Fumaroyl chloride

Whereas for the hexamethyl compound 150 only products formed by the linear route have been detected with a sizeable number of dienophiles (X=X inter alia TCNE, maleic anhydride, benzoquinone, 1,4-naphthoquinone, acrolein, methyl acrylate102), the parent system 4 undergoes threefold Diels-Alder addition in a star-shaped manner leading to 164 with dimethyl acetylenedicarboxylate and to 165 with fumaroyl chloride followed by methanolysis (equation 20)92. 

FNA was synthesized by reaction of /(-naltrexamine (48) with the monomethyl ester of fumaroyl chloride [79], Amine (48) was prepared first from naltrexone by reductive amination with sodium cyanoborohydride in the presence of ammonium acetate to give 6a- and 6/i-epimers (ratio ca. 2 1). Separation was achieved by fractional crystallization [83], An improved synthesis of (48) was reported via the dibenzyliminium salt of naltrexone (46 easily accessible from naltrexone and dibenzylamine) which was reduced with sodium cyanoborohydride to give exclusively the 6/i-epi-mer (47). Catalytic hydrogenolysis afforded /i-naltrexamine (Scheme 3.6) [84]. 

Since the [6]radialenes are triple-diene systems, it comes as no surprise that they have been used in multiple Diels-Alder reactions. In fact, after a first 1 1 addition with 150, leading to 161, has taken place, the reaction could proceed in two fashions—a linear course of addition leading to a ara-xylylene 162, and an angular route which produces an crf/ic-xylylene intermediate 163 (equation 19)102-103 Whereas for the hexamethyl compound 150 only products formed by the linear route have been detected with a sizeable number of dienophiles (X=X inter alia TCNE, maleic anhydride, benzoquinone, 1,4-naphthoquinone, acrolein, methyl acrylate ), the parent system 4 undergoes threefold Diels-Alder addition in a star-shaped manner leading to 164 with dimethyl acetylenedicarboxylate and to 165 with fumaroyl chloride followed by methanolysis (equation 20). ... 

The first 5-fluorouracil containing polymer had the 5-FU units in the polymer backbone and this structure is shown below as (XVI). This was claimed to be biologically active (47). More recently, monomer (XVII) was prepared by the reaction of 5-FU with methyl fumaroyl chloride. The polymers and copolymers of (XVII) do show antitumor activity but this may be due to the hydrolysis of this unit to release 5-FU (48). 

Fumaroyl chloride 1115 Maleic anhydride (98 g), ca. 94% phthaloyl chloride (230 g), and anhydrous ZnCl2 (2 g) are placed in a flask fitted with a thermometer reaching almost to the bottom and with a 30-cm column which has a heating mantle and is attached to a descending condenser. The mixture is heated for 2 h in an oil-bath so that the internal temperature of the mixture is 130-135° (not higher ) and then allowed to cool to 90-95°, whereafter the crude fumaroyl dichloride is distilled off as fast as possible (b.p. 60-85°/14 mm). Slow fractionation of the distillate gives a 82-95% yield of chloride, b.p. 62-64°/13 mm. This is best stored in a sealed vessel. 

We had previously sought to determine the configuration of C9 through X-ray analysis but stmggled to obtain crystals of sufficient quality despite several attempts with different intermediates. In the end, we decided to use the previously described Curtius rearrangement sequence with p-bromobenzoyl chloride in place of the fumaroyl chloride. Gratifyingly, amide 68 did provide crystals suitable for X-ray analysis (Figure 5). 

Poly(bis-l,2,4-triazole)s are a class of polymers in which two triazole rings are immediately adjacent. These polymers can be obtained by the reaction of oxalic acid bis-amidrazone with aromatic dicarboxylic acid dihalides or with fumaroyl chloride and subsequent cyclodehydration of the poly(acyl oxamidrazone)s. The process is shown in Figure 9.3. 

Fumaric acid, 2, 24, 146, 147, 150, 400 Fumaroyl chloride, 305 Germanium oxide, 351 Glycidyl acrylate, 312 Af-Glycidylcarbazole, 13 Glycidyl methacrylate, 314, 365 7-Glycidylpropylmethoxysilane, 404 Glyeidyl tosylate, 151 Heteropolyacid, 294... 

Fumaroyl chloride is a useful acetylene equivalent in the Diels-Alder reaction. After hydrolysis of the adduct to the dicarboxylic acid, oxidative decarboxylation serves to generate the olefin double bond. 

Recently Butler, et al have prepared another vinyl-type monomer containing 5-fluorouracil by the reaction of 5-FU with methyl fumaroyl chloride and this is shown below as (V). This monomer hydrolyzes rapidly in water but many of the copolymers hydrolyze more slowly and these polymers show promise as an anti-tumor system (47). Controlled release of 5-FU from various polymeric matrices has also been reported recently (48). 

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