1,4-Dihydropyridine and its derivatives (1,4-DHPs) are ubiquitous in nature and common to a number o — Organic Chemistry Chemistry Question

1,4-Dihydropyridine and its derivatives (1,4-DHPs) are ubiquitous in nature and common to a number of bioactive molecules that include antitumor, antimutagenic, and antidiabetic agents. 1,4-DHPs are also known as therapeutic agents of an important class of calcium channel blockers. Recently, 1,4-DHPs have played a new role in organic chemistry—as alternative hydrogen sources. They have been used instead of gaseous hydrogen to reduce various organic compounds containing C=C, C=N, and C=O bonds, with or without the aid of appropriate catalysts.

A Hantzsch 1,4-DHP ester (or simply a Hantzsch ester), represented by 1,4-dihydro^-2,6-dimethylpyridine^-3,5-dicarboxylic acid diethyl ester, is one such compound in which synthesis is accomplished conveniently by a one-pot multi-component reaction of commercially available reagents. In this experiment, you will synthesize the Hantzsch ester according to the scheme illustrated below.

[VISUAL]

Chemicals
* ammonium carbonate, solid
* anhydrous sodium sulphate, solid
* 1,4-dihydro^-2,6-dimethylpyridine^-3,5-dicarboxylic acid diethyl ester, solid
* ethyl acetate, liquid
* ethyl acetoacetate, liquid
* hexamethylenetetramine (hexamine), solid
* hexane, liquid

Apparatuses and glassware
* Büchner funnel
* glass capillary
* Erlenmeyer flasks (25 cm₃ and 100 cm₃)
* filter paper
* graduated pipette
* hot-plate magnetic stirrer (magnetic stirrer with heating plate)
* magnetic stirring bar
* suction flask
* test tube (100 cm₃)
* thermometer
* thin layer chromatography plate (silica gel 60 F254; layer thickness: 0.25 mm on a glass support)
* UV lamp equipped with short and long waves (254 and 365 nm)
* water aspirator (or diaphragm vacuum pump)
* wide-mouth bottle with cap (developing chamber)

Procedure
(1) In a fume hood, enter 1.30 g of ethyl acetoacetate and 50 cm₃ of water into a 100-cm₃ Erlenmeyer flask. Add 1.00 g of ammonium carbonate powder and place the magnetic stirring bar in the flask; stir at room temperature on a hot-plate magnetic stirrer until the ethyl acetoacetate is completely dissolved. Add 7.00 g of hexamethylenetetramine and place a cork stopper on the flask. Heat the mixture to 70 °C (use a thermometer) while stirring on a preheated hot-plate magnetic stirrer. After heating for 1 h, cool the mixture to room temperature by removing it from the hot-plate stirrer.

(2) As the mixture cools down, take a small portion of the reaction mixture using a glass capillary and load it to make two spots in the center and right positions on a thin layer chromatography (TLC) plate. Load an appropriate amount of ethyl acetoacetate in the center and left positions, so that there are three spots on the plate, the central of which spots contains both the reaction mixture and ethyl acetoacetate. Develop the LC plate using hexane/ethyl acetate (2/1) as a developer. Use a pencil to trace the outlines of the spots detected using a UV lamp (254 and 365 nm).

[VISUAL]

(3) After a crystalline product has been precipitated out of the reaction mixture, filter the product through a Büchner funnel under reduced pressure, wash the solid product obtained with small portions of water, and dry it in order to weigh the product. Identify the product with the authentic Hantzsch ester by TLC analysis as described above. Use hexane/ethyl acetate (2/1) as a developer.

(4) Place the filtrate and your magnetic stirring bar in a 100 cm₃ test tube. Add 10 cm₃ of ethyl acetate to the test tube and stir the solution vigorously for 30 s over a magnetic stirrer. Stop stirring and wait for the solution to separate into two layers. Transfer the upper organic layer into a 25 cm₃ Erlenmeyer flask using a graduated pipette. Repeat the extraction twice using ethyl acetate (2 * 5 cm₃) and add anhydrous sodium sulfate (1 g) to the Erlenmeyer flask to dry the combined organic layer. Check the organic layer with TLC to determine whether or not it still contains the Hantzsch ester.