CRSI Life Time Achievement Award

1
CRSI Life Time Achievement Award 7th February,
2004, I.I.T., Kanpur
Symphony of Chemistry Chemical Engineering
Professor M. M. Sharma, FRS Emeritus Professor of
Eminence Mumbai University Institute of Chemical
Technology
2
Removal of Carbonyl Sulphide from Mixtures of
Gases
Sharma M.M., Transactions of The Faraday Society,
1965, 61(4) 681-688,
3
Linear Free Energy
Sharma M.M., Transactions of The Faraday Society,
1965, 61(4) 681-688,
4
Reaction Between CS2 and Amines
Reaction Involving Primary Amines
Reaction Involving Secondary Amines
P. J. Kothari M. M. Sharma Chemical
Engineering Science, 1966, 21, 391-396.
5
Reaction of Amines with Alkene Oxides
Which may be followed by
6
Kinetics of Very Fast Reaction

• The reaction of solute A with the reactant B
  occurs entirely in the film
• while the solute is diffusing
• Diffusion and chemical reaction occur
  simultaneously.
• Concentration of species B is practically the
  same as that in the bulk liquid phase
• Conditions
• 1.A reacts entirely in the film
• 2.No depletion of B in the film
• Specific rate of absorption

7
In the case of alkanolamines the advantage of
using faster reacting amines, based on a simple
theory, was brought out particularly for
relatively very slow reacting carbonyl
sulphide. Thus, the use of methylaminoethanol in
place of diethanolamine can provide an increase
in rate of absorption by a factor exceeding 4 for
carbonyl sulphide.
8
Stirred Cell
The study of kinetics of gas-liquid reactions
has become delightfully simple through the use of
stirred cell, where the gas liquid interface is
flat and the interfacial area is thus known
9
Stirred Cell
10
MODEL STIRRED CONTACTOR
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Measurement of Rate Constant Without Knowing
Solubility and Diffusivity

• The theory of gas absorption accompanied by
  pseudo first order reaction provides an
  interesting basis to approach this problem
• Consider the following expression
• Provided k1t gt1
• A plot of RA vs 1/t allows, from the slope and
  intercept, the value of k1to be calculated
  without knowing A and DA
• Examples
• N2O4 in water ( Kramers and coworkers, 1963 )
• CO2 in carbonate buffer solutions with
  catalysts
• (Sharma and Dankwerts, 1963)

13
Measurement of Solubility in Reacting Systems
Solubility of Phosgene in
Water Reaction occurs with half life below 0.05
sec ., Measurement through absorption in
laminar jet apparatus
Provided k1t ltlt 1 From the measured values of
RA and the estimated values of DA, the value of
solubility A can be calculated
14
The problem of simultaneous absorption and
reaction of two gases A B, where the reaction
of a result in the formation of B, is considered.
Analytical equations are derived to predict the
decrease in the rate of absorption of the gas B
due to the presence of the gas A. It is shown
that under certain conditions, no B will be
absorbed, even when the concentration of
dissolved B in the bulk liquid is zero.
Ramachandran Sharma, Chemical Engineering
Science (1970) 25 1743-1749.
15
Figure Showing the Partial Pressure Ratio above
which no CO2 will be Absorbed as a Function of
Temperature
16
Measurement of True Mass Transfer Coefficients
and Interfacial Area by Chemical Methods
The use of chemical method for measuring
interfacial area in liquid-liquid systems was
pioneered in the author's laboratory and was even
quoted in the column Indicators for tomorrow of
the famous journal Industrial and engineering
chemistry (anonymous, 1966) Westerterp
et at. (1963)deployed the chemical method for
measuring interfacial area in gas-liquid
mechanically agitated contactors and indeed the
1963 paper in Chemical Engineering Science
became a citation classic. The system employed
was air oxidation of aqueous alkaline solutions
of sodium sulphite, catalysed by copper and
cobalt ions
17
In the case of Gas-Liquid contactors, bubble
colums, etc., the theory of mass transfer
accompanied by pseudo-zero order reaction, as in
the case of absorption of oxygen in aqueous
alkaline solutions of sodium dithionite, has been
used imaginatively by Juvekar Sharma (1973) to
measure both a and kLa and hence true kL, under
otherwise uniform conditions.
18
Absorption of CO2 in Primary and Secondary
Alkanolamines
Only if primary equilibrium is set up, the
carbamate is formed. But, if secondary
equilibrium is allowed to be attained, then we
have bicarbonate and carbonate ions and this
leads to different free amine concentrations and
different equilibrium partial pressure of CO2
under otherwise uniform conditions
19
The careful selection of a proper amine is
central to newly announced process of the Dow
chemical company for selective absorption of lean
SO2 from flue gases where a large amount of CO2
is present and some O2is also present Here, a
tertiary amine ,containing an OH group, would be
welcome to provide the desired selectivity and to
inhibit the oxidation of amine sulphite which
gives a product which cannot be thermally
regenerated
20
Absorption of Nitrous Gases Gas Phase Liquid
Phase
21
Absorption of NO x
The recent work has brought out the intricacies
of simulation and modeling in this system,
particularly with respect to absorption in
aqueous solutions of NaOH, and for lean NOx,
remove NOx to acceptable levels but also to
realise high selectivity for saleable sodium
nitrite Over 95 selectivity for sodium nitrite
can be realised by proper manipulation of the
operating parameters which could be mapped only
after a detailed simulation
22
Use of Model Contactors For The Design Of
Industrial Equipment
For a variety of complicated systems, involving
gas-liquid reactions with a part occurring in the
bulk, simultaneous absorption of two gases, one
gas- two reactants, etc. It was possible to
demonstrate the versatility and utility of model
contractors The model contactor need not be
geometrically similar to the industrial
contractor under simulation
23
Mass Transfer with Chemical Reaction Involving
Microphases
Microphases consists of very small, dispersed
phase particle/droplets whose size ( saylt10
micron) is much smaller than the diffusional
length scale (typically gt 30 micron) of the rate
limiting, diffusing solute. The continuous phase,
comprising the microphase , is referred to as the
microheterogeneous medium. Typical microphases of
practical importance are micelles, microemulsion
droplets (not seen by naked eye), an emulsified
second phase, fine particles of reactants such as
calcium hydroxide or catalysts like activated
carbon , colloidal particles, fine bubbles etc.
24
Physical Picture for Mass Transfer With Chemical
Reaction in the Presence of a Microphase
25
The real impact of this novel ideal was to be
seen in the flue gas desulphurisation where very
lean SO2 is absorbed in aqueous slurries of lime
or limestone the enhancement could be by a factor
of seven The following simplified equation holds
when gas absorption or extraction of a solute is
accompanied by instantaneous reaction and
sparingly soluble particles constitute a
microphase Thus, RA becomes directly
proportional to dp, as for small size particles ,
ap is inversely proportional to dp and kSL also
varies inversely with dP
26
Intensification of Heterogeneous Reactions
Through the use of Microphases

• Use of emulsified second liquid phase
• (Alkaline hydrolysis of solid esters Mehra,
  Pandit and Sharma 1987)
• Microemulsion media for conducting solid-liquid
  reactions
• (Alkaline hydrolysis of solid esters Mehra,
  Pandit and Sharma, 1987and
• Bhagwat and Sharma, 1988)
• Hydrotropes as solubility enhancing agents
• (Alkaline hydrolysis of solid esters Mehra,
  Pandit and Sharma 1987)
• Colloidal product as catalyst
• (Absorption of hydrogen sulfide in iodine/ iodide
  solutions Mehra and Sharma,1987)

27
Intensification of Heterogeneous Reactions
Through the use of Microphases
Sparingly soluble reactant in the form of fine
particles ( Ramachandran Sharma, 1969) Fine
Carbon particles as catalysts (Oxidation of
aqueous sodium sulfide solutions Pal, Juvekar
Sharma, 1982) Fine carbon particles for
facilitated transport (Oximation reactions
Janakriaman Sharma, 1985) Micelles as
catalytic agents (Alkaline hydrolysis of esters,
oximation of cyclododecanone Janakiraman
Sharma, 1985)
28
Some catalyst particles can be conveniently
manipulated to constitute a microphase. The
industrially important system of air oxidation of
aqueous solutions of dilute and concentrated
solutions of sodium sulphide, as encounted in
pulp and paper industries, proved to a good
example. A carefully planned set of experiments
with that Powerful stirred cell with a flat
Gas-Liquid interface, now in a pressurized vessel
( magnetically stirred autoclave), allowed the
experiments to be checked with the theory, which
in turn was improved along with the experimental
work (Pal et al. 1992) This was an important
example of a slurry reactor with resistances in
parallel rather that the ubiquitous case of
resistances in series. The case of reaction
occurring entirely in the diffusion film probably
originated at Bombay.
29
Effect of Particle Size on the Specific Rate of
Absorption at 80OC (14.5 cm i. d. contactor)
Concentration of Na2SO4 0.29 mole/l Reaction
Volume 1400 cm3 Speed of stirring 38 rev/min
Ionic strength of the solution 0.99 gion/l
A Darco G 60 make ( Average particle size 4.33
micron) B Engelhard cut 30 make ( Average
particle size 1.70 micron) D Cparse particle
obtained from G 60
Ref S. K. Pal, M. M. Sharma V. A. Juvekar
Chemical Engineering Science 1982, 37(2) 327-336
30
The idea of facilitated transport by using the
microphase particles which exhibit strong
adsorption for the sparingly soluble solute was
experimentally verified with delightfully simple
systems of alkaline hydrolysis of sparingly
soluble solid esters and oximation of solid
cyclododecanone. Further, the smallest particle
microphase is through micelles which are 30-40A0
and the above systems could be conveniently
employed to test the theory with micelles and
with micro-emulsion. ( Janakiraman Sharma, 1982)
31
Alkaline Hydrolysis of TDF in Two Phase
System Enhancement in Rate by Fine Carbon
Particles
32
Absorption of H2S in Iodine Solutions
The specific rates of absorption of H2S in Iodine
solution may exceed the theoretical maximum rates
by factors as high as 8. This unusual effect
appears to be due to the interaction of H2S and
sulfur which carries the dissolved H2S into the
bulk liquid. A two parameter model incorporating
H2S interaction and sulfur agglomeration explains
the results sufficiently well.
33
Effect of Isopropanol Sodium Sulfate and Excess
Potassium Iodide on the Specific rate of
absorption of H2S into Iodide solution in a batch
stirred cell Experimental Versus Calculated
rates, Bo0.1M speed of stirring 1.5rps.
34
Simultaneous Absorption of Olefin and Chlorine in
Water in the Presence of Microphase

• Basic idea
• Preferential partitioning of the species
  (chlorine, olefin ) into the microphase can lead
  to enhanced rates of absorption of both the gases
• Presence of microphase can give rise to a higher
  yield of byproduct dichloroalkane.

Reaction scheme
(a) In continuous phase
(b) In microphase
35
Effect of Microphase Hold-up on the Yield of
Dichloride
36
Desorption of HOCl From Strong Alkaline Solution
Region I
Region II
Region III
Interface
First Reaction Plane
Second Reaction Plane
C?
Bo
1
-
HClO(C)
OH
C
HClO(C )
Concentration
-
Cl ( C)
C
-
ClO (E)
A
-
-
Eo
Cl (C)
ClO (E)
Cl2(A)
Co
?1
?2
0
Distance
37
Conversion of Single Liquid Phase Reaction into
Two Phase Liquid-Liquid Reaction
This may be triggered by an improvement in
conversion, yield, the use of cheaper reagents
and the ease of heat removal. This strategy can
also be useful in biotransformations. Thermodynam
ically, equilibrium conversion in two phase
systems can be markedly higher than in a single
phase liquid system.
38
Engineering Through Conversion of Single Liquid
Phase Reaction into Liquid Liquid (or Even
Solid-Liquid ) Mode
Advantages Higher conversions compared to that
obtained in either of the two phase alone Use of
cheaper chemicals, adoption of milder conditions,
avoidance of filtration from toxic mixtures,
avoidance of exothermic runway conditions etc.
Examples Esterification and Trans-esterification
reactions 1,6-Hexanedol to its mono-bromo
derivative Epoxidation of olefinic
compounds Hydrolysis for marking an intermediate
for the drug primaxin
39
Hofmann Reaction
Cyclohexane carboxamide
Cyclohexyl isocyanate
40
Phase Transfer Catalysis
In the manufacture of triaryl phosphates by the
reaction of POCl3 with sodium salts of
substituted phenols, phase transfer catalysis may
be conveniently used in an elegant, room
temperature process with cheap solvents, giving
yields gt90.
Aliquot
3ArONa POCl3
(ArO)3PO 3NaCl
H2O/CHCl3 or CH3
In the recent past, this strategy has been
adopted to make the corresponding
phosphorothionates by using PSCl3
Ref V. K. Krishankumar M. M. Sharma
Synthesis 1983, 7, 557-559.
41
Benzyl Chloride Reactions for CEPTC and SEPTC
Processes
42
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43
A novel Method of Recovering Phenolic Substances
from Aqueous Alkaline waste Streams
A novel two-phase method has been proposed to
remove as well as to recover phenolic materials
from aqueous alkaline waste streams. This is
based on the phenolic materials with substances
such as benzyl chloride, p-toluenesulfonyl
chloride, etc. dissolved in water-immiscible
solvent as toluene in the presences of phase
transfer catalyst. In a continuous
reactor-settler arrangement it was possible to
bring down the phenolic content of an aqueous
alkaline steam from 2035 ppm to 45 ppm with
phenol recovered as phenyl benzoate.
44
Conversion of Homogeneous Acid Catalyzed Reaction
to Heterogeneous Systems with Cationic Ion
Exchange Resins as Catalyst
The changeover is very attractive as no washing
of the corrosive homogeneous catalyst is
required. In some cases, ion exchange resins may
even exhibit higher rates at Equilibrium
Acidity, compared to homogeneous catalysted
reaction ,due to higher distribution coefficient
of the reactants in the resin phase. Better
selectivities are often realised. A variety of
etherification and esterification reaction are
now widely practised with cationic ion exchange
resins.
45
Homogeneous vs Heterogeneous Systems

• Higher rates can be realised with cation
  exchange
• resin catalysts
• Examples
• Dehydration of tert -butanol
• Reaction of linear ketones and alcohols to give
• ketone acetals
• Addition of alcohols to olefins
• Etherification of ethylene and propylene
  glycols
• with isobutylene
• Etherification of phenols with isobutylene

46
Ion Exchange Resins as Catalysts

• Facilitate continuous operation and obviate
  liquid effluent
• problems
• Perfluorosulfonic acid based resins e.g.
  Nafion can withstand
• temperatures upto 200oC
• High proportions of the para- isomer can be
  obtained in the
• alkylation of phenol with olefins (e.g.
  Isobutylene, alpha-
• methyl styrene, etc.)

47
The etherification of phenol and substituted
phenols, such as o-chlorophenol, o-ethyl phenol
and guaiacol ? ? -naphthols with isobutylene
and isoamylene was studied. The etherification
was carried out in the presences of an acidic ion
exchange resin, Amberlyst 15, as a catalyst and
in the temperature range 5 to 30oc . The relative
rate of etherification of phenol /o-chlorophenol,
o-ethylphenol/ guaiacol and ? ? - naphthol were
measured. A novel separation strategy, based on
selective etherification and subsequent cracking
of tert-butyl /tert-amyl ethers, was successfully
applied for the close boiling phenols and
naphthols. The purification of ? - naphthol
containing ? -naphthol impurity through the
selective acid catalyzed C-alklyation of ? -
naphthol with isobutylene and isoamylene was also
found to be successful
48
Reaction Scheme for Alkylation of DPA with AMS
49
Separation Through Reaction
Effect of solvent on separation efficiency
2,6-Xylenol pKa 0.62b.p.202.8
p-Cresol pKa 10.28 b.p. 202
KB/KA 2.18
Solvent Dp-C D2,6-X Dp-C/D2,6-X a Benzene 12 73 0
.16 13 Cyclohexane 0.8 10 0.08 28
Inert solvent is a better choice for this
separation
50
Separation of m-/p-Cresols By Dissociation
Extractive Crystallization
OH
OH
CH
3
CH
3
Isopropyl ether
H
N
N
H
p-Cresol precipitates as complex with piperazine
from organic solution in 100 pure form. Yield
depends on solvent and temperature.
51
Reaction in Distillation Column Reactor
Synthesis of Acetals/ Removal of Formaldehyde
Synthesis of Cyclohexyl Esters
52
Oxidation of Cyclic Alkenes
53
Importance of Continuous Processes

• Advantages
• Stirred reactors and small tubular reactors
• Provide high heat transfer coefficients
• Have low inventory
• Withstand high pressures
• Can be easily stopped
• May be operated adiabatically without problems of
  runway conditions by introduction of precooled
  reactant streams

54
Role of Mixing, including Micromixing
A common fallacy in bench scale experiments is to
use a round bottom glass flask which has poor
mixing and scale-up is not possible It is
essential to use a fully-baffled cylindrical
reactor with a provision of proper baffles and a
turbine impeller The Role of micromixing is
important when mixing time and reaction time are
comparable A striking example is bromination of
resorcinol where even at high resorcinol to
bromine mole ratios dibromo product may dominate
instead of the monobromo due to poor
micromixing The problem gets aggravated when we
have two phase and three phase systems.
55
Micromixing
The role of micromixing becomes significant when
the half-life time of reaction and the half life
time of micro mixing are comparable. e. g.
bromination of resorcinol, where disubstituted
products can predominate even with high
resorcinol/ bromine ratios. Strong need to study
the effect of micromixing on selectivity in
multiphase reaction
56
Static Mixers
57
Pipe
Phase A
Phase B
Phase A and B To Separator
Helical Baffle
Horizontal Pipeline Mixer (Static Mixer)
58
Improved Mixer Designs
Optimize introduction of reactants
Upper pitched blade to increase circulation

• Circulation time increases with
• scale this is harmful for reaction
• in which micro mixing effects
• are important

Static Mixers
A

• Reliable scale-up
• Plug flow

R
B
Micromixing Effects in Scale- up
59
Merck
Ours
A
Static mixer
A
R
R
B
B
60
Ethos of Process Development (PD)
The PD group is charged with the responsibility
of producing inherently safe, reliable,
reproducible, robust processes at low cost for
new and existing products, with full respect for
quality standards and safety, health and
environment (SHE). Chemists have different
perspective as they tend to get swayed by the
elegance of chemistry rather than real cost
effectiveness coupled with an intrinsically safe
process. The ubiquitous round bottom flask in
which reactions are invariably carried out at the
first go can do a lot of disservice.
61
A recent example by Dale et al. of Pfizer (2000)
of Sildenafil (Viagra, a blockbuster drug)
dramatize the difference between the medicinal
chemistry (MC) and the process development (PD)
route the former was a linear with nine linear
steps. The PD was a four-step route. The
consumption, in kilolitre, of toluene with MC
route (MCR) was 39 and only 2.8 in the PD route
ethyl acetate consumption was 19 vs. 10.7. It is
really striking to note that the MCR had an
overall yield of 7.5 but the commercial route
has a yield of 75.8. Thus telescoping of steps
has a major impact on the overall process on
account of capital investment and variable cost.
62
A more recent example, which received the
Presidential Green Chemistry Award in USA, is
that of Pfizers Sertraline HCl (Zoloft)- an
antidepressant drug.The original three-step
process was converted into a single step. This
resulted in the solvent requirement to almost 10
of the original value of about 2,40,000 litres
per ton of Sertraline.
63
Dow has telescoped the four-step conversion of
papaverine hydrochloride to landanosoline
hydrobromide to one step. The overall yield of
glaucine from papaverine was tripled to 35.