Malonic butyl-, diethyl ester

Fig. 12.11. Mechanism of the tert-butylation of malonic acid diethyl ester. From the point of view of tert-butyl chloride it is an SN1 reaction with the malonic ester enol (B) acting as the nucleophile.

One equivalent of NaOEt in EtOH deprotonates malonic acid diethyl ester completely to give the sodium enolate A (Figure 10.33). This enolate is monoalkylated upon addition of an alkylating reagent such as BuBr, and a substituted malonic ester C is formed. During the alkylation reaction, the substituted malonic ester C reacts to a certain extent with some of the enolate A, resulting in the butylated enolate B and unsubstituted neutral malonic ester. It is for this reason that the reaction mixture contains two nucleophiles— the original enolate A and the butylated enolate B. The alkylation of A with butyl bromide is much faster than that of B, since A is less sterically hindered than B. The main product is therefore the product of monoalkylation. Distillation can be used to separate the main product from small amounts of the product of dialkylation. 

DIETHYL f-BUTYLMALONATE (Malonic acid, f-butyl-, diethyl ester)... 

Although azide reagents have been utilized in a number of chemical transformations, to date PS-TsA has only been utilized for the direct transfer of a diazo function to methylene groups flanked by either two carbonyls (eq 2), a carbonyl and an aryl sulfonyl (eq 3), or the methylene of lO/ anthracen-9-one. Diazodicarbonyl compounds such as 5-diazo-2,2-dimethyl-[l,3]dioxane-4,6-dione, 2-diazo-3-oxo-butyric acid ethyl ester, lO-diazo-lO/ anthracen-9-one, 2-diazo malonic acid diethyl ester, and 2-diazo-3-oxo-butyric acid ter/-butyl ester, as well as... 

C11H20O4 2-butyl-malonic acid diethyl ester 133-08-4... 

C11H20O4 2-sec-butyl-malonic acid diethyl ester 83-27-2... 

C12H22O4 2-(2-methyl-butyl)-malonic acid diethyl ester 1561-12-2... 

C21H40O4 2-butyl-2-decyl-malonic acid diethyl ester 52303-68-1... 

The cyanoacetic acid obtained from monochloroacetic acid and sodium cyanide, is treated with hydrochloric acid and ethanol to yield the diethyl ester of malonic acid. The ester, in absolute ethanol, is reacted with the stoichiometric proportion of metallic sodium so as to replace only one active hydrogen of the methylene (CH2) group. Thereupon, a slight excess of the calculated amount of allyl bromide is added. The second replaceable hydrogen is abstracted with 1-methyl butyl bormide and the resulting product is made to react with a theoretical amount of thiourea to yield thiamylal. The free acid thus obtained is conveniently transformed into the official sodium salt by neutralization with a stoichiometric proportion of sodium hydroxide (1 1). 

In the first step the diethyl ester of malonic acid is treated with ethyl bromide in the presence of sodium ethoxide when one of the active hydrogen atoms in the former gets eliminated with bromine atom in the later as a molecule of hydrobromic acid resulting into the formation of the corresponding diethyl ester of ethyl malonic acid. This on subsequent addition of 2-monobromopentane and in the presence of sodium ethoxide gives rise to diethyl ether of ethyl-(l-methyl butyl) malonate with the elimination of one molecule of hydrobromic acid. Urea is made to condense with the product obtained from the previous step when pentobarbital is formed with the elimination of two moles of ethanol. Finally, the pentobarbital is treated with a calculated amoimt of sodium hydroxide when the required official compoimd is formed. 

Preparation of Diethyl ester of ethyl-(l-methyl butyl) malonate ... 

Preparation of diethyl ester of allyl-(l -methyl butyl) malonate (//) Condensation of (/) above with urea and Hi) Preparation of the sodium salt. 

Diethyl malonate on reaction with sodium metal gives rise to sodium malonic ester which on treatment with ethyl bromide results into the formation of diethyl ester of ethyl malonic acid with the elimination of hydrobromic acid. The resulting ester on further reaction with 2-bromopentane gives the desired eompound, i.e., diethyl ester of ethyl (1-methyl butyl) malonic acid which on subsequent treatment with thiourea forms thiopental with the elimination of two moles of ethanol. Ultimately, the enol-iorm of thiopental when reaeted with a ealeulated amoimt of sodium hydroxide, it gives thiopental sodium. 

Diethyl ester of ethyl-(1-methyl butyl) malonic acid... 

DI-ier<-BUTYL ESTER, 34, 26 Malonic acid, ethyl half ester, 37,34 Malonic acid, ethylidene, diethyl ESTER, 32, S4... 

ETHYL BUTYL ESTER, 37, 34 METHYLENE-, DIETHYL ESTER, 38, 22 Malonic ester, acylation by o-nitro-benzoyl chloride, 30, 70 ethoxymagnesium derivative, solution of, 30, 70 37, 20 Malonic ester syntheses, 30, 7 Malononitrile, 37, S3 Malonyl dichloride, 33, 20 Mandelic acid, 36, 3 -bromo-, 35, 11... 

T) Diethyl sec.-Butylmalonate.—To 700 cc. of absolute alcohol in a 2-1. three-necked, round-bottomed flask equipped with a long, wide-bore reflux condenservs added 35 g. (1.52 gram atoms) of sodium cut in pieces of suitable size. When all the sodium has reacted, the flask is placed on a steam cone and fitted with a mercury-sealed stirrer, a dropping funnel, and a reflux condenser bearing a calcium chloride tube (Note 1). The flask is heated, and 250 g. (1.56 moles) of diethyl malonate is added in a steady stream with stirring. After the ester addition, 210 g. (1.53 moles) of see.-butyl bromide is added at such... 

Treatment of diethyl malonate and related compounds with 1,2-dihaloethane in the presence of base constitutes a classical method of cyclopropane synthesis296"300. The reaction can be conveniently carried out under PTC conditions. An improved method utilizing solid-liquid phase transfer catalysis has been reported298. The reaction of dimethyl or diethyl malonate with 1,2-dibromoalkanes except for 1,2-dibromethane tends to give only low yields of 2-alkylcyclopropane-l, 1-dicarboxylic esters. By the use of di-tm-butyl malonate, their preparations in satisfactory yields are realized (equation 134)297. The 2-alkylcyclopropane derivatives are also obtained from the reaction of dimethyl malonate and cyclic sulfates derived from alkane-1,2-diols (equation 135)301. Asymmetric synthesis... 

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