Activity and selectivity of different base catalysts in synthesis of guaifenesin from guaiacol and glycidol of biomass origin

Article abstract of DOI:10.1016/j.cattod.2016.12.008

Guaiacol and glycidol can be obtained from biomass valorization. Guaiacol (2-methoxyphenol) and glycidol (2,3-epoxy-1-propanol) have been used for the efficient synthesis of guaifenesin ((RS)-3-(2-methoxyphenoxy) propane-1,2-diol). Different catalysts such as hydrotalcite (HT), calcined hydrotalcite (CHT), calcinated hydrotalcite supported on hexagonal mesoporous silica, magnesium oxide, alumina and, potassium promoted zirconium oxide were synthesized, out of which CHT was found to be the most active, selective and reusable catalyst. The catalyst characterization was done by different techniques. Both Oxide and hydroxide phases were observed on calcination of HT in air at 450?°C for 6?h. CHT possess both acidic and basic sites and basicity of CHT was the highest. Crystallite size, surface area and pore size of CHT play important role in catalytic activity and selectivity. Reaction was carried out in a batch reactor and influence of different parameters was systematically studied. The reaction mechanism involving two sites, acidic and basic, was proposed. A suitable kinetic model was developed and fitted against experimental data. A second order rate equation was derived on the basis of Langmuir–Hinshelwood–Hougen–Watson mechanism with weak adsorption of reactants, intermediates and products. Kinetics was used to predict reaction conditions to obtain guaifenesin selectively. Guaifenesin was efficiently obtained with 94.8% selectivity at guaiacol conversion of 38.2% over CHT at 80?°C after 4?h.

Full text of DOI:10.1016/j.cattod.2016.12.008

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Activity and selectivity of different base catalysts in synthesis of
guaifenesin from guaiacol and glycidol of biomass origin
∗
Shivaji L. Bhanawase, Ganapati D. Yadav
Department of Chemical Engineering, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400 019, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 July 2016
Received in revised form 27 October 2016
Accepted 1 December 2016
Available online xxx
Guaiacol and glycidol can be obtained from biomass valorization. Guaiacol (2-methoxyphenol) and
glycidol (2,3-epoxy-1-propanol) have been used for the efficient synthesis of guaifenesin ((RS)-3-(2-
methoxyphenoxy) propane-1,2-diol). Different catalysts such as hydrotalcite (HT), calcined hydrotalcite
(CHT), calcinated hydrotalcite supported on hexagonal mesoporous silica, magnesium oxide, alumina
and, potassium promoted zirconium oxide were synthesized, out of which CHT was found to be the most
active, selective and reusable catalyst. The catalyst characterization was done by different techniques.
Keywords:
Guaifenesin (or
◦
Both Oxide and hydroxide phases were observed on calcination of HT in air at 450 C for 6 h. CHT possess
both acidic and basic sites and basicity of CHT was the highest. Crystallite size, surface area and pore size of
CHT play important role in catalytic activity and selectivity. Reaction was carried out in a batch reactor and
influence of different parameters was systematically studied. The reaction mechanism involving two sites,
acidic and basic, was proposed. A suitable kinetic model was developed and fitted against experimental
data. A second order rate equation was derived on the basis of Langmuir–Hinshelwood–Hougen–Watson
mechanism with weak adsorption of reactants, intermediates and products. Kinetics was used to predict
reaction conditions to obtain guaifenesin selectively. Guaifenesin was efficiently obtained with 94.8%
(
RS)-3-(2-methoxyphenoxy)
propane-1,2-diol)
Guaiacol (or 2-methoxyphenol) and
glycidol (or 2,3-epoxy-1-propanol)
Biomass valorization
Hydrotalcite
Calcined hydrotalcite
Green chemistry
◦
selectivity at guaiacol conversion of 38.2% over CHT at 80 C after 4 h.
Kinetics
©
2016 Elsevier B.V. All rights reserved.
1
. Introduction
paths to produce guaifenesin is based on biomass-derived guaia-
col and glycidol by using heterogeneous catalysis which has been
at the hub of green chemistry leading to waste reduction, process
intensification and profitability. Hydrotalcites (for instance, Mg6
Al2 (OH) 16 CO ·4H O) have been used as solid base catalysts for
In the foreseeable future, the stocks of fossil fuels would have
been exhausted and it would be necessary to derive chemicals
and fuels from renewable resources [1–3]. A variety of fresh and
waste biomass ought to be subjected to chemical, biological and
extractive technologies to derive platform chemicals, fuels and
materials [4]. Lignin is abundantly available as a waste from the
paper and pulp industries. In this regard, lignin will be an impor-
tant source for conversion into a spectrum of intermediates which
could be further valorized [5]. Similarly, glycerol, a co-product of
biodiesel production, can be catalytically transformed into a num-
ber of bulk chemicals such as acrolein, acrylic acid, 1,2-propanediol,
3
2
various reactions [11–17] and can be used for the production of
guaifenesin. Hydrotalcite is a bifunctional catalyst having both base
(major) and acid (minor) sites. It has a layered double hydroxide
structure in which positively charged magnesium-aluminum lay-
ers are formed due to defects in the structure. Defects are formed by
replacement of magnesium by aluminum. Anions such as carbon-
ate, nitrate, hydroxide and chloride are present at the interlayer. On
◦
calcination at 500–800 C, mixed magnesium-aluminum oxides are
1
,3-propanediol, etc. [6–8]. Guaiacol (2-methoxyphenol) and glyci-
formed with large surface area with basic and acidic sites. Acid and
basic properties can be adjusted with change in metal and metal
composition [18,19].
dol (2,3-epoxy-1-propanol) have been obtained from biomass from
lignin and glycerol, respectively [9,10].
Synthesis of guaifenesin from renewable sources should result
in a greener and more sustainable process. One of the possible
Guaifenesin is an expectorant drug used in racemic form for
the treatment of cough, asthma, gout, fibromyalgia, to facili-
tate conception and to improve voice [20]. Generally, guaifenesin
is synthesized by Williamson’s etherification reaction in which
nucleophile of guaiacol attacks on glycidol, epichlorohydrin,
∗ Corresponding author.
E-mail addresses: gdyadav@yahoo.com, gd.yadav@ictmumbai.edu.in
1
-chloroglycerol, glycerol carbonate, 3-bromo-1-propene and iso-
(
G.D. Yadav).
propylidene glycerol [21–26]. Homogeneous bases such as triethyl
http://dx.doi.org/10.1016/j.cattod.2016.12.008
920-5861/© 2016 Elsevier B.V. All rights reserved.
0
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from guaiacol and glycidol of biomass origin, Catal. Today (2016), http://dx.doi.org/10.1016/j.cattod.2016.12.008

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Table 1
2
amine, sodium hydroxide, potassium carbonate are used in stoi-
chiometric quantities and neutralized at the end of reaction causing
environmental pollution problems. The literature review suggests
that guaifenesin synthesis has not been so far reported using het-
erogeneous catalysis. In this work, we report a novel protocol for
the synthesis of guaifenesin using guaiacol and glycidol catalyzed
by calcined hydrotalcite (CHT). The reaction is additive and 100%
atom economical. Influences of different parameters are studied
including reaction mechanism and kinetics.
TPD analysis of catalysts, PMZH, MgO, CHT, HMSSH, and Al2O3.
Catalyst
PMZH
MgO
CHT
HMSSH
Al2O3
−1
Acidity (mmol g
)
0.09
0.49
0.41
0.75
0.68
1.53
0.63
0.48
0.76
0.32
Basicity (mmol g−1)
described in preparation of hydrotalcite (Section 2.1.1). Aluminium
hydroxide was calcined at 450 C in a furnace for 6 h to get alu-
◦
minium oxide (Al O ).
2
3
2
. Experimental
2.1.5. Magnesium oxide
Magnesium hydroxide was synthesized by co-precipitation
Following catalysts were prepared and further characterized by
various techniques, details of which are included in supporting
information.
method from magnesium nitrate. The same procedure described
in preparation of hydrotalcite (Section 2.1.1) was followed. Mag-
◦
nesium hydroxide was calcined at 450 C in a furnace for 6 h to get
magnesium oxide (MgO).
2.1. Preparation of catalysts
2.1.1. Hydrotalcite (HT)
2.2. Reaction procedure
The synthesis process is different and modified from that
reported in literature [27]. HT of Mg: Al ratio 3:1 was prepared
by co-precipitation method. Solution of magnesium nitrate (7.66 g,
In a typical reaction, autoclave reactor (details included in sup-
porting information) was charged with guaiacol (0.0081 mol), gly-
cidol (0.020 mol), tetrahydrofuran (THF) (10 mL) and 0.03 g mL
−
1
0
.03 mol) and aluminium nitrate (3.79 g, 0.01 mol) in 30 mL distilled
water was prepared. Solution of sodium hydroxide (3.6 g, 0.09 mol)
and sodium carbonate (2.8 g, 0.027 mol) in 30 mL distilled water
was prepared. At constant pH (9), both the solutions were added
simultaneously to a round bottom flask (500 mL) with overhead
(0.9 g) of the catalyst. The total organic phase volume was made to
30 mL with THF. An initial sample was taken at the desired temper-
ature. The reaction mixture was stirred with mechanical stirrer at
the desired speed, and samples were collected periodically. For con-
stirrer at a speed of 300 rpm immersed in oil bath at temperature
trol reaction, speed of agitation was 1000 rpm and temperature was
◦
120 ◦C at self-generated pressure. Reaction samples were analyzed
3
0 C. White precipitate of HT was obtained and further digested
◦
by HPLC (details included in supporting information). Synthe-
sis of guaifenesin (3-(2-methoxyphenoxy)propane-1,2-diol) and
byproduct (2-(2-methoxyphenoxy)propane-1,3-diol) from con-
densation reaction of guaiacol and glycidol is shown in Scheme 1.
at 60 C for 12 h. HT obtained was washed with distilled water to
get neutral pH to the supernatant solution. HT was filtered and
then dried at 100 C for 24 h to obtain dry lumps. HT lumps were
◦
crushed in mortar to get fine powder of weight 2.8 g. HT powder
◦
was calcined at 450 C for 6 h to get calcined HT (CHT) [27].
3. Results and discussions
2
(
.1.2. Hexagonal mesoporous silica supported hydrotalcite
HMSSH)
Hexagonal mesoporous silica (HMS) was prepared by a known
3.1. Catalyst characterization
procedure [28]. HMSSH (10% w/w) of Mg: Al ratio 3:1 was prepared
by co-precipitation method. In a conical flask, solution of mag-
nesium nitrate (2.29 g, 0.009 mol) and aluminium nitrate (1.14 g,
TPD (temperature programmed desorption) analysis of the cat-
alysts PMZH, MgO, CHT, HMSSH, and Al2O3 was carried out to find
out the strength of acidic and basic sites (Table 1). Acidity (except
Al2O3) and basicity of CHT was the highest. In the case of CHT, NH3
0.003 mol) in 50 mL distilled water was prepared. In another conical
◦
flask, solution of sodium hydroxide (1.08 g, 0.027 mol) and sodium
carbonate (0.85 g, 0.008 mol) in 50 mL distilled water was prepared.
Five g of HMS was added to a round bottom flask (250 mL) with
overhead stirrer at a speed of 300 rpm immersed in oil bath at tem-
desorption peak was observed at 123 C corresponding to weak
−
1
as well as strong acidic sites of concentration 0.68 mmol g (Fig.
◦
S1). Two CO2 desorption peaks were observed, first peak at 116 C
corresponding to weak basic sites of concentration 0.95 mmol g
and second peak at 264 C corresponding to strong basic sites of
−
1
◦
◦
perature 30 C. At constant pH (9), both the solutions were added
−
1
simultaneously to the round bottom flask, white precipitate of HT
concentration 0.58 mmol g (Fig. S2) [12,17,33].
◦
was obtained, which further was digested at 60 C for 12 h. Material
All the catalysts were analyzed for surface area analysis. All
showed, type IV adsorption–desorption isotherm with hysteresis
loop of type H1, which is a characteristic of a mesoporous solid
(Fig. 1). The Brunauer–Emmett–Teller (BET) surface area, Langmuir
surface area, pore size, and pore volume of all the catalysts are
shown in Table 2. Surface area of PMZH was the lowest. Surface
area of HMSSH was the highest while pore size was the lowest. After
calcination, surface area of hydrotalcite increases due to formation
of mixed Mg-Al metal oxides. On calcination, due to evolution of
CO2 and H2O, more porous material is formed by the formation of
pores through the layers. Hydrotalcites containing carbonates and
showing such behavior have been reported [27]. BET surface area of
so obtained was washed with distilled water to get neutral pH to
the supernatant solution. Then material was filtered and dried at
◦
1
00 C for 12 h to obtain dry powder. It was crushed in mortar to
◦
get fine powder which was calcined at 450 C for 6 h [11,29].
2.1.3. Potassium modified zirconium hydroxide (PMZH)
PMZH (8.8% w/w) was prepared by wet impregnation method.
Zirconium hydroxide was synthesized by a known procedure
30,31]. 0.25 g of potassium nitrate was dissolved in 1.5 mL of dis-
[
tilled water. This solution was added to 1 g of zirconium hydroxide
◦
under stirring to get wet material which was dried in oven at 100 C
2
−1
for 12 h. It was crushed in mortar to get fine powder which was
CHT was measured to be 240.5 m g . The pore volume and pore
◦
−1
calcined at 600 C for 3 h [32].
diameter were 0.97 mL g and 159.2 Å, respectively. Pore width of
CHT was in range of 100–600 Å (Fig. S3).
2
.1.4. Aluminium oxide
Aluminium hydroxide was synthesized by co-precipitation
The XRD (X-ray diffraction) pattern of HT have sharp reflec-
tions at 11.2 , 22.5 , 34.2 , 38.2 , 45.0 , 60.0 , and 61.3 (JCPDS
22-700) corresponding to (003), (006), (012), (015), (018), (110),
◦
◦
◦
◦
◦
◦
◦
method from aluminium nitrate by following the same procedure
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3
O
OH
O
OH
O
OH
O
CHT
THF, 120 ºC
[95%]
3
-(2-methoxyphenoxy)propane-1,2-diol
+
OH
O
O
OH
Guaiacol
Glycidol
OH
2
-(2-methoxyphenoxy)propane-1,3-diol[5%]
Scheme 1. Condensation of guaiacol and glycidol.
Table 2
Surface area analysis of catalysts, PMZH, MgO, CHT, HMSSH, Al2O3, and HT.
BET Surface Area (m2
g
−1
)
Langmuir Surface Area (m2
g
−1
)
Pore Volume (cm3
g
−1
)
Pore Size (Å)
Catalyst
PMZH
HT
MgO
CHT
Al2O3
HMSSH
16.7
76.7
140.5
240.5
273.1
344.4
24.2
0.12
0.84
0.36
0.97
0.51
0.45
290.7
388
84.1
159.2
70.4
56.9
113.5
207.7
352.4
401.3
504.2
in literature [12]. In presence of water, mixed Mg-Al metal oxides
is again converted to corresponding hydroxides. This is the rea-
son for the incomplete oxidation of HT, even after calcination in
1
000
◦
air at 450 C. Crystallite size of the HT and CHT was 25.8 and
(
a)
7
.7 nm, respectively, which also proves that amorphous nature of
CHT.
FTIR analysis of HT and CHT is shown in Fig. S4. HT have char-
8
6
4
2
00
00
00
00
0
−
1
2−
acteristic bands of water at 1650 cm , interaction of H O CO3
2
(b)
−
1
−1
around 3000 cm , hydroxyls in the 3400–3600 cm region and
carbonates at 1517 cm . In the case of CHT, the bands below
are the vibration modes for Mg O and Al O in
the mixed oxide [16]. In CHT, peaks of water at 1650 cm
−
1
−
1
1
000 cm
(
c)
−1
,
2−
−1
interaction of H O CO3
3400–3600 cm
around 3000 cm , hydroxyls in the
region and carbonates at 1517 cm
2
−1
−1
(
d)
disappear
or peaks intensity decreases which indicates formation of mixed
metal oxide.
TGA of the HT and CHT is shown in Fig. S5. HT loses 34% of a
(
e)
◦
total weight; the first weight loss at temperatures below 200 C was
attributed to the loss of physically adsorbed and interlayer water
◦
molecules, whereas the second weight loss (200–450 C) originates
(
f)
from the conversion of metal hydroxide to metal oxide and decom-
position of carbonates in the interlayer. CHT loses 23% of the total
weight which may be due to the presence of both oxide and hydrox-
ide phases, the moisture content, and the adsorbed CO2 in the
sample.
Figs. S6 and S7 show SEM images of HT and CHT, respectively.
Both show irregular particle shape and the average particle size is
in the range of 50–100 ␮m. EDXS analysis confirmed the presence
of Mg and Al elements. In the case of HT, the observed Mg and
Al mol ratio was 2.9:1 and for CHT, the observed Mg and Al mol
ratio was 3.1:1 which was in agreement with expected mol ratio,
0
0.2
0.4
0.6
0.8
1
Relative Pressure (P/P0)
Fig. 1. N2 adsorption-desorption isotherm of catalysts (a) PMZH, (b) MgO, (c) CHT,
d) HMSSH, (e) Al2O3, and (f) HT.
(
(
4
113) planes, respectively (Fig. 2). HT after calcination in air at
◦
50 C for 6 h gives amorphous structure (CHT), showing reflec-
◦
◦
◦
◦
◦
◦
tions at 11.4 , 23.0 , 34.2 , 38.2 , 43.3 and 62.6 (JCPDS 87-0653)
corresponding to (003), (006), (012), (015), (200) and (220) planes,
respectively (Fig. 2). The layered double hydroxide was con-
verted to mixed oxide manifested by the presence of new broad
reflections at 43.31 , 62.58 which correspond to the (200) and
220) planes. CHT has almost all the reflections shown by HT
3
:1 (Table S1). TEM images of HT and CHT are shown in Figs. S8
and S9, respectively. HT particles are of spherical shape while par-
ticles of CHT are irregular spherical shape and relatively porous in
nature.
◦
◦
(
but the intensity of peaks is low and some new peaks of mixed
oxides structure have appeared. Due to incomplete oxidation, both
hydroxide and oxide phases were obtained. In general, calcina-
tion of HT in nitrogen at 450 C gives pure mixed metal oxide
phase. Hydrotalcite shows memory effect which is well reported
3.2. Efficacy of various catalysts
◦
Activity of different catalysts such as HMSSH, PMZH, MgO,
Al O , HT, and CHT was evaluated for conversion and selectivity
2
3
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Fig. 2. X-ray diffraction (XRD) of catalysts HT and CHT.
of the reaction (Fig. 3). In the absence of catalyst (Nil) only negligi-
ble conversion (0.7%) was observed. Order of catalysts conversion
was as follows: PMZH (99%) > HT (70.3%) > CHT (66.5%) > MgO
(except Al O ) in comparison to other catalysts (Table 1). CHT was
2 3
found to be best for the reaction considering selectivity and activ-
ity of catalyst towards the product. Hence CHT was used in further
experiments.
(
42.5%) > HMSSH (5%) > Al O (1.3%). While order of catalysts selec-
2 3
tivity was as follows: Al O3 (100%) > CHT (93.5%) > MgO (92%) > HT
2
(
87.6%) > PMZH (81.8%) > HMSSH (59%). PMZH appeared to be the
3
.3. Effect of speed of agitation
best for conversion but its selectivity for product was the low-
est which was due to lowest surface area and larger pore size
with respect to CHT (Table 2). HT and CHT gave almost the same
conversion, but selectivity of CHT for the product was greater
than HT which might be due to crystallite size, surface area and
pore size. Crystallite size of the CHT was lower (7.7 nm) than HT
Fig. 4 depicts the effect of speed of agitation on conversion from
00 to 1200 rpm to observe that the conversion profile. At 1000
8
and 1200 rpm, conversion was almost the same thereby indicating
the absence of external mass transfer resistance for transport of
reactants to the external surface of the catalyst particle from the
bulk liquid phase. A theoretical calculation was also done as delin-
eated in some of our earlier work to confirm that there was no
influence of external mass transfer resistance [31,34]. Thus, further
experiments were carried out at 1000 rpm.
2
−1
(
(
25.8 nm). Surface area of CHT (240.5 m g ) was higher than HT
76.7 m g ). Pore size of CHT (159.2 Å) is lower than HT (388 Å).
2
−1
Lower pore size of CHT was contributing for its superior selectiv-
ity. High activity of CHT was due to its highest basicity and acidity
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5
1
00
7
6
0
0
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
50
4
3
2
0
0
0
10
0
0
30
60
90
120
150
180
210
240
Nil
HMSSH PMZH
MgO
Al2O3
HT
CHT
Time (min)
Fig. 3. Efficacy of various catalysts: guaiacol; 0.0081 mol, glycidol; 0.02 mol, speed
Fig. 5. Effect of catalyst loading: catalyst; CHT, guaiacol; 0.0081 mol, glycidol;
−1
◦
◦
of agitation; 1000 rpm, catalyst loading; 0.03 g mL , temperature; 120 C, solvent;
THF, total volume; 30 mL, duration; 4 h, autogenous pressure, % conversion ( ), %
selectivity ( ).
0.02 mol, speed of agitation; 1000 rpm, temperature; 120 C, solvent; THF, total vol-
ume; 30 mL, duration; 4 h, autogenous pressure, 0.02 g mL−1 ( ), 0.03 g mL−1 ( ),
0.04 g mL−1 ( ).
3
3
2
2
.50
.00
.50
.00
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
y = 725.5x
R² = 0.99
1.50
1.00
0
.50
.00
0
0
30
60
90
120
150
180
210
240
0
0.001
0.002
0.003
0.004
0.005
-1
Catalyst loading (g ml )
Time (min)
Fig. 6. Plot of initial rate versus catalyst loading: catalyst; CHT, guaiacol; 0.0081 mol,
glycidol; 0.02 mol, speed of agitation; 1000 rpm, temperature; 120 C, solvent; THF,
total volume; 30 mL, autogenous pressure.
Fig. 4. Effect of speed of agitation: catalyst; CHT, guaiacol; 0.0081 mol, glycidol;
◦
−
1
◦
0
.02 mol, catalyst loading; 0.03 g mL , temperature; 120 C, solvent; THF, total
volume; 30 mL, duration;4 h, autogenous pressure, 800 rpm ( ), 1000 rpm ( ),
200 rpm ( ).
1
proportional to the catalyst loading (Fig. 6) which was due to the
proportional increase in active sites thereby confirming the absence
of external mass transfer and intra-particle diffusion resistances.
In order to ascertain that the intra-particle diffusion resistance
was totally absent, the Wiesz-Prater modulus was calculated using
observed rates of reaction, as discussed earlier, which showed val-
ues far less than one [31,34].
3
.4. Effect of catalyst loading
After confirmation of absence of external mass transfer resis-
tance, the effect of catalyst loading on initial rate of reaction and
−
1
overall conversion was studied from 0.02 to 0.04 g mL of total
volume of reaction mass (Fig. 5). A plot of initial rate against
catalyst loading showed that initial rate of reaction was directly
Please cite this article in press as: S.L. Bhanawase, G.D. Yadav, Activity and selectivity of different base catalysts in synthesis of guaifenesin
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6
1
00
7
6
0
0
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
50
40
30
20
10
0
0
30
60
90
Time (min)
Fig. 8. Effect of temperature: catalyst; CHT, guaiacol; 0.0081 mol, glycidol; 0.02 mol,
speed of agitation; 1000 rpm, catalyst loading; 0.03 g mL , solvent; THF, total vol-
ume; 30 mL, duration; 4 h, autogenous pressure, 80 C ( ), 100 C ( ), 120 C ( ),
40 C ( ).
120
150
180
210
240
0
30
60
90
120
150
180
210
240
Time (min)
−
1
Fig. 7. Effect of mole ratio: catalyst; CHT, guaiacol; 0.0081 mol, speed of agitation;
000 rpm, catalyst loading, 0.03 g mL , temperature; 120 C, solvent; THF, total
volume; 30 mL, duration; 4 h, autogenous pressure, 1:1 ( ), 1:2.5 ( ), 1:5 ( ).
◦
◦
◦
−1
◦
1
◦
1
100
3.5. Effect of mole ratio
9
0
In the absence of external mass transfer and intra-particle dif-
fusion resistances, overall rate of reaction would be controlled by
other resistances, namely, adsorption, surface reaction and des-
orption. Adsorption of the reacting species will be key factor for
the rate of reaction. To verify this fact, the effect of mole ratio
was studied. Mole ratio of guaiacol to glycidol was varied from
80
7
6
5
0
0
0
1
:1 to 1:5 by keeping the total volume the same. With increase
in concentration of glycidol, conversion was found to increase. As
concentration of glycidol with respect to guaiacol increases, greater
will be the adsorption of glycidol on the catalyst sites which will
increase the concentration of electrophile to react with guaiacol
resulting in higher conversion of guaiacol. At 1:5 mol ratio the high-
est conversion was obtained (Fig. 7), while at 1:1 mol ratio the least
conversion was obtained which was due to the concentration effect
of typical power law rate.
40
30
2
1
0
0
0
3
.6. Effect of temperature
This is a parallel reaction. Selectivity of products may change
with increase in temperature. Effect of temperature on the selec-
tivity and rate of reaction was studied at 80, 100, 120, and 140 C
◦
Fresh
1st Reuse
2nd Reuse
3rd Reuse
(Fig. 8). With increase in temperature, conversion was found to
increase and selectivity of guaifenesin was found to decrease. From
an Arrhenius plot, calculated energy of activation for formation
of guaiacol was 16.8 kcal mol . The rates and conversions were
strongly dependent on temperature, suggest kinetically controlled
regime.
Fig. 9. Catalyst reusability: catalyst; CHT, guaiacol, 0.0081 mol, glycidol; 0.02 mol,
speed of agitation; 1000 rpm, catalyst loading; 0.03 g mL , temperature; 120 C,
solvent; THF, total volume; 30 mL, duration; 4 h, autogenous pressure, % conversion
−
1
◦
−1
(
), % selectivity ( ).
◦
by drying at 100 C for 12 h to get an off-white material which was
◦
3.7. Reusability of catalyst
calcined at 450 C for 6 h to get whitish material. In all processes,
catalyst loss during filtration and handling was compensated by
addition of corresponding fresh catalyst for next three experiments.
There was no significant decrease in conversion of guaiacol and
selectivity of product (Fig. 9).
Regenerated catalyst was characterized different techniques to
verify the properties in comparison with fresh catalyst. Surface area
Reusability studies were conducted for three experiments. After
completion of the reaction and lowering the temperature, the reac-
tion mass was filtered to separate the catalyst. The catalyst was
refluxed with 30 mL THF for 1 h to remove any adsorbed reaction
ingredients. Then the catalyst was separated by filtration followed
Please cite this article in press as: S.L. Bhanawase, G.D. Yadav, Activity and selectivity of different base catalysts in synthesis of guaifenesin
from guaiacol and glycidol of biomass origin, Catal. Today (2016), http://dx.doi.org/10.1016/j.cattod.2016.12.008

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7
2
−1
of regenerated catalyst was 233.9 m g while of fresh catalyst was
2
CT2 = CS2 + CBS2 + CES2 + CDS2
(8)
2
−1
40.5 m g (Table S2). FTIR analysis of fresh and regenerated cat-
The concentrations of adsorbed species are given by the follow-
ing equations:
alyst revealed that all functional groups were intact and showed
similar bands in FTIR spectra (Fig. 6). NH3 and CO2 TPD analysis of
freshand regeneratedcatalystshowedthe same acidityand basicity
Table S2). Also rate of reaction and turn over frequency for reused
catalysts remain constant which confirmed that catalyst is stable
and reusable (Table S3).
CAS1 = K C C
(9)
(10)
(11)
(12)
A
A
S1
(
CBS2 = KBCBCS2
CES2 = KECECS2
4
. Reaction kinetics
CDS2 = KDCDCS2
Now Eq. (7) can be written as:
4.1. Reaction mechanism
CT2 = CS1 + K C C
(13)
(14)
A
A
S1
In CHT, Al3+ ions replace some Mg2+ ions which gives positively
Or
charged layered structure. It consists of both basic sites and acidic
sites; basic sites are due to O2 anions in the layer structure and
−
CT1
1+K C
CS1 = (
acidic sites are due to positively charged layered structure.
A
A)
A possible mechanism has been proposed in Scheme 2, con-
sidering two different sites i.e. weak acid sites and basic sites.
Glycidol and guaiacol get adsorbed on acidic sites and basic sites,
respectively. The activation of epoxide ring at acidic sites results in
formation of positive charge on the oxygen of epoxide ring. At basic
And Eq. (8) can be written as:
CT2 = CS2 +KBCBCS2 +KDCDCS2 +KECECS2
Or
(15)
(16)
1−
sites, hydroxyl functional group of guaiacol gives
O
species. The
CT2
CS2 = (
adsorbed species reacts on the surface of catalyst and results in the
formation of product guaifenesin and the byproduct. Subsequently
guaifenesin and byproduct get desorbed from the surface into the
reaction mixture to vacate catalyst site. This catalyst site can further
get involved for next catalytic cycle.
1+KBCB+KDCD+KECE)
The rate of formation of product D, assuming reaction to be
irreversible, is given by:
dCD
dt
=
=
k K C C KBCBCS2
(17)
(18)
1
A
A
S1
4.2. Kinetic model
dCD
dt
k1KACAKBCBCT CT
1 2
(1+K C ) (1+KBCB+KDCD+KECE)
The catalyst CHT is bifunctional with sites S1 (basic) and
A A
S2 (acidic) uniformly distributed on the pore surface. According
to the Langmuir–Hinshelwood–Hougen–Watson (LHHW) mecha-
nism, guaiacol (A) and glycidol (B) were assumed to adsorb on S1
The value of reaction rate constant, k , can thus be evaluated by
1
solving Eq. (18) using Polymath 6.0. We can also obtain values for
equilibrium adsorption coefficients for the species A, B, D and E by
solving this equation. The adsorption constants (Table 3) showed
that all species were weakly adsorbed and thus an overall second
order rate equation was valid.
and S2, respectively.
4.2.1. Adsorption
Adsorption of guaiacol (A) on a vacant site S1 is given by:
Similarly, we can write the rate of formation of byproduct E from
Eq. (4) as
K
A
A + S ↔AS
(1)
(2)
1
1
dCE
dt
k2KACAKBCBCT CT
1 2
=
(19)
Adsorption of glycidol (B) on a vacant site S2 is given by:
(1+K C ) (1+KBCB+KDCD+KECE)
A
A
KB
B + S ↔BS
The instantaneous selectivity of product D over E, SD/E, is given
2
2
by
4
.2.2. Surface reaction
Surface reaction of AS1 and BS2 leads to the formation
dCD
⁄
dt
k1
k2
SD/E = dCE
=
(20)
of DS2 (chemisorbed guaifenesin) and ES2 (chemisorbed 2-(2-
methoxyphenoxy) propane-1, 3-diol) by two parallel reactions
given by:
⁄dt
Thus using Eq. (20) and selectivity ratio, the value for kinetic
rate constant, k2 can be evaluated (Table 3). Using the values of k1
and k2 obtained at different temperatures; Arrhenius plots were
made for both the reactions (Fig. 10). The activation energy for the
reaction guaiacol to guaifenesin (E1) and guaiacol to byproduct (E2)
k
1
AS + BS ↔DS + S
(3)
(4)
1
2
2
1
k
2
AS + BS ↔ES + S
−1
−1
1
2
2
1
are 16.8 kcal mol
and 18.3 kcal mol , respectively. It indicates
that the reactions are intrinsically kinetically controlled. This is an
overall second order reaction.
4
.2.3. Desorption
Desorption of guaifenesin (DS ) and 2-(2- methoxyphenoxy)
2
It was observed that rate constant k > k2 (Table 3) and energy
1
propane-1, 3-diol (ES ) is given by:
2
of activation related to these reactions; E < E . The selectivity ratio
1
2
1
/KD
(
k /k ) decrease with increase in temperature (Table 3), and acti-
DS2 ↔ D + S
(5)
(6)
1 2
2
vation energy for formation of byproduct is higher than activation
energy for formation of guaifenesin. Thus the selectivity of guaife-
nesin decreases with increase in temperature due to its lower
1
/KE
ES2 ↔ E + S
2
The total concentration of the basic and acidic sites, CT expressed
activation energy (E ), while selectivity of byproduct increases with
1
as:
increase in temperature due to its higher activation energy (E ).
2
CT1 = CS1 + CAS1
(7)
Hence guaifenesin synthesis is favorable at lower temperature.
Please cite this article in press as: S.L. Bhanawase, G.D. Yadav, Activity and selectivity of different base catalysts in synthesis of guaifenesin
from guaiacol and glycidol of biomass origin, Catal. Today (2016), http://dx.doi.org/10.1016/j.cattod.2016.12.008

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S.L. Bhanawase, G.D. Yadav / Catalysis Today xxx (2016) xxx–xxx
Scheme 2. Catalytic cycle for condensation of guaiacol and glycidol over CHT (S1: base sites, S2: acid sites).
Table 3
Reaction constant, equilibrium adsorption coefficient and selectivity ratio of reaction at different temperatures.
◦
−1
)
Reaction temperature,
C
Equilibrium adsorption coefficient, (lit mol
Reaction constant,
Selectivity ratio, (k1/k2)
2
−1 −1 −1
s g
(
lit mol
of cat)
KA
KB
KD
KE
k1
k2
−
−
3
3
−
−3
−3
−3
−3
8
1
1
1
0
0.029
0.024
0.019
0.014
0.013
0.011
0.0094
0.0080
0.0012
0.010
0.0086
0.007
0.005
3.7 × 10
9.5 × 10
0.2 × 10
0.6 × 10
3.1 × 10
8.5 × 10
18.2
17.4
14.4
13.9
00
20
40
0.0046
0.0040
0.0033
3
45.0 × 10
−
3
119.0 × 10
4.3. Validation of kinetic model
nesin. Guaifenesin was obtained with 86% selectivity at guaiacol
conversion of 92% over CHT at 120 C after 4 h. Reaction kinet-
◦
A parity plot was made to prove the fit of experimental data
ics was studied using LHHW model. All species were found to be
weakly adsorbed and the overall reaction was second order. Activa-
to the predicted according to the mathematical model (Fig. 11).
Experimental rates of reaction and predicted rates of reaction show
very good match which demonstrate that the assumptions made to
establish kinetic model were correct.
−1
tion energy for formation of guaifenesin is 16.8 kcal mol . Kinetics
was used to predict reaction conditions to obtain guaifenesin selec-
tively. To obtain guaifenesin selectively, reaction may be done at
following conditions: speed of agitation; 1000 rpm, temperature;
◦ −1
8
0 C, catalyst loading; 0.03 g mL , mole ratio of guaiacol to glyci-
5
. Conclusion
dol; 1:5 and solvent; THF. Guaifenesin can be efficiently obtained
with 94.8% selectivity at guaiacol conversion of 38.2% over CHT at
80 C after 4 h. Guaifenesin can be commercially synthesized by this
◦
Heterogeneous base catalyzed condensation of guaiacol with
glycidol was studied using various catalysts. Among all catalysts,
basicity and acidity (except Al O ) of calcined hydrotalcite (CHT)
process.
2
3
◦
was the highest. Calcination of hydrotalcite at 450 C in air gave
both hydroxide and oxide phases. CHT is a mesoporous material
with high surface area. On the basis of catalyst activity and selectiv-
ity, CHT was the best and reusable catalyst due to synergistic effect
of acidic and basic sites. Reaction conditions were optimized to
give maximum guaiacol conversion and high selectivity for guaife-
Acknowledgements
S.L.B. thanks University Grants Commission (UGC) for awarding
the Junior Research Fellowship under its Green Technology spe-
cial meritorious fellowship program. G.D.Y. acknowledges support
Please cite this article in press as: S.L. Bhanawase, G.D. Yadav, Activity and selectivity of different base catalysts in synthesis of guaifenesin
from guaiacol and glycidol of biomass origin, Catal. Today (2016), http://dx.doi.org/10.1016/j.cattod.2016.12.008

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