Carboxylic acids transformation

Not surprisingly, the hydrolysis of nitriles is the most atom economical reaction. The isohypsic transformations are the acid chloride-Schotten-Baumann sequence, carbodiimide and carbonyl-diimidazole methods, and the hydrolysis of nitriles. The oxidation of nitriles with hydrogen peroxide is hyperhypsic for the reasons mentioned in Section 9.1.1 for the nitrile to carboxylic acid transformation. The umpolung method, which electronically reverses the roles of the reacting partners, is hypohypsic since a net oxidation has occurred at the reactive carbon atom. This is a novel... 

The reaction of alkenyl mercurials with alkenes forms 7r-allylpalladium intermediates by the rearrangement of Pd via the elimination of H—Pd—Cl and its reverse readdition. Further transformations such as trapping with nucleophiles or elimination form conjugated dienes[379]. The 7r-allylpalladium intermediate 418 formed from 3-butenoic acid reacts intramolecularly with carboxylic acid to yield the 7-vinyl-7-laCtone 4I9[380], The /i,7-titisaturated amide 421 is obtained by the reaction of 4-vinyl-2-azetidinone (420) with an organomercur-ial. Similarly homoallylic alcohols are obtained from vinylic oxetanes[381]. 

Both the Clemmensen and the Wolff-Kishner reductions are designed to carry out a specific functional group transformation the reduction of an aldehyde or ketone carbonyl to a methylene group Neither one will reduce the carbonyl group of a carboxylic acid nor... 

Although the present chapter includes the usual collection of topics designed to acquaint us with a particular class of compounds its central theme is a fundamental reaction type nucleophilic addition to carbonyl groups The principles of nucleophilic addition to aide hydes and ketones developed here will be seen to have broad applicability m later chap ters when transformations of various derivatives of carboxylic acids are discussed... 

The chemistry of carboxylic acids is the central theme of this chapter The impor tance of carboxylic acids is magnified when we realize that they are the parent com pounds of a large group of derivatives that includes acyl chlorides acid anhydrides esters and amides Those classes of compounds will be discussed m Chapter 20 Together this chapter and the next tell the story of some of the most fundamental struc tural types and functional group transformations m organic and biological chemistry... 

Overall the carboxylation of Grignard reagents transforms an alkyl or aryl halide to a carboxylic acid in which the carbon skeleton has been extended by one carbon atom... 

Most methods for their preparation convert one class of carboxylic acid derivative to another and the order of carbonyl group stabilization given m Figure 20 1 bears directly on the means by which these transformations may be achieved A reaction that converts one carboxylic acid derivative to another that lies below it m the figure is pracfical a reacfion fhaf converts if fo one fhaf lies above if is nol This is anofher way of saying fhaf one carboxylic acid derivative can be converted to another if the reaction leads to a more stabilized carbonyl group Numerous examples of reacfions of fhis fype will be pre senfed m fhe secfions fhaf follow... 

Hydroxy-6-methyl-2-phenylpyridazin-3(2Fr)-one and 4-hydroxy-5-nitropyridazin-3(2FT)-one rearrange in acidic medium to 3-methyl-l-phenylpyrazole-5-carboxylic acid and 4-nitropyrazole-5-carboxylic acid. 4-Hydroxypyridazin-3(2FT)-ones with a hydroxy group or other group at positions 5 or 6, which is easily replaced in alkaline medium, are transformed into 5-(or 3-)pyrazolones with hot alkali. An interesting example is ring contraction of 5-chloro-4-(methylthio)-l-phenylpyridazin-6(lFT)-one which gives, besides pyrazole derivative (127), 4-hydroxy-5-methylthio-l-phenylpyridazin-6(lFf)-one (128 Scheme 41). 

Potassium t-butoxide in t-butyl alcohol requires powerful electron-attracting substituents at C-4 to effect ring opening of pyrazoles but sodamide does not (Scheme 26) (B-76MI40402). As the key to the transformation is the generation of the anion, similar results were obtained by heating some pyrazole-3-carboxylic acids with quinoline. 

We have already noted (Section 4.04.2.1.4(xi)) that alkyl groups on pyrazoles are oxidized with permanganate to carboxylic acids. Silver nitrate and ammonium persulfate transform 4-ethyl-1-methylpyrazole (436) into the ketone (437) (72JHC1373). The best yield was obtained starting with the alcohol (438) and using an acid dichromate solution as oxidizing agent. 

Lithiated pyrazoles prepared from CtH or preferably from C-Br pyrazoles (B-76MI40402) can be transformed into carboxylic acids. In this way pyrazole-4-carboxylic acids (504 ... 

In common with other carboxylic acids, the 3-carboxyl of penicillins can be subjected to a variety of transformations, provided that they can be effected under conditions compatible... 

Some further transformations involving reduction of the 3-carboxylic acid group are shown in Scheme 21 (66JOC1922, 64JMC483, 70JMC389). 

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

According to Quinkert, photoexcited cyclic ketones may be transformed to open-chain unsaturated carboxylic acids in the presence of molecular oxygen. This reaction may compete efficiently with a-cleavage and secondary transformations thereof. Thus, both stereo iso meric 17-ketones (109) and (110) yield as much as 20% of the unsaturated acid (111) when irradiated in benzene under a stream of oxygen. This photolytic autoxidation has been used notably for partial syntheses of naturally occurring unsaturated 3,4-seco-acids from 3-oxo triterpenes (for references, see ref. 72). 

Reactant and product structures. Because the transition state stmcture is normally different from but intermediate to those of the initial and final states, it is evident that the stmctures of the reactants and products should be known. One should, however, be aware of a possible source of misinterpretation. Suppose the products generated in the reaction of kinetic interest undergo conversion, on a time scale fast relative to the experimental manipulations, to thermodynamically more stable substances then the observed products will not be the actual products of the reaction. In this case the products are said to be under thermodynamic control rather than kinetic control. A possible example has been given in the earlier description of the reaction of hydroxide ion with ester, when it seems likely that the products are the carboxylic acid and the alkoxide ion, which, however, are transformed in accordance with the relative acidities of carboxylic acids and alcohols into the isolated products of carboxylate salt and alcohol. 

In 1934 the transformation of 2 -hydroxychalcones to flavonols in the presence of hydrogen peroxide and sodium hydroxide was reported simultaneously by Algar and Flynn in Ireland and Oyamada in Japan However, many reports following the original disclosures showed that the Algar-Flynn-Oyamada reaction could lead to several products including aurones 4, dihydroflavonols 5, 2-benzyl-2-hydroxydihydrobenzofuran-3-ones 6, and 2-arylbenzofuran-3-carboxylic acids... 

Nonclassical Wittig reaction, olefination by phosphoranes interaction with carboxylic acid derivatives, in transformation of heterocycles 99JCS(P1)3049. 

The a-bromo or a-chloro carboxylic acids 2 are versatile intermediates for further synthetic transformations. For example they can be converted into a-hydroxy carboxylic acids by reaction with water by reaction with cyanide a-cyanocarboxylic acids 7 are obtained, which can be further converted to... 

TheNef reaction of primary nitro compounds gives iildehydes or carboxylic acids, depending on the reaction conditions. Each transformation provides an important tool in organic synthesis. Primary nitro compotmds are converted into carboxylic acids vrith concentrated mineriil acids. Because such harsh conditions iilso lead to side reactions, a milder method is required inorganic synthesis. Basic phosphate-buffered KMnO rapidly converts primary nitroalkanes into carboxylic acids in 90-99% yield fEq. 6.13. "... 

Perhaps the most useful reaction of carboxylic acids is their conversion into esters. There are many methods for accomplishing the transformation, including the S -2 reaction of a carboxylate anion with a primary alkyl halide that we saw in Section 11.3. 

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