Propionic anhydride, acylation

Liquid crystal polyesters are made by a different route. Because they are phenoHc esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenoHc hydroxyl groups are acylated with a lower aHphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxyHc acid, sometimes in the presence of a catalyst. The phenoHc polyester forms readily as the volatile lower acid distills from the reaction mixture. Many Hquid crystal polymers are derived formally from hydroxyacids (97,98) and thein acetates readily undergo self-condensation in the melt, stoichiometric balance being automatically obtained. 

Oil-soluble derivatives of testosterone itself predate those of its 19-nor congener these agents too are used to administer depot injections so as to provide in effect long-term blood levels of drug. Thus, acylation of testosterone with propionyl chloride in the presence of pyridine yields testosterone propionate (76a)acylation by means of decanoic anhydride yields testosterone decanoate (76b).Finally, reaction of 75 with 3-cyclopentylpropionyl chloride affords testosterone cypionate (76c)This last undergoes hydrolysis unusually slowly because of the presence of two substituents at the 5 position (see Newman s Rule of 6). ... 

The ring-contracted analog of alphaprodine is prepared by a variation of the scheme above. Alkylation of 109 with ethyl bromoacetate affords the lower homolog diester (115). Dieckmann cyclization followed by saponification-decarboxylation yields the pyrrolidine (116). Reaction with phenylmagnesium bromide leads to the condensation product (117) acylation with propionic anhydride gives the analgesic agent prolidine (118)... 

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-... 

The acylation of diethyl /V-ethyl-N-(2-thienyl)aminomethylenemalonate with acetic anhydride and propionic anhydride in the presence of A1C13 in methylene chloride gave the 5-acyl-2-thienyl derivatives in 35% and 40% yields, respectively (88M112). 

Rate constants and Arrhenius parameters for the reaction of Et3Si radicals with various carbonyl compounds are available. Some data are collected in Table 5.2 [49]. The ease of addition of EtsSi radicals was found to decrease in the order 1,4-benzoquinone > cyclic diaryl ketones, benzaldehyde, benzil, perfluoro propionic anhydride > benzophenone alkyl aryl ketone, alkyl aldehyde > oxalate > benzoate, trifluoroacetate, anhydride > cyclic dialkyl ketone > acyclic dialkyl ketone > formate > acetate [49,50]. This order of reactivity was rationalized in terms of bond energy differences, stabilization of the radical formed, polar effects, and steric factors. Thus, a phenyl or acyl group adjacent to the carbonyl will stabilize the radical adduct whereas a perfluoroalkyl or acyloxy group next to the carbonyl moiety will enhance the contribution given by the canonical structure with a charge separation to the transition state (Equation 5.24). 

Synthesis The acylation of 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide (valdecoxib), with propionic anhydride in a solution of TEA and DMAP in tetrahydrofurane gives A/-(4-(5-methyl-3-phenylisoxazol-4-yl)phenylsulfonyl)propionamide, which is treated with NaOH in ethanol to give parecoxib sodium salt (Talley (Parmacia Corp.), 1996 2000b Sorbera, 2001b). 

The 1-methylpyrrole complex 21 undergoes clean acylation at the P-position in the presence of Ac20/DMAP to give the 3-acetyl-1-methylpyrrole complex, 38 (Figure 10).12b Propionic anhydride reacts with 21 in a similar manner to form 39. Under these reaction conditions, the parent pyrrole complex (20) undergoes exclusive A-acylation to give 40, and the 2,5-dimethylpyrrole complex (22) gives a 7 3 ratio of N- to P-acylation. 

Fentanyl and its analogs are made from TV-substituted-4-piperidones [i.e., from the same intermediates of the reversed esters of pethidine (p. 266)]. These ketones condense with aniline under the influence of catalysts such as toluene-p-sulfonic acid(2) and zinc chloride(18) to give Schiff bases, which are reduced to diamines 4 by NaBH4 or LAH. Recently, the direct conversion of 4-piperidones to 4-anilino derivatives 4 has been achieved by reductive amination with aniline and sodium cyanoborohydride (NaBH3CN).(19) The diamines are acylated with propionic anhydride. 

Primary and secondary amines can be acylated readily by treatment with acid anhydrides and heat. Acetic anhydride, propionic anhydride, and trifluo-... 

Although this is the classical method of anhydride formation it has been replaced to a large extent by the acylation of free carboxylic acids (method 341). The conditions employed and the solvents used in this reaction vary widely. Excellent directions are given for the preparations of nicotinic anhydride (89%) and acetic propionic anhydride (60%) from the respective potassium and sodium salts of the carboxylic acids. Silver salts of acids have also been used. The reaction has been extended to the preparation of mixed anhydrides of short- and long-chain fatty acidsbut has failed in the preparation of mixed anhydrides of substituted benzoic acids. ... 

The kinetics of acylation of a series of complexes by propionic anhydride and... 

Synthesis from anisole and propionic acid derivatives. Anisole is converted into 4-methoxypropiophenone by Friedel-Crafts acylation with propionyl chloride or propionic anhydride. The ketone is hydrogenated to the corresponding alcohol with a copper chromite catalyst. The alcohol is dehydrated in the presence of acidic catalysts to a cis/trans mixture of anetholes [163b]. 

Table 3.16 Aluminum-hydrogensulfate-promoted acylation of aromatic ethers with acetic and propionic anhydrides...

Introduction of two acyl groups into an amine, and acylation of an amide, naturally require more drastic conditions.727,728 For conversion into the diacetyl derivative, for instance, 2,6-dibromo-p-toluidine (NH2 = 1) was heated with twice its volume of acetic anhydride at 150-160°.729 Twelve hours refluxing is required for preparation of A-propionylphthalimide from phthal-imide and propionic anhydride.625... 

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