5-氯甲酰氧基异肽酰氯的制备

以三光气(简称BTC)为酰氯化剂,与 5 -羟基异酞酸在复合催化剂作用下制备了 5- 氯甲酰氧基异肽酰氯(简称CFIC),收率最高可达 42 .3%。分析了反应条件的改变对产品收率的影响。反应物量比R〔n(三光气)∶n(5- 羟基异酞酸)〕≤1 .1时,产品收率很低,几乎得不到产品; 1. 11 7时,影响不大。溶剂极性越大,反应越快,收率越高。复合催化剂(三乙胺 /咪唑、吡啶 /咪唑)的催化效果远远优于单一催化剂(N,N -二甲基甲酰胺、三乙胺、吡啶和咪唑)。反应适宜在 5 ~20℃操作,温度高于 30℃时,反应很难进行。反应时间较短时,对产品收率影响较大,当时间大于 24h后,影响不大。利用正交实验确定的最佳工艺条件为:反应物量比为 1. 67;催化剂为m(咪唑)∶m(吡啶) =1∶4及m(吡啶+咪唑)∶m(三光气) =0. 08∶1;反应温度5~10℃。用红外光谱仪分析产品的主要官能团:在 1785. 24、1764 .12、1603 .20cm-1和 1557. 99cm-1处有强吸收峰,它们分别为Ar—OCOCl、Ar—COCl与三取代基苯环。用高效液相色谱仪测得w(CFIC) =99. 4%,用数字熔点仪测得产品熔点为 56. 7~57. 0℃。推测了三光气在催化剂作用下的反应机理。

Preparation of 5-Chloroformyloxyisophthaloyl Chloride

Triphosgene(BTC) was used as a carbonyl chlorinating agent to prepare 5-chloroformyloxyisophthaloyl chloride(CFIC) from 5-hydroxyisophthalic acid(HIA) in the presence of composite catalysts,and the top yield of CFIC was 42.3%.Effects of reaction conditions on the product yield were discussed.If the mole ratio of BTC to HIA was less than 1.1,few products could be obtained.When the ratio was between 1.1 and 1.7,the higher the ratio,the more the yield.Mole ratio higher than 1.7 hardly affected the yield.The higher polarity the solvent has,the quicker the reaction was.Effect of composite catalysts (triethylamine/imidazole,pyridine/imidazole) was more excellent than the single catalysts (N,N-dimethylformamide,triethylamine,pyridine,imidazole).Low temperature of 5～20 ℃ was suitable to the reaction,and the reaction hardly carried out at temperature higher than 30 ℃.Short reaction time affected the yield obviously,but reaction time longer than 24 h was not neccessary.Suitable preparation technology was obtained by orthogonal tests,i.e.,n(BTC)/n(HIA)=1.67,the composite catalyst n(imidezole)∶n(pyridine)=1∶4,m(BTC)∶m(CATALYST)=1∶0.08,and reaction temperature 5～10 ℃.The main functional groups were analyzed by IR 200.The strong absorption peaks at 1785.24,1764.12,1603.20 and 1557.99 cm~(-1) indicated respectively the function groups Ar—OCOCl,Ar—COCl and 1,3,5-tri substituted benzene ring.Weight percent of the product CFIC was 99.4% as measured by P680 HPLC.The melting point of CFIC was 56.7～57.0 ℃.Reaction mechanism of BTC and effects of the composite catalyst were assumed.