Carboxylic from nitriles

Synthesis of 2-pyridone-5-carboxylates from nitriles and propiolates by Blaise reaction Chun, Y.S., Ryu, K.Y., Ko, Y.O.,... 

Under a pressure of 4,5 ml the 1 methyl-4-phenyl-piperidine-4-carboxylic acid nitrile passes over at a temperature of about 148°C in the form of a colorless oil under a pressure of 6 ml it passes over at about 158°C. After having been allowed to cool the distillate solidifies completely to form a crystalline mass. Its solidification point is at 53°C the yield amounts to about 135 parts, that is, about % of the theoretical yield. When recrystallized from isopropyl alcohol the hydrochloride of the nitrile forms colorless crystals, readily soluble in water and melting at 221° to 222°C. 

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). 

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). 

The reactivity of oxiranes with lithium enoiates and related compounds has been widely explored and reviewed . Dianions derived from carboxylic acids react readily with oxiranes, but the reaction can be slowed by steric hindrance . The reaction of oxiranes with dianions of acetoacetates is greatly accelerated by the addition of BF3 Et20 " . Oxiranes react readily with lithium salts derived from nitriles , malonates and analogues , lithiated oxazolines and lithio enamines . 

Ketenimines are usually prepared from carboxylic acid derivatives such as amides and imino chlorides via elimination and from nitriles via alkylation with alkyl halides under strong basic conditions (21,64). 

Amides are also available from nitriles, which have the same oxidation level. Direct acid or base hydrolysis of a nitrile usually requires fairly severe conditions and often does not stop at the amide stage but goes on the carboxylic acid. Treatment of nitriles with a solution of HC1 in ethanol furnishes an imidate ester which is hydrolyzed in aqueous acid to the amide. Because a nitrile is the starting material, only primary amides can be produced by this process. 

Here, isoxazole-3-carboxylic acid (IV)-the main product of the reaction-is formed from nitrile oxide (III) on adding acetylene to it. 

Structure of the Carbonyl Group 817 18-3 Nomenclature of Ketones and Aldehydes 818 18-4 Physical Properties of Ketones and Aldehydes 820 18-5 Spectroscopy of Ketones and Aldehydes 822 18-6 Industrial Importance of Ketones and Aldehydes 828 18-7 Review of Syntheses of Ketones and Aldehydes 829 18-8 Synthesis of Ketones from Carboxylic Acids 833 18-9 Synthesis of Ketones and Aldehydes from Nitriles 833... 

In the following sections, we consider additional syntheses of ketones and aldehydes that we have not covered before. These syntheses form ketones and aldehydes from carboxylic acids, nitriles, acid chlorides, and alkyl halides. 

Although nitriles lack an acyl group, they are considered acid derivatives because they hydrolyze to carboxylic acids. Nitriles are frequently made from carboxylic acids (with the same number of carbons) by conversion to primary amides followed by dehydration. They are also made from primary alkyl halides and tosylates (adding one carbon) by nucleophilic substitution with cyanide ion. Aryl cyanides can be made by the Sandmeyer reaction of an aryldiazonium salt with cuprous cyanide. a-Hydroxynitriles (cyanohydrins) are made by the reaction of ketones and aldehydes with HCN. 

CL-Cyano esters are synthesized by this method from nitriles. Phenyl-acetonitrile, CjHjCHjCN, is carboxylated in 79% yield by diethyl carbonate and sodium ethoxide or sodium amide. Simple aliphatic nitriles give lower yields of the corresponding a-cyano esters. ... 

Preparations of guanidinocarbonylpyrazines, guanidinocarbamoylpyrazines, and ureidocarbonylpyrazines from esters have been described in Section 2C(2), from carboxylic acids in Section 1C(5), from amides in Section 3C(2), and from nitriles in Section 4C(2). 

Alcohols from carboxylic acid esters Bouveault-Blanc reduction s. 1, 64, 75 2, 89/90 new procedures s. 3, 49/50 also amines from nitriles s. 4, 89 Preparation of anhydrous alcohols s. 4,90 Alcohols from ethylenecarboxylic acid esters s. 4, 91 Hydroxyacetals from carbalkoxyacetals s. 4, 92 Acridines from acridones s. 2, 91 COOR -V CH2OH... 

Carboxylic acid amides from nitriles via imino ester hydrochlorides... 

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