Lecture Chemistry 337

Notes Unit 2 Synthesis of salicylic acid

Introduction to Unit 2

The centerpiece of this unit is the synthesis of salicylic acid for which we will employ the saponification of methyl salicylate. The
crude product will be purified by recrystallization. The crude and purified products will be characterized by melting point
determination.

O O

OCH3 OH
1. 5 M aq NaOH, 100oC
+ CH3OH
2. 1 M aq H2SO4, room temperature
OH OH

methyl salicylate salicylic acid methanol

Purpose of Unit 2

To become familiar with the theoretical and practical aspects of recrystallization as an isolation/purification technique
To become familiar with the theoretical and practical aspects of melting point determination
To employ the saponification of methyl salicylate in the synthesize of salicylic acid
To characterize the crude and purified samples of salicylic acid by melting point determination

Topics of these lecture notes

These lecture notes examine the theoretical and practical aspects of recrystallization as an isolation/purification technique.
The theoretical and practical aspects of melting point determination were discussed in the Unit 1 lecture notes.

Lecture notes

Recrystallization

Mohrig, third edition Mohrig, fourth edition

General comments Chapter 15 intro Chapter 15 intro
Introduction to recrystallization 15.1 15.1
Carrying out successful recrystallizations 15.2 15.3
How to select a recrystallization solvent (testing a solvent section only) 15.3 15.4
Microscale recrystallization 15.6 15.6
Summary of the miniscale recrystallization procedure 15.5 15.6

Some important statements/questions

1. A pure organic compound has no detectable impurities

2. Recrystallization is the major mode of purification for 501 Ids

3. What are the three basic steps in recrystallization?

a) preparation of a hot, saturated solution at the solvent’s boiling point followed by removal* of any insoluble impurities
b) gradual cooling of the hot, saturated solution
c) collection of crystalline material by vacuum filtration

* by hot gravity filtration

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4. How does the rate of cooling affect crystal growth?

Slow cooling promotes slow crystal growth. Slow crystal growth promotes the formation of larger , purer
crystals
Rapid cooling promotes rapid crystal growth. Rapid crystal growth promotes the formation of smaller, less pure
crystals
5. In order to obtain a purer sample what must be true about the impurities?

In the best case scenario the impurities dissolve in the hot solvent and remain in solution even as the

hot saturated solution is cooled

Alternatively the impurities do not dissolve in the hot solvent (this would require a hot, gravity

filtration step after which the hot saturated solution would be allowed to cool).

6. An effective recrystallization solvent must:

a) be chemically inert ;

b) have a very high capacity (per unit volume) for the solute of interest at the boiling point of the

solvent AND have a very low capacity (per unit volume) for the solute of interest at a temperature just
above the solvent’s freezing point; and

c) dissolve impurities at all temperatures OR not dissolve impurities at any temperature

7. The adage “ like

-

dissolve -

like” is a useful guide during the trial-and-error process of solvent selection.

The following generalizations may be quite useful in predicting solvent suitability

-a substance is most soluble in that solvent to which it is closely related structurally

-low-melting solids are generally more soluble in a given solvent than high-melting compounds of comparable structure

-in any homologous series, the higher members become more and more “hydrocarbon-like” in their physical properties

e.g.
OH

OH OH

9.1 g/100 mL 2.7 g/100 mL 0.35 g/100 mL

water water water

-as the number of functional groups present increases, solubility increases

e.g.
O O O

4 g/100 mL 12 g/100 mL
water water

8. What two high-polarity solvents are commonly used for recrystallization? ethanol 4 methanol

nor ~

9. What two low-polarity solvents are commonly used for recrystallization? diethyl ether ethyl acetate

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10. The Erlenmeyer flask used to carry out the recrystallization should be 21-03 times larger than the volume of solvent
one expects to use.

11. In the absence of specific solubility data:

a) solvent volume should be 201-040 times the mass of the sample to be recrystallized;

b) solvent should be added incrementally .

12. What steps are undertaken in order to judge whether or not a particular solvent will be a suitable recrystallization solvent?

Step 1
Combine a small quantity of the test solvent (5-10 drops) and a small quantity of sample (20-30 mg) in a test tube at room
temperature. Mix by shaking. If the sample dissolves the solvent will not be an effective recrystallization solvent. If the
sample does not dissolve proceed to Step 2.

Step 2
Heat the contents of the test tube to the boiling point of the solvent. If the sample does not dissolve the solvent will not be
an effective recrystallization solvent. If the sample dissolves proceed to Step 3.

Step 3
Allow the contents of the test tube to gradually cool. If crystals do not form within 10-20 minutes the solvent will not be an
effective recrystallization solvent. If crystals do form within 10-20 minutes the solvent is likely to be an effective
recrystallization solvent.

13. Why is it advisable to set aside a small amount of the crude material before performing a recrystallization?

For use as seed crystals should they be required.

14. After the flask has cooled to room temperature is there any advantage to cooling it in an ice-water bath?

Yes . The advantage to cooling in an ice-water bath is that it facilitate maximum

. crystallization

15. What actions could one take in the event that no material crystallizes after 15 minutes of cooling in an ice-water bath?
↳ Add a few seed crystals

16. For how long should one dry a product that has been recrystallized from a high boiling-point solvent? At least
overnight

17. Why should one pull some of the recrystallizing solvent through the filter paper, by application of the vacuum source, prior
to filtration?

↳ To seat the filter paper

18. Aside from mechanical losses during recrystallization what other factors might lead to low recovery of material?

a) TOO much solvent used

b) crystallization during hot , gravity filtration

c) vacuum filtration performed prior to complete crystallization

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19.

What quantity of water should be used to recrystallize a 1.20 g quantity of salicylic acid (solubility of salicylic acid in water:
o o
1g/460 mL at 25 C, 1g/15 mL at 100 C)?

( 15 mL / I g) = 18.0mL
1. 20g ✗

How much salicylic acid will crystallize when the solution prepared above is allowed to cool to 25º?
1. 16g

18.0mL ✗ 1191460mL) =
0.04g

I. 20g -0.049=1 .
16g

What is the maximum percent recovery of salicylic acid in this scenario?

(1.169/1.209) × 100 = 96.71 .

20. Assuming 26.5 mL of water was used in the preceding question what is the maximum percent recovery of salicylic acid
o
given that the solution was cooled to 25 C?

(1.149/1.209)×100=95 %

26 -5mL ✗ ( 191460mL)= 0.06g

1. 20g -0-069=1 14g .

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