Transcription
Welcome Alar Ringa viewers. In this video, I will be synthesizing two amino-1-phenylpropane by the reductive amination of 1-phenyl-2-propanone with sodium cyanoborohydride.
Sodium cyanoborohydride is a versatile reagent that will reduce a variety of organic functional groups with remarkable selectivity. For example, in our case, the reductive amination of a ketone with sodium cyanoborohydride proceeds smoothly at room temperature to form the amine.
To start the experiment, add 15.5 mL of methanol into a suitable glass container. Then, add in 11.42 G of ammonium acetate. Stopper the flask and start stirring for a few minutes. As you can see, all of the ammonium acetate crystals will not dissolve in the methanol; this is normal.
To the mixture, add in 2 G of 1-phenyl-2-propanone. The mixture turns cloudy. Finally, carefully add 1.8 G of sodium cyanoborohydride into the mixture. Taking a closer look, the mixture has darkened and some bubbles seem to be emitted, resembling the Coca-Cola soft drink.
Stopper the flask and stir the mixture for 36 hours at room temperature. You may wrap the flask with some aluminum foil or leave it to stir in a dark place. After 11 hours, we can observe that the mixture still has a black color and there is no other observable reactions taking place. After 22.5 hours, again, the mixture's color hasn't changed and there is no other visible reactions taking place.
Okay, now let's have a look at the chemistry. 1-phenyl-2-propanone dissolved in a mixture of methanol and ammonium acetate reacts in the presence of sodium cyanoborohydride at room temperature to form 2-amino-1-phenylpropane. This is a reductive amination reaction. After 36 hours, the mixture still looks the same. Stop the timing and stirring.
Okay, now get a beaker and pour in one liter of distilled water. To it, add 5 mL of concentrated 32% hydrochloric acid. Swirl the solution. Now, decant around 80 mL of the solution into a small beaker. Get the mixture and pour it into the aqueous solution. The dark mixture swiftly turns to a beige color, giving off a light mist. Rinse out the reaction vessel with the 80 mL aqueous solution we divided earlier and pour it into the large beaker. Mix everything thoroughly.
Okay, now we have to extract the unreacted 1-phenyl-2-propanone from the reaction mixture with dichloromethane. Add 100 mL of dichloromethane. Stir the mixture thoroughly. Pour the contents into a separatory funnel and conduct the first extraction. The bottom layer is the organic layer, which contains the unreacted 1-phenyl-2-propanone that we don't want. The upper layer is the aqueous layer, which contains our product. Swirl the separatory funnel, vent, and decant the bottom layer to a beaker and discard. Drain the upper layer to the beaker. This is the first washing with dichloromethane complete. Carry out another two more extractions with 100 mL of dichloromethane each. This is now a cleaned aqueous solution, free from 1-phenyl-2-propanone.
Now, basify the aqueous layer to pH 12 with 1 mol sodium hydroxide solution. The addition of the sodium hydroxide solution was around 200 mL. Also, the mixture has turned to a more brown color. Now, use pH paper to check that the correct pH of 12 is obtained.
Okay, now we need to extract the basified mixture using dichloromethane. Add 100-50 mL of dichloromethane into the mixture and mix thoroughly. Again, pour the contents into a separatory funnel and carry out the first extraction. The bottom layer is the organic layer, which contains our product, 2-amino-1-phenylpropane, in the free base form. The upper layer is the aqueous layer that contains salts and other unwanted byproducts that we don't want. Swirl the separatory funnel, vent, and drain the bottom layer into a suitable flask. Drain the upper aqueous layer into a beaker. The first washing with dichloromethane is now complete.
Return the aqueous layer back and conduct another two more extractions with 150 mL of dichloromethane each. This is the cleaned lower dichloromethane layer that contains our product, 2-amino-1-phenylpropane, in free base form. Decant the remaining upper aqueous layer and discard it. Get the cleaned organic layer and remove the dichloromethane using a rotary evaporator or by distillation. As we can see, there is a yellow oil. This is 2-amino-1-phenylpropane free base.
Okay, now cool the free base in an ice bath and add cooled 10 mL of isopropanol. Mix thoroughly. Now, transfer the mixture into a suitable container and start adding concentrated 32% hydrochloric acid slowly to pH 3. As we can see, a white mist is given off. Swirl the mixture. Now, add 10 mL of ether. If there is no precipitation of a crystalline material, slowly evaporate the solvents with low heat. As we can see, there is a light orange-pink crystalline material in the beaker. This should be our crude 2-amino-1-phenylpropane hydrochloride.
In order to purify our product, we need to conduct a recrystallization in acetone. Add around 10 mL of acetone into the crude product and start heating. Place a watch glass over the beaker and as the acetone starts to boil, stir the material until most of the product is dissolved. Remove the heating and quickly conduct a hot filtration. As the mixture cools down, pinkish white colored crystals are observed. This should be moderately pure 2-amino-1-phenylpropane hydrochloride. Note: a few more crystallizations are needed to achieve a pure white crystalline material.
Now, to check that we did successfully synthesize 2-amino-1-phenylpropane hydrochloride, we need to conduct a few presumptive color tests: the Mandelin and the Marquis tests. First up is the Mandelin test. This reagent is composed of a mixture of ammonium vanadate and concentrated sulfuric acid. A small amount of the product was added into the glass vial, swirled, and in a few seconds later, a color change from yellow to a dark green-brown color was observed. This is a positive test for 2-amino-1-phenylpropane hydrochloride.
Now, the Marquis test. This reagent is composed of a mixture of formaldehyde and concentrated sulfuric acid. A small amount of the product was placed onto a watch glass and a few drops of the reagent was added onto the material. In a few seconds, there is fizzing and a color change from a clear to an orange hue. After 30 seconds, the fizzing has subsided and it seems to have a brown tint. This is a positive test for 2-amino-1-phenylpropane hydrochloride.
From the tests conducted, we can conclude that we have successfully synthesized 2-amino-1-phenylpropane hydrochloride by the reductive amination of 1-phenyl-2-propanone with sodium cyanoborohydride. The material isn't completely dry, and the product can be left out at room temperature to fully dry for a day or two. The yield is 1.90 G. Store the product in a dry, cool, and dark place.