Hydrolysis of acetanilide

Hydrolysis of Acetanilide. Anilides in general, such as acetanilide and benzanilide (p. 245), may be hydrolysed by caustic alkalis or by acids. Alkaline hydrolysis, however, is usually very slow, and therefore... 

Hydrolysis of Benzanilide. For this hydrolysis, it is necessary to use 70% sulphuric acid (see Hydrolysis of Acetanilide, p. 108). Add I g. of benzanilide to 10 ml. of 70% sulphuric acid, and boil the mixture gently in a small flask under a reflux water-condenser for 30 minutes. Hydrolysis will now be complete, but much of the benzoic acid will have vaporised in the steam and then solidified in the conden-... 

M. Kiese, G. Renner, The Hydrolysis of Acetanilide and Some of Its Derivatives by Enzymes in the Microsomal and Soluble Fraction Prepared from Livers of Various Species , N.-S. Arch. Exp. Path. Pharmakol. 1966, 252, 480-500. 

The decrease in the water content by the dehydration process also have influence on the by-products, that mainly correspond to the products from the hydrolysis of acetanilide (2), acetic acid and aniline. 

On the basis of the general mechanism for amide hydrolysis in acidic solution shown in Mechanism 19.6, write an analogous sequence of steps for the hydrolysis of acetanilide, 0 II... 

Hydrolysis to p-Nitroaniline. For this purpose use 70 sulphuric acid, the usual reagent employed for the hydrolysis of anilides (p. 108). Add 5 g. of the recrystallised />-nitro-acetanilide to 30 ml. of 70%sulphuric acid, and boil the mixture gently under a reflux water-condenser for 20 minutes. Then pour the clear hot solution into about 150 ml. of cold water, and finally add an excess of sodium hydroxide solution until precipitation of the yellow p-nitroaniline is complete. Coo the mixture in ice-water if necessary, and then filter at the pump, wash well... 

Mono-substitution products of primary amines cannot easUy be prepared by direct action of the appropriate reagent for example, bromination of aniline yields largely the 2 4 6-tribomo derivative and nitration results in much oxidation. If, however, the amino group is protected as in acetanilide, smooth substitution occurs. Thus with bromine, />-bromoacetanilide is the main product the small quantity of the ortlio isomeride simultaneously formed can be easily eliminated by crystallisation. Hydrolysis of p-bromoacetanilide gives/ -bromoaniline ... 

Hydrolysis of a substituted amide. A. With 10 per cent, sulphuric acid. Reflux 1 g. of the compound (e.g., acetanilide) with 20 ml. of 10 per cent, sulphuric acid for 1-2 hours. Distil the reaction mixture and collect 10 ml. of distillate this will contain any volatile organic acids which may be present. Cool the residue, render it alkaline with 20 per cent, sodium hydroxide solution, cool, and extract with ether. Distil off the ether and examine the ether-soluble residue for an amine. 

The drugs are available by one of two fairly straightforward routes. Chlorosulfonation of acetanilide gives the corresponding sulfonyl chloride (88) reaction with the appropriate amine gives the intermediate, 89. Hydrolysis in either acid or base leads to the sulfanilamide (90). 

Friedel-Crafts alkylations and acylations of N-arylamides also proceed normally. For example, benzoylation of acetanilide (iV-acetylaniline) under Friedel-Crafts conditions gives 4-aminobenzophenone in 80% yield after hydrolysis. 

Chlorinated anilines are produced by the hydrolysis of a range of acetanilide, urea, and carbamate herbicides, and are therefore widely distributed in agricultural soils. Mechanisms for their loss... 

Modifications of the arylamino moiety profoundly influence the rate of hydrolysis. Thus, the hydrolysis of N- ace ty 1 -4-am i no be n zo i c acid was ca. 1000-fold slower than that of acetanilide [66]. Sorci and Macalady [67] investigated the influence of ring substitution on the hydrolysis of para-substituted acetanilides (4.104) in alkaline solution and in soil bacteria. No correlation was found between alkaline and biotic hydrolysis, which appeared to be controlled by different physicochemical properties. Bacterial hydrolysis was best correlated with the Van der Waals radius of the substituent, whereas chemical hydrolysis was correlated with the Hammett constant characterizing the electron-withdrawing capacity of the substituent. Other studies confirmed that a correspondence between bacterial and mammalian esterases... 

The hydrolysis of the positional isomers of acetaminophen (4.113) and phenacetin (4.114) were compared in homogenates of rat brain, liver, and kidney [74], Hydrolytic activity in the liver was higher than in the kidney and very low in the brain. The phenacetin analogues were better substrates than the acetaminophen analogues, as were the ortao-substituted compounds relative to their corresponding meta- or para-isomers. The hydrolysis of meta-acetophenetidine was comparable to that of acetanilide. No convincing arguments can be formulated to explain these observations. 

J. J. Sorci, D. L. Macalady, Quantitative Structure-Activity Relationships in Bacterial and Abiotic Alkaline Hydrolysis of Para-Substituted Acetanilides , J. Agric. Food Chem. 1993, 41, 1760-1766. 

J. H. Weisburger, C. M. Goodall, Steric Inhibition of Enzyme Reactions. Lack of Enzymatic Hydrolysis of 2, 4, 6 -Trimethyl-Acetanilide , Life Sci. 1968, 7, 263-267. 

The neutral and acid-catalysed mechanisms of hydrolysis of formamide, HCONH2, have been revisited and a comparison made between ab initio, semiempirical and DFT results Ab initio MO calculations on the alkaline hydrolysis of para-substituted acetanilides (135) in the gas phase have shown that the activation energy depends on the nature of electron-withdrawing groups (e.g. X = NO2, CN, Cl) but is invariant for electron-donating groups (X = NH2, OMe). ... 

Most acetanilides are biodegraded rapidly in soil, but alachlor appears to be degraded by a mechanism different from that for other members of this group of herbicides. The presence of either the 2, 6 -dialkyl substituents, the N-alkoxylmethyl substituent, or both, may preclude enzymatic hydrolysis of the carbonyl or... 

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