5,5-acetal acetamido malonic acid diethyl

An aqueous solution of sodium nitrite that is treated with HC1 contains nitrosyl cations 0=N . These can react with the enol E of the malonic acid diethyl ester (cf. Figure 12.9, bottom). First, a nitroso compound (F) is formed, which then undergoes acid-catalyzed isomerization to give the oxime A. Usually, the oxime is reduced by zinc, which is dissolved in acetic acid, to yield an amine that normally undergoes in situ acetylation in acetic acid. In this way the (acetamido)malonic acid diethyl ester B is obtained as the reduction/acetylation product, which can be employed, for example, in the synthesis of amino acids (Figure 13.39). 

Figure 13.39 shows that malonic ester syntheses can also lead to acetic acid derivatives with a heteroatom in the a-position. The benzylation of (acetamido)malonic acid diethyl ester... 

Acylaminomalonic esters and related reagents are widely used for the synthesis of a-amino acids. The method differs from those syntheses already discussed in that the amino group is incorporated into the system from the outset. A popular reagent is diethyl acetamidomalonate (35). The acetamido group can readily be introduced into the reactive methylene position in diethyl malonate by first converting the latter into the hydroxy-imino derivative (33) by reaction with nitrous acid or an alkyl nitrite (cf. Section 4.2.7, p. 413). This derivative is then reduced catalytically to diethyl aminomalonate (34) which is acetylated using acetic anhydride. 

---