Esterification, acid-mediated

To obtain sufficient quantities of benzazepinone 10 for large-scale synthesis of 1, the Yamanouchi process group subsequently turned to the preparation of 10 in a five-step sequence commencing with anthranilic acid 16.33 Acid-mediated esterification of 16 followed by aniline tosylation provided sulfonamide 17, which was subsequently alkylated with 4-chlorobutyronitrile to furnish the jV-(3-cyanopropyl)anthranilate 18. Dieckmann cyclization of 18 with sodium hydride in DMF then established the... 

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

In 2008, the group of Williams [15] reported the first total synthesis of ( )-2-0-methylneovibsanin H (33) (Scheme 14.6). The diterpene, isolated from the leaves of Viburnum awabuki [16], was prepared by employing an acid-catalyzed domino sequence. Thus, the key transformation was the conversion of advanced intermediate 28 to cyclohexene 32 upon treatment with an excess of sulfuric acid in anhydrous methanol. Acid-mediated silyl deprotection first revealed alcohol 29, which readily underwent an intramolecular oxa-Michael addition to yield tricyclic 30. It was postulated that solvolysis and nucleophilic addition of methanol to the intermediary allyl cation then furnished acid 31, which underwent Fischer esterification. The resultant highly functionalized cyclohexene 32 was isolated in 50% yield as a mixture of diastereomers at C2 (diastereomeric ratio (dr) = 85 15). The observed stereochemistry at the newly created stereocenters, i.e., at C2 and C5, was postulated to arise from the preexisting sterically congested stereocenters in the starting material (i.e., 28). Cyclohexene 32 was eventually taken on to provide the natural... 

J. Rebek, Jr., (1987) first developed a new synthesis of Kemp s acid and then extensively explored its application in model studies. The synthesis involves the straightforward hydrogenation (A. Steitz, 1968), esterification and methylation of inexpensive 1,3,5-benzenetricar-boxylic acid (trimesic acid 30/100 g). The methylation of the trimethyl ester with dimethyl sulfate, mediated by lithium diisopropylamide (V. J. Shiner, 1981), produced mainly the desired aff-cis-1,3,5-trimethyl isomer, which was saponified to give Kemp s acid. 

The SEM ester was used to protect a carboxyl group where DCC-mediated esterification caused destruction of the substrate. It was formed from the acid and SEM chloride (THF, 0°, 80% yield) and was removed solvolytically. The ease of removal in this case was attributed to anchimeric assistance by the phosphate group. Normally SEM groups are cleaved by treatment with fluoride ion. Note that in this case the SEM group is removed considerably faster than the phenyl groups from the phosphate. ... 

A mediated reaction is required to enable a rapid esterification of the acid end groups at room temperature, hence avoiding generation of additional acid end... 

In a related study by the same authors, the effect of microwave irradiation on car-bodiimide-mediated esterifications on a solid support was investigated, employing benzoic acid [29]. The carboxylic acid was activated using N,N -diisopropylcarbodi-imide (DIC) through the O-acyl isourea or the symmetrical anhydride protocol (Scheme 7.9). The isourea protocol was carried out in a dichloromethane/N,N-di-methylformamide mixture in sealed vessels, whereas the anhydride reactions were carried out in l-methyl-2-pyrrolidinone (NMP) at atmospheric pressure. 

There are a few reported cases of esterases that catalyze not only hydrolysis but also the reverse reaction of ester formation, in analogy with the global reaction described for serine peptidases (Fig. 3.4). Thus, cholesterol esterase can catalyze the esterification of oleic acid with cholesterol and, more importantly in our context, that of fatty acids with haloethanols [54], Esterification and transesterification reactions are also mediated by carboxyleste-rases, as discussed in greater detail in Sect. 7.4. 

With the carboxylic acid 123, dicyclohexylcarbodiimide (DCC) mediated esterification and amidation reactions can be carried out (Scheme 4. 27) [113]. For example, the reaction of 123 with EtOH in the presence of DCC and IH-benzotriazol (BtOH) in bromobenzene with a catalytic amount of 4-(dimefhylamino)pyridine (DMAP)... 

Schreiber and co-workers (436) prepared a library calculated to contain 2.18 million polycyclic compounds through the 1,3-dipolar cycloaddition of a number of nitrones with alkenes supported on TentaGel S NH2 resin (Scheme 1.83). (—)-Shikimic acid was converted into the polymer bound epoxycyclohexenol carboxylic acid 376 (or its enantiomer), coupled to the resin via a photolabile linker developed by Geysen and co-workers (437) to allow release of the products from the resin in the presence of live cells by ultraviolet (UV)-irradiation. A range of iodoaromatic nitrones (377) was then reacted with the ot,p-unsaturation of the polymer-bound amide in the presence of an organotin catalyst, using the tandem esterification/ dipolar cycloaddition methodology developed by Tamura et al. (84,85) Simultaneous cyclization by PyBrop-mediated condensation of the acid with the alcohol... 

Fatty acids of sugars are potentially useful and fully green nonionic surfactants, but the lipase-mediated esterification of carbohydrates is hampered by the low solubility of carbohydrates in reaction media that support lipase catalysis in general. Because the monoacylated product (Figure 10.8) is more soluble in traditional solvents than is the starting compound, the former tends to undergo further acylation into a diester. In contrast, the CaLB-catalyzed esterification of glucose with vinyl acetate in the ionic liquid [EMIm][BF4] was completely selective. The reaction became much faster and somewhat less selective when conducted in... 

In this expression, a depends on thuse rale coefficients in the above mechanism whose values are assumed to be high. Other mechanisms for the acid hydrolysis and esterification differ mainly with respect to the number of participating water molecules and possible inlet mediates. 

DCC/DMAP mediated esterification of 2-butynoic acid using (+)-(/ )-89 followed by intramolecular Diels-Alder cycloaddition of the resulting ester in refluxing n-decane [cone. 0.07 M] provided the tricyclic lactone (+)-47 in 60% overall yield [Scheme 21]. Epoxidation of (+)-47 using m-CPBA led to P-epoxy lactone (+)-48 in 64% yield. The P-epoxy lactone (+)-48 is highly crystalline, unlike the racemic form. 

---