Concentrated Ammonia

Experiment 2 Name ………………………… . Reg. No ……………………… Date ………………………… ... SYNTHESIS OF BENZOCAINE Objective The objective of the experiment was to synthesize benzocaine Introduction Historically benzocaine has been used as an anesthetic which is said to be naturally found in plants. Centuries ago the Amerindians used the found Coco plant and started to chew its leaves, they noticed that as aconsequence of chewing the extract obtained acted as amild stimulant. It was supposedly from there on used as an integral part (exigencies) to cope with life. Chemists in due time took interest to investigate the leaves so the Coco plant and within no time they discovered that the leaves had the active ingredient which is an alkaloid, ‘cocaine; ’which is isolated in 1862. After afew years the properties of the alkaloid were investigated and was then a certified medical anesthetic in surgery and dentistry. But with time medical practitioners realized that besides the positive applications in medical procedures, cocaine and its derivatives had major disadvantages, in that, ithard severe and irreversible nervous system breakdown. As awake-up call, chemists resorted to finding the analogous drug of the parent structure of cocaine which could be an otherwise alternative and less lethal to human health. One that was successfully synthesized was Novocain ,which, overtly, its still being used across the world. The other simpler analogue is an ethyl ester of para-aminobenzoic acid, which is called "Benzocaine ". Most routes to medicinal products involve multi-step syntheses. In this case, commercially available 4-nitrobenzoic acid is initially converted to 4-aminobenzoic acid, followed by reaction with ethanol, under acidic conditions, to give the target benzocaine. +H2 +EtOH/H + Benzocaine In this first part of the two-stage preparation of benzocaine you will carry out the reduction of the nitro group in 4-nitrobenzoic acid (using zinc and hydrazinium monoformate) to generate 4aminobenzoic acid. In the second step, you will start from the 4-aminobenzoic acid that you prepared in Part 1. You will carry out an acid-catalyzed (Fischer) esterification of the carboxyl group using ethanol. The product, ethyl 4-aminobenzoate, is commonly known as benzocaine. Reagents and Apparatus 1. Para- nitrobenzoic acid 2. ethanol 3. concentrated H2SO 4 4. 10% sodium carbonate solution Procedure - In a1oomL volumetric flask and astirrer they added para-nitrobenzoic acid (5 g) and zinc powder (3.91 g) in absolute ethanol (20 mL) and stirred under anitrogen atmosphere. - In aseparate 100 mL conical flask they slowly added hydrazine hydrate (11 mL) dropwise to formic acid (8 mL) in an ice bath with constant and swirled for 2minutes. - They then added the obtained hydrazinium monoformate solution (12 mL) to the round bottom flask slowly and stirred for 3minutes - They filtered off the mixture using Buchner filtration and washed any excess residue with IMS. - Then transferred the liquid to apre-weighed 100 mL round bottom flask and evaporated the solvent on arotary evaporator. - They then recorded the yield and IR of the 4-aminobenzoic acid, and then added an absolute ethanol (10 mL) and acouple of anti-bumping granules to the 4-aminobenzoic acid from the previous step - Carefully, with gentle swirling, they added concentrated sulfuric acid (1 mL) with caution; the fitted areflux condenser and heated under reflux using aheating mantle for 1hour, thereafter cooled the clear solution under atap, and then poured into ice (around 10-20 g) in a100 mL beaker. - In afume-hood, they added concentrated ammonia (with CAUTION, FUMES) until a precipitate formed, then filtered off the solid, washed with alittle ice-cold water, sucked the dry at the pump and then recorded the yield and IR of the product finally formed. Results The IR spectra obtained for the first product obtained in step 6and in step 9are as shown in the data paper from the machine. The product formed in step 6was para-aminobenzoic acid and the last formed as ethyl-4-aminobenzoate (benzocaine). ASSESSED ASSIGNMENT 1. Benzocaine is an over the counter drug, but what are three of side effects from using this drug? - Some of the side effects of using benzocaine are such as sore throat, red and sore eyes, stinging or burning of the skin, fever and blistering, just to mention afew. 2. What potential stability problems might there be with benzocaine? Explain your answer with reference to the structure? - The stability problems with using the drug with reference to the structure, is that, a potential possibility of hydrolysis of the ester group is possible with HCl in the stomach is the drug is administered orally. Also, the amino group could take part reaction in the acidic environment in the stomach thus rendering the drug less potent. 3. Assign the 1H-NMR spectrum of benzocaine (include explanations for splitting, chemical shift and integration). - There are two pairs of aromatic protons, each is split into adoublet ,and occur at around (2H)7.81 and (2H) 6.52 ppm. This implies the pair at 7.81ppm is more deshielded and in close proximity to an electron withdrawing group (keto group) - There is -CH2- group (2H) that is split into aquartet .This implies the neighboring carbon has 3H protons (CH3). The -CH2- protons are very deshielded and occur at around 4.3ppm. this also means that the protons carbon is attached to an oxygen atom - CH2 -O-COO- - Lastly, we have atriplet .This is aCH3- group which is bonded to -CH2- group. It occurs at around 1.9ppm. - Note: the NH2 protons are not observed since there is an exchange of the protons with the solvent protons used for the instrument. 4. Draw the conjugate acid of benzocaine 5. 4-Aminobenzoic acid is the hydrolysis product of benzocaine. It has two pKavalues of 2.4 and 4.9. Assign these pKavalues to the appropriate functional groups and explain your answer. - The amino group is more basic therefore in the conjugate acid of aminobenzoic acid the a mino group will have apKa of 4.9 and the acyl group will have 2.4 6. The pKa of benzocaine is 2.4 and using the Henderson-Hasselbalch equation. Identify if it is absorbed in the stomach or intestine and briefly explain your answers. pH =pKa +Log ([A-]/]HA]) pH = 0.00398. the drug will be absorbed in the intestine, since the pH of the stomach is slightly above the calculated from our experiment. 7. Write down amechanism for the hydrolysis of the ester group in benzocaine. Would you expect the amino group to exert an electronic influence to speed up or slow down the reaction? 8. Benzocaine has been tested as an anesthetic for inhibition of m1 Muscarinic Acetylcholine Signaling. Using the data below, plot agraph and determine the IC 50. - The equation of the curve is y=-417.69x +74.735 The value of xwill give us the IC 50 and 417.69/74.735 =5.589, which is the IC 50 9. Propose a retrosynthetic analysis of benzocaine from the starting material shown. Your answer should include both the synthons and the reagents that would be employed in the actual synthesis. 10. How is benzocaine synthesized industrially from p-nitrobenzoic acid? Discussion The synthesized benzocaine and the spectra obtained, both the IR and the NMR were not all clear but they gave arough idea of the two products obtained at each stage of the procedure. The experiment as carried out had some errors which could be classified as indeterminates errors, since the results as obtained could as much correspond to the reference theoretical values. The peaks on IR spectra as shown can only give the functional groups. The prominent peak in IR spectrum was that of the keto group, that ranged somewhere around 1650cm -1and the amino group (-NH2-) around 3340 cm -1which gave aclue that our final product (benzocaine) contains an amino group, alongside the keto group. The fingerprint region of the IR spectrum could not be fully elucidated for the finer details of the possible functional groups in the product owing to the close proximity of the peaks. The functional groups predicted on IR were to be ascertained on NMR spectrum, which gave us the splitting patterns and the bonding coordination system. Conclusion The experiment was not all perfect, arepetition of the same could be recommended since the pKa and the pH values as calculated may not be all aligned with the theoretical values as found in literature. From the NMR splitting and the bonding system confirmed that the spectra of the intermediate product and the final synthesis of the benzocaine do correspond. It is of vital importance to note that the results as obtained may not have been absolutely accurate owing to the aforementioned errors, and therefore stands aroom of warrant to redoing the experiment to obtain abetter version of the experiment and overt accurate. From the questions as handled, itis of relief to note that the much the done on the final product does at least correspond to the theoretical figures and numbers. References 1. https://www.chemistry.mcmaster.ca/~chem2ob3/2004labmanual/2004_exp4.pdf 2. https://chem.libretexts.org/Ancillary_Materials/Laboratory_Experiments/Wet_Lab_Exper iments/Organic_Chemistry_Labs/The_Synthesis_and_Characterization_of_Carbonyl_Co mpounds/3:_Esterification_(Experiment) 3. https://www.google.com/search?q=ethyl+4- aminobenzoate&tbm=isch&ved=2ahUKEwjPorGn9tDwAhVU-4UKHeQuDuMQ2- cCegQIABAA&oq=ethyl+4- aminobenzoate&gs_lcp=CgNpbWcQA1CPyglYj8oJYMjRCWgAcAB4AIABAIgBAJIB AJgBAKABAaoBC2d3cy13aXotaW1nwAEB&sclient=img&ei=VX2iYI- kCNT2lwTk3biYDg