Acetanilide, hydrolysis reactions

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. 

Conversion of aniline to acetanilide [103-84-4] by reaction with acetic anhydride, is a convenient method for protecting the amino group. The acetyl group can later be removed by acid or base hydrolysis. 

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). 

Substituted amides suffer hydrolysis with greater difficulty. The choice of an acid or an alkaline medium vill depend upon (a) the solubility of the compound in the medium and (b) the effect of the reagent upon the products of hydrolysis. Substituted amides of comparatively low molecular weight (e.g., acetanilide) may be hydrolysed by boiling either with 10 per cent, sodium hydroxide solution or with 10 per cent, sulphuric acid for 2-3 hours. Other substituted amides are so insoluble in water that little reaction occurs when they are refluxed with dilute acid or dilute alkali for several hours. These include such substances as benzanilide (C(H(CONHC,Hg) and the benzoyl derivative of a naphthylamine (C.HjCONHCioH,) or a toluidine (C gCONHCjH,). For these substances satisfactory results may be obtained with 70 per cent, sulphuric acid this hydrolysis medium is a much better solvent for the substituted amide than is water or more dilute acid it also permits a higher reaction temperature (compare Section IV 192) ... 

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. 

Activity on cell proliferation is maintained when a major part of the side chain is replaced by an amide linkage. The tetralin-based compound tamibarotene (15-7) has been tested as an agent for treating leukemias. Reaction of the diol (15-1) with hydrogen chloride affords the corresponding dichloro derivative (15-2). Aluminum chloride-mediated Friedel-Crafts alkylation of acetanilide with the dichloride affords the methylated tetralin (15-3). Basic hydrolysis then leads to the primary... 

Protection of the amino group by acetylation, as in acetanilide, therefore usually permits monosubstitution reactions with appropriate electrophilic reagents to proceed smoothly. Thus with bromine, p-bromoacetanilide is the main product the small quantity of the ortho isomer simultaneously formed can be easily eliminated by recrystallisation (Expt 6.67) hydrolysis of p-bromoacetanilide gives p-bromoaniline. Nitration leads similarly to p-nitroacetanilide which can be hydrolysed to p-nitroaniline (Expt 6.68). 

The Friedel-Crafts acylation of acetanilide with chloroacetyl chloride yields l-acetamido-4-chloroacetylbenzene. The trimethylammonium group is introduced by reaction with trimethylamine, followed by hydrolysis of the acetamide group. This diazo component is a constituent of numerous yellow, orange, and red cationic azo dyes. Using diethyl- m-toluidine as the coupling component, the lightfast red dye 35 [67905-12-8] is obtained [99],... 

Preparation of diazoketones and their rearrangements during hydrolysis (method 271) and alcoholysis (method 295) are discussed elsewhere. Ammonolysis of diazoketones leads to amides of acids containing one more carbon atom than the original acyl halide. Halogen atoms may be present in a remote position on an aliphatic chain. The reaction is carried out by heating the diazoketone in alcohol or dioxane solution with aqueous ammonia in the presence of silver oxide or silver nitrate catalysts. Substituted acetanilides are formed when aniline is used in place of ammonia. ... 

Trapping of intermediate Product identity attributable only to diversion of intermediate by reaction with added trapping nucleophile Acetanilid formation in acetate-catalyzed hydrolysis of aryl acetates in presence of aniline 87... 

---