BF_3·Et_2O催化Pechmann反应一锅合成3-氨基-5,7-二羟基-4-甲基香豆素
|
摘要
3-氨基-5,7-二羟基-4-甲基香豆素(4)是一种新的重要有机合成中间体,可用于多种潜在生物活性物质的合成。本文将间苯三酚与2-乙酰氨基乙酰乙酸乙酯(2)在BF_3·Et_2O催化下,经串联的Pechmann缩合反应和脱乙酰基反应一锅合成4。化合物2由乙酰乙酸乙酯经成肟、还原、酰化反应制得。中间体和目标物的结构均经1H NMR、13C NMR、MS表征。该方法具有原料廉价易得、步骤短、操作简便易控、反应条件温和、收率高的优点。
3-Amino-5,7-dihydroxy-4-methyl coumarin(4) is a new important organic intermediate,which can be used to synthesize various bioactive agents.In this work,compound 4 was synthesized in one pot from phloroglucinol and ethyl 2-acetylamino acetoacetate(2),which was prepared from ethyl acetoacetate by oxime formation,reduction and acylation successively,by Pechmann condensation and deacetylation in series under the catalysis of BF_3·Et_2O.All intermediates and the final product were confirmed by ~1H NMR、~(13)C NMR and MS.This method has considerable advantages in terms of the use of easily available raw material,less steps,simple operation,mild reaction conditions and high yield.
3-Amino-5,7-dihydroxy-4-methyl coumarin(4) is a new important organic intermediate,which can be used to synthesize various bioactive agents.In this work,compound 4 was synthesized in one pot from phloroglucinol and ethyl 2-acetylamino acetoacetate(2),which was prepared from ethyl acetoacetate by oxime formation,reduction and acylation successively,by Pechmann condensation and deacetylation in series under the catalysis of BF_3·Et_2O.All intermediates and the final product were confirmed by ~1H NMR、~(13)C NMR and MS.This method has considerable advantages in terms of the use of easily available raw material,less steps,simple operation,mild reaction conditions and high yield.
引文
[1]丰翠,闵曼,谢蓉蓉等.应用化学,2018,35(5):538~543.
[2]K Shylaja,V Srinivas,V Ravinder.World J.Pharm.Sci.,2016,4(3):375~383.
[3]A A H Kadhum,A B Mohamad,A A Al-Amiery et al.Molecules,2011,16(8):6969~6984.
[4]B S Shyamala,V J Tyagaraju,P V Ananthalakshmi et al.Acta Cienc.Indica Chem.,2010,36(3):225~230.
[5]R Sharma,S S Soman.Pharmanest,2015,6(1):2679~2684.
[6]M J Matos,S Vilar,S Kachler et al.Bioorg.Chem.,2015,61:1~6.
[7]H Matla,R S Bhosale,S Polepalli et al.Chem.Bio.Interf.,2015,5(1):34~43.
[8]V Maddi,S N Mamledesai,D Satyanarayana et al.Indian J.Pharm.Sci.,2007,69(6):847~849.
[9]M Cussac.FR:2699175 A1,1994.
[10]S Sen,V Srivastava.J.Indian Chem.Soc.,1989,66(3):166~168.
[11]S L Guo,G Liu,C B Fan.RSC Adv.,2018,8(40):22786~22798.
[12]张珍英,邓慧敏,邓芹英.分析化学,2008,36(10):1419~1422.
[13]冯雷,禹兴海,金淑萍等.化学试剂,2012,34(3):257~260.
[14]J E T Corrie.J.Chem.Soc.Perkin Transac.,1990,(7):2151~2152.
[15]张小蓉,张晓婷,黄婉云等.合成化学,2018,26(3):183~185.
[16]汪廷贵.中国科学院大学博士学位论文,2013.
[17]陈文,范长利,曾理强等.高分子学报,2008,(9):861~866.
[18]万益群,马木林,徐景坤.南昌大学学报(理科版),2008,32(6):580~582.
[19]M N Sun,J F Hu,X Y Song et al.Eur.J.Med.Chem.,2013,67:39~53.
[20]G Li,D M Wang,M N Sun et al.J.Med.Chem.,2010,53(4):1741~1754.
[21]A Homer,R E Wilkins.J.Am.Chem.Soc.,1938,60(6):1328~1331.
[22]N F Albertson,B F Tullar,J A King et al.J.Am.Chem.Soc.,1948,70(3):1150~1153.
[2]K Shylaja,V Srinivas,V Ravinder.World J.Pharm.Sci.,2016,4(3):375~383.
[3]A A H Kadhum,A B Mohamad,A A Al-Amiery et al.Molecules,2011,16(8):6969~6984.
[4]B S Shyamala,V J Tyagaraju,P V Ananthalakshmi et al.Acta Cienc.Indica Chem.,2010,36(3):225~230.
[5]R Sharma,S S Soman.Pharmanest,2015,6(1):2679~2684.
[6]M J Matos,S Vilar,S Kachler et al.Bioorg.Chem.,2015,61:1~6.
[7]H Matla,R S Bhosale,S Polepalli et al.Chem.Bio.Interf.,2015,5(1):34~43.
[8]V Maddi,S N Mamledesai,D Satyanarayana et al.Indian J.Pharm.Sci.,2007,69(6):847~849.
[9]M Cussac.FR:2699175 A1,1994.
[10]S Sen,V Srivastava.J.Indian Chem.Soc.,1989,66(3):166~168.
[11]S L Guo,G Liu,C B Fan.RSC Adv.,2018,8(40):22786~22798.
[12]张珍英,邓慧敏,邓芹英.分析化学,2008,36(10):1419~1422.
[13]冯雷,禹兴海,金淑萍等.化学试剂,2012,34(3):257~260.
[14]J E T Corrie.J.Chem.Soc.Perkin Transac.,1990,(7):2151~2152.
[15]张小蓉,张晓婷,黄婉云等.合成化学,2018,26(3):183~185.
[16]汪廷贵.中国科学院大学博士学位论文,2013.
[17]陈文,范长利,曾理强等.高分子学报,2008,(9):861~866.
[18]万益群,马木林,徐景坤.南昌大学学报(理科版),2008,32(6):580~582.
[19]M N Sun,J F Hu,X Y Song et al.Eur.J.Med.Chem.,2013,67:39~53.
[20]G Li,D M Wang,M N Sun et al.J.Med.Chem.,2010,53(4):1741~1754.
[21]A Homer,R E Wilkins.J.Am.Chem.Soc.,1938,60(6):1328~1331.
[22]N F Albertson,B F Tullar,J A King et al.J.Am.Chem.Soc.,1948,70(3):1150~1153.