由2-乙氧羰基-3-硝基-1,1,1-三氟丁烷(1b)与异氰基乙酸乙酯发生Barton-Zard反应制备2-乙氧羰基-3-三氟甲基-4-甲基吡咯(1)的过程中,分别用K<,2>CO<,3>和乙醇代替有机碱1,8-二氮杂二环[5.4.0]十一碳-7-烯(DBU)和四氢呋喃溶剂,这种改进的Barton-Zard方法具有操作简便、试剂价廉易得、溶剂毒性低和产率更高等优点.另外,在3-硝基-1,1,1-三氟-2-丁醇(1a)通过乙酰化反应转变为中间体1b的过程中,用沸腾温度下的甲苯溶液与乙酰氯代替浓硫酸催化下的酸酐反应体系;合成化合物1b的最优化的反应条件被确定为:乙酰氯与反应物1a之间的摩尔比为1.2:1,反应时间为3～3.5 h.又根据改进的卟啉合成法,在低温下用过量氢化铝锂还原吡咯1,将还原所得的尚未干燥或储存的粗产物α-羟甲基-三氟甲基-4-甲基吡咯(1c),立即在未经处理的三氯甲烷溶剂中,以三氟化硼·乙醚(BF<,3>·OEt<,2>)为催化剂进行四聚化反应,然后用2,3-二氯-5,6-二氰基-1,4-苯醌(DDQ)氧化,合成出含三氟甲基取代的卟啉衍生物2.研究发现,由化合物1c制备产物2时,用BF<,3>·OEt<,2>取代p-TsOH作为催化剂,在确定的反应条件下,能够将产物2的收率由14%提高至50%.
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- diazabicyelo [5.4.0] undec-7-ene (DBU) and the solvent tetrahydrofuran (THF) were replaced with K<,2>CO<,3> 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 LiAlH<,4> 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 BF<,3>·OEt<,2> and in CHCl<,3>, followed by oxidation of 2,3-dicldoro-5,6-dicyano-1, 4- benzoquinone(DDQ) to provide the corresponding trifluoromethylated porphyrin derivative 2.The results indicate that synthesis of compound 2 from compound 1c can significantly increases the yield of product 2 up to 50% from 14%.
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