Chemistry 211-212 Preparative Experiments

Name:_____________________________ TA Name:__________________________

Experiment # 17 ______________________Lab Day:________________________

Pre-lab exercises (20 points)

Pre-lab write-up (Sections I-VI) (92 points)

Completed report (Sections VII-IX) ( 6 points)

Answers to Assigned Problems (Section X) (20 points)

Product (yield, purity, appearance) ____________ (20 points)

TOTAL: __________ (218 points)

SCORE ___________ (percent)

This is your report cover. Please fill this form out and attach it to your write-up form.

PLEASE NOTE: THIS IS A FORM WRITE-UP. Form is at the end of experiment.

17-1

General Safety ConsiderationsExperiment 17

The Haloform Reaction of Acetophenoneand

The Aldol Reaction

1. All the organic chemicals used in these reactions should be considered to be flammable, toxic irritants.

2. Bleach is an irritant and is harmful if swallowed. Bleach can give off chlorine gas which is a respiratory and eye irritant.

3. Concentrated HCI is corrosive.

4. As always, constantly wear gloves, goggles and work in the hood. In the event that you come in contact with any of the chemicals being used, flush the exposed area with cold water for fifteen minutes. Alert your instructor when chemical exposure occurs and when large spills occur.

A flow chart for the Aldol reaction is not included because the procedure is so simple.

Experiment 17The Haloform Reaction of Acetophenone

The Aldol Reaction

By now you should be acquainted with the fact that hydrogens in the alpha position to a carbonyl are relatively acidic. For example, the hydrogens in acetone have a pKa of approximately 20, whereas the hydrogens of ethane have a pKa of approximately 50. If treated with a suitable base, these “acidic" hydrogens can be abstracted forming an enolate anion which can be used as a nucleophile in a variety of reactions, e.g., aldol reaction, Claisen condensation, alpha-alkylation, haloform, etc. The following equations outline the abstraction of an alpha hydrogen by a base (B:) and the subsequent reaction of the resulting nucleophile with an electrophile (E+).

If the electrophile used is a halogen, the resulting product will have substitution of halogen for hydrogen as shown in the following equation.

If a molecule has multiple alpha hydrogens, all can be substituted with halogen if excess base and halogen are used. In fact, methyl ketones go one step further. When treated with excess base and halide, all three hydrogens are replaced with halogen and the carbon-carbon bond between the carbonyl and the alpha carbon will cleave due to the final nucleophilic attack of the base on the carbonyl. This process is outlined below using NaOH as the base.

The products of this reaction are haloform (H-CX3 - hence the name of the reaction!) and the salt of a carboxylic acid.

The haloform reaction was used more typically in the years when spectroscopy was less available as a test for methyl ketones where an unknown compound is treated with I2 and NaOH (Iodoform test). The formation of iodoform (a yellow, crystalline solid) is taken as evidence for the presence of a methyl ketone grouping. Methyl secondary alcohols, methyl primary alcohols and methyl aldehydes also give positive iodoforms.

In this week's experiment you will convert acetophenone into benzoic acid and chloroform using bleach (NaOCl(sodium hypochlorite - active ingredient) as the base and chlorine source as outlined in the following equation:

acetophenone benzoic acid chloroform

In addtion to the haloform reaction, this week's experiment will include the microscale synthesis of tetraphenylcyclopentadienone via double aldols followed by double hydrolyses. The overall reaction is as follows.

17-6

In preparation for this week's lab, you should read about the haloform and aldol reactions in your textbook and answer the following questions.

1. In terms of resonance theory, explain the markedly increased acidity of acetone relative to ethane.

2. Explain the following reaction results in terms of electrophilicity and leaving group ability.

3. Which of the following compounds should give a positive iodoform test. Explain, a. 2-pentanone b. 3-hexanol c. acetone

17-7

Haloform Reaction

Procedure

1. Add 40 mL of bleach, 1.0 mL of acetophenone and a boiling stone to a 100 ml round-bottom flask.

2. Vigorously swirl the flask and then equip it with a reflex condenser. Heat the flask over a hot water bath (at or near boiling) for 15 minutes.

3. Remove the flask from the heat source and add 8-10 drops of acetone.

4. Equip the round-bottomed flask for simple distillation. Use a 10 ml graduated cylinder as a receiver. During the distillation, cool the receiver in an ice bath. Distill the mixture until the still head reaches 7 0 ° C . Remove the heat source. Identify any chloroform (CHCl3) obtained using its density vs. H2O. You may not isolate any CHCI3 depending on lab temperatures and yield.

5. When the still pot is sufficiently cool, remove the round-bottom and add a small amount of decolorizing carbon. While intermittently swirling the mixture, heat it to the boiling point and gravity filter.

6. Add concentrated hydrochloric acid (HCl)dropwise to the hot solution to achieve a pH = 2. Use care when using HCl. Wear gloves goggles and aprons and clean up your area. If you have a bad spill, notify your instructor or TA. Use your pH paper to measure the pH. Allow the mixture to cool to room temperature.

7. Further cool the mixture in an ice bath and collect the resulting crystals by vacuum filtration. Rinse the crystals with a small amount of ice cold water.

8. Allow the crystals to dry for several days and then weigh them and measure the dried crystal melting point range .

Aldol Reaction

Procedure no. A – microscale using a microwave

Procedure

1. Add 0.11 gram of benzil and 0.11 gram of 1.3-diphenylacetone to a standard test tube.

2. Using a Pasteur pipette, wash down the sides of the test tube with 1 mL of triethylene glycol.

3. Mix the contents of the tube and irradiate the tube in the microwave (see your instructor for guidance before you begin) for 1 minute at fifty percent power. We will be doing the irradiations in groups of one to five in a large beaker.

4. Add approximately 1 pellet of crushed KOH to the hot tube. Do not handle KOH with your hands or your gloved hands. Close the lid on the KOH bottle as it is hygroscopic.

5. Using a Pasteur pipette wash down the sides of the tube with 5 drops of methanol.

6. Irradiate the tube in the microwave for one minute at fifty percent power.

7. When the tube becomes cool enough to handle, add 1 mL of methanol and cool it in ice.

8. The solid, deep purple tetraphenylcyclopentadienone can be isolated by vacuum filtering out the crystals (be sure to use your micro vacuum apparatus). Rinse the test tube out with 1 mL of cold methanol several times. Pour these rinsings through the Buchner (Hirsch) funnel.

9. The sample can be weighed and the melting point can be measured after drying the tetraphenylcyclopentadienone for several days. Unrecrystallized tetraphenylcyclopentadienone typically has a melting point range of 218-220°.

10. The UV/visible spectrum ( llambda max) of your product may also be measured (ask your instructor). To measure llambda max for your compound, take several crystals of tetraphenylcyclopentadienone and dissolve them in approximately 5 mL of cyclohexane in a vial. The solution should look like very dilute grape juice. This solution must be transferred into a cuvette (the special test tubes used with the Spec 20). You will make a series of measurements from 480-520 nm. You will be looking for the wavelength at which the maximum amount of light is absorbed (minimum transmittance). It is up to you to determine how many measurements to make. The Spec 20 must be 'blanked" prior to each measurement at a new wavelength using a cuvette containing pure cyclohexane.

Blanking instructions are given on the instrument. CLEAN OUT THE CUVETTES AFTER USING THEM.

The following "color wheel" will be useful to you in interpreting your UV/vis results.

Review color using your textbook. It is often a subtractive phenomeonon. The color on the wheel corresponding to the llambda max you measure is the color absorbed. The color directly opposite is that corresponding to the combination of "leftover" wavelengths that you observe.

Larger Scale Aldol Procedure for Synthesis of Tetraphenylcyclopentanone (normally gives

larger yield)

Procedure:1. Obtain a large test tube from your TA or instructor. To this test tube, add 0.82 gram of 1,3-diphenylpropanone (1,3-diphenylacetone), 0.82 g of benzil and 6 mL of absolute ethanol. To a smaller test tube (from your locker) add 1 crushed pellet of potassium hydroxide and 1.2 rnL of absolute ethanol. Do not handle potassium hydroxide with your gloved or ungloved hand. Make sure you place the lid back on the bottle as it is hygroscopic. Make sure each test tube has a boiling stoned contained within. Gently heat both test tubes on a hot water bath until all solids dissolve. This dissolution can be a little challenging and occasionally a little extra anhydrous ethanol has to be added (by little I mean a few drops).

2. When dissolution has been achieved, raise the temperature of the large test tube ( the one containing the benz.il and 1,3-diphenylpropanone) so that it is hovering between boiling and just below boiling. This may require taking the tube out of the bath occasionally. Maintaining the elevated temperature, very cautiously (slowly) add the potassium hydroxide solution to the large test tube. If the reaction is working properly, the reaction mixture will turn dark purple (it will look black). After the base addition is complete, allow the contents of the test tube to reflux very gently for 15 minutes with some mild agitation_ The reflux must be monitored very closely because you do not have a condenser. The problem is, that it can bump over, so if it appears to be boiling too vigorously raise it out of the hot water bath for a minute or two.

3. The solid, deep purple tetraphenylcyclopentadienone can be isolated by cooling the test tube in an ice bath for ten minutes and then vacuum filtering out the crystals (be sure to use your smaller vacuum apparatus – one larger than the micro set up – it will be a substantial amount of material. ). Rinse the crystals with three small portions of cold, 95 % ethanol. The melting point can be measured after drying the tetraphenylcyclopentadienone for several days. Unrecsystallized, tetraphenylcyclopentadienone typically has a melting point range of 218-220°. Without recrystallization, it is normally extremely pure. The reaction is also very high yielding. Why

Lab Report

In addition to the normal components of a preparative lab report, be sure to include the following.

1. An analysis of the IR and 1H NMR spectra of benzoic acid (spectra on reserve in the Collier Science Library).

2. The answers to the following questions.

b. Why is the acetone added to the reaction mixture?

c. Predict the major product for the following reaction. (Hint: Bronsted Acid/Base reaction only ).

d. Why is tetraphenylcyclopentadienone colored? Explain in terms of pi to pi* transitons.

Experiment 17

Worksheet Name:

TA:

Prelab Questions

1. (6 points)

2. a. ( 4 points)

b. (4 points)

3.a. 2-pentanone (2 points) b.3-pentanol (2 points) c.acetone

(2 points)

a. (4 points)

b. (4 points)

c. (4 points)

Postlab questions

d. ( 8 points)

I n t r o d u c t i o n

The purpose of this investigation is to carry out a microscale aldol reaction and a microscale haloform reaction. The products will be characterized by melting point determination. Additionally, a visible spectrum of the highly colored aldol adduct will be measured. (+ 6 points) Through these experiences an appreciation of enolate chemistry and a better understanding of how the absorption of visible l ight relates to color and how color relates to the structure of organic compounds will be obtained. (+ 1 point)

The procedures for these experiments are as found in the Bryn Mawr College Organic Chemistry L a b o r a t o r y Manual, pages ####. (+ 1 point)

Main R e a c t i o n s

1. haloform (2 points)

2. aldol ( 2 points)

Mechanisms (20 points)

l.haloform

2. Aldol

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Side Reactions

Self-aldols are possible

Haloform

(+ 6 points for reaction)

Minimization

Excess hypochlorite drives the equilibrium to the right, lowering the concentration of the unreacted acetophenone. As soon as one hydrogen is deprotonated and replaced with chlorine the pK a of the other hydrogens goes done increasing the concentration of deprotonated species, decreasing the likelihood of self-aldol.(+ 2 points)

Aldo1

(+ 6 points for reaction)

Minimization

The extra resonance stabilization of the enolate means that the pKa is lower than twenty for the conjugate acid. This means that there will be more 1,3-diphenylacetone ionized than a typical aldol and it makes it even more probable that the attack will occur on benzilwhich can't ionize in this way. The insolubility and high stability of tetraphenylcyclopentadienone drives the reaction almost exclusively in the desired direction. This is the most important issue. (+ 2 points)

P u r i f i c a t i o n

Haloform

1. Addition of acetone:

(+ 2 points)

2. Addition of carbon

(+ 2 points)

3. Vacuum filtration

(+ 2 points)

4. Rinsing the crystals with cold water

(+ 2 points)

Aldol

1. Vacuum filtration:

(+ 4 points)

2. Rinsing with 95% ethanol:

(+ 4 points)

Table of Reagents

Haloform

Reactant grams (mL) MW moles density m.p. b.p.

acetophenone

(+ 5 points )

bleach5.25% NaOCl(+3 points)

Aldol

Reactant grams (mL) MW moles density m.p. b.p.

1,3-diphenyl-2-propanone(+4 points )

benzil(+4 points)

Table of Products (theoretical)

Haloform

Product grams (mL) MW moles density m.p. b,p.

benzoic acid

(+ 6 points)

Aldol

tetraphenyl-cyclopentadienone

(+6 points)

Observations and Data (8 points)

Haloform Reaction (4 points)

Aldol Reaction (4 points)

Resul ts

Yield benzoic acid in grams: (1 point)

Yield benzoic acid in moles: (2 points)

Percent yield benzoic acid: (2 points)

Melting point benzoic acid: (2 points)

Interpretation of literature IR benzoic acid ( 4 points)

Interpretation of literature NMR benzoic acid ( 6 points)

Yield aldol product grams: (1 point)

Yield aldol product moles: (2 points)

Percent yield aldol product: (2 points)

Melting points aldol product: ( 2 points)

lambda max for aldol product: ( 4 points)

Discussion/

Conclusion

Haloform (15 points)

c

Aldol Reaction (15 points)