Ethyl fumarate reactions

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

Heat is developed during the reaction, and the mixture may be kept boiling by adding the ethyl fumarate at a suitable rate. 

The results under flow conditions showed a slight improvement in nearly all areas compared with the representative batch reaction - importantly, both the yield and chemoselectivity were significantly improved - but all reactions still produced a significant amount of the dimerized by-products (ethyl fumarate (57) and ethyl maleate (58)). The solventless system allowed larger quantities of material to be prepared, whereas the scC02 system provided products contaminated with only traces of ruthenium (less than 1 ppm). 

J-Cyclodextrin catalyzes the reaction of ethyl fumarate with cyclopentadiene, also in water, with enantioselectivity 21 + 5.5%14. 

The principles of conservation of orbital synunfetry can be applied to inter-molecular cycloaddition reactions and to what can be thought of as their reverse, the fragmentation of one molecule into two or more smaller fragments. Let us consider first the Diels-Alder reaction, a reaction of great synthetic usefulness as well as the subject "oT many theoretical and mechanistic speculations and studies. In its simplest form, this reaction is the addition of an olefin to a conjugated diene to give a cyclohexene. It is termed a [4 -I- 2]-cycloaddition reaction, since it involves a four-7r-electron system and a two-7r-electron system. All available data indicate that the reaction is a concerted one that proceeds stereospecifically by cis addition to the double bond. This stereospecificity is exemplified by the formation of stereoisomeric products from the reaction of butadiene with ethyl maleate and ethyl fumarate ... 

In this reaction the thermodynamically favoured enantiomeric pair Z-67 is preferentially formed. A complication is that ethyl diazoacetate can dimerise to form ethyl fumarate and maleate so the rate of addition of ethyl diazoacetate has to be slow to achieve high conversions. 

Occasionally, a contaminant in unsaturated polyester resins due to the reaction between free fumaric acid and ethanol. Sometimes occurs as contaminant in the insecticide Malathion Synonyms ethyl fumarate 2-butenedioic acid (E) diethyl ester... 

The reaction rate of fumarate polyester polymers with styrene is 20 times that of similar maleate polymers. Commercial phthaHc and isophthaHc resins usually have fumarate levels in excess of 95% and demonstrate full hardness and property development when catalyzed and cured. The addition polymerization reaction between the fumarate polyester polymer and styrene monomer is initiated by free-radical catalysts, commercially usually benzoyl peroxide (BPO) and methyl ethyl ketone peroxide (MEKP), which can be dissociated by heat or redox metal activators into peroxy and hydroperoxy free radicals. 

A solution of 3-dimethylsulfamoylphenthiazine (5 g) in anhydrous xylene (100 cc) is heated under reflux for 1 hour with sodamide (0.67 g). 3-(4-methyl-1-piperazinyl)-1 heated under reflux for 5 hours. After treatment of the reaction products, a crude oily base (2.5 g) is obtained after treatment. By the addition of a solution of fumaric acid in ethanol to an ethanolic solution of the base, 3-dimethylsulfamoyl-10-(3-4 -methyl-1 -piperazinylpropyD-phenthiazine diacid fumarate (2.6 g) is obtained, melting point 182°C. The base recrystallized from ethyl acetate melts at about 140°C. 

The importance of the relationship between the macrocycle cavity and the binding of two reagents is shown by the cycloadditions of cyclopentadiene with diethyl fumarate and ethyl acrylate in aqueous solution. The presence of jS-CD strongly accelerates the first cycloaddition, while it slows down the reaction rate of the second, probably because the cavity favors the binding of two molecules of either diene or dienophile [65c]. 

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. 

The possibility of recycling the catalyst was also studied. In order to decrease the amount of ethyl maleate and fumarate, the addition rate of ethyl diazoacetate was reduced and the reaction temperature was kept low during the addition. Furthermore, the catalyst concentration was reduced by doubling the volume of ionic liquid. Under these conditions the catalyst was reused seven times, although both the yield and the enantioselectivity decrease from the fourth reuse on (entry 6 in Table 6). 

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... 

Reaction of the imine moiety of 278 with excess ethyl diazoacetate in the presence of Cu(acac)2 led to the cyclopentane-annulated product 279 the structure of which was confirmed by an X-ray analysis 262. It is assumed that 279 results from reaction between a carbene dimer (diethyl fumarate) and an intermediate N-ylide or the... 

The EfZ ratio of stilbenes obtained in the Rh2(OAc)4-catalyzed reaction was independent of catalyst concentration in the range given in Table 22 357). This fact differs from the copper-catalyzed decomposition of ethyl diazoacetate, where the ratio diethyl fumarate diethyl maleate was found to depend on the concentration of the catalyst, requiring two competing mechanistic pathways to be taken into account 365), The preference for the Z-stilbene upon C ClO -or rhodium-catalyzed decomposition of aryldiazomethanes may be explained by the mechanism given in Scheme 39. Nucleophilic attack of the diazoalkane at the presumed metal carbene leads to two epimeric diazonium intermediates 385, the sterically less encumbered of which yields the Z-stilbene after C/C rotation 357,358). Thus, steric effects, favoring 385a over 385 b, ultimately cause the preferred formation of the thermodynamically less stable cis-stilbene. 

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. 

In addition to the reactions mentioned, ethyl diazoacetate takes part in many condensations with acetylene and ethylene derivatives, when the nitrogen is retained in the molecule. Thus, with esters of fumaric acid, for example, pyrazoline tricarboxylic esters are produced ... 

Ethyl mercaptan reacts with DMAD to give a 1 1 adduct through a trans mode of addition. WeibulP has reported that a mixture of both fumarate and maleate is formed from cyclohexyl mercaptan with propiolic acid. A similar observation has been made in the reaction of cyclohexyl mercaptan with acetylenedicarboxylic acid. ... 

---