7-keto carboxylic acids/esters

The direct fluorination with elemental fluorine at — 78 "C of trimethylsilyl enol ethers derived from diketones results in the formation of the corresponding monofluoro diketones 11 in moderate yield. The trimethylsilyl ethers from cyclic diketones undergo smooth fluorination to give the enol forms, c.g. 12, and not the keto forms.Higher yields are generally observed for the analogous reactions of silyl derivatives of esters, carboxylic acids, malonates, dimethyl amides and lactones (Table 4). ... 

In the following discussion we will consider the oxidation of carboxylic acids in the general order monocarboxylic acids, hydroxy carboxylic acids, keto carboxylic acids, polycarboxylic acids, esters, and finally ascorbic acid (see table 6). Oxidation of aminopolycarboxylic acids has been reviewed in sect. 3.3 of this report. 

The most widely used method for the preparation of carboxylic acids is ester hydrolysis. The esters are generally prepared by heterocyclization (cf. Chapter II), the most useful and versatile of which is the Hantzsch s synthesis, that is the condensation of an halogenated a- or /3 keto ester with a thioamide (1-20). For example ethyl 4-thiazole carboxylate (3) was prepared by Jones et al. from ethyl a-bromoacetoacetate (1) and thioformamide (2) (1). Hydrolysis of the ester with potassium hydroxide gave the corresponding acid (4) after acidification (Scheme 1). 

Trimethylsilyl trichloroacetate, K2CO3, 18-crown-6, 100-150°, 1-2 h, 80-90% yield.This reagent silylates phenols, thiols, carboxylic acids, acetylenes, urethanes, and /3-keto esters, producing CO2 and chloroform as byproducts. 

However, for the preparation of derivatives which contain a functional group directly attached to position 6, the application of the foregoing cyclization method is considerably limited by the availability or existence of the required derivatives of -keto acids and may also be affected by differences in their reactivity. Cyclization of thiosemicarbazones was, therefore, used for these substances only in the case of the 6-carboxylic acid (see also Section II,B,2,a). Of the other derivatives known, the 6-acetic acid ester should be mentioned. Recently some further derivatives of dioxotriazine-6-carboxylic acid were reported. ... 

Most carbonyl compounds exist almost exclusively in the keto form at equilibrium, and it s usually difficult to isolate the pure enol. For example, cyclohexanone contains only about 0.0001% of its enol tautomer at room temperature, and acetone contains only about 0.000 000 1% enol. The percentage of enol tautomer is even less for carboxylic acids, esters, and amides. Even though enols are difficult to isolate and are present only to a small extent at equilibrium., they are nevertheless responsible for much of the chemistry of carbonyl compounds because they are so reactive. 

The oxidation of aldehydes to carboxylic acids can proceed by a nucleophilic mechanism, but more often it does not. The reaction is considered in Chapter 14 (14-6). Basic cleavage of (3-keto esters and the haloform reaction could be considered at this point, but they are also electrophilic substitutions and are treated in Chapter 12 (12-41 and 12-42). 

RCH(OH)=CHCOR or p-keto esters RCH(OH)=CHCOOR ) dissolve in dilute sodium hydroxide solution, i.e., contain an acidic group of sufficient strength to react with the alkah. Carboxylic acids and sulphonic acids are soluble in dilute solutions of sodium bicarbonate some negatively-substituted phenols, for example, picric acid, 2 4 6-tribromo-phenol and 2 4-dinitrophenol, are strongly acidic and also dissolve in dilute sodium bicarbonate solution. 

Nitroalkenes react with lithium dianions of carboxylic acids or with hthium enolates at -100 °C, and subsequent treatment of the Michael adducts with aqueous acid gives y-keto acids or esters in a one-pot operation, respectively (Eq. 4.52).66 The sequence of Michael addition to nitroalkenes and Nef reaction (Section 6.1) provides a useful tool for organic synthesis. For example, the addition of carbanions derived from sulfones to nitroalkenes followed by the Nef reaction and elimination of the sulfonyl group gives a,P-unsaturated ketones (Eq. 4.53).67... 

A complicating feature of studies of carboxylic acid and their corresponding esters, having proximate keto or formyl groups, is the occurrence of ring-chain tautomerism, as in Scheme 1 (Valters and Flitsch, 1985). The rates of conversion of the ring and chain acids ([1] and [2] R = H) are rapid. However, both the pseudo and normal esters ([1] and [2], R = alkyl or aryl) can be isolated in favourable circumstances. The latter esters can also be interconverted by base- or acid-catalysis under suitable conditions. 

Reactions with Carboxylic Acid Esters Alkyl nitrones can be metallized upon treatment with phenyl lithium in ether solution. The Li-derivatives react with carboxylic acid esters to give 3-oxo nitrones (305)- the analogs of 3-diketones and j3-keto esters (545). With the help of the 13C NMR method it has been found that 3-oxo nitrones (305) exist as an equilibrium mixture... 

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