The tautomerism of carbostyril derivatives

Summary

• 1. By the action of bromomethyl methyl ether, of chloromethyl methyl ether, of bromomethyl ethyl ether, of chloromethyl ethyl ether, of bromomethyl propyl ether, and of chloromethyl propyl ether on the sodium and silver derivatives of carbostyril, the corresponding ethers were obtained: Carbostyril methoxymethyl ether, m.p. 66–67° Carbostyril ethoxymethyl ether, m.p. 39–40° Carbostyril propoxvmethyl ether, b.p. 192–193° at 12 mm.

• 2. On hydrolysis, carbostyril methoxymethyl ether gave carbostyril (in almost quantitative yield) and formaldehyde.

• 3. The ethoxymethyl and propoxymethyl derivatives of carbostyril do not undergo hydrolysis in dilute alkali or acid. This has been confirmed in repeated experiments. When the propoxymethyl derivative was heated with dilute acid at 140–150°, a high-melting product was obtained.

• 4. By the action of chlorotriphenylmethane, of benzyl bromide and chloride, and ofa-bromo-p-xylene on the sodium and silver derivatives of carbostyril the following products were obtained: (triphenylmethyl) carbostyril of m.p. 180–181°, benzylcarbostyril in two forms of m.p. 50–51° and 95–96° respectively; and (P-tolylmethyl)carbostyril in two forms of m.p. 71–72° and 131–132° respectively.

• 5. On hydrolysis, (triphenylmethyl)carbostyril gave triphenylmethanol and carbostyril in almost quantitative yields.

• 6. Attempts to hydrolyze the two forms of benzylcarbostyril and the two forms of (p-tolylmethyl)carbostyril in dilute alkali did not give positive results. They were hydrolyzed. in dilute acid, yielding carbostyril.

• 7. The sodium and potassium salts of carbostyril gave identical products when they reacted with benzyl bromide (or chloride); they gave identical products also when they reacted with bromomethyl methyl ether (or chloromethyl methyl ether).

• 8. An attempt to isomerize the methoxymethyl derivative of carbostyril in presence of bromomethyl methyl ether led to the formation of a high-melting product.

• 9. The lower-melting forms of benzylcarbostyril and (p-tolylmethyl)carbostyril were found to be isomerized when heated with the corresponding aralkyl halides into the higher-melting forms of these substances.