Amides, acidity alcoholysis

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

The reaction of phosphonic acid chloride (254) with (S)-proline ethyl ester afforded a mixture of diasteromeric amides (255) in high diastereoselectivity. The diastereomers (255) can easily be purified by chromatography. The chiral, practically optical pure organophosphorus compound (256) was obtained from purified (255) by acid alcoholysis. 

The various ways in which esters of cellulose and phosphorous adds can be synthesized are esterification cellulose with free acids alcoholysis, with cellulose, of the esters and amides of phosphoric adds and esterification with mixed anhydrides df phosphoric adds and carboxylic adds. 

Pinner synthesis of orthoesters starting from alkoxymethyleneiminium salts (410 equation 192) (imino ester hydrohalides) is a standard procedure, which has been reviewed several times.For some more recent results see ref. 7. Closely related to this reaction is the alcoholysis of IV-alkyl- and NJ -di-alkyl-alkoxymethyleneiminium salts or acid amide-acid halide adducts. Orthoesters are formed via N//-dialkylalkoxymethyleneiminium salts when amide acetals (411 Scheme 74) are alcoholyzed in the presence of acetic acid. - ... 

Acylation of the bis-enamines (196) by acid chlorides followed by acidic alcoholysis leads to a wide variety of yields (highest in the absence of an a-H in the chloride) of 6-keto-esters (197) in an alternative to the direct Claisen method. The intermediate acylated enamines can also be converted into 6-keto-amides 185... 

Adiponitrile undergoes the typical nitrile reactions, eg, hydrolysis to adipamide and adipic acid and alcoholysis to substituted amides and esters. The most important industrial reaction is the catalytic hydrogenation to hexamethylenediarnine. A variety of catalysts are used for this reduction including cobalt—nickel (46), cobalt manganese (47), cobalt boride (48), copper cobalt (49), and iron oxide (50), and Raney nickel (51). An extensive review on the hydrogenation of nitriles has been recendy pubUshed (10). 

The most common reactions of carboxylic acid derivatives are substitution by water (hydrolysis) to yield an acid, by an alcohol (alcoholysis) to yield an ester, by an amine (aminolysis) to yield an amide, by hydride ion to yield an alcohol (reduction), and by an organometallic reagent to yield an alcohol (Grignard reaction). 

Acid chloride, alcohols from, 804 alcoholysis of, 802-803 amides from, 803-804 amines from, 933-935 amjnolysis of, 803-804 carboxylic acids from, 802 electrostatic potential map of, 791... 

In a similar way to the aminolysis of the P-N bond mentioned above (Scheme 9), alcoholysis of phosphinous amides leads to the alkyl esters of the respective phosphinous acids [30, 121]. This reaction occurs with inversion of the absolute configuration of the phosphorus atom, and has been used in a synthetic sequence leading to optically active tertiary phosphanes 22 [122] (Scheme 23). 

The alcoholysis and transamination of various aminophosphines have been studied as functions of the basicity of the attacking nucleophile and the substituents on phosphorus. As might be expected the reaction is facilitated by electron-withdrawing groups on phosphorus. The hydrolysis of tris(dimethylamino)phosphine (90) to phosphorous acid has been investigated using thin-layer chromatography and the amides (91) and (92) have been identified as intermediates. 

The compounds referred to as azolides are heterocyclic amides in which the amide nitrogen is part of an azole ring, such as imidazole, pyrazole, triazole, tetrazole, benzimidazole, benzotriazole, and their substituted derivatives. In contrast to normal amides, most of which show particularly low reactivities in such nucleophilic reactions as hydrolysis, alcoholysis, aminolysis, etc., the azolides are characterized by high reactivities in reactions with nucleophiles within the carbonyl group placing these compounds at about the same reactivity level as the corresponding acid chlorides or anhydrides. 11... 

Thus, the family of azolides represents a versatile system of reagents with graduated reactivity, as will be shown in the following section by a comparison of kinetic data. Subsequent chapters will then demonstrate that this reactivity gradation is found as well for alcoholysis to esters, aminolysis to amides and peptides, hydrazinolysis, and a great variety of other azolide reactions. The preparative value of azolides is not limited to these acyl-transfer reactions, however. For example, azolides offer new synthetic routes to aldehydes and ketones via carboxylic acid azolides. In all these reactions it is of special value that the transformation of carboxylic acids to their azolides is achieved very easily in most cases the azolides need not even be isolated (Chapter 2). 

For the mechanism of azolide hydrolysis under specific conditions like, for example, in micelles,[24] in the presence of cycloamyloses,[25] or transition metals,[26] see the references noted and the literature cited therein. Thorough investigation of the hydrolysis of azolides is certainly important for studying the reactivity of those compounds in chemical and biochemical systems.[27] On the other hand, from the point of view of synthetic chemistry, interest is centred instead on die potential for chemical transformations e.g., alcoholysis to esters, aminolysis to amides or peptides, acylation of carboxylic acids to anhydrides and of peroxides to peroxycarboxylic acids, as well as certain C-acylations and a variety of other preparative applications. 

The present procedure provides a facile and versatile synthesis, on large scale, of a variety of pyrrole-2-carboxylic acid derivatives without necessitating the use of moisture-sensitive organometallic reagents. The use of alcohols other than ethanol in the alcoholysis reaction provides virtually any desired ester. Ammonia or aliphatic amines readily give amides in high yields, and aqueous base can be used to give the free acid. 

Esters are less reactive than acid chlorides and acid anhydrides. They are converted to carboxylic acid hy acid or base hydrolysis, and to another ester by acid or base alcoholysis (transesterification). The 1°, 2° or 3° amides are obtained from esters by treatment with ammonia or 1° or 2° amines, respectively. 

Later investigators alcoholyzed imidate salts of other monobasic acids to obtain ortho esters of acetic [13, 14], propionic [15], butyric, valeric, caproic, isocaproic, benzoic [16], and phenylacetic acids [17]. For the latter alcoholysis reactions, the reaction time varies from a few days for the production of methyl orthopropionate to six weeks for ethyl orthobenzoate. McElvain reported that the reaction time is drastically cut by carrying out the reaction in boiling ether [18] or petroleum ether [19]. These conditions provide a reaction temperature below the decomposition point of the imidate salt to the amide. 

Adipimilrile undergoes the typical nitrile reactions, e.g.. hydrolysis to adipamide and adipic acid and alcoholysis to substituted amides and esters. 

Methylindoline and 1,3-dimethylindoline are phosphorylated by phosphorus trichloride at 100-120°C (3 h). Here 5-dichlorophosphinylindoline 36a,b is obtained from approximately half the indoline, while the other half is converted into the corresponding hydrochloride (indoline is regenerated from it by treatment with alkali) [34, 35]. With phosphorus trichloride 1,2,3,3-tetramethylindoline forms dichlorophosphine 36c with a quantitative yield [36]. The acid chlorides 36 undergo hydrolysis (37), amidation (38), and alcoholysis (39). Phosphonites 38 and 39 are converted into thiophosphonates and phosphonates 40, 41 and enter into the Arbuzov reaction (42) [160] ... 

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