Fall19 Chapter 9 Recrystallization T PDF

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x Chapter 9 Recrystallization Technique Report July 5, 2021 Purpose The purpose of this experiment was to synthesize a chalcone product from 3-chlorobenzaldehyde and 4’-methoxyacetophenone. The chalcone product was synthesized via base catalyzed ClaisenSchmidt condensation. Recrystallization, which allows for the purification of a solid with trace impurities, was used to purify the product. The crude chalcone product was collected via vacuum filtration. The product was then characterized by melting point, 1H NMR, and IR data analyses. Results, Discussion, and Conclusions Claisen-Schmidt condensation is a common reaction utilized to synthesize chalcones and involves the formation of a carbon-carbon bond. The active reagent, sodium hydroxide, deprotonates the most acidic proton attached to the α-carbon of the ketone. The resonance stabilized enolate is formed by deprotonation with the hydroxide ion to give a nucleophilic intermediate. The nucleophile attacks the electrophile, the carbonyl carbon of the aldehyde. The newly generated tetrahedral intermediate regains charge neutrality to form the aldol product by abstracting a proton from water and thus regenerating the base catalyst. The acidic alpha proton is removed by the reformed hydroxide catalyst to generate another enolate. Finally, the hydroxide ion is lost to regenerate the catalyst, leaving the final condensation product as an α, β-unsaturated ketone stabilized by alkene formation. The equilibrium favored product formation because the chalcone product precipitated as it formed. Recrystallization is important in the purification of a solid contaminated with trace amounts of impurities and was used to purify the product. The solvent used was ethanol, and reagents included 3-chlorobenzaldehyde and 4’methoxyacetophenone as starting material. Sodium hydroxide was used as the base catalyst. Saturated 1

aqueous sodium chloride was used to wash the organic layer. Distilled water was used to wash the product and for testing recrystallization solvents. Additional reagents used for solvent testing were methanol, ethanol, ethyl acetate, dichloromethane, and hexanes. Because the produce precipitates out as the reaction progresses, this reaction was not suitable to monitor by TLC. Monitoring with Mini GC was unnecessary because the product visibly precipitated out. The reaction was seen progressing based on a change from liquid to solid. The reaction reached equilibrium, because there was a visible change as the product precipitated out, which forced the equilibrium to the right to favor product formation. The crude product was isolated via vacuum filtration and washed with cold water. There was no other work-up. A suitable recrystallization solvent was chosen based on polarity that was similar but not the same. The following solvents were tested: water, ethyl acetate, dichloromethane, hexanes, methanol, and ethanol. The chalcone’s polarity is based on the dipole moment due to the carbonyl, the ability to accept hydrogen-bonds, and the p-orbital due to the carbonyl which gives some polarizability. The compound’s conjugated system also affords a large p-orbital, which gives some polarizability. Further, the methoxy and alkyl halide introduce additional polar atoms, and the chlorine’s large size attributes to high polarizability. Because of water’s ability to hydrogen bond, its small size, and large net dipole moment, it was too polar and too dissimilar. Dichloromethane was too similar in polarity due to the introduction of two polar atoms and the large halides (chlorines), which contribute to high polarizability because of size. Ethyl acetate was also too similar because it has multiple electronegative atoms and a large dipole moment due to the carbonyl of the ester. Hexanes was too nonpolar and dissimilar because of its many carbon-hydrogen bonds and inability to bond with electronegative atoms, making it insoluble at all temperatures. The solvents suitable for recrystallization were methanol and ethanol. Both small organic molecules are primarily made of carbon-carbon, carbon-oxygen, and carbon-hydrogen bonds. Methanol and ethanol’s polarity come from their alcohol functional groups, which have the ability to hydrogen bond and introduce an electronegative atom. The chalcone product is primarily composed of similar bonds, so methanol and ethanol were similar in polarity but not the same. For methanol and ethanol, the 2

product was completely soluble at high temperatures but only partially soluble at low temperatures, which would allow the product to precipitate out during cooling. Recrystallization was used to purify the crude chalcone product by removing trace impurities. The chosen solvent system, ethanol, was successful, because the compound was completely soluble at higher temperatures during the heating process. However, the compound was sparingly soluble at room temperature, which allowed the chalcone product to precipitate out during cooling. Impurities were removed in the process because of their solubility or insolubility at all temperatures. Purification proved successful based on a change in appearance as well. The crude product was initially light yellowish, chalky, and powdery, but after purification, crystallization afforded yellowish, fluffy crystals. Based on reported literature, the crystals appeared yellowish in color as expected (2). The crude chalcone product afforded a 74% yield. The purification process was somewhat successful, given a 51% yield based on 1.149g of isolated product and 77% recovery of chalcone product. The purified percent yield was relatively low, which could have in part been due to product loss. Loss of product may have occurred due to product solubility, because some crystals were soluble in the solvent, and so some would stay in it. A major source of error may have been the solubility of the solvent. Solvent testing also led to some product loss. However, the recovery yield was relatively high. The recovery value does show a small presence of impurities and product loss during recrystallization due to the solubility of the chalcone in the solvent. Finally, 1H NMR, IR, and melting points analyses used to characterize the product confirmed product formation and further demonstrated purification success. The 1H NMR spectral analysis allowed for characterization of the product. The NMR shows a doublet integrating to 2 at 7.97 ppm, which is indicative of the hydrogens ortho to the carbonyl. A doublet integrates to 2 at 7.06 ppm, representing the hydrogens ortho to the methoxy and meta to the carbonyl. The methoxy hydrogens are a singlet and integrate to 3 at 3.89 ppm. Hydrogens of the trans alkene and the hydrogen para to the chlorine atom overlap and are seen as multiplet integrating to 3 at 3

7.39 ppm. Additionally, hydrogens ortho and meta to the chlorine of the chlorobenzene overlap and are seen as a multiplet integrating to 3 at 7.60 ppm. An 1H NMR for starting material would have shown a singlet integrating to 3 at around 2.1-2.4 ppm, representing the methyl hydrogens of the ketone contained in 4’-methoxyacetophenone (3). Additionally, the NMR would have shown a singlet integrating to 1 at around 9.0-10.0 ppm, indicative of the hydrogen of the aldehyde contained in 3chlorobenzaldehyde (4). Absence of the ketone methyl group and the aldehyde hydrogen prove conversion of starting material to product. The peaks key to product formation were those of the trans alkene hydrogens. Altogether, 1H NMR analysis confirms product formation, and recrystallization proved effective in purifying the product. The IR spectral analysis further supports formation of the chalcone product. The carbonhydrogen bond of the trans alkene is seen at 3065 cm-1. The carbon-hydrogen of the aromatic is at 2974 cm-1, while the peak at 2842 cm-1 represents the carbon-hydrogen aliphatic bond. The ketone next to the alkene is at 1660 cm-1, and the carbon-carbon double bond of the trans alkene is seen at 1591 cm-1. A peak at 1508 cm-1 is indicative of the carbon-carbon double bond of the aromatic, and the peak at 1466 cm-1 represents the methyl umbrella bend. The carbon-oxygen of the ether is seen at 1255 cm-1, while the carbon-chlorine bond is seen at 745 cm-1. Peaks for the carbon-carbon double bond and carbon-hydrogen bonds of the trans alkene were key to product formation and provide strong evidence for the conversion of starting material to product. An IR for starting material would have shown a peak at 1703 cm-1, representing the carbonyl of the aldehyde contained in 3-chlorobenzaldehyde (4). There would have also been a key peak at 2720 cm-1, indicative of the carbon-hydrogen bond of the aldehyde (4). Further, if 4’methoxyacetophenone was still present, the ketone contained within this compound would have a slightly different frequency than that of the product, and the IR would have shown two ketones (3). The IR data matches the NMR data, which shows product formation and absence of starting material hydrogens.

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The pure melting point (mp) data further provided evidence of chalcone synthesis. The reported literature for the chalcone product is 118oC (2). The crude melting point was 109.1-112.8oC. The broad range and significantly lower values of the crude melting point indicate a high presence of impurities. The pure melting point observed for the product was 119.7-120.3oC. The narrow range of this melting point confirms the success of purification and purity of the product as shown by the NMR and IR analyses. The lack of impurities observed in the melting point and spectral data, as well as consistency between techniques, indicate the successful formation and purification of the chalcone product. In conclusion, the synthesis of 3-chloro-4’-methoxychalcone via Claisen-Schmidt Condensation and subsequent purification by recrystallization was successful with an overall 51% product yield. The 1H NMR, IR, and mp analyses confirmed product formation and purification success. A major source of error was product solubility in the solvent. The take-home message was recrystallization allows for the purification of compounds with trace impurities. Overall, further improvement for this experiment could be to use a co-solvent system, such as water, which would help the product have less solubility at lower temperatures and increase pure product yield when the product precipitates out at cooler temperatures. Experimental 3-chloro-4’-methoxychalcone. 3-chlorobenzaldehdye (0.93mL, 8.21mmol), 4’methoxyacetophenone (1.29g, 8.59mmol), and 95% ethanol (30 mL) were combined and stirred. Once dissolved, sodium hydroxide solution (3M, 0.5mL) was added all at once. Upon equilibrium, the crude chalcone product was collected and isolated via vacuum filtration. The crystals were washed with cold water (3 x 10 mL), then recrystallized (ethanol, 100mL). Recrystallization afforded fluffy, yellowish crystals (1.149g, 51% yield). mp 119.7-120.3oC; 1H NMR (60 MHz, CDCl3) δ (ppm) 7.97 (d, 2H), 7.60 (m, 3H), 7.39 (m, 3H), 7.06 (d, 2H), 3.89 (s, 3H); IR Vmax (cm-1) 3065, 2974, 2842, 1660, 1591, 1508, 1466, 1255, 745.

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References 1. Dykstra, S.A.; Beiswinger, K.M.; Bischof, A.M.; Rose, H.C.; Williams, R.R.; Lab Guide for Chem 213W: Introductory Organic Chemistry Laboratory, Macmillian Learning Curriculum Solutions: Plymouth, MI, 2020. 2. 3-chloro-4’-methoxychalcone, CAS No. 52182-25-9 PubChem.

https://pubchem.ncbi.nlm.nih.gov/ (accessed 10/20/19). 3. 4’-methoxyacetophenone, SDS No. 117374 Sigma Aldrich. www.sigmaldrich.com (accessed

10/20/19). 4. 3-chlorobenzaldehyde, SDS No. C23403 Sigma Aldrich. www.sigmaldrich.com (accessed

10/20/19).

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