How do we synthesize new substances? (Two-Week Experiment) Lab Session 12 This is a two-week experiment in which they will explore how to use chemical reactions to synthesize new substances. How do we synthesize new substances? (Two-Week Experiment)

The End is Near(ing) 9 10 11 VTs Day No classes 12 13 VTs Day Make up 16 CHEM 151 Exam 3 17 18 19 20 23 No Labs 24 25 26 Thanksgiving 27 30 Lab Finals Week 1 December 2 3 4 7 Exam 4 8 Last Day DEAD DAY No Classes Finals Begin Calendar review. Point out the following: This week. Week one of the aspirin synthesis. Make some aspirin. Next week. Week two. Characterize the aspirin. Thanksgiving week. No labs (except for Tuesday labs). Study for final. Week of Dec. 1. Lab final and checkout. Written & practical. Structured like the midterm. All outstanding work (reports, etc) due.

Until now we have been focused on Chemical Analysis. What have we done? Until now we have been focused on Chemical Analysis. Detection: Does the sample contain substance X? Identification: What is the identity of the substance in this sample? Central Goals and Questions Separation: How can the substances present in the sample be separated? Quantitation: How much of substance X is in the sample? Emphasize that all that we have done until this point is to learn about how to answer the central questions in chemical analysis

Synthesis How do I make it? Where are we going? Analysis What is this? Synthesis How do I make it? Transformation How do I change it? This is the first experiment that has do to with chemical synthesis. They will continue in CHEM 152. Modeling How do I explain it? We will now start to explore the ideas and techniques used to “synthesize” new substances.

Personalized drugs – Soon (perhaps) Chemical Synthesis Chemical synthesis has given us, among other things, many of the medicinal drugs that have dramatically increased life quality and span in the past 100 years. Aspirin - 1880s Heroin – 1890’s Sulfa drugs – 1940’s Statins – 1980’s Viagra – Y2K Personalized drugs – Soon (perhaps) Aspirin (1880s) – the first mass marketed manufactured drug. Often considered the start of the drug industry Heroin (1890s) – the success of aspirin applied to a different material with a wholly different outcome. The acylation of morphine produced another “wonder drug” that wasn’t as wonderful as aspirin. Sulfa drugs (1940s) – a class of anti-bacterial drugs. the “wonder drugs’ of WWII credited with saving the lives of thousands of wounded soldiers. Statins (1980s) – a class of modern drugs developed to counter the deleterious effects of modern living (high cholesterol) (the pictured molecule is the first commercially marketed statin) Viagra (1998) – a drug emblematic of the broad spectrum of problems we currently attempt to address with synthesized drugs.

What do you have to do to complete your task? Your Challenge Imagine that you work for a drug company interested in testing a new procedure to synthesize aspirin. You have been asked to evaluate whether the procedure is feasible and marketable. Introduce the challenge to be faced in this two-week experiment. What do you have to do to complete your task?

Acetyl salicylic acid (Aspirin) Initial Ideas Discuss in your groups what types of tests you have to do and what type of information you need to evaluate the feasibility and marketability of this procedure. C7H6O3 + C4H6O3  C9H8O4 + C2H4O2 Salicylic acid Acetic anhydride Acetyl salicylic acid (Aspirin) Acetic acid Analyzing the problem they are to address. Can this procedure be used to PROFITABLY make aspirin tablets? Cost of Ingredients and manufacture; Safety issues; Reaction yield.

We need to find out the cost of the reactants. Costs We need to find out the cost of the reactants. C7H6O3 + C4H6O3  C9H8O4 + C2H4O2 Salicylic acid Acetic anhydride Acetyl salycilic acid (Aspirin) Acetic acid What do we need to complete the table? Click on banner to load up Fisher catalog. Type name of chemical into search bar. Select the first entry. Have the students search their own stuff (ask them to bring a laptop per group) Chemical Cost Amount http://www.fishersci.com/

Other Costs Make a list of other costs that would have to be determined. Make an estimate for each. People to perform the reaction; Packaging; Marketing; Management. This is not an exclusive list and the estimates can be all over the place. The idea is to begin to develop thoughts. A consensus is not necessary.

Safety While we’re looking up chemicals, let’s also look at the best source of information regarding the dangers of chemicals – The Material Safety Data Sheet. Now go back and for each of the three bring up the MSDS sheets. Go through the various categories of information provided. For the acetic anhydride note that it is a Lachrymator (substance which increases the flow of tears). Have the students search their own stuff (ask them to bring a laptop per group) http://www.fishersci.com/

Safety As you can see, the reagents used in this reaction have the potential to cause chemical burns and possibly allergic reactions. To protect yourself from inadvertent contact with these chemicals you must wear gloves while performing the experiment. None of the reagents are poisonous (unless they drink them). We’re concerned about chemical burns from contact with spills, etc.

How many moles of C7H6O3 will you use? Reaction Analysis Acid Catalyst It is proposed to use 2.0 g of C7H6O3 with 9 mL of C4H6O3 (r = 1.082 g/mL ) to do the reaction. Stoichiometry has not yet been covered. Walk students through this analysis. The Acetic anhydride is added in excess. Thus, the maximum amount of aspirin that can be synthesized is determined by the initial amount of Salicylic acid. How many moles of C7H6O3 will you use?

Why should you expect a lower yield than this? Theoretical Yield Acid Catalyst Calculate the maximum amount of Aspirin, in grams, that you will be able to synthesize? This amount is called the “Theoretical Yield.” Introduce and discuss the idea of theoretical yield Why should you expect a lower yield than this?

Actual or Percent Yield How are you going to calculate the actual yield of your reaction? What measurements and calculation do you need to make? Discuss the concept of actual yield and what they need to do to get it once they do their reaction.

Once you finish, report your percent yield on the board. Your Challenge Following the procedure given in your lab manual, manufacture some aspirin. Available resources: Salicylic acid and acetic anhydride. Balances (TC 4). Volumetric glassware. You have 90 minutes Before sending to the lab, go over the next slide. Once you finish, report your percent yield on the board. BUT, before you go…….

The acetic anhydride is destroyed by water. All glassware must be dry. Safety Precautions The acetic anhydride is destroyed by water. All glassware must be dry. Step 3 - The cotton plug is to keep water vapor out of the reaction flask. Step 6 – The reaction of acetic anhydride with water can be violent. Step 6 - When transferring the product keep the amount of water added to a minimum. The last item has to do with the crystallization of the raw product. It won’t happen if there is too much water.

Claims and Evidence Based on the results of your experiments, present your major claims (percent yield) and the evidence that you have to support the answer to the challenge. Are their claims clear? Is the evidence reliable? Is the evidence appropriate to support the claims? How do you explain the results? Ask each of the groups to report their results on the board. Have the rest of the groups question the claims and the evidence using the questions on the slide as a guide. They should be able to the calculation by themselves. Does anyone have a value greater than 100%? Discuss how that can be. Have them note the appearance of their products. Do they look to be pure, white crystalline materials? If no, why not? The next issue to address is purity.

Can we put our crude aspirin into tablets? Reflections What’s next? Can we put our crude aspirin into tablets? What do we need to do now? We need to purify our product Make students discuss what they can do to purify their product. How?

Recrystallization In your group, create an outline of the various things you will need to do to successfully recrystallize your aspirin. Have the students come up with a plan and then have a whole class discussion. Discuss methods to recrystallize (evaporation, scrapping, seeding)

Your Next Challenge Recrystallize your aspirin product. Available resources: Ethanol Glassware Ice bath Hot plate You have 60 minutes Two notes The manual calls for an eyedropper. A transfer pipette will work as well. Water is your enemy here. If the ethanol gets too wet or if the product is damp the solubility of the aspirin will greatly increase reducing the ultimate yield. Too much water and the aspirin will not recrystallize at all. Hint: Minimize ethanol use to less than ten drops during recrystallization Once you finish, report your new percent yield on the board.

Claims and Evidence Based on the results of your experiments, present your major claims (percent yield) and the evidence that you have to support the answer to the challenge. Are their claims clear? Is the evidence reliable? Is the evidence appropriate to support the claims? How do you explain the results? Ask each of the groups to report their results on the board. Have the rest of the groups question the claims and the evidence using the questions on the slide as a guide. Once you have all or at least most of their yields, have them discuss the values in their groups As a class try to decide what a “good” yield is for this experiment.

Final Reflections What did you learn from doing your experiment? How would you improve what you did? How have your ideas changed as a result of this lab? What do you not completely understand? What new questions do you have? Use these questions to motivate a discussion and emphasize major points you want students to understand.

Next Week No Report due Next Week Can we put our recrystallized aspirin into tablets? What kind of chemical analysis remains to be done? How are we going to achieve it? Melting point TLC Titration Set up for next week The answers are 1) rhetorical question (2) no, or more accurately we can’t yet SELL the tablets (3) identification and quantification Click on banner to load up Fisher catalog. Type name of chemical into search bar. Select the first entry. No Report due Next Week