Of diethyl maleate and

A plausible reaction mechanism for this reaction was proposed by the authors. The Cu(i) carbene 182 generated from ethyl diazoacetate and the chiral Gu(i) complex can either react with another molecule of ethyl diazoacetate to form a mixture of diethyl maleate and fumarate 183, or with the imine lone pair to form a Gu(i)-complexed azomethine ylide... 

The copper-catalyzed decomposition of ethyl diazoacetate in the presence of a ketene acetal also leads to the corresponding cyclopropane in addition to larger quantities of diethyl maleate and diethyl fumarate ]f p-unsubstituted or... 

Ethyl maleate of almost equal purity may be obtained by refluxing a mixture of 20 g. of pure maleic a.oid, 37 g. (47 ml.) of absolute ethyl alcohol, 05 ml. of sodium-dried benzene and 4 ml. of concentrated sulphuric acid for 12 hours. The ester is isolated as described for Diethyl Adipate (Section 111,100). The yield of diethyl maleate, b.p. 219-220°, is 26 g. 

More recently, Cheeseman and coworkers have investigated cycloaddition reactions of 2,6-dioxypyrazines (80jCS(Pl)1603). 2,6-Dihydroxy-3,5-diphenylpyrazine (77) reacts with electron deficient dienophiles such as iV-phenylmaleimide, diethyl maleate and diethyl fumarate (Scheme 26) to yield adducts of the 3,8-diazabicyclo[3.2.1]octane class such as (78). This reaction is believed to proceed by way of the betaine (79) and has precedent (69AG(E)604) in that photolysis of the bicyclic aziridine (80) generates analogous betaines which have been trapped in cycloaddition reactions. 

In contrast, addition of dimethyl acetylenedicarboxylate to cyclopent[6]azepine (6) is slow and furnishes, in 53% yield, a mixture of the dimeric 1 2 adduct 7 (red crystals), the 1 3 adduct 8 (yellow oil), and an unidentified purple oil.2 Surprisingly, cyclopent[6]azcpine fails to react with other common dienophiles such as ethenetetracarbonitrile, diethyl maleate and chlorosulfonyl isocyanate. 

The results of Diels-Alder reactions of cyclopentadiene with diethyl fumarate, diethyl maleate and ethyl acrylate carried out in SC-H2O are reported in Scheme 6.32 [79]. The cycloaddition of diethyl fumarate occurred with low yield. 

Surprisingly, the 7t-system geometry in a substrate has a notable influence in the enzymatic aminolysis of esters. The reaction of diethyl fumarate with different amines or ammonia in the presence of CALB led to the corresponding trans-amidoesters with good isolated yields, but in the absence of enzyme, a high percentage of the corresponding Michael adduct is obtained (Scheme 7.9). Enzymatic aminolysis of diethyl maleate led to the recovery of the same a, P-unsaturated amidoester, diethyl fumarate, and diethyl maleate. The explanation of these results can be rationalized via a previous Michael/retro-Michael type isomerization of diethyl maleate to fumarate, before the enzymatic reaction takes place. In conclusion, diethylmaleate is not an adequate substrate for this enzymatic aminolysis reaction [23]. 

The common by-products obtained in the transition-metal catalyzed reactions are the formal carbene dimers, diethyl maleate and diethyl fumarate. In accordance with the assumption that they owe their formation to the competition of olefin and excess diazo ester for an intermediate metal carbene, they can be widely suppressed by keeping the actual concentration of diazo compound as low as possible. Usually, one attempts to verify this condition by slow addition of the diazo compound to an excess (usually five- to tenfold) of olefin. This means that the addition rate will be crucial for the yields of cyclopropanes and carbene dimers. For example, Rh6(CO)16-catalyzed cyclopropanation of -butyl vinyl ether with ethyl diazoacetate proceeds in 69% yield when EDA is added during 30 minutes, but it increases to 87 % for a 6 h period. For styrene, the same differences were observed 65). 

EvenPd(OAc)2 is not effective in catalyzing the cyclopropanation of a,P-unsaturated nitriles by ethyl diazoacetate. Instead, vinyloxazoles 92 are formed from acrylonitrile or methacrylonitrile by carbenoid addition to the CsN bond 143 Diethyl maleate and diethyl fumarate as well as polyketocarbenes are by-products in these reactions the 2-pyrazoline which would result from initial [3 + 2] cycloaddition at the C=C bond and which is the sole product of the uncatalyzed reaction at room temperature, can be avoided completely by very slow addition of the diazoester... 

A somewhat unusual copper catalyst, namely a zeolite in which at least 25% of its rhodium ions had been exchanged by Cu(II), was active in decomposition of ethyl diazoacetate at room temperature 372). In the absence of appropriate reaction partners, diethyl maleate and diethyl fumarate were the major products. The selectivity was a function of the zeolite activation temperature, but the maleate prevailed in all cases. Contrary to the copper salt-catalyzed carbene dimer formation 365), the maleate fumarate ratio was found to be relatively constant at various catalyst concentrations. When Cu(II) was reduced to Cu(I), an improved catalytic activity was observed. 

Kluwe WM, Hook JB. 1981. Potentiation of acute chloroform nephrotoxicity by the glutathione depletor diethyl maleate and protection by the microsomal enzyme inhibitor piperonyl butoxide. Toxicol Appl Pharmacol 59 457-466. 

Savage RE Jr., Nofzinger K, Bedell C, et al. 1989. Chloroform-induced multiple forms of ornithine decarboxylase Differential sensitivity of forms to enhancement by diethyl maleate and inhibition by ODC-antizyme. J Toxicol Environ Health 27 57-64. 

Stevens JL, Anders MW. 1981. Effect of cysteine, diethyl maleate, and phenobarbital treatments on the hepatotoxicity of [IH]- and [2H]chloroform. Chem Biol Interact 37 207-217. 

In order to prevent phenylacetylene hydrogenation, and to eliminate the evolution of hydrogen, other unsaturated compounds such as diethylfumarate, diethyl-maleate and diphenylacetylene were added as a hydrogen scavengers [45]. 

Conjugated double bonds were also reduced in methyl 3-methyl-2-buten-oate with tributylstamane on irradiation with ultraviolet light at 70° (yield of methyl isovalerate was 90%) [1071], and in diethyl maleate and diethyl fu-marate which afforded diethyl succinate in respective yields of 95% and 88% on treatment with chromous sulfate in dimethylformamide at room temperature [974,1072]. 

Harris RN, Anders MW. 1980. Effect of fasting, diethyl maleate and alcohols on carbon tetrachloride-induced heptotoxicity. Toxicol AppI Pharmacol 56 191-198. 

In an unusual reaction, involving a Meisenheimer intermediate, 3,5-dinitrobenzophenone reacted with A/.A-dimethylphenylacetamidine to give either a quinoline (519) or an isoquinoline (520) (77JOC435). Enamines (521) react with diethyl maleate and aluminum chloride at room temperature to give good yields of the unusual 3,6-dihydropyrid-2-ones (522)... 

A. Diethyl propionylsuccinate (1). A solution of 412 g. (2.4 mole) of diethyl maleate (Note 1), 278 g. (4.8 mole) of freshly distilled propionaldehyde (Note 2), and 1.2 g. (0.0048 mole) of benzoyl peroxide in a normal 2-1. Pyrex flask is heated under reflux while undergoing irradiation with an ultraviolet lamp (Note 3). The initial reflux temperature is 60°. After 2 hours another 1.2 g. (0.0048 mole) of benzoyl peroxide is added. Strong reflux and irradiation are maintained throughout the entire reaction period. After 18 hours total time, the internal pot temperature reaches 68°. At this point the last 1.2 g. (0.0048 mole) of benzoyl peroxide is added, and the reaction is continued for a total of 30 hours, at which time the pot temperature reaches 74.5°. The reflux condenser is then replaced by a distillation head. The excess propionaldehyde (119 g.) is distilled under atmospheric pressure, b.p. 48-49°. Succinate 1 is distilled under reduced pressure. The main fraction, b.p. 145-151.5° (15-16 mm), provides 417-449 g. (75-81%) of product having sufficient purity for use in the next step (Note 4). 

Cyclopropanation.2 This metal carbonyl cluster is an effective catalyst for cyclo-propanation of alkenes with ethyl diazoacetate. Minor by-products are diethyl maleate and fumarate, but products of allylic C -H insertion are not formed. The yield of the cyclopropane can be increased if the ethyl diazoacetate is added slowly over a period of 6 hours to the olefin and catalyst. Under these conditions yields of eyclopropanes are 85 -90%. 

As expected, azide addition to dimethyl maleate is very sluggish, and a triazoline is not isolated32 because the LUMOfumarale < LUMOmaleale.304a Recently, however, it has been found that azide coordinated in a cobalt chelate complex [N3Co(DH)2NH3] is sufficiently reactive to add to diethyl maleate, and 25% of the pure triazoline has been obtained (Scheme 80).30 5... 

Nishihata, T., et al. 1987. Influence of diethyl maleate-induced loss of thiol on cefmetazole uptake into isolated epithelical cells and on cefmetazole absorption from ileal loop of rats. Chem Pharm Bull 35 2914. 

A mixture of the oxazole (I) with two moles of diethyl maleate (Ila) is heated and the adduct cleaved with ethanolic hydrogen chloride to form the diethyl ester of 2-methyl-3-hydroxy-pyridine-4,5-dicarboxylic acid hydrochloride (Ilia) (85%). This diester is reduced with lithium aluminum hydride to pyridoxine (41-42) isolated as its hydrochloride. 

Mixed coupling of two dissimilar activated olefins A and B is best rationalized by path 3). To suppress the formation of symmetric dimers AA and BB besides the wanted mixed dimer AB the difference in reduction potential between A and B should be 0,2 to 0,4 V. Cpe at the potential of the more easily reducible olefin A with an excess of B present in the electrolyte yields predominantly AB. With equal amounts of A and B AA and AB are obtained and with small differences in the reduction potentials of A and B all three possible dimers are formed. Thus coreduction of diethyl maleate (Ei/2 = -1,32 V.) and acrylonitrile (E j. 2 = -1,94 V.) by cpe at -1,4 V yielded 15-3 (AA) and 154 (AB). Cpe at -1,7 V of 6 equivalents of AN and one equivalent of cyanobutadiene (Ejy2 =... 

A reaction in which the oxidized or reduced form of a compound isomerizes via a first-order process on the voltammetric time-scale is common for a wide range of organometallic and organic compounds (for example Bard etal., 1973 Bond et al., 1986,1988,1992). An example from the field of organic chemistry involves the reduction of diethyl maleate to its radical anion which then isomerizes to the diethyl fumarate anion, again an overall EC mechanism (Bard et al., 1973). There is a wide range of examples of other EC mechanisms such as the reduction of the antibiotic chloramphenicol in which a nitro unit (-NO2) is reduced to a hydroxylamine (-NHOH) (E step) which rapidly converts into a nitroso (-NO) species (C step) (Kissinger and Heineman, 1983). 

These methods stiU show limitations. The reduction of (550a) with activated nickel in the presence of diethyl maleate gave a 50 50 mixture of cis and trans adducts (entry 4), probably due to a nickel-promoted cisitrans isomerization of the dienophile prior to cycloaddition. Homogeneous reduction using (ZrCh failed with a dibromide precursor containing a quinone moiety. ... 

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