Malonic acid, acetamido-, diethyl ESTER

DIETHYL ACETAMIDOMALONATE (Malonic acid, acetamido-, diethyl ester)... 

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... 

Mildly basic liquiddiquid conditions with a stoichiometric amount of catalyst prevent hydrolysis during alkylation [101] and, more recently, it has been established that solid-liquid or microwave promoted reactions of dry materials are more effective for monoalkylation [102-106] of the esters and also permits dialkylation without hydrolysis. Soliddiquid phase-transfer catalytic conditions using potassium f-butoxide have been used successfully for the C-alkylation of diethyl acetamido-malonate and provides a convenient route to a-amino acids [105, 107] use of potassium hydroxide results in the trans-esterification of the malonate, resulting from hydrolysis followed by O-alkylation. The rate of C-alkylation of malonic esters under soliddiquid phase-transfer catalytic conditions may be enhanced by the addition of 18-crown-6 to the system. The overall rate is greater than the sum of the individual rates observed for the ammonium salt or the crown ether [108]. 

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. 

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