Chapter 1.
Background
All of the possible products in this experiment belong to a particular class of molecules called chalcones. Chalcones (kal-cones) are biosynthesized in plants and have impressive biological activity including anti-oxidant, anti-fungal, anti-bacterial, anti-tumor, and anti-inflammatory properties.1 All chalcones share the same basic structural skeleton, which is composed of an α,β-unsaturated ketone linking two aromatic rings. Many can be isolated from plant material and can also be synthetically prepared using the aldol condensation reaction.
Reaction
1. Neves, M.P. et al. Bioorg. Med. Chem.2012, 20, 251–65
Lab Objective
To perform an Aldol condensation reaction using the procedure provided. Each student should select an aldehyde and ketone from the reagents table and look up the appropriate information for the pre-lab portion of the laboratory notebook pages. The Aldol product should be purified by recrystallization and characterization carried out using m.p., Infrared spectroscopy, and Thin Layer Chromatography.
Procedure
Place ~ 1 mmol (weigh accurately) of the aldehyde into a conical vial equipped with a magnetic spin vane. Add one mole equivalent amount of the ketone and 1 mL of 95% ethanol to the vial and start stirring. Add 0.10 mL of a 50% w/w aqueous sodium hydroxide solution to the vial, cap, and stir at room temperature until it solidifies (CAUTION! NaOH is a strong base). Depending on how you’ve altered the reaction conditions the reaction may take more or less time.
Most of the chalcone products will precipitate out of solution after forming. Break up the solid with a spatula and dilute with ~ 2 mL of ice water. Transfer the mixture into another ~ 3 mL of ice water in a small Erlenmeyer flask. Stir thoroughly, then vacuum filter, wash with cold water, and allow to air dry before you determine the crude yield. All aldol condensation products should be purified by recrystallization, and most can be recrystallized from 95% ethanol.
The purity of all products should be checked by TLC and m.p., and their IR spectrum recorded. Note the m.p. data for some products is not available in the literature.
Techniques
Table 3-1
R |
R’ |
mp (°C) |
H |
4′–OCH3 |
106 |
H |
4′–Cl |
100 |
H |
4′–Br |
104–105; 113 |
H |
4′–CH3 |
59–60; 77–78 |
4–NO2 |
H |
165 |
4–NO2 |
4′–OCH3 |
167–168 |
4–NO2 |
4′–Cl |
163–164 |
4–NO2 |
4′–Br |
166 |
4–NO2 |
4′–CH3 |
162 |
4–CH3 |
H |
96.5 |
4–CH3 |
4′–OCH3 |
? |
4–CH3 |
4′–CI |
165 |
4–CH3 |
4′–Br |
? |
4–CH3 |
4′–CH3 |
127.5 |
4–OCH3 |
H |
77 |
4–OCH3 |
4′–OCH3 |
102 |
4–OCH3 |
4′–Cl |
121–122; 128 |
4–OCH3 |
4′–Br |
142–143 |
4–OCH3 |
4′–CH3 |
94 |
4–Cl |
H |
103; 113–114 |
4–Cl |
4′–OCH3 |
130–131 |
4–Cl |
4′–Cl |
156–157 |
4–Cl |
4′–Br |
? |
4–Cl |
4′–CH3 |
? |
3,4 –O–CH2–O– |
H |
122 |
3,4 –O–CH2–O– |
4′–OCH3 |
129 |
3,4 –O–CH2–O– |
4′–Cl |
128 |
3,4 –O–CH2–O– |
4′–Br |
? |
3,4 –O–CH2–O– |
4′–CH3 |
130 |