3-甲基-2-[3-(2-呋喃基)丙烯甲酰]-喹喔啉-1,4-二氮氧化物合成研究
|
摘要
为改善3-甲基-2-[3-(2-呋喃基)丙烯甲酰]-喹喔啉-1,4-二氮氧化物的制备工艺,寻找一种与喹烯酮结构相似,但药效更好、毒性更低的喹喔啉类兽药,参考喹烯酮的制备工艺,对苯并呋咱-N-氧化物环氧化反应条件,乙酰甲喹制备工艺,目标物制备条件进行了研究。试验用25%氨水作为催化剂,优化了催化剂用量,缩短了反应时间,提高了目标物产率,使目标物产率达到88.95%。合成的产物理化性质和光谱分析证明系为所合成的目标物。
In order to improve the preparation process of study on the synthesis of 3- methyl- 2-[3-( 2- furyl)propylene formyl- quinoxaline- 1,4- two oxides of nitrogen,and seek a similar structure with quinocetone,but have better efficacy, less toxicity quinoxaline veterinary drugs, this paper refers to preparation method of quinocetone and studies the reaction conditions of benzofurazan- N- compoundepoxidation,the process of mequindox preparation and the preparation conditions of the target. It uses 25% ammomia as catalyst and optimizes the dosage of the catalyst,shortens the reaction time and improves the yield of target product which runs up to88. 95%. The product is synthesized by physical and chemical properties and spectral analysis,and it proves the synthesized product for the target.
In order to improve the preparation process of study on the synthesis of 3- methyl- 2-[3-( 2- furyl)propylene formyl- quinoxaline- 1,4- two oxides of nitrogen,and seek a similar structure with quinocetone,but have better efficacy, less toxicity quinoxaline veterinary drugs, this paper refers to preparation method of quinocetone and studies the reaction conditions of benzofurazan- N- compoundepoxidation,the process of mequindox preparation and the preparation conditions of the target. It uses 25% ammomia as catalyst and optimizes the dosage of the catalyst,shortens the reaction time and improves the yield of target product which runs up to88. 95%. The product is synthesized by physical and chemical properties and spectral analysis,and it proves the synthesized product for the target.
引文
[1]李岚,孙凌莉,江才鑫.2,6-二氯喹喔啉的合成研究[J].浙江化工,2011,(6):11.
[2]赵翠花,陈奕,丁健,等.喹喔啉衍生物的设计合成及抗肿瘤活性研究[J].药学学报,2005,(9):46-51.
[3]Carta A,Pagliteei G,Rahbar Nikookar M E,et al,Zanetti S.Novel substituted quinoxaline 1,4-dioxides with in vitro antimycobacterialand anticandida activity[J].European Journal of Medicinal Chemistry,2002,37(5):355-366.
[4]李荀,杨康辉,曲显俊,等.喹喔啉酮类化合物的研究进展[J].中国药物化学杂志,2007,(3):62-66.
[5]马敬中,占升卫,胡超男,等.1,4-二氧喹喔啉甲醛亚胺的合成和抑菌活性[J].应用化学,2006,(6):63-66.
[6]许建宁,王全凯,崔涛,等.新兽药喹烯酮亚慢性经口毒性研究[J].中国兽药杂志,2005,39(3):13-18.
[7]李娟,刘东升,许东宝,等.喹烯酮对仔猪生产性能影响的研究[J].中国饲料,2004,(23):29.
[8]P.F.Barbara,P.M.Rentzepis,L.E.Brus.Thermochemical studies on the 3-methyl-quinoxaline-2-carboxamide-1,4-dioxide derivatives:enthalpies of formation and of N-O bond dissociation[J].The Journal of Physical Chemistry,2007,12(4):231-240.
[9]John P.Dirlam,Joseph E.Presslitz.Synthesis and Antibacterial activity of isomeric 6-and 7-acetyl-3-methyl-2-quinoxalinecarboxamide 1,4-dioxides[J].Journal of Medicinal Chemistry,1978,21(4):121-130.
[10]蔡佩君,马恒俊,赵长春.2,6-二氯喹喔啉的合成[J].徐州师范大学学报(自然科学版),1999,(2):33-35.
[11]王厚勇,刘方明,阎琴,等.5-甲基-3-喹喔啉-2-基-4-乙氧羰基异噁唑及其衍生物的合成[J].有机化学,2005(1):13-16.
[12]范磊刚,杨晓慧.聚乙二醇及其衍生物催化合成苯并呋咱-N-氧化物-N-氧化物-N-氧化物的研究[J].工业催化,2005,13(12):43-47.
[16]6H-吲哚并[3,2-b]喹喔啉衍生物的合成[A].中国化学会第十届全国有机合成化学学术研讨会会议论文集[C].2012.
[13]Yoshiro Kobayashi,Itsumaro Kumadaki,Haruo Sato.Studies on the reaction of heterocyclic compounds.Ⅶ.Oxidative Cyanation of heteroaromatic N-Oxides[J].Journal of Organic Chemistry,1972,23(5):234-240.
[14]Pranab Ghosh,Amitava Mandal.Synthesis of functionalized benzimidazoles and quinoxalines catalyzed by sodium hexafluorophosphate bound Amberlite resin in aqueous medium[J].Tetrahedron Letters,2012,53(48):6483-6488.
[15]张道凌,梁剑平,崔颖.等.喹噁啉类药物抗肿瘤与抗菌活性的研究进展[J].中国兽药杂志,2008,42(4):37-40.
[16]张道陵.喹喔啉类化合物及其构效关系的研究[J].北京:中国农业科学院,2008.
[2]赵翠花,陈奕,丁健,等.喹喔啉衍生物的设计合成及抗肿瘤活性研究[J].药学学报,2005,(9):46-51.
[3]Carta A,Pagliteei G,Rahbar Nikookar M E,et al,Zanetti S.Novel substituted quinoxaline 1,4-dioxides with in vitro antimycobacterialand anticandida activity[J].European Journal of Medicinal Chemistry,2002,37(5):355-366.
[4]李荀,杨康辉,曲显俊,等.喹喔啉酮类化合物的研究进展[J].中国药物化学杂志,2007,(3):62-66.
[5]马敬中,占升卫,胡超男,等.1,4-二氧喹喔啉甲醛亚胺的合成和抑菌活性[J].应用化学,2006,(6):63-66.
[6]许建宁,王全凯,崔涛,等.新兽药喹烯酮亚慢性经口毒性研究[J].中国兽药杂志,2005,39(3):13-18.
[7]李娟,刘东升,许东宝,等.喹烯酮对仔猪生产性能影响的研究[J].中国饲料,2004,(23):29.
[8]P.F.Barbara,P.M.Rentzepis,L.E.Brus.Thermochemical studies on the 3-methyl-quinoxaline-2-carboxamide-1,4-dioxide derivatives:enthalpies of formation and of N-O bond dissociation[J].The Journal of Physical Chemistry,2007,12(4):231-240.
[9]John P.Dirlam,Joseph E.Presslitz.Synthesis and Antibacterial activity of isomeric 6-and 7-acetyl-3-methyl-2-quinoxalinecarboxamide 1,4-dioxides[J].Journal of Medicinal Chemistry,1978,21(4):121-130.
[10]蔡佩君,马恒俊,赵长春.2,6-二氯喹喔啉的合成[J].徐州师范大学学报(自然科学版),1999,(2):33-35.
[11]王厚勇,刘方明,阎琴,等.5-甲基-3-喹喔啉-2-基-4-乙氧羰基异噁唑及其衍生物的合成[J].有机化学,2005(1):13-16.
[12]范磊刚,杨晓慧.聚乙二醇及其衍生物催化合成苯并呋咱-N-氧化物-N-氧化物-N-氧化物的研究[J].工业催化,2005,13(12):43-47.
[16]6H-吲哚并[3,2-b]喹喔啉衍生物的合成[A].中国化学会第十届全国有机合成化学学术研讨会会议论文集[C].2012.
[13]Yoshiro Kobayashi,Itsumaro Kumadaki,Haruo Sato.Studies on the reaction of heterocyclic compounds.Ⅶ.Oxidative Cyanation of heteroaromatic N-Oxides[J].Journal of Organic Chemistry,1972,23(5):234-240.
[14]Pranab Ghosh,Amitava Mandal.Synthesis of functionalized benzimidazoles and quinoxalines catalyzed by sodium hexafluorophosphate bound Amberlite resin in aqueous medium[J].Tetrahedron Letters,2012,53(48):6483-6488.
[15]张道凌,梁剑平,崔颖.等.喹噁啉类药物抗肿瘤与抗菌活性的研究进展[J].中国兽药杂志,2008,42(4):37-40.
[16]张道陵.喹喔啉类化合物及其构效关系的研究[J].北京:中国农业科学院,2008.