e芳酸及其酯類

1、1會計學(xué)e芳酸及其酯類芳酸及其酯類n水楊酸類藥物的分析 The analysis of salicylic acidsn苯甲酸類藥物的分析 The analysis of benzoic acidsn其它芳酸類藥物的分析 The analysis of other aromatic acidsOHOOHSection 1OHCOOH(C2H5)2NH2+ COOHOOCOCH3COOHOHCOONaNH2OCOCH3CONHCOCH3OOCOONaCOOHSalicylic acidDiethyamine salicylateAspirin Sodium aminosalicylateBeno

2、rilate Salsalate OHCOOH 4FeCl3 COOO2Fe3Fe 12HCl 6 pH 4-6the minimum limit of detection ：1g. 阿司匹林碳酸鈉水解 加熱水楊酸鈉 醋酸鈉 醋酸水楊酸 （白色）100105干燥 加熱水楊酸結(jié)晶 (m.p 156-161) 稀硫酸 Hydrolysis HeatingSodium salicylate Sodium acetate Salicylic acid （white）HeatingCrystal of salicylic acid (m.p 156-161) Sulfuric acid Aspirin

3、Sodium carbonateAcetic acid Desiccation at 100105OCOCH3COONHCOCH3 3H2O HCl OHNH2 HCl OHCOOH 2CH3COOH OHNH2 NaNO2 2HCl OHNN+Cl NaCl 2H2OOHNN+ClOH NaOH OHOHNN NaCl H2O Salmon FamiliarIR absorption spectrogram of salicylic acid波數(shù)cm1 歸屬33002300 羧基及羥基 OH1660 羧酸 CO1610，1570，1480，1440 苯環(huán) CC775 鄰位取代苯 CH890

4、苯環(huán) 環(huán)ONaCO2Heating COONaONaH+ COOHOHCOOHOH (CH3CO)2O Acetylation COOHOCOCH3 CH3COOH OH(CH3CO)2O OCOCH3OH OHCOOHOHCOOOH OCOCH3COOHOCOCH3COOPhenyl salicylate Acetylphenyl salicylate NH2OHCOONaCO2 H2ONH2OHOOHNH2OOOHNH2OOHNH2OOOHOHn Applications: n Advantages n Limitations 適合于原料藥物 n Direct acid-base titr

5、ationTitration curve for 25 mlof a 1.0 M solution of aspirin(pKa3.5) titratedwith 1.0 M NaOHExactlyweighingNeutral ethanolPhenolphthalein Sodium hydroxide Neutralization Pink Hydrolysis and titration Calculation ASA為標(biāo)示量百分含量= (V0-V)M18.0210-3 0.05 W1標(biāo)示量 W 100% Section 2(CH3CH2CH2)2NSO2COO3Fe Decompos

6、ed product reaction (分解產(chǎn)物的反應(yīng)) 紫外吸收與紅外吸收光譜紫外吸收與紅外吸收光譜 HPLC 測定丙磺舒原料藥含量 Section3v Structure SO3HOHOH HNC2H5C2H5Estamsylate SO3HOHOH NHC2H5C2H5 NaOH OHOHSO3H HN(C2H5)2 H2O酚磺乙胺加硝酸水浴上蒸干 硫酸根離子 氯化鋇硫酸鋇沉淀溶解水溶液加硝酸 無硫酸鋇沉淀Estamsylate Sulfate ion Barium sulfate(precipitation) DissolveAqueous solution Nitric acid

7、No precipitationNitric acidEvaporation to dryness Barium chloride (C2H5)2NHSO2H2 OC2H5OH(C2H5)2NH H2SO3OO(C2H5)2NHH2SO3C2H5OHSO3HOHOH NHC2H5C2H5+Sulfonation ClOCCH3CH3COOCH3 Clofibrate Propanoic acid, 2-(4-chlorophenoxy)-2-methyl-, ethyl ester. Ethyl 2-(p-chlorophenoxy)-2-methylpropionate 氯貝丁酯堿水解加鹽酸

8、羥胺異羥肟酸鹽酸性異羥肟酸鐵加三氯化鐵ClofibrateHydrolysisBaseHydroxylamine hydrochloride Iso-hydroximic acid saltAcidity Iso-hydroximic acid ferricFeCl3OHCl縮合,HydrolysisCH3COCH3,CHCl3,NaOHOClCCOONaCH3CH3AcidificationHClOClCCOOHCH3CH3Esterification C2H5OH,H2SO4OClCCOOC2H5CH3CH3n Tests Salicylic acids Typical drugs Str

9、ucture Identification Impurities Assays Salicylic acid OHCOOHFerric chloride reaction (Violet color) Chloride, Sulfate, Heavy metals Related compounds Neutralization titrationDiethylamine salicylate (C2H5)2NH2+ COOHOFerric chloride reaction (Violet color) Non-aqueous titration Aspirin OCOCH3COOHFerr

10、ic chloride reaction (Violet color) Infrared absorption Readily carbonizable substances, Readily carbonizable substances,impurities, free salicylic acid Acid/base titration HPLC (suppository) Sodium amino-salicylate OHCOONaNH2Diazotization reaction Ferric chloride reaction m- aminophenol Diazotizati

11、on titration Benoriate Typical drugs Structure Identification Impurities Assays OCOCH3CONHCOCH3OAdding sodium hydroxide to hydrolysis, then reacting with Ferric chloride Diazotization reaction Diazotization titration Salsalate OCOONaCOOHHydrolysis Ferric chloride reaction Infrared absorption Dimethy

12、laniline, isopropyl, ethyl, and methyl salicylates, related compounds, organic volatile impurities Chroma-tography Benzoic acids Typical drugs Structure Identification Impurities Assays Benzoic acid and sodium benzoate COOHFerric chloride reaction Decomposed product reaction Readily carbonizable sub

13、stances, readily oxidizable substances, heavy metalsNeutralization titrationBumetanide HOOCSO2NH2NHO(CH2)3CH3Ultraviolet absorption Infrared absorption Heavy metals Titration Probenecid SO2HOOC.N(CH2CH2CH3)2Ultraviolet absorption Infrared absorption Heavy metals organic volatile impurities Chroma-to

14、graphy Other aromatic acids Typical drugs Structure Identification Impurities Assays Etamsylate SO3HOHOH HNC2H5C2H5Ferric chloride reaction Decomposed reaction after heated Oxidation reaction Benzoquinone, Hydroquinone HPLC UV Clofibrate ClOCCH3CH3COOC2H5Reaction with hydroxyl-amine hydrochloride UV and IR Acidity, p-chlorophenol Volatile impurities Two-step titration UV after ion exchange Section 1Hydrolysis HeatingSodium salicylate Sodium acetate Salicylic acid （white）HeatingCrystal of salicylic acid (m.p 156-161) Sulfuric acid Aspirin Sodium carbonateAcetic ac