Carboxylic from halogenated aliphatic acids

Halogen in positions other than next to the carboxyl group of aliphatic acids is somewhat less reactive. For preparation of methyl 4-(diethylamino)-butyrate from the 4-chloro compound the detour through the 4-iodo compound was chosen, this being easily accessible by means of sodium iodide.521... 

The Perkin reaction is capable of numerous modifications, since in place of benzaldehyde, its homologues, its nitro- and oxy-derivatives, etc., may be used. On the other hand, the homologues of sodium acetate may be used as has been pointed out. The condensation in these cases always takes place at the carbon atom adjoining the carboxyl group. Halogen substituted aliphatic adds will also react thus from benzaldehyde and chloracetic add, chlordnnamic acid is obtained ... 

Silver salts of carboxylic acids react with bromine or chlorine in an inert solvent to give carbon dioxide, a silver halide, and the halide containing one less carbon atom than the acid. The method has been reviewed. " Both low- and high-molecular-weight aliphatic bromides have been prepared. "t i i The degradation of silver salts of aromatic acids is complicated by nuclear halogenation." The procedure is valuable as a step in the synthesis of oi-bromo esters (C, to C,) from dicarboxylic acids. ... 

If an excess of phosphorus pentahalides is used on aliphatic carboxylic acid amides, having a-hydrogens, further halogenation occurs. For example, the reaction of propionic acid ethylamide (XV) with 3 equivalents of phosphorus pentachloride yields the imidoyl chloride XVI, which can also be obtained from a,a-dichloropropionic acid ethylamide (XVII) and one equivalent of phosphorus pentachloride (5 ). 

Haloform reactions are generally performed with halogens in the presence of hydroxide [251] or directly with hypohalites [252]. Alternative methods affording carboxylic acids from methyl ketones (or other enolizable substrates) include the aerobic oxidation in the presence of a catalytic amount of dinitrobenzene [253] with a base in a dipolar aprotic solvent such as DMF [254] or HMPT (hexamethylphospho-ric triamide) [255, 256] and the use of stoichiometric quantities of hypervalent iodide derivatives [95, 257] or nitrosylpentacyanoferrate [258]. Furthermore, metal catalysts can be used, and systems such as tert-butyl hydroperoxide in the presence of rhenium oxide [259], oxygen in combination with a copper complex [260], heteropolyacids [261] and Mn"/Co" systems [262] were found to be applicable. Finally, aryl ketones are selectively oxidized to aliphatic carboxylic acids by treatment with periodate [81] in the presence of ruthenium trichloride [263]. 

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