Preparation carboxylic acids from nitriles

Esters may also be prepared by hydrolysis of nitriles to carboxylic acids followed by esterification. See section 28 (Carboxylic Acids from Nitriles)... 

Carboxylic acids can be prepared from nitriles by reaction with hot aqueous acid or base by a mechanism that we ll see in Section 20.9. Since nitriles themselves are usually made by Sts 2 reaction of a primary or secondary7 alkyl halide with CN , the two-step sequence of cyanide displacement followed by nitiile hydrolysis is a good way to make a carboxylic acid from an alkyl halide (RBr —> RC=N RC02H). 

Many other examples of synthetic equivalent groups have been developed. For example, in Chapter 6 we discussed the use of diene and dienophiles with masked functionality in the Diels-Alder reaction. It should be recognized that there is no absolute difference between what is termed a reagent and a synthetic equivalent group. For example, we think of potassium cyanide as a reagent, but the cyanide ion is a nucleophilic equivalent of a carboxy group. This reactivity is evident in the classical preparation of carboxylic acids from alkyl halides via nitrile intermediates. 

The classification is unaffected by allylic, vinylic, or acetylenic unsaturation appearing in both starting material and product, or by increases or decreases in the length of carbon chains for example, the reactions f-BuOH f-BuCOOH, PhCHgOH PhCOOH, and PhCH=CHCH20H PhCH=CHCOOH would all be considered as preparations of carboxylic acids from alcohols. Conjugate reduction and alkylation of unsaturated ketones, aldehydes, esters, acids, and nitriles have been placed in Sections 74D and 74E (Alkyls from Alkenes), respectively. 

Nitriles are considered carboxylic acid derivatives because they are often prepared from acids through the primary amides. Show how you would convert the following carboxylic acids to nitriles. 

Oxazolines and oxazines are easily prepared from amino alcohols and carboxylic acids or nitriles, as was shown in an early work of Witte and Seeliger (Scheme 4). 

In this section, we first consider oxidative methods of preparing carboxyhc acids. Then, we discuss two general methods that are useful in preparing carboxyhc acids from starting materials containing one less carbon atom than the product. These methods, the carboxylation of a Grignard reagent and the hydrolysis of a nitrile, are based in part on reactions we have studied in earher chapters. 

Ress-Loeschke M, Friedrich T, Hauer B, Mattes R, Engels D, inventors BASF A.-G., Ltd., assignee. Preparation of chiral carboxylic acids from racemic nitriles by resolution with a... 

Mathews reaction is a one-pot preparation of carboxylic acids from their corresponding nitriles or amides by a dry hydrolysis with phthalic acid or anhydride in the absence of water and solvent. Excellent isolated yields and selectivity (upto 99%) were attained within short reaction times (typically 30 min) when the reaction was performed under microwave heating (Chemat, 2002). 

Benzyl-4,4,6-trimethyl-5,6-dihydro-4H-1,3-oxazine dissolved in tetrahydro-furan-ethanol (1 1), 9 N HGl added to pH 7, then aq. NaBH4 added at -30° with simultaneous addition of more HGl to keep the pH at 7, and stirred 1 hr. at -30° after the addition 2-benzyl-4,4,6-trimethyltetrahydro-l,3-oxazine. Y 88%. - Via this reduction, aldehydes, inch deuterioaldehydes, can be prepared from carboxylic acids and nitriles. F. e. s. A. I. Meyers and A. Nabeya, Ghem. Gommun. 1967, 1163. 

Section 19.12 Nitriles, which can be prepared from primary and secondary alkyl halides by nucleophilic substitution with cyanide ion, can be converted to carboxylic acids by hydrolysis. 

The following carboxylic acid can t be prepared from an alkyl halide by either the nitrile hydrolysis route or the Grignard carboxylation route. Explain. 

The alkylation of activated halogen compounds is one of several reactions of trialkylboranes developed by Brown (see also 15-16,15-25,18-31-18-40, etc.). These compounds are extremely versatile and can be used for the preparation of many types of compounds. In this reaction, for example, an alkene (through the BR3 prepared from it) can be coupled to a ketone, a nitrile, a carboxylic ester, or a sulfonyl derivative. Note that this is still another indirect way to alkylate a ketone (see 10-105) or a carboxylic acid (see 10-106), and provides an additional alternative to the malonic ester and acetoacetic ester syntheses (10-104). 

The addition of dry HCl to a mixture of a nitrile and an alcohol in the absence of water leads to the hydrochloride salt of an imino ester (imino esters are also called imidates and imino ethers). This reaction is called the Pinner synthesisThe salt can be converted to the free imino ester by treatment with a weak base such as sodium bicarbonate, or it can be hydrolyzed with water and an acid catalyst to the corresponding carboxylic ester. If the latter is desired, water may be present from the beginning, in which case aqueous HCl can be used and the need for gaseous HCl is eliminated. Imino esters can also be prepared from nitriles with basic catalysts. ... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

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