chp07 Analysis of heterocyclic drugs.ppt

1、CHAPRER 7 The Analysis of Heterocyclic drugs,SECTION 1 INTRODUCTION,The non-carbon atoms such as oxygen, nitrogen, and sulfur etc. in organic ring compounds are known as heterocyclic atoms, The ring compounds contain the heterocyclic atoms are called as heterocyclic compounds.,Native (natural) heter

2、ocyclic drugs Alkaloids(natural base) Vitamins Antibiotics Synthetic heterocyclic compounds Pyridines Phenothiazines Benzodiazepines,Properties: 1. pentatomic ring & hexatomic ring monocyclic or dicyclic and polycyclic system 2. stable 3. alkalinity of nitrogen atom on heterocyclic nitrogen compound

3、 4. absorption spectra ( UV, IR ),SECTION 2 ANALYSIS OF PYRIDINE DRUGS,1. General considerations Typical drugs pyridine Isoniazide(INH) Nikethamide,Properties: 1) pyridinewith heavy metal 2) tertiary aminealkaline pkb8.8 (in water) 3) acyl hydrazine (INH) reducing property condensation reaction with

4、 carbonyl reagents 4) acyl aminehydrolysis,2. Identification 1) Reaction of pyridine stem nucleus A . precipitation INH, Nikethamide + HgCl2 INH +CuSO4（Cu2O） Nikethamide + CuSO4 + KSCN B . ring-opening reaction of pyridine ring -non-substituted, and ,-substituted with alkyl, and carboxyl group,I pen

5、tenedinal reaction (Konig reaction) Nikethamide INH,II dinitrochlorobenzene reaction (Vongerichten reaction),II dinitrochlorobenzene reaction (Vongerichten reaction),2）Reaction of hydrazideINH A . Reduction reaction Silver mirror reaction : INH + AgNO3 + H2O (NH3H2O) Ag Oxidant: I2、Br2、KBrO3、AgNO3,B

6、. Condensation reaction . hydrazine non-substituted condense with aromatic aldehydes to form hydrazone condensating reagent: vanillin, salicylal(salicylic aldehyde) para-dimethylaminobenzaldehyde,II . hydrazine non-substituted condense with 1,2-naphthoquinone-4-sulfonic acid to produce red color,3）I

7、dentification after acid or alkali degradation A. INH, Nilithamide + Na2CO3 odorous pyridine B. Nikethamide + alkali sol. odorous diethylamine 4）UV-spectrophotometry 3. Test for free hydrazine in Isoniazide(INH) TLC Turbidimetric method Difference spectrophotometry,4. Assay (oxidant) : iodine；bromin

8、e； potassium brominate 1) iodometric method: I2(the excess) +2Na2S2O3(VS)2NaI+Na2S4O6,INH : I = 1 : 4 Titer(T) =a/bMWmg/mmol0.1mmol/ml1ml =1/4137.140.11 = 3.429mg/ml,2) bromometric method:,3) potassium bromate method: The indicator was oxidized into colorless by bromine. T=3/2MW0.01667 =3/2137.145/3

9、00 =137.145/200=3.429(mg/ml),4) Colorimetric method: ring-opening reaction of pyridine reduction and condensation reaction of hydrazide 5) non-aqueous titration method: non-aqueous alkalimetry non-aqueous acidimetry,SECTION 3 Analysis of Phenothiazine Drugs,1. General considerations basic structure:

10、 sulfur nitrogen heterocyclic anthracene R: dimethylamino, diethylamino group nitrogen heterocyclic ring R: -H, -Cl, -COCH3, -CF3, -SCH2CH3,2. Identification 1) UV-spectrum : (n-, -) conjugated system of skeleton structure max: 205, 254, 300nm min: 220nm, 280nm oxidazed products : sulfone (砜5,5-diox

11、ide) and sulfoxide (亚砜 5-oxide) 4 maximums of absorption: #test of oxidazed products, and #assay,2) color (-producing) reaction: A. phenothiazines + oxidizing agents cherry-red red oxidants: sulfuric acid, bromine, ferric chloride hydrogen peroxide B. phenothiazines + metallic ion (PdCl2) red (500nm

12、),3. assay: non-aqueous alkalimetric method UV-spetrophotometric method redox titration, colorimetry electrochemical method chromatography 1) Non-aqueous alkalimetric method : 2) Ceriometry (硫酸铈滴定法):,3) palladium ion colorimetry: 4) ultra-violet spetrometric methods: double wavelength 5) ferric ion

13、colorimetry,SECTION 4 ANALYSIS OF BENZODIAZEPINES,1. General considerations typical drugs:,chlordiazepoxide Diazepam,Property: 1) heptatomic ring: nitrogenalkalinity phenyl groupalkalinity decrease 2) in strong acidic solution: hydrolysisbenzophenone derivative (二苯甲酮),glycocoll,3) UV: chlordiazepoxide,2. Identification: 1) aromatic primary amino group reaction after hydrolys