aspirin synthesis from ester, Lecture notes of Pharmaceutical Chemistry

Download aspirin synthesis from ester and more Lecture notes Pharmaceutical Chemistry in PDF only on Docsity! Pharmaceutical organic chemistryll 4* stage pharmacy college Acetylsalicylic acid synthesis (Aspirin) Out $12 a.a Properties of acetylsalicylic acid 1- Aspirin occurs as white crystals or as a white crystalline powder. 2- It is slightly soluble in water (1:300), soluble in alcohol (1 :5), chloroform (1:17) & ether (1:15). It dissolves easily in glycerin. 3- Practically all salts of aspirin (soluble in aqueous media) except those of aluminum and calcium (insoluble in aqueous media) . Ox 0H 4-Aspirin give no color with FeCl3 solution. Y, 8-Aspirin itself is acidic enough to produce effervescence with carbonates. ee COO Na [ yo eos Cree + NaHCO; | + H2CO3 a © Sodium: ~ = = ° : Carbonic Bicarbonate acid of co,t+ H:0 Carbon dioxide Acetylsalicylic acid: Aspirin contains three groups: ¢Carboxylic acid functional group (R-COOH) + eEster functional group (R-O-CO-R') e Aromatic group (benzene ring) COOH O Carboxylic acid derivatives oO O O O | | ! | Acid halide Acid anhydride Ester X=Cl, Br O O i i io R~ °NH, R~°>sR’ Rofo Ainide Thioester Acyl phosphate OQ Relative reactivity of carboxylic acid derivatives: Steric and electronic factors are both important in determining reactivity. Sterically, Within series of similar acid derivatives that unhindered , accessible carbonyl groups react with nucleophiles more readily than do sterically hindered groups. The reactivity order is; 2-Esterification using acid chlorides: Acid chlorides reacts readily with primary & secondary alcohols to give esters in very good yields. 0 0 0 if SOC, ete. // ROH / R—C cl R—C. —_—_—_— R-C ; ‘OH C|_ —-Prridine ‘9 R' Act Acid chloride Ester The reaction is fast but it's not safe and it produces HCI gas so pyridine should be used as a base to pick up a proton (H+) and gives pyridinium chloride. Pyridine is teratogenic and air pollutant. 3-Esterification using acid anhydries Esterification can be carried out with acid anhydrides in the presence of a suitable catalyst either an acidic catalyst such as sulphuric acid, or a basic catalyst. ¢ The order of acetylating power: Acetyl chloride » Acetic anhydride » Aeeti acid Preparation of acetyl salicylic acid: Method |: Preparation of aspirin by using acetyl chloride with salicylic acid Acetyl chloride is an acyl chloride, is very reactive it reacts vigorously with Salicylic acid to form aspirin. GOOH COOH oO: wn OO ~ i Qt TT: | 2 O7 CHa Cc N + H3C cl Mechanism _II: 90 ° Oo Oo oo» | ® ce | HaC— C——O——C— CH + H H,C— C— 0——C—CH, “UY H oxonium acetic anhydride | yon Name of Experiment: Esterification using acid anhydride Aim of experiment: Preparation of aspirin Procedure: 1) Put 2.5 gm of S.A in a dry conical flask*. 2) Add 5 ml of acetic anhydride**. 3) Shake well. 4) Add 3-5 drops conc. H2SO4 ***, 5) Warm on water bath to (50-60) oC for about (10-15) minutes. 6) Stirring, cooling (ppt. of aspirin ) then add 75 ml D.W. ***** . 7) Filtration, wash the ppt. with cold D.W. and collect the product (aspirin). Notes: “The conical flask should be ~ dried well since the presence of ~ moisture could hydrolyze acetic anhydride to acetic acid . / 9 O | | + HO ——> 2 H3C— °—~o—©~cH, Acetic anhydride At this point the excess unreacted Acetic anhydride must be hydrolyzed (split apart by the addition of water ) to acetic acid. Acetic anhydride is veryreactive toward water, so the hydrolysis must be done slowly, water should be added drop-wisely. More water is then added and the flask is placed in an ice bath to lower the solubility and precipitate the prepared aspirin. nC an 7 ~t It serves to measure the effectiveness of a synthetic procedure. % To calculate the percent yield of \ a reaction: 1- Write a balanced equation for the reaction. 2- Finding the limiting reagent. 3- Determination of the theoretical yield. 4- Determination of the actual yield. 5- Calculation of the percent yield. Actual yield ee . 100% Theoretical yield Percent yield = lin our experiment today COOH © o— fo CH; +H;cC—C—o— I cH, ——> + CH,;COOH 1 mole 1 mole 1 mole S.A, Acetic anhydride Aspirin - We used acetic anhydride in excess so salicylic acid is the limiting reagent. - Use salicylic acid to calculate the theoretical yield.