Ammonia reaction with acyl chlorides

The use of ethylene adduct lb is particularly important when the species added to activate catalyst la is incompatible with one of the reaction components. Iridium-catalyzed monoallylation of ammonia requires high concentrations of ammonia, but these conditions are not compatible with the additive [Ir(COD)Cl]2 because this complex reacts with ammonia [102]. Thus, a reaction between ammonia and ethyl ciimamyl carbonate catalyzed by ethylene adduct lb produces the monoallylation product in higher yield than the same reaction catalyzed by la and [Ir(COD)Cl]2 (Scheme 27). Ammonia reacts with a range of allylic carbonates in the presence of lb to form branched primary allylic amines in good yield and high enantioselectivity (Scheme 28). Quenching these reactions with acyl chlorides or anhydrides leads to a one-pot synthesis of branched allylic amides that are not yet directly accessible by metal-catalyzed allylation of amides. 

Water, alcohols, ammonia, or amines are the nucleophiles that are usually employed in reactions with acyl chlorides. The products of these reactions are carboxylic acids, esters, or carboxamides according to the following reactions. 

Methylamine, like ammonia, reacts readily with acyl chlorides. The equations for the reactions in the case of acetyl chloride are,—... 

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. 

As these mechanisms show, the formation of amides from acid chlorides and amines is accompanied by production of one equivalent of HCI, which needs to be neutralized by a second equivalent of amine. An alternative method for making amides is to carry out the reaction in the presence of another base, such as NaOH, which then does the job of neutralizing the HCI. The trouble is, OH- also attacks acyl chlorides to give carboxylic acids. Schotten and Baumann, in the late nineteenth century, published a way round this problem by carrying out these reactions in two-phase systems of immiscible water and dichloromethane.The organic amine (not necessarily ammonia) and the acyl chloride remain in the (lower) dichloromethane layer, while the base (NaOH) remains in the (upper) aqueous layer. Dichloromethane and chloroform are two common organic solvents that are heavier (more dense) than water. The acyl chloride reacts only with the amine, but the HCI produced can dissolve in, and be neutralized by, the aqueous solution of NaOH. 

Amides can be prepared in a variety of ways, starting with acyl chlorides, acid anhydrides, esters, carboxylic acids, and carboxylate salts. All of these methods involve nucleophilic addition—elimination reactions by ammonia or an amine at an acyl carbon. As we might expect, acid chlorides are the most reactive and carboxylate anions are the least. 

Amination Reactions. Hexamethyldisilazane is a useful syn-thon for ammonia in amination reactions. Preparation of primary amides by the reaction of acyl chlorides and gaseous Ammonia, for example, is not an efficient process. Treatment of a variety of acyl halides with HMDS in dichloromethane gives, after hydrolysis, the corresponding primary amide (eq 10). Omitting the hydrolysis step allows isolation of the corresponding monosilyl amide. 

The reaction of acyl chlorides with ammonia, primary, or secondary amines is probably the most generally applicable method of preparing amides in the laboratory. A large variey of acid chlorides are available commercially, others are readily prepared from the acids. Not only halides of carboxylic acids but also those of sulfonic and phosphonic acids and of picric acid may be converted to amides. Both aliphatic and aromatic amines may be subjected to acylation with acid halides. The reactions of aliphatic acid chlorides have been extensively reviewed [8]. 

Reaction with ammonia and amines (Sec tion 20 14) Acyl chlorides react with am monia and amines to form amides A base such as sodium hydroxide is normally added to react with the hydrogen chio ride produced... 

In a similar vein, acylation of ami noketone 67 with chloroacetyl chloride affords the corresponding chloroamide 68. Reaction of that intermediate with ammonia serves to form the diazepine ring, possibly via the glycinamide. The product bentazepam (69) is described as a tranquilizer. ... 

The intermediate products, which are represented within brackets, are exceptionally labile since they contain OH and the negative acetoxyl group attached to the same carbon atom (cf. p. 103) they therefore decompose into two molecules of acid or, in the case of ammonia, into acetic acid and acetamide. The reaction with alcohols is to be formulated in the same way. It will be observed that, when an acyl group is introduced (into an alcohol, amine, etc.) by means of an anhydride, one of the two acid radicles in the molecule is always converted into the acid and is consequently not used in the acylation. The great reactivity of the acid chlorides has the same cause as that discussed in connexion with the anhydrides. 

Ammonolysis. Reactions involving ammonia. Ammonolysis of esters, acyl chlorides, and anhydrides give amides aniline is produced by ammonolysis of chlorobenzene. The reaction is analogous to hydrolysis, with ammonia substituted for water. 

By far the most common method for preparation of amides is the reaction of ammonia or a primary or secondary amine with one of the reactive reagents described in Section 3.4.1. When acyl halides are used, some provision for neutralizing the hydrogen halide is necessary, because it will otherwise react with the reagent amine to form the corresponding salt. Acid anhydrides give rapid acylation of most amines and are convenient if available. The Schotten-Bauman conditions, which involve shaking an amine with excess anhydride or acyl chloride and an alkaline aqueous solution, provide a very satisfactory method for preparation of simple amides. 

The reaction of an acyl chloride with an excess of ammonia represents one of the best procedures for the preparation of primary amides (Expt 5.154). 

The use of primary or secondary amines in place of ammonia yields the corresponding secondary or tertiary amides in reaction with an acyl chloride. These compounds often serve as crystalline derivatives suitable for the characterisation of either the acyl chloride (and hence of the carboxylic acid itself) or the amine (Sections 9.6.16, p. 1265 and 9.6.21, p. 1273). 

Step 2 Reaction of the acyl chloride with ammonia (NH3) affords the amide. 

Amides are most commonly prepared by reaction of an acyl chloride or an anhydride with ammonia or an amine. Because the by-products of these reactions are acidic, base must also be added to the reaction. An excess of the amine can be employed as the base if it is inexpensive, or the reaction may be done in the presence of sodium hydroxide or some other base. Following are several examples. 

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