Allylbenzene trans-β methylstyrene

trans-isoeugenolEugenol

Allylbenzene trans-β methylstyrene

trans-isoeugenolEugenol

Microwave assisted isomerization of alkenyl aromatics over MgAl

LDHs – Beneficial and green over conventional thermal heating is

demonstrated

99% conversion of estragole to anethole is achieved under energy and

material efficient conditions

pKa of the protons of alkenyl aromatics governs the activity

Theoretical calculations validate the experimental data

Microwave assisted isomerization of alkenyl

aromatics over hydrotalcite-like materials

Manuscript under review with RSC Advances

Microwave assisted isomerization of alkenyl

aromatics over hydrotalcite-like materials

3.1 Introduction

3.2 Experimental

3.2.1 Catalyst synthesis

3.2.2 Physicochemical characterization

3.2.3 Catalytic isomerization of alkenyl aromatics

3.2.4 Hammett indicator studies

3.2.5 Computational methods

3.3 Results and discussion

3.3.1 Physicochemical characterization

3.3.2 Catalytic studies

3.3.2.1 Estragole isomerization-parametric optimization

3.3.2.2 Basicity measurements

3.3.2.3 Effect of solvent on isomerization of estragole

3.3.2.4 Influence of substrate:catalyst weight ratio

3.3.2.5 Isomerization of different alkenyl aromatics

3.3.2.6 Scale up studies over MgAl4

3.4 Conclusions

3.5 References

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

71

3.1 Introduction

Isomerization of alkenyl aromatics has high industrial demand as

intermediates for various perfumery chemicals [1, 2]. Among alkenyl aromatics trans-

anethole has significant application in food and beverage industry, formulation of oral

sanitation products, pharmaceutical compounds, and perfumery chemicals [3-6].

Anethole, also known as isoestragole occurs in nature as both cis and trans forms,

wherein trans-isomer being more abundant. Anethole is a major component of several

essential oils, including anise seed oil (80-90%), star anise oil (>90%) and sweet

fennel oil (80%). The total global production of trans-anethole is approximately 0.75

million metric tonne per annum. Increasing demand for anethole led to development

of new synthetic routes other than isolation from essential oils. The most viable one is

simple base catalyzed isomerization of estragole (methyl chavicol) to its propenyl

derivative, anethole (Scheme 3.1). Conventionally alkalis such as KOH in alcoholic

solutions (most often in higher alcohols) at high temperatures were used for

isomerization of alkenyl aromatics [7, 8]. Kameda and Yoneda [9] had reported

homogeneous isomerization of estragole over [RhH2(Ph2N3)(PPh3)2] in dimethyl

sulfoxide (DMSO) under hydrogen atmosphere (1 atm) at 30 oC. Later on solid base

catalysts were tried for this isomerization reaction which provides better effluent

control, facile separation and easy handling [10, 11]. Recent works on isomerization

of estragole to anethole comprises using K2CO3 on alumina [12] and Ru-complexes

[13, 14]. It was reported that under homogeneous conditions using Ru-complexes

highly trans selective products were obtained. We have reported earlier the utility of

as-synthesized layered double hydroxides (LDHs) as promising heterogeneous solid

base catalysts for such double bond isomerization of alkenyl aromatics [15-17].

Detailed literature survey over these types of isomerization reactions is given in

Chapter 2.

Our group here at CSMCRI’s previous report on isomerization of estragole to

anethole over binary hydrotalcite revealed MgAl4 was the most active catalyst and the

conversion increased slightly upon incorporation of Ru and Cs under conventional

heating [18]. Under thermal conditions draw backs are high reaction temperature (200

oC), larger solvent volume (20 ml) and longer reaction time (6 h). Microwave

irradiation (MWI) which involves dielectric heating is simple fast and advantageous,

thereby provide significant enhancement in reaction rates. MWI processes are more

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

72

economical by minimizing the energy consumption and it also reduces the reaction

times (comparison of MWI and conventional heating is given in Table 3.1) [19, 20].

MWI had also been used in organic transformation involving hydrotalcite as catalyst

[21, 22]. Thach and Strauss [23] previously used microwave batch reactor for

isomerization of estragole under aqueous conditions using 0.2M NaOH and obtained a

conversion of 81% at 230 oC. Recently Crochet and co-workers reported 99% yields

of anethole with high trans selectivity from estragole within 15 min under microwave

irradiation using Ru-complexes as homogeneous catalyst [14].

Table 3.1 Comparison of microwave heating vs. conventional heating

Microwave Conventional

Direct coupling of energy - internal

heating Conduction/convection- external heating

Volumetric (whole material heated

simultaneously) Superficial heating (surface)

Selective absorption of radiation by polar

substances Non selective

Rapid heat transfer Slow heat transfer

With this knowledge, in this Chapter, we disclose isomerization of alkenyl

aromatics using MgAl series of hydrotalcite as heterogeneous catalyst under

microwave and theoretical studies to evaluate the variation in isomerization activity of

different alkenyl aromatics which will validates earlier reports. Our aim was to

overcome challenges like higher temperature, larger solvent volume, longer reaction

time, and unproductive recylability. Attempts were done to correlate the activity with

basicity using Hammett indicators studies. The cause of variation in isomerization

activity of different alkenyl aromatics over same base catalyst was proved through

theoretical study. The alkenyl aromatics had similar reaction sites on the MgAl4

surface; however, the conversion highly depends on the aromatic substitution. To

examine the difference in the isomerization of these systems, computational studies

have been carried out.

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

73

3.2 Experimental

3.2.1 Catalysts synthesis

The MgAl series of hydrotalcites were prepared by low supersaturation

technique whose details were given as in section 2.2.1 in Chapter 1 [24]. Samples thus

prepared were named as M(II)M(III)x where x stands for M(II)/M(III) atomic ratio for

binary systems and An-

stands for interlayer anions. The samples are represented here

either as M(II)M(III)x where ‘x’ stands for the M(II)/M(III) atomic ratio for binary

systems For all samples, the atomic ratio of M(II):M(III) was kept between 2 to 4.

3.2.2 Physicochemical characterization

Physicochemical characterization of all the samples synthesized was done

using various analytical techniques as given in section 2.2.2 (Chapter 1). The samples

were characterized by Powder X-ray diffraction (PXRD; Rigaku-MiniFlex) system

using Cu K radiation ( = 1.5406 Å). Identification of the crystalline phases was

made by comparison with the JCPDF files [25].

3.2.3 Catalytic isomerization of alkenyl aromatics

Isomerization of alkenyl aromatics was conducted in a microwave synthesis

work station (Sineo, MAS-II) equipped with direct sensing; microwave power could

be adjusted between 0-1000W in order to achieve the desired reaction temperature.

The substrate, solvent and catalyst were charged at once and subjected to reaction

temperature using 100% MWI. The products were analyzed by gas chromatography

(Varian 450-GC) with a capillary column (Factor Four VF-1) and FID detector.

Scheme 3.1 Isomerization of alkenyl aromatics

Identification of the products was also further verified using GC-MS

(Shimadzu QP 2010). Quantification of the products was done using tetradecane as

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

74

internal standard. For conventional heating studies, isomerization was conducted in a

batch reactor (50 ml), wherein the substrate, solvent and catalyst were charged at once

and kept in a preheated oil bath at desired reaction temperature [25]. The

isomerization of the alkenyl aromatics along with the geometries are given in scheme

3.1.

3.2.4 Hammett indicator studies

In order to evaluate the Bronsted basicity associated with the hydroxyl groups,

Hammett indicator measurements were carried out. 25 mg of catalyst was taken along

with 2.5 ml of dry methanol and to that calculated amount of indicators with different

pKa ranges were added separately and kept in a shaker for 3 h under N2 atmosphere

[27]. The solution was then titrated against 0.02 M benzoic acid in dry methanol to

determine the basicity. The indicators used were methyl red (pKa = 5.1), neutral red

(pKa = 6.8), phenolphthalein (pKa = 8.2), nile blue (pKa = 10.1), tropaeolin O (pKa =

11), 2, 4-dinitro aniline (pKa = 15).

3.2.5 Computational methods

All calculations were performed with density functional theory (DFT) using

Becke’s three-parameter exchange functional with the correlation functional of Lee,

Yang, and Parr (B3LYP) [28, 29] All species were fully optimized with the 6-31+G*

basis set [30], and harmonic vibrational frequency calculations were used to confirm

that the optimized structures were minima, as characterized by positive vibrational

frequencies. The gas phase basicities (GB) were calculated from the energy change of

the protonation reaction:

GB is defined as the negative Gibbs free energy of the reaction,

Solvent effects were taken into account by means of the polarizable continuum

model (PCM) through single-point energy calculations at the B3LYP/6-31+G* level

of theory (using the gas-phase optimized geometries) with DMF as the solvent

(dielectric constant, ε = 38.2) [31-35]. The PCM calculations, using Gaussian 03,

employ the UA0 (Simple United Atom Topological Model) atomic radii when

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

75

constructing the solvent cavity for the calculation of the Gibbs free energy of

solvation. The pKa calculations were performed using the standard thermodynamic

cycle depicted in Scheme 3.2 [36-40]. The pKa value of the acid BH+ was related to

the Gibbs free energy change for the deprotonation process, which is shown below,

where ΔGsol = ΔGgas + ΔΔGsolv + ΔGcorr.

where ΔGsol = ΔGgas + ΔΔGsolv + ΔGcorr.

ΔGgas is the Gibbs free energy change of the reaction in the gas phase and ΔΔGsolv is

the difference in solvation free energies (ΔGsolv) between products and reactants.

ΔGcorr is the correction associated with the change in the standard state from the gas

phase (1 atm) to solution (1 mol L-1

) and its value at 298.15 K is 1.89 kcal mol-1

[41].

Now ΔGsol can be expressed as:

ΔGsol = Ggas(B) + ΔGsolv(B) + Ggas(H+) + ΔGsolv(H

+) - Ggas(BH)

+ - ΔGsolv(BH)

+ +

1.89.

Here, the value of Gibbs free energy of the proton in the gas phase was set to -

6.28 kcal mol-1

using translational entropy calculated according to the well-known

Sackur–Tetrode equation [42] and the value of Gibbs free energy of the proton in the

DMF solvent phase was taken as -263.8 kcal/mol-1

[43].

Scheme 3.2 Thermodynamic cycle for calculating pKa

The ΔGsolv values in this study were determined from PCM/B3LYP/6-31+G*

single-point calculations on the gas phase B3LYP/6-31+G* optimized geometry with

UA0 radii and ‘scfvac’ keyword using DMF as a solvent [44, 45]. Both electrostatic

and nonelectrostatic (i.e., cavitation, repulsion and dispersion) terms were included in

the calculation of ΔGsolv values. All quantum chemical calculations were performed

using Gaussian 03, Revision E.01 program [46].

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

76

3.3 Results and discussion

3.3.1 Physicochemical characterization

The elemental analysis results are shown in Table 3.2. It showed that the

composition of solid LDH was in reasonable agreement with the initial concentration

of metal ions suggesting completion of precipitation. The phase purity of all catalysts

under study was monitored through PXRD, given in Figure 3.1. The samples show

sharp and symmetric reflections at lower diffraction angles and broad asymmetric

reflections at higher angles, characteristics of hydrotalcite [24].

10 20 30 40 50 60 70

500

f

d

e

c

b

a

Inte

nsit

y, c/s

2 Theta, deg

Figure 3.1 Powder X-ray diffraction patterns of (a) NiAl2, (b) NiAl3, (c) NiAl4, (d)

MgAl2, (e) MgAl3, (f) MgAl4

Table 3.2 Physicochemical properties of the samples synthesized

Catalyst Lattice

parameters

Crystallite

size (Å)a

Surface

Areab

Pore

Volumec

a (Å) c (Å)

[Mg0.72Al0.33(OH)2](CO3)0.17.0.75H2O 3.049 23.03 56 97 0.40

[Mg0.78Al0.22(OH)2](CO3)0.11.0.86H2O 3.068 23.75 62 94 0.68

[Mg0.80Al0.20(OH)2](CO3)0.10.0.67H2O 3.075 24.00 79 91 0.41

[Ni0.70Al0.30(OH)2] (CO3)0.15.0.75H2O 3.021 22.94 57 152 0.33

[Ni0.75Al0.25(OH)2] (CO3)0.13.0.73H2O 3.040 23.22 53 146 0.42

[Ni0.82Al0.18(OH)2] (CO3)0.09.0.52H2O 3.053 23.28 57 126 0.36

aCalculated using Debye-Scherrer equation taking (003) and (006) planes;

bspecific surface

area in m2g

-1;

cpore volume in cc g

-1;

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

77

Insignificant variation in the crystallinity was noted with an increase in the

Mg/Al ratio. The crystallinity for Ni containing samples was lesser (broad reflections)

compared to the Mg containing samples. The peak close to 11, 23 and 34º,

corresponds to spacing 7.7 (d003), 3.8 (d006), and 2.57 (d009) respectively, are ascribed,

assuming a 3R packing of the layers. Lattice parameters of the samples are shown in

Table 3.2. It was found that with an increase in the Mg/Al ratio both the parameters

‘a’ and ‘c’ increased. The reason was due to the higher octahedral ionic radius of

Mg2+

than Al3+

. The increase in the ‘c’ parameter is due to the increase in Mg2+

content which decreases the electrostatic interaction between layers and inter layer.

All the samples under study have carbonate in the interlayer. This was further

confirmed through FT-IR whose spectra are given in Figure 3.2. The main band

recorded around 3500 cm-1

was due to OH stretching of hydroxyl groups from the

layers and interlayer water molecule. The weak band observed at 1630 cm-1

was due

to H2O mode of interlayer water molecules and strong band at 1363 cm-1

was

attributed to 3 asymmetric stretching of carbonate vibrations shifted from its position

in free carbonate species (≈1450 cm-1

). It was found that the OH stretching band

slightly shifts to higher values with an increase in Mg concentration indicate stronger

hydrogen bonding between the hydroxyl groups.

4000 3500 3000 2500 2000 1500 1000 500

e

d

f

13551630

3500

c

b

a

Tra

nsm

itta

nce, %

Wavenumber, cm-1

Figure 3.2 FT-IR spectra of (a) NiAl2, (b) NiAl3, (c) NiAl4, (d) MgAl2, (e) MgAl3,

(f) MgAl4

Thermal analysis of all the samples showed two well-defined weight losses as

evidenced from the Figure 3.3. The first weight loss T1 oC at around 150-180

oC was

due to removal of the water molecules present in the interlayer while the second

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

78

weight loss T2 oC at around 360-375

oC was ascribed to the dehydroxylation and

decarbonation from hydrotalcite network. A decrease in the transformation

temperatures were observed with increase Mg/Al atomic composition. This could be

due to the decrease in the electrostatic interaction attributed to decrease in Al3+

content.

0 200 400 600 800

dW

/dT

d

e

f

c

b

a

We

igh

t lo

ss

, %

Temperature,oC

Figure 3.3 TG-DTG profiles of (a) NiAl2, (b) NiAl3, (c) NiAl4, (d) MgAl2, (e)

MgAl3, (f) MgAl4

0.0 0.2 0.4 0.6 0.8 1.0

d

e

f

c

b

a

Vo

l. a

dso

rbed

, cc/g

Relative Pressure, P/Po

0 200 400 600 800 1000

e

d

f0.0005

c

b

a

Po

re v

olu

me

, cc

/g

Pore Diameter, Å

Adsorption-desorption isotherm Pore size distribution curves

Figure 3.4 N2 adsorption-desorption analysis of (a) NiAl2, (b) NiAl3, (c) NiAl4, (d)

MgAl2, (e) MgAl3, (f) MgAl4

The textural parameters of the samples (Table 3.2) measured through nitrogen

adsorption-desorption measurements (Figure 3.4) showed a decrease in the specific

surface area and pore volume with an increase in M(II)/Al atomic ratio. All samples

exhibit type II isotherm (according to IUPAC classification) with pore size

distribution falling in mesopore region. Among the samples NiAl series gave

relatively high surface area (<130 m2g

-1) than MgAl series which gave aound 100

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

79

m2g

-1. The SEM measurements, given in Figure 3.5, which showed similar

morphology for all samples exhibiting hexagonal rose petal structures which are quite

common for MgAl layered double hydroxides.

MgAl2 MgAl3

MgAl4

Figure 3.5 SEM micrographs of MgAl series of HTs

3.3.2 Catalytic studies

3.3.2.1 Estragole isomerization-parametric optimation

The microwave assisted isomerization of estragole to anethole was conducted

over different MgAl and NiAl binary hydrotalcites. Initial studies were done over

MgAl4 at different microwave power (300, 500 and 700 W). Conversion was similar

(around 17%) irrespective of the power applied and further studies were conducted

with 300 W. Influence of reaction temperature was done in the temperature range 80-

140 oC and results are given in Figure 3.6. The results showed an increase in

conversion with temperature. A conversion of 94% with cis:trans ratio 13:87 was

obtained with a substrate to catalyst weight ratio 2:1 at 140 oC within 1 h in 8 ml

DMF. Further increase in temperature (150 oC) was not achieved under MWI with

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

80

DMF as solvent. The results obtained were very interesting as more than 90%

conversion was achieved at relatively lesser temperature and time in comparison with

conventional heating (200 oC, 97% conversion in 6 h) [18]. Under conventional

heating condition only 77% conversion was obtained within 6 h at similar 140 oC as

per report. In anticipation we have checked this isomerization under our reaction

condition at 140 oC thermally and within 1 h we got only 6% conversion with regard

to 94% under microwave.

70 80 90 100 110 120 130 140 150

0

20

40

60

80

100

Co

nvers

ion

, %

Temperature, oC

Figure 3.6 Influence of reaction temperature over isomerization of estragole over

MgAl4

Formation of anethole with reaction time was monitored and the results are

given in Figure 3.7. The results show that within 90 min 99% of anethole yield was

observed with cis:trans ratio 14:86 at 140 oC. The conversion increases linearly with

time upto 60 min and then slowly till 90 min. Hence for all the further studies we

optimized time as 60 min and temperature as 140 oC with 300 W. The catalytic

activities of different hydrotalcites with varying M(II)/Al atomic ratio are given in

Table 3.3. MgAl4 gave a maximum conversion of 97% in 1 h at 140 oC. MgAl2 and

MgAl3 gave 17% and 20% conversion respectively. For NiAl series, NiAl4 showed a

maximum conversion of 40%, while NiAl2 and NiAl3 gave 6% and 20% conversion

respectively. In all cases, trans-isomer of anethole was predominant (82-90%). In

other words, the activity increased with an increase in M(II)/Al atomic ratio. Similar

observation for alkenyl aromatics was reported earlier under conventional heating

[16].

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

81

0 20 40 60 80

0

20

40

60

80

100

Co

nversio

n, %

Time, min

Figure 3.7 Influence of reaction time over isomerization of estragole over MgAl4

3.3.2.2 Basicity measurements

To understand the basicity-activity relationship, Hammett indicator

measurements were carried out whose results are given in Table 3.3. As the reaction

under this study is a base-catalyzed reaction, Bronsted basic sites associated with

surface hydroxyl groups are likely to be involved in the reaction and Hammett studies

are reliable for assessing the basicity of hydrotalcite [47]. All catalysts possessed a

basic strength of similar range 11< H _< 15. The values are deduced and computed

from the weakest indicator that showed color change (tropaeolin O, pKa = 11) to the

strongest indicator that failed to give color change (2, 4-dinitro aniline, pKa = 15)

[27]. MgAl4 showed a maximum basicity of 1.28 mmol/g among the catalysts studied

and gave maximum isomerization activity (Table 3.3). MgAl2 and MgAl3 showed

basicity values of 0.24 and 0.48 mmol/g respectively. In the case of NiAl samples,

NiAl4 gave maximum basicity value of 0.64 mmol/g and in turn showed highest

activity among NiAl samples. A good correlation was observed between basicity and

activity wherein activity increased with an increase in the basic strength as illustrated

in Figure 3.8. The trend was in good agreement with the literature wherein with an

increase in Mg and Ni content the basicity as well as activity increased for

hydrotalcites [48].

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

82

Table 3.3 Isomerization of estragole over binary hydrotalcites

Catalysta Basic strength Basicity, mmol/g

c Conversion, % Selectivity, %

cis trans

MgAl2 11< H _ < 15 0.24 17 17 83

MgAl3 11< H _ < 15 0.48 20 16 84

MgAl4 11< H _ < 15 1.28 97 17 83

NiAl2 11< H _ < 15 0.04 6 10 90

NiAl3 11< H _ < 15 0.12 18 18 82

NiAl4 11< H _ < 15 0.64 40 17 83

MgAl4b 11< H _ < 15 0.48 47 13 87

aSubstrate: Estragole (200 mg); catalyst weight: 100 mg; solvent, DMF (4 ml); reaction

time./temp: 60 min/140 oC; power: 300 W;

bMgAl after 6 cycle;

cBasicity was calculated on

the basis of the endpoint of the titration

0 20 40 60 80 100 120

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

R2-0.969

NiAl4

NiAl2

NiAl3

MgAl3

MgAl2

MgAl4

Basic

ity, m

mo

l/g

Conversion, %

Figure 3.8 Hammett basicity-activity relationships; Error bar for basicity is taken as

5%

3.3.2.3 Effect of solvent on isomerization of estragole

The solvent variation studies were done and the results over the volume of

solvent are given in Table 3.4. The activity decreased with an increase in the volume

of solvent; with 16 ml of DMF only 46% conversion was observed while under

identical conditions, 97% conversion was observed using 4 ml of solvent. However,

on further decrease in the volume of solvent (2 ml), the reaction temperature was not

achieved.

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

83

The isomerization activity of MgAl4 in different solvents was also studied

whose results are given in Table 3.5. The solvents were categorized as high boiling-

high polar, high boiling-low polar, low boiling-high polar and low boiling-low polar.

The results revealed that only those solvents with high polarity and relatively high

boiling favored the reaction as it was well known that influence of MWI depends on

the polarity/dielectric of the medium.

Table 3.4 Effect of volume of solvent over MgAl4

Solvent volumea Conversion, % Product distribution, %

cis trans

16 46 17 83

12 60 17 83

8 94 17 83

4 97 17 83

2 Failed - -

aSubstrate: Estragole (200mg); catalyst weight: 100 mg; reaction time./temp: 60 min/140

oC;

power: 300 W

Table 3.5 Effect of solvents on isomerization of estragole over MgAl4

Solventa Dielectric

constant

Boiling point, oC Conversion, % Selectivity, %

cis trans

DMSO 47.2 189 93 19 81

DMF 38.2 152 97 17 83

DMA 37.8 166 99 14 86

Nitrobenzene 34.8 211 12 13 87

Acetonitrile 36.6 82 1 0 0

Methanolb 33 65 1 0 100

Butanol 18 118 0 0 0

Heptanolc 6.7 178 33 17 83

Dodecanolc 6.5 259 11 12 88

Ethanediol 6.9 197 0 0 0

Waterb 80 100 0 0 0

aSubstrate: Estragole (200 mg); catalyst weight: 100 mg; solvent (4 ml); reaction time./temp:

60 min/140 oC; power: 300 W:

bvapor loss observed:

creaction temperature not attained

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

84

High boiling-high polar solvents like DMF, DMSO, and dimethyl acetamide

(DMA) gave good conversion of 95 ± 3% in 1 h, while all other solvents failed in

giving good conversion. In the case of acetonitrile and methanol at 140 oC, vapor loss

was observed. So we tried at 100 oC and but conversion was not obtained. However

for high boiling-low polar solvent like heptanol, dodecanol and ethanediol reaction

temperature (140 oC) was not reached as the MWI depends on polarity of solvents.

3.3.2.4 Influence of substrate:catalyst weight ratio

Substrate to catalyst weight ratio variation (Figure 3.9) revealed that the conversion

increased with an increase in the weight of catalyst (i.e., decrease in substrate:catalyst

weight ratio). A maximum conversion of 97% in 1 h was observed with a

substrate:catalyst weight ratio of 2:1 with a cis:trans ratio of 17:83 at 140 oC. The

results obtained are promising and encouraging as more than 90% conversion was

achieved at relatively lesser temperature and time in comparison with conventional

heating (200 oC, 97% conversion in 6 h) [18]. Under similar condition at 140

oC

through thermal heating for 1 h showed only 6% conversion (94% under microwave).

2:1 4:1 6:1 8:1 10:1 20:1

0

20

40

60

80

100

Co

nv

ers

ion

, %

Substrate:catalyst weight ratio

Figure 3.9 Effect of substrate:catalyst weight ratio for isomerization of estragole over

MgAl4 (conditions similar to Table 3.3 except for substrate amount)

. After optimizing all these parameters, studies were extended for attaining

stoichiometric conversion. The reactions were done by increasing the time to 90 min

over selected/best reaction conditions whose results are given in Table 3.6. The results

showed that with 4 ml DMF and 2:1 substrate:catalyst weight ratio, >99% conversion

was achieved at 140 oC. But by increasing the substrate amount to 400 mg and 800

mg the conversion drops to 95% and 80% respectively. Around 99% of conversion

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

85

was obtained in the case of DMA (4 ml). This reveals that under microwave

irradiation our challenges for decreasing time, temperature and solvent volume were

achieved and this lights a path for getting anethole from estragole in eco-friendly

manner. Thus high conversion of estragole to anethole was obtained in shorter

reaction time, lesser temperature and by using reduced volume of solvent under MWI.

To check the reusability of the active catalyst, MgAl4, recycle studies were done for

up to six cycles (Figure 3.10).

Table 3.6 Time variation studies over MgAl4 under best conditions

Solventa Substrate amount, mg Conversion, % Product distribution, %

cis trans

DMF - 8ml 200 99 16 84

DMF - 4ml 200 99.5 17 83

DMF - 4ml 400 95 18 82

DMF - 4ml 800 80 19 81

DMA - 4ml 200 99 14 86

aSubstrate: Estragole (200mg); catalyst weight: 100 mg; reaction time./temp: 90 min/140

oC;

power: 300 W

I II III IV V VI

0

20

40

60

80

100

Co

nvers

ion

, %

Cycle

Figure 3.10 Recycle studies over MgAl4 for isomerization of estragole (conditions

similar to Table 3.3)

Stable activity of around 95% conversion was noted for the first two cycles. A

continuous although marginal decrease in the conversion was noted with the further

increase in the number of cycles; catalyst exhibited 47% conversion for the sixth

cycle. It was found from Hammett study that MgAl4 after six cycles showed basicity

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

86

of 0.48 mmol/g (Table 3.3). The decrease in the basicity value (from 1.28 mmol/g for

fresh catalyst to 0.48 mmol/g after sixth cycle) correlated well with the activity.

3.3.2.5 Isomerization of different alkenyl aromatics

In previous Chapter on isomerization of alkenyl aromatics under conventional

thermal condition, it was disclosed that the catalyst with similar basicity will not be

effective for isomerizing different alkenyl aromatics of perfumery interest [section

2.3.1.4, Chapter 2]. Isomerization of different alkenyl aromatics was carried out under

MWI for MgAl4 at the optimized conditions that were determined for estragole

(Table 3.7). Among the alkenyl aromatics studied, allylbenzene showed maximum

conversion to β-methyl styrene (>99%) while eugenol showed minimum conversion

to isoeugenol (19%). Allylveratrole gave 88% conversion and safrole exhibited 64%

conversion. The variation in the activity of different alkenyl aromatics could be due to

variation in the adsorption potential or mode of adsorption of the substrates on the

surface of the catalyst in turn due to the variation in the substituent’s attached to the

aromatic ring. It must be mentioned here that similar activity trend was observed

under conventional thermal heating for NiAl4 [section 2.3.1.4, Chapter 2].

The difference in the activity is generally governed by the molecular

dimension, functionality and mode of adsorption of the substrate on the surface. It is

known that the acidity of the methylene proton (–CH2–) of allylic moiety is the key

parameter and its abstraction by the basic site is critical for the double bond migration

[15]. In order to confirm the trend under conventional conditions, isomerization of

alkenyl aromatics was assessed under optimized conditions for microwave (140 oC for

6 h with substrate to catalyst ratio 2:1 with 4ml DMF as solvent). Allybenzene and

estragole showed a conversion of 45% and 11% respectively while allylveratrole and

eugenol did not show conversion. This confirms that at lower temperature under

thermal heating the energy needed for the reaction was not attained. To discern the

factors responsible for the observed difference in the isomerization activities of the

alkenyl aromatics, DFT B3LYP/6-31+G* level calculations were performed. The

isomerization reaction could be perceived to occur through the deprotonation of the

allyl proton H1 by the hydroxyl group of MgAl4 catalyst (explanation and mechanism

given in section 4.2.3.2.1 of Chapter 4). The B3LYP/6-31+G* calculated pKa for the

allyl protons of the alkenyl aromatics at the experimental temperature of 140 °C, are

given in Table 3.7. The calculated pKa results indicated that the extent of conversion

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

87

towards the isomerization of all the studied alkenyl aromatics should be similar.

However, the observed isomerization activites of these alkenyl aromatics i.e.,

allylbenzene to eugenol varied significantly. It was then perceived that the substituted

alkenyl aromatics (estragole to eugenol) have also other deprotonation sites, which

can interfere with the abstraction of allyl proton H1.

Table 3.7 B3LYP/6-31+G* calculated pKa values of the allyl protons and the protons

of the substituent groups attached to the alkenyl aromatics at 140°C are given here.

Experimental conversion percentage of the alkenyl aromatics are also given here.

Substratesa Conversion, % pKa at

140 °C for H1

pKa at

140 °C for H1a

Allylbenzene

>99 26.28 --

Estragole

97 27.58 41.18

Allylveratrole

88 26.25 40.70

Safrole

64 26.98 35.38

Eugenol

19 27.84 13.43

aSubstrate: 200 mg; catalyst weight: 100 mg; solvent (4 ml); reaction time/temp: 60 min/140

oC; power: 300 W

. The pKa calculations performed with the deprotonation (H1a

) of the

susbtituent’s attached to the aromatic rings are given in Table 3.7. The calculated

results showed an interesting trend for the deprotonation process, which would

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

88

eventually control the isomerization of these alkenyl aromatics. Going from estragole

to safrole, the pKa of H1a

has reduced by several units. Thus, the deprotonation

process of H1a

would start competing with the allyl deprotonation H1 and hence the

conversion would decrease on going down from estragole to safrole. The observed

conversion in these cases supports the above rationalization for the isomerization

process.

Table 3.8 B3LYP/6-31+G* calculated relative energies with respect to the reactant

species in gas phase are given in kcal/mol. Solvent phase data are given in

parentheses (). Experimental ratios of the cis- and trans- product formation are also

given [Carbon: grey; Oxygen: red; Hydrogen: white]

Method Trans- product Cis- product

Allylbenzene

B3LYP/6-31+G* -6.29 (-6.63) -3.58 (-3.49)

Selectivity 88 12

Estragole

B3LYP/6-31+G* -6.47 (-6.80) -3.39 (-3.36)

Selectivity 83 17

Allylveratrole

B3LYP/6-31+G* -6.23 (-6.61) -3.37 (-3.41)

Selectivity 81 19

Safrole

B3LYP/6-31+G* -5.95 (-6.60) -2.89 (-3.16)

Selectivity 87 13

Eugenol

B3LYP/6-31+G* - 6.47 (-6.78) -4.02 (-4.04)

Selectivity 81 19

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

89

Interestingly, the calculated pKa of H1a

was found to be lower than the pKa of

H1

for eugenol, which suggests that there should be minimal conversion in the

isomerization process (Table 3.7) as there would be strong interference in the

abstraction of allyl proton by the hydroxyl proton. Indeed, the least conversion (19%)

for isomerization of eugenol observed over MgAl4 catalyst corresponded well with

this theoretical prediction. The experimentally observed results show that the

isomerization leads to trans product as the major isomer in all cases. Table 3.8 gives

the gas phase relative energies calculated at B3LYP/6-31+G* level of theory of the

trans and cis products with respect to the corresponding reactant molecules. The

calculated energies show that the trans products are energetically more favourable

than the cis products which is in accordance to the experimental results. Solvent phase

calculations performed with the PCM solvation model with DMF as the solvent

(dielectric constant 36.2) also showed similar results (Table 3.8).

3.3.2.6 Scale up studies over MgAl4

After optimizing the condition for viable isomerization of estragole to anethole

under MWI, the scaling up of reaction to 20 g were conducted. As in the case of

eugenol (section 2.3.2 of Chapter 2), scale up studies that conducted was not effective

as of lab scale. The results of scale up studies are given in Figure 3.11. The results

showed that conversion increased slowly and 90% conversion was achieved around

13 h. After 13 h an increase of only 1% conversion was only achieved in each hour.

The reaction was stopped after 21 h and 96% conversion of estragole was observed.

In the initial hours the kinetics of reaction was very slow and only 17% conversion

was observed in 1 h to 94% in lab scale. In order to find the reason for drop in activity

the effect of diffusion were checked. The reactions were done in 1 g scale (5 times to

that of optimized lab scale) with different stirring speed. The results in Table 3.9

showed that stirring had no influence on the reaction. With 450 and 900 rpm the

reaction was almost similar.

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

90

0 2 4 6 8 10 12 14 16 18 20

0

20

40

60

80

100

Co

nve

rsio

n,

%

Time, h

Figure 3.11 Scale up studies over MgAl4

Table 3.9 Isomerization of estragole over MgAl4 with varying stirring speed

Catalysta Conversion, % Selectivity, %

cis trans

450rpm 5 16 84

700rpm 5 15 85

900rpm 9 16 84

aSubstrate: Estragole (2 g); catalyst: 1 g; solvent, DMF (40 ml); reaction time./temp: 60

min/140 oC; power: 300 W.

3.4 Conclusions

Isomerization of alkenyl aromatics over MgAl and NiAl series of layered

double hydroxides was successfully carried out under microwave irradiation. Under

optimized conditions, MgAl4 showed 99% conversion of estragole to anethole with

86% trans selectivity. Significant variation in the conversion was noted under

identical conditions for thermal heating. The trans form is favourable than the cis

form in all the cases. A good correlation was observed between the activities of the

catalysts and the basicity derived using Hammett measurements. High boiling-high

polar solvents like DMF, DMSO, and DMA gave high conversion (95 ± 3%) in

shorter time (1 h), while high boiling-low polar, low boiling-high polar and low

boiling-low polar solvents showed poor activity. The MgAl4 catalyst was recyclable

for up to six cycles without significant activity loss. The isomerization of different

alkenyl aromatics over MgAl4 showed substantial variation in the activity depending

Chapter 3 Microwave assisted isomerization

Ph.D Thesis

91

on the groups attached to the aromatic ring irrespective of the nature of heating. The

relative pKa of the protons of the substituent groups attached to the alkenyl aromatics

governs the conversion of isomerization process. To surmise, reaction under

microwave offered both energy and environmental benefits by using reduced volume

of solvent, shorter reaction time and at lesser reaction temperature.

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