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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K2CO3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(BF3.OEt2)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BF3.OEt2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%。
Barton-Zard reaction of 2-methoxycarbonyl-3-nitro-1,1,1-tri-fluorobutane (1b) with ethyl isocyanoacetate to prepare 2-carbomethoxy-3-trifluoromethyl- Methylpyrrole (1), K2CO3 and ethanol were used instead of the organic base 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and the tetrahydrofuran solvent, respectively, The improved Barton-Zard method has the advantages of simple operation, cheap reagents, low toxicity and higher yield. In addition, in the conversion of 3nitro-1,1,1-tris-fluoro-2-butanol-alcohol (1a) to the intermediate 1b by acetylation, a toluene solution of boiling temperature and acetyl chloride were used in place of concentrated sulfuric acid The optimized reaction conditions of synthesizing compound 1b were determined as follows: the molar ratio of acetyl chloride to reactant 1a was 1.2:1, and the reaction time was 3 ~ 3.5 h. According to the improved porphyrin synthesis method, the pyrrole 1 is reduced with an excess of lithium aluminum hydride at a low temperature, and the crude α-hydroxymethyl-trifluoromethyl-4-methylpyrrole (1c ), The tetramethylation reaction was immediately carried out in untreated chloroform solvent using boron trifluoride diethyl ether (BF3.OEt2) as a catalyst, and then 2,3-di-chloro-5,6-dicyano -1,4-benzene-quinone (DDQ) was oxidized to synthesize trifluoromethyl-substituted porphyrin derivative 2. It was found that when product 2 was prepared from compound 1c, p-TsOH was replaced with BF3.OEt2 as a catalyst to increase the yield of product 2 from 14% to 50% under the indicated reaction conditions.