Practical Organic Chemistry III PDF

Practical Organic chemistry III ‫ عبدالرحمن األهدل‬/‫دكتور المادة‬  Preparation of Acetanilide Chemical structure : Benzene ring Amin group Acetyl group Class of : analgesic drugs. Type of reaction : Nucleophilic substitution ( acetylation )...

Practical Organic chemistry III ‫ عبدالرحمن األهدل‬/‫دكتور المادة‬  Preparation of Acetanilide Chemical structure : Benzene ring Amin group Acetyl group Class of : analgesic drugs. Type of reaction : Nucleophilic substitution ( acetylation ) , affinity to protons. M.Wt = 135 g/mol. Physical properties : help to identification of substance. 1. White shining crystals. ( if appear yellow or other color , that means presence of impurities ) 2. Insoluble in cold water ( used in filtration , crystallization ) , but soluble in hot water. 3. M.P = 113 ºC. ( If M.P be reduced , that means presence of impurities ) 4. Soluble in acetone and chloroform. Clinical uses : 1) Antipyretic. 2) Analgesic. 3) Moderate headache sedative. 4) Used as base for manufacturing other drugs such as paracetamol ( PCT ). Acetanilide has been not used as sedative or antipyretic , because the over dose of it cause methemoglobinemia. How Acetanilide cause methemoglobinemia ?! the mechanism. The natural Hemoglobin in blood is globin (protein ) + fe+2 ( ferrous ). in case of over dose of Acetanilide , The Acetanilide will oxidize iron in hemoglobin from ferrous ( fe+2) state to ferric state (fe+3) , this called methemoglobin. 1 which unable to bind oxygen to carry it into cells , that cause methemoglobinemia disease. 𝑜𝑥𝑖𝑑𝑖𝑧𝑒 𝑓𝑒+2 + Acetanilide →−−−−→𝒇𝒆 +𝟑 {ferric 𝑖𝑟𝑜𝑛} The symptoms of methemoglobinemia : dyspnea , due to deficiency of oxygen. skin rush. jaundice. ‫يفرق بين االصفرار بسبب الكبد او نقص تروية االكسجين أن مرضى الكبد ال يشعر باالختناق‬ principle of reaction : Procedure : a) requirement : - Anillin 9 ml. - Acetic anhydride 15 ml. - Acetic acid 15ml as catalyst. - Beaker. - Conical flask , bottom flask. - Reflux water condenser. b) Steps : 1. in beaker add Acetic anhydride 15 ml and Acetic acid 15ml (beaker A ). 2. In conical flask add Anillin 9 ml. 3. Pour beaker A on anillin in flask. 4. Then fitted the condenser. 5. Boiling for 10 minutes , to allow condensation on good way , Not heat , to evaporate liquid. 6. Pour the hot liquid to 50 ml cold water , to form crystals. 7. Filtration. 2  If the crystals are white shing : pure.  If the crystals are yellow : not pure , need purification. Different between crystallization and recrystallization : - crystallization : filtration on hot. - recrystallization : repeat filtration on cold ,to give high pure compound. Importance of Reflux water condenser ❖ To allow condensation. ❖ To avoid lose of substance , in boiling. ❖ To catalyze the reaction.  Other method for Preparation Acetanilide : - principle of reaction : - Procedure : a) requirement : - Anillin 9 ml. - Acetic anhydride 11 ml. - Acetic acid 18 ml as catalyst. - Beaker , ice bath. - Conical flask , Funnel , filter paper. b) Steps : 1) in beaker add anillin and put it in ice bath. 2) slowly add Acetic acid gradually with continuous stirring. 3) then add the amount of Acetic anhydride slowly with stirring. 4) leave the mixture in ice bath until observe formation of crystals. 5) after that leave it at room temperature for 10-15 minutes. 6) return it to ice bath again. to speed up complete formation of crystals. 7) Do cold Filtration , Drying , weighting , Calculation  Do purification. 3  ❖ Calculation : Synthesis of acetanilide from anillin 9ml and acetic anhydride 11ml , if you know the density of anillin = 1.022 g/mole and the density of acetic anhydride = 1.08 g/mole. Calculate the % of yield. C6H5NH2 + C4H6O3 C8H9NO ⸪ density of anillin = 1.022 g/mole. W = D  V → 1.022  9 = 9.20 g. ⸪ density of acetic anhydride = 1.08 g/mole. W = D  V → 1.08  11 = 11.88 g. Theoretical Anillin Acetic anhydride Acetanilide Wt. 9.20g 11.88 g ---- M.Wt 93 g/mole 102 g/mole 135 g/mole Number of 0.098 mole 0.116 mole ---- Theoretical mole Number of 1 mole 1 mole 1 mole practical mole Total mole 0.098 mole 0.116 mole ----  limiting agent is anillin. ⸪ 1 mole of anillin ͢→ 1 mole of Acetanilide 0.098 mole →  = 0.098 mole. 𝑊𝑡 Number of mole for product = 𝑊𝑡 0.098 = wt.= 13.23g 𝑀𝑤𝑡 135 𝑝𝑟𝑎𝑐𝑡𝑖𝑐𝑎𝑙 𝑣𝑎𝑙𝑢𝑒 % Yield = 𝑡ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑣𝑎𝑙𝑢𝑒  100 11.25 = 13.23 𝑋 100 = 85  4  Purification of Acetanilide Definition of purification : The Process to remove unwanted impurities or foreign bodies from substance ( product ). Method of purification : depends on the nature of substance and impurities present. Solid : purification by : 1) Crystallization. 2) Recrystallization. 3) Decolorization , colored impurities by charcoal. 4)Sublimation , heat directly pass from solid state into gas. 5) Extraction. 6) Filtration. liquid : purification by : 1) Extraction. 2) Distillation. - Method of purification of Acetanilide : by Crystallization , Recrystallization with decolorization. - The different between : Crystallization Recrystallization Do on hot filtration On cold filtration Occur Before recrystallization. After crystallization. Form Pure subs in filtrate. Pure subs in residue of filter paper. Polarity Less. More. Procedure : 1. in beaker put Acetanilide crystal. 2. add 40 ml of water and 20 ml Acetic acid ( catalyst , dissolving agent ). 3. heating till complete dissolving of crystals. 5  4. add 1g of charcoal ?! to adsorbed color impurities , continue heating till boiling (1-2) minute. 5. Make hot filtration , ( crystallization ). 6. Receive hot filtration to beaker and add 50 ml cold water (recrystallization), to form crystals. 7. Then , stay for few minutes till complete formation of crystals and make cold Filtration , now there is residue on filter paper is pure Acetanilide. 8. Drying , weighting , calculation.  Important Notes : - When filtration , must be sure to clean and purity of tools that used. - Why we Add just 1g of charcoal not more ?! because , if we add more than 1g it will adsorb color impurities and some crystals of acetanilide. to over come (solve ) this problem , boil some water and pour on the F.P. to allow crystals to dissolve and return into filtrate. - If do not form crystals in step 6 : 1- add pure crystals of Acetanilide to form as nucleus to aggregate crystals. 2- Evaporation , to decrease the volume of solvent. 3- Scratching by glass rod. - When repeat filtration more , the substance will be stander , to compare it at purity examining of the same substance. 6  Nitration of Acetanilide  principle of reaction :  Procedure : a) requirement : - Acetanilide 5g. - glacial Acetic acid 5ml as solvent. - conc H2SO4 10ml , for 1st step. - HNO3 2ml. Preparing nitrite - H2SO4 1.5ml mixture - Beaker , ice bath , Conical flask , Funnel , filter paper. b) Steps : 1. in beaker add pure acetanilide. 2. add Acetic acid. 3. then add H2SO4 slowly  gradually with continuous stirring. obtain warm clear solution , exothermic reaction. 4. transfer beaker to ice bath ?! H2SO4 is exothermic. 5. Prepare nitrating mixture. (HNO3 + H2SO4 ) in ice bath 6. Add complete of beaker B + A gradually with stirring in cold ice bath ?!* 7. then leave mixture at room temperature for 30-60 minutes with stirring on periods. 8. after that add 100 ml of cold water observe formation of para – nitro acetanilide crystals allow it to 15 minutes to sedimented. 9. Do Filtration , Drying , weighting. 7   p– nitro acetanilide :. colorless , (diazonium salt) ‫مادة كيميائية نتنج من عملية النيترة ل االستانيليد بدون تكوين‬ ‫( لذا يتم‬miner ) ortho ‫ واألخر‬para (major ) ‫ أحدهما في وضع‬isomer ‫عند تحضيره قد ينتج لنا مركبين في نفس الوقت وهما‬ ‫ فقط وذلك الن‬para– nitro acetanilide ‫إضافة االيثانول للتأكد من الحصول‬ para- nitro acetanilide insoluble in ethanol , but ortho- soluble in ethanol. ❖ Uses of H2SO4 : as solvent , catalyst , dehydrated. must be gradually , if was fast that will form Di-nitrate ( para – ortho nitro acetanilide) , and must be in cold ice bath if was warm that will form over- nitration ( para – ortho – meta nitro acetanilide. ❖ Uses of para- nitro acetanilide : 1- manufacturing of pesticides , rubber. 2- base for preparation another compounds as paracetamol , paracetin. why nitro acetanilide form at para more ortho ? because , there is acetyl group near , ‫ تعمل إعاقة فراغية للوضع اورثو فتتجه الى الوضع بارا‬. Calculation the % of yield : C8H 9NO + HNO3 C8H8N2O3 ⸪ density of HNO3 = 1.51 g/mole. W = D  V → 1.18  1.6 = 2.4 g. Theoretical ACETANILIDE HNO3 P-ACETANILIDE Wt. 4g 2.4 g ---- M.Wt 135 g/mole 63g/mole 180 g/mole Number of 0.0296 mole 0.038 mole ---- Theoretical mole Number of 1 mole 1 mole 1 mole practical mole Total mole 0.0296 mole 0.038 mole ----  limiting agent is acetanilide. 8  Preparation of salicylamide ❖ Chemical structure: - hydroxy benzamide ❖ Physical properties : -White crystalline powder. -Insoluble in cold water and acid solution but soluble in hot water and basic solution as NaOH ? because , it basic substance. Different between salicylamide  Aspirin Amide derivative. Ester derivative. Odorless. Acidic Odor. ❖ Principle of reaction: 𝑆ℎ𝑎𝑘𝑖𝑛𝑔 CH3OH NH3 →−−−−→ Excess ❖ Clinical uses : Similar to aspirin, 1- Analgesic 2- antiseptic 3- weak anti-inflammatory. It is not use now , because it is expensive.. 9 ❖ Procedure: 1) Add Methyl salicylate 5ml. 2) Add Ammonia 30ml. 3) Close the flask tightly. 4) Shaking into stage. ▪ Stage I : Continuous Shaking for 3-4 hours, till appearance rose color mixture.. ( that mean The beginning of the interaction) Open the top , for remove ammonia gas to avoid pumping.. ▪ Stage II : Shaking for long time from time to time for 1 week , till color change to deep violet or deep rose color. 5) Evaporation after 1 week , to remove excess of ammonia, and separation. 6) Collect the powder and weight. 7) Calculation ❖ Identification of salicylamide by adding FeCl3 ?! Because, it has hydroxyl group free , (violet color). + Fecl3 3 Fe (VIOLET COMPLEX) Fecl3 use for test purification of aspirin and for identification of salicylamide. * Why use excess amount of ammonia? 1- Because ammonia is gas , maybe occur Evaporation , because the reaction is exothermic ( irreversible ). 2- if the ammonia is not enough it will form byproduct ( complex) NH 10  * Why do shaking for long time ? Because , we have two immiscible layers ( oil \ liquid ). There is an instrument instead , but it is expensive. * Why we can not use external catalyst ? Because , it will be acidic or basic. If it acidic , that will react with ammonia ( depletion ). If it basic , that will competition with ammonia and will react with methylsalycylate. * Why we use volumetric flask , not other tool ? Because , we can tightly close it. * Methanol is positive product in reaction ? Because , it is internal catalyst act as S.A.A increase immiscible between ( O \ L). Type of method of this preparation : evaporation. Calculation the % of yield : C8H8O3 + NH3 C7H7NO2 ⸪ density of methylsalycylate = 1.18 g/mole. W = D  V → 1.18  5 = 5.9 g. ⸪ density of ammonia = 0.84 g/mole. W = D  V → 0,84  30 = 25.2 g. Theoretical methylsalycylate ammonia Salicylamide Wt. 5.9 g 25.2 g ---- M.Wt 152 g/mole 17g/mole 137 g/mole Number of 0.039 mole 1.482 mole ---- Theoretical mole Number of 1 mole 1 mole 1 mole practical mole Total mole 0.039 mole 1.482 mole ----  limiting agent is methylsalycylate. 11  Def: it is process or technique for purification of liquid product or to separate between two liquids. Methods of distillation : determination B.P , identification liquid – liquid distillation. 1. Simple distillation : 2. Fractional distillation : 2. when liquid – liquid when liquid – liquid differ differ in B.P more () 20 in B.P less (