Acidic conditions esterification

Proton transfer from the water to the alcohol converts the latter into a better leaving group (G). Incidentally, this mechanism is the reverse of the mechanism for formation of an ester from an acid and an alcohol under acidic conditions (esterification). 

Usually no difficulties are encountered in the esterification of thiazole acids. Direct esterification with alcohol and add in the presence of an acid catalyst (7, 61, 62), or prior conversion to the add chloride (6, 63, 64) followed by reaction with an alcohol in basic conditions give good yields. 

Hydrolysis in neutral aqueous solutions proceeds slowly at room temperature and more rapidly at acidic conditions and elevated temperatures. The hydrolysis—esterification reaction is reversible. Under alkaline conditions hydrolysis is rapid and irreversible. Heating the alkaline hydrolysis product at 200—250°C gives 4,4 -oxydibutyric acid [7423-25-8] after acidification (148). 

Somewhat milder oxidative conditions lead to loss of but one carbon. Periodic acid cleavage of the side chain in 65, leads to the so-called etio acid (66). Reaction with propionic anhydride leads to acylation of the 17-hydroxyl group (67). Possibilities for neighboring group participation severely limit the methods available for activating the acid for esterification. Best results seemed to have been obtained by use of a mixed anhydride from treatment with diphenyl chloro-... 

Esterification of 22 with diol 24 (DCC/DMAP/BtOH) gave 29 in 84% yield (Fig. 12) and subsequent hydrolysis of the f-butyl ester group under acidic conditions afforded the third-generation carboxylic acid 23. All of the spectroscopic... 

Milieu conditions in gastrointestinal tract can influence the pectin structure and properties. Under the acid conditions of the stomach (pH 2-4) extraction of pectin from plant cell walls and hydrolysis of side chains can occur. In small intestine (pH 5-6) -elimination of main chains or de-esterification seems to be possible. In caecum and colon (pH 6-8) a strong fermentation of pectin takes place causing depolymerization to oligomers and leading to formation of short chain fatty acids and gases. The presence of OligoGalA is not yet clarified. 

Most hterature references to pharmaceutical primary process monitoring are for batch processes, where a model of the process is built from calibration experiments [110, 111]. Many of these examples have led to greater understanding of the process monitored and can therefore be a precursor to design of a continuous process. For example, the acid-catalysed esterification of butan-l-ol by acetic acid was monitored through a factorial designed series of experiments in order to establish reaction kinetics, rate constants, end points, yields, equilibrium constants and the influence of initial water. Statistical analysis demonstrated that high temperatures and an excess of acetic acid were the optimal conditions [112]. 

Finally, Lecomte and coworkers reported the synthesis of mikto-arm star-shaped aliphatic polyesters by implementing a strategy based on click chemistry (Fig. 36) [162]. Firstly, the polymerization of sCL was initiated by a diol bearing an alkyne function. The chain-ends were protected from any further undesired reaction by the esterification reaction with acetyl chloride. The alkyne was then reacted with 3-azidopropan-l-ol. The hydroxyl function located at the middle of the chain was then used to initiate the ROP of sCL and y-bromo-s-caprolactone. Finally, pendant bromides were reacted successfully with sodium azide and then with N, N-dimethylprop-2-yn-l-amine to obtain pendant amines. Under acidic conditions, pendant amines were protonated and the polymer turned out to exhibit amphiphilic properties. 

Protection of an alcohol function by esterification sometimes offers advantages over use of acetal or ether groups. Generally, ester groups are stable under acidic conditions. Esters are especially useful in protection during oxidations. Acetates and benzoates are the most commonly used ester derivatives. They can be conveniently prepared by reaction of unhindered alcohols with acetic anhydride or benzoyl chloride, respectively, in the presence of pyridine or other tertiary amines. 4-Dimethylaminopyridine (DMAP) is often used as a catalyst. The use of A-acylimidazolides (see Section 3.4.1) allows the... 

Fio. 11. Concentration profiles as measured with the equipment depicted in Fig. 10 (open symbols) and by GC analysis (closed symbols) for an esterification reaction between octanol and hexanoic acid. Conditions 200 ml, of reactant, 0.4mol/L of octanol, 0.4mol/L of hexanoic acid, l.Og Nafion resin/ silica, 447 K. The profiles were constructed from signals at 1720 and 1745 cm , and the spectra were corrected for solvent, octanol, and catalyst (74). 

Both aliphatic alcohols and phenols have been immobilized as esters of support-bound carboxylic acids. The esterification can be achieved by treatment of resin-bound acids with alcohols and a carbodiimide, under Mitsunobu conditions, or by acylation of alcohols with support-bound acyl halides (see Section 13.4). 

The esterification of support-bound carboxylic acids has not been investigated as thoroughly as the esterification of support-bound alcohols. Resin-bound activated acid derivatives that are well suited to the preparation of esters include O-acylisoureas (formed from acids and carbodiimides), acyl halides [23,226-228], and mixed anhydrides (Table 13.15). A-Acylurea formation does not compete with esterifications as efficiently as it does with the formation of amides from support-bound acids. Esters can also be prepared from carboxylic acids on insoluble supports by acid-catalyzed esterification [152,229]. Alternatively, support-bound carboxylic acids can be esteri-fied by O-alkylation, either with primary or secondary aliphatic alcohols under Mitsu-nobu conditions or with reactive alkyl halides or sulfonates (Table 13.15). 

For most cases, common fluoroacyl derivatives are sufficiently reactive and selective Thus conversion of perfluoroglutaric dichloride to a monomethyl ester by methanol proceeds smoothly under the appropriate reaction conditions [17] (equation 9) Perfluorosuccinic acid monoester fluoride, on the other hand, is prepared most conveniently from perfluorobutyrolacetone [IS] (equation 10) Owing to the strong acidity of a fluonnated carboxylic acids, Fischer esterification with most aliphatic alcohols proceeds autocatalytically [79 20]... 

Formation of hemiacetals and acetals, as well as of hemiketals and ketals, is reversible under acidic conditions, as we already have noted for acid-catalyzed esterification. The reverse reaction is hydrolysis and the equilibrium for this reaction can be made favorable by having an excess of water present ... 

BASIC PROTOCOL I PREPARATION OF FATTY ACID METHYL ESTERS FROM LIPID SAMPLES CATALYZED WITH BORON TRIFLUORIDE IN METHANOL In this method, lipid samples are first saponified with an excess of NaOH in methanol. Liberated fatty acids are then methylated in the presence of BF3 in methanol. The resulting fatty acid methyl esters (FAMEs) are extracted with an organic solvent (isooctane or hexane), and then sealed in GC sample vials for analysis. Because of the acidic condition and high temperature (100°C) used in the process, isomerization will occur to those fatty acids containing conjugated dienes, such as in dairy and ruminant meat products, that contain conjugated linoleic acids (CLA). If CLA isomers are of interest in the analysis, Basic Protocol 2 or the Alternate Protocol should be used instead. Based on experience, this method underestimates the amount of the naturally occurring cis-9, trans-11 CLA isomer by -10%. The formulas for the chemical reactions involved in this protocol are outlined in Equation D1.2.1 Saponification RCOO-R + NaOH, RCOO-Na + R -OH v 100°C DC Esterification RCOO-Na + CH,OH r 3 v RCOO-CH, + NaOH ioo°c ... 

Amino group reactions (e.g. acylation) proceed best under basic conditions, whereas carboxyl group reactions (e.g. esterification) are effected under acidic conditions with the amino function protected by protonation. 

The O-alkylation of carboxylates is a useful alternative to the acid-catalyzed esterification of carboxylic acids with alcohols. Carboxylates are weak, hard nucleophiles which are alkylated quickly by carbocations and by highly reactive, carbocation-like electrophiles (e.g. trityl or some benzhydryl halides). Suitable procedures include treatment of carboxylic acids with alcohols under the conditions of the Mitsunobu reaction [122], or with diazoalkanes. With soft electrophiles, such as alkyl iodides, alkylation of carboxylic acid salts proceeds more slowly, but in polar aprotic solvents, such as DMF, or with non-coordinating cations acceptable rates can still be achieved. Alkylating agents with a high tendency to O-alkylate carboxylates include a-halo ketones [42], dimethyl sulfate [100,123], and benzyl halides (Scheme 6.31). 

Acrylic acid esters can polymerize readily this must be taken into account during their preparation. Thus, attempts to prepare pentafluorophenyl acrylate from acrylo-yl chloride in the presence of pyridine led to extensive polymerization of the product [24], This polymerization can be prevented by using the less nucleophilic 2,6-dimethylpyridine as base and diethyl ether or pentane instead of THF as solvent (Scheme 7.5). Esterifications of acrylic acid under acidic conditions should be conducted in the presence of small amounts of hydroquinone as radical scavenger. Acrylic acid derivatives can also be prepared by acylation with a propionic acid with a leaving group at C-3 followed by/3-elimination. 

Aminophenols can be selectively esterified by deprotonation of the hydroxyl group followed by treatment with an acylating reagent of low reactivity (Scheme 7.17). Treatment with a strong acylating agent under acidic conditions will also result in clean esterification. In the presence of weak bases the regioselectivity of the acyla-... 

For such a modular configuration, it is claimed that a large number of heterogeneously catalyzed reactions can be performed, e.g. Heck and Suzuki coupling, acid-catalyzed esterifications and reductions of functional groups [83], However, for the mentioned process, the catalyst and reactants are not named and no reaction conditions or experimental results, e.g. yield, selectivity or nature of side products, are given. 

In this process, epoxidation of the double bonds was followed by reduction to obtain the tert-alcohol which was esterified with methacryloyl chloride in the subsequent step. While epoxidation was found to be close to quantitative based on double bond content, reduction was incomplete and the residual epoxy functional PIB (24-47%) had to be separated by column chromatography before esterification. It should be noted that this macromonomer was a tert-ester which might be quite unstable in acidic conditions, and is also more hindered than the... 

Esters can be hydrolyzed to carboxylic acids under either acidic or basic conditions. Under acidic conditions the mechanism is the exact reverse of the Fischer esterification mechanism shown in Figure 19.3. Again, because the acid and the ester have comparable reactivities, some method must be used to drive the equilibrium toward the desired product—the acid in this case. This can be accomplished by using water as the solvent, providing a large excess of this reagent that, by Le Chatelier s principle, shifts the equilibrium toward the carboxylic acid. 

The combination of these compounds will generate methyl salicylate when conditions for an acid-mediated esterification, illustrated below, are applied. The... 

Cliffe et al. [212] studied the use of TFA-methyl esters of amino acids for quantitative analysis. The yields of the derivatives depend on the reaction conditions esterification was performed with 4 M methanolic HC1 for 90 min at 65°C and acylation with 20% TFA anhydride in dichloromethane at 120°C for 20 min. Injection into the chromatograph was carried out with the aid of a pre-column and the analysis was accomplished on the above-mentioned mixed stationary phase. Fig. 5.16 shows a typical analysis of a known mixture performed by this procedure. Replicate analysis showed a poor reproducibility for Met, Tyr, Arg and Cys (coefficient of variation 20%) and His was not acylated at all. This result is mainly caused by the strong dependence of the yield on the reaction conditions and the instability and high volatility of the derivatives (XE-60 is present in the stationary phase). 

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