Diethyl malonate, alkylation

Sodium salt of diethyl malonate alkyl halide... 

Naphthyridones 22, which are of interest as pharmacological preparations, have been synthesized by the reaction of vicinal aminopyridinecarbonitriles 23 with diethyl malonate. Alkylation of these products with ethyl monobromoacetate results in N-substituted compounds 24 (1990ZC20)... 

The carbopalladation is extended to homoallylic amines and sulfides[466. Treatment of 4-dimethylamino-l-butene (518) with diethyl malonate and Li2PdCl4 in THF at room temperature leads to the oily carbopalladated complex 519, hydrogenation of which affords diethyl 4-(dimethylamino) butylmalonate (520) in an overall yield of 91%. Similarly, isopropyl 3-butenyl sulfide (521) is carbopalladated with methyl cyclopentanonecarboxylate and Li2PdCl4. Reduction of the complex affords the alkylated keto ester 522 in 96% yield. Thus functionalization of alkenes is possible by this method. 

Treatment of the anion of diethyl malonate with alkyl halides leads to alkylation at C 2... 

We see that a secondary alkyl halide is needed as the alkylating agent The anion of diethyl malonate is a weaker base than ethoxide ion and reacts with secondary alkyl halides by substitution rather than elimination Thus the synthesis of 3 methylpentanoic acid begins with the alkylation of the anion of diethyl mal onate by 2 bromobutane... 

As actually carried out and reported in the chemical literature diethyl malonate has been alkylated with 2 bromobutane in 83-84% yield and the product of that reaction converted to 3 methylpentanoic acid by saponification acidification and decarboxylatlon in 62-65% yield j... 

These compounds are prepared m a manner analogous to that of barbituric acid itself Diethyl malonate is alkylated twice then treated with urea... 

Thiourea (H2NCNH2) reacts with diethyl malonate and its alkyl derivatives in the same way that urea does Give the structure of the product obtained when thiourea is used instead of urea in the synthesis of pentobarbital The anesthetic thiopental (Pentothal) sodium is the sodium salt of this product yWhat IS the structure of this compound ... 

Aryl halides react too slowly to undergo substitution by the Sn2 mechanism with the sodium salt of diethyl malonate and so the phenyl substituent of phenobarbital cannot be introduced in the way that alkyl substituents can... 

Section 21 8 Alkylation of diethyl malonate followed by reaction with urea gives derivatives of barbituric acid called barbiturates, which are useful sleep promoting drugs... 

Section 21 9 Michael addition of the enolate ions derived from ethyl acetoacetate and diethyl malonate provides an alternative method for preparing their a alkyl derivatives... 

The use of epoxides as alkylating agents for diethyl malonate provides a useful route to y lactones Wnte equations illustrating such a sequence for styrene oxide as the starting epoxide Is the lactone formed by this reaction 3 phenylbutanohde or is it 4 phenylbutanohde ... 

The most widely used method for the laboratory synthesis of a ammo acids is a modification of the malonic ester synthesis (Section 21 7) The key reagent is diethyl acetamidomalonate a derivative of malonic ester that already has the critical nitrogen substituent m place at the a carbon atom The side chain is introduced by alkylating diethyl acetamidomalonate m the same way as diethyl malonate itself is alkylated... 

Malonic ester synthesis (Section 21 7) Synthetic method for the preparation of carboxylic acids involving alkylation of the enolate of diethyl malonate... 

Thiourea (H2NCNH2) reacts with diethyl malonate and its alkyl... 

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