An improved method for aldol condensation catalyses by Amberlyst A-26 OH: application in the synthesis of pseudoionone derivative, 11,15-dimethylhexadeca-8,10,14-trien-7-one

2.1 Instrumentation

Ultraviolet-visible (UV-Vis) (Shimadzu UV 2450, Japan) analysis was run in ethanol, Fourier transform infrared (FTIR) (Perkin Elmer Model Spectrum GX, USA) and gas chromatography (GC)/GC-mass spectrometry (MS) analyses were performed on an Agilent 7890A (USA) gas chromatograph coupled with a mass spectrometer system of an Agilent 5975C inert mass selective detector with a triple-axis detector. The gas chromatograph was equipped with a fused silica capillary column DB-5 (5% phenylmethylpolysiloxane, 30 m×0.32 mm, film thickness 1.50 μm). The injector and interface were operated at 250°C and 300°C, respectively. The oven temperature was raised from 50°C to 300°C at a heating rate of 8°C/min and then isothermally held for 5 min. The constant head pressure was 0.6 bars. As a carrier, gas helium was used at 1.0 ml/min. The samples were injected in a pulsed split mode. The mass selective detector was operated at the ionization energy of 70 eV, in the 35–500 amu range with a scanning speed of 0.34 s and nuclear magnetic resonance (NMR) (600 MHz, Bruker, USA) was used in the characterization process in the experiment. The calculation was done using an external calibration curve prepared from the pure product isolated, using preparative thin layer chromatography (hexane:ethyl acetate=9.5:0.5). All chemicals used were purchased from Aldrich (Reagent grade) and used without further purification.

2.2 Aldol condensation between citral and 2-octanone

The reaction was carried out in a 250 ml three-necked bottom flask equipped with a thermometer and a reflux condenser. Some 0.975 g (0.156 mmol) of Amberlyst A-26 OH was stirred in 30 ml of ethanol for 10 min. Citral (0.5 g, 3.12 mmol) and 2-octanone (4.00 g, 0.0312 mol) were added, and the mixture was heated at 60°C for 3.5 h. The reaction mixture was cooled to room temperature. The catalyst was filtered and washed with ethanol. The combined organic phases were concentrated by vacuum evaporation. The pure product was isolated by preparative thin layer chromatography with hexane:ethyl acetate (9.5:0.5) and characterised using UV-Vis, FTIR, GC-MS and NMR. 2-Octanone/citral molar ratio was tested first. Once the best molar ratio was achieved, the catalyst amount (5%, 10% and 15%) and temperature (25°C, 40°C and 60°C) were optimized.

3.1 2-Octanone/citral molar ratio

Figure 1 shows the influence of the molar ratio of 2-octanone on the yield of 11,15-dimethyl-hexadeca-8,10,14-trien-7-one. The basic sites of Amberlyst A-26 OH are responsible for the proton abstraction of the aldehyde or ketone. Increasing the molar ratio of 2-octanone/citral from 1 to 10 does not improve the yield significantly. The little increase in yield may be contributed to by the increased chances of α-proton abstraction from 2-octanone, therefore reducing the possibility of α-proton abstraction from the citral molecule. Thus, a molar ratio of 10 was chosen to investigate the effect of catalyst amount used.

Figure 1:

Effect of 2-octanone/citral molar ratio on yield of 11,15-dimethyl-hexadeca-8,10,14-trien-7-one. (Catalyst amount of 5%, 60°C, 3.5 h).

3.2 Catalyst amount

The study on catalyst amounts of 5%, 10% and 15% (% mole of citral) was done to investigate its effect on the yield of 11,15-dimethyl-hexadeca-8,10,14-trien-7-one. It can be understood that the increase in the amount of catalysts allows higher chances of α-proton abstraction from citral that may lead to more side reaction products. Five percent catalyst usage was found to produce almost no side reaction products with a yield of 93% (Figure 2). Therefore, it was selected to study the influence of temperature on the yield of 11,15-dimethyl-hexadeca-8,10,14-trien-7-one.

Figure 2:

Effect of catalyst amount on yield of 11,15-dimethyl-hexadeca-8,10,14-trien-7-one. (2-Octanone/citral molar ratio of 10, 60°C, 3.5 h).

3.3 Temperature

The effect of temperature on the yield of 11,15-dimethyl-hexadeca-8,10,14-trien-7-one was evaluated at 25°C (room temperature), 40°C and 60°C. In Figure 3, it was observed that the yield increased with the increase of temperature. This is because a higher temperature provides more kinetic energy for the reaction that hastens the conversion rate of citral. At 60°C, a maximum yield of 93% was achieved.

Figure 3:

Effect of temperature on yield of 11,15-dimethyl-hexadeca-8,10,14-trien-7-one. (2-Octanone/citral molar ratio of 10, catalyst amount of 5%, 3.5 h).

3.4 Catalyst reusability

Amberlyst A-26 OH used in the reaction was regenerated from a basic treatment and reused several times without loss of activity. The catalyst was filtered after an experiment and washed several times with ethanol, followed by treatment with aqueous 1.0 m NaOH solution for 2 h. The catalyst was then washed with distilled water until the eluate was neutral. This efficient catalyst is proven to be economical, useful and suitable for this aldol condensation reaction with excellent regeneration and reusability shown. Table 2 shows the number of runs completed on the regenerated and reused Amberlyst A-26 OH on the aldol condensation of citral and 2-octanone.

3.5 GC-MS analysis

Figure 4 shows the chromatogram of the optimized reaction parameter carried out in the experiment. The peaks in the chromatogram are analysed using MS and the compounds are listed in Table 3.

Figure 4:

Gas chromatogram of the optimised parameters for aldol condensation of citral and 2-octanone.

The characteristic fragmentations in the mass spectrum of peaks 4 and 5 are m/z 262.3, m/z 179.2, m/z 109.1, m/z 81.1, m/z 69.1, m/z 69.1 and m/z 41.1. The molecular ion shown from the mass spectrum is the same as the molecular weight number of the expected 11,15-dimethyl-hexadeca-8,10,14-trien-7-one isomers (Figure 6). As an initial assumption, E and Z isomers are expected to form because of the existence of E and Z citral isomers used as starting materials. Therefore, further confirmations were performed to confirm the structure of the 11,15-dimethyl-hexadeca-8,10,14-trien-7-one isomers.

3.6 UV-Vis spectroscopy

Each compound gives out a characteristic wavelength when put under the UV-Vis test depending on its structure. Woodward’s rules can be used to predict the particular wavelength. Figure 5 shows the UV-Vis spectrum of the isolated 11,15-dimethyl-hexadeca-8,10,14-trien-7-one isomers. In Table 4, it can be observed that the predicted UV-Vis wavelength number (293) is similar to the experimental wavelength number (292.6) of the 11,15-dimethyl-hexadeca-8,10,14-trien-7-one isomers.

Figure 5:

Ultraviolet-visible (UV-Vis) spectrum of 11,15-dimethyl-hexadeca-8,10,14-trien-7-one isomers.

Figure 6:

Expected structures.

3.7 FTIR spectroscopy

FTIR provides powerful information on the functional group present in the compound. Figure 7 shows the FTIR spectrum of the isolated 11,15-dimethyl-hexadeca-8,10,14-trien-7-one isomers. Table 5 summarises the absorption peak in the FTIR spectrum where one can observe that the C=O stretch at 1680.83 cm^-1 is the result of the conjugation effect where C=O stretch absorbs at a lower frequency than normal. The C=C absorption at 1628.72 cm^-1 and 1588.47 cm^-1 absorptions belong to the C=C bond.

Figure 7:

Fourier transform infrared (FTIR) spectrum of isolated 11,15-dimethyl-hexadeca-8,10,14-trien-7-one isomers.

Table 5:

11,15-Dimethyl-hexadeca-8,10,14-trien-7-one isomers absorption peaks in Fourier transform infrared (FTIR) spectrum.

Functional group	Absorption value (cm-1)
sp3 C-H stretch	2956.34, 2927.31, 2857.46
C=O stretch	1680.83
C=C	1628.72, 1588.47
-CH3 bend	1452.02, 1376.06
	1275.89, 1194.05
sp2 C-H out of plane bend	976.57, 891.68

3.8 NMR spectroscopy

The structures of dimethyl-hexadeca-8,10,14-trien-7-one are characterized using ¹H (Figure 8A–D) and ¹³C (Attached Proton Test) NMR spectroscopy. Figure 6 shows the two isomeric structures of dimethyl-hexadeca-8,10,14-trien-7-one synthesized. The double bond at the carbon positions 8 and 9 is the bond formed in the aldol condensation reaction. This double bond raises the possibility of a cistrans isomerism in the new structure formed. From the ¹H NMR spectrum obtained, the proton positions 8 and 9 of both isomers are assigned to a trans configuration because of the j value of 15 Hz shown.

Figure 8:

¹H Nuclear magnetic resonance (NMR) spectrum of 11,15-dimethyl-hexadeca-8,10,14-trien-7-one isomers.

Due to the use of the starting material citral which consisted of geranial and neral as Z and E isomer, respectively, the PSI derivative formed in the aldol condensation process was expected to have a mixture form of Z and E isomers too. This was because the chain at the stereoisomer point of Z and E isomers was not involved in the aldol condensation process.

¹³C NMR spectroscopy is a valuable tool to identify E and Z isomerism. The gamma effect shown by the E and Z isomers allows us to differentiate them by their chemical shift shown. A gamma effect is defined as the replacement of an H by X on the second atom. An alkyl group which is cis to a substituent will have a lower frequency (upfield) of the isomer in which the carbon substituent is cis to a hydrogen [14]. Therefore, the gamma effect of carbon at positions 12 and 18 is identified. The chemical shifts at carbon 18 of 25.7 Hz and 24.6 Hz belong to the Z and E isomers, respectively. This is because the CH₃ group of carbon 18 is cis to an H rather than a long alkyl chain, as shown in the E isomer. This also applies to the chemical shifts at carbon 12 of 31.6 Hz and 33.0 Hz where they belong to the Z and E isomers, respectively. By assigning these two important peaks of the spectrum, we can distinguish the two sets of ¹H and ¹³C data of which the major intensity peaks belong to the Z isomer while the minor intensity peaks belong to the E isomer.

Being closely related to the structure of PSI, the ¹H and ¹³C NMR of PSI are referred to as the assignation of the PSI derivative and the signals summarized below.

(11Z)-11,15-dimethyl-hexadeca-8,10,14-trien-7-one ¹H NMR (600 MHz, CDCl₃): δ 7.48(C₉-H, 1H, dd, J=15, 11.4), 6.11(C₈-H, 1H, d, J=15), 6.00(C₁₀-H, 1H, d, J=12), 5.07(C₁₄-H, 1H, t, J=6.6), 2.54(C₆-H, 2H, t, J=7.2), 2.32(C₁₂-H_a, 1H, t, J=7.8), 2.16(C₅-H, 2H, overlap), 2.14(C₁₂-H, 1H, t, J=overlap), 1.91(C₁₆-H, 3H, s), 1.68(C₁₇-H, 3H, s), 1.62(C₁₃-H_a, 1H, t, J=overlap), 1.61(C₁₈-H, 3H, s), 1.42(C₁₃-H_b, 1H, d, J=6.6), 1.35-1.26(m, 6H, bulk-CH₂), 0.88(C₁-H, 3H, J=6.6).¹³C NMR (600 MHz, CDCl₃): δ 201.4(C₇=O), 151.0(C₁₁=C), 138.7(C₉=C), 132.3(C₁₅=C), 127.5(C₈), 123.7(C₁₀=C), 123.3(C₁₄=C), 41.0(C₆), 40.4(C₅), 31.6(C₁₂), 29.0(C₄), 26.3(C₁₃), 25.7(C₁₈), 24.5(C₃), 22.5(C₂), 17.7(C₁₆), 17.5(C₁₇), 14.0(C₁).

(11E)-11,15-dimethyl-hexadeca-8,10,14-trien-7-one ¹H NMR (600 MHz, CDCl₃): 7.45(C₉-H, 1H, dd, J=15, 11.4), 6.07(C₈-H, 1H, d, J=15.6), 6.00(C₁₀-H, 1H, d, J=12), 5.10(C₁₄-H, 1H, t, J=6.6), 2.52(C₆-H, 2H, t, J=7.2), 2.32(C₁₂-H_a, 1H, t, J=7.8), 2.16(C₅-H, 2H, overlap), 2.14(C₁₂-H, 1H, t, J=overlap), 1.89(C₁₆-H, 3H, s), 1.67(C₁₇-H, 3H, s), 1.62(C₁₃-H_a, 1H, t, J=overlap), 1.61(C₁₈-H, 3H, s), 1.42(C₁₃-H_b’, 1H, d, J=6.6), 1.35-1.26(m, 6H, bulk-CH₂), 0.88(C₁-H, 3H, J=6.6).¹³C NMR (600 MHz, CDCl₃): δ 201.4(C₇=O), 151.1(C₁₁=C), 138.5(C₉=C), 132.6(C₁₅=C), 127.4(C₈=C), 124.6(C₁₀), 123.2(C₁₄=C), 40.8(C₆), 40.4(C₅), 33.0(C₁₂), 29.0(C₄), 26.9(C₁₃), 24.6(C₁₈), 24.6(C₃), 22.5(C₂), 17.7(C₁₆), 17.5(C₁₇), 14.0(C₁).