CN1139575C - 喹啉-5,8-二酮的制备方法 - Google Patents
喹啉-5,8-二酮的制备方法 Download PDFInfo
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- CN1139575C CN1139575C CNB008116423A CN00811642A CN1139575C CN 1139575 C CN1139575 C CN 1139575C CN B008116423 A CNB008116423 A CN B008116423A CN 00811642 A CN00811642 A CN 00811642A CN 1139575 C CN1139575 C CN 1139575C
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- 238000000034 method Methods 0.000 title claims abstract description 13
- NVJSPQCVDHGYRE-UHFFFAOYSA-N quinoline-5,8-dione Chemical class C1=CC=C2C(=O)C=CC(=O)C2=N1 NVJSPQCVDHGYRE-UHFFFAOYSA-N 0.000 title abstract 2
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 claims abstract description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- YYFLDZZDOUDZQM-UHFFFAOYSA-N 3-[1-[[4-(3-phenylquinolin-2-yl)phenyl]methyl]piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC=CC=C2N1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC2=CC=CC=C2C=C1C1=CC=CC=C1 YYFLDZZDOUDZQM-UHFFFAOYSA-N 0.000 claims description 7
- 239000003504 photosensitizing agent Substances 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 230000005855 radiation Effects 0.000 claims description 3
- YNHJECZULSZAQK-UHFFFAOYSA-N tetraphenylporphyrin Chemical class C1=CC(C(=C2C=CC(N2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3N2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 YNHJECZULSZAQK-UHFFFAOYSA-N 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 4
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 239000005725 8-Hydroxyquinoline Substances 0.000 abstract 1
- 238000006213 oxygenation reaction Methods 0.000 abstract 1
- 229960003540 oxyquinoline Drugs 0.000 abstract 1
- 239000000047 product Substances 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- -1 methoxy quinoline-5 Chemical compound 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WTRLGKKTVRQALM-UHFFFAOYSA-N anthracene-1,2-dicarbonitrile Chemical compound C1=CC=CC2=CC3=C(C#N)C(C#N)=CC=C3C=C21 WTRLGKKTVRQALM-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 2
- HELOQQSOLYCAKN-UHFFFAOYSA-N 5,8-dimethoxyquinolin-6-amine Chemical compound C1=CN=C2C(OC)=CC(N)=C(OC)C2=C1 HELOQQSOLYCAKN-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- DWJFGGVNPNGBBN-UHFFFAOYSA-N N1C=2C=C(N=3)C=CC=3C=C(N3)C=CC3=CC(=N3)C=CC3=CC1=CC=2C1=CC=NC=C1 Chemical class N1C=2C=C(N=3)C=CC=3C=C(N3)C=CC3=CC(=N3)C=CC3=CC1=CC=2C1=CC=NC=C1 DWJFGGVNPNGBBN-UHFFFAOYSA-N 0.000 description 1
- RSPISYXLHRIGJD-UHFFFAOYSA-N OOOO Chemical compound OOOO RSPISYXLHRIGJD-UHFFFAOYSA-N 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- ZWMFUFUJHSFPGL-UHFFFAOYSA-N anthracene-9,10-dione 1H-azepine Chemical class C1=CC=CC=2C(C3=CC=CC=C3C(C12)=O)=O.N1C=CC=CC=C1 ZWMFUFUJHSFPGL-UHFFFAOYSA-N 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- CSNXUYRHPXGSJD-UHFFFAOYSA-N isoquinolin-5-ol Chemical compound N1=CC=C2C(O)=CC=CC2=C1 CSNXUYRHPXGSJD-UHFFFAOYSA-N 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 238000007539 photo-oxidation reaction Methods 0.000 description 1
- 230000003351 photoxidation Effects 0.000 description 1
- XQZYPMVTSDWCCE-UHFFFAOYSA-N phthalonitrile Chemical class N#CC1=CC=CC=C1C#N XQZYPMVTSDWCCE-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 239000002683 reaction inhibitor Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Quinoline Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
本发明涉及一种通过光诱导8-羟基喹啉的氧化制备式I的喹啉-5，8-二酮的方法，其中R1，R2和R3如权利要求1所定义。
Description
本发明涉及喹啉-5，8-二酮的制备方法，该化合物可用作中间体产物，尤其是在制药工业中。
Bracher(Heterocycles，29，2093，1989)曾描述过一种通过用重铬酸盐氧化从5-氨基-8-羟基喹啉制备喹啉-5，8-二酮的方法。该方法需要带有两种功能基的喹啉母核，因此涉及昂贵且不易获得的原料。S.Ghosh(J.Fluorine Chem.，1994；67：53-56)描述了通过对苯醌和取代的二烯之间的环加成反应制得的喹啉-5，8-二酮衍生物。4-氯喹啉-5，8-二酮是合成更复杂的三环或四环化合物的中间体(M.Croisy-Delsey等，J.HeterocyclicChem.1993；30：55-60)，而2-甲氧基喹啉-5，8-二酮是2，5，8(1H)-喹啉-三酮N-烷基化的副产物(C.Avendano等，Synthesis 1991；727-730)。4-羟基-5，8-喹啉醌可以从2，5-二甲氧基苯胺以及甲基丙烯酸的酯合成(P.Withopf等，Tetrahedron，1987；43(20)：4549-4554)。喹啉-5，8-二酮和2-氯-4-甲基喹啉-5，8-二酮是合成氮杂蒽醌衍生物的原料(K.T.Potts等，J.Org.Chem.，1986：2011-2021)。由6-氨基-5，8-二甲氧基喹啉衍生的抗疟药可以用2-三氟-4-甲基或2，4-二甲基-喹啉-5，8-二酮制备(C.Temple等，J.Med.Chem.，1974；17(6)：615-619)。此外，EP 0433679描述了作为体内美拉德反应抑制剂的喹啉-5，8-二酮衍生物，该反应与糖尿病的许多后果(神经病、视网膜病)有关(通过糖使蛋白质变性)。
还存在通过苯酚类化合物的光氧化制备醌的方法(例如Chem.Comm.，2173，1996)，但从未用该方法合成过杂环化合物、特别是喹啉衍生物。
其原因是，该方法不会因为存在拉电子的吡啶母核而受到阻碍，这一点并不是显而易见的。醌和吡啶母核的氮之间的反应会生成有颜色的聚合物，并且还可能有危险。在使用5-羟基-异喹啉时会观察到这种情况。
现已发现，一组特定的8-羟基喹啉化合物可以通过在光敏剂的存在下进行光氧化反应然后分解中间体羟基过氧化物高产率地生成喹啉-5，8-二酮。
本发明的一个目的是制备下式的喹啉-5，8-二酮的方法：
其中：R1、R2和R3选自氢、卤原子、C1-C6烷基、-CHO、-OH、-OR、-COOH、-CN、-CO2R、-CONHR、-CONRR′-、-NH2、-NHCOR、
吗啉和SO3H，R和R′选自C1-C6烷基，Ar选自C6-C14芳基，其中，将下式的8-羟基喹啉用氧在光化辐射的作用下、在有机溶剂中和催化量的光敏剂的存在下氧化：其中R1、R2和R3具有以上给出的含义，然后将形成的下式的氢过氧化物：
分解形成式I化合物。
与氧的氧化反应在可以溶解式II的8-羟基-喹啉原料的有机溶剂中进行。所述溶剂优选还可以溶解光敏剂。
光敏剂可以是四苯基卟吩(或TPP)，在该情况下，溶剂可以是二氯甲烷。
还可以使用其它适宜的光敏剂和溶剂，特别是：-玫瑰红在CH3CN、MeOH、EtOH、CHCl3或水中；-亚甲蓝在CH3CN、MeOH、EtOH、CHCl3或水中；-四(4-吡啶基)卟吩在CH2Cl2或CHCl3中；-二氰基萘(DCN)、二氰基蒽(DCA)或二氰基苯(DCB)；-N，N′-二甲基-2，7-二氮杂pyrenium(DAP2+)二(四氟硼酸盐)。
该反应优选在室温(15至25℃)以及用可见光照射下进行，并同时喷射氧气，反应时间为2至8小时。
形成的式III的氢过氧化物在搅拌时、特别是在硫酸钠的存在下搅拌时会自发的分解。
本发明还涉及下式的喹啉-5，8-二酮：
其中：R1、R2和R3选自氢、卤原子、C1-C6烷基、-CHO、-OH、-OR、-COOH、-CN、-CO2R、-CONHR、-CONRR′-、-NH2、-NHCOR、吗啉和SO3H，R和R′选自C1-C6烷基，Ar选自C6-C14芳基，但不包括如下化合物，其中：R1＝H、R2＝H并且R3选自H、CH3、CN和CHO，R1＝H或CH3、R2＝F并且R3＝HR1＝Cl、R2＝H并且R3＝HR1＝OH、R2＝H并且R3＝COOH、COOCH3或CH3R1＝OH、R2＝COOH或COOC2H5并且R3＝HR1＝H、R2＝H并且R3＝OCH3R1＝OH、R2＝H并且R3＝HR1＝OCH3、R2＝H并且R3＝HR1＝CH3、R2＝H并且R3＝ClR1＝CH3、R2＝H并且R3＝CH3
实施例
以下将给出用于实施本发明方法的实施例。一般方法
将式II化合物(2mmol)的二氯甲烷(或其它溶剂，如果不溶的话)(20ml)溶液在含有催化量四苯基卟吩(TPP，6mg，即0.5mol％)的Pyrex平底烧瓶中于20℃下(用水冷却)用可见光(1500W氙弧光灯，用滤光片使照射光＞495nm)照射并同时喷射氧气2-8小时(通过TLC监测反应)。然后将照射后的溶液倒在干燥的硫酸钠(3g)上，室温搅拌12小时然后过滤。蒸除溶剂并将得到的粗品醌通过硅胶柱色谱纯化。
在下表中总结了各实施例的情况。
以下将给出所得产物的特征。
实施例1的产物：- 深黄色固体；m.p.＝120-122℃- IR(CHCl3)：1670cm-1- 1H NMR 300MHz(CDCl3)：δ7.08(d，1H，J＝11Hz)；7.18(d，1H，
J＝11Hz)；7.73(m；1H)；8.44(m，1H)；9.07(m，1H))ppm- 13C NMR 75MHz(CDCl3)：δ127.9(d)；129.1(s)；134.6(d)；138.0
(d)；139.1(d)；147.4(s)；154.8(d)；183.2(s)；184.5(s)ppm。- MS C9H5NO2(相对强度)：m/z 159(M+，100)；131(25)；103(51)。
实施例2的产物：- 深黄色固体；m.p.＝135-140℃(分解)- IR(CHCl3)：1670cm-1- 1H NMR 300MHz(CDCl3)：δ2.80(s，3H)7.03(d，1H，J＝11Hz)；
7.13(d，1H，J＝11Hz)；7.58(d，1H，J＝8Hz)；8.30(d，1H，J＝8Hz)
ppm。- 13C NMR 75MHz(CDCl3)：δ25.3(q)；127.0(s)127.8(d)；134.6(d)；
137.9(d)；138.8(d)；146.9(s)；165.2(s)；183.5(s)：184.6(s)ppm。
实施例3的产物：- 深黄绿色固体；m.p.＝170-172℃- IR(CHCl3)：2250；1680cm-1- 1H NMR 300MHz(CDCl3)：δ7.20(d，1H，J＝11Hz)；7.30(d，1H，J
＝11Hz)；8.12(d，1H，J＝8Hz)；8.64(d，1H，J＝8Hz)ppm。- 13C NMR 75MHz(CDCl3)：δ115.7(s)；130.1(s)；131.9(d)；136.4
(d)；138.2(s)；138.3(d)；139.7(d)；147.9(s)；181.1(s)；182.8(s)
ppm。
实施例4的产物：- 深黄绿色固体；m.p.＝185-187℃- IR(CHCl3)：1720；1680cm-1- 1H NMR 300MHz(CDCl3)：δ7.20(d，1H，J＝11MHz)7.30(d，1H；
J＝11Hz)；8.34(d，1H，J＝8Hz)；8.6(d，1H，J＝8Hz)；10.32(s，1H)
ppm。- 13C NMR 75MHz(CDCl3)：δ124.9(d)；131.2(s)136.4(d)；138.3
(d)；139.6(d)；147.6(s)；155.5(s)；182.4(s)；183.6(s)；191.8(d)
ppm。- MS C10H5NO3(相对强度)：m/z 187(M+，17)；159(100)；103(32)。
实施例5的产物：- 1H NMR 300MHz(CDCl3)：δ4.07(s，3H)；7.16(d，1H，J＝10.5Hz)；
7.27(d，1H，J＝10.5Hz)；8.50(d，1H，J＝8.1Hz)；8.61(d，1H，J＝
8.1Hz)ppm。
实施例6的产物：- 1H NMR 300MHz(CDCl3)：δ1.25(d，6H，J＝7.2Hz)；1.55(d，6H，
7.2Hz)；3.62(七重峰，1H，J＝7.2Hz)；3.82(七重峰，1H，J＝7.2
Hz)；7.07(d，1H，J＝10.5Hz)；7.17(d，1H，J＝10.5Hz)；7.88(d，1H，
J＝8.2Hz)；8.49(d，1H，J＝8.2Hz)ppm。
实施例7的产物：- 1H NMR 300MHz(CDCl3)：(2种旋转异构体，约50∶50)δ1.40和
1.50(s，9H)；4.50和4.55(s，2H)；4.70和4.77(s，2H)；7.03(d，1H，J＝
10.5Hz)；7.14(d，1H，J＝10.5Hz)；7.15-7.35(m，5H)；7.48和7.61(d，
1H，J＝8.2Hz)；8.33(d，1H，J＝8.2Hz)ppm。
实施例8的产物：- 1H NMR 300MHz(CDCl3)：(2种旋转异构体，约50∶50)δ1.40和
1.47(s，9H)；3.70和3.72(s，3H)；4.02和4.13(s，2H)；4.80和4.83(s，
2H)；7.04和7.06(d，1H，J＝10.5Hz)；7.13和7.15(d，1H，J＝
10.5Hz)；7.89和7.91(d，1H，J＝8.3Hz)；8.42和8.45(d，1H，J＝8.3
Hz)ppm。
实施例9的产物：- 1H NMR 300MHz(CDCl3)：δ2.81(s，3H)；7.00(d，1H，J＝10.4Hz)；
7.11(d，1H，J＝10.4Hz)；7.48(d，1H，J＝4.9Hz)；8.86(d，1H，J＝
4.9ppm)。- MS[C10H7NO2](相对强度)：m/z 173(M+，100)；145(35)；117(23)；
91(28)。
实施例10的产物：- 1H NMR 300MHz(CDCl3)：δ2.55(s，3H)；7.04(d，1H，J＝10.4Hz)；
7.14(d，1H，J＝10.4Hz)；8.20(s，1H)；8.88(s，1H)ppm- MS[C10H7NO2](相对强度)：m/z 173(M+，100)；145(23)；117(34)；
91(28)。
可以看出，该方法的成功严格地取决于原料的性质。例如，其中R3是-CH2OH基团的式II化合物不能转化成式I的产物，而是形成了棕色的颜色并发生了聚合反应。
Claims (6)
1.制备下式的喹啉-5，8-二酮的方法：
其中：R1、R2和R3选自氢、卤原子、C1-C6烷基、-CHO、-OH、-OR、-COOH、-CN、-CO2R、-CONHR、-CONRR′-、-NH2、-NHCOR、和SO3H，R和R′选自C1-C6烷基，Ar选自C6-C14芳基，其中，将下式的8-羟基喹啉用氧在光化辐射的作用下、在有机溶剂中和催化量的光敏剂的存在下氧化：
其中R1、R2和R3具有以上给出的含义，然后将形成的下式的氢过氧化物：
分解形成式I化合物。
2.权利要求1所述的方法，其中的光敏剂是四苯基卟吩。
3.权利要求1或2所述的方法，其中的溶剂是二氯甲烷。
4.下式的喹啉-5，8-二酮：其中：R1选自氢、-CHO、-OH、-OR、-COOH、-CN、-CO2R、-CONHR、-CONRR′-、-NH2、-NHCOR、
和SO3H；R2和R3选自氢、卤原子、C1-C6烷基、-CHO、-OH、-OR、-COOH、-CN、-CO2R、-CONHR、-CONRR′-、-NH2、-NHCOR、
和SO3H；R和R′独立地选自C1-C6烷基，Ar是C6-C14芳基，但不包括如下化合物，其中：R1＝H、R2＝H并且R3选自H、CH3、CN和CHOR1＝H、R2＝F并且R3＝HR1＝OH、R2＝H并且R3＝COOH、COOCH3或CH3R1＝OH、R2＝COOH或COOC2H5并且R3＝HR1＝H、R2＝H并且R3＝OCH3R1＝OH、R2＝H并且R3＝HR1＝OCH3、R2＝H并且R3＝H。
5.权利要求4所述的式I的喹啉-5，8-二酮，其中R3选自-CONRR′-、
和
6.权利要求4所述的式I的喹啉-5，8-二酮，其中R1选自氢、-CHO、-COOH、-CN、-CO2R、-CONHR、-CONRR′-、-NH2、-NHCOR、
和SO3H；R2选自氢、-CHO、-OH、-OR、-COOH、-CN、-CONHR、-CONRR′-、-NH2、-NHCOR、和SO3H；R3选自氢、-CHO、-COOH、-CN、-CONHR、-CONRR′-、-NH2、-NHCOR、
和SO3H；R和R′独立地选自C1-C6烷基且Ar是C6-C14芳基，除了下列化合物，其中R1＝H，R2＝H且R3选自H，CN和CHO。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9910491A FR2797443B1 (fr) | 1999-08-13 | 1999-08-13 | Procede de prepartion de quinoleine-5,8-diones |
| FR99/10491 | 1999-08-13 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
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| CN1139575C true CN1139575C (zh) | 2004-02-25 |
Family
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|---|---|---|---|
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|---|---|
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| EP (1) | EP1202972A2 (zh) |
| JP (1) | JP2003507363A (zh) |
| KR (1) | KR100719398B1 (zh) |
| CN (1) | CN1139575C (zh) |
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| HU (1) | HUP0202890A3 (zh) |
| IL (2) | IL148042A0 (zh) |
| MX (1) | MXPA02001494A (zh) |
| NO (1) | NO322649B1 (zh) |
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| PL (1) | PL203362B1 (zh) |
| SK (1) | SK287416B6 (zh) |
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| ZA (1) | ZA200200970B (zh) |
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| CN100519533C (zh) * | 2006-12-01 | 2009-07-29 | 广东工业大学 | 5-芳胺喹啉-7,8-二酮类衍生物及其在制备抗菌药物中的应用 |
| WO2010127208A1 (en) * | 2009-04-30 | 2010-11-04 | Forest Laboratories Holdings Limited | Inhibitors of acetyl-coa carboxylase |
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| US4692449A (en) * | 1986-06-20 | 1987-09-08 | American Cyanamid Company | Substituted quinolinediones |
| US4742059A (en) * | 1986-06-20 | 1988-05-03 | American Cyanamide Company | Substituted quinoxalinediones and their methods of use |
| JPH03161441A (ja) * | 1989-11-20 | 1991-07-11 | Senjiyu Seiyaku Kk | メイラード反応阻害剤 |
| JPH04336792A (ja) * | 1991-05-13 | 1992-11-24 | Nippon Musen Denki Saabisushiya:Kk | グラフィック表示処理装置 |
| FR2790954B1 (fr) * | 1999-03-18 | 2003-08-08 | Lafon Labor | Composition pharmaceutique a base de composes polyaromatiques |
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| JP2003507363A (ja) | 2003-02-25 |
| KR20020023418A (ko) | 2002-03-28 |
| AU779500B2 (en) | 2005-01-27 |
| US6515127B1 (en) | 2003-02-04 |
| WO2001012597A2 (fr) | 2001-02-22 |
| SK287416B6 (sk) | 2010-09-07 |
| CA2393951C (fr) | 2010-05-25 |
| PL203362B1 (pl) | 2009-09-30 |
| EP1202972A2 (fr) | 2002-05-08 |
| AU7011200A (en) | 2001-03-13 |
| NO20020670D0 (no) | 2002-02-11 |
| FR2797443A1 (fr) | 2001-02-16 |
| FR2797443B1 (fr) | 2003-10-31 |
| NO322649B1 (no) | 2006-11-13 |
| CN1370149A (zh) | 2002-09-18 |
| KR100719398B1 (ko) | 2007-05-17 |
| PL353457A1 (en) | 2003-11-17 |
| CA2393951A1 (fr) | 2001-02-22 |
| ZA200200970B (en) | 2003-04-30 |
| IL148042A (en) | 2007-06-03 |
| WO2001012597A3 (fr) | 2001-07-19 |
| MXPA02001494A (es) | 2002-07-02 |
| BR0013547A (pt) | 2002-04-09 |
| HUP0202890A2 (hu) | 2003-01-28 |
| CZ2002530A3 (cs) | 2002-05-15 |
| NO20020670L (no) | 2002-04-15 |
| HUP0202890A3 (en) | 2003-04-28 |
| IL148042A0 (en) | 2002-09-12 |
| SK2052002A3 (en) | 2002-09-10 |
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