Of malonic esters

An example of an intermolecular aldol type condensation, which works only under acidic catalysis is the Knoevenagel condensation of a sterically hindered aldehyde group in a formyl-porphyrin with a malonic ester (J.-H. Fuhrhop, 1976). Self-condensations of the components do not occur, because the ester groups of malonic esters are not electrophilic enough, and because the porphyrin-carboxaldehyde cannot form enolates. 

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... 

Uses. Although cyanoacetic acid can be used in appHcations requiring strong organic acids, its principal use is in the preparation of malonic esters and other reagents used in the manufacture of pharmaceuticals, eg, barbital, caffeine, and B vitamins (see Alkaloids Hypnotics Vitamins). Cyanoacetic acid can be used for the preparation of heterocycHc ketones. 

NaCN (for decarboxylation of malonic esters) DMSO, 160°, 4 h, 70-80% yield ... 

The formation of adducts of enamines with acidic carbon compounds has been achieved with acetylenes (518) and hydrogen cyanide (509,519,520) (used as the acetone cyanohydrin). In these reactions an initial imonium salt formation can be assumed. The addition of malonic ester to an enamine furnishes the condensation product, also obtained from the parent ketone (350,521). 

Syntheses of 4-substituted isoxazoles from -diketones and hydrox-amic acid chlorides were reported earlier. A recent investigation has realt with the behavior in this reaction of malonic ester. ... 

The reactive species is the corresponding enolate-anion 4 of malonic ester 1. The anion can be obtained by deprotonation with a base it is stabilized by resonance. The alkylation step with an alkyl halide 2 proceeds by a Sn2 reaction ... 

The product of malonic ester alkylation has one acidic o hydrogen atom left, so the alkylation process can be repeated a second time to yield a dialkyl-ated malonic ester. 

An electrochemical method for amination has been reported by Shono et al. Derivatives of malonic esters containing an N-tosyl group were cyclized in high... 

Manganese in its various oxidation states, such as, Mn+7, Mn+4 and Mn+3, had been exploited in several studies. An electron transfer mechanism for the inter-molecular arylation of malonate esters in the presence of manganese (III) triacetate... 

Meciarova M, Toma S, Luche J-L (2001) The sonochemical arylation of malonic esters mediated by manganese triacetate. Ultrason Sonochem 8(2) 119-122... 

A novel series of 5//-thiazolo[3,2-a]pyridine-5-ones 64 is prepared by addition of malonic esters 59 to 2-alkynylthiazoles 60 <06H(67)523>. A plausible reaction mechanism involves an intramolecular cyclization of the initial adduct 61 to give the cyclobutenoxide intermediate 62. Ring-opening of this intermediate and subsequent cyclization lead to 5//-thiazolo[3,2-a]pyridine-5-one 64. 

It is noteworthy that ZnEt2 has been used as a base in enantioselective allylic substitutions. A remarkable increase in ee was observed when ZnEt2 was used instead of KH, NaH, LiH, LDA, or BuLi in the Pd-catalyzed alkylations of allylic acetates by enolates of malonic esters and related compounds.403 In contrast, application of ZnEt2 was not as very effective as in similar iridium-catalyzed allylic alkylations.404... 

The title compounds, which are of pharmaceutical interest, are easily obtained in a one-pot procedure as a result of the formal amidation of malonic ester derivatives with an aniline followed by the cydization of the intermediate malondianilides [102] (Scheme 8.73). 

Intramolecular C,C-Coupling Reactions of Bis-N,N-(trimethylsiloxy) Iminium Cations Here we consider one of the mechanistic schemes of intramolecular C,C-coupling reactions of bis-/V,/V-(siloxy)iminium cations generated by silylation of P-nitroalkylated derivatives of malonic ester (382) (Scheme 3.216). 

This reaction was easily performed with malonic ester derivatives using approaches described above for nitro carbanions. It should be noted that the anion of malonic ester can be prepared not only by the reactions of bases with malonates but also by desilylation of silyl ketene acetal (449) with fluoride anion. 

The reaction of NO with a variety of compounds containing acidic protons in the presence of strong base was described long ago (Scheme 3.11, Eq. (1)) [138]. This work was largely ignored as a preparative method until a Russian group extended the methodology for the preparation of diazeniumdiolates of malonate esters (Scheme 3.11, Eq. (2)) [139, 140] and a variety of ketones [141, 142]. 

Finally, the synthesis of allenyl ketones is also possible by carbonylation if carbonates 103 are treated with C-H acidic compounds 104 such as /3-diketones or derivatives of malonic ester to yield products of type 105 [143],... 

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]. 

Reaction of malonic esters with 1,2-dibromoethane and 1,3-dibromopropane under liquiddiquid two-phase conditions produces the cyclopropane- and cyclobutane- 1,1 -dicarboxyl ic esters, which can be hydrolysed under the basic conditions (6.2.24.C) [e.g. 75, 109] and decarboxylated to give the monocarboxylic acid [e.g. 109]. 

Michael adducts (Table 6.16) are obtained from the reaction of malonic esters and... 

Esters are hydrolysed under basic conditions in the presence of quaternary ammonium salts [e.g. 1-7], Microwave activation of basic soliddiquid systems without an added solvent enhances the rate of saponification and the reaction is not affected by steric factors [3], Microwave irradiation has also been used in the hydrolysis and decarboxylation of malonic esters [8] and p-keto esters [9] (>90%). Lactones... 

Method D (hydrolysis and decarboxylation of malonic esters and fi-keto esters) LiBr (1.73 g), TBA-Br (0.32 g, 1 mmol), the malonic ester or p-keto ester (10 mmol) and H20 (360 ml) are subjected to microwave irradiation for 15 min. The cooled mixture is extracted with EtOAc (50 ml) and the organic solution is filtered through Florisil and evaporated to yield the decarboxylated compound. 

Cathodic reduction of retinal leads to a regioselective coupling in the presence of malonic ester to produce the corresponding pinacol (Fig. 26) [129]. Chromium(III) ions facilitate the reduction and favor the regioselective coupling of conjugated dienones to pinacols. A Cr(III)-carbonyl compound complex is evidenced as the reason for the selectivity [130]. 

The ring opening of glycidic acids and their derivatives by reactants such as the sodium salt of malonic ester has been reviewed in Russian. ... 

Anodic oxidation of malonate esters in alkaline solution gives the dehydrodimerization product by carbon-carbon coupling. The reaction mechanism has been... 

The chemical dehydrodimcnzaiion of malonate esters can be carried out by the action of iodine on the sodium enolate [23], This route is adapted as an electrochemical process using alcoholic sodium iodide as electrolyte in an undivided cell with carbon electrodes [24, 25]. Base generated at the cathode and iodine generated at the anode serve in a catalytic cycle. 

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