Acyl chlorides, identification

Unambiguous identification of carboxyl groups was achieved by two reactions of the acyl chlorides 35). 

The ammonolysis of acyl chlorides is commonly employed whenever the preparation of an amide is desired for the identification of a carboxylic acid. The acyl chloride is prepared and treated with aqueous ammonia, or, if the amide is very soluble in water, with ammonia in benzene. In the latter case the ammonium chloride is filtered off, and the amide obtained by evaporation of the benzene with powdered ammonium carbonate. The preparation of amides from carboxylic acids is based upon the formation of an equilibrium mixture when the ammonium salts of the acid are heated ... 

Identification of Acyl Chlorides.—The reactions of acyl chlorides which are most helpful in their identification, are those which take place when they are treated with water, with alcohol, and with ammonia. Reaction takes place readily with these substances. When an acyl chloride is mixed with a small quantity of water or alcohol, hydrogen chloride is evolved. In the case of certain chlorides gentle heat is necessary to bring about reaction. The physical properties of the chloride together with those of the acid, ester, or amide prepared from it serve to complete its identification. 

The chlorides derived from the aromatic acids, of which benzoyl chloride, CeHs.COCl, is an example, do not react rapidly with water. They are readily converted into salts when shaken with a solution of an alkali, and into esters when shaken with ethyl alcohol and a solution of sodium hydroxide. The identification of acyl chlorides is best effected by converting them into amides by the action of ammonia —... 

The Schotten-Baumann reaction is widely used, particularly for the preparation of derivatives for the identification of small amounts of amines or acyl chlorides by shaking the reagents together in a glass-stoppered bottle. Sonntag [8] extensively reviewed this reaction. 

Norethindrone may be recrystakhed from ethyl acetate (111). It is soluble in acetone, chloroform, dioxane, ethanol, and pyridine slightly soluble in ether, and insoluble in water (112,113). Its crystal stmcture has been reported (114), and extensive analytical and spectral data have been compiled (115). Norethindrone acetate can be recrystakhed from methylene chloride/hexane (111). It is soluble in acetone, chloroform, dioxane, ethanol, and ether, and insoluble in water (112). Data for identification have been reported (113). The preparation of norethindrone (28) has been described (see Fig. 5). Norethindrone acetate (80) is prepared by the acylation of norethindrone. Norethindrone esters have been described ie, norethindrone, an appropriate acid, and trifiuoroacetic anhydride have been shown to provide a wide variety of norethindrone esters including the acetate (80) and enanthate (81) (116). 

Primary and secondary amines are acylated by acid chlorides and anhydrides, in particular also by the chloride of benzene sulphonic add (p. 192). The preparation of acetanilide has already been described (pp. 125, 128). The acetyl- and benzoyl-derivatives of all the simpler primary amines of the benzene and naphthalene series are known, so that these derivatives can always serve for purposes of identification. 

Primary and secondary amines possess replaceable amino hydrogen atoms. With acid chlorides (RCOCl) or anhydrides, (RCO)jO, they yield crystalline derivatives which are very useful in their separation and identification. Benzoyl derivatives are often preferred to acetyl derivatives because the former are less soluble and have higher melting points further, benzoyl chloride, unlike acetyl chloride, is not ea.sily hydrolyzed in water, and hence the acylation can be carried out in aqueous solutions. Tertiary amines do not react and therefore can be obtained unchanged. 

The constitnents of binary phenol mixtnres can be identihed by differential thermal analysis of a sample to which any of the aroyl chlorides 184-186 has been added. The thermogram is compared with a bank of differential thermograms of phenols, binary phenol mixtures and binary phenol derivatives. Most snch systems show weU-resolved endotherms corresponding to the melting points of the phenols and their acylated derivatives. The method is proposed for rapid identification of phenols in the solid state . 

The introduction to acyl addition in Chapter 16 avoided or minimized identification of the nucleophiles because nucleophiles of different strength react differently. Acyl addition is simply the reaction of a nucleophile with the carbonyl of an aldehyde or ketone. If nucleophiles of different electron-donating ability (differing nucleophilic strength) react differently, there should be a reasonable evaluation of the strength of different nucleophiles. One measure of nucleophilic strength is certainly whether or not a nucleophile reacts reversibly or irreversibly, at least in terms of product isolation. This discussion begins with the reaction of a weak nucleophile, the chloride ion, which adds to carbonyl compounds reversibly. 

For the identification of amines acylation methods (acetylation, benzoylation, 3,5-dinitrobezoylation), reaction with p-toluenesulfonyl chloride, preparation of substituted thioureas, diazotization and coupling (for aromatic primary amines), and the preparation of salts (picrates, tetraphenylboron salts) are most commonly used. 

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