Transcript Lab 9
EXPERIMENT SIX SYNTHESIS AND PURIFICATION OF BENZOCAINE Key concepts A topical medication is a medication that is applied to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes including but not limited to creams, foams, gels, lotions and ointments. Anesthesia, or anaesthesia (from Greek αν-, an-, "without"; and αἴσθησις, aisthēsis, "sensation") traditionally meant the condition of having sensation (including the feeling of pain) blocked or temporarily taken away. Local anesthesia is drug induced reversible local blockade of pain sensation in specific part of the body that doesn't alter consciousness or block sensation in other part ESTERS DEFINITION An ester is fragrant organic compound where the hydrogen in the compound's carboxyl group is replaced with a hydrocarbon group INTRODUCTION: Benzocaine is one of the widely used local anesthetics that act by preventing the impulse transmission along the nerve fibers. Benzocaine is the common name of ethyl aminobenzoate, normally prepared by acid catalyzed esterification. PHARMACOLOGY AND USE: Benzocaine is a local anesthetic commonly used as a topical pain reliever. It is the active ingredient in many over-the-counter analgesic ointments. It is also indicated for general use as a lubricant and topical anesthetic on intratracheal catheters and pharyngeal and nasal airways to obtund the pharyngeal and tracheal reflexes; on nasogastric and endoscopic tubes; urinary catheters; laryngoscopes; proctoscopes; sigmoidoscopes and vaginal specula. It is also used to suppress gag reflex. [gag: a surgical device for holding the mouth open.or to strive to vomit.] Benzocaine is a local anesthetic commonly used as a topical pain reliever or in cough drops. It is the active ingredient in many overthe-counter anesthetic ointments such as products for oral ulcers. It is also combined with antipyrine to form A/B Otic Drops to relieve ear pain and remove earwax. Benzocaine is used as a key ingredient in numerous pharmaceuticals: Over the counter throat lozenges such as Anbesol and Cepacol. Some glycerol-based ear medications for use in removing excess wax as well as relieving ear conditions such as Otitis Media and swimmers ear. Some previous diet products such as Ayds. Some condoms designed to prevent premature ejaculation. Benzocaine acts to desensitize the penis, and theoretically allows an erection to be maintained. MECHANISM OF ACTION A surface anesthetic that acts by preventing transmission of impulses along nerve fibers and at nerve endings. Benzocaine binds to sodium channel and reversibly stabilizes the neuronal membrane which decreases its permeability to sodium ions. Depolarization of the neuronal membrane is inhibited thereby blocking the initiation and conduction of nerve impulses. DOSAGE FORMS Benzocaine products—which are sold as gels, liquids, sprays and lozenges …. Precausions But the use of benzocaine gels and liquids for mouth and gum pain can lead to a rare but serious—and sometimes fatal—condition called methemoglobinemia, a disorder in which the amount of oxygen carried through the blood stream is greatly reduced. And children under 2 years old appear to be at particular risk. What parents do? Advise your adult patients “ Do not use them more than 4 times a day”. PHYSICOCHEMICAL PROPERTIES: Description: white, crystalline powder. Sparingly soluble in water. Mwt = 165.2 g/mole Melting point = 92 °C [between 88and 92,but the range between beginning and end of melting does not exceed 2], so Melting range. 88-92°C SYNTHETIC PROCEDURE: In a100 mL round bottom flask, add 2.5 mg of 4-aminobenzoic acid (often called PABA for Para aminobenzoic acid), 20 mL of absolute ethanol and 3 boiling chips. Heat this mixture on a sand bath until all the solid dissolves. Cool in ice and then add 2 mL of concentrated sulfuric acid drop wise. 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 and reflux gently for 60 min. Check periodically to be sure that the mixture is refluxing gently. Allow the reaction mixture to cool to room temperature. Transfer the reaction solution to an Erlenmeyer flask and add 40 mL of distilled water. Drop wise, add saturated sodium bicarbonate to neutralize the excess sulfuric acid and the ammonium sulfate salt form of the amino ester (making it neutral and insoluble in water). 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. Collect the benzocaine by vacuum filtration. Use three 1-mL portions of cold water to wash the product crystals from the flask onto the funnel. Dried thoroughly by leaving it in an open container until the next lab, weigh it, calculate the % yield, and determine its melting point. The m.p. of pure benzocaine is 92°C. Mechanism of reaction HEATING METHODS steam bath hot water bath sand bath oil bath hot plate heating mantle What other equipment you can add? DRYING AGENTS Drying agent is a chemical used to remove water from an organic compound that is in solution. Drying agents should be insoluble in the solvent to be dried as well as unreactive toward both the solvent and the solute. Drying agents should also remove water quickly and be easily removed by filtration. EXAMPLES OF DRYING AGENTS Class of compounds: Recommended drying agent Alkane, alkyl halides: MgSO4, CaCl2, CaSO4, H2SO4, P4O10 Aromatic hydrocarbons, ethers: MgSO4, CaCl2, CaSO4, P4O10, Na-metal Aldehydes, ketones, esters: Na2SO4, MgSO4, K2CO3, CaSO4 Alcohols: MgSO4, K2CO3, CaSO4, CaO, BaO Amines: KOH, K2CO3 Acidic compounds: Na2SO4, MgSO4, CaSO4 CALCULATIONS: Mwt of benzocaine = 165.2 g/mole Mwt of p-aminobenzoic acid=137.14 g/mole Mwt of ethanol=46.07 g/mole Density of ethanol=0.789 g/ml Note : flaky crunchy bowtie crystals. IDENTIFICATION A: Infrared Absorption á197Kñ:previously dried over phosphorus pentoxide for 3hours. B: Ultraviolet Absorption á197Uñ—Solution: 5µg per mL. Medium: chloroform. Absorptivities at 278nm,calculated on the dried basis,do not differ by more than 3.0%. C: Dissolve about 20mg in 10mLof water with the aid of a few drops of 3Nhydrochloric acid,and add 5drops of a solution of sodium nitrite (1in 10),followed by 2mLof a solution of 100mg of 2-naphthol in 5mLof 1Nsodium hydroxide:an orange-red precipitate is formed. NMR Gas chromatography–mass spectrometry (GC-MS) is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample. NMR Assay Nitrite titration,. Each ml of sodium nitrite (0.1 mol/l) VS is equivalent to 16.52 mg of C9H11NO2. chromatography Accepted Ranges Benzocaine,dried over phosphorus pentoxide for 3hours,contains not less than 98.0percent and not more than 101.0percent of C9H11NO2. For lozenges:85-120% Quiz Write the name of reactants & products of our today experiment. Write 4 informations about drying agent with examples.