Acetylators rapid

Acetylation rates have also been studied by Centola37 who treated natural and mercerized ramie fibers for varying times with acetic anhydride and sodium acetate and examined the reaction products chemically and by X-ray diffraction. The reagent was considered to penetrate into the interior of fibers. A heterogeneous micellar reaction was believed to occur that converted a semi-permeable elastic membrane around the micelles into the triacetate. The rate of acetylation of mercerized ramie was observed to be faster than that of unmercerized fiber. Centola concluded that about 40 % of the cellulose in native ramie is amorphous and acetylates rapidly. 

Isoniazid is acetylated to acetyl isoniazid by A-acetyl-transferase, an enzyme in fiver, bowel, and kidney. Individuals who are genetically rapid acetylators will have a higher ratio of acetyl isoniazid to isoniazid than will slow acetylators. Rapid acetylators were once thought to be more prone to hepatotoxicity, but this is not proved. The slow or rapid acetylation of isoniazid is rarely important clinically, although slow inactivators tend to develop peripheral neuropathy more readily. Metabolites of isoniazid and small amounts of unaltered drug are excreted in the urine within 24 hours of administration. 

Acetylation of phenols and anilines. These substrates can be acetylated rapidly and in generally high yield by reaction with acetyl chloride using powdered NaOH and tetrabutylammonium hydrogen sulfate in an organic solvent (CH2CI2, dioxane, THE). Even 2,6-di-f-butyI-p-cresol can be acetylated in this way in 72% yield. Selective acylation of the phenolic hydroxyl group of estradiol is possible. ... 

While whole starch is very slowly or incompletely dissolved by mixtures of acetic acid, acetic anhydride, and sulfuric acid, the acetyl content of the dissolved portion rises rapidly with increased amounts of sulfuric acid or the application of higher temperatures." In contrast to whole starch a finely divided, fluffy starch, prepared as described in Section II, might be expected to be acetylated rapidly and completely by mixtures of acetic acid, acetic anhydride, and sulfuric acid. 

Acetylation. Rapid peracetylation of carbohydrates can be effected in the presence of iodine. With more iodine and longer reaction times the selective acetolysis of primary benzyl ethers is achieved. Perbenzyl ethers of mono- and disaccharides undergo group exchange (OBn —> OAc) at the primary carbon atoms on treatment with ACjO-HOAc-ZnClj. 

The metabolism of xenobiotics proceeds at different rates for different individuals. This is because of genetic variations. Two examples demonstrate this point. CYP450 enzyme production (required for Phase I metabolism) varies by as much as 30% in healthy individuals. TV-acetyltransferase reaction rates (an example of a Phase II metabolism reaction) vary widely. Some individuals acetylate rapidly and others slowly, with the slow acety-lators having lower toxic thresholds. 

One disadvantage of using acetic anhydride is that with primary amines, traces of the diacctyl compound, RN(COCH3)2, niay be formed the chances of this secondary acetylation are, however, usually remote, and recrystallisation from an aqueous solvent will generally hydrolyse the diacetyl derivative rapidly back to the mono-acetyl compound. 

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... 

Dissolve 10 g. of salicylic acid (o-hydroxybenzoic acid) in 7 ml. of dry pyridine contained in a too ml. conical flask. Then without delay (since this solution if allowed to stand tends to become a semi-solid mass) run in 7 5 ml. (8 3 g.) of acetyl chloride, adding about i ml. of the chloride at a time, and shaking the mixture continuously during the addition. The heat of the reaction causes the temperature of the mixture to rise rapidly ... 

Transfer the reaction product to a 500 ml. Claisen flask and distil over a wire gauze or from an air bath. Some acetyl chloride and acetic acid passes over first, the temperature then rises, and the fraction, b.p. 150-200°, is collected separately run out the water from the condenser when the temperature reaches 150°. The fraction, b.p. 150-200°, solidifies on cooling. Drain off any hquid from the crystals as rapidly as possible, and redistil the solid using an air condenser. CoUect the fraction b.p. 182-192° this sets to a sohd mass on cooling and melts at 63°. The yield of monochloroacetic acid is 150-175 g. 

A. Maleic acid. Assemble the apparatus shown in Fig. Ill, 28, 1. Place 45 g. of dry mahc acid in the 200-250 ml. distilling flask and cautiously add 63 g. (57 ml.) of pure acetyl chloride. Warm the flask gently on a water bath to start the reaction, which then proceeds exothermically. Hydrogen chloride is evolved and the malic acid passes into solution. When the evolution of gas subsides, heat the flask on a water bath for 1-2 hours. Rearrange the apparatus and distil. A fraction of low boiling point passes over first and the temperature rises rapidly to 190° at this point run out the water from the condenser. Continue the distillation and collect the maleic anhydride at 195-200°. Recrystallise the crude maleic anhydride from chloroform (compare Section 111,93) 22 g. of pure maleic anhydride, m.p. 54°, are obtained. 

In general, however, the diacetyl derivatives are unstable in the presence of water, undergoing hydrolysis to the mono-acetyl compound, so that when they (or a mixture of mono- and di-acetyl derivatives) are crystallised from an aqueous solvent, e.g., dilute alcohol, only the mono-acetyl derivative is obtained. A further disadvantage of the use of acetic anhydride in the absence of a solvent is that all the impm-ities in the amine are generally present in the reaction product. Heavily substituted amines, t.g., 2 4 6-tribromoaniline, react extremely slowly with acetic anhydride, but in the presence of a few drops of concentrated sulphuric acid as catalyst acetylation occurs rapidly, for example ... 

Crystalline derivatives, suitable for identification and characterisation are dealt with in Section IV, 114, but the preparation of the following, largely liquid, derivatives will be described in the following Sections. When phenols are dissolved in aqueous sodium hydroxide solution and shaken with acetic anhydride, they undergo rapid and almost quantitative acetylation if the temperature is kept low throughout the reaction. This is because phenols form readily soluble sodium derivatives, which react with acetic anhydride before the latter undergoes appreciable hydrolysis, for example ... 

Evidence from the viscosities, densities, refractive indices and measurements of the vapour pressure of these mixtures also supports the above conclusions. Acetyl nitrate has been prepared from a mixture of acetic anhydride and dinitrogen pentoxide, and characterised, showing that the equilibria discussed do lead to the formation of that compound. The initial reaction between nitric acid and acetic anhydride is rapid at room temperature nitric acid (0-05 mol 1 ) is reported to be converted into acetyl nitrate with a half-life of about i minute. This observation is consistent with the results of some preparative experiments, in which it was found that nitric acid could be precipitated quantitatively with urea from solutions of it in acetic anhydride at —10 °C, whereas similar solutions prepared at room temperature and cooled rapidly to — 10 °C yielded only a part of their nitric acid ( 5.3.2). The following equilibrium has been investigated in detail ... 

Certain features of the addition of acetyl nitrate to olefins in acetic anhydride may be relevant to the mechanism of aromatic nitration by this reagent. The rapid reaction results in predominantly cw-addition to yield a mixture of the y -nitro-acetate and y5-nitro-nitrate. The reaction was facilitated by the addition of sulphuric acid, in which case the 3rield of / -nitro-nitrate was reduced, whereas the addition of sodium nitrate favoured the formation of this compound over that of the acetate. As already mentioned ( 5.3. i), a solution of nitric acid (c. i 6 mol 1 ) in acetic anhydride prepared at — 10 °C would yield 95-97 % of the nitric acid by precipitation with urea, whereas from a similar solution prepared at 20-25 °C and cooled rapidly to —10 °C only 30% of the acid could be recovered. The difference between these values was attributed to the formation of acetyl nitrate. A solution prepared at room... 

The nitric acid used in this work contained 10% of water, which introduced a considerable proportion of acetic acid into the medium. Further dilution of the solvent wnth acetic acid up to a concentration of 50 moles % had no effect on the rate, but the addition of yet more acetic acid decreased the rate, and in the absence of acetic anhydride there was no observed reaction. It was supposed from these results that the adventitious acetic acid would have no effect. The rate coefficients of the nitration diminished rapidly with time in one experiment the value of k was reduced by a factor of 2 in i h. Corrected values were obtained by extrapolation to zero time. The author ascribed the decrease to the conversion of acetyl nitrate into tetranitromethane, but this conversion cannot be the explanation because independent studies agree in concluding that it is too slow ( 5.3.1). 

Acid anhydrides are more stable and less reactive than acyl chlorides Acetyl chlo ride for example undergoes hydrolysis about 100 000 times more rapidly than acetic anhydride at 25°C... 

Procainamide may be adininistered by iv, intramuscular (im), or po routes. After po dosing, 75—90% of the dmg is absorbed from the GI tract. About 25% of the amount absorbed undergoes first-pass metaboHsm in the fiver. The primary metabolite is A/-acetylprocainamide (NAPA) which has almost the same antiarrhythmic activity as procainamide. This is significant because the plasma concentration of NAPA relative to that of procainamide is 0.5—2.5. In terms of dmg metabolism there are two groups of patients those that rapidly acetylate and those that slowly acetylate procainamide. About 15—20% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 60—90 min. Therapeutic plasma concentrations are 4—10 lg/mL. Plasma half-lives of procainamide and NAPA, which are excreted mainly by the kidneys, are 2.5—4.5 and 6 h, respectively. About 50—60% is excreted as unchanged procainamide (1,2). 

Ca.ta.lysts for Acetylation. Sulfuric acid is the preferred catalyst for esterifying cellulose and is the only known catalyst used commercially for this function. The role of sulfuric acid during acetylation has been discussed (77,78). In the presence of acetic anhydride, sulfuric acid rapidly and almost quantitatively forms the cellulose sulfate acid ester (77). Even in the absence of anhydride, the sulfuric acid is physically or mechanically retained (sorbed) on the cellulose. The degree of absorption is a measure of the reactivity or accessibiUty of different celluloses. 

The acetylation reaction is stopped by the addition of water to destroy the excess anhydride, causing rapid hydrolysis of the combined sulfate acid ester (Eig. 7). This is followed by a much slower rate of hydrolysis of the acetyl ester groups. The rate of hydrolysis is controlled by temperature, catalyst concentration, and, to a lesser extent, by the amount of water. Higher temperatures and catalyst concentrations increase the rate of hydrolysis. Higher water content slightly iacreases the hydrolysis rate and helps minimize degradation (85). The amount of water also influences the ratio of primary to secondary... 

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