TP Synthèse de la menthone BTS 2 SYNTHÈSES DE LA BENZOCAÏNE L’assistant ingénieur a commencé à rassembler un corpus documentaire. Les informations fournies sont susceptibles de vous permettre de gérer vos démarches. Votre travail consiste à adapter le protocole au cahier des charges ci-après : BENZOCAÏNE Caractéristiques Etat (25 °C, 1 atm) Solide Couleur Blanc Aspect Poudre cristalline Odorant Sans odeur caractéristique Contraintes économiques Masse théorique attendue 4g Rendement > 70 % Pureté > 90 % Prix, 250 g (en ne considérant que les prix des matières premières principales : acide paraminobenzoÏque et éthanol) < 70 € Avant de commencer toute démarche expérimentale, les listes de matières premières et matériel doivent être rédigées. En outre, la matière d’œuvre (quantité d’espèces chimiques utilisées) permettant la synthèse, le traitement du milieu réactionnel, la purification et les éventuelles analyses) doit être explicitée au professeur encadrant l’équipe. Page 1 sur 4 TP Synthèse de la menthone BTS 2 CORPUS DOCUMENTAIRE Document 1 To a 100-mL round bottom flask fitted with a stir bar, add 2.50 g of p-aminobenzoic acid and 20 mL of ethyl alcohol. While stirring, add 2.0 mL of concentrated H2SO4 dropwise. The precipitate that forms upon the addition of sulfuric acid should dissolve when the solution is heated. Reflux, with stirring, for 1 hour. If you notice that the white suspension persist, add 1 additional mL of concentrated H 2SO4 dropwise. Cool to room temperature. Neutralize cautiously with dropwise addition of 10% Na2CO3 until the pH is approximately 8. (Gas evolution will be vigorous.) Extract with two 10-mL portions of methylene chloride. Wash the combined methylene chloride layers with two 8mL portions of water. Dry the methylene chloride solution over anhydrous sodium sulfate. Gravity filter into a clean Erlenmeyer flask containing a boiling stone. Evaporate the methylene chloride using the rotary evaporator. Cool the oil. Recrystallize the whitish residue using as a solvent pair, ethyl alcohol and water 50/50. Suction filter the product, and let air dry. Weigh the white crystals and take the melting point. Perform IR spectroscopy and compare the IR of the p-aminobenzoic acid to that of the product (collect 2 IR spectra: 1 of the starting material and 1 of the product). Fischer Esterification of p-aminobenzoic acid : Synthesis of Benzocaine adapted from the Revised Procedure: Expt. 21.1 Multistep Synthesis of Benzocaine Analogs Document 1 Synthesis In a 5-mL round bottom flask, add 120 mg of 4-aminobenzoic acid (often called PABA for p-aminobenzoic acid), 1.5 mL of absolute ethanol (absolute ethanol is completely free of water and can be found on the hooded shevles), and 3 boiling chips. Heat this mixture on a sand bath until all thesolid dissolves. Cool in ice and then add 0.25 mL of concentrated sulfuric acid dropwise. (One drop at a time.) A large amount of precipitate will form when the sulfuric acid is added, but this will dissolve during the reflux that follows. Attach an air condenser from the microscale kit, and reflux gently for 60-75 min. Check periodically to be sure that the mixture is refluxing gently, and that the ring of condensation of solvent lies somewhere along the inner surface of the air condenser; loss of solvent will cause overheating and significant decrease in yield. Isolation and Purification Detach the air condenser from the reaction tube and allow the reaction mixture to cool to room temperature. Take a TLC of the reaction mixture. TLC plates should have three spots (or lanes) on the origin: one for the main organic starting material that is being transformed (aminobenzoic acid), one for a cospot (starting material and the reaction mixture), and one for the reaction mixture. Find an appropriate mobile phase; start with 50% EtOAc in hexanes. Using a Pasteur pipet, transfer the reaction solution to a 10-mL Erlenmeyer flask and add 3 mL of distilled water. Dropwise, add saturated sodium bicarbonate (about 3 mL, approximately 10% or 1 M) to neutralize the excess sulfuric acid and the ammonium sulfate salt form of the amino ester (making it neutral and insoluble in water). After each addition of the sodium bicarbonate, agitate the solution to mix thoroughly. Extensive CO2 evolution (gas) and frothing will be observed until the mixture is nearly neutralized. As the pH increases, a white precipitate of benzocaine is produced. When gas no longer evolves as you add a drop of sodium bicarbonate, check the pH of the solution with "Alkacid" pH paper and, if it is less than 8, add further portions of saturated sodium bicarbonate solution. Collect the benzocaine by vacuum filtration using a Hirsch funnel. Use three 1-mL portions of cold water to wash the product crystals from the flask onto the funnel. Make sure the product is rinsed thoroughly with cold Page 2 sur 4 BTS 2 TP Synthèse de la menthone water water. After the product has dried thoroughly by leaving it in an open container until the next lab period, weigh it, calculate the % yield, and determine its melting point. The m.p. of pure benzocaine is 92°C. Although the product should be fairly pure, it may be recrystallized by the mixed solvent method using methanol and water. Place the product in a preweighed reaction tube, and while stirring with a boiling stick and heating in a sand bath, add methanol dropwise until the solid just dissolves. Add 2 to 3 additional drops of EtOH and then add hot water dropwise until the mixture turns slightly cloudy or a white precipitate forms. Add methanol again while heating until the cloudiness or solid just disappears. Let cool slowly to room temperature and then complete the crystallization by cooling in an ice bath. Collect the solid by drawing the solvent off through a pipet using the pipet filtration technique. After the solid has dried in the open tube until the next lab period, reweigh the tube to determine the weight of recrystallized material and then take its melting point. Analyze the product as directed on your experimental assignment sheet. If you are doing an NMR analysis, you may have to use deutero-DMSO as the NMR solvent as the product may have partial solubility in CDCl 3. Refer to Chap 11 of the Lab Guide for instructions on sample preparation. Analysis In addition to TLC analysis, you may be instructed to analyze your final product by IR, NMR or MS. Analyze your sample according to your assignment sheet and prepare it as per the instructions on Sample Preparation in the Lab Guide. Document 2 CCM ….. Contrôles Pour contrôler la synthèse, une chromatographie sur couche mince peut être réalisée. Les conditions de la CCM sont les suivantes : ● phase stationnaire : silice sensible aux UV, ● éluant : cyclohexane/acétate d’éthyle10/10 et deux gouttes d’acide acétique, ● solvant pour la préparation des échantillons : éthanol. Dissoudre de l’ordre de 50 mg de benzocaïne synthétisée dans 2 mL d’éthe diéthylique puis analyser cette solution en CPG The Preparation of the Local Anesthetic, Benzocaine, by an Esterification Reaction Adapted by R. Minard (Penn State Univ.) from Introduction to Organic Laboratory Techniques: A Microscale Approach, Pavia, Lampman, Kriz & Engel, 1989. Revised 06/27/06 Document 3 Données Solubilité dans 100 mL d'eau d'éthanol d'éther acide 4-aminobenzoïque très faible 0,7 g à 25 °C 1,1 g à 90 °C 11,3 g 8,2 g 4-aminobenzoate de sodium benzocaïne éthanol éther très soluble très faible infinie 7,5 g très faible très faible 20,0 g 14,3 g infinie Page 3 sur 4 infinie TP Synthèse de la menthone BTS 2 DONNEES SOUS 1,013 BAR Espèce chimiques Benzocaine Données physico-chimiques Sécurité M = 165,19 g.mol-1 Tf = 88 à 90°C Teb = 172 °C H336 P261 Ethanol 25 € pour 1 L M = 46,07 g.mol-1 Tf = -114°C Teb = 79 °C d20 = 1,83 H225, P210, P305+P351+P338, P370 +P378 et P403+P235 20 n D = 1,3594 Acide sulfurique concentré M = 98,08 g/mol d20 = 0,789 20 n D = 1,4184 Éther diéthylique (éthoxyéthane) H290, H314, P280, P309, P310, P301 +P330+P331 et P305+P351+P33 M = 74,1 g.mol-1 Tf = -116 °C Teb = 35 °C d20 = 0,789 20 H224, H302, H336, EUH019, EUH066 n D = 1,3506 Sulfate de magnésium anhydre 37 € pour 250 g M = 137,14 g.mol-1 Tf = 188,5 °C Téb = 188,5 °C Dichlorométhane M = 84,93 g.mol-1 Tf = -95,1°C Teb = 40 °C d20 = 1,33 Acide paraminobenzoïquel 20 H351 n D = 1,421 Données Page 4 sur 4
