Discover The Product Of The Reaction Between 3-Pentanone And P-Chlorobenzaldehyde
Abstract
In the process of developing novel molecules, an abnormally low yield of desired molecules usually represent a presence of unexpected products. Researchers could determine the identification and deduce the chemical structure of the unexpected product by the assistance of analytic instruments, such as IR spectroscopy and NMR spectroscopy, and hence discovering novel synthetic methods and improving the yield of desired product. This experiment is designed to identify the final product of the reaction between 3-pentanone and p-chlorobenzaldehyde by performing a mixed aldol condensation and Michael Addition reaction and to use an IR spectroscopy and a 1H NMR spectroscopy to confirm the structure of the product. My result suggested that the product between 3-pentanone and p-chlorobenzaldehyde is 2,6-bis(4-chlorophenyl)-3,5-dimethyltetrahydro-4H-pyran-4-one and a variety of side products might be synthesized leading of a low yield of desired product.
Introduction
As a spread fundamental reaction of new carbon-carbon bond construction, aldol condensation is regarded as a significant method of novel organic molecular synthesis in biological and medical areas, such as the development in chemical pharmaceuticals (1). In the preparation of aldol reactants, aldehyde or ketone is converted to enolate nucleophile and attacks the α-carbon on the other carbonyl group carrying with an acidic or basic condition (2). With the constant presence of an acid or a base, an enantioselectivity of α, β-unsaturated carbonyl compounds might be showed by a crossed aldol condensation due to the possibility of enolate formed by both crossed and direct aldol addition.
However, the formation of kinetic enolates and thermodynamic enolates could be mediated with the presence of different strong base (2) and the result aldol could be regulated by controlling the number of α-hydrogen available for deprotonation. In this experiment, the reactant p-chlorobenzaldehyde is designed to be attacked by 3-pentanone since there is no accessible α-hydrogen adjacent to the aldehyde group. With a presence of sodium hydroxide providing basic condition and an ethanol solvent, 1 equivalence of 3-pentanone reacts with 2 equivalence of p-chlorobenzaldehyde as there are two α-carbon atoms available for p-chlorobenzaldehyde to bond with.
Followed by a Michael addition occurring on 1,4 position, an intramolecular reaction undergone between the nucleophile of oxygen and the carbon-carbon double bond in α, β-unsaturated carbonyl group. As important as aldol condensation, Michael addition, also called conjugated addition or 1,4-addition, is another one of the most common and useful methods contributing to the formation of carbon-carbon bonds. This facile reaction occurs between activated olefins and nucleophiles adding to alkynes via a carbon-carbon multiple bond (3) and is widely used in polymerization of chain growth and step growth due to its relatively high conversion factors and reaction rates with a tolerance of a variety of functional groups (4). A combination of aldol condensation and Michael addition performed in this experiment allows a wide range of polymers derived from different monomers giving rise to more possibilities in developing novel organic materials, such as the syntheses of hydrogels, thermoset resins and coatings which are recently founded in more impressive conversions and lower cure times (4). This experiment also shows the possibilities of constructing stereo conjugated drugs due to the high flexibility of crossed and direct reactions, arousing our inspirations of meeting clinical uses in medical and biomaterial fields on the molecular level.
Results
- Mechanism
- Yield and Observations
- IR Spectroscopy
- 1H NMR Spectroscopy
The given reagents 3-pentanone and p-chlorobenzaldehyde underwent an aldol condensation and follows by a Michael addition. The reaction scheme is showed in Figure 1 and the mechanism is showed in Figure 2. Figure 1: The reaction scheme of the the reaction between 3-pentanone and p-chlorobenzaldehyde Figure 2: The mechanism of the reaction between 3-pentanone and p-chlorobenzaldehyde3-Pentanone converted to an enolate under a basic condition and attacked the carbonyl group of p-chlorobenzaldehyde creating a new carbon-carbon bond and forming a β-hydroxy ketone, followed by an irreversible dehydration producing an α, β-unsaturated carbonyl intermediate. The α-carbon on the other side of 3-pentanone underwent the same aldol addition but followed by an intramolecular Michael addition between the oxygen nucleophile and the α, β-unsaturated ketone group, resulting in a ring formation and producing 2,6-bis(4-chlorophenyl)-3,5-dimethyltetrahydro-4H-pyran-4-one as a final product.
The crude product of 2,6-bis(4-chlorophenyl)-3,5-dimethyltetrahydro-4H-pyran-4-one was a pale yellow crystal and the crude yield was 0. 37 g (a recovery rate of 7%). The purified product was a white crystal with a yield of 0. 24 g and a melting point of 184-188 ℃ was obtained. Refer to a melting point of 189-191 ℃ (5), the product was confirmed.
The purpose of this part was to confirm the structure of the product by IR spectroscopy, the IR data is showed in Figure 3. Figure 3: IR Spectrum for the synthesized 2,6-bis(4-chlorophenyl)-3,5-dimethyltetrahydro-4H-pyran-4-oneThe significant peak at 1702. 78 cm-1 attributed to the unsaturated carbonyl group and a troop of stretches between 830. 98 cm-1 and 1491. 10 cm-1 indicated the aromatic region, showing a presence of 2,6-bis(4-chlorophenyl)-3,5-dimethyltetrahydro-4H-pyran-4-one. A set of peaks banded around 3000 cm-1 represented the sp3 C-H stretches.
This part was designed to further confirm the structure of the product and to identify the hydrogen atoms attaching to the product.
Other coupling constants were calculated in the same way.
Discussion: In this experiment, the yield of 2,6-bis(4-chlorophenyl)-3,5-dimethyltetrahydro-4H-pyran-4-one was extremely low and the possibility of the production of side products during the reactions cannot be ruled out. As a starting reagent, 3-pentanone could be both the nucleophile attacking carbonyl group with a presence of α-carbon, and the electrophile as a site accepting electrons due to its ketone group. So a side product of 5-ethyl-4-methylhept-4-en-3-one might be produced by 2 molecules of 3-pentanone presenting an aldol addition. Furthermore, a third molecule of 3-pentanone could be attached to the previous 5-ethyl-4-methylhept-4-en-3-one by a Michael addition, synthesizing 5,5-diethyl-4,6-dimethylnonane-3,7-dione. Moreover, when the second molecule of p-chlorobenzaldehyde was added to the 3-pentanone, an aldol condensation might take place instead of a Michael addition, resulting in a production of (1E,4E)-1,5-bis(4-chlorophenyl)-2,4-dimethylpenta-1,4-dien-3-one.
A variety of other side products might also be produced by Michael additions due to a high compositionality of the intermediates. Figure 5 shows the schemes of the synthesises of 5-ethyl-4-methylhept-4-en-3-one, 5,5-diethyl-4,6-dimethylnonane-3,7-dione and (1E,4E)-1,5-bis(4-chlorophenyl)-2,4-dimethylpenta-1,4-dien-3-one. Figure 5: The schemes of the synthesizes of some side productsIR spectroscopy and 1H NMR spectroscopy were used to analyze the structural conformation of the product. The stretches in IR spectrum could indicate the key function groups presenting in the compound, and the chemical shifts in 1H NMR determine the shielding degree of the nuclei from the magnetic field and higher chemical shift values represent more deshielded protons.
Since the induced aromatic ring current create a local magnetic field sharing the same direction with the external field, resulting in the nuclei deshielding, protons attaching to a aromatic ring have relatively higher chemical shift. The hydrogen atoms adjacent to the chlorine are more deshielded than the hydrogen atoms adjacent to alkyls, so the positions of HA and HB were conformed. By the multiplicity (the number of coupled hydrogens plus one) of peaks and the integration (shows the ratio of hydrogens in distinguish types), the left hydrogen atoms given rise to their signals could be determined and their coupling constants measure the interactions between coupled protons. In my 1H NMR data, there was a singlet peak at 7. 35 ppm with relatively high integration (5. 66) and it might be a presence of impurity since there were no other peaks suspected of impurity and it was not a common solvent peak (6). Thomas et al. (5) detected a peak at 7. 73 ppm (4H; s; aromatic) (5) which was similar to my data, however, I think there are only two types of hydrogens attaching to the aromatic ring due to the symmetric structure and each hydrogen gives rise to a doublet. So Thomas et al. (5) might produce the same impurity in the experiment as I did, but there is no reasonable inference of the conformation of the impurity so far.
Experimental
Procedure: 3-pentanone (0. 86 g, 10 mmol, 1 eq. ) and p-chlorobenzaldehyde (3. 5 g, 25 mmol, 2 eq. ) were added to a 125 Erlenmeyer flask containing ethanol. After the dissolution of solutes, sodium hydroxide solution (15 mL, 2N) was added and then the flask was fluxed at 70℃ for 30 minutes with stirring. Upon cooling in an ice bath at 0℃, pale yellow crystals formed and were collected by vacuum filtration. And then these crude crystals were recrystallized using ethanol as a solvent, white crystals were collected as the purified product (0. 24 g, 7% recovery).
Chemical Safety
All reactions were carried out in the fume hood. 3-pentanone was highly flammable and could cause serious eye irritation (7). p-Chlorobenzaldehyde was harmful if swallowed and could cause skin, eye and respiratory irritation (8). Ethanol was highly flammable and could cause serious eye irritation (9). Sodium hydroxide could cause metallic corrosion, skin burns, eye damage and respiratory irritation (10).
