CHEMICAL ENGINEERING RESEARCH AND DESIGN 9 O ( 2 O I 2 ) 1 2 8 1 - 1 2 9 1

Contents lists available at SciVerse ScienceDirect

Chemical Engineering Research and Design

journal homepage: www.elsevier.com/locate/cherd
ELSEVIER

Process intensication and waste minimization in

liquid-liquid-liquid phase transfer catalyzed
selective synthesis of mandelic acid
Ganapati D. Yadav*, P.R. Sowhna
Department of Chemical Engineering, Institute of Chemical Technology Matunga, Mumbai 400 019, India

A B S T R A C T

Conversion of biphasic reactions into triphasie reaetions ean lead to process intensification, waste minimization
and selectivity enhancement. Unlike liquid-liquid (L-L) PTC, the Liquid-Liquid-Liquid phase transfer eatalysis (L-L-L
PTC) offers high order of intensifieation of rates of reaction and catalyst reuse. The rate of reaetion is remarkably
enhaneed by the catalyst-rich middle phase, which is the main reaetion phase. Separation of catalyst can be done
easily and the separated catalyst ean be reused several times by using L-L-L PTC. This leads to waste minimization and
other benefits of Creen Chemistry. Mandelic acid and its derivatives are used for their dual activities as antibaeterial
and anti-aging agents. In this work, mandelic acid was produced by L-L-L PTC reaction of dichlorocarbene with
benzaldehyde. Diehloroearbene was generated in situ by the reaction of chloroform and sodium hydroxide in the
presence of poly ethylene glycol (PEC) 4000 as the catalyst. The seleetivity to mandelie acid was 98%. The reaction
mechanism and kinetics model were established to validate the experimental data.
2012 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
Keyu;ords: Multiphase reactions; Phase Transfer eatalysis; Kineties; Creen ehemistry; Mandelic acid

1. Introduction of hazardous reactions by using PTC in a safe and efficient way

Phase transfer catalysis (PTC) is a well established technique,
which aims at cost and waste minimization (Yadav, 2005). PTC
has proved to be a very important means of transcending
phase barriers in heterogeneous systems. Although the use of
agents for anion transfer has been mentioned in some early
publications and patents (Jarrouse, 1951), the foundation of
PTC were laid in the late 1960s and early 1970s by the studies
of Makosza (1975), Starks (1971), Yadav (1975), and Brandstorm
(1978). PTC has been applied to over 700 processes in a variety
of industries such as intermediates, dyestuffs, agrochemicals,
perfumes, flavours, pharmaceuticals and polymers (Naik and
Doraiswamy, 1998; Starks et al., 1994; Sasson and Neumann,
1997; Yadav and Sharma, 1981; Yadav and Bisht, 2004,2005).
Application of PTC instead of traditional technologies for man-
ufaeture of organic chemicals provides substantial benefits for
the environment (Makosza, 2000). One of the main benefits to
adopt PTC reaetions is that it requires mild operating eondi-
tion and eheaper reagents. It is possible to earry out a variety
(Sharma, 2002).
PTC reactions have been studied as liquid-liquid (L-L) PTC,
solid-liquid (S-L) PTC, gas-liquid (C-L) PTC, solid-liquid-liquid
(S-L-L) PTC, and liquid-liquid-liquid (L-L-L) PTC including
those with a synergistie combination of microwaves (Yadav,
2004; Yadav and Bisht, 2004,2005). The main disadvantage of
PTC in commercial applications is the need to separate the
catalyst from the produet in the organic phase. This can be
eliminated by using L-L-L PTC in which high order of inten-
sification of rates of reaction oeeurs. The middle eatalyst-rieh
phase can be created between the organic and aqueous phase
(Fig. 1), which contains the reactants through a proper balance
of lipophilieity, hydrophilicity, interfacial tension, solubilities,
phase equlibria, and density. This third liquid phase will be
formed only when the catalyst has limited solubility in both
organic and aqueous phase (Starks et al., 1994; Yadav and
Naik, 2001). Most of the eatalyst is found in the eatalyst-rieh
middle phase, where the main reaetions take plaee and the
presenee of this third phase leads to remarkable enhaneement

Corresponding author. Tel.: +91 22 33611001/1002; fax: +91 22 33611002/1020.

E-mail addresses: gdyadav@yahoo.eom, gd.yadav@ietmumbai.edu.in (CD. Yadav).
Received 16 September 2011; Received in revised form 21 Deeember 2011; Accepted 13 January 2012
0263-8762/$ - see front matter 2012 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.cherd.2012.01.007
1282 C H E M I C A L E N G I N E E R I N G RESEARCH A N D D E S I G N gO ( 2 0 I 2) 1281-1291

that by L-L-L PTC enhancement of both the rates and selec-

Nomenclature tivity can be achieved, thereby reducing reaction time and
separation cost.
A benzaldehyde The current work focuses on the production of mandelic
B chloroform acid by L-L-L PTC reaction of dichlorocarbene with benzalde-
C'^^ concentration of benzaldehyde in the organic hyde. Dichlorocarbene is generated in situ by the reaction
phase, mol/cm^ of organic phase of chloroform and sodium hydroxide in the presence of poly
C^ concentration of benzaldehyde in the third ethylene glycol 4000 (PEG) as the catalyst. There is no report
phase, mol/cm^ of third phase on this system. Mandelic acid and its derivatives are used con-
C"^ concentration of chloroform in the organic comitantly as antibacterial and anti-aging agents. PEGs and
phase, mol/cm^ of organic phase their derivatives have been extensively used as phase transfer
C^'^ concentration of chloroform in the third phase, agents. PEG is very cheap, non-toxic and easily biodegradable.
mol/cm^ of third phase PEGs are also more stable at higher temperature and show
C*g concentration of peg in the third phase higher stability to acidic and basic conditions than quater-
aCA a-chloro acid nary onium salts (Chen et al., 2005). The work also deals with
K1-K6 equilibrium constants mechanism and kinetics of the reaction.
k* rate constant for the formation of mandelic
acid in the third phase 2. Experimental
MA mandelic acid
NpEG tot total moles of catalyst PEG added 2.1. Materials
t time of reaction (min)
V^' volume of aqueous phase (cm^) Benzaldehyde, chloroform, hexane, undecane, diethyl ether,
V'^ volume of organic phase (cm^) sodium hydroxide, sodium sulphate (all AR grade), acetoni-
V'^ volume of third phase (cm^) trile and acetic acid (both of HPLC grade) and PEG 4000 were
XA fractional conversion obtained from M/S s.d. fine Chem. Ltd., Mumbai, India.
Greek letters
2.2. Experimental set-up and procedure
a - v*/vrg ratio of third to organic phase volumes
ratio of third to aqueous phase volumes
The reaction was studied in a 4 cm i.d. fully baffled mechani-
7'""2' molar ratio of PEG in the form of cally agitated glass reactor of 100 cm^ total capacity which was
PEG
equipped with a 6-blade-pitched turbine impeller and a reflux
PEGNaOH(nH2O) at any time in the third phase
condenser. The reactor was kept in an isothermal water bath
whose temperature was maintained at a desired value and the
in reaction rates and selectivity. Separation of catalyst can be
reaction mixture was agitated mechanically with the help of
done easily to reuse it several times. Side reactions are sup-
an electric motor. Typical runs were conducted at 55 C with
pressed or totally eliminated (Yadav and Reddy, 1999). These
organic phase (0.01 mol benzaldehyde, 0.02 mol chloroform,
factors lead to the waste minimization and better selectiv-
0.0025 mol undecane as internal standard dissolved in hexane
ity, which are the major theme of Green Chemistry. Recently
to make the volume of organic phase to 20 cm^) and aque-
various reactions have been reported on liquid-liquid-liquid
ous phase (0.16 mol sodium hydroxide dissolved in water to
(L-L-L) PTC by Yadav and Naik (2001), Yadav et al. (2003), Yadav
make up volume of aqueous phase to 20 cm^) with 0.0007 mol
and Jadhav (2003), Yadav and Bisht (2004), Yadav and Lande
PEG 4000 as the catalyst. The amount of PEG 4000 and sodium
(2005a,b, 2007), Yadav and Desai (2005), Yadav and Desai (2006),
hydroxide determined the formation of third liquid phase. The
Yadav and Badure (2007), Yadav and Badure (2008) and Yadav
reaction was carried out in the presence of nitrogen atmo-
and Motirale (2010). Other reactions reported on L-L-L PTC
sphere. Typically the reaction was carried out for 90 min, and
include (Neumann and Sasson, 1984; Huang and Yang, 2005;
then the organic phase was removed. The reaction was con-
Goto et a l , 2000; Hsiao et al., 2000; Hsiao and Weng, 2001; Ido
tinued for another 2 h with the catalyst-rich middle phase and
et a l , 1997; Jen et al., 2005; Jin et al., 1999, 2001, 2003; Wang and
the aqueous phase. This was done to improve the selectivity,
Weng, 1995; Yang and Li, 2006). All these reports have shown
because the conversion of the intermediate a-chloro acid to
mandelic acid was slow.
The product mandelic acid appeared in the aqueous phase
as sodium salt of mandelic acid. This could be recovered as
discussed below. The aqueous phase was separated and neu-
tralized with dil. HCl. Then the entire mixture was evaporated
under vacuum to reduce the aqueous phase volume to 25 cm^.
Liquid fiims This aqueous phase was saturated with sodium chloride. Then
the mandelic acid present in this aqueous phase was extracted
with diethyl ether, which was dried with sodium sulphate and
the solvent was evaporated to leave the product mandelic acid.

2.3. Method o/analysis

Samples of the organic phase were withdrawn periodically

and analyzed by GC on a Chemito 8610 model. 10% SE 30 stain-
Fig. 1 - L-L-L PTC. less steel packed column was used for analysis in conjunction
 C H E M I C A L E N G I N E E R I N G RESEARCH A N D D E S I G N 9 O ( 2 0 I 2) 1281-1291 1283

with a flame ionization detector. The conversion was based

on disappearanee of benzaldehyde. The eonversion was
defined with referenee to limiting reaetant benzaldehyde.
Traee amount of benzyl aleohol was found in the organie
phase analysis.
HPLC was used with UV deteetor and C-18 eolumn to
analyze the dried solid left after extraetion and drying of
the aqueous phase. The mobile phase eomposition was aee-
tonitrile:water:aeetie aeid 60:39:1 by volume at a flow rate
of 0.5ml/min. UV detection wavelength was set at 231 nm. Organic Phase
The product mandelic acid and byproduct benzoic acid were
confirmed by LCMS. Synthetic mixture was prepared for cali-
bration and used to ealeulate the eoneentration and seleetivity Catalyst Phase
of mandelie aeid.
The following are the eompositions of the reaetants for Aqueous Phase
the preparation of ~11.8g of mandelie aeid: benzaldehyde:
0.08 mol, chloroform: 0.01 mol, NaOH: 0.64 mol, peg 4000
0.0028 mol, hexane: 80 em^ (made up), water:80 em^ (made up). Fig. 2 - L-L-L PTC Actual reactor operation.

100 T
2.4. Reaction scheme
90
The overall reaction is shown in Scheme 1.
80
3. Results and discussion

3.1. Formation of third phase

Several experiments were eondueted to understand the eriti-

eal parameters for maintaining three immiseible phases at all o
temperatures from 30 C to 55 C under agitation and without
agitation. The formation of third phase oeeurred between the
aqueous phase, whieh was saturated with sodium hydroxide
and organie phases of hexane as solvent, when the eatalyst
eoneentration was beyond a eritieal eoneentration. During
agitation, the reaetion mass had droplets of organic phase
surrounded by a thin film of catalyst-rich phase in a pool of
aqueous phase, which was the continuous phase (Fig. 2). When
the agitation was stopped the three phases would emerge as
three different layers as shown in Fig. 1. Time (min)

Fig. 3 - The comparison of L-L and L-L-L PTC.

3.2. Comparison o/L-L and L-L-L PTC
In L-L PTC reaetion the reaetion reaehed a maximum eonver-
sion of 47% and selectivity towards mandelic acid was 74%
in 90min at 55-C. But in L-L-L PTC reaction, the conversion
increased to 99% within 30 min and selectivity towards man-
delic aeid was 98% (Fig. 3 and Table 1).
3.3. E//ecto/catalyst
The reaction was carried out under similar conditions in the
absenee of any eatalyst. Fig. 4 shows a eonversion of about 49%
in 30 min, but there was no formation of mandelie aeid, only
Benzaldehyde 0.01 mol, chloroform 0.02 mol, undecane
0.0025 mol, hexane 20 cm^ (made up), PEG4000 0.0007 mol,
NaOH 0.03 mol for L-L, 0.16 mol for L-L-L water 20 cm^
(made up), temperature 55 C, speed of agitation 1000 rpm,
under N2 atmosphere. A, L-L-L; , L-L.
benzyl alcohol and benzoic acid are formed by Cannizzaro
reaction. This also demonstrates the prowess of creation
of three phases and phase transfer eatalyst in dramatically
ehanging seleetivity to the desired produet. It eould also be
observed from Fig. 4 and Table 2 that as the PEGs molecular
weight increases the conversion and selectivity increases.
PEG 4000 gave the best result. When the same reaction

+ CHCI3 + 3NaOH 3NaCI

Benzaldehyde
Mandelic acid

Scheme 1 - Overall reaction scheme for mandelic acid from benzaldehyde under L-L-L PTC.
1284 CHEMICAL ENGINEERING RESEARCH AND DESIGN 9 0 (2OI 2) 1281-1291

Table 1 - The comparison of L-L and L-L-L PTC.

Method Selectivity to mandelic acid (%)
L-L 74
L-L-L 98

Benzaldehyde 0.01 mol, chloroform 0.02mol, undecane 0.0025mol,

hexane 20 cm^ (made up), PEG4000 0.0007 mol, NaOH 0.03 mol for
L-L, 0.16mol for L-L-L water 20cm^ (made up), temperature 55 C,
fspeed of agitation 1000 rpm, under N2 atmosphere.

30

20

10

30 40
Time (min)

Fig. S - Effect of speed of agitation. Benzaldehyde 0.01 mol,

chloroform. 0.02 mol, undecane 0.0025 mol, hexane 20 cm^
u
(made up), PEG4000 0.0007 mol, NaOH 0.16 mol, water
20 cm^ (made up), temperature 55 C, under N2 atmosphere.
0, 600 rpm; , 800 rpm; A, 1000rpm;0,1200 rpm.

Table 3 - Effect of speed of agitation.

30 40
Time (min)
Fig. 4 - Effect of catalyst. Benzaldehyde 0.01 mol,
chloroform 0.01 mol, undecane 0.0025 mol, hexane
(made up), PEGs 0.00093 mol, NaOH 0.16 mol, water 20 cm^
(made up), temperature 55 C, speed of agitation 1000 rpm,
under N2 atmosphere. , PEG 4000; , PEG 600;A, PEG 400;
D, no catalyst.
under similar conditions was carried out with PTCs like ethyl
triphenyl phosphonium bromide, cyphose 163 etc., there was
also formation of phenyl tri chloro methyl carbinol, but this
was not observed when PEG 4000 was used as catalyst. PEG
4000 as a catalyst resides mainly in the middle phase and the
reactions in aqueous phase are suppressed.
3.4. Effect of speed of agitation
To ascertain the influenee of mass transfer resistanee of the
reactants to the reaction phase, the speed of agitation was
varied in the range of 600-1200 rpm under otherwise similar
conditions with PEG 4000 at 55 C. The conversion and selec-
Speed of agitation (rpm) Selectivity to mandelic acid (%)
600 97
800 97
1000 98
1200 98
Benzaldehyde 0.01 mol, chloroform 0.02 mol, undecane 0.0025 mol,
hexane 20 cm^ (made up), PEG4000 0.0007 mol, NaOH 0.16 mol, water
20cm^ (made up), temperature 55 C, under N2 atmosphere.
tivity were practically the same at 1000 and 1200 rpm (Fig. 5
and Table 3). Further increase in speed of agitation had prac-
tically no effect on the conversion and selectivity and hence
there was no mass transfer resistance from 1000 rpm onwards.
Thus, further experiments were carried out at 1000 rpm.
3.5. Effect 0/catalyst loading
The catalyst concentration is the most important variable
in L-L-L PTC. The concentration was varied over a range
of 3 X 10~*-9 X 10"* mol, under otherwise similar conditions
(Fig. 6). The formation of third phase occurred only after a crit-
ical amount of catalyst was added to the reaction mixture. The
selectivity towards mandelic acid increased from 87% to 98%
as the concentration of catalyst was increased from 0.0003 mol
(Table 4). This shows that the catalyst concentration was one

Table 2 - Effect of catalyst. Table 4 - Effect of catalyst loading.

Catalyst Selectivity to mandelic acid (%) Catalyst amount (mol) Seleetivity to mandelic acid (%)
No catalyst 0 0.0003 87
PEG 400 61.3 0.0005 92
PEG 600 80 0.0007 98
PEG 4000 98 0.0009 98

Benzaldehyde 0.01 mol, chloroform 0.01 mol, undecane 0.0025 mol, Benzaldehyde 0.01 mol, chloroform 0.02 mol, undecane 0.0025 mol,
hexane 20cm^ (made up), PEGs 0.00093mol, NaOH 0.16mol, water hexane 20 cm^ (made up), NaOH 0.16 mol, water 20 cm^ (made up),
20 cm^ (made up), temperature 55 C, speed of agitation 1000 rpm, temperature 55 C, speed of agitation lOOOrpm, under N2 atmo-
under N2 atmosphere. sphere.
 C H E M I C A L E N G I N E E R I N G RESEARCH A N D D E S I G N 9 O ( 2 0 I 2) 1281-1291 1285

10

iO 20 30 40 50 60
30 40 Time (min)
Time (min)
Fig. 7 - Effect of mole ratio. Benzaldehyde 0.01 mol,
Fig. 6 - Effect of catalyst loading. Benzaldehyde 0.01 mol, undecane 0.0025 mol, hexane 20 cm^ (made up), PEG4000
chloroform 0.02 mol, undecane 0.0025 mol, hexane 20 cm^ 0.0007 mol, NaOH 0.16 mol, water 20 cm^ (made up),
(made up), NaOH 0.16 mol, water 20 cm^ (made up), temperature 55 C, speed of agitation 1000 rpm, under N2
temperature 55 C, speed of agitation 1000 rpm, under N2 atmosphere. , 1:1; ^, 1:2; A, 1:3.
atmosphere. , 3 x 10"* mol; D, 5 x 10"'* mol; ,
7 X 10-* mol; A, 9 x lO"* mol.
3.8. E^ect of nitrogen atmosphere
of the important parameters in L-L-L PTC reaction for control-
ling the selectivity. Reaction under inert (nitrogen) atmosphere was also one of
the factors to improve the selectivity towards mandelic acid.
3.6. Effect of mole ratio Under similar conditions experiments were conducted under
N2 atmosphere and under normal atmosphere. There were no
Effect of mole ratio of benzaldehyde to chloroform was stud- changes in conversion (Fig. 9). However, the selectivity was
ied in the range from 1:1 to 1:3 under similar conditions. As reduced to 90% under normal atmosphere due to formation of
the mole ratio was increased from 1:1 to 1:2, there was suf- benzoic acid by air oxidation (Table 7).
ficient change in conversion as well as selectivity; however,
there was only a marginal change between 1:2 and 1:3 mole
ratios (Fig. 7 and Table 5). Thus, the desired conversion and
selectivity could be achieved with the mole ratio of 1:2.

3.7. Efecto/NaOH concentration

Effect of NaOH concentration was studied by varying the con-

centration of NaOH in the range from 0.08 mol to 0.19 mol
under similar conditions. When the concentration of NaOH
was increased from 0.08 mol to 0.16 mol, the selectivity
towards mandelic aeid was increased from 88% to 98% (Fig. 8
and Table 6). At NaOH concentrations at and beyond 0.16 mol,
there was no change in conversion and selectivity. NaOH
forms a complex with PEG and appears in the middle phase,
which was the reaction phase.

Table 5 - Effect of mole ratio.

Mole ratio Selectivity to mandelic acid (%) 10 20 30 40 50 60
1:01 91 Time (min)
1:02 98
1:03 98 Fig. 8 - Effect of NaOH concentration (mol). Benzaldehyde
0.01 mol, chloroform 0.02 mol, undecane 0.0025 mol,
Benzaldehyde 0.01 mol, undecane 0.0025 nnol, hexane 20 cm^ (made hexane 20 cm^ (made up), PEG4000 0.0007 mol, water
up), PEG4000 0.0007 mol, NaOH 0.16 mol, water 20 cm^ (made up), 20 cm^ (made up), temperature 55 C, speed of agitation
temperature 55-'C, speed of agitation lOOOrpm, under N2 atmo-
1000 ipm, under N2 atmosphere. 0,0.08; , 0.1; A, 0.12; A,
sphere.
0.14; O, 0.16; , 0.189.
1286 C H E M I C A L E N G I N E E R I N G RESEARCH A N D D E S I G N 90 ( 2 0 I 2) 1281-1291

displacement reaction takes place with NaOH to produce a-

ehloro aeid (Seheme 2).

3.10. Kinetic model for L-L-L PTC reaction

The overall reaction is:

RCHOHCOOH (1)

Diehloroearbene formation in the third phase is an instanta-

neous reaetion.
Transport of RCHO from organie phase into the third liquid
phase with equilibrium eonstant Ki is given by:

(2)
^RCHO

10 20 30 50 60
Transport of the complex PECNaOHn(H2O) from aqueous
Time (min) phase to third phase with equilibrium constant K2 is as fol-
lows:
Fig. 9 - Effect of Nitrogen atmosphere. Benzaldehyde
0.01 mol, chloroform 0.02 mol, undecane 0.0025 mol,
K2 C*
hexane 20 cm^ (made up), PEG 4000 0.0007 mol, NaOH
0.16 mol, water 20cm'' (made up), temperature 55 C, speed PEGNaOH(nH2O)
of agitation 1000 rpm. 0, with nitrogen; , without nitrogen. (3)

3.9. Reaction mechanism The equilibrium reaetion of benzaldehyde with diehloroear-

bene to form a-ehloro aeid in the third phase with equilibrium
The proposed reaetion mechanism is shown in Seheme 2. eonstant K3 is represented by:
PEC forms a eomplex with NaOH as PECNaOH(nH2O), making
a separate third phase. Chloroform from the organic phase K3

is transferred to the third phase, where the reaetion occurs (4)

^RCHO
to form diehloroearbene. This diehloroearbene formed in the
third phase subsequently reacts with benzaldehyde, whieh The conversion of a-ehloro aeid (aCA) to mandelie aeid
is transferred from the organie phase to the middle (third) (MA)occurs in the third phase.
phase, thus produeing the desired produet mandelic aeid
which is then transferred to the aqueous phase. Benzaldehyde
reacts with dicloroearbene to form dichloro oxirane which (5)
on rearrangement forms a-chloro acetyl chloride and further

(6)
Table 6 - Effect of NaOH concentration.
dNlMA _ wthuth^th
NaOH Cone, (mol) Selectivity to mandelic acid (%) pth
(7)
dt
0.08 88
0.1 93 The eritieal analysis of the rate data suggested that the eon-
0.12 93 version of benzaldehyde follows a first order reaction. The
0.14 94 rate of formation of mandelie aeid will be equal to the rate
0.16 98
0.189
of disappearance of benzaldehyde.

Benzaldehyde 0.01 mol, chloroform 0.02 mol, undecane 0.002S mol, dNMA h (th
hexane 20 cm^ (made up), PEG4000 0.0007 mol, water 20 cm^ (made dt dt CA^PEGNaOH(nH2O)
up), temperature 55 C, speed of agitation 1000 rpm, under N2 atmo-
sphere.
- V K '^3>-RCHO"-pEGNaOH(nH2O) (9)

Table 7 - Effect of Nitrogen atmosphere. (10)

N2 effect Seleetivity to mandelie aeid (%)
98 porg org - (11)
Without N2 90 -RCHO

Benzaldehyde 0.01 mol, chloroform 0.02 mol, undecane 0.0025 mol,
hexane 20 cm^ (made up), PEG 4000 0.0007 mol, NaOH 0.16 mol,
water 20 cm^ (made up), temperature 55 C, speed of agitation
where A is benzaldehyde (RCHO). NA and NMA are moles of A
and mandelie aeid, respectively. V^i, V**^ and V'^ are the vol-
umes of the aqueous, third and organic phases, respectively.
The total numbers of moles of A at any time are distributed
 CHEMICAL ENGINEERING RESEARCH AND DESIGN 9O ( 2 0 12) 1281-1291 1287

Organic phase
CHCI.,

Chloroform
Benzaldehyde

CHCI3+

PEGNa*CCl3(nH2O) Na'CI (nHp)+ CCI2:

CI XI

CCU:

Dichloro oxirane a chloro acetyl chloride

OH CI

Catalyst rich third phase

Mandelic acid
ex Chloro acid

PEGNa PEG, NaCI

Mandelic acid Aqueous phase

CCI2:

Benzaldehyde
a Chloro acid
Scheme 2 - Reaction mechanism.

between the organic and third phase and none in the aqueous + (NA - N'^^)V*Ki = N A V * K I -I- (17)
phase.
(18)
(12)

pth (19)
K (13)
(20)

(14)
N' org
(21)
(15)

(22)
(16)
1288 CHEMICAL ENGINEERING RESEARCH AND DESIGN 9O (2OI2) 1281-1291

The total mass balance for the eatalyst (NPEG tot. the total moles
added initially) whieh is distributed in the aqueous and third
phases is as follows:

"th
'PEGNaOH(?iH2O)

(23)

fth _ pth I pth pth

^PEG PEGNaOH(nH2O) ^ ^

Let the amount of eatalyst in the third phase be denoted by

pth

rth
PEGNaOH(?iH2O) PEGNaOH(nH2O) 10
(25) 20 30 40 50 60
7 = ;;
Time (min)

rth Fig. 10 - Effect of temperature. Benzaldehyde 0.01 mol,

PE
(26) chloroform 0.02 mol, undecane 0.0025 mol, hexane 20 cm^
(made up), PEG4000 0.0007 mol, NaOH 0.16 mol, water
20 cm^ (made up), speed of agitation 1000 rpm, under N2
pth pth (27) atmosphere. 0, 35 C; , 45 C; A, 55 C.

Eq. (24) beeomes.

^PEGNaOH(nH2O)
Let a = V*/V"g and /; = V (35)

N A N p E G t o t
"th
(28) dt

NpEGtot
CPEGNaOH(nH2O) (37)
"th dt
PEGNaOH(nH2O)

(29) = rtfe*K K (^ '^ -^A) (38)

dt '^ ^ ^voi-g-f KiVth) ((I/K2)

N peg tot - ^ = feapp(l - (39)

C
-PEGNaOH(nH2O) where
th
^PEGNaOH(nH2O) -PEGNaOH(nH2O)

(40)

Integrating Eq. (39) gives,

ln(l - XA) = (41)

("th
j ^PEGNaOH(nH2O)
C*
. ^ t h ^PEGNaOH(iiH2O)
N, peg tot -
K2 ;; ^^^^ feapp is apparent first order rate eonstant.
In order to verify the proposed meehanism of the reaetion
and validate the model, the effeet of temperature on the rates
(32)
of the reaction was studied.

("th
3.11. E//ect 0/ temperature
^PEGNaOH(nH2O) (33)
The effect of temperature on the rate of reaction was stud-
Substituting the appropriate variables from Eqs. (22) and ied under otherwise similar conditions from 35 C to 55 -C. In
(33) in Eq. (10), the following rate is obtained. all cases, the third phase was maintained. With increase in
temperature, the conversion and rate of reaction increased
dNA (Fig. 10). The selectivity increased from 78% at 35 =C to 98%
at 45 C and thereafter it remained constant (Table 8). Eq. (41)
(34) was fitted to the experimental data at different temperature
 CHEMICAL ENGINEERING RESEARCH AND DESIGN 9 O ( 2 0 I 2 ) 1281-1291 1289

-10.2
Table 8 - Effect of temperature.
Temperature Selectivity to mandelic acid (%)
-10.4
35 78
45 95
55 98
-10.6
Benzaldehyde 0.01 mol, chloroform 0.02 mol, undecane 0.0025 mol,
hexane 20cm^ (made up), PEG4000 0.0007mol, NaOH 0.16mol,
water 20 cm^ (made up), speed of agitation 1000 rpm, under N2 2 -10.8
atmosphere.

-II
2.5

-11.2

1.4

0.003 0.0031 0.0032 0.0033

1/T, K '

Fig. 12 - Arrhenius plot.

y = M4\
R' = 0.954

10 20 30
Time (min)

Fig. 11 - Kinetic plot. Benzaldehyde 0.01 mol, chloroform

0.02 mol, undecane 0.0025 mol, hexane 20 cm^ (made up),
PEG4000 0.0007 mol, NaOH 0.16 mol, water 20 cm^ (made
up), speed of agitation 1000 rpm, under N2 atmosphere. ,
35C;O, 45C; A, 55C.

(Fig. 11) showing that the reaction follows the first order kinet-
ics. The Arrhenius plot was made to determine the apparent
activation energy as 11.06 kcal/mol (Fig. 12). Thus, it is an 0 O.I 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 I

intrinsically kinetically controlled reaction. Experimental fractional conversion

Fig. 13 - Parity plot between experimental and simulated

3.12. Validation 0/the model fractional conversion.

To verify the proposed mechanism of the reaction and validate

the model, the above model was fitted to the collected data.
Kinetic model accounting for the observed rates were fitted
using Polymath 6.0 software. This model was used to simulate
the conversion profile, which are in good agreement with the
experimental conversion profile (Fig. 13). The kinetic parame-
ters determined by the above method are given in Table 9.
Table 9 - Kinetic parameters.
Kinetic parameters
K2
K3
k* (cmVmolesmin)
3.13. Reusability 0/catalyst
Agitation was stopped after completion of the experiment and
the three phases were allowed to separate. The aqueous and
organic phases were removed and only the eatalyst-rieh mid-
dle phase was reused with fresh aqueous and organic phases
with the reactants. The catalyst was reused four times after
the fresh run. Fig. 14 shows that even in the fourth time reuse
there was only small difference in conversion at the end of
90 min. For the first and second reuse, the selectivity was
Values maintained almost as 98% (Table 10). During the fourth reuse,
0.755
the selectivity was reduced to 83%. Because of the loss of cat-
25.09 alyst, the amount of third phase was reduced compared to the
32.85 fresh run and hence it affected the selectivity. It is important
195.6 to maintain the same volume of the third phase which in turn
0.97 is related to the amount of catalyst and phase equilibria.
1290 C H E M I C A L E N G I N E E R I N G RESEARCH A N D D E S I G N
10 20 30 40
Time (min)
Fig. 14 - Reusability of catalyst. 0, Fresh; , first reuse; A,
second reuse; G, third reuse; , forth reuse.
T^ble 10 - Reusability of catalyst.
Catalyst reusability Selectivity to mandelic acid (%)
Fresh 98
First reuse 97
Second reuse 93
Third reuse 93
Fourth reuse 83
4. Conclusions
L-L-L PTC leads to process intensification and enhanced selec-
tivity in comparison with L-L PTC which was exemplified
in the case of preparation of mandelic acid from benzalde-
hyde and dichlorocarbene using PEG4000 as the catalyst.
Separation of catalyst was very easy and it could be reused
several times. Waste minimization was achieved in two ways
in this process, namely, the catalyst rich middle phases was
reused several times which reduces the waste. There is 98%
selectivity to mandelic acid due to the creation of the third
phase. The creation of third phase allows minimization of
waste with 98% selectivity, thereby improving profitability
and environmental benefits. Effects of various parameters
were studied. A kinetic model accounting for the observed
rates was proposed and validated against experimental data
using Polymath 6.0 software.
Acknowledgements
GDY acknowledges support from Darbari Seth Professor
Endowment and R.T. Mody Distinguished Professor Endow-
ment as well as J.C. Bose National Fellowship from DST-GOl.
PRS thanks University Grant Commission, India for financial
support as Senior Research Fellow.
References
Brandstorm, A., 1978. Principles of phase transfer catalysis by
quaternary ammonium salts. Adv. Phys. Org. Chem. 15,
267-330.
Chen, J., Spear, S.K., Huddleston, J.G., Rogers, R.D., 2005.
Polyethylene glycol and solutions of polyethylene glycol as
green reaction media. Green Chem. 7, 64-82.
90 ( 2 0 I 2) 1281-1291
Goto, S., Ido, T., Susaki, T., Jin, G., 2000. Characteristics of third
phase for reaction of benzyl chloride with sodium sulfide in
phase transfer catalytic system. Appl. Catal. A 201,139-143.
Hsiao, H.C.W., Kao, S.M., Weng, H.S., 2000. Synthesis of n-Butyl
phenyl ether by tri liquid phase catalysis using poly(ethylene
glyeol)-600 as a catalyst. 1. Analysis of factors affecting the
formation of a third liquid phase. Ind. Eng. Chem. Res. 39,
2772-2778.
Hsiao, H.C.W., Weng, H.S., 2001. Synthesis of n-butyl phenyl ether
by tri liquid phase catalysis using poly (ethylene glycol)-600 as
a catalyst. Analysis of factors affecting the reaction in a bateh
reactor. J. Chem. Technol. Bioteehnol. 76, 959-965.
Huang, C.C., Yang, H.H., 2005. Kinetics for benzoylation of sodium
4-acetylphenoxide via third-liquid phase in the
phase-transfer catalysis. Appl. Catal. A 290, 65-72.
Ido, T., Yamamoto, T., Goto, S., 1997. Third-phase catalytic activity
of halogen exchange reactions in phase transfer catalytic
system. Chem. Eng. Sei. 52, 3511-3520.
Jarrouse, M.J., 1951. The influence of quaternary ammonium
chloride on the reaction of labile hydrogen compounds and
50 60 chlorine-substituted chlorine derivatives. C.R. Acad. Sei. Ser.
232, 1424-1426.
Jen, P., Lin, Hing, H., 2005. Kinetics for etherification of sodium
o-nitrophenoxide via third-liquid phase-transfer catalysis. J.
Mol. Catal. A: Chem. 235, 293-301.
Jin, G., Ido, T., Goto, S., 1999. Synergetic effect of two kinds of
phase transfer catalysts in third phase for dehydro
halogenation of 2-Bromooetane. J. Chem. Eng. Jpn. 32,417-423.
Jin, G., Ido, T., Goto, S., 2001. Effect of third-phase properties on
benzyl-n-butyl ether synthesis in phase transfer catalytic
system. Catal. Today 64, 279-287.
Jin, G., Ido, T., Goto, S., 2003. Rate enhancement effeet of third
liquid phase on dibenzyl ether production in
solid-liquid-liquid phase transfer catalytic system. Catal.
Today 79-80, 471-478.
Makosza, M., 1975. TWo-phase reactions in the chemistry of
carbanions and halocarbenes: a useful tool in organic
synthesis. Pure Appl. Chem. 43, 439^62.
Makosza, M., 2000. Phase-transfer catalysis. A general green
methodology in organic synthesis. Pure Appl. Chem. 72,
1399-1403.
Naik, S.D., Doraiswamy, L.K., 1998. Phase transfer catalysis:
chemistry and engineering. AIChE J. 44, 612-646.
Neumann, R., Sasson, Y, 1984. Mechanism of base-catalyzed
reactions in phase-transfer systems with poly(ethylene
glycols) as catalysts. The isomerization of allylanisole. J. Org.
Chem. 49, 3448-3451.
Sasson, Y, Neumann, R. (Eds.), 1997. Handbook of Phase Transfer
Catalysis. Blaekie Academic and Professional, London.
Sharma, M.M., 2002. Strategies of conducting reactions on a small
scale. Selectivity engineering and process intensification. Pure
Appl. Chem. 74, 2265-2269.
Starks, CM., 1971. Phase-transfer catalysis. I. Heterogeneous
reactions involving anion transfer by quatemary ammonium
and phosphonium salts. J. Amer. Chem. Soc. 93,195-199.
Starks, CM., Liotta, C, Halpern, M., 1994. Phase Transfer
Catalysis: Fundamentals and Perspectives. Chapman and
Hall, New York.
Wang, D.H., Weng, H.S., 1995. Solvent and salt effects on the
formation of third liquid phase and the reaction mechanisms
in the phase transfer catalysis systemreaction between
n-butyl bromide and sodium phenolate. Chem. Eng. Sei. 50,
3477-3486.
Yadav, G.D., 1975. Phase transfer catalysis 9, 16-25.
Yadav, G.D., 2004. Insight into green phase transfer catalysis. Top.
Catal. 29,145-161.
Yadav, CD., 2005. Phase transfer catalysisunderstand basics
better for a profitable industrial practice. Chem. Ind. Digest.,
49-61 (July).
Yadav, CD., Badure, O.V., 2007. Role of third phase in
intensification of reaction rates and selectivity:
phase-transfer catalyzed synthesis of benzyl phenyl ether.
Ind. Eng. Chem. Res. 46, 8448-8458.
 C H E M I C A L E N G I N E E R I N G RESEARCH A N D D E S I G N
Yadav, CD., Badure, O.V., 2008. Seleetive engineering in
0-alkylation of m-eresol with benzyl ehloride using
liquid-liquid-liquid phase transfer eatalysis. J. Mol. Catal. A:
Chem. 288, 33^1.
Yadav, CD., Bisht, P.M., 2004. Seleetivity engineering in
multiphase transfer catalysis in the preparation of aromatic
ethers. J. Mol. Catal. A: Chem. 223, 93-100.
Yadav, CD., Bisht, P.M., 2005. Fundamental analysis of microwave
irradiated liquid-liquid phase transfer eatalysis (MILL-PTC):
Simultaneous measurement of rate and exehange equilibrium
constants in selective 0-alkylation of p-tert-butylphenol with
benzyl chloride. J. Mol. Catal. A: Chem. 236, 54-64.
Yadav, CD., Desai, N.M., 2005. Selectivity engineering of phase
transfer catalyzed alkylation of 2-hydroxy aectophenone:
enhancement in rates and seleetivity by creation of a third
liquid phase. Org. Proeess. Res. Dev. 9, 749-756.
Yadav, CD., Desai, N.M., 2006. Novelties of low energy microwave
irradiation in tri-phase vis-a-vis bi-liquid phase-transfer
catalysis in selective etherification of aromatic phenols. Catal.
Commun. 7, 325-330.
Yadav, CD., Lande, S.V., 2005a. Liquid-liquid-liquid phase transfer
catalysis: a novel and green concept for seleetive reduction of
substituted nitroaromatics. Adv. Synth. Catal. 347,
1235-1241.
Yadav, CD., Lande, S.V., 2005b. Novelties of reaction in the middle
liquid phase in tri-liquid phase transfer catalysis: kinetics of
selective 0-alkylation of vanillin with benzyl ehloride. Appl.
Catal. A 287, ii^l-ilS.
9 O ( 2 0 1 2) 1281-1291 1291
Yadav, CD., Lande, S.V., 2007. Intensifieation of rates and
selectivity using tri-liquid versus bi-liquid phase transfer
catalysis: insight into reduction of 4-nitro-o-xylene with
sodium Sulfide. Ind. Eng. Chem. Res. 46, 2951-2961.
Yadav, CD., Motirale, B.C., 2010. Selective oxidation of methyl
mandelate to methyl phenyl glyoxylate using
liquid-liquid-liquid phase transfer catalysis. Chem. Eng. J.
156, 328-336.
Yadav, CD., Naik, S.S., 2001. Novelties of liquid-liquid-liquid
phase transfer catalysis. Alkoxylation of
p-chloronitrobenzene. Catal. Today 66, 345-354.
Yadav, CD., Sharma, M.M., 1981. Kinetics of reaction of benzyl
chloride with sodium acetate/benzoate: phase transfer
catalysis in solid-liquid system. Ind. Eng. Chem. Process. Des.
Dev. 20, 385-390.
Yadav, CD., Jadhav, Y.B., Sengupta, S., 2003. Selectivity
engineered phase transfer catalysis in the synthesis of fine
chemicals: reactions of p-ehloronitrobenzene with sodium
sulphide. J. Mol. Catal. A: Chem. 200, 117-129.
Yadav, CD., Jadhav, Y.B., 2003. Cascade engineered phase transfer
catalysis: a novel concept in green chemistry. Clean Teehnol.
Environ. Poliey 6, 32^2.
Yadav, CD., Reddy, CA., 1999. Kinetics of the n-butoxylation of
p-chloronitrobenzene under liquid-liquid-liquid phase
transfer catalysis. Ind. Eng. Chem. Res. 38, 2245-2253.
Yang, H.M., Li, C.C, 2006. Kinetics for synthesizing benzyl
salicylate by third-liquid phase-transfer catalysis. J. Mol.
Catal. A: Chem. 246, 255-262.
Copyright of Chemical Engineering Research & Design: Transactions of the Institution of Chemical Engineers
Part A is the property of Elsevier Science and its content may not be copied or emailed to multiple sites or
posted to a listserv without the copyright holder's express written permission. However, users may print,
download, or email articles for individual use.