Liquid-liquid-liquid phase transfer catalysis: A novel and green concept for selective reduction of substituted nitroaromatics

Article abstract of DOI:10.1002/adsc.200404364

The selective reduction of nitroaromatics to the corresponding amines is an important transformation since many aromatic amines exhibit biological activities and find a multitude of industrial applications, being intermediates for the synthesis of dyes, pharmaceuticals and agrochemicals. A variety of nitroaromatics dissolved in organic solvents was reduced by using aqueous sodium sulfide, and tetrabutylammonium bromide (TBAB) as the phase transfer catalyst by choosing appropriate concentrations which resulted in three immiscible liquid phases. Compared to L-L PTC, the L-L-L PTC offers much higher rates of reaction, better selectivities and repeated use of catalyst. The selectivities for the desired products were 100%.

Full text of DOI:10.1002/adsc.200404364

FULL PAPERS
Liquid-Liquid-Liquid Phase Transfer Catalysis: A Novel and
Green Concept for Selective Reduction of Substituted
Nitroaromatics
Ganapati D. Yadav,* Sharad V. Lande
Department of Chemical Engineering, University Institute of Chemical Technology, University of Mumbai, Matunga,
Mumbai – 400019, India
Fax: (þ91)-22-2410-2121, (þ91)-22-2414-5614, e-mail: gdyadav@yahoo.com, gdyadav@udct.org
Received: November 30, 2004; Accepted: April 11, 2005
Abstract: The selective reduction of nitroaromatics to choosing appropriate concentrations which resulted
the corresponding amines is an important transforma- in three immiscible liquid phases. Compared to L-L
tion since many aromatic amines exhibit biological ac- PTC, the L-L-L PTC offers much higher rates of reac-
tivities and find a multitude of industrial applications, tion, better selectivities and repeated use of catalyst.
being intermediates for the synthesis of dyes, pharma- The selectivities for the desired products were 100%.
ceuticals and agrochemicals. A variety of nitroaromat-
ics dissolved in organic solvents was reduced by using Keywords: amines; liquid-liquid-liquid PTC; nitroaro-
aqueous sodium sulfide, and tetrabutylammonium matics; phase transfer catalysis; reduction; triphasic
bromide (TBAB) as the phase transfer catalyst by catalysis
Introduction
from the environmental point of view is that the homo-
geneous catalyst is normally not recovered and reused.
The selective reduction of substituted nitroaromatic The bulk cost of catalyst ranges from US $ 2.00 to
compounds has been a major challenge in synthetic or- 400.00 per kg, crown ethers being the most expensive
ganic chemistry.[1] Stoichiometric reagent-based proc- and hence catalyst recovery or reuse is most desirable.
esses are very selective towards reduction of the nitro The separation of phase-transfer catalysts from the reac-
function but generally not ecofriendly.[2] Catalytic hy- tion mixture can be achieved by extraction, distillation
drogenation using molecular hydrogen is less chemose- and adsorption. Extraction needs an additional solvent
lective than the stoichiometric methods; therefore the that has to be distilled off to recover the catalyst. Distil-
catalysts have to be poisoned or tailored to achieve the lation becomes feasible only if the catalyst has a lower
desired selectivity.[3–7] The use of homogeneous iron boiling point than the reactants, products and the sol-
complexes for the hydrogenation of nitro compounds vents. Otherwise, distillation is an energy intensive proc-
has been also reported.[8]
ess to recover catalysts from dilute solutions. In the case
Phase-transfer catalysis (PTC) has been applied to of adsorption, the catalyst has to be eluted using a sol-
over 600 processes in a variety of industries such inter- vent. Since the quantities of the catalyst used are small,
mediates, dyestuffs, agrochemicals, perfumes, flavours, they do not contribute much to the expensive product
pharmaceuticals and polymers.[9–11] Yadav[12] has dis- cost. The catalyst is usually not recovered but removed
`
cussed recently the advantages of multiple phase vis-a- by washing the organic phase with copious quantities
vis the conventional two-liquid PTC and demonstrated of water which are disposed to the effluent treatment
how all three-phase PTC reactions are by definition ex- plant as an end-of-the-pipe approach for pollution pre-
cellent examples for the practice of green chemistry. vention. Although milder reaction conditions and use
PTC has been quite successful for C-, N-, O- and S-alky- of cheap solvents in L-L PTC improve the economics,
lation in fine chemical industries, beside in dehydrohalo- PTC need to be practised from the green chemistry per-
genations. The effluent treatment problems associated spective such as solventless synthesis and catalyst reuse,
with soluble L-L PTC requiring a large quantity of water and an overall strategy of waste reduction.
to wash the organic phase has hampered exploitation of
As compared to L-L PTC, in liquid-liquid-solid (L-L-S)
PTC in many other bulk industries. The applications of PTC, the expensive catalyst is bound to a solid matrix
PTC thus are practically confined to the synthesis of like a polymeric resin or clay and can be recovered.
low-volume and high-cost, specialty, agro and pharma- However, there is a substantial reduction in rates of re-
ceutical chemicals. The main drawback of L-L PTC actions due to associated diffusion limitations. Capsule
Adv. Synth. Catal. 2005, 347, 1235–1241
DOI: 10.1002/adsc.200404364
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membrane phase-transfer catalysis (CMPTC) involves a the selective reduction of p-nitroanisole to p-methoxy-
catalyst anchored to a capsule membrane which is recov- aniline with sodium sulphide under L-L PTC.
ered and reused. CMPTC has been exploited in our lab-
So here we have developed an efficient methodology
oratory in a number of reactions of industrial impor- for selective reduction of different nitroaromatics with
tance.[13,14] Furthermore, a third, catalyst-rich, phase sodium sulphide using L-L-L PTC leading to 100% se-
can be created between the aqueous and organic phases lectivity for the amine (Scheme1).
containing the reactants whereby the reaction occurs in
the middle phase through a proper balance of liphophi-
licity, hydrophilicity, interfacial tension, solubilities, Results and Discussion
phase equilibria and density; and this constitutes the
so-called liquid-liquid-liquid (L-L-L) PTC. It was ob- Several experiments were done to understand the criti-
served that when the amount of catalyst exceeds a criti- cal parameters for maintaining three immiscible phases
cal value the rate of reaction increases sharply. Indeed, at 808C under agitation. The L-L-L system depends on
we have found in a number of reactions that not only the nature of the substrate and solvent, type and amount
the rates of reaction but also the selectivity can be en- of the catalyst, composition of the aqueous phase and
hanced dramatically thereby reducing reaction time the temperature. Thus, there is a range over which three
and separation costs.[15] The third liquid phase is the immiscible liquid phases are created. For each system
main reaction phase for the phase-transfer catalyst to this was verified at the operating conditions. The compo-
catalyse the reaction and the recovery and reuse of the sition was such that the fidelity of the three separate
catalyst is easier since it forms an immiscible third liquid phases was maintained at all temperatures between 50
phase. The advantages of L-L-L PTC over L-L PTC are: and 808C both during intense agitation and without ag-
(i) enhanced reaction rates and milder reaction con- itation. When the agitation was stopped, the reaction
ditions such as lower temperature, (ii) easier catalyst re- mass had droplets of organic phase covered by a thin
covery and reuse, (iii) suppression of by-products and in- dark film in a pool of aqueous phase, which was a contin-
creased yields and selectivity with respect to the desired uous phase (Figure 2), and which would slowly disinte-
product, and (iv) the catalyst need not be bound to a sol- grate and the three phases would emerge out as shown
id support. Hence the attendant difficulties of reduced in Figure 1. Even after cooling the mixture to room tem-
activity and mechanical strength associated with L-L-S perature, the phases would retain their identity.
PTC can be avoided. This is the major advantage of L-
The rate of reaction depends on the speed of agitation
L-L PTC over L-L-S PTC. The L-L-L PTC requires up to a certain value since it affects the rates of mass
more catalyst (PTC) but since it is recovered and reusa- transfer from the aqueous and the organic phases to
ble, it is an excellent way of reducing waste. The rates are the middle catalyst-rich phase. We studied the effect of
very high and thus reduce the reaction times and reactor speed over a range of 1000–1800 rpm for each system.
volumes, leading to economic advantages.
There was an increase in the rate of reaction when the
The reduction of nitroaromatics to the corresponding speed was increased from 1000 to 1500 rpm. However,
amines can be affected by aqueous inorganic sulphides there was no further increase in the rate beyond
and polysulphides and the rates of these biphasic reduc- 1500 rpm. Thus, a speed of agitation of 1500 rpm was
tions are amenable to intensification under PTC. There chosen.
are quite a few reports on phase-transfer-catalysed sul-
Although the catalyst is soluble in both phases under
phide reductions in the literature. The reduction of p-ni- normal PTC, depending on the type of catalyst, its distri-
trotoluene[16] with sodium sulphide and bisulphide to se- bution coefficient is affected by the presence of salts and
lectively obtain p-toludine is also reported. Reductions the type of solvent. The aqueous phase is saturated by
of o-chloronitrobenzene[17] and p-chloronitrobenzene[18] sodium sulphidethereby partitioningthe catalystprefer-
with sodium sulphide/disulphide have been carried out entially in the middle phase and the solubility of the cat-
by using polar solvents such as dimethylformamide alyst phase in the organic phase is very low due to the use
and N-methylpyrrolidone (NMP) with good yields of
the corresponding products. Uncatalysed[19] and
PTC[20] reductions of nitroaromatics such as m-nitro-
chlorobenzene, m-dinitrobenzene and p-nitroaniline
by aqueous solutions of sodium monosulphide and di-
sulphide have been reported. The phase-transfer-cata-
lysed[21] reduction of aromatic nitro compounds such
as nitrobenzene, m-dinitrobenzene, o-chloronitroben-
zene, p-chloronitrobenzene to the corresponding mono-
amino compounds with sodium sulphide, with tetrabuty-
lammonium bromide (TBAB) as the phase-transfer cat-
alyst has also been investigated. Yadav et al.[22] reported Scheme 1.
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Mechanism of L-L-L PTC
Since the stoichiometryof the overall reaction suggests a
complex mechanism, the following steps were envis-
aged. S is a multivalent species and thus different mono-
valent anions, such as HSꢀ, HSOꢀ, HSO2ꢀ, and HSO3ꢀ,
can be formed sequentially which are capable of produc-
ing ion-pairs with single quaternary cations more readily
than those multivalent anions which require ion-pairing
with multiple quaternary cations. In the aqþueous phase
S2– reacts with OHꢀ to form HSꢀ. Thu s Q HSꢀ which
is readily formed in the aqueous phase is transferred to
the middle (third) phase where several consecutive
and parallel reactions occur as shown in Figure 3. The
contribution to the overall rate of the reaction can be
shown by three mechanisms. Since it is known that the
creation of a third catalyst-rich phase enhances the
rate of the reaction, it should be the main reaction phase
into which the substrate from the organic phase and the
nucleophile from the aqueous phase are transferred.
However, the aqueous phase reagent in the form of
the ion-pair can also transfer across the third phase-or-
ganic phase interface and there is a possibility of some
reaction occurring in the organic phase. Similarly, the re-
action can occur near the interface between the third
and the aqueous phase on the aqueous phase side due
to the very limited solubility of the substrate in the aque-
ous phase. It should be pointed out, however, that the
substrate would have already reacted in the third phase.
Thus the contribution of the reaction in the aqueous
phase is negligible.
Figure 1. Top phase: organic phase, middle phase: catalyst-
rich phase, bottom phase: aqueous phase.
Figure 2. L-L-L PTC: Locale of reaction phases. Type III is
the main contributor to the overall rate of reaction. The nor-
mal L-L PTC is type II. The rate enhancement in type III is
compared with that in type II.
Since the third phase is generated beyond the critical
concentration of the catalyst, the locale of the PTC reac-
of toluene as a solvent. Because of this more of catalyst is tion occurring in the organic phase in the biphasic condi-
available in the middle phase and is subsequently reused tion is shifted to the third phase. Depending on the
for further reaction. This can be seen in Figure 1. Waste amount of catalyst beyond the critical value, the contri-
minimization is a theme of green chemistry. Thus, there bution to the overall rate of reaction would be either to-
is reduction in waste, due to reuse of catalyst, enhance- tally by the reaction in the third phase or in the organic
ment of rates by an order of magnitude and a decrease phase. The thickness of the third phase also matters
in reaction times and thus an increase in profitability.
since the reactive species have to diffuse from the organ-
ic phase to third phase as an ion-pair.
Just below the critical concentration for third phase
formation, the biphasic reaction has the maximum con-
version. In the absence of any mass transfer limitation,
Overall Stoichiometry
The reduction reaction of nitroarenes by negative diva- the reaction is kinetically controlled and occurs in the or-
lent sulphur (sulphide, sulphahydrate, and polysul- ganic phase. However, after the formation of the third
phide) is called the Zinin reduction. The overall stoichi- phase, there is a likelihood of mass transfer resistance
ometry of this reaction using sulphide as reducing agents setting in due to the higher rates of reaction in the third
is as follows:
phase which deplete the concentration of the reactants
in the third phase.
The model of the reaction shows that the quaternary
cation of the catalyst, Qþ, pairs up with different anions
for its reaction with the substrate but most of it remains
in the form of QþHSꢀ in the reaction medium and
makes possible a cycle of the catalyst in that form among
Obviously this reaction involves a complex mecha- the phases.
nism and the rate-determining step has to be evaluated.
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Figure 3. Mechanism of reduction of nitro- to aminoaromatic compounds under L-L-L PTC.
Reusability of Catalyst
Conclusions
The novelty of our work is the reusability of the catalyst. Total waste-free process, although ideal, are not realisa-
After completion of the experiment, the reaction mix- ble in practice and thus waste minimisation, by any and
ture was allowed to settle and which formed clearly all means, fits into the themeof green chemistry. An end-
three distinct phases. The upper organic phase contain- of-pipe solution as a regulatory approach has been
ing the product was removed. The catalyst reusability adopted by several industries assuming that the technol-
studies could be done in two ways, either by using the ogy is perfect, economical and only the effluent should
catalyst-rich phase alone or by using the catalyst-rich be treated. Phase-transfer catalysis is a popular techni-
and the aqueous phases together.
que having around 600 industrial applications but with
very few attempts to improve the process from environ-
mental perspectives. The L-L PTC reactions are con-
ducted under milder conditions, using cheaper solvents
at much faster reaction rates and improved selectivities
Reuse of Third Catalyst-Rich Phase Only
The third phase was separated from the previous experi- to the desired products and are thus by definition waste
ment and then reused by adding fresh aqueous and or- reduction processes. However, the phase-transfer cata-
ganic phase reactants. In this method the third phase lyst is not recovered but treated as a waste since the
was used three times starting with the fresh use. As ex- quantities are very small and do not contribute much
plained earlier, there is a distribution of catalyst in the to the expensive product. L-L PTC can be elegantly
catalyst-rich third phase and the organic phase and modified to convert it into L-L-L PTC, to recover and
aqueous phase. Since both the aqueous and organic reuse the catalyst and also to enhance selectivity.
phases were freshly used, there was a loss of the catalyst
with the discarded organic and aqueous phases. There-
fore, there is once again a distribution of catalyst availa-
ble from the third phase to the organic phase which re-
duces the volume of the third phase and hence the rates
Experimental Section
Reaction Procedure
of the reaction.
All reactions were studied in a 5.0 cm i.d. fully baffled mechan-
ically agitated contactor of 100 cm3 total capacity, which was
equipped with a 6-blade-turbine impeller. The reactor was
kept in a constant-temperature water bath. Typical runs were
Reuse of Catalyst and Aqueous Phase
conducted by taking sodium sulphide 0.15 mole in water and
Thus, the second method was adopted wherein the aque-
made up to 25 cm3. To this 0.0075 mol of TBAB catalyst was
ous phase and the catalyst phase were reused five times
added. The organic phase comprised 0.0075 mole of nitroaro-
and the organic phase along with the aqueous reactants
was replenished every time. The reusability was found to
be good up to 4 uses.
matics, made up to 15 cm3 with toluene. All the typical reac-
tions were carried out at 808C and 1500 rpm under variable
times. This the composition of the reaction mixture created
three distinct and stable phases at the operating conditions.
The said composition of the reaction mixture created three dis-
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Table 1. Reduction of substituted nitroaromatics with sodium sulphide under L-L and L-L-L PTC.
No. Reactant
Product
Enhancement factor[a] Time t [min] Yield [%] after time t
L-L PTC[b] L-L-L PTC[c]
1
2
4.8
4.0
20
45
34.2
32.5
98.6
98.6
3
4
5
6
7.1
3.4
3.1
4.3
60
45
45
30
38.6
43.5
35.6
37.5
98.4
98.7
96.8
97.5
7
8
3.2
7.0
45
60
42.5
35.4
96.7
95.7
9
3.8
3.7
45
45
41.7
44.3
97.8
98.4
10
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Ganapati D. Yadav, Sharad V. Lande
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Table 1 (cont.)
No. Reactant
Product
Enhancement factor[a] Time t [min] Yield [%] after time t
L-L PTC[b] L-L-L PTC[c]
11
12
6.0
4.6
60
60
28.6
33.5
96.7
95.4
The yield is the amount of product formed relative to the amount of substrate reacted. The yield is equal to selectivity here.
[a]
Enhancement factor is defined as the ratio of the initial rate of reaction under L-L-L PTC to that under L-L PTC (before
the third phase is created).
[b]
L-L PTC: nitroaromatics 0.0075 mol, sodium sulphide 0.1125 mol, TBAB 0.0025 mol, toluene 15 cm3, water 25 cm3, speed of
agitation 1500 rpm, temperature 808C.
L-L-L PTC: All same as for L-L PTC except TBAB 0.0075 (reusability of catalyst).
[c]
tinct and stable phases at the operating conditions (Figure 1).
The analysis of all reactions was done by GC (Chemito 8610)
using a stainless steel column (3.25 mmꢁ2 m) packed with a
liquid stationary phase of 10% SE-30, with a flame ionisation
detector.
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[11] E. V. Dehmlow, S. S. Dehmlow, Phase Transfer Catalysis,
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Isolation of the Product
The isolation of product is very simple. At the end of the reac-
tion, the organic phase, which contained the corresponding
amine and toluene, was washed with copious quantities of wa-
ter to remove any traces of catalyst and the solvent was distilled
under vacuum to get a pure product. All the products were also
confirmed by GC-MS. All the compounds reported are shown
in Table.1.
Acknowledgements
G. D. Yadav acknowledges Darbari Seth Endowment for sup-
porting the Chair. S. V.Lande acknowledges CSIR-NMITLI
for awarding JRF.
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