Question- Several students had trouble recrystallizing the final product. The co

Question

Question-

Several students had trouble recrystallizing the final product. The common problem was that no crystals formed after dissolving the crude product in a large quantity of hot ethanol. In concise bullet points, please list four possible solutions to this problem.

Background

The field of medicinal chemistry combines the specialties of synthetic organic chemistry and biology, and biochemistry. Compounds are generated and biological activity is screened using target specific assays. . These assays are commonly cellular. To identify drugs that produce biological activity, high-throughput-screening campains are commonly employed. Molecules that produce a response improved through iterative processes.. In some instances compounds are isolated from natural sources e.g. Taxol, and synthetic modifications can be performed to improve efficacy.. In practice, the iterative process is as follows: a positive screening result justifies the synthesisof a library of structural analogues to see if a change in substructure leads to increased potency in the standardized assay.. In concert, DMPK (Drug metabolism and pharmacokinetics) assays are run to test the ability of the drug canadite to withhold stresses like oxidation by a range of cytochrome P450 enzymes. The more reactive the drug is to these types of assays, the faster it is metabolized. Fast metabalizom leads to shorter half lives in the body. Candadets of interest can also be run in animal models at any point. For neourscience aplications, it is common to quantify the amount of the drug that has passed through the blood- brain barrier by decapitating the dosed rats and quantifying the amount of drug in the pulverized head. For antidepressants, a number of tests can be performed e.g. the forced swim test. Toxicity studys are run on the promising canadite(s). With these canadites, larger animal models are used. These can include dogs, pigs, and monkeys to name a few common ones.

Acetaminophen, the major ingredient in the NSAID Tylenol, is readily accessible by the reaction of p-aminophenol and acetic anhydride following the first reaction in the scheme above. An effective structural analogue of acetaminophen is phenacetin, a component of several headache and cold medicines. Phenacetin is produced by converting the hydroxyl group of acetaminophen to an ether group by a Williamson Ether reaction as shown in reaction 2 in the scheme above. Experiment 4 provides an opportunity to synthesize, purify, and analyze acetaminophen and phenacetin.

Reaction 1 – Acetylation of an Aminophenol

To a 10 mL round-bottomed flask equipped with a magnetic stir bar, add 1.1 g of your assigned aminophenol and 3.0 mL of water. Carefully add 1.2 mL of acetic anhydride and stir vigorously a hot water bath. Continue stirring until the solid has completely dissolved which should take

approximately 10 minutes. Remove the flask from the hot water bath and allow the reaction to come to room temperature on the benchtop. Place the flask in an ice bath to complete the cooling process. Set up a vacuum filtration to isolate the precipitated product, using a minimum amount of cold water to wash the solid. Keep the solid on the vacuum filter for ~10 minutes to complete the drying process. Weigh the crude product and record the mass. Purify the crude product by recrystallization using water as the solvent. Repeat the vacuum filtration process to isolate the pure acetylated aminophenol product and measure a final mass. Obtain an IR, 1H NMR, and melting point for the product.

Reaction 2 – Williamson Ether Synthesis of an Acetylated Aminophenol

To a clean and tared 25 mL round-bottomed flask, carefully add ~160 mg of solid sodium. Use extreme caution when handling the sodium pieces as they readily react with water. Be sure to use gloves and keep away from all sources of water. Set-up a water cooled reflux condenser equipped with a CaCl2 drying tube. Add 4.0 mL of absolute ethanol through the top of the reflux condenser and quickly place the drying tube on top again. The sodium/ethanol reaction should happen very quickly with all of the sodium dissolving. If solid does remain in the flask, place the reaction on a steam bath to promote dissolving. Bring the reaction to room temperature and add a predetermined mass ~1.0 g of your acetylated aminophenol to the flask. Carefully obtain and add 0.8 mL of ethyl iodide to the reaction flask. Use extreme caution when adding the ethyl iodide as it is a powerful alkylating agent. Be sure to use gloves when adding to the reaction and work in the hood for the addition. Return the reaction to the lab bench and reflux the reaction for 45 minutes using a steam bath. Quench the reaction with 10 mL of water added through the top of the condenser. Remove the apparatus from the steam bath and cool the reaction to room temperature. Complete the cooling process by immersing the flask in an ice bath. Collect the resulting product via vacuum filtration and wash the crystals with a minimum amount of cold water. Purify the crystals by recrystallization using ethanol as the solvent. Repeat the vacuum filtration process to collect the pure product and measure a final mass. Obtain an IR, 1H NMR, and melting point of your pure product.

Explanation / Answer

Basic principles behind effective decentralization is

1) Selection of suitable solvent- In order to carry out exercise solvent should be selected on the basis of polarity .If crude compound is polar ,then select mild polar solvent such as ethyl acetate.It dissolved solute and forms supernate solution ,so if you started recovery of dissolved solute ,you get it ...

At same time solution amount is also important.

2) Temperature- add predecided quantity of boiling solvent so maximum amount of solute dissolved in solvent,so you could get better recovery of pure compound.

3) Seeding- if your solute dissolved completely,not precipitated a even after cooling then add pure compound as seeding agent .Then time required for precipitation may suppressed.

4) Slow agitation while recrystalization is also important.It minimizes chances of coprecipitation and post precipitation.

Related Questions

Navigate

• Browse (All)
• Browse Q
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.