Diethyl malonate, reaction with

Diethyl malonate, reaction with formaldehyde to form diethyl bis-(hydroxy methyl) malonate, 40, 27... 

Diethyl malonate reacts with iodine under basic soliddiquid conditions (procedure 6.4.20 omitting the alkene) to produce tetraethyl ethane-1,1,2,2-tetracarboxylate (Scheme 6.28) [110] the ethenetetracarboxylate is also formed, presumably from the reaction of the initially formed iodomalonate with its carbanion and subsequent elimination of hydrogen iodide. 

Potent nucleophiles can be generated from C-H acidic compounds by deprotonation. Diethyl malonate reacted with diethyl cyclopropane-1,1-dicarboxylate (1) in the presence of sodium ethoxide to give tetraethyl butane-1,1,4,4-tetraoate (2). Isopropylidene cyelo-propanedicarboxylate (3) underwent an analogous reaction when treated with dimethyl malonate or methyl 2-oxocyclohexanecarboxylate. ... 

As depicted in Scheme 4, oxazinanes 31 (R = Ph, Me, CH2COOEt) and oxazoli-dine 30 (R = CH2COPh) react with 1,3-cyclohexanediones 61 (R1 = Me, H) to form the corresponding 1 2 stoichiometric products 62 and xanthene derivatives 63. However, 30 (R = CH2COCH2COMe/OEt, in similar reactions form functionalized a-tetralones 64a-c. Acyclic carbon nucleophiles, such as ethyl acetoacetate, mal-ononitrile, nitromethane, dibenzoylmethane, and diethyl malonate, react with 31 (R = Ph) in the presence of an acid to form the corresponding styrene derivatives 65 (X = MeCO, CN, N02, COPh, COOEt Y = COOEt, CN, H, COPh, COOEt) only. 

The conjugate addition of an enolate to an a,/ -unsaturated carbonyl compound is called the Michael reaction or Michael addition. A good example is the following, where an enolate derived from diethyl malonate reacts with methyl vinyl ketone. 

The reaction of diethyl malonate (90) with sodium hydride generates enolate anion 91 as the conjugate base, and hydrogen gas is the conjugate acid. It has the three resonance contributors shown in the illustration, although 91A has the highest concentration of electron density, and 91 will react as a carbanion nucleophile. There is one extra resonance form in the malonate enolate anion relative to a simple ester due to the second carbonyl unit, and it means that 91 is more stable than the enolate derived from a monoester. In part, this accounts for the enhanced acidity and easier formation of the enolate anion using a weaker base. Once formed, 91 is a carbon nucleophile and it will react with both aldehydes and ketones, as well as with other esters. 

In the late nineteenth century, Michael found that the enolate anion (46) derived from diethyl malonate reacts with ethyl acrylate at the P-carbon (as shown in the illustration) to give an enolate anion, 47, as the product. Remember from Chapter 22 (Section 22.7.4) that the a-proton of a 1,3-dicarbonyl compound such as diethyl malonate is rather acidic (pK of about 11), and even a relatively weak base will deprotonate to form the enolate anion. Michael addition of 46 with ethyl acrylate will give enolate anion 47, and aqueous acid workup leads to the isolated product, 48. Attack at the -carbon is possible because that carbon is less hindered than the acyl carbon, so reaction at the C=C unit is somewhat faster than attack at the acyl carbon. Michael addition occurs with relatively stable carbanion nucleophiles, such as malonate derivative 46 and some other common nucleophiles. Other conjugated carbonyl derivatives react similarly. 

The Michael reaction is an alkylation in which carbanions, such as the enolates derived from (3-diketones, p-keto esters, and diethyl malonate, react with a,p-unsaturated ketones by conjugate addition. The a,p-unsaturated ketone serves the same kind of electrophilic role that alkyl halides do toward the enolate. 

With the assistance of the La-BINOL complex, the dibenzyl malonate reacted well with either 2-cyclopenten-1-one or 2-cyclohexen-l-one to afford more than 92% yields and enantioselectivities (Table 9.2). In addition, the dibenzyl a-methylmalonate could also be successfully employed in this reaction system. However, stericaUy less-demanding dimethyl and diethyl malonate provided with no more than 80% ee. 

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... 

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

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... 

Carbon Monoxide Process. This process involves the insertion of carbon monoxide [630-08-0] into a chloroacetate. According to the hterature (34) in the first step ethyl chloroacetate [105-39-5] reacts with carbon monoxide in ethanol [64-17-5] in the presence of dicobalt octacarbonyl [15226-74-1], Co2(CO)g, at typical temperature of 100°C under a pressure of 1800 kPa (18 bars) and at pH 5.7. Upon completion of the reaction the sodium chloride formed is separated along with the catalyst. The ethanol, as well as the low boiling point components, is distilled and the nonconverted ethyl chloroacetate recovered through distillation in a further column. The cmde diethyl malonate obtained is further purified by redistillation. This process also apphes for dimethyl malonate and diisopropyl malonate. 

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

Beryllium, calcium, boron, and aluminum act in a similar manner. Malonic acid is made from monochloroacetic acid by reaction with potassium cyanide followed by hydrolysis. The acid and the intermediate cyanoacetic acid are used for the synthesis of polymethine dyes, synthetic caffeine, and for the manufacture of diethyl malonate, which is used in the synthesis of barbiturates. Most metals dissolve in aqueous potassium cyanide solutions in the presence of oxygen to form complex cyanides (see Coordination compounds). 

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