Hydrolysis, of acetic anhydride

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]. 

The overall reaction stoichiometry having been established by conventional methods, the first task of chemical kinetics is essentially the qualitative one of establishing the kinetic scheme in other words, the overall reaction is to be decomposed into its elementary reactions. This is not a trivial problem, nor is there a general solution to it. Much of Chapter 3 deals with this issue. At this point it is sufficient to note that evidence of the presence of an intermediate is often critical to an efficient solution. Modem analytical techniques have greatly assisted in the detection of reactive intermediates. A nice example is provided by a study of the pyridine-catalyzed hydrolysis of acetic anhydride. Other kinetic evidence supported the existence of an intermediate, presumably the acetylpyridinium ion, in this reaction, but it had not been detected directly. Fersht and Jencks observed (on a time scale of tenths of a second) the rise and then fall in absorbance of a solution of acetic anhydride upon treatment with pyridine. This requires that the overall reaction be composed of at least two steps, and the accepted kinetic scheme is as follows. 

Sketch the reaction progress diagram for the pyridine-catalyzed hydrolysis of acetic anhydride. 

Direct detection of an intermediate. A nice example, the pyridine-catalyzed hydrolysis of acetic anhydride, was discussed in Chapter 1. Spectroscopic techniques are of great value, because they do not perturb the kinetic system, and because they are selective and sensitive. If the intermediate can be detected, the time course of its appearance and disappearance may be followed. 

Figure 4-12. Stopped-flow study of the pyridine-catalyzed hydrolysis of acetic anhydride, showing the formation and decay of the acetylpyridinium ion intermediate. Initial concentrations were 0.087 M pyridine, 2.1 x im M acetic anhydride the pH was 5.5 ionic strength, 1.0 M temperature, 25 C. Five hundred data points tabsorbance at 280 nm) were measured in I s. The smooth curve is a ht to Eq. (3-27). Source Data of D. Khossravi and S.-F. Hsu, University of Wisconsin.

Figure 4-12 shows a stopped-flow study of the pyridine-catalyzed hydrolysis of acetic anhydride. The absorbance-time curve reveals tbe formation and decay of the reactive intermediate acetylpyridinium ion. 

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. 

Chromium (III) oxide hydrate had been introduced into acetic anhydride causing a very violent hydrolysis of acetic anhydride and the spreading of the products. 

HYDROL - Batch Reactor Hydrolysis of Acetic Anhydride... 

BATCH HYDROLYSIS OF ACETIC ANHYDRIDE EXAMPLE OF REACTION WITH HEAT EFFECTS UNDER ADIABATIC CONDITIONS... 

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. 

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). 

Consider the hydrolysis of acetic anhydride carried out in dilute aqueous solution in a batch reactor ... 

Transient Holdup Profiles in an Agitated Extractor 459 Homogeneous Free-Radical Polymerisation 310 Batch Reactor Hydrolysis of Acetic Anhydride 247 Continuous Bioreactor with Inhibitory Substrate 543 Dynamic Oxygen Electrode 462... 

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. 

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... 

Catalysis of the hydrolysis of acetic anhydride by acetate ion cannot be explained in this way, since nucleophilic displacement simply generates another molecule of acetic anhydride. The mechanism of this reaction is presumed to be general base catalysis, usually written as... 

It may be concluded from the known rate coefficients for the hydrolysis of acetic anhydride, for example, that the hypothetical k0H value is larger than a diffusion-controlled rate constant. If Xd is taken as about 107 for acetic anhydride, then from k0n = h2o where kHiQ is the second-order water... 

The acid catalysis of the hydrolysis of acetic anhydride was later investigated by Gold and Hilton292 using aqueous solutions of hydrochloric, perchloric, sulphuric and phosphoric acids at 0°C. The first-order rate coefficient for hydrolysis is approximately proportional to h0 for all of these acids over a wide range of concentrations and this correlation is far better than with log [H+ ]. The mechanism proposed by these authors is... 

A re-investigation of the mechanism of the hydrolysis of acetic anhydrides in water was made by Bunton and Fendler4. They found that the hydrolysis of trimethylacetic anhydride follows an A-2 mechanism both in water and in aqueous dioxan and is slower than that of acetic anhydride. If acetic anhydride follows an A-l mechanism in water, both anhydrides should have the same mechanism and both should have similar reactivities in aqueous acids. If the A-2 mechanism is followed, steric effects should make trimethylacetic anhydride the less reactive compound. The entropy of activation of the hydrolysis catalysed by perchloric acid was re-estimated, taking into account the electrolyte effect of the perchlorate ions upon the rate of spontaneous hydrolysis, and a new value for A5 of—35 eu (for the spontaneous hydrolysis) and — 10 eu at 2 M HC104 for the acid-catalysed hydrolysis was obtained, compared with the value of + 2.2eu obtained previously. The new value is in the order of magnitude of A 5 for A-2 reactions but smaller than that observed for trimethylacetic anhydride under similar acidic conditions (— 26 eu). Plots... 

Nucleophilic and general base catalysis of the hydrolysis of acetic anhydrides are closely related. The hydrolysis of acetic anhydride is catalysed by formate and nitrite ions by nucleophilic catalysts296. Evidence for the postulated intermediate in the latter case, acetyl nitrite, has been obtained by the addition of a-naphthylamine to the system, trapping the intermediate to form 4-amino-1,1-azonaphthalene, viz. 

Although, so far in this section, we have discussed the kinetic evidence in terms of the A-l and A-2 mechanisms favoured by Bunton et al. (p. 224), the same points which give rise to differences in detailed interpretation of mechanism for hydrolysis of acyl halides apply with equal weight to the hydrolysis of anhydrides. Butler and Gold67,68,298,299 have studied the spontaneous hydrolysis of acetic anhydride and presented the following scheme. 

The mechanism proposed by Johnson300 for the general base-catalysed hydrolysis of acetic anhydride, viz. 

Kivinen proposes that the neutral hydrolysis of acetic anhydride is promoted by water acting as a weak base. The solvent isotope effect, kH20lkDl0 — 3, is suggestive of general base catalysis. 

The above types of catalysis function by stabilizing the transition state of the reaction without changing the mechanism. Catalysts may also involve a different reaction, pathway. A typical example is nucleophilic catalysis in an acyl transfer or hydrolytic reaction. The hydrolysis of acetic anhydride is greatly enhanced by pyridine because of the rapid formation of the highly reactive acetylpyridinium ion (equation 2.12). For nucleophilic catalysis to be efficient, the nucleophile... 

Benzofuran. Heat under reflux for 8 hours a mixture of 20 g (0.11 mol) of o-formylphenoxyacetic acid, 40 g of anhydrous sodium acetate, 100 ml of acetic anhydride and 100 ml glacial acetic acid. Pour the light brown solution into 600 ml of iced water, and allow to stand for a few hours with occasional stirring to aid the hydrolysis of acetic anhydride. Extract the solution with three 150 ml portions of ether and wash the combined ether extracts with 5 per cent aqueous sodium hydroxide until the aqueous layer is basic the final basic washing phase acquires a yellow colour. Wash the ether layer with water until the washings are neutral, dry the ethereal solution over anhydrous calcium chloride and remove the ether on a rotary evaporator. Distil the residue and collect the benzofuran as a fraction of b.p. 170-172°C. The yield of colourless product is 9.5 g (91%). 

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