# Synthesis and Phase Transition Behaviours of New Chalcone Derivatives

Authors: S. T. Ha; Y. W. Low
Journal: Journal of Chemistry
 (2013)

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## Abstract

A series of new chalcone derivatives with a general formula of C11H27COOC6H4COCH=CHC6H4X where X=F, Cl, Br, and NO2 were well synthesized and crystallized from organic solution. The physical properties as well as the chemical formulations of these compounds were determined by spectroscopic techniques (FTIR, and 1H and 13C NMR). Differential scanning calorimetry (DSC) and polarizing optical microscopy (POM) techniques were employed to study their transition temperatures and mesophase characteristics. DSC thermograms of compounds with fluoro and nitro substituents displayed direct isotropization and recrystallization during heating and cooling processes. Chloro and bromo analogues exhibited Cr1-to-Cr2 transition within the crystal phase region. It was also found that enone linkage showed fewer tendencies to exhibit mesomorphic property compared to imine linkage. However, when enone linkage is combined with other central linkages and additional phenyl rings, it turns conducive to mesomorphism.


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## Body

## 1. Introduction

Chalcone is a compound consists of two aromatic rings linked by an unsaturatedα, β-ketone, with various substituents on the two aromatic rings. Chalcone could be easily found in most of the plants naturally and is an intermediate precursor of flavonoids and isoflavonoids [1]. It was reported to have wide range of applications in the fields of biology and biochemistry [2, 3] such as antitumor [4, 5], antiinflammatory [6–8], and antimalaria [9] agents. Besides, it is also reported in its photochemical and photophysical properties as well, including being used as photoalignment and photocrosslinking unit in polymerization process [10], fluorescent dyes, light-emitting diodes (LEDs), and so forth [11].Liquid crystals with a chalcone central linkage are relatively rare. In the literature, there are several reports of mesogenic compounds having chalcone linkage. However, many years ago Chudgar and Shah [12] and Yeap et al. [13] have reported homologous series containing ester-chalcone linkages. Recently, Thaker et al. [14] have also synthesized mesomorphic compounds containing Schiff base-chalcone linkage. In our previous works, we have studied liquid crystals with a Schiff base central linkage and terminal halogen group [15–18]. It was found that the halogen substituents are able to influence the mesomorphic properties of the Schiff bases. In view of the outstanding behavior of chalcone, the polar halogen and nitro groups have been introduced to the existing core system. Here, we report a series of newly derived analogues (Figure 1), 1-(4′-undecylcarbonyloxyphenyl)-3-(X-substituted phenyl)-2-propen-1-one, where X-substituted is 4-fluoro, 4-chloro, 4-bromo, and 4-nitro.Figure 1
Synthetic scheme towards formation of chalcones2a–d.


## 2. Experimental

Dodecanoic acid, 4-fluorobenzaldehyde, 4-chlorobenzaldehyde, 4-nitrobenzaldehyde, 4-hydroxyacetophenone, N,N-dicyclohexylcarbodiimide, 4-bromobenzaldehyde, and 4-dimethylaminopyridine were of analytical grade and were used without further purification. The intermediate and title compounds were prepared according to previously reported methods [13].FTIR data were acquired with a Perkin Elmer 2000-FTIR spectrophotometer in the frequency range of 4000–400 cm−1 with samples embedded in KBr pellets. 1H and 13C NMR spectra were recorded in CDCl3 using a JEOL JNM ECP 400 MHz NMR spectrometer with TMS as the internal standard.The phase transition temperatures were measured using a Mettler Toledo DSC823 differential scanning calorimeter (DSC) at a scanning rate of 10°C min−1. Optical texture studies were investigated by Carl Zeiss polarizing optical microscope attached to a Linkam Hot stage. The texture of the compounds was observed using polarized light with crossed polarizers, the sample being prepared as a thin film sandwiched between a glass slide and a cover. A video camera (Video Master coomo20P) was installed on the polarizing microscope and coupled to a video capture card (Video master coomo600), allowing real-time video capture and image saving.


### 2.1.   Synthesis of 3-(X-Substituted Phenyl)-1-(4′-hydroxyphenyl)-2-propen-1-one (1a–d, Where X-Substituted = 4-Fluoro, 4-Chloro, 4-Bromo, and 4-Nitro, Respectively)

Equimolar (10 mmol) of 4-hydroxyacetophenone and 4-fluorobenzaldehyde were dissolved in an aqueous solution of potassium hydroxide (2.24 g in 15 mL of a mixture of ethanol/water 1 : 1). The mixture was stirred well for 18 hours. The solution was then neutralized with 20 mL of 2 M HCl in an ice bath. The product was filtered and recrystallized from ethanol.


### 2.2. Synthesis of 1-(4′-Undecylcarbonyloxyphenyl)-3-(4-chlorophenyl)-2-propen-1-one,2b

Equimolar (2 mmol) of compound1b and dodecanoic acid were dissolved in 10 mL mixture of solvents DCM/DMF (1 : 1). DCC (4 mmol) and DMAP (0.4 mmol) were added to the mixture before it was stirred for an hour at 0°C and continued stirring for 12 hours at room temperature. The solution was filtered, and the filtrate was left standing overnight to evaporate the solvent. The crystals formed were then washed with petroleum ether and recrystallized by using ethanol. Compounds 2a, 2c, and 2d were prepared according to the similar method as that described for compound 2b.IR,1H, and 13C NMR data of the representative compound 2b are given as follows.IR (KBr)vmax cm−1 3069 (sp2 C–H), 2916, 2848 (C–H aliphatic), 1753 (C=O ester), 1655, 1635 (C=O ketone), 1611, 1597 (C=C olefinic) 1222 (C–O ester). 1H NMR (400 MHz, CDCl3): δ/ppm 0.9 (t, 3H, CH3–), 1.3-1.4 (m, 16H, CH3– (CH2)8–), 1.8 (p, 2H, –CH2–CH2–COO–), 2.6 (t, 2H, –CH2–COO–), 7.47 (d, 1H, olefinic-H), 7.75 (d, 1H, olefinic-H), 7.23 (d, 2H, Ar-H), 7.39 (d, 2H, Ar–H), 7.57 (d, 2H, Ar-H), 8.05 (d, 2H, Ar–H). 13C NMR (100 MHz, CDCl3): δ/ppm 189.08 (C=O keto), 171.90 (C=O ester), 154.47, 136.61, 135.54, 133.38, 130.19, 129.71, 129.37, 122.00 for aromatic carbons, 122.25, 143.60 for olefinic carbons, 34.52 (–COO–CH2–), 32.00 (–COO–CH2–CH2–), 29.69, 29.54, 29.43, 29.34, 29.18 for methylene carbons [–(CH2)6 CH2CH2CH3], 24.94 (–CH2CH2CH3), 22.78 (–CH2CH3), 14.22 (–CH3).


## 2.1.   Synthesis of 3-(X-Substituted Phenyl)-1-(4′-hydroxyphenyl)-2-propen-1-one (1a–d, Where X-Substituted = 4-Fluoro, 4-Chloro, 4-Bromo, and 4-Nitro, Respectively)

Equimolar (10 mmol) of 4-hydroxyacetophenone and 4-fluorobenzaldehyde were dissolved in an aqueous solution of potassium hydroxide (2.24 g in 15 mL of a mixture of ethanol/water 1 : 1). The mixture was stirred well for 18 hours. The solution was then neutralized with 20 mL of 2 M HCl in an ice bath. The product was filtered and recrystallized from ethanol.


## 2.2. Synthesis of 1-(4′-Undecylcarbonyloxyphenyl)-3-(4-chlorophenyl)-2-propen-1-one,2b

Equimolar (2 mmol) of compound1b and dodecanoic acid were dissolved in 10 mL mixture of solvents DCM/DMF (1 : 1). DCC (4 mmol) and DMAP (0.4 mmol) were added to the mixture before it was stirred for an hour at 0°C and continued stirring for 12 hours at room temperature. The solution was filtered, and the filtrate was left standing overnight to evaporate the solvent. The crystals formed were then washed with petroleum ether and recrystallized by using ethanol. Compounds 2a, 2c, and 2d were prepared according to the similar method as that described for compound 2b.IR,1H, and 13C NMR data of the representative compound 2b are given as follows.IR (KBr)vmax cm−1 3069 (sp2 C–H), 2916, 2848 (C–H aliphatic), 1753 (C=O ester), 1655, 1635 (C=O ketone), 1611, 1597 (C=C olefinic) 1222 (C–O ester). 1H NMR (400 MHz, CDCl3): δ/ppm 0.9 (t, 3H, CH3–), 1.3-1.4 (m, 16H, CH3– (CH2)8–), 1.8 (p, 2H, –CH2–CH2–COO–), 2.6 (t, 2H, –CH2–COO–), 7.47 (d, 1H, olefinic-H), 7.75 (d, 1H, olefinic-H), 7.23 (d, 2H, Ar-H), 7.39 (d, 2H, Ar–H), 7.57 (d, 2H, Ar-H), 8.05 (d, 2H, Ar–H). 13C NMR (100 MHz, CDCl3): δ/ppm 189.08 (C=O keto), 171.90 (C=O ester), 154.47, 136.61, 135.54, 133.38, 130.19, 129.71, 129.37, 122.00 for aromatic carbons, 122.25, 143.60 for olefinic carbons, 34.52 (–COO–CH2–), 32.00 (–COO–CH2–CH2–), 29.69, 29.54, 29.43, 29.34, 29.18 for methylene carbons [–(CH2)6 CH2CH2CH3], 24.94 (–CH2CH2CH3), 22.78 (–CH2CH3), 14.22 (–CH3).


## 3. Results and Discussion

### 3.1.   Phase Transition Behaviours and Optical Texture Studies of Chalcone Derivatives

All of the compounds2a-d were analyzed by DSC to study their thermal properties. It is used to determine whether a mesophase of liquid crystal is present in the compounds synthesized. DSC data upon heating and cooling cycles are tabulated in Tables 1 and 2, respectively. All members were nonmesogenic compounds. The representative DSC thermogram of compound 2a (Figure 2) showed single endotherm and exotherm, respectively, during both heating and cooling cycles. This observation indicates direct melting of the crystal phase to the isotropic liquid phase and vice versa. Under POM observation, crystal changed to dark region isotropic during heating run. No liquid crystal texture was observed during cooling process. However, the observation under polarized microscope showed the presence of subphases within the crystal region especially in compounds 2b and 2c of which the Cr1-to-Cr2 transitions occurred at 79.1 and 87.0°C, respectively.Table 1
Transition temperature and enthalpy changes of compounds2a–d during heating cycle.
Compounds
Transition
Temperature (°C)
Δ
H (kJ mol−1)
2a
Cr1-I
90.1
36.60
2b
Cr1-Cr2
79.1
0.80
Cr2-I
104.3
40.06
2c
Cr1-Cr2
87.0
6.71
Cr2-I
116.8
42.44
2d
Cr1-I
123.5
26.71Table 2
Transition temperature and enthalpy changes of compounds2a–d during cooling cycle.
Compounds
Transition
Temperature (°C)
Δ
H (kJ mol−1)
2a
I-Cr1
62.1
−39.19
2b
I-Cr3
96.7
−34.35
Cr3-Cr2
70.2
−1.58
Cr2-Cr1
63.5
−0.77
2c
I-Cr2
111.5
−42.96
Cr2-Cr1
81.7
−7.27
2d
I-Cr1
112.8
−28.38Figure 2
DSC thermogram of compound2a.During the cooling cycle, compounds2a and 2d directly crystallized into a stable state of crystal without any transition within the crystal region. However, compound 2c exhibited transition of Cr2-Cr1 within the crystal region at 81.7°C after it cooled from liquid state. For compound 2b (Figure 3), it also directly crystallized into crystalline state from isotropic liquid, but it undergoes 2 times transitions within the crystal region, which are Cr3-Cr2 at 70.2°C and Cr2-Cr1 at 63.5°C.Figure 3
DSC thermogram of compound2b.


### 3.2. Influence of Terminal Substituents on Thermal Properties of Chalcone Derivatives

The influence of terminal group on thermal stability can also be considered as one of the factors contributing towards the difference in melting temperature. Among compounds2a–2c, wherein each compound possesses the halogen in the aldehyde fragment, the melting temperature for compound 2a is very much lower in comparison with 2b and 2c (Figure 4). This comparison proposes that the fluorine (F) atom, which is the most electronegative, reduces the degree of molecular order. This thermal data also indicates that the influence of steric hindrance caused by the asymmetry of the central core of compound 2a is the least in comparison with compounds 2b and 2c, which possess higher melting temperatures. This has also been confirmed by the polarizability values wherein the calculated polarizability (Table 3, calculated using ACD ChemSketch) increases from compound 2a [(49.46±0.5) × 1024 cm−3) to compound 2b [(51.40±0.5) × 1024 cm−3) and compound 2c [(52.51±0.5) × 1024 cm−3). Melting point increases when polarizability of the compounds within the same series increases.Table 3
Polarizability values of compounds2a–d.
Compounds
Polarizability volume(×10−24 cm3)
Melting temperature (°C)
2a
49.46
±
0.5
90.1
2b
51.40
±
0.5
104.3
2c
52.51
±
0.5
116.8
2d
52.06
±
0.5
123.5Figure 4
Graph of melting temperature versus terminal substituent of compounds2a–d.It needs to be pointed out that while the fluorine atom shows very low polarizability because the valence electrons residing at this atom are tightly held to the nucleus, bromine atom is considered to be larger than fluorine and hence is more easily polarized because electrons on this atom are far from the nucleus [20]. Compound 2d has the highest melting point probably due to the delocalization of electrons between the two oxygen atoms (O=N+–O−) that increased the polarizability largely compared to 2a, 2b, and 2c.


### 3.3.  Structure-Mesomorphic Property Relationships

Molecular structure of organic compounds and their liquid crystalline properties are closely related. Table4 summarizes the transition temperatures, mesomorphic behavior, and molecular structures of 2b and structurally related compounds reported in the literature [13, 14, 16, 19].Table 4
Comparison of compound2b with other related compounds.
Compounds
Structure and phase transition (°C)
2b
A [13]
B [16]
C [19]
D [14]CompoundA having enone (–CH=CH–CO–) group as central linkage did not exhibit liquid crystal mesophase. This could be attributed to the enone group in chalcone consists of odd number atoms, thus is less conducive to mesomorphism compared to the linkages with even number atoms. Odd number atoms of linkages often cause a major problem to the mesogen, which is a nonlinearity in the linking group. By replacing enone group with imine linking group, higher linearity molecule of compound B exhibited smectic A phase. As calamitic liquid crystal requires its molecular axis to be linear for mesomorphism, this nonlinear linking group often causes the core to be deviated from its linear molecular axis [19]. Besides, the angular shape of keto group causes angle strain in the linking group, which makes the chalcone derivatives even less conducive to mesomorphism [21]. Therefore, we introduce a polar substituent (F, Cl, Br, and NO2) into the aldehyde fragment of chalcone structure in order to influence the phase behavior of existing chalcone. However, the introduction of terminal substituents is not sufficient to induce mesophase in chalcone. Incorporation of additional phenyl rings and imine linking group into compounds C and D caused the molecules to be longer and more linear. Both additional features are essential for inducing smectic C and nematic phases in compounds C and D.


## 3.1.   Phase Transition Behaviours and Optical Texture Studies of Chalcone Derivatives

All of the compounds2a-d were analyzed by DSC to study their thermal properties. It is used to determine whether a mesophase of liquid crystal is present in the compounds synthesized. DSC data upon heating and cooling cycles are tabulated in Tables 1 and 2, respectively. All members were nonmesogenic compounds. The representative DSC thermogram of compound 2a (Figure 2) showed single endotherm and exotherm, respectively, during both heating and cooling cycles. This observation indicates direct melting of the crystal phase to the isotropic liquid phase and vice versa. Under POM observation, crystal changed to dark region isotropic during heating run. No liquid crystal texture was observed during cooling process. However, the observation under polarized microscope showed the presence of subphases within the crystal region especially in compounds 2b and 2c of which the Cr1-to-Cr2 transitions occurred at 79.1 and 87.0°C, respectively.Table 1
Transition temperature and enthalpy changes of compounds2a–d during heating cycle.
Compounds
Transition
Temperature (°C)
Δ
H (kJ mol−1)
2a
Cr1-I
90.1
36.60
2b
Cr1-Cr2
79.1
0.80
Cr2-I
104.3
40.06
2c
Cr1-Cr2
87.0
6.71
Cr2-I
116.8
42.44
2d
Cr1-I
123.5
26.71Table 2
Transition temperature and enthalpy changes of compounds2a–d during cooling cycle.
Compounds
Transition
Temperature (°C)
Δ
H (kJ mol−1)
2a
I-Cr1
62.1
−39.19
2b
I-Cr3
96.7
−34.35
Cr3-Cr2
70.2
−1.58
Cr2-Cr1
63.5
−0.77
2c
I-Cr2
111.5
−42.96
Cr2-Cr1
81.7
−7.27
2d
I-Cr1
112.8
−28.38Figure 2
DSC thermogram of compound2a.During the cooling cycle, compounds2a and 2d directly crystallized into a stable state of crystal without any transition within the crystal region. However, compound 2c exhibited transition of Cr2-Cr1 within the crystal region at 81.7°C after it cooled from liquid state. For compound 2b (Figure 3), it also directly crystallized into crystalline state from isotropic liquid, but it undergoes 2 times transitions within the crystal region, which are Cr3-Cr2 at 70.2°C and Cr2-Cr1 at 63.5°C.Figure 3
DSC thermogram of compound2b.


## 3.2. Influence of Terminal Substituents on Thermal Properties of Chalcone Derivatives

The influence of terminal group on thermal stability can also be considered as one of the factors contributing towards the difference in melting temperature. Among compounds2a–2c, wherein each compound possesses the halogen in the aldehyde fragment, the melting temperature for compound 2a is very much lower in comparison with 2b and 2c (Figure 4). This comparison proposes that the fluorine (F) atom, which is the most electronegative, reduces the degree of molecular order. This thermal data also indicates that the influence of steric hindrance caused by the asymmetry of the central core of compound 2a is the least in comparison with compounds 2b and 2c, which possess higher melting temperatures. This has also been confirmed by the polarizability values wherein the calculated polarizability (Table 3, calculated using ACD ChemSketch) increases from compound 2a [(49.46±0.5) × 1024 cm−3) to compound 2b [(51.40±0.5) × 1024 cm−3) and compound 2c [(52.51±0.5) × 1024 cm−3). Melting point increases when polarizability of the compounds within the same series increases.Table 3
Polarizability values of compounds2a–d.
Compounds
Polarizability volume(×10−24 cm3)
Melting temperature (°C)
2a
49.46
±
0.5
90.1
2b
51.40
±
0.5
104.3
2c
52.51
±
0.5
116.8
2d
52.06
±
0.5
123.5Figure 4
Graph of melting temperature versus terminal substituent of compounds2a–d.It needs to be pointed out that while the fluorine atom shows very low polarizability because the valence electrons residing at this atom are tightly held to the nucleus, bromine atom is considered to be larger than fluorine and hence is more easily polarized because electrons on this atom are far from the nucleus [20]. Compound 2d has the highest melting point probably due to the delocalization of electrons between the two oxygen atoms (O=N+–O−) that increased the polarizability largely compared to 2a, 2b, and 2c.


## 3.3.  Structure-Mesomorphic Property Relationships

Molecular structure of organic compounds and their liquid crystalline properties are closely related. Table4 summarizes the transition temperatures, mesomorphic behavior, and molecular structures of 2b and structurally related compounds reported in the literature [13, 14, 16, 19].Table 4
Comparison of compound2b with other related compounds.
Compounds
Structure and phase transition (°C)
2b
A [13]
B [16]
C [19]
D [14]CompoundA having enone (–CH=CH–CO–) group as central linkage did not exhibit liquid crystal mesophase. This could be attributed to the enone group in chalcone consists of odd number atoms, thus is less conducive to mesomorphism compared to the linkages with even number atoms. Odd number atoms of linkages often cause a major problem to the mesogen, which is a nonlinearity in the linking group. By replacing enone group with imine linking group, higher linearity molecule of compound B exhibited smectic A phase. As calamitic liquid crystal requires its molecular axis to be linear for mesomorphism, this nonlinear linking group often causes the core to be deviated from its linear molecular axis [19]. Besides, the angular shape of keto group causes angle strain in the linking group, which makes the chalcone derivatives even less conducive to mesomorphism [21]. Therefore, we introduce a polar substituent (F, Cl, Br, and NO2) into the aldehyde fragment of chalcone structure in order to influence the phase behavior of existing chalcone. However, the introduction of terminal substituents is not sufficient to induce mesophase in chalcone. Incorporation of additional phenyl rings and imine linking group into compounds C and D caused the molecules to be longer and more linear. Both additional features are essential for inducing smectic C and nematic phases in compounds C and D.


## 4.  Conclusions

A series of new chalcone derivatives, 1-(4′-undecylcarbonyloxyphenyl)-3-(X-substituted phenyl)-2-propen-1-one, has been synthesized and characterized. The physical properties as well as their mesomorphic behaviors were studied by using spectroscopic techniques (IR and NMR). It has been observed that enone (–CO–CH=CH–) linkage is less conducive to mesomorphism compared to –CH=N– (imine) linkage due to the nonlinearity and angle strain arising from the keto group. The presence of polar terminal halogen and nitro substituent is unable to induce mesomorphism of chalcone derivatives. But when enone linkage is coupled with other central linkages and new phenyl rings, it becomes conducive to mesomorphism.



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