Aromatic esters hydrolysis

The catalysis of hydrolysis of carboxylic acid derivatives by weak bases has not been carefully studied until relatively recently. Koshland reported in 1952 the catalysis of acetyl phosphate hydrolysis by pyridine Bafna and Gold (1953) reported the pyridine-catalyzed hydrolysis of acetic anhydride. A short time later the catalysis of aromatic ester hydrolysis by imidazole was demonstrated (Bender and Turnquest, 1957 a, b Bruice and Schmir, 1957). Since that time a large amount of work has been devoted to the understanding of catalyzed ester reactions. Much of the work in this area has been carried out with the purpose of inquiry into the mode of action of hydrolytic enzymes. These enzymes contain on their backbone weak potential catalytic bases or acids, such as imidazole in the form of histidine, carboxylate in the form of aspartate and glutamate, etc. As a result of the enormous effort put into the study of nucleophilic displacements at the carbonyl carbon, a fair understanding of these reactions has resulted. An excellent review is available for work up to 1960 (Bender, 1960). In addition, this subject has been... 

The experimental details already given for the detection and characterisation of aliphatic esters (determination of saponification equivalents h3 diolysis Section 111,106) apply equally to aromatic esters. A sfight modification in the procediu-e for isolating the products of hydrolysis is necessary for i)henolic (or phenyl) esters since the alkaline solution will contain hoth the alkali phenate and the alkali salt of the organic acid upon acidification, both the phenol and the acid will be hberated. Two methods may be used for separating the phenol and the acid ... 

Adjacent formyl groups facilitate the hydrolysis of certain aromatic esters, as illustrated by the examples below. Indicate a mechanism for this rate enhancement. ... 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

Diels-Alder reaction, 493 El reaction, 391-392 ElcB reaction, 393 E2 reaction, 386 Edman degradation, 1032 electrophilic addition reaction, 147-148. 188-189 electrophilic aromatic substitution, 548-549 enamine formation, 713 enol formation, 843-844 ester hydrolysis, 809-811 ester reduction, 812 FAD reactions. 1134-1135 fat catabolism, 1133-1136 fat hydrolysis, 1130-1132 Fischer esterification reaction, 796 Friedel-Crafts acylation reaction, 557-558... 

Some male arctiid moths produce their courtship pheromone from dietary pyrrolizidine alkaloids acquired during feeding by the larvae [ 126]. Conversion of monocrotaline to hydroxydanaidal by males is accomplished by aromatiza-tion, ester hydrolysis and oxidation of an alcohol to the aldehyde [7]. In the case of Utetheisa ornatirx the stereo-configuration at C7 of the dietary alkaloid is the same as the pheromone released (R). In contrast, another arctiid, Creatono-tos transiens, can convert a dietary precursor alkaloid with the (S) configuration at C7 (heliotrine) to (l )-hydroxydanaidal. The biosynthesis occurs by first oxidation-reduction at C7 to convert the stereochemistry and then proceeds through aromatization, hydrolysis, and oxidation [7]. 

Nuclear motion, the principle of least, and the theory of stereoelectronic control, 24, 113 Nucleophiles, partitioning of carbocations between addition and deprotonation. 35, 67 Nucleophilic aromatic photosubstitution, 11,225 Nucleophilic catalysis of ester hydrolysis and related reactions, 5,237 Nucleophilic displacement reactions, gas-phase, 21, 197... 

Mammalian esterases have been classified into three groups according to specificity for substates and inhibitors (110). In terms of overall hydrolytic activity in mammals, the most important class of esterases is that of the B-esterases, which are principally active with aliphatic esters and amides. A-Esterases are important for aromatic esters and organophosphorus esters, and C-esterases are active with acetyl esters. In general, the specificity of mammalian esterases is determined by the nature of substituent groups (acetyl, alkyl, or aryl) rather than the heteroatom (O, N, or S) that is adjacent to the carboxy group. That is, the same esterase would likely catalyze hydrolysis of an ester, amide, or thioester as long as the substituents were identical except for the heteroatom (110). 

This method for preparing 2-phenyl-1-pyrroline, and assorted 2-substituted 1-pyrrolines, is one of the best currently available, particularly because it reproducibly affords clean materials. Generally, the procedure is amenable to various aromatic esters 2 it has also been applied successfully to aliphatic esters (Table I).3 An advantage of this method is the use of readily available, inexpensive N-vinyl-pyrrolidin-2-one as a key starting material. This compound serves effectively as a 3-aminopropyl carbanion equivalent. The method illustrated in this procedure has been extended to include the synthesis of 2,3-disubstituted pyrrolines. Thus, alkylation of the enolate of the intermediate keto lactam, followed by hydrolysis, leads to various disubstituted pyrrolines in good yields (see Table II).3... 

Actually, this is not that difficult to understand. We all know that the more stable form of diesters between fumarate and maleate is the fumarate due to the trans configuration, which minimizes the crowdedness of the esters. In the case of phthalic esters, the aromatic esters cannot possibly rotate to any trans forms and are therefore in a state with a high strain energy. In order to release this energy, these esters would rather prefer to kick-off the esters. This is why they are so prone to attack by hydrolysis, and is why GP resins will fail in any water-immersion type of test, especially under elevated temperature. 

Aromatic substituent effects due to phosphorus groups have been studied for a number of reactions.47 Thus ester hydrolysis and fluoride-displacement rates, for (56) and (57) respectively, are enhanced by phosphorus substituents (X = O or ), while the rate of hydrolysis of the halide (58) is enhanced for X = , but slowed for X = O.47 A perturbation M.O. analysis of these observations has been presented.48... 

Carbonic anhydrase (carbonate dehydratase, EC 4.2.E1) is a small, monomeric zinc-containing metalloenzyme that catalyzes the reversible hydration of C02 to bicarbonate [101][102], In addition to this activity, carbonic anhydrase also catalyzes the hydrolysis of many aromatic esters [103]. 

Fig. 9.8 presents another, more complex type of phosphate prodrugs, namely (phosphoryloxy)methyl carbonates and carbamates (9-26, X = O or NH, resp.) [84], Here, the [(phosphoryloxy)methyl]carbonyl carrier appears quite versatile and of potential interest to prepare prodrugs of alcohols, phenols, and amines. The cascade of reactions leading from prodrug to drug as shown in Fig. 9.8 involves three steps, namely ester hydrolysis, release of formaldehyde, and a final step of carbonate hydrolysis (X = O) or A-decar-boxylation (X = NH). Three model compounds, a secondary alcohol, a primary aliphatic amine, and a primary aromatic amine, were derivatized with the carrier moiety and examined for their rates of breakdown [84], The alcohol, indan-2-ol, yielded a carrier-linked derivative that proved relatively... 

Aspirin is an ester, bnt it still contains a carboxylic acid fnnction (p/Ca 3.5). In aqueous solntion, there will thus be significant ionization. However, this ionization now provides an acid catalyst for ester hydrolysis and initiates autolysis (autohydrolysis). The hydrolysis product salicylic acid (pACa 3.0) is also acidic both aspirin and salicylic acid are aromatic acids and are rather stronger acids than aliphatic compounds such as acetic acid (pACa 4.8) (see Section 4.3.5). An aqueous solution of aspirin has a half-life of about 40 days at room temperature. In other words, after about 40 days, half of the material has been hydrolysed, and the biological activity will have deteriorated similarly. 

Fig. 3 Mechanisms for enzymatic supramolecular polymerisation (a) Formation of supramolecular assembly via bond cleavage, (b) Formation of supramolecular assemblies via bond formation. Examples are shown of biocatalytic supramolecular polymerisation of aromatic peptide amphiphiles via (i) phosphate ester hydrolysis, (ri) alkyl ester hydrolysis, and (iii) amide condensation or reversed hydrolysis using protease...

In a number of classes of systems, the catalytic and other chemical effects of metal ions on reactions of organic and inorganic molecules are generally recognized the catalysis of nucleophilic reactions such as ester hydrolysis the reactions of alkenes and alkynes in the presence of metal carbonyls (8, 9, 69) stereospecific polymerization in the presence of Ziegler catalysts (20, 55, 56) the activation of such small molecules as H2 (37), 02 (13), H202 (13), and possibly N2 (58) and aromatic substitution reactions of metal-cyclopentadienyl compounds (59, 63). 

The intramolecular C-H insertion reaction of phenyldiazoacetates on cyclohexadiene, utilizing the catalyst Rh2(S-DOSP)4, leads to the asymmetric synthesis of diarylacetates (Scheme 8). Utilizing the phenyl di azoacetate 38 and cyclohexadiene, the C-H insertion product 39 was produced in 59% yield and 99% ee. Oxidative aromatization of 39 with DDQ followed by catalytic hydrogenation gave the diarylester 40 in 96% ee. Ester hydrolysis followed by intramolecular Friedel-Crafts gave the tetralone 31 (96% ee) and represents a formal synthesis of sertraline (5). Later studies utilized the catalyst on a pyridine functionalized highly cross-linked polystyrene resin. ... 

This would have both a solvent effect and a mass law effect on the rate of ester formation. The error is systematic, since it is most serious for the slower ester formation reactions, and consequently the p value calculated by Jaffe144 from the data of Hartman and Borders142 is not accurate. Later workers allowed for this side-reaction 46 or used aromatic sulphonic acids rather than HC1 as the catalyst145147. However, whatever the exact p values, it is quite clear that the polar effects of substituents on acid-catalyzed ester hydrolysis and formation are small. 

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