由α-羰基二硫缩烯酮合成吡啶酮衍生物的方法研究
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摘要
作为医药和有机合成中间体,杂环化合物的合成一直受到人们的广泛关注,尤其在多功能化合物的合成或天然产物的合成中。N-取代吡啶酮类化合物具有多方面的生理活性,如杀菌、镇痛、抗肿瘤和治疗帕金森氏症等。由于这类吡啶酮化合物具有很强的配位能力,能与铁等金属离子配位,对治疗地中海贫血症有很好的疗效。它们的衍生物还可以开发成具有识别功能的药物前体。
二硫缩醛/酮是一类重要的有机合成中间体,自1885年被首次合成以来,在有机合成,尤其是多步合成和药物合成中有重要和广泛的应用。它既可作为羰基的极性翻转试剂,还可以在反应中提供硫源,作为硫醇的替代试剂,后者为避免硫醇的使用提供了有效的方法。近十年来,我们研究组一直致力于α-羰基二硫缩烯酮的合成与应用研究,取得了一系列研究成果,合成出了多种多取代的杂环化合物,提出了一系列新颖的合成方法。
本论文的研究工作主要结合α-羰基二硫缩烯酮类化合物的特殊性质,开发出了新型的含氮杂环化合物,工作主要有以下三方面:
1.根据文献报道的合成方法,对α-羰基二硫缩烯酮的合成进行了拓展,合成了2种新的α-羰基二硫缩烯酮化合物。
2.发现了一类新的N-取代吡啶酮化合物,并给出了一种以α-羰基二硫缩烯酮氮芳基取代丁酰胺类化合物和N,N-二甲基甲酰胺二甲基缩醛(DMFDMA)为原料,高效一锅法合成N-取代吡啶酮的新方法。且该方法操作简单、条件温和、产物易于分离、产率高,利用该方法合成同类化合物的可扩展性高。
3.运用量子化学方法,对E-5-二甲氨基-2-(1,3-亚乙二硫)亚甲基-3-羰基-4-烯基苯基戊酰胺和E-5-二甲氨基-2-(1,3-亚乙二硫)亚甲基-3-羰基-4-烯基苯基戊酰胺氮负离子的电荷分布(NBO)情况进行了量化计算分析,结合实验中获得的反应中间体,探讨了N-取代吡啶酮的合成机理。
总之,我们发现了一类新的吡啶酮化合物,给出了其合成方法,该方法简单、条件温和、反应快速、产率高。因此,这类新的吡啶酮化合物在基础研究和实际应用中都具有较好前景。
Synthesis of heterocyclics have been extensively investigated as medicine and versatile intermediates in the synthesis of multi-functional complex molecules and natural products. N-Substituted pyridone compounds have verastile physiological activity.For instance,they can sterilize,ease pain,resist tumour and cure parkinsonism and so forth.These compounds have powerful ability to form coordination compounds,which can cureβ-thalassemia beyond compare.The ramification of N-Substituted pyridone can be made to drug precursors.
α-oxo ketene-S,S-acetals,which are first synthesis from 1885,have been proven to be useful in organic synthesis.Besides the use as thiol equivalents and an umpolung of the carbonyl group,the synthetic potential of dithioacetal functionality has been widely expanded in recent years.The former has provided effective method to avoiding thiols.For the recent decade,during the course of our studies on the chemistry ofα-oxo ketene-S,S-acetals,our group successfully developed novel strategies for the synthesis of highly substituted heterocycles,relying upon the utilization ofα-alkenoyl ketene-S,S-acetals.
Combining with the special properties ofα-oxo ketenedithioacetals,we have succeeded in exploring a new kind of heterocycles.This work mainly based on the following three aspects:
1.We enlarge the synthesis of 2-(1,3-dithiolan-2-ylidene)-3-oxo-N-phenylbutanamides, two newα-oxo-N-phenylbutanamides were synthesised.
2.A facile and efficient one-pot synthesis of substituted pyridine-2,4(1H,3H)-diones has been developed.Subjected to N,N-dimethylformamide dimethyl acetal(DMFDMA) in DMF, a series ofα-acyl,α-carbamoyl ketene-S,S-acetals were converted into the corresponding substituted pyridine-2,4(1H,3H)-diones in high yields.The simple procedure,mild conditions,easy separation,high yields,and wide range of synthetic potential of the products make this protocol much attractive.So these new reagents have good perspective in the field of academic research and practical applications.
3.We calculate the NBO state of(E)-5-(dimethylamino)-2-(1,3-dithiolan-2- ylidene)-3-oxo-N-phenylpent-4-enamide and it's negative ion by quantum chemistry method,and study the mechanism of the reaction acoording to the intermediate that we gain in the experiment.
In summary,we have succeeded in exploring a new kind of N-Substituted pyridones, moreover,providing mechanism of the reaction by quantum chemistry method.This method is associated with some synthetic advantages,such as simple procedure,fast reaction rate, high yields,mild conditions and wide range of synthetic potential of the products make this protocol much attractive.So these new reagents have good perspective in the field of academic research and practical applications.
二硫缩醛/酮是一类重要的有机合成中间体,自1885年被首次合成以来,在有机合成,尤其是多步合成和药物合成中有重要和广泛的应用。它既可作为羰基的极性翻转试剂,还可以在反应中提供硫源,作为硫醇的替代试剂,后者为避免硫醇的使用提供了有效的方法。近十年来,我们研究组一直致力于α-羰基二硫缩烯酮的合成与应用研究,取得了一系列研究成果,合成出了多种多取代的杂环化合物,提出了一系列新颖的合成方法。
本论文的研究工作主要结合α-羰基二硫缩烯酮类化合物的特殊性质,开发出了新型的含氮杂环化合物,工作主要有以下三方面:
1.根据文献报道的合成方法,对α-羰基二硫缩烯酮的合成进行了拓展,合成了2种新的α-羰基二硫缩烯酮化合物。
2.发现了一类新的N-取代吡啶酮化合物,并给出了一种以α-羰基二硫缩烯酮氮芳基取代丁酰胺类化合物和N,N-二甲基甲酰胺二甲基缩醛(DMFDMA)为原料,高效一锅法合成N-取代吡啶酮的新方法。且该方法操作简单、条件温和、产物易于分离、产率高,利用该方法合成同类化合物的可扩展性高。
3.运用量子化学方法,对E-5-二甲氨基-2-(1,3-亚乙二硫)亚甲基-3-羰基-4-烯基苯基戊酰胺和E-5-二甲氨基-2-(1,3-亚乙二硫)亚甲基-3-羰基-4-烯基苯基戊酰胺氮负离子的电荷分布(NBO)情况进行了量化计算分析,结合实验中获得的反应中间体,探讨了N-取代吡啶酮的合成机理。
总之,我们发现了一类新的吡啶酮化合物,给出了其合成方法,该方法简单、条件温和、反应快速、产率高。因此,这类新的吡啶酮化合物在基础研究和实际应用中都具有较好前景。
Synthesis of heterocyclics have been extensively investigated as medicine and versatile intermediates in the synthesis of multi-functional complex molecules and natural products. N-Substituted pyridone compounds have verastile physiological activity.For instance,they can sterilize,ease pain,resist tumour and cure parkinsonism and so forth.These compounds have powerful ability to form coordination compounds,which can cureβ-thalassemia beyond compare.The ramification of N-Substituted pyridone can be made to drug precursors.
α-oxo ketene-S,S-acetals,which are first synthesis from 1885,have been proven to be useful in organic synthesis.Besides the use as thiol equivalents and an umpolung of the carbonyl group,the synthetic potential of dithioacetal functionality has been widely expanded in recent years.The former has provided effective method to avoiding thiols.For the recent decade,during the course of our studies on the chemistry ofα-oxo ketene-S,S-acetals,our group successfully developed novel strategies for the synthesis of highly substituted heterocycles,relying upon the utilization ofα-alkenoyl ketene-S,S-acetals.
Combining with the special properties ofα-oxo ketenedithioacetals,we have succeeded in exploring a new kind of heterocycles.This work mainly based on the following three aspects:
1.We enlarge the synthesis of 2-(1,3-dithiolan-2-ylidene)-3-oxo-N-phenylbutanamides, two newα-oxo-N-phenylbutanamides were synthesised.
2.A facile and efficient one-pot synthesis of substituted pyridine-2,4(1H,3H)-diones has been developed.Subjected to N,N-dimethylformamide dimethyl acetal(DMFDMA) in DMF, a series ofα-acyl,α-carbamoyl ketene-S,S-acetals were converted into the corresponding substituted pyridine-2,4(1H,3H)-diones in high yields.The simple procedure,mild conditions,easy separation,high yields,and wide range of synthetic potential of the products make this protocol much attractive.So these new reagents have good perspective in the field of academic research and practical applications.
3.We calculate the NBO state of(E)-5-(dimethylamino)-2-(1,3-dithiolan-2- ylidene)-3-oxo-N-phenylpent-4-enamide and it's negative ion by quantum chemistry method,and study the mechanism of the reaction acoording to the intermediate that we gain in the experiment.
In summary,we have succeeded in exploring a new kind of N-Substituted pyridones, moreover,providing mechanism of the reaction by quantum chemistry method.This method is associated with some synthetic advantages,such as simple procedure,fast reaction rate, high yields,mild conditions and wide range of synthetic potential of the products make this protocol much attractive.So these new reagents have good perspective in the field of academic research and practical applications.
引文
[1]Dieter R K.α-Oxo ketene dithioacetals and related compounds:versatile three carbon synthons[J].Tetrahedron,1986,42:3029～3031
[2]Junjappa H,Ila H,Asokan C.α-Oxo ketene-S,S-N,S-and-N,N-acetals:Versatile intermediates in organic synthesis[J].Tetrahedron,1990,4:5423～5425
[3]Kolb M,Umpolung of the reactivity of carbonyl compounds through sulfur-containing ketene dithioacetals in organic synthesis:Recent development reagents[J].Synthesis,1997,357～359
[4]Yakoyama M,Imamot T.Organic Reactions of Carbon Disulfide[J].Synthesis,1984,797～799
[5]Tse-Lok Ho著,刘培文,丁革非,操时杰译.有机化学中的硬软酸碱理论,科学出版社,1984
[6]Choi E B,Youn I K,Pak C S.Preparation of Protected β-keto Aldehydes from β-keto Esters via Seiective Reduction of Acyl(alkoxycarbonyl)ketene Dithioacetals[J].Synthesis,1988,792～794.
[7]刘群,张殊佳,张景萍.α-羰基烯酮式环二硫代缩醛类化合物的制备[J].高等学校化学学报,1992,13:56～59
[8]Corey,E.J.,Chem,R.H.K.α-Dithomethylenes:Generation and application to synthesis[J].Tetrahedron Letters,1973,39:3817～3189
[9]方群欣,刘群,胡玉兰等.α-芳甲酰基烯酮二硫缩醛的新合成方法[J].Chem J Chinese Universities,1995,16,1896-1898.
[10]赵玉龙,刘群,孙然等.α-溴代二硫缩烯酮的制备及其反应[J].高等学校化学学报,2002,23:1901～1902.
[11]赵玉龙,刘群,孙然等.α-硝基二硫缩烯酮的制备[J].高等学校化学学报,2004,25:297～298.
[12]Mehta B K,Ila H,Junjappa H.Highly chemoselective and stereoselective conjugate addition of benzyl copper reagents toα-Oxo ketene dithioacetals[J].Tetrahedron Lett,1995,36:1925～1927
[13]Liu Qun,Kocienski P.A new method for the preparation of phenols and its derivatives[J].Chinese Chem Lett,1991,2:353～355
[14]Junjappa H,Pranab K,Syam Kumar Vet al.1-Bis(methoxy)-4-bis(methylthio)-3-buten-2-one:useful three carbon synthon for synthesis of five and six membered heterocycles with masked(or unmasked) aldehyde functionality[J].Tetrahedron,2003,5:2631～2639
[15]Kolb M.Ketene dithioacerals in organic synthesis recent developments[J].Synthesis,1984,797～799
[16]Chakrasali R T,Ila H,Junjappa H.Reygio and chemoselective conjujate 1,4-reduction of α-Oxo ketene dithioacetals with sodium borohydride and sodium cyanoborohydride[J].Tedrahedron,1990,46:2195～2197
[17]Asokan C V,Ila H,Junjappa H.Methylthio-2,4-dimethyl-5-aryl or styryl-1,4-pentadien-3-ols to cyclopentenone derivatives[J].Tetrahdron Letter,1985,26:1087～1090
[18]Hojo M,Harada H,Yoshizawa J,et al.Samarium diiodide-promored reductive cieavage of carbon-sulfur bomds:a novel stereoselective generation of functionalized vinglsamarium species and synthesis ofβ-thiobutenolides[J].J.Org.Chem,1993,58:6541～6543
[19]Hojo M,Harada H,Hosomi A.A novel and efficient generation of functionalized vinylcopper reagents and their reactions with electrophiles synthesis of β-methylthiobutenolides[J].Chem.Lett,1997,437～439
[20]Singh G,Ila H,Junjappa H.Cationic benzoannelation of active methylene ketones via oxoketendithioacetals[J].Tetrahedron Letters,1984,25:5059～5061
[21]Balu M P,Singh G,Ila H.Cycloaromatization of ct-oxoketen dithiacetals with benzylmagnesium chloride:A novel naphthalene annelation reaction[J].Tetrahedron Lett,1986,27:117～119
[22]刘群,徐柏玲,杨智蕴.α-氧代烯酮环二硫代缩酮化学(Ⅹ.Ⅻ)-硫醇(酚)为亲核体的α-氧代烯酮环二硫代缩酮与2-甲基烯丙基氯化镁加成物的取代-环合芳构化反应[J].高等化学学报,1995,16:1047～1050
[23]Ila H,Junjappa H.Novel cycloaromatization in Reformatsky reaction onα-oxoketen dithiacetals:A regioselective synthesis of substituted ethyl 2-hydroxy-6-methylthiobenzoates[J].Tetrahedron Lett,1988,29:497～499
[24]Balu M P,Ila H,Junjappa H.Cycloaromatization ofα-oxoketen dithiacetals with 2-picolyllithium:A facile quinolizinium cation annelation[J].Tetrahedron Lett,1987,28:3023～3025
[25]Gupta A K,Ila H,Junjappa H.Aromatic annelation viaα-oxoketen dithiacetals:synthesis of thioreoycind dimetylethers[J].Tetrahedron Lett,1987,28:1459～1461
[26]Balu M P,Pooraneh D.Cycloaromatization ofα-oxoketen dithiacetals with 3-methyl-5-lithiomethylisoxazole:A new general approach for synthesis of substituted and annelated 1,2-benzisoxazoles[J].Tetrahedron Lett,1988,29:501～503
[27]杨智蕴,王子苓,刘群等.α-羰基烯酮环二硫代缩醛(XV) -β,β-(1,3-亚丙二硫基)-α,β-不饱和芳酮与2-甲基烯丙基Grignard试剂加成物的酸催化取代-环合芳构化反应[J].高等学校化学学报,1994,15:697～699
[28]Liu,Qun.,Yang,Zhiyun.Progress on the chemistry ofct-oxoketen dithiacetals[J].Chinese J.Org.Chem.1992,1:225～227
[29]彭勃,李慕洁,程侣柏.N 一烷基吡啶酮系列染料研究及进展.染料工业.1997,34(4):8～14
[30]Hirose,Masashi.Ink-jet recording inks and their use in the manufacture of color filters for liquid-crystald isplayp anels[p].JP 2002265834
[31]Kaneko,Yoshikazu.Thermal recording material containing leuco dye and pyridone der iv at ived eveloper[P].J P2001353969(2001)
[32]Haifeng Song,Kongchang Chen,He Tian.Synthesis and absorption properties of some new azo-metal chelates and their ligands.Dyes and Pigments[J].2004,60(1):11～119
[33]Kraus Helmut,Klausener Alexander,Fuerstenwerth Hauke.Process for the preparation of 2-Substituted-5-Methyl-Pyridine.1995,US 5 420 284
[34]高建荣,程侣柏,高昆玉.吡啶酮系化合物的合成与应用[J].浙江化工,1993,24:43～48
[35]孙强,高世萍,姚小华等.对δ-酮腈异构化成吡啶酮反应中催化剂的筛选[J].东北师大学报自然科学版,1995,2:71～74
[36]孙强,张振权,孙云鸿等.有机锡用于δ-酮腈异构化成吡啶酮的研究[J].合成化学,1993,4:351～355
[37]韦红映.2-氯吡啶和2,6-二氯吡啶的合成[J].杭州化工,2004,34(4):23～24
[38]梁诚.2-氯吡啶和2,6-二氯吡啶[J].中国氯碱,2002,5:10～12
[39]郑淑玲,张明华.6-氯-2吡啶酮的合成和表征[J].天津化工,2006,20:16～18
[40]陈卓,胡高云,龚娟等.5-甲基-2(1H)吡啶酮的合成[J].合成化学,2004,12:89～93
[41]谢文林,马林,郭刚军等.N-取代-6-芳硫基吡啶酮类化合物的合成与生物活性研究[J].有机化学,2002,22:999～1003
[42]路再生,倪兆平,牛德仲.N-芳基-2-乙基-3-羟基-4-吡啶酮的微波合成[J].有机化学,2003,23:89～91
[43]李玉娟,王钝,于鑫等.6-甲基-4-(1H)-吡啶酮-3-羧酸的制备[J].沈阳药科大学学报,2005,22(1):17～18
[44]Hartmann Ludwig A,Stephen Jon F.Synthesis of 2-Substituted-5-Methyl-Pyridine.1984,US 4473696
[45]廖琪丽,王建营,胡文祥.超声波催化合成3-羟基-4-n比啶酮[J].科技导报,2008,26(3):44～45
[46]Pachter I J,Kloetzel M C.J Am Chem Soc[J].1952,74:1321～1324
[47]孙强,高世萍,姚小华等.5,6-二取代-3,4-二氢-2-吡啶酮的氮烷基化反应[J].合成化学,1995,3(1):84～87
[48]Yangcu Yan,Dong Dewen,Yu Haifeng.A Clean,Facile and Practical Synthesis of α-Oxoketene-S,S-Tacetals in Water[J].Adv,Synth,Catal,2006,348:206～210.
[49]Bi Xihe,Zhang Jingping,Liu Qun,et al.Intramolecular Aza-Anti-Michael Addition of an Amide Anion to Enones:A Regiospecific Approach to Tetramic Acid Derivatives[J].Adv.Synth.Catal,2007,349:2301～2306
[2]Junjappa H,Ila H,Asokan C.α-Oxo ketene-S,S-N,S-and-N,N-acetals:Versatile intermediates in organic synthesis[J].Tetrahedron,1990,4:5423～5425
[3]Kolb M,Umpolung of the reactivity of carbonyl compounds through sulfur-containing ketene dithioacetals in organic synthesis:Recent development reagents[J].Synthesis,1997,357～359
[4]Yakoyama M,Imamot T.Organic Reactions of Carbon Disulfide[J].Synthesis,1984,797～799
[5]Tse-Lok Ho著,刘培文,丁革非,操时杰译.有机化学中的硬软酸碱理论,科学出版社,1984
[6]Choi E B,Youn I K,Pak C S.Preparation of Protected β-keto Aldehydes from β-keto Esters via Seiective Reduction of Acyl(alkoxycarbonyl)ketene Dithioacetals[J].Synthesis,1988,792～794.
[7]刘群,张殊佳,张景萍.α-羰基烯酮式环二硫代缩醛类化合物的制备[J].高等学校化学学报,1992,13:56～59
[8]Corey,E.J.,Chem,R.H.K.α-Dithomethylenes:Generation and application to synthesis[J].Tetrahedron Letters,1973,39:3817～3189
[9]方群欣,刘群,胡玉兰等.α-芳甲酰基烯酮二硫缩醛的新合成方法[J].Chem J Chinese Universities,1995,16,1896-1898.
[10]赵玉龙,刘群,孙然等.α-溴代二硫缩烯酮的制备及其反应[J].高等学校化学学报,2002,23:1901～1902.
[11]赵玉龙,刘群,孙然等.α-硝基二硫缩烯酮的制备[J].高等学校化学学报,2004,25:297～298.
[12]Mehta B K,Ila H,Junjappa H.Highly chemoselective and stereoselective conjugate addition of benzyl copper reagents toα-Oxo ketene dithioacetals[J].Tetrahedron Lett,1995,36:1925～1927
[13]Liu Qun,Kocienski P.A new method for the preparation of phenols and its derivatives[J].Chinese Chem Lett,1991,2:353～355
[14]Junjappa H,Pranab K,Syam Kumar Vet al.1-Bis(methoxy)-4-bis(methylthio)-3-buten-2-one:useful three carbon synthon for synthesis of five and six membered heterocycles with masked(or unmasked) aldehyde functionality[J].Tetrahedron,2003,5:2631～2639
[15]Kolb M.Ketene dithioacerals in organic synthesis recent developments[J].Synthesis,1984,797～799
[16]Chakrasali R T,Ila H,Junjappa H.Reygio and chemoselective conjujate 1,4-reduction of α-Oxo ketene dithioacetals with sodium borohydride and sodium cyanoborohydride[J].Tedrahedron,1990,46:2195～2197
[17]Asokan C V,Ila H,Junjappa H.Methylthio-2,4-dimethyl-5-aryl or styryl-1,4-pentadien-3-ols to cyclopentenone derivatives[J].Tetrahdron Letter,1985,26:1087～1090
[18]Hojo M,Harada H,Yoshizawa J,et al.Samarium diiodide-promored reductive cieavage of carbon-sulfur bomds:a novel stereoselective generation of functionalized vinglsamarium species and synthesis ofβ-thiobutenolides[J].J.Org.Chem,1993,58:6541～6543
[19]Hojo M,Harada H,Hosomi A.A novel and efficient generation of functionalized vinylcopper reagents and their reactions with electrophiles synthesis of β-methylthiobutenolides[J].Chem.Lett,1997,437～439
[20]Singh G,Ila H,Junjappa H.Cationic benzoannelation of active methylene ketones via oxoketendithioacetals[J].Tetrahedron Letters,1984,25:5059～5061
[21]Balu M P,Singh G,Ila H.Cycloaromatization of ct-oxoketen dithiacetals with benzylmagnesium chloride:A novel naphthalene annelation reaction[J].Tetrahedron Lett,1986,27:117～119
[22]刘群,徐柏玲,杨智蕴.α-氧代烯酮环二硫代缩酮化学(Ⅹ.Ⅻ)-硫醇(酚)为亲核体的α-氧代烯酮环二硫代缩酮与2-甲基烯丙基氯化镁加成物的取代-环合芳构化反应[J].高等化学学报,1995,16:1047～1050
[23]Ila H,Junjappa H.Novel cycloaromatization in Reformatsky reaction onα-oxoketen dithiacetals:A regioselective synthesis of substituted ethyl 2-hydroxy-6-methylthiobenzoates[J].Tetrahedron Lett,1988,29:497～499
[24]Balu M P,Ila H,Junjappa H.Cycloaromatization ofα-oxoketen dithiacetals with 2-picolyllithium:A facile quinolizinium cation annelation[J].Tetrahedron Lett,1987,28:3023～3025
[25]Gupta A K,Ila H,Junjappa H.Aromatic annelation viaα-oxoketen dithiacetals:synthesis of thioreoycind dimetylethers[J].Tetrahedron Lett,1987,28:1459～1461
[26]Balu M P,Pooraneh D.Cycloaromatization ofα-oxoketen dithiacetals with 3-methyl-5-lithiomethylisoxazole:A new general approach for synthesis of substituted and annelated 1,2-benzisoxazoles[J].Tetrahedron Lett,1988,29:501～503
[27]杨智蕴,王子苓,刘群等.α-羰基烯酮环二硫代缩醛(XV) -β,β-(1,3-亚丙二硫基)-α,β-不饱和芳酮与2-甲基烯丙基Grignard试剂加成物的酸催化取代-环合芳构化反应[J].高等学校化学学报,1994,15:697～699
[28]Liu,Qun.,Yang,Zhiyun.Progress on the chemistry ofct-oxoketen dithiacetals[J].Chinese J.Org.Chem.1992,1:225～227
[29]彭勃,李慕洁,程侣柏.N 一烷基吡啶酮系列染料研究及进展.染料工业.1997,34(4):8～14
[30]Hirose,Masashi.Ink-jet recording inks and their use in the manufacture of color filters for liquid-crystald isplayp anels[p].JP 2002265834
[31]Kaneko,Yoshikazu.Thermal recording material containing leuco dye and pyridone der iv at ived eveloper[P].J P2001353969(2001)
[32]Haifeng Song,Kongchang Chen,He Tian.Synthesis and absorption properties of some new azo-metal chelates and their ligands.Dyes and Pigments[J].2004,60(1):11～119
[33]Kraus Helmut,Klausener Alexander,Fuerstenwerth Hauke.Process for the preparation of 2-Substituted-5-Methyl-Pyridine.1995,US 5 420 284
[34]高建荣,程侣柏,高昆玉.吡啶酮系化合物的合成与应用[J].浙江化工,1993,24:43～48
[35]孙强,高世萍,姚小华等.对δ-酮腈异构化成吡啶酮反应中催化剂的筛选[J].东北师大学报自然科学版,1995,2:71～74
[36]孙强,张振权,孙云鸿等.有机锡用于δ-酮腈异构化成吡啶酮的研究[J].合成化学,1993,4:351～355
[37]韦红映.2-氯吡啶和2,6-二氯吡啶的合成[J].杭州化工,2004,34(4):23～24
[38]梁诚.2-氯吡啶和2,6-二氯吡啶[J].中国氯碱,2002,5:10～12
[39]郑淑玲,张明华.6-氯-2吡啶酮的合成和表征[J].天津化工,2006,20:16～18
[40]陈卓,胡高云,龚娟等.5-甲基-2(1H)吡啶酮的合成[J].合成化学,2004,12:89～93
[41]谢文林,马林,郭刚军等.N-取代-6-芳硫基吡啶酮类化合物的合成与生物活性研究[J].有机化学,2002,22:999～1003
[42]路再生,倪兆平,牛德仲.N-芳基-2-乙基-3-羟基-4-吡啶酮的微波合成[J].有机化学,2003,23:89～91
[43]李玉娟,王钝,于鑫等.6-甲基-4-(1H)-吡啶酮-3-羧酸的制备[J].沈阳药科大学学报,2005,22(1):17～18
[44]Hartmann Ludwig A,Stephen Jon F.Synthesis of 2-Substituted-5-Methyl-Pyridine.1984,US 4473696
[45]廖琪丽,王建营,胡文祥.超声波催化合成3-羟基-4-n比啶酮[J].科技导报,2008,26(3):44～45
[46]Pachter I J,Kloetzel M C.J Am Chem Soc[J].1952,74:1321～1324
[47]孙强,高世萍,姚小华等.5,6-二取代-3,4-二氢-2-吡啶酮的氮烷基化反应[J].合成化学,1995,3(1):84～87
[48]Yangcu Yan,Dong Dewen,Yu Haifeng.A Clean,Facile and Practical Synthesis of α-Oxoketene-S,S-Tacetals in Water[J].Adv,Synth,Catal,2006,348:206～210.
[49]Bi Xihe,Zhang Jingping,Liu Qun,et al.Intramolecular Aza-Anti-Michael Addition of an Amide Anion to Enones:A Regiospecific Approach to Tetramic Acid Derivatives[J].Adv.Synth.Catal,2007,349:2301～2306