Carboxyl derivatives, hydrolysis

Although not of industrial importance, several asymmetric syntheses of (R)-pantolactone (9) have been developed. Stereoselective abstraction of the j Z-proton of the achiral 1,3-propanediol derivative (23) by j -butyUthium-(-)-sparteine, followed by carboxylation and hydrolysis, results in (R)-pantolactone in 80% yield and 95% ee (53). 

Treatment of alkyl 9-benzyloxycarbonyl-3-methyl-6-oxo-2/7,6//-pyr-ido[2,l-f ][l,3]thiazine-4-carboxylates with BBr3 in CH2CI2 at -70 °C for 0.5-1 h and at room temperature for 3h yielded 9-carboxyl derivatives. The decarboxylation of these acids was unsuccessful. Hydrolysis of diethyl cA-3,4-H-3,4-dihydro-3-methyl-6-oxo-2//,6//-pyrido[2,l-f ][l,3]thiazine-4,9-dicarboxylate in aqueous EtOH with KOH at room temperature for 3 days yielded 4-ethoxycarbonyl-3,4-dihydro-3-methyl-6-oxo-2//,6//-pyrido-[2,l-f ] [1,3]thiazine-9-carboxylic acid (00JCS(P1)4373). Alkyl 9-hydroxy-methyl-3-methyl-6-oxo-3,4-dihydro-2//,6//-pyrido[2,l-f ][l,3]thiazine-4-car-boxylates were O-acylated with AC2O and (PhC0)20 in pyridine at room temperature for 12-48h. 

Dunn and Bruice (1970, 1971) presented evidence that the mechanism of hydrolysis of methoxymethoxybenzoic acid is actually A-1. Evidence included a Bronsted coefficient for intramolecular catalysis of DO, based upon points for the unsubstituted compound and the 5-NO2 derivative, and p -values that were the same (—3-0) for both the methyl ester and the carboxyl derivatives of [72] when... 

An enolate anion generated from a carboxylic acid derivative may be used in the same sorts of nucleophilic reactions that we have seen with aldehyde and ketone systems. It should be noted, however, that the base used to generate the enolate anion must be chosen carefully. If sodium hydroxide were used, then hydrolysis of the carboxylic derivative to the acid (see Section 7.9.2) would compete with enolate anion formation. However, the problem is avoided by using the same base, e.g. ethoxide, as is present in the ester... 

Carboxylic derivs., reaction, 230-244 acid hydrolysis, 240, base hydrolysis, 238 electronic effects in, 237 Grignard reagents, 238... 

Whereas most carboxylic derivatives, after enzymatic hydrolysis, dissociate from the active surface, so as to permit attack on new substrate molecules, this is not true for the reactive derivatives of phosphoric acid. Here, after the initial step of hydrolysis (see V, 2), a portion of the molecule adheres to the enzyme in a form, which cannot be easily split and thus produces irreversible inhibition. 

H. Bazin, A. Bouchu, and G. Descotes, Hydrolysis of cyanoethylated carbohydrates Synthesis of new carboxylic derivatives of sucrose, D-glucose and D-fructose, J. Carbohydr. Chem., 14... 

All the reactions and compounds covered in this section will yield Carboxylic Acids on hydrolysis, and thus are known as Carboxylic Acid Derivatives. Hydrolysis is one example of Nucleophilic Acyl Substitution, which is a very important two step mechanism that is common is all reactions that will be covered here. 

Amides are the least reactive of the carboxylic acid derivatives they can be prepared from any of the other acid derivatives. Hydrolysis, either acid- or base-catalyzed, to form acids is the only nucleophilic acyl substitution reaction. 

An obvious starting point was to look for general acid catalysis of the attack of nucleophiles on a methyoxymethyl acetal known to be subject to efficient carboxyl-catalyzed hydrolysis. Participation by nucleophiles other than water in the hydrolysis of the salicylic acid derivative 3.17 could not be convincingly distinguished from specific salt effects (the range of nucleophiles is limited by the requirement that the COOH group (pKa 3.77) be protonated) [49]. On the other hand there is clear involvement of nucleophiles, including carboxylate anions, in the reaction of the dimethylammonium system 3.18 [44] (Scheme 2.24). The difference is presumably simply quantitative. 

The intrinsically high reactivity of the furan nucleus is further exempUlied by the reaction of furfural with excess halogen to produce mucohalic acids incidentally, mucobromic acid reacts with formamide to provide a useful synthesis of 5-bromopyrimidine. On the other hand, with control, methyl furoate can be cleanly converted into its 5-monobromo or 4,5-dibromo derivatives hydrolysis and decarboxylation of the latter then affording 2,3-dibromofuran bromination of 3-furoic acid produces 5-bromofuran-3-carboxylic acid. ... 

For designing enzyme-mimicking catalysts exploiting metal ions as catalytic centers, it is necessary to understand catalytic repertories (32, 33) of metal ions acting as Lewis acid catalysts in the hydrolysis of peptide bonds and related carboxyl derivatives (e.g., esters). Although esters are much easier to hydrolyze than peptides, important mechanistic information for catalysis in peptide hydrolysis can be obtained from that in ester hydrolysis. 

Alkyl groups can be introduced in phthalimidomalonic esters by way of the sodio derivative. Hydrolysis then leads to <%-amino carboxylic acids through various intermediates. A good synthesis of asparagine, for example, is described in Organic Syntheses.458 Other examples are syntheses of lanthionine and ethionine,459 also of kynurenine.460... 

A Zerewitinoff determination showed the presence of two hydroxyls, but crystalline acetyl or benzoyl derivatives could not be prepared. The UV-spectrum indicates no carbonyl but a double bond apparently in conjugation with the carboxyl. Acid hydrolysis of cassaidine generates... 

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