Analgesic Pill Synthesis Lab Report

Unlike the ideal, most things are not pure in composition. Unfortunately to achieve a specific reaction without any unexpected and possibly unwanted reactions one must purify the desired compounds. To purify a compound one must use the difference of chemical and physical properties. In this lab a analgesic pill is the start of the purification process. In total there are four main steps that are necessary in order to isolate the list of three drugs given. These three drugs are Ibuprofen, Naproxen, and Aspirin. Each pill has a set of impurities other than the drug itself. Those can be grouped into basic soluble fillers and acid soluble fillers. First the pill is crushed and brought into a powder. The next step is to dissolve the powder is a

basic solution. This will dissolve the basic soluble fillers and thus will isolate the drug and the acid soluble fillers. Next a vacuum filtration is done in order to separate the soluble from the insoluble. This leaves just the acid soluble fillers and the drug itself. Obviously the next step is to place a large amount of hydrochloric acid into the solution in order to precipitate out the drug. To accelerate this process the solution is chilled in an ice bath. The resulting mixture is then filtered via vacuum filtration in order to remove the precipitated drug from the mixture.
This drug is not entirely pure however. The purification is achieved by recrystallization. Recrystallization can be achieved by heating the drug in a minimal amount of ethanol until the drug entirely dissolves. Then the drug is cooled very slowly and the crystals form without the impurities in their solid matrix. This is due to the fact “more than 40% NCEs (new chemical entities) developed in pharmaceutical industry are practically insoluble in water” (Savjani, Ketan T., et al.).
To find out what the unknown drugs identity is, one must use a difference in physical or chemical properties. The properties used in this lab are melting point and and properties used in Thin Layer Chromatography. Thin Layer Chromatography or TLC is a method of determining how well a compound will travel with a solvent. The RF value is the ratio of that travel. It gives the value for how far a compound travels over how far a solvent travels. The maximum RF possible is a value of 1. The application in this lab is if we have a sample of the unknown and we have samples of all of the known examples of the drugs it can be we can easily figure out which drug it is. In this instance we use the values if the unknown drug, aspirin, ibuprofen, and naproxen. Whichever value matches that of the unknown is the correct compound.
In the last part the melting point of the compounds is used to find what the identity of our unknown compound is. The melting point can be used because for the most part different compounds tend to have different melting points. Thus if we have two of the same/similar compound then we know for a fact that if the melting points are the same that the compounds are the same. If the substance was impure then it would mess with the temperature slightly.

Methods
Part 1: Purification and crystallization of ethanol
Three pills of the same type were retrieved and crushed into a fine powder. The pills were placed in a small erlenmeyer flask with about 15ml of water. The solution was stirred profusely until the pills had completely disintegrated. 6 ml of 8% NaOH is added to solution and then was allowed to rest for 15 minutes. The insoluble fillers and binders are then removed via suction filtration. 10% HCl was then added until the solution was strongly acidic on Ph paper. The solution was then chilled via an ice bath to accelerate the precipitation process. Once entirely precipitated suction filtration was then used again in order to remove the solution from the solids. The solid was then transferred to an erlenmeyer flask along with 5 ml of ethanol. This was then heated until all of the solid was in solution. The solution was then allowed to slowly cool to room temperature and allowed to recrystallize.
Part 2: TLC
A thin layer chromatography test was used on aspirin, naproxen, and ibuprofen.
Part 3: TLC of unknown as well as melting point analysis
The sample of the unknown drug from part 1 was obtained and dissolved in a small amount of ethanol. This was then placed alongside stand aspirin, ibuprofen, and naproxen solutions on a TLC plate and 13ml of a mixture of 3 parts ethanol 8 parts ethyl acetate and 40 parts pentane was then used as the solvent for the TLC process. The plate was then analyzed under UV light. The melting point machines were then setup with 5 different samples. Each sample was the isolated drug, the drug from the TLC plate that matched the unkown, unkown mixed with the TLC match, the unknown drug mixed with one of the incorrect drugs, the unknown drug mixed with the other incorrect drug. They were each brought to melting point and the values for when it started melting and when it finished melting were recorded.

Results
Final Mass: N/A
Percent Recovery: N/A
I was unable to retrieve a final recrystallized sample so I do not have values for my final mass and percent recovery.

This is the classes average data for the Rf values of Ibuprofen, Naproxen, and Aspirin for each mixture.
Solvent Mixture
Dielectric Constant
Ibuprofen
Naproxen
Aspirin
Mixture 1
2.039
0.19
0.16
0.13
Mixture 2
2.716
0.24
0.15
0.22
Mixture 3
3.309
0.35
0.28
0.39
Mixture 4
3.832
0.57
0.49
0.56
Mixture 5
4.296
0.63
0.57
0.69

Values of the initial and final melting temperature
Sample
Initial temperature of melting
Final temperature of melting
Unknown
134.8°C
144°C
A
135.3°C
141.2°C
U/A
125.2°C
131.6°C
U/N
146°C
153.7°C
U/I
74°C
80.9°C

Discussion
My solvent mixture was mixture 4 which was 3 parts ethanol, 8 parts ethyl acetate, and 40 parts pentane.

This mixture was very good at separating the mixtures because its dielectric constant is 3.832. This relatively high value for the dielectric constant gives a strong effect towards moving the compounds up the TLC plate. The way that I visualized the spots on the TLC plate is first I placed the plate under a UV light. This showed most but not all the spots. The next way was to dip the TLC plate into bromocresol green. The best mixture was mixture 5 at separating the compounds due to the greatest dielectric constant. The worst mixture being the first mixture this is due to the very low dielectric constant. The general values between the ibuprofen and the aspirin are almost the same most of the time while the naproxen is very low in

comparison.

This is what it looked like:

As can be seen in the above graph there is a definite trend in the mixture number and the average RF value.

Since each mixture contained a larger and larger dielectric constant it is fair enough to say that the trend fits to the dielectric constant.

I think that the compound I had is aspirin mixed slightly with ibuprofen. I think this due to the fact that the TLC plate has a match on both the aspirin and the unknown as well as the melting point of the unknown and the aspirin are almost exactly the same. My compound is very pure. I think this because of how similar it was to the standard. The standard and the compound were on top of each other and so I think it's fair enough to say that they are of very similar purity.

If my drug broke down during a specific condition then it would have resulted in different properties in the melting machine and in the TLC test. In the TLC test I probably would have noticed multiple marks for where the drug traveled. This is due to there being more than one compound. In the melting machine there would have been a greater temperature range for

melting.