Abstract:

In the synthesis of pyrrole 2-ethoxycarbonyl-3-trifluoromethyl-4-methylpyrrole(1) from 2-acetoxy-3-nitro-1,1,1-trifluorobutane(1b) and ethyl isocyanoacetate according to the BartonZard reaction, the organic base 1,8-diazabicyclo-[5.4.0-] undec-7-ene(DBU) and the solvent tetrahydrofuran(THF) were replaced with K2CO3 and ethanol, respectively. The improved Barton-Zard procedure had advantages such as less expensive and safe reagents, higher yield and more convenient operation procedures than original Barton-Zard method. Moreover, the preparation of the intermediate 1b from compound 1a by acetylation reaction was carried out by employing acetyl chloride in boiling toluene solution instead of acetic anhydride and the catalyst concentrated sulfuric acid. Its optimum reaction conditions were that the molar ratio of acetyl chloride to compound 1a and reaction time were set as 1.2∶1 and 3～3.5 h, respectively. After treatment of compound 1 with excess LiAlH4 at low temperature, it affords the crude product-α-(hydroxymethyl)-3-trifluoromethyl-4-methylpyrrole(1c), which immediately reacted via a tetramerization in the presence of the catalyst BF3·OEt2 and in CHCl3, followed by oxidation of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone(DDQ) to provide the corresponding trifluoromethylated porphyrin derivative 2. The results indicate that using boron trifluoride diethyl etherate (BF3·OEt2) as catalyst instead of p-toluenesulphonic acid(p-TsOH) in the synthesis of compound 2 from compound 1c can significantly increases the yield of product 2 up to 50% from 14%.

Key words: thoxycarbonyl-trifluoromethyl-methylpyrrole, acetyl chloride, BF3·OEt2 catalyst, Barton-Zard reaction, trifluoromethylated porphyrin