Diethyl fumarate

The diethyl fumarate is readily prepared as follows. Reflux a mixture of 146 g. of fumaric acid (Section 111,143), 185 g. (236 ml.) of absolute ethanol, 450 ml. of boizene and 20 g. of concentrated sulphuric acid for 12 hours. Pour into a large volume of water, separate the benzene layer, wash successively with water, saturated lodium bicarbonate solution and water, dry with anhydrous magnesium sulphate, and remove the solvent on a steam bath. Distil the residue and collect the diethyl fumarate at 213-215° the yield is 150 g. 

Reaction of arninoacetonitrile hydrochloride with sodium nitrite provides diazoacetonittile (62). The product undergoes a 1,3-dipolar cycloaddition with diethyl fumarate to yield a pyrazoline intermediate, which without isolation reacts with ammonia in water to furnish the pyrazole [119741-54-7] (63) (eq. 14) (43). 

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. 

Diethyl fumarate [623-91-6] M 172.2, b 218°, d 1.052, n 1.441. Washed with aqueous 5% Na2C03, then with saturated CaCl2 soln, dried with CaCl2 and distd. 

In a similar manner diethyl maleate (actually diethyl fumarate since the basic enamine catalyzes the maleate s isomerization upon contact) forms unstable 1,2 cycloadducts with enamines with hydrogens at temperatures below 30°C (37). At higher temperatures simple alkylated products are formed (41). Enamines with no )3 hydrogens form very stable 1,2 cycloadducts with diethyl maleate (36,37,41). The two adjacent carboethoxy groups of the cyclobutane adduct have been shown to be Irons to one another (36,37). 

Chromium (II) sulfate is capable of reducing a variety of functional groups under mild conditions 10). Of particular interest is its ability to reduce a,jS-unsaturated esters, acids, and nitriles to the corresponding saturated compounds. This capability is illustrated in the procedure by the reduction of diethyl fumarate. 

Bamford and Mullik [23] have also investigated a new photoinitiating system composed of Mn2(CO)io or Re2(CO)io with acetylene, acetylene dicarboxylic acid, diethyl fumarate, diethyl maleate, or maleic anhydride. It was concluded that the primary radical responsible... 

The Diels-Alder cycloaddition reaction (Section 14.4) is a pericvclic process that takes place between a diene (four tt electrons) and a dienophile (two tr electrons) to yield a cyclohexene product. Many thousands of examples of Diels-Alder reactions are known. They often take place easily at room temperature or slightly above, and they are stereospecific with respect to substituents. For example, room-temperature reaction between 1,3-butadiene and diethyl maleate (cis) yields exclusively the cis-disubstituted cyclohexene product. A similar reaction between 1,3-butadiene and diethyl fumarate (trans) yields exclusively the trans-disubstituted product. 

IPreparation of 2-trimethylsilyloxybuta-l,3-diene and Diels-Alder addition Iwith diethyl fumarate. 

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. 

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]. 

These investigators also found that dl and meso diethyl 2,3-dibromosuccinate 47, R = C02Et) are both reduced to diethyl fumarate 52>. 

Treatment of 41 with diethyl fumarate under similar conditions gave 50, which displayed physical and spectroscopic properties similar to those of 49. 

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