The Synthesis of a Benzoic Acid Derivative
Introduction
The Grignard reagents are strong organometallic nucleophiles formed by reacting an alkyl or aryl halide with magnesium metal. The nucleophiles were discovered by a French Chemist, Victor Grignard.1 Grignard reagents are highly appreciated in organic synthesis due to their ability to act as nucleophiles, adding to various electrophiles such as carbonyl compounds (aldehydes, ketones, esters), epoxides, and carbon dioxide. Grignard reagents find applications in various organic reactions, including nucleophilic addition, nucleophilic substitution, and synthesis of complex organic molecules. They are widely used in synthesizing alcohols, carboxylic acids, ketones, i.e., the benzoic acid derivative, aldehydes, and other functional groups.
Scheme 1: Preparation of the Grignard Reagent
Scheme 2: Reaction of a Grignard Reagent with CO2 to form a Carboxylic Acid
Aim
The experiment aimed to explore the application of Grignard reagents in the synthesis of carboxylic acids. An unknown aryl halide was used in this process.
Procedure
Preparation of Grignard Reagent
A 25 ml dry round-bottomed flask without scar cracks was used for the preparation of the Grignard reagent. A dry flask was put in a beaker. 0.272g of magnesium turnings were added to a dry flask. In the fume chamber, 2.5 ml of tetrahydrofuran (THF), the solvent, was dispensed into the flask. The flask was removed from the beaker and attached to a Claisen head and air condenser. A glass pipette was then used for pipetting 1 ml of aryl bromine. The hot plate was set at five, and the contents stirred rapidly. As the solution turned gray and cloudy, the rest of the aryl bromine was added dropwise. The contents were heated moderately for fifteen minutes until they turned chalky brown.
Addition of Solid CO2
A small piece of dry ice was wrapped in a paper towel. The ice was broken into 2g chunks and transferred to a 150 ml beaker with a stir bar. The Grignard reagent was added to the ice, and the reaction was stirred for 10 minutes. Water had to be added to enhance the stirring. The beaker was placed in an ice bath to cool down. 5 ml of 6M solution of HCl was added, and the contents were stirred.
Work-Up and Isolation of the Benzoic Acid Derivative
The solution was poured into a separating funnel, and the beaker was rinsed with dichloromethane. The contents were shaken gently to separate into two layers. In two beakers, the layers were separated. The aqueous phase was restored in the separating funnel, 15 ml of dichloromethane was added, and separation was done again. 5 ml of 3 M NaOH was used to extract the combined phases. The separation was repeated, and aqueous extracts were combined. 5 ml of 6 M HCl was added to the basic solution, and the pH was verified until the solution was acidic. The beaker with acidic aqueous suspension was put in an ice bath. 10 ml of distilled water was placed in a test tube. The VF was turned on, and the product was collected from filtration. It was rinsed with water and dried. 100g were collected, labeled, and the dry mass recorded. The product was analyzed through IR and NMR, and its melting point was determined. The waste products were disposed of in their respective containers, and the glassware was washed.
Results
Several observations were made during the experiment. First, the cloudy and gray color of the solution turned brown until the magnesium metal was dissolved. Second, while adding the aryl bromide dropwise, the contents sizzled, coupled with a pungent smell. After adding HCl, the contents turned cloudy, but the addition of DCM made it clear, and two layers were formed.
The most identifiable peaks in the spectrum are the broad peak starting from around 2500 cm-1 to around 3300 cm-1, the peak at 1668.92 cm-1, the peak at 2828 cm-1, and the one at 752.51.
The H-NMR spectra show three peaks with two peaks between 7 and 8 ppm. The one close to 7.2 seems like a doublet, while the one at 8 is a doublet. There is also a peak at 2.5 which is a singlet with a strong signal. The C-NMR spectra show several peaks between 110 and 170 ppm, there is also a distinctive peak at 170 ppm and another at just above 20 ppm.
Discussion
The compound produced is p-toluic acid. Identifiable peaks in the IR spectrum are the broad peak starting from around 2500 cm-1 to around 3300 cm-1, the peak at 1668.92 cm-1, the peak at 2828 cm-1, and the one at 752.51. Based on IR absorption data from Libretexts, the broad peak corresponds to the stretching vibration of the O-H in carboxylic acids indicating the product is a carboxylic acid.2 The peak at 1668.92 cm-1, which is sharp and strong, corresponds to the stretching vibration of the carbonyl group in the carboxylic acid (C=O).2 The peak at 2828 cm-1 peak is due to the C-H stretching in the attached CH3 group in the para-position.2 The peak at 752.51 is due to C-H bending in a benzene derivative. This information shows that the product is a carboxylic acid derived from benzene and has an aliphatic group.
From the IR spectroscopy, there are three prominent peaks. The singlet at 2.3 ppm is for the aliphatic protons bonded to carbon with no hydrogens in the para position. The doublet at 7.3 ppm is for one pair of protons in the benzene ring. This is the pair furthest from the carboxylic acid. They are, therefore, more shielded. The signal is a doublet because they are bonded to carbon with one hydrogen. They have the same environment. At 8 ppm, there is another doublet for the second pair of hydrogens in the benzene group. This pair is less shielded and, therefore, more downfield. Like the other pair, the neighboring carbon has one proton. However, the H-NMR misses a peak between 10-12 ppm, which is consistent with the hydrogen atom in the carboxylic acid. This does not affect the hypothesis because the IR spectrum provides proof of the existence of a carboxylic group.
From the C-NMR spectra, the peaks between 110 and 170 ppm are for the carbons in the aromatic chain of the compound. The peak at around 170 ppm is consistent with the peak expected for the carboxylic carbon, which absorbs at 170 ppm. Finally, the peak at just above 20 ppm is for the aliphatic carbon at the para position. However, there seem to be impurities in the compound presented because the number of peaks in the spectra exceeds the expected number of peaks expected from the hypothesis. Nonetheless, data from IR spectra and H-NMR spectra, for the most part, support the hypothesis.
Aggregating this information, the product has the following structure;
The mechanism of the reaction is as follows; Starting with p-bromotoluene, reaction with magnesium in the presence of a solvent, tetrahydrofuran, to form the Grignard reagent. The Grignard reagent attacks the carbon in CO2, and electrons move to one carbon while the MgBr leaves the toluene. This leaves a positive charge on the magnesium and a negative charge on the oxygen on one end of the carbon atom derived from CO2. After the introduction of HCl in the contents, the protons are abducted by the oxygen atom with a negative charge, and the now negative chlorine bonds to the positive end of magnesium bromide. The end product is p-toluic acid.
Conclusion
This experiment aimed to demonstrate the significance of Grignard reagents in the preparation of carboxylic acids and their derivatives. The experiment’s aim was met because by following the procedure, p-toluic acid was created as per the data from the spectra. Based on the protocol, some errors are expected in the following aspects; First, Errors can occur during the measurement of reagents, such as the weight of magnesium turnings or the volume of liquids. It is important to use calibrated and precise measuring instruments to minimize this error and follow proper measurement techniques. Second, incomplete reactions and inefficient separation which can be addressed by optimizing reaction conditions and discarding the mixed phase if the quantitative data is not required. Otherwise, appropriate filtration techniques can help improve on this. Finally, there might have been contamination during IR and NMR analysis. Clean storage and handling can help reduce this error.
References
(1) Peltzer, R. M.; Gauss, J.; Eisenstein, O.; Cascella, M. The Grignard Reaction – Unraveling a Chemical Puzzle. Journal of the American Chemical Society 2020, 142 (6), 2984–2994. https://doi.org/10.1021/jacs.9b11829.
(2) Libretexts. Infrared Spectroscopy Absorption Table. Chemistry LibreTexts. https://chem.libretexts.org/Ancillary_Materials/Reference/Reference_Tables/Spectroscopic_Reference_Tables/Infrared_Spectroscopy_Absorption_Table.
Chris Cavanaugh
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