Synthesis of p-nitroacetanilide-Nitration-Lu Le Laboratory

        The aromatic nitration of acetanilide is an exothermic reaction ; the temperature must be carefully controlled by chilling, stirring, and the slow addition of reagents. Acetanilide is first dissolved in the solvent, glacial acetic acid, by warming. Glacial acetic acid is used because it is a polar solvent capable of dissolving acetanilide and the acetate ion is a poor nucleophile so no substitution is possible. After the solution is cooled, sulfuric acid is added; however, even with cooling, the temperature of the solution rises almost 40E. Both the acetanilide solution and the nitrating solution (a mixture of HNO3, and H2SO4) must be chilled to about 10EC before the reaction is begun.

To prevent dinitration of the acetanilide, the nitrating mixture is added in small portions to the acetanilide solution (and not vice versa) so that the concentration of HNO3, is kept at a minimum. After all the HNO3, H2SO4 solution has been added, the reaction mixture is allowed to warm slowly to room temperature. If the reaction mixture has been kept excessively cold during the addition, there will be a relatively large amount of unreacted HNO3, present, which may cause the temperature to rise above room temperature. If this should happen, the mixture must be rechilled.

The work-up procedure consists of removal of the acids and crystallization of the product. Every trace of acid must be removed because hydrogen ions catalyze the hydrolysis of the amide to p-nitroaniline or its protonated cation. Most of the acid is removed by pouring the reaction mixture onto ice and water, then filtering the flocculent yellow precipitate of p-nitroacetanilide. The last traces of acetic acid are removed by neutralization. Because bases also catalyze the hydrolysis of amides, the neutralizing agent used is disodium hydrogen phosphate (Na2HPO4). This reagent reacts with acids to yield NaH2PO4. The result is a buffered solution with a pH near neutral.

The crude product is air-dried before crystallization. If all of the acid was removed, the product will be light yellow. A deep yellow to yellow-orange product is indicative of the presence of p-nitroaniline from hydrolysis. Unfortunately, p-nitroaniline is difficult to remove from p-nitroacetanilide by crystallization.

Mechanism

Preparation of Nitronium Ion:

Nitration

Chemicals

1.      Acetanilide: 1.625g

2.      Disodium hydrogen phosphate: 3.75g

3.      95% ethanol: 15mL

4.      Glacial acetic acid: 2.5mL

5.      15M nitric acid: 0.875mL

6.      18.4M sulfuric acid: 3.75mL

Procedure

1.      Place 1.625 g of acetanilide in a Erlenmeyer flask, add 2.5 mL of glacial acetic acid(CAUTION: strong irritant), and warm the flask on a hot plate in a fume hood until the acetanilide dissolves. 

 

2.      Cool the flask in an ice bath to about 20℃

3.      Add 2.5 mL of cold, conc. sulfuric acid. The temperature of the mixture will rise to about 60℃. Chill the solution to about 10℃ in an ice bath. (The solution will become very viscous.)

4.      Mix 0.875 mL of conc. nitric acid and 1.25 mL of conc. sulfuric acid in a test tube, and chill the flask in an ice bath. 

5.      When both solutions are cold, slowly add the HNO3, H2SO4 solution, 1 mL at

a time, to the acetanilide solution. Keep the reaction flask in an ice bath so that the temperature of the reaction mixture is maintained between 10-20℃. Stir the reaction mixture carefully after each addition. The entire addition requires about 15 minutes.

 

6.      After the addition is completed, allow the reaction flask to stand at room temperature for 30 minutes. Monitor the temperature; if it rises above 25℃, chill the flask in an ice bath. Should the rechilling be necessary, allow the flask to stand for 30 minutes or more at room temperature after the rechilling.

7.      Pour the reaction mixture into a beaker containing 25 mL of water and 6.25 g of cracked ice. 

8.      Using a large Buchner funnel, filter the heavy lemon-yellow precipitate with vacuum. Press out as much aqueous acid from the filter cake as possible with a spatula or clean cork while suction is being applied. The precipitate is voluminous; use care in transferring it to the Buchner funnel or a substantial amount of product will be lost.

9.      Transfer the filter cake to a clean 250-mL beaker, and add 100 mL of 15% aqueous disodium hydrogen phosphate. Stir the mixture to a paste-like consistency and refilter using vacuum. 

 

 

   

10.  Wash the beaker with two 30-mL portions of cold water. Finally, wash the filter cake with an additional 50 mL of cold water. Press the filter cake with a spatula or clean cork to remove as much water as possible, then dry the solid overnight on a watch glass. Determine the yield and melting point.

 

 

Experimental Record

Weight of p-nitroacetanilide(Theory)	2.170g
Weight of p-nitroacetanilide	1.650g
Yield	76.0%
Melting Point of p-nitroacetanilide (theory)	216℃
Melting Point of p-nitroacetanilide	210~214℃

Sodium Borohydride Reduction of Acetophenone - Lu Le Laboratory

Sodium borohydride is an odorless white to gray-white microcrystalline powder which often forms lumps. It is soluble in water, without decomposition, however it reacts vigorously with acid solutions. The salt can be recrystallized by dissolving in warm (50 °C) diglyme followed by cooling the solution.    (Wikipedia)

The reduction of an aldehyde or ketone with sodium borohydride is straight forward and usually affords a high yield of the alcohol. The usual procedure (and the one employed in thi sex periment) involves dissolving the borohydride in 95% ethanol and adding the carbonyl compound to this solution. To ensure complete reaction, an excess of sodium borohydride is used.

The reaction between sodium borohydride and acetophenone is exothermic. Therefore, it is important to add the acetophenone drop-wise and to control the reaction temperature with an ice bath. After the reaction has been completed, the excess borohydride and the ethoxyborohydridesare destroyed with aqueous acid. Because hydrogen gas is evolved, this treatment with acid must be carried out in a fume hood or a very well-ventilated room.

Because ethanol, the reaction solvent, is water-soluble, a clean separation of organic and inorganic products cannot be achieved by a simple extraction with water and diethyl ether at this point. (Too much product would be lost in the aqueous ethanol layer.) To circumvent thisproblem, the first step in the work-up is to boil off much of the ethanol. In a larger-scale reaction, the ethanol would be distilled and collected. In a small-scale reaction such as in this experiment, the ethanol can be boiled away in the fume hood. When most of the ethanol has been removed, the product 1-phenylethanol oils out.

Water and diethyl ether are then added to the residue for the extraction of the organic compounds from the inorganic salts. The ether extract is dried with either sodium sulfate or magnesium sulfate. The crude product is obtained by distilling the ether.

Because of its high boiling point, 1-phenylethanol cannot be distilled at atmospheric pressure. Although it could be vacuum-distilled, distillation could not separate it from unreacted starting material (if any) because the two compounds have boiling points only 1E apart. (An infrared spectrum can be used to determine if any ketone is present in the product.)

Chemicals

1.      Acetonphenone: 4.000g

2.      Anhydrous sodium sulfate

3.      Diethly ether: ~15mL

4.      95% ethanol: 10mL

5.      3M hydrochloric acid: 3~4mL

6.      Sodium borohydride: 0.500g

Procedure

1.      Place 0.5 g sodium borohydride in a beaker.

2.      Add 10mL of 95% ethanol and stir until the solid is dissolved.

3.      Weight 4.0g of acetophenone into a conic flask and prepare an ice bath.

4.      Add the acetophenone dropwise to the borohydride solution while stirring the mixture continuously. Keep the temperature of the reaction mixture between 30~50℃ by controlling the rate of addition and by cooling the beaker in an ice bath.

 

5.      After the addition is completed, allow the mixture to stand at room temperature for 15 minutes with occasional stirring.

6.      Add about 4mL of 3M hydrochloric acid to the reaction mixture.

7.      Heat the mixture to boil on a hot plate until the mixture separates into two layers.

8.      Cool the reaction mixture in an ice bath.

9.      Transfer the mixture in a separatory funnel and add 7mL diethyl ether and add some water to dissolve the precipitate.

10.  Extract aqueous layer with the diethyl ether and do it again with another portion of diethyl ether.

11.  Combine the ether extracts and wash them with an equal volume of water.

12.  Dry them with anhydrous sodium sulfate.

13.  Filter the dried solution into a round-bottom flask.

14.  Use a Rotary to dry the solvent ether.

15.  Measure the yield and refractive rate.

Experiment Record

Weight of 1-phenylethanol	2.850g
Theoretical weight	4.066g
Yield	70.07%
Reflective Index in 30.1℃	1.5023