Construction of Highly Substituted Nitroaromatic Systems by Cyclocondensation. Part I. Synthesis of 4‐nitro‐3‐oxobutyrate

Methyl 4‐nitro‐3‐oxobutyrate ( 1 ) is prepared by substitution of 4‐bromo‐ and 4‐iodo‐3‐oxobutyrate enol ether or enol acetate derivatives with nitrite and deprotection of the keto function ( Schemes 2 and 3 ). A much more convenient access to 1 is, however, the nitration of acetoacetate dianion with alkyl nitrates (Scheme 4) . Compound 1 is stable and storable, and can be handled safely. Its use in cyclocondensations is established by the reaction with acetylacetone (Scheme 5) , affording 4,6‐dimethyl‐3‐nitrosalicylate 48 in 70% yield. The halogen‐substitution method for the synthesis of 1 gives also access to the crystalline ( E )‐enol ether 18 of 1 , as well as to its dimethyl acetal 25 , ( Z )‐enol acetate 32 , and ( E )‐enol acetate 33 . The 3‐substituted 4‐bromobutenoates 15, 16 and 26 have been prepared from 4‐bromo‐3‐oxobutyrate 12 , a useful alternative to existing methods applying N ‐bromo‐succinimide.