Pre Lab:

Pre-Lab Questions 

1. Copy the table below into you lab notebook and create a list of the work that you need to do in this first lab period for each of the three labs you are working on

Cyclohexene Lab

What analysis work do you still need to do? The post-lab is due this weekend

All experimental procedures completed, results, discussion, conclusion, and post-lab questions in lab book must be completed before the due date on 02/22/2025.

Grignard Lab

What workup and analysis work do you still need to do? The postlab is due in two weeks.

All of Activity #5 must be completed:

• Add 20 mL of "wet" ether to the RBF kept in lab drawer from last week. 

• Shake the flask vigorously to clear all product from the side of the container.

• Sonicate the flask in the sonicator.

• Transfer all product from the RBF into a beaker.

• If clumps of product remain add acetone to the beaker and to the ether layer until clumps dissolve.

• Add 25 mL of 10% sulfuric acid and 15 of ice to the beaker.

• Once bubbling stops, transfer the solution into a separatory funnel.

• Wash the ether layer with 10% sulfuric acid.

• Dry the ether filter and add 25 mL of hexane, ligroin, or petroleum ether. 

• Evaporate the ether-ligroin mixture using a steam bath until about 5 mL of solvent remains or crystals begin to appear.

• Remove the filter flask from the heat, place on ice and add hexane to form the precipitate. 

• Weigh your product and determine percent yield.

• Analyze product by TLC, melting point, and Mass Spec.  

Perform Benzoic Acid Workup:

• Heat the mixture to evaporate the ether until a precipitate is formed.

• Isolate the benzoic acid by filtering.

• Wash the precipitate with cold water and allow the crystals to dry for a week. 

Write all experimental steps, results for part one of activity 5. Final part of lab next week. 

Esterification Lab

What synthesis are you going to conduct 1st this week and what are the steps you will do in the lab (1st will… 2nd will…etc)

One (possibly two if enough time) esterification will be performed this week!

Instructions for Activity #1:

• Add 5.0 g of benzoic acid and 13 mL of methanol to 50 mL RBF.

• Cool this mixture on ice.

• Add 3 mL concentrated sulfuric acid. 

• Swirl the contents and add boiling stones.

• Connect RBF to reflux condenser and reflux the mixture for 1hr.  

• At the end of the hour, cool the reaction mixture.

• Transfer reaction mixture into a separatory funnel.

• Dilute 1:1 with water.

• Extract with ether and wash the ether layer with water.

• Was with saturated sodium bicarbonate.

• Wash with a saturated salt solution. 

• Dry the solution and remove the ether by vacuum evaporation in the hood using heat until the ether is gone or no time remains. 

• When pure product has been obtained, collect and record yield.

• Perform analysis through TLC,  refractive index, and IR data.  

• Pour products into the “Student Prepared Methyl Benzoate” bottle.

Instructions for Activity #2 (If Time):

• Add 3.0 g of salicylic acid and 4.2 mL acetyl chloride in a 100 mL Erlenmeyer flask.

• Add 3 drops of concentrated sulfuric acid.

• Swirl the solution to combine all the chemicals in the solution.

• Place the flask in a steam bath.

• Cover the steam bath with a watch glass and allow it to run for 15-20 minutes.

• Remove from the steam bath and add 5 mL of ice water.

• After the reaction has run to completion add 35 mL of water to the flask and place on ice. 

• Collect product via vacuum filtration. 

• Wash the solid using cold water.

• Calculated yield percent.

• Performed Trinder Qualitative test.

• Further analysis of the product using TLC and IR.

Write experimental procedures for all lab activities. The other synthases will be performed in the following lab weeks.

2. Using curved arrow formalism, in single steps, draw the mechanism of the reaction to create the 1st ester that you are going to make.  It is easiest to draw the mechanism ton paper and then upload the photo. Make sure that you refer either to the text or your class notes for the Esterification mechanism and draw it exact.  For good practice you should draw all 3 mechanisms however, you only need to draw 1.

See Image Labeled "2.)."

3.  Why is it important to measure out the salicylic acid accurately but not necessarily the acetyl chloride/acetic anhydride in activity #1?

The reaction with salicylic acid affects the stereochemistry of the reaction and will change the theoretical yield of the desired ester product. If an incorrect amount of alicyclic acid is used, a lower yield of the final product could be created than the desired theoretical yield. Acetyl chloride/acetic anhydride are highly reactive and large amounts in solution can help to ensure that the reaction runs to completion.

4.  An acetyl chloride molecule contains a better leaving group than a carboxylic acid molecule which is why it is often used as an electrophilic compound. What is the leaving group carboxylic acids? What is the leaving group for acetyl chloride?

The leaving group in a carboxylic acid is the hydroxyl group (-OH), a generally poor leaving group that often has to be protonated into the very good leaving group (HOH). 

The leaving group fro acetyl chloride is the chloride ion (-Cl), a very good halide leaving group. 

5.  When we use an anhydride as a reagent, the workup step requires hydrolysis of the anhydride to “destroy” it so that it is easily washed away during the extraction process. Using curved arrow formalism, draw the reaction that happens between acetic anhydride and water in the hydrolysis step.  What is the product?  

• The oxygen of water is your nucleophile

• The carbonyl carbon of the anhydride is the electrophile.  

• Draw the mechanism from what you know about how electrons usually move with an ester (especially in the month of February 🙂).

See Image Below labeled "5.)."

6. There is a lot of extraction in this laboratory and it is important to make sure that you always keep the correct layer.  Consider these two scenarios

• When you have a mixture of dichloromethane and a solution saturated with sodium bicarbonate, which layer contains the DCM, the top or the bottom?  

Dichloromethane will be at the bottom of a separatory funnel as it is more dense than sodium bicarbonate.

• When you have a mixture of ether and a solution saturated with salt, which layer contains the ether, the top or the bottom?

The saturated salt solution will be at the bottom of a seperatory funnel as it more dense than ether, making ether the top layer. 

7.  After extraction and washing steps, experiments in this lab state to dry and then evaporate.  What is the process of “drying” and what must you do between drying and evaporation?  It might be good to visualize in your mind these steps to answer the question.

"Drying" a solution means to remove any excess water from within it. One of the ways we most commonly dry a solution in our lab is by using sodium sulfate.  By adding sodium sulfate and swirling it in the solution until no more obvious clumps form you cause water within the solution to bond to the "dry" material. 

The sodium sulfate is then filtered out of the solution using gravity filtration and the solution can then be evaporated using heat to remove all remaining organic solvent, leaving behind only the desired product.

8. For making the two liquids methyl salicylate and methyl benzoate, you evaporate all ether or DCM to isolate the final product and a common question is, how do I know when it is all evaporated.  One method is to evaporate until you have heated the flask to the boiling point of the solvents.  What is the boiling point of ether and DCM in oC and oF?  And finally for comparison, what is the boiling point of water in oC and oF. Since day-to-day, we use oF, it is sometimes easier to think in Fahrenheit when assessing the temperature by feel.  

Boiling Point of Ether (Diethyl Ether):

• In Celsius: 34.6°C

• In Fahrenheit: 94.3°F

 Boiling Point of Dichloromethane (DCM):

• In Celsius: 39.6°C

• In Fahrenheit: 103.3°F

 Boiling Point of Water:

• In Celsius: 100°C

• In Fahrenheit: 212°F

9. Again for making the two liquids methyl salicylate and methyl benzoate, you can assess complete evaporation by yield.   To explain, if you know you should only have a yield of 10 mL however there is 20 mL in your flask then evaporation is not complete. Calculate the theoretical yield for both reaction #2 and #3.   You must calculate the moles of expected product from the moles of starting material, convert the moles to grams using molar mass and then convert from grams to mL using density. You need to show your calculations.

See Image Below Labeled "9.)" for work.

Theoretical Yield:

Methyl Salicylate: 3.34 mL

Methyl Benzoate: 3.12 mL

10. The lab reading includes special notes for each kind of analysis so as to ensure that you have good data to interpret

• For TLC, what is likely the reason why your standard and your product have very close Rf values but not exactly the same value?  What can you do to correct this?

The esterification reaction produces esters, which might have slightly different polarity than expected due to solvent retention. 

Rf values may also differ from impurities caused by an incomplete reaction or side reactions. These differences could be addressed by ensuring that the standard and product are dissolved in the same solvent before spotting, making sure the TLC plate is completely dry before running it, and using a more dilute sample to prevent impurities from appearing on the TLC plate. 

• For IR, what is likely the reason why you might have really broad peaks and transmission only 0-10%? What can you do to correct this?

Broad peaks are often the result of moisture contamination when water is absorbed in the system during workup. This can be prevented by ensuring the sample is completely dry before analysis.

• For MP/RI, what is likely the reason why you have bad data although all indications are that you made the correct product and that it is pure? What can you do to correct this?

Bad data may be caused by residual solvent present in the system, which can lower melting points or shift the refractive index. Experimental errors in temperature control (for MP) or improper calibration of the refractometer (for RI) can also lead to incorrect values. For both RI and MP analysis, allowing the product to dry will allow the solvent to be fully removed from the system to prevent inaccurate data.

Results

Activity #2: Acetylsalicylic acid

Theoretical Yield: 3.34 g

Isolated Yield: 3.12 g of white powder

% yield: 3.12 g / 3.34 g = 93% yield.

Tinder Test: Positive

Melting Point: 126.2-128.4°C

TLC: TLC was performed using a solvent with a ratio of 3:1 hexane to ethyl acetate. Lab-prepared acetylsalicylic acid was compared with an instructor-provided standard.

IR: See below image.

TLC: Acetylsalicylic Acid:

Solvent Front: 5.2 mm

Spot 1: 3.5 mm

Rf Value: 0.67

Activity #4: Isoamyl acetate 

 Theoretical yield: 4.1 mL

Isolated Yield: 2.6 mL / 2.6 g of pale yellow, pleasant-smelling liquid.

% yield:  2.6 mL/4.1 mL = 63% yield

TLC: TLC was performed using a solvent with a ratio of 3:1 hexane to ethyl acetate. 

RI: 1.3990

IR: See below image.

TLC: Isoamyl Acetate:

Student Prepared Sample

Solvent Front: 3.7 mm

Spot 1: 1.9 mm

Rf Value: 0.51

Lab Standard:

Solvent Front: 3.7 mm

Spot 1: 0.9 mm

Spot 2: 2.3 mm

Rf Value of Spot 1: 0.24

Rf Value of Spot 2: 0.62

Conclusion:

The results of this experiment indicate that, based on IR testing (and the trinder test for acetylsalicylic), both acetylsalicylic acid and isoamyl acetate were likely synthesized with good yield despite some impurities. The IR of methysalicylate indicates that another compound may have been synthesized with a lower-than-anticipated yield.