Propionic anhydride hydrolysis

The first examples of a homogeneous reduction of this type were reported in 1971. Cobalt carbonyl was found to reduce anhydrides such as acetic anhydride, succinic anhydride and propionic anhydride to mixtures of aldehydes and acids. However, scant experimental details were recorded [94]. In 1975, Lyons reported that [Ru(PPh3)3Cl2] catalyzes the reduction of succinic and phthalic anhydrides to the lactones y-bulyrolaclone and phthalide, respectively [95], The proposed reaction sequence for phthalic anhydride is shown in Scheme 15.15. Conversion of phthalic anhydride was complete in 21 h at 90 °C, but yielded an equal mixture of the lactone, phthalide (TON = 100 TOF 5) and o-phthalic acid, which is presumably formed by hydrolysis of the anhydride by water during lactoniza-tion. Neither acid or lactone were further hydrogenated to any extent using this catalyst system, under these conditions. 

Triphenylmethyl fluoroborate is prepared by dissolving 27 g. (0.104 mole) of triphenylmethanol ( purum, Fluka A G) in 260 ml. of propionic anhydride by warming on a steam bath. With an acetone-dry ice bath the solution is cooled to 10° and maintained between 10° and 20° while 31 ml. of 43% w/w fluoroboric acid is added portionwise with swirling. The yellow solid is collected, washed well with dry ether, and dried in a desiccator under vacuum to yield 34 g. (90-99%). The product is very hygroscopic, taking up water with hydrolysis. It is desirable to prepare this reagent immediately before use. 

For the reaction of MOH(n 1)+ with propionic anhydride,200 the Bronsted plot of log kMOH versus the pKa of MOH2n+ follows a smooth curve if the values for HzO and OH- are included (Figure 4). However, if the line is drawn to exclude the fcHj0 value, a Bronsted /3 of ca, 0.25 is obtained. Although kMOH for [Co(NH3)5OH]2+ (3 M s 1) is some 103-fold less than k0H, this reaction will compete favourably at neutral pH with base hydrolysis. At pH 7 where the cobalt(III) complex exists almost completely as the MOH2+ species the observed first order rate constant for nucleophilic attack by OH would be ca. 10-4 s 1. AIM solution of [Co(NH3)5OH]2+ would give a value of kobs 2.5 s 1, a rate acceleration of > 104-fold. Since the effective concentration of a nucleophile in the intramolecular reaction could be ca. 102 M, rate accelerations of 10° are possible. The role of the metal ion in such reactions is to provide an effective concentration of an efficient nucleophile at low pH. 

Buckingham and Engelhardt200 have studied the hydrolysis of propionic anhydride in the presence of kinetically inert complexes of the type [M(NH3)5OH]n+. These reactions occur by nucleophilic attack of coordinated hydroxide on the anhydride (Scheme 32). For reactions of M-OHl" l,+ with propionic anhydride, the Bronsted plot of log kMOH versus the p.Ka of M—OH2k+ is a smooth curve if values for reaction with HzO and OH- are included. Although Icmoh for [(NH3)5CoOH]2+ (3 M-1 s-1) is about 103-fold less than fcoH. its reaction will compete favourably at neutral pH with base hydrolysis. Such effects are considered in more detail in Section 61.4.2.2.3. 

For the preparation of 70-72 Koyama etal. (28) employed the 5-3 -(indolyl)-oxazole 88 obtained from ethylindole-3-carboxylate (87) and isocyanomethyl lithium. The oxazole 88 was refluxed in acetic anhydride—acetic acid or propionic anhydride-propionic acid to afford pimprinine (70) and pimprinethine (71) in 13 and 19% yield, respectively. Hydrolysis of these reaction mixtures and that produced with phenylacetic acid anhydride-phenylacetic acid gave high yields (84-92%) of the 3-acylamidoindoles 79-81, which could be smoothly cyclized with phosphorus oxychloride to the natural products 70-72 (28). 

If the addition of aq HBF to h -CjH5Co(PMe3)2 is not carefully controlled, the heat from hydrolysis of the propionic anhydride solvent causes Hj evolution and formation... 

The C-methyl derivatives (350) and (351) have been synthesized by hydrolysis and thiolysis of ethylidene bis(dibromoarsine) (349) (Equation (53)). The adamantane (350) was also synthesized simply by heating potassium arsenite with propionic acid in propionic anhydride <69ZAAC(370)3l>. The tetra-A-ethyl compound (352) was obtained from (349 Hal = Cl) by the same method as described for the synthesis of (348). 

Propionic acid [79-09-4] M 74.1, b 141 , d 0.992, n 1.3865, n25 1.3843, pK 5-6.8 (Ho scale, aq H2SO4), pK2 4.88. Dried with Na2S04 or by fractional distn, then redistd after refluxing with a few crystals of KMn04. An alternative purification uses the conversion to the ethyl ester, fractional distn and hydrolysis. [Bradbury J Am Chem Soc 74 2709 1952.] Propionic acid can also be heated for 0.5h with an amount of benzoic anhydride equivalent to the amount of water present (in the presence of Cr03 as catalyst), followed by fractional distn. [Cham and Israel 7 C/iem 5oc 96 I960.]... 

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). ... 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

Cellulose esters (e.g., cellulose triacetate, cellulose diacetate, cellulose propionate, and cellulose butyrate) are prepared by initially treating cellulose with glacial acetic acid (or propionic acid and butyric acid) followed by the corresponding acid anhydride with a trace of strong acid as a catalyst in chlorinated hydrocarbon. Complete esterification reactions result in the formation of a triester, which undergoes water hydrolysis to form a diester. Cellulose acetate alone or in combination with cellulose triacetate or cellulose butyrate is used as a semipermeable membrane for osmotic pumping tablets, primarily in controlled release systems. The permeability of the membrane can be further modulated by adding water-soluble excipients to the cellulose esters. 

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