To first synthesize the Grignard reagent,p-tolyl magnesium bromide, and use it for the subsequent synthesis of p-toluic acid.
2. Results and Calculations:
Grignard Synthesis of p-Toluic Acid:
Weight of crude product: 7.38g
Mass of empty plastic bag: 0.68g
Mass of plastic bag and purified product: 3.69g
Mass of purified product: 3.69 – 0.68 = 3.01g
Melting-point range: 178.8°C – 179.5°C
Percentage Yield of p-Toluic Acid:
Amount of magnesium used: 40.0 x 10-3mol
Amount of p-bromotoluene: = 40.9 x 10-3mol
Since ratio of p-bromotoluene :p-tolyl magnesium bromide : p-toluic acid = 1 and magnesium is the limiting reagent,
Theoretical yield of p-toluic acid = 40.0 x 10-3× 136.15 = 5.45g
Percentage yield of p-toluic acid = (3.01÷ 5.45) ×100% = 55.3%
3.1 Synthesis of Grignard Reagent:
During the first part of the experiment, Grignard reagent, p-tolyl magnesium bromide, was synthesized by adding p-bromotoluene and anhydrous tetrahydrofuran to magnesium turnings. To protect against atmospheric moisture, this was carried out in a round bottom flask with two guard tubes connected to the reflux condenser and dropping funnel. The guard tubes were packed with anhydrous calcium chloride, which is hygroscopic . The anhydrous calcium chloride prevented atmospheric water vapour from entering the setup by acting asa drying agentas follows:
CaCl2 + 2H2O → CaCl2∙2H2O
This prevention was crucial asthe Grignard reagents were highly sensitive to water and would react rapidly and exothermically with water, to produce alkanes as shown below.The hydrocarbon and magnesium salt formed might have coated the surface of the unreacted magnesium turnings and inhibited further formation of the Grignard reagent .
For example: R—MgBr + H2O R—H + Mg(OH)Br R = alkyl chain
Tetrahydrofuran (THF) was used as a solvent for a number of reasons. Firstly, THF was an organic solvent which dissolved organic compounds including the Grignard Reagents. Also, the solvent was a neutral aprotic solvent which did not participate in the reaction for it contained no dissociable H+ ions that would react with the Grignard reagent to form toluene. Thirdly, THF can be easily separated in subsequent steps to obtain the crude product. While neutral, THF was still polar and helped to stabilize the Grignard reagent through the formation of ligand bonds. The Grignard reagents were unstable and highly reactive; any stabilization at the covalent-ionic bond between the polarized carbon (more electronegative) and magnesium would favor the forward reaction.
However, with THF as a solvent, another consideration must be factored in as well. THF is a volatile solvent and the synthesis of Grignard reagent is exothermic; these factors caused THF to vaporize rapidly. The reaction mixture was thus refluxed and a condenser was connected to cool the organic vapor back to the solvent state. This prevented the Grignard reagent from “drying up” and reduced the probabilities of byproducts forming.
As a good measure, all reactants were added quickly and the guard tubes, replaced as soon as possible. Besides reacting with water, Grignard reagent might have participated in other side reactions, as shown below:
With Oxygen: R—MgBr + O2 ROO—MgBr RO—MgBr
The aforementioned steps sought to minimize the entry of atmospheric oxygen and the subsequent decomposition to undesired side products.
The introduction of p-bromotolueneand THFinto the round bottom flask from the dropping funnel was done slowly in a drop-wise manner. Asthe reaction between magnesium and the alkyl halide was strongly exothermic, the significant amount of heat produced might evaporate the solvent, forming byproducts. Drop-wise addition of the reagents reduced the occurrences of side reactions.
Because magnesium turnings were covered with an unreactive oxide layer, the reaction was expected to be slow. Iodine crystals were added into the mixture to catalyse the process by reacting with the magnesium turnings to form iodine-activated magnesium, magnesium (I) iodide.Magnesium(I) iodide functioned as an active agent in the formation of Grignard reagent as it was more soluble and reactive than the magnesium metal alone. Since a small amount of iodine was used and was regenerated at the end of the reaction, iodine served as a catalyst . The regeneration of iodine was indicated by the reappearance of the brown colouration. While some side reactions occurred with the use of such activating agents, the amount of byproducts formed were considered to be insignificant relative to the expected mass of the Grignard reagent; there was a slight compromise between maintaining the yield and rate of reaction. The Grignard reagent had to be used immediately as it was unstable.
3.2Grignard reaction with Carbon Dioxide to synthesize p-Toluic Acid:
In this second part of the experiment, the freshly prepared Grignard reagent was added to crushed solid carbon dioxide (dry ice) to form a carboxylic acid. Dry ice served as both a reagent and a cooling agent. The mechanism is displayed below:
The Grignard reagent attacked the electrophillic carbonyl C atom to form a conjugate base of the p-toluic acid. Grignard reagent was added quickly to thebeaker of dry ice as the dry ice sublimed quickly. The resulting semi solid substance in the beaker was stirred continuously to ensure maximum reaction between the reagents.
In order to recover the carboxylic acid from its salt, concentrated hydrochloric acid (HCl) and ice water was added to the beaker of bromomagnesium salt. As a strong inorganic acid, HCl would dissociate completely in the presence of water to give hydrogen (H+) and chloride ions (Cl-). Then, the hydrogen ions protonated the salt to recoverp-toluic acid; for once protonated, the acid was no longer soluble in water and would be precipitated. De-ionized water was used as it contained no undesirable contaminants such as fluoride compounds and trihalomethanes which might cause side reactions to occur and reduce the percentage yield. A cold aqueous work-up with low temperature caused further precipitation and compensated for the significant heat of neutralization released when the concentrated acid was added. The solution was tested with a Congo Red paper, which turned blue, to ensure that the solution was acidic, and that the toluic-salt had been completely protonated and precipitated.
3.3 Separation by solvent extraction
Prior to separation, the separatory funnel was filled with de-ionized water and checked for leakage from the stopcock. It was then inverted to confirm that the stopper was not leaking. This ensured that there would be no loss of reactants due to equipment flaws as the solvent extraction progressed.
In order to separate the solvent from the crude product,dichloromethane (DCM) was used to completely dissolve the crude product. To ensure that all crude product was collected, the beaker was swirled with DCM and the washings added to the separatory funnel.The theory of solvent extractionsuggested that additional solvent and multiple extractions would result in a greater separation, as described in the equation below:
where: q is the fraction remaining after one extraction
n is the number of extraction carried out
V1is the volume of solute in phase 1
V2is the volume of solute in phase 2 (the extraction solvent)
K is the partition coefficient
DCM, being an organic solvent, dissolved the organic p-toluic acid due to favorable solute-solvent interactions. However, DCM dissolved organic impurities too, including THF, unreacted p-bromotoulene and undesired byproducts. To solve this problem, sodium hydroxide (NaOH) was added to form a conjugate base of p-toluic acid, as shown below:
R-COOH + NaOH → R-COO-Na+ + H2O
This acid-base neutralization allowedp-toluic acid to form an ionic salt whichwas soluble in water and thus, be extracted into the aqueous phase. The organic impurities would remain dissolved in the organic phase.
The separatory funnel was shakenvigourously in the fumehood. Shaking ensured that there was even mixing between the reagents such that most of the p-toluic acid came into contact with NaOH, reacted to produce a water-soluble conjugate base and was extracted into the aqueous phase. As DCM was volatile, the mechanical agitation would cause it to vaporize. Built-up pressure in the funnel was released by slowly opening the stopcock after a few shakes. The separatory funnel was left to stand to allow the mixture to separate into two immiscible layers.
DCM, being denser, would be collected at the bottom of the separatory funnel, while the aqueous layer, containing the conjugate base of p-toluic acid, would be collected at the top.The DCM layer was collected and multiple extractions were repeated to ensure maximal separation of compounds. The resultant aqueous layers were combined and cooled in an ice-water bath.
In order to recover the p-toluic acid from its salt, concentrated hydrochloric acid (HCl) to the beaker containing the aqueous layers. As a strong acid, HCl would dissociate completely in the presence of water to give hydrogen (H+) and chloride ions (Cl-). Then, the hydrogen ions protonated the conjugate salt and precipitated p-toluic acid. A cold aqueous condition with low temperature caused further precipitation and compensated for the significant heat of neutralization released when the concentrated acid was added. The solution was tested with a Congo Red paper, which turned blue, to ensure that the solution was acidic, and that p-toluic acid had been completely protonated and precipitated.
3.4 Purification by recrystallization
The most common method of purifying solid organic compounds is by recrystallization. In this technique, an impure solid compound is dissolved in a solvent and then allowed to slowly crystallize out as the solution cools. As the compound crystallizes from the solution, the molecules of the other compounds dissolved in solution are excluded from the growing crystal lattice, giving a pure solid.
Crystallization of a solid is not the same as precipitation of a solid. In crystallization, there is a slow, selective formation of the crystal framework resulting in a pure compound. In precipitation, there is a rapid formation of a solid from a solution that usually produces an amorphous solid containing many trapped impurities within the solid's crystal framework. For this reason, experimental procedures that produce a solid product by precipitation always include a final recrystallization step to give the pure compound.
The process of recrystallization relies on the property that for most compounds, as the temperature of a solvent increases, the solubility of the compound in that solvent also increases. p-toluic acid is insoluble in ethanol at room temperature, soluble in the boiling solvent and has a higher boiling point than the solvent. The heating rate was controlled such that ethanol was not completely evaporated off, thereby preventing the product from decomposing.
After p-toluic acid dissolved in boiling ethanol, water was added to the mixture until the mixture became cloudy, indicating that p-toluic acid was precipitating from the solution. A few drops of ethanol was added to redissolve the precipitate, producing a clear solution. This ensured that the solution was saturated. The solvent-pair of ethanol-water was chosen as the two solvents were miscible with each other, but have opposite abilities to dissolve p-toluic acid. The acid was soluble in ethanol and was relatively insoluble in water.
The mixture was left to cool to room temperature for 10 minutes before being placed in an ice-bath for 10 more minutes. If crystal formation occurred too rapidly, impurities may become trapped in the crystals. The p-toluic acid crystals were then obtained by vacuum filtration and tested for its purity by determining its melting point.
3.5 Discussion on experimental and theoretical yield
From the results obtained, the experimental yield was only 55.3%. This yield, while reasonable, could be higher if not due to several factors. One reason might be due to the destruction of Grignard reagent by atmospheric water vapourand oxygen while it was prepared, despite the use of calcium chloride guard tubes. Also, some reactants dripped out from the inverted separatory funnel’s stopper due to internal accumulated pressure, before the stopcock could be opened.
Melting point range was used to determine the purity of the compounds. Pure crystalline compounds possess characteristic melting points; therefore any deviations in the experimental melting points of the compounds would mean the presence of impurities. From the results below, the experimental melting point range was within its given literature value:
Theoretical melting point range
178°C – 182°C
Experimental melting point range
178.8°C – 179.5°C
Table comparing experimental and theoretical melting point ranges of p-toluic acid
This translated to a high percentage purity of p-toluic acid.
Grignard reagents are extremely useful in extending the carbon chain on organic compounds. However, as they are reactive and unstable, the process of synthesizing and using Grignard reagents has to be conductedunder strict experimental conditions. In this experiment, a Grignard reagent, p-totylmagnesium bromide, was synthesized from p-bromotoluene and this reagent was subsequently reacted with dry ice, solid carbon dioxide, to form p-toluic acid. The final purified product obtained was 3.01g of white needle-like crystals with a melting point range of 178.8°C – 179.5°C and a percentageyield of 55.3%. The experimental melting point range of p-toluic acid compared favorably to its literature values, suggesting that the eventual product was of a high purity.
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