Ketone-aldehydes => keto-acids

An important general method of preparing indoles, known as the Fischer Indole synthesis, consists in heating the phenylhydrazone of an aldehyde, ketone or keto-acid in the presence of a catalyst such as zinc chloride, hydrochloric acid or glacial acetic acid. Thus acetophenone phenylhydrazone (I) gives 2-phenylindole (IV). The synthesis involves an intramolecular condensation with the elimination of ammonia. The following is a plausible mechanism of the reaction ... 

The spectrum of applications of potassium permanganate is very broad. This reagent is used for dehydrogenative coupling [570], hydrox-ylates tertiary carbons to form hydroxy compounds [550,831], hydroxylates double bonds to form vicinal diols [707, 296, 555, 577], oxidizes alkenes to a-diketones [560, 567], cleaves double bonds to form carbonyl compounds [840, 842, 552] or carboxylic acids [765, 841, 843, 845, 852, 869, 872, 873, 874], and converts acetylenes into dicarbonyl compounds [848, 856, 864] or carboxylic acids [843, 864], Aromatic rings are degraded to carboxylic acids [575, 576], and side chains in aromatic compounds are oxidized to ketones [566, 577] or carboxylic acids [503, 878, 879, 880, 881, 882, 555]. Primary alcohols [884] and aldehydes [749, 868, 555] are converted into carboxylic acids, secondary alcohols into ketones [749, 839, 844, 863, 865, 886, 887], ketones into keto acids [555, 559, 590] or acids [559, 597], ethers into esters [555], and amines into amides [854, 555] or imines [557], Aromatic amines are oxidized to nitro compounds [755, 559, 592], aliphatic nitro compounds to ketones [562, 567], sulfides to sulfones [846], selenides to selenones [525], and iodo compounds to iodoso compounds [595]. 

The addition of lithium and Grignard reagents to isocyanides which do not contain a-hydrogens proceeds by an a-addition to produce a metalloaldimine (7, an acyl anion equivalent). The lithium aldimines are versatile reagents which can be used as precursors for the preparation of aldehydes, ketones, a-hy-droxy ketones, a-keto acids, a- and 3-hydroxy acids, silyl ketones and a-amino acids (Scheme 5). - ... 

Oxidation of hydioxyl groups to carbonyl groups can form molecules with two aldehyde groups (dialdoses), two ketone groups (diuloses), or an aldehyde and a ketone group (osuloses). Keto acids are known as ulosonic acids. 

Esters, like aldehydes and ketones, are weakly acidic. When an ester with an a- hydrogen is treated with 1 equivalent of a base such as sodium ethoxide, a reversible carbonyl condensation reaction occurs to yield a /3-keto ester. For example, ethyl acetate yields ethyl acetoacetate on base treatment. This reaction between two ester molecules is known as the Claisen condensation reaction. (We ll use ethyl esters, abbreviated "Et," for consistency, but other esters will also work.)... 

The reaction therefore constitutes a method for converting an organometallic compound R M to aldehyde R CHO (see also 12-30), an a-keto acid, a ketone... 

Certain ketoximes can be converted to nitriles by the action of proton or Lewis acids. Among these are oximes of a-diketones (illustrated above), a-keto acids, a-dialkylamino ketones, a-hydroxy ketones, p-keto ethers, and similar compounds. These are fragmentation reactions, analogous to 17-25 and 17-26. For example, ot-dialkylamino ketoximes also give amines and aldehydes or ketones besides nitriles. 

Pd-catalyzed carbonylation of heteroaryl halides provides a quick entry to heteroaryl carbonyl compounds such as heteroaryl aldehydes, carboxylic acids, ketones, esters, amides, a-keto esters and a-keto amides. In addition, Pd-catalyzed alkoxycarbonylation and aminocarbonylation are compatible with many functional groups, and therefore, are more advantageous than conventional methods for preparing esters and amides [78],... 

Typical examples are listed in Table 2.1. A few oxidations are effected by RuO but in general it is too powerful an oxidant for this purpose. The system RuCyaq. NaCl-CCy Pt anode oxidised benzyl alcohol to benzaldehyde and benzoic acid and p-anisaldehyde to p-anisic acid [24], and a wide range of primary alcohols and aldehydes were converted to carboxylic acids, secondary alcohols to ketones, l, -diols to lactones and keto acids from RuOj/aq. NaCl pH 4/Na(H3PO )/Pt electrodes (Tables 2.1-2.4). The system [RuO ] "/aq. K3(S303)/Adogen /CH3Cl3 oxidised benzyhc alcohols to aldehydes [30]. The oxidation catalyst TPAP (( Pr N)[RuO ]) (cf. 1.3.4) is extremely useful as an oxidant of primary alcohols to aldehydes and secondary alcohols to ketones without... 

The reaction takes place in a two-phase medium. Secondary alcohols form ketones (90%), primary alcohols and aldehydes are oxidized to carboxylic acids (60-77%), 1,2-diols are cleaved to carboxylic acids (75%), 1,4- and 1,5-diols are transformed to lactones and keto acids (75 %). 

We have previously seen (0-96) that dianions of carboxylic acids can be alkylated in the a position. These ions can also be acylated on treatment with a carboxylic ester1705 to give salts of p-keto acids. As in 0-96, the carboxylic acid can be of the form RCH2COOH or RR"CHCOOH. Since p-keto acids are so easily converted to ketones (2-40), this is also a method for the preparation of ketones R COCHiR and R COCHRR", where R can be primary, secondary, or tertiary alkyl, or aryl. If the ester is ethyl formate, an a-formyl carboxylate salt (R = H) is formed, which on acidification spontaneously de-carboxylates into an aldehyde.1706 This is a method, therefore, for achieving the conversion RCH2COOH — RCH2CHO, and as such is an alternative to the reduction methods discussed in 0-83. When the carboxylic acid is of the form RR CHCOOH. better yields are obtained by acylating with acyl halides rather than esters.1707... 

The reaction therefore constitutes a method for converting an organometallic compound R M to an aldehyde R CHO (see also 2-32), an oi-keto acid,809 a ketone R COR (see also 2-32), an a-hydroxy ketone, or a p-hydroxy ketone. In each case the C=N bond is hydrolyzed to a 0=0 bond (6-2). 

Kinetic template effects have been postulated in more typical organic aldol condensations, where metals such as lithium and zinc are likely to coordinate both the enolate or enamine nucleophile and the aldehyde in the transition state. The examples shown in Schemes 58184 and 59185 are illustrative of these reactions and the degree of selectivity obtained. The carboxylation of ketones and nitroalkanes by methyl magnesium carbonate to produce P-keto acids and a-nitro acids respectively provides early examples of similar reactions (Scheme 60).186 187 See also Section 61.1.4.4. 

Protection of aldehydes and ketones.1 Bis-o-nitrobenzyl acetals or ketals are removable in 85-95% yield on irradiation at 350 nm in benzene. The acetals or ketals are easily prepared from 1 by an exchange reaction using 2,2-dimethoxy-propane (1, 268-269) catalyzed by an arenesulfonic acid. In the case of hindered ketones (17-keto steroids), the glycol o-N02C6H4CH(OH)CH2OH (2) can be used. 

This reaction is quite special in that it is an aldol-type addition in which a thioester is the donor (nucleophile) and a keto acid is the acceptor (electrophile). From the discussion in Section 18-8E, you will see that reactions of this kind involving an ester as the donor and an aldehyde or ketone as the acceptor can be achieved in the laboratory only under rather special conditions. For the thioester to function as a nucleophile at the a carbon under the restraints imposed by having the reaction occur at the physiological pH, the catalyzing enzyme almost certainly must promote formation of the enol form of the thioester. The enol then could add to the ketone carbonyl with the assistance of a basic group on the enzyme. This kind of catalysis by enzymes is discussed in Section 25-9C. 

Ascorbic acid, known more familiarly as vitamin C, is used not only as on acidulant but also as a stabiliser within the soft drinks system, and its antioxidant properties serve to improve the shelf-fife stability of flavour components. Many of the ingredients used in flavourings are susceptible to oxidation, particularly aldehydes, ketones and keto-esters. Ascorbic acid shields these from attack by being preferentially oxidised and lost, leaving the flavour component unaffected. 

The enol tautomers of many ketones and aldehydes, carboxylic acids, esters and amides, ketenes, as well as the keto tautomers of phenols have since all been generated by flash photolysis to determine the pH rate profiles for keto-enol interconversion. Equilibrium constants of enolization, KB, were determined accurately as the ratio of the rate constants of enolization, kE, and of ketonization, kK, Equation (1). 

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