Solvents acyl esters

Cellulose esters of unsaturated acids, such as the acetate methacrylate, acetate maleate (34), and propionate crotonate (35), have been prepared. They are made by treating the hydrolyzed acetate or propionate with the corresponding acyl chloride in a pyridine solvent. Cellulose esters of unsaturated acids are cross-linkable by heat or uv light solvent-resistant films and coatings can be prepared from such esters. 

Transesterifications. Use of titanates for transesterification has been described in the patent literature for some time and has now been recommended for research purposes by Seebach et al. In the presence of catalytic amounts of a tetraalkyl titanate, esters undergo transesterification with the alcohol solvent. Acyl-protected alcohols are deprotected in the process, but a wide variety of functional groups are unaffected, such as C=0, OH, OSi(CH3)2C(CH3)3, acetonide, lactam. One advantage is that completely dry alcohols are not required. 

A mixture of O-acyl ester (1 mmol) of A-hydroxy-2-thiopyridone and benzoquinone (5-7 mmol) in degassed dichloromethane (20 ml) was irradiated with a 300 W tungsten lamp for 30 min. under a nitrogen atmosphere at 0 °C. After the reaction, the solvent was removed and the residue was chromatographed on silica gel to give 1,2-disubstituted benzoquinone [63]. 

Finally, as examples of similar types of reactions, photolytic treatment of O-acyl ester (D) of benzophenone oxime, A-acyloxy-phthalimide (E), and O-acyl ester (F) of A-hydroxy-2-pyridone with a mercury lamp generates the corresponding alkyl radicals via decarboxylation. However, these reactions can be used only for the alkylation of aromatics (solvents such as benzene) and reduction [86-89], so their synthetic utility is extremely limited. 

FIGURE 9.3 Partial capillary gas chromatograms of lipid fractions from blue whale Bal-aenoptera musculus) lipid samples, (a) Total FA (analyzed as methyl esters) derived from the solvent fractionation of lipid classes from a subcutaneous blubber lipid extract by the hydrolytic reaction of O-acyl ester lipids (b) the neutral hpid fraction, containing nonsaponifiable lipids (analyzed as bis(trimethylsilyl)trifluoroacetamide (OTMS) esters), derived from the solvent fractionation of lipid classes from a dorsal blubber hpid extract. In this case, FA have contaminated the neutral lipid fraction and have been detected as OTMS esters. 

Some applications may require additional cleanup and the Goto method provides an excellent example of a solvent partition with chloroform and then a silica SPE cleanup however it should be noted that during the hexane cleanup, the nonpolar C-7 acyl esters of OA group toxins will partition into hexane, and hydrolysis must be performed on crude methanolic extracts. 

Acylation of the hydroxyl groups of carbohydrates with acyl chlorides or acid anhydrides in pyridine as the solvent yields esters. The configuration at each chirality center, including the anomeric carbon, is retained. Thus, a-D-glucopyranose is converted to the pentaacetate shown. 

With the dicyclohexylcarbodiimide (DCQ reagent racemization is more pronounced in polar solvents such as DMF than in CHjCl2, for example. An efficient method for reduction of racemization in coupling with DCC is to use additives such as N-hydroxysuccinimide or l-hydroxybenzotriazole. A possible explanation for this effect of nucleophilic additives is that they compete with the amino component for the acyl group to form active esters, which in turn reaa without racemization. There are some other condensation agents (e.g. 2-ethyl-7-hydroxybenz[d]isoxazolium and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline) that have been found not to lead to significant racemization. They have, however, not been widely tested in peptide synthesis. 

Acylation. Aliphatic amine oxides react with acylating agents such as acetic anhydride and acetyl chloride to form either A[,A/-diaLkylamides and aldehyde (34), the Polonovski reaction, or an ester, depending upon the polarity of the solvent used (35,36). Along with a polar mechanism (37), a metal-complex-induced mechanism involving a free-radical intermediate has been proposed. 

The polymeric acyl titanate esters are viscous Hquids or waxes that are soluble ia hydrocarbon solvents and can be used as Ti02-dispersiag agents, water-repellent agents for textile fabrics, and mst inhibitors for steel. 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

Unprotected racemic amines can be resolved by enantioselective acylations with activated esters (110,111). This approach is based on the discovery that enantioselectivity of some enzymes strongly depends on the nature of the reaction medium. For example, the enantioselectivity factor (defined as the ratio of the initial rates for (3)- and (R)-isomers) of subtiHsin in the acylation of CX-methyl-ben zyl amine with tritiuoroethyl butyrate varies from 0.95 in toluene to 7.7 in 3-methyl-3-pentanol (110). The latter solvent has been used for enantioselective resolutions of a number of racemic amines (110). 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

In the second major method of peptide synthesis the carboxyl group is activated by converting it to an active ester, usually a p-nitrophenyl ester. Recall from Section 20.12 that esters react with ammonia and amines to give fflnides. p-Nitrophenyl esters are much more reactive than methyl and ethyl esters in these reactions because p-nitrophenoxide is a better (less basic) leaving group than methoxide and ethoxide. Simply allowing the active ester and a C-protected amino acid to stand in a suitable solvent is sufficient to bring about peptide bond formation by nucleophilic acyl substitution. 

Esters can also be synthesized by an acid-catalyzed nucleophilic acyl substitution reaction of a carboxylic acid with an alcohol, a process called the Fischer esterification reaction. Unfortunately, the need to use an excess of a liquid alcohol as solvent effectively limits the method to the synthesis of methyl, ethyl, propyl, and butyl esters. 

The solvent system N2O4/DMF has been employed for the preparation of inorganic esters, e.g., phosphates and sulfates [221] as well as organic esters. The latter products were obtained by reacting the polymer with acyl chlorides, or acid anhydrides in the presence of a pyridine base. The nitrite ester formed has been successfully trans-esterified by the reaction with RCOCl... 

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