Hydrolysis of acid anhydrides

Suppression of water-dependent side reactions (e.g., hydrolysis of acid anhydrides and halides, polymerization of quinones)... 

Differentiation between esters and anhydrides. The following simple test relies on the fact that hydrolysis of acid anhydrides is more rapid than that of esters under basic conditions. Add 1 ml of the compound to 2 ml of water to which has been added 1 drop of 1 m sodium hydroxide solution and a trace of phenolphthalein indicator. Warm the solution gently on a water bath with anhydrides the pink colour is discharged within about 1 minute and the further dropwise addition of alkali enables the rate of hydrolysis to be monitored. With most esters hydrolysis is very slow under these conditions. For the preparation of derivatives of esters and anhydrides see Sections 9.6.17, p. 1266 and 9.6.16, p. 1265 respectively. 

As with the hydrolysis of acid chlorides, the hydrolysis of acid anhydrides will occur without an added acid or base catalyst (although sometimes acid is used) therefore, the mechanism is similar to that given above. The acid-catalyzed mechanism is analogous to that with esters, discussed in the next section. 

Although the acetylation of alcohols and amines by acetic anhydride is almost invariably carried out under anhydrous conditions owing to the ready hydrolysis of the anhydride, it has been shown by Chattaway (1931) that phenols, when dissolved in aqueous sodium hydroxide solution and shaken with acetic anhydride, undergo rapid and almost quantitative acetylation if ice is present to keep the temperature low throughout the reaction. The success of this method is due primarily to the acidic nature of the phenols, which enables them to form soluble sodium derivatives, capable of reacting with the acetic... 

The disadvantages attending the use of acetic anhydride alone are absent when the acetylation is conducted in aqueous solution according to the following procedure. The amine is dissolved in water containing one equivalent of hydrochloric acid, slightly more than one equivalent of acetic anhydride is added to the solution, followed by enough sodium acetate to neutralise the hydrochloric acid, and the mixture is shaken. The free amine which is liberated is at once acetylated. It must be pointed out that the hydrolysis of acetic anhydride at room temperature is extremely slow and that the free amine reacts much more readily with the anhydride than does the water this forms the experimental basis for the above excellent method of acetylation. 

The acetylation reaction, [1], is carried out in pyridine to avoid the hydrolysis of acetic anhydride by water. After the acetylation is complete, water is added to convert the remaining acetic anhydride to acetic acid, [2]. 

Chlorendic Acid. Chlorendic acid [115-28-6] and its anhydride [115-27-5] are widely used flame retardants. Chlorendic acid is synthesized by a Diels-Alder reaction of maleic anhydride and hexachlorocyclopentadiene (see CyclopentadlENE and dicyclopentadiente) in toluene followed by hydrolysis of the anhydride using aqueous base (60). The anhydride can be isolated directly from the reaction mixture or can be prepared in a very pure form by dehydration of the acid. The principal use of chlorendic anhydride and chlorendic acid has been in the manufacture of unsaturated polyester resins. Because the esterification rate of chlorendic anhydride is similar to that of phthalic anhydride, it can be used in place of phthalic anhydride in commercial polyester... 

These are rate constants for the hydrolysis of cinnamic anhydride in bicarbonate-carbonate buffers. The pK of bicarbonate is 10.22. Find the rate constant for hydrolysis, at each pH, at zero buffer concentration. Analyze the data to determine if the acid or base component of the buffer, or both, are responsible for catalysis, and give the catalytic rate constant(s). 

Reactions of acid anhydrides (Section 21.5) (a) Hydrolysis to yield acids... 

A further observation is the fact that differences in rates of nitration between the reagents prepared at different temperatures tended to zero as the water concentration of the added nitric acid was decreased to zero73. It has been argued that, since the acid-catalysed hydrolysis of acetic anhydride must be very rapid at 25 °C and removes water which initially competes with acetic anhydride and acetyl nitrate for protons, this removal permits equilibria (30) and (31) to be displaced towards products. The more anhydrous the nitric acid, the less important is this initial hydrolysis of the acetic anhydride and so the difference in the nitrating power of the differently prepared mixtures becomes less. When reagents are mixed at low temperatures, the hydrolysis of the anhydride is very slow, but once this is accomplished, formation of the protonated acetyl nitrate and subsequent nitration is rapid as observed73. 

A good deal of heat is evolved when the hydrochloric acid is added to the reaction mixture, owing to the hydrolysis of acetic anhydride. The reaction mixture will become excessively hot unless it is cooled in an ice bath. 

Dining an attempt to prepare an anhydrous 25% solution of peroxyacetic acid in acetic acid by dehydrating a water-containing solution with acetic anhydride, a violent explosion occurred. Mistakes in the operational procedure allowed heated evaporation to begin before the anhydride had been hydrolysed. Acetyl peroxide could have been formed from the anhydride and peroxyacid, and the latter may have detonated and/or catalysed violent hydrolysis of the anhydride [1], A technique for preparing the anhydrous acid in dichloromethane without acetyl peroxide formation has been described [2],... 

Boyd, G. V. etal., J. Chem. Soc., Perkin Trans. 1, 1978, 1346 Interaction to give /V-fert-butylphthalisoimidium tetrafluoroborate was very violent, possibly because of exothermic hydrolysis of the anhydride by the 40% aqueous tetrafluoroboric acid. 

Addition of acetic anhydride to a solution of chromium trioxide in water caused violent boiling [1], due to the acid-catalysed exothermic hydrolysis of the anhydride [2],... 

Addition of the dehydrated salt to acetic anhydride caused an exothermic reaction which accelerated to explosion. Presence of acetic acid (including that produced by hydrolysis of the anhydride by the hydrate water) has a delaying effect on the onset of violent reaction, which occurs where the proportion of anhydride to acid (after hydrolysis) exceeds 0.37 1, with an initial temperature above 35°C. Mixtures of dichromate (30 g) with anhydride-acid mixtures (70 g, to give ratios of 2 1, 1 1, 0.37 1) originally at 40°C accelerated out of control after 18, 43 and 120 min, to 160, 155 and 115°C, respectively. 

Poly(A) synthesis also occurred in the second system, but the product remained within the vesicles. Walde also determined the increase of the vesicle concentration, which corresponds to that expected for an autocatalytic process. In this experiment, the enzyme PNPase is first captured by the vesicle envelope, and in the second step, ADP and oleic anhydride are added the anhydride is hydrolysed to the acid. ADP passes through the vesicle double layer and is polymerized in the interior of the vesicle by PNPase to give poly(A). Hydrolysis of the anhydride causes a constant additional delivery of vesicle-forming material, so that the amount of vesicle present increases during the poly(A) synthesis. These experiments demonstrated a model for a minimal cell. Autocatalytically synthesised giant vesicles could be prepared under similar conditions and observed under a microscope (Wik et al., 1995). 

The hydrolysis of acetic anhydride is being studied in a laboratory-scale continuously stirred tank reactor (CSTR). In this reaction acetic anhydride [(CH3C0)20] reacts with water to produce acetic acid (CH3COOH). 

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. 

Super or near-critical water is being studied to develop alternatives to environmentally hazardous organic solvents. Venardou et al. utilized Raman spectroscopy to monitor the hydrolysis of acetonitrile in near-critical water without a catalyst, and determined the rate constant, activation energy, impact of experimental parameters, and mechanism [119,120]. Widjaja et al. tracked the hydrolysis of acetic anhydride to form acetic acid in water and used BTEM to identify the pure components and their relative concentrations [121]. The advantage of this approach is that it does not use separate calibration experiments, but stiU enables identihcation of the reaction components, even minor, unknown species or interference signals, and generates relative concentration profiles. It may be possible to convert relative measurements into absolute concentrations with additional information. 

Figure 7 shows the results of methyl acetate carbonylation in the presence of water. Methanol and dimethyl ether were formed up to 250 C suggesting that hydrolysis of methyl acetate proceeded. With increasing reaction temperature, the yield of acetic acid increased remarkably, while those of methanol and dimethyl ether decreased gradually. Figure 8 shows the effects of partial pressures of methyl iodide, CO, and methyl acetate in the presence of water. The rate of acetic acid formation was 1.0 and 2.7 order with respect to methyl iodide and CO, respectively. Thus, the formation of acetic acid from methyl acetate is highly dependent on the partial pressure of CO. This suggests that acetic acid is formed by hydrolysis of acetic anhydride (Equation 6) which is formed from methyl acetate and CO rather than by direct hydrolysis of methyl acetate. 

As the loading of STA on the catalyst support is decreased, incomplete anhydride conversion is observed and significant hydrolysis of the anhydride to form iso-butyric acid is observed (Table 2). Use of silica supported phosphoric acid results in lower ketone yields and significant hydrolysis of the iso-butyric anhydride. Blank reactions (catalyst and anhydride, 90°C, 30 min) indicates that hydrolysis of anhydride is observed in the presence of these catalysts and may result from either dehydroxylation of the silica support or residual water in the catalyst, ffowever this reaction is slow (42%STA/silica, 44% conversion and 70%P[3PO4/silica, 86% conversion respectively). 

The results reported in this paper show that supported STA catalysts are efficient catalysts for the acylation of thioanisole and related activated aromatic molecules in the presence of iso-butyric anhydride as the acylating agent. The para- substituted ketone isomer is the major acylation product. Optimal catalyst activity is in the range of 60°C to 90°C. Use of either lower STA concentrations or use of weaker acids eg phosphoric acid, decreases the reaction rate and selectivity this results in greater hydrolysis of the anhydride. Use of supported STA catalysts is more efficient than bulk STA since the reaction medium is much cleaner and enables easier removal of the catalyst. 

Si02 is the best catalyst support for this reaction. As AI2O3 is incorporated into the Si02 the catalyst activity and selectivity decreases significantly. In these mixed oxide support materials Bronsted acid sites favour acylation, whilst the presence of Lewis acid sites results in hydrolysis of the anhydride. 

Figure 7.17 Hydrolysis of oleic anhydride catalyzed by spontaneously formed oleic acid vesicles at 40 °C, (a) during the first 3 h, and (b) during a long observation time. A vesicle suspension (10 ml in 0.2 M bicine buffer (pH 8.5)) was overlaid with 0.25 mmol oleic anhydride and 0.025 mmol oleic acid. The increase of the concentration of oleic acid/oleate is plotted as a function of reaction time. Initial concentration of oleic acid/oleate 0 mM ( ), 5 mM ( ), 10 mM (o), 20 mM ( ). For an initial oleic acid/oleate concentration of 20 mM, the concentration of oleic anhydride (A) present in the vesicles during the reaction is also plotted (b, right axis). (From Walde et al, 1994b.)...

Figure 7.18 Hydrolysis of caprylic anhydride leading to the formation of self-reproducing caprylic acid vesicles. A mixture of 10 ml 0.265 M NaOH, 0.1 M NaCI, and 2.5 mmol of caprylic anhydride was incubated at a fixed temperature under slight stirring, (a) Change in pH and caprylic acid/caprylate concentration in the aqueous phase as a function of reaction time at 40 °C. (b) Variation of the reaction temperature. (From Walde et al, 1994b.)...

All the models mentioned thus far are based on autopoietic self-reproduction experiments. The experimental implementation of a homeostatic mode of the autopoietic minimal system, which is also illustrated in Figure 8.3, proved to be much more difficult, and was realized only in 2001 (Zepik et al., 2001). It is based on the oleic acid surfactant system and is schematized in Figure 8.5 (respecting the theoretical scheme of Figure 8.3) there are two competitive reactions, the reaction Up forms oleate surfactant from the hydrolysis of the anhydride and the other reaction destroys oleate via oxidation of the double bond. 

Carboxylic acids are prepared hy the hydrolysis of acid chlorides and acid anhydrides, and acid- or hase-catalysed hydrolysis (see Section 5.6.1) of esters, primary amides and nitriles (see Section 5.6.1). 

Initially, water can cause the hydrolysis of the anhydride or the isocyanate, Scheme 28 (reaction 1 and 2), although the isocyanate hydrolysis has been reported to occur much more rapidly [99]. The hydrolyzed isocyanate (car-bamic acid) may then react further with another isocyanate to yield a urea derivative, see Scheme 28 (reaction 3). Either hydrolysis product, carbamic acid or diacid, can then react with isocyanate to form a mixed carbamic carboxylic anhydride, see Scheme 28 (reactions 4 and 5, respectively). The mixed anhydride is believed to represent the major reaction intermediate in addition to the seven-mem bered cyclic intermediate, which upon heating lose C02 to form the desired imide. The formation of the urea derivative, Scheme 28 (reaction 3), does not constitute a molecular weight limiting side-reaction, since it too has been reported to react with anhydride to form imide [100], These reactions, as a whole, would explain the reported reactivity of isocyanates with diesters of tetracarboxylic acids and with mixtures of anhydride as well as tetracarboxylic acid and tetracarboxylic acid diesters [101, 102]. In these cases, tertiary amines are also utilized to catalyze the reaction. Based on these reports, the overall reaction schematic of diisocyanates with tetracarboxylic acid derivatives can thus be illustrated in an idealized fashion as shown in Scheme 29. 

Anhydrides are somewhat more difficult to hydrolyze than acyl halides, but here too water is usually a strong enough nucleophile. The mechanism is usually tetrahedral. Only under acid catalysis does the SnI mechanism occur and seldom even then.s06 Anhydride hydrolysis can also be catalyzed by bases. Of course, OH- attacks more readily than water, but other bases can also catalyze the reaction. This phenomenon, called nucleophilic catalysis (p. 334). is actually the result of two successive tetrahedral mechanisms. For example, pyridine catalyzes the hydrolysis of acetic anhydride in this manner.507... 

RGURE 8-40 The phosphate ester and phosphoanhydride bonds of ATP. Hydrolysis of an anhydride bond yields more energy than hydrolysis of the ester. A carboxylic acid anhydride and carboxylic acid ester are shown for comparison. 

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