Separation of the Constituents of an Analgesic Preparation

Objective

The objective of this experiment was to separate individual constituents of a given organic sample that had various solubility properties. The chemical process involved extraction of constituent elements because some solutes are highly soluble than others.

Drug manufacturers have exploited differences in solubility of individual components in drugs to analyze a pharmaceutical preparation. For instance, some forms of binders and fillers are soluble in water, but are not soluble in organic solvents. Conversely, most active constituents are highly soluble in organic solvents relative to water. Instead, other functional elements contained in organic components may undergo normal chemical reactions. These differences have been applied to attain separation of individual components.

Physical properties

  1. Sucrose1 (National Center for Biotechnology Information 1)
    Phase: Solid
    Molar mass: 342.3 g/mol
    Melting point: 185-187°C
    Hazards: Irritant
    Sucrose1
  2. Acetanilide 2 (National Center for Biotechnology Information)
    Molar mass: 135.197 g/mol
    Melting point: 113-115 °C
    Hazards: toxic, irritant
    Acetanilide 2
  3. Acetylsalicylic Acid (National Center for Biotechnology Information 1)
    Phase:
    Solid
    Molar mass: 180.16 g/mol
    Melting point: 134-136 °C
    Hazards: Irritant, poison
    Acetylsalicylic Acid 3
  4. Dichloromethane4
    Phase: liquid
    Molar mass: 84.93 g/mol
    Boiling point: 39.8-40 °C
    Density: 1.325 g/mL at 25 °C
    Hazards: toxic, flammable, irritant
    Dichloromethane4
  5. Sodium Bicarbonate 5 (National Center for Biotechnology Information 1)
    Phase
    : Solid
    Molar mass: 84.01 g/mol
    Melting point: <300 °C (270 °C)
    Hazards: Toxic and irritant
    Sodium Bicarbonate 5
  6. Sodium Sulfate 6 (National Center for Biotechnology Information 1)
    Phase:
    Solid
    Molar mass: 142.04 °C
    Melting point: 884 °C
    Hazards: irritant
    Sodium Sulfate 6
  7. Hydrochloric acid (National Center for Biotechnology Information)
    Molar mass:
    36.46 g/mol
    Boiling point: >100 °C
    Density: 1.2 g/ mL at 25 °C
    Hazards: poison, toxic, irritant
    Hydrochloric acid 7

Procedures

A sample of Phensuprin accurately weighing 2 grams was added into a 125 ml Erlenmeyer flask. Dichloromethane weighing 50 ml was added into the flask and stirred thoroughly until no more solid particles could dissolve further. The solid was then filtered to obtain sucrose.

After the sucrose in the filter paper was totally dry, the weight of the filter paper was again recorded alongside the solid content and the weight of the sucrose was calculated and reported as the actual weight and percentage of the aggregated weight of the Phensuprin.

The next procedure involved extraction of acetylsalicylic acid. The dichloromethane solution was added to the filtrate via another funnel and two 25 ml portions containing 5 percent of sodium bicarbonate solution was used to extract the acid. The funnel was shaken gently for a period of between 1 to 2 minutes. Pressure was then released safely from the bottle. The content was drained to 125 ml of dichloromethane in the Erlenmeyer flask. The aqueous was poured from the funnel into a different 400 ml beaker. The dichloromethane layer was returned through the funnel and the procedure was conducted again for another portion of sodium bicarbonate solution. The two aqueous layers were combined while the dichloromethane layer was left for the last stage.

The combined aqueous layers was cooled in ice cubes. A transfer pipette was used to 10 ml of concentrated hydrochloric acid when stirring. This procedure is known to release a lot of foam. The pH of the solution was gauged on a piece of pH paper using drops collected by glass rod. It was expected to be less than 2. Hydrochloric acid was added in small volumes until the desired pH was obtained. The content was cooled to obtain solid acetylsalicylic acid. A vacuum filtration was used to collect the solid. It was later washed with almost 5 ml of cold water. The solid was then transferred to uncapped sample glass bottle to dry for one week. A completely dry solid was weighed and the exact amount of acetylsalicylic acid recovered was noted.

The leftover organic solution was dried over anhydrous sodium sulfate. Anhydrous sodium sulfate was placed on damp methylene chloride solution and swirled for few minutes, added in small quantities until some elements of the drying materials started to flow freely. The content was swirled, decanted through fluted filtering paper into a clean, dry and pre-weighed 100 ml round bottom flask. The solvent of methylene chloride was evaporated using a rotary evaporator until all solvent contents had disappeared. The solid acetanilide element was collected and stored for the next laboratory experiment. After all the three separated solids had dried, they were weighed and weight calculated to determine how much of these elements were separated from the process to show percentage of the total weight of the Phensuprin composition. The melting point of each element was recorded to determine purity of each substance separated and compared with literature melting points.

Calculation of percentage composition of compounds used in the experiment

Mass of the Phensuprin: 2.0g
Mass of the filter paper used to separate the sucrose: 0.95g
Mass of the filter paper+ sucrose: 1.33g
Mass of sucrose obtained: 0.38g
Mass of acetanilide obtained: 0.64g
Mass of the round bottom flask: 61.0g
Mass of acetylsalicylic obtained: 0.39g
Total mass: 0.38+0.64+0.39=1.41 g
Total percent recover: [1.41g/2.0] x 100= 70.5%
Percent composition of sucrose: [0.38/1.41] x100= 33.33%
Percent composition of acetanilide: [0.64/1.41] x100= 45.39%
Percent composition of acetylsalicylic: [0.39/1.41] x100= 27.65%

Synopsis of the results obtained

Once all the three solid elements were separated, the melting points were recorded to establish whether any forms of impurities were present. The focus was not on establishing the melting point of sucrose because the substance was already known. The mass of sucrose separated from the mixture was 0.38 g (representing 33.33%) of the total mass of the substance. It was imperative to note that no solid materials were gathered after the filtration of the aqueous solution through the vacuum filtration. From the experiment, it was determined that the melting point for Acetylsalicylic acid was 98 0C. The recorded melting point for the substance was lower relatively to other melting points reported in literature. For instance, Maryadele J. O’Neil reported a melting point of 135 0C in the chemical book (O’Neil 140). This variation could have depicted that the low boiling point of the solid showed potential impurities in the solid or errors during the experiment. The percentage composition of Acetylsalicylic was 27.65% – a small percentage relative to other constituents. It remains unclear why a small percentage of the element was determined in the solid. During the experiment, the melting point for Acetanilide was determined at 113.4 0C. Available literature reported the melting point at 113.7 0C (OECD SIDS 3). Therefore, there was a possibility that acetanilide was a pure constituent.8 The percentage composition of acetanilide was 45.39% of the total mass, but the total percentage recovered was 70.5%. This implied that a significant quantity of the element was recovered from the original Phensuprin.

Discussion

Many organic reaction elements and other commercial products are compounds containing various substances. To get pure forms of such substances, each element must be separated from the mixture by exploiting variations in their physical and chemical properties.9 In this experiment, sucrose was soluble in water, but not in non-polar organic solvent, dichloromethane. Acetylsalicylic acid was soluble in dichloromethane but not in water. Finally, acetanilide was soluble in non-polar solvent, dichloromethane, but insoluble in water. They were turned into salts with sodium and HCL. In the experiment, variations in acid-base and solubility properties of each mixture of the compound were used to separate components.

The experiment involved separation of various elements found in Phensuprin because they had differences in solubility feature. It was noted that sucrose could not dissolve in dichloromethane because it cannot form hydrogen bonds with the reactant (Lide 3-172). Consequently, it was simple to separate sucrose from the mixture in the initial stage because of its inability to dissolve in dichloromethane.10 On the other hand, acetanilide and Acetylsalicylic acid were part of the dissolved constituents in the dichloromethane.

The sodium bicarbonate was used to extract the Acetylsalicylic acid. Sodium bicarbonate provided the basic condition while the acetylsalicylic acid provided acidity for the reaction to take place. During this reaction, salt was released as a byproduct and was moved to the aqueous layer because of the same polarities. It was observed that no hydrogen bond formation could result between dichloromethane and water, these two elements formed separate layers. Given the differences in density of the two materials, the dichloromethane layer was formed at the bottom of the flask due to its relatively higher density of 1.325 g/mol at 25 °C while that of water is the standard for reference at (1.0 g/mol). Sodium bicarbonate was used to separate the dichloromethane twice to ensure that most acetylsalicylic acid was obtained during the separation process.

The purpose of hydrochloric acid was to ensure that acetylsalicylic was obtained as a solid product. To obtain acetylsalicylic, the basic aqueous solution was acidified with hydrochloric acid, which reacted with the sodium elements and acetylsalicylate to generate acetylsalicylic, a substance insoluble in water (Zubrick 110-122). Acetylsalicylic was precipitated from the solution and was collected through filtration.

The pH of 2 was necessary to ensure that acidity of the content was lowered. Generally, sodium bisulfate was used specifically to reduce the pH of the solution.11 It was also noted that acetylsalicylic acid was mostly stable at the pH of 2, less stable at pH of 4 while poorly stable at higher pH (McEvoy 2037).

Vacuum filtration was found to be useful and suitable for dichloromethane as a solvent, was faster and could work with higher boiling points of most substances. In addition, it ensured that small-sized particles could be extracted where gravity filtration could not work.

After separation, the only constituent left in the solution of dichloromethane was acetanilide. Acetanilide was easily separated by the use of rotary evaporator in which all solvent contents were evaporated to leave solid particles for collection (National Center for Biotechnology Information 1).

Rotary evaporator works with vacuum filtration to ensure efficiency and gentleness when solvents are separated through evaporation. Vacuum evaporators are normally responsible for reducing the pressure to lower the boiling of the aqueous solution.

From the compounds recovered, Phensuprin had high contents of sucrose (33.33%), acetanilide (45.39%) and acetylsalicylic acid (27.65%). The percentage composition showed that acetylsalicylic acid was the least common substance in the compound.

Notable variations were noted in the melting points. These were unprecedented outcomes. For instance, the literature melting point of acetylsalicylic acid did not match the melting point noted during the experiment. This variation in melting points was attributed to possibilities of impurities. Unfortunately, chemical extraction is not always completely efficient. Therefore, it is nearly impossible to extract all original materials as pure components. Moreover, every component of Phensuprin was most likely to contain small quantities of one or more the separated compounds. To obtain pure compounds, recrystalization is required by following appropriate lab procedures.

References

Lide, David R. CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc, 1999. Print.

McEvoy, GK. ed. American Hospital Formulary Service. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 2007. Print.

National Center for Biotechnology Information. Acetanilide. 2015. Web.

—. Acetylsalicylic Acid. 2015. Web.
—. Hydrochloric Acid. 2015. Web.
—. Sodium Bicarbonate. 2015. Web.
—. Sodium Sulfate. 2015. Web.
—. Sucrose. 2015. Web.

OECD SIDS. Acetanilide. Republic of Korea: UNEP Publications, 2001. Print.

O’Neil, Maryadele J, ed. The Merck Index – An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th ed. Whitehouse Station, NJ: Merck and Co., Inc, 2006. Print.

Zubrick, James W. The Organic Chem Lab Survival Manual. 5th ed. New York: John Wiley & Sons, Inc, 2001. Print.

  1. The original organic solution was extracted two times with aqueous sodium bicarbonate. After the extraction, what compound(s) were in the organic layer? What compound(s) were in the aqueous layer?
    The aqueous layer contained acetylsalicylic acid while was found in the Acetanilide was in the organic layer
  2. Assume that both acetylsalicylic acid and acetanilide are soluble in diethyl ether, and that diethyl ether was used in place of the methylene chloride. Would the ether layer be the bottom layer in the separatory funnel or the top layer? Explain your answer.
    The density of water, 1.0g/mL, is relatively higher than the density of diethyl ether, 0.71g/mL and, therefore, diethyl ether can be found on the upper layer.
  3. Assume that both acetylsalicylic acid and acetanilide are soluble in methanol, and that methanol was used in place of the methylene chloride. What problem(s) might occur during the extractions? (Careful, this is a trick question.)
    The solubility challenge arises. When methanol is used, hydrogen bonds are most likely to be formed and then mixed with water. These two elements would then form a single layer. Thus, separating this form of mixture is extremely difficult. Hence, extraction of
    As a result, methanol will be mixed with water (miscible) to form one layer. That means that there will be no separation of two layers. Due to the solubility of both the acetanilide and the acetylsalicylic acid in methanol can be extremely difficult. These two elements could be extremely difficult to separate.
  4. Historically, the solid residue that is left after the methylene chloride solution is evaporated has a lower melting point that its literature value, due to impurities. Explain what impurities are present and why.
    Used elements from the acetylsalicylic acid are the most possible impurities affecting boiling point. In addition, experimentation errors may also occur and interfere with outcomes. Advanced techniques and procedures could be used to overcome such challenges.

Footnotes

  1. National Center for Biotechnology Information. Sucrose. 2015. Web.
  2. National Center for Biotechnology Information. Acetanilide. 2015. Web.
  3. National Center for Biotechnology Information, Acetylsalicylic Acid. 2015. Web.
  4. Maryadele J O’Neil, The Merck Index – An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th ed, Whitehouse Station, NJ: Merck and Co., Inc, 2006, p. 140.
  5. National Center for Biotechnology Information. Sodium Bicarbonate. 2015. Web.
  6. National Center for Biotechnology Information. Sodium Sulfate. 2015. Web.
  7. National Center for Biotechnology Information. Hydrochloric Acid. 2015. Web.
  8. OECD SIDS, Acetanilide. Republic of Korea: UNEP Publications, 2001. P. 3
  9. James W Zubrick, The Organic Chem Lab Survival Manual. 5th ed. New York: John Wiley & Sons, Inc, 2001. p 110-122.
  10. David R Lide, CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc, 1999. pp. 3-172.
  11. GK McEvoy. ed. American Hospital Formulary Service. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 2007. p. 2037.