3-氨基呋咱-4-羧酸的合成
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摘要
以氰基乙酸甲酯为原料,经过取代、环化成盐、水解制备3-氨基呋咱-4-羧酸。利用红外光谱、核磁共振波谱、元素分析及质谱确证了产物结构,并考察了物料比、反应温度、反应时间和溶剂用量对环化成盐反应的影响及反应溶剂、pH、温度对酸化反应的影响,发现增加氢氧化钾用量、提高反应温度、降低体系pH有利于目标物收率提高。得到的最佳环化成盐反应条件为∶n(盐酸羟胺)∶n(氢氧化钾)∶n(2-氰基-2-肟基乙酸甲酯)=1∶2∶1,缩合温度25℃,缩合时间2h,环化温度80℃,环化时间2h,溶剂水50 mL;最佳酸化反应条件为:溶剂水30 mL,pH≤1,反应温度5℃,环化成盐反应和酸化反应的总收率为79.73%,高于文献报道的64%。
3-Aminofurazan-4-carboxylic acid was synthesized from methyl cyanoacetate via substitution,annulation-salt forming reaction and hydrolysis. The structure of the product was characterized by FTIR,NMR and MS. The effects of molar ratio of reactants, reaction temperature, reaction time and solvent dosage on the annulation-salt forming reaction were investigated. The effects of solvent, p H and reaction time on the acidification reaction were also studied. It was found that increasing the dosage of potassium hydroxide, raising the reaction temperature, and decreasing the pH value of the system were beneficial to increasing the yield of the target product. The best annulation-salt forming reaction conditions were as follows∶n(hydroxylamine hydrochloride)∶n(KOH)∶n〔methyl-2-cyano-2-(hydroxyimino)acetate〕=1∶2∶1, condensation reaction temperature 25 ℃, condensation reaction time 2 h, cyclization temperature80 ℃, reaction time 2 h, water as solvent 50 m L. The best acidification reaction conditions were that reaction temperature 5 ℃, pH≤1 and water 30 mL. The total yield of annulation-salt forming reaction and hydrolysis was 79.73%, higher than 64% reported in literature.
3-Aminofurazan-4-carboxylic acid was synthesized from methyl cyanoacetate via substitution,annulation-salt forming reaction and hydrolysis. The structure of the product was characterized by FTIR,NMR and MS. The effects of molar ratio of reactants, reaction temperature, reaction time and solvent dosage on the annulation-salt forming reaction were investigated. The effects of solvent, p H and reaction time on the acidification reaction were also studied. It was found that increasing the dosage of potassium hydroxide, raising the reaction temperature, and decreasing the pH value of the system were beneficial to increasing the yield of the target product. The best annulation-salt forming reaction conditions were as follows∶n(hydroxylamine hydrochloride)∶n(KOH)∶n〔methyl-2-cyano-2-(hydroxyimino)acetate〕=1∶2∶1, condensation reaction temperature 25 ℃, condensation reaction time 2 h, cyclization temperature80 ℃, reaction time 2 h, water as solvent 50 m L. The best acidification reaction conditions were that reaction temperature 5 ℃, pH≤1 and water 30 mL. The total yield of annulation-salt forming reaction and hydrolysis was 79.73%, higher than 64% reported in literature.
引文
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[2]Rodney L,Robson F,William L,et al.Synthesis and crystal structure of octahydro-5H,12H-4,11-methano-1H,7H-bis[1,2,5]oxadiazolo[3,4-d:3',4'-j]-[1,7,3,9]dioxadiazacyclododecine[J].Journal of Heterocyclic Chemistry,2012,45:705-709.
[3]Catrow J,Zhang Y,Zhang M,et al.Discovery of selective smallmolecule inhibitors for theβ-catenin/T-cellfactor protein-protein interaction through the optimization of the acylhydrazone moiety[J].Journal of Medicinal Chemistry,2015,46:113-128.
[4]Sheremeteev A.Chemistry of furazan fused to five-membered rings[J].Journal of Heterocyclic Chemistry,1995,32(2):371-385.
[5]Churakov A,Semenov S,Ioffe S,et al.The oxidation of the heterocyclic amines to nitro compounds using dinirogen pentoxide[J].Mendeleev Communication,1995,(3):102-103.
[6]He Liqin(何黎琴),Gu Hongxia(顾宏霞),Yin Dengke(尹登科),et al.Synthesis and anticancer activity of nitric oxide donorbased matrine derivatives[J].Chemical Journal of Chinese Universities(高等学校化学学报),2010,31(8):1541-1547.
[7]Huo Huan(霍欢),Wang Bozhou(王伯周),Wang Xijie(王锡杰),et al.Research progress in synthesis of furazan energetic compounds and reaction of their derivatives[J].Chemical Propellants&Polymeric Materials(化学推进剂与高分子材料),2013,11(3):15-22.
[8]Li Yanan(李亚南),Zhang Zhizhong(张志忠),Zhou Yanshu:(周彦水),et al.Synthesis and thermal decomposition mechanism of3,4-bis(3',5'-dinitrobenzene-1'-yl)furoxan[J].Chinese Journal of Energetic Materials(含能材料),2011,19(3):262-268.
[9]Zhai Lianjie(翟连杰),Luo Yifen(罗义芬),Li Yanan(李亚南),et al.Synthesis and properties of 3-cyano-4-nitrofuroxan[J].Chinese Journal of Energetic Materials(含能材料),2017,25(6):503-507.
[10]Willer R,Storey R,Deschamps J,et al.Synthesis and crystal structure of4,4'-(methylenediimino)bis-1,2,5-oxadiazole-3-carboxylic acid and carboxamide[J].Journal of Heterocyclic Chemistry,2013,50:949-954.
[11]Zhai Lianjie(翟连杰),Wang Bozhou(王伯周),Li Yanan(李亚南),et al.Crystal structure and thermal behavior of 3,4-bis(3-cyanofurazan-4-oxy)furazan(FOF-12)[J].Chinese Journal of Explosives&Propellants(火炸药学报),2013,50:949-954.
[12]Michels H,Montgomery J,Christe K,et al.Theoretical prediction of the structures and stabilities of azidamines[J].Journal of Physical Chemistry,1995,A99:187-194.
[13]Cousins,Poulsen A,Sanders,J.Dynamiccombinatorial libraries of pseudo-peptide hydrazone macrocycles[J].Chemistry Communication,1999,28:1575-1576.
[14]Poulsen.Direct screening of a dynamic combinatorial library using mass spectrometry[J].Journal of American Society Mass Spectrom,2006,17:1074-1080.
[15]Bhat V,Caniard A,Luksch T,et al.Nucleophilic catalysis of acylhydrazone equilibration for protein-directed dynamic covalent chemistry[J].Nature Chemistry,2010,2(6):490-497.
[16]Bunyapaiboonsri T,Ramstrom O,Lohmann S,et al.Dynamic deconvolution of a pre-equilibrated dynamic combinatorial library of acetylcholinesterase inhibitors[J].Chem Bio Chem,2001,2(6):438-444.
[17]Bunyapaiboonsri T,Ramstrom H,Ramstrom O,et al.Generation of bis-cationicheterocyclic inhibitors of Bacillus subtilis HPr kinase/phosphatase from a ditopic dynamic combinatorial library[J].Journal of Medicinal Chemistry,2003,46:5803-5811.
[18]Eddy W,Brent D,Brian W,et al.Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanomamodel[J].Journal of Medicinal Chemistry,2009,52:7364-7367.
[19]Shen Huaping(沈华平),Lu Yanhua(卢艳华),Cao Yilin(曹一林),et al.Synthesis and characterization of novel insensitive energetic plasticizer 3-nitrofurazan-4-monomethyl ether[J].Chinese Journal of Energetic Materials(含能材料),2011,19(6):735-738.
[20]Sheremetev B,Konkina S,Yudin I,et al.(Pyrrol-1-yl)furazans[J].Russian Chemical Bulletin,International Edition,2003,52(6):1413-1418.
[21]Kevin G.Improved synthesis of 3-aminofurazan-4-carboxylic acid[J].Organic Preparations and Procedures international:The New Journal for Organic Synthesis,2004,36(4):361-362.
[22]Aleksei B,Nataliya S,Dmitrii E.Synthesis and X-ray study of novel azofurazan-annulatedmacrocyclic lactams[J].Journal of Heterocyclic Chemistry,2005,42:519-525.
[23]Rodney L,Robson F,Mark F,et al.Crystal structures of the"Two"4-aminofurazan-3-carboxylic acids[J].Journal of Heterocyclic Chemistry,2012,49:227-231.
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