Journal of Electroanalytical Chemistry, 375 (1994) II-27
17
Review
The electrochemistry
of L-cystine and L-cysteine
Part 2 *: Electrosynthesis
of L-cysteine at solid electrodes
T.R. Ralph
Johnson Matthey Technology Centre, Blount’s Court, Sonning Common, Reading RG4 9NH (UK)
M.L. Hitchman
Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow, Gl 1XL (UK)
J.P. Millington
EATechnology, Capenhurst,
Chester CHl 6ES (UK)
F.C. Walsh **
Applied Electrochemistry Group, Chembtry Department, Universiry of Portsmouth, St. Michael’s Building, White Swan Road, Portsmouth,
PO1 2DT (UK)
(Received 23 November 1993; in revised form 22 February 1994)
Abstract
The industrial uses of L-cysteine are summarized and alternative synthesis routes are critically considered. The electrosynthesis of
r_-cysteine free base and the acid salt form of the product at solid electrodes are reviewed. The performance of several flow-through
parallel plate cell designs is shown to be very dependent upon the electrolysis conditions. The role of current density and the rate
of mass transport in the cells is discussed. It is seen that the choice of electrode material, the flow conditions within the cell, the
provision of turbulence promoters and the operating current density are critical factors in obtaining a high fractional conversion
and a high current efficiency with a reasonable electrolytic power consumption.
-
1. Uses of L-cysteine
The current industrial route to L-cysteine is by the
electroreduction
of L-cystine, usually in acid solution.
The estimated world market for L-cysteine is approximately 1000-1500 tonnes per annum [21, with the high
value product commanding prices from X30 kg-’ [2] for
large up to E55 kg-’ [3] for small quantities. All applications use either the free base or the hydrochloride
l
l
For Part 1, see ref. 1.
* To whom correspondence
0022-0728/94/$7.00
SSDI 0022-0728(94)03408-U
should be addressed.
salt, with L-cysteine hydrochloride preferred in many
instances because of its greater resistance to oxidation.
Indeed, the free base should be converted into the
hydrochloride salt for storage. It will be seen that
electrochemical routes exist for both the acid salt and
the free base. In common with almost all amino acids,
there is no demand for the D-isomer or the racemic
mixture owing to their lack of function in biological
systems. The major application areas are in the foodstuffs, cosmetics and pharmaceutical industries.
L-cysteine is added to wheat flour by the baking and
pasta industry to improve dough flexibility, which improves the baked product and reduces baking time. It
0 1994 - Elsevier Science S.A. All rights reserved
18
T.R. Ralph et al. / Electrochemistry of L-cystine and L-cysteine: Part 2
is the major component of the recipe for the meaty
flavouring used in savoury snacks and pet foods and it
is effective as an antioxidant in natural fruit juices and
other foodstuffs. L-Cysteine and numerous derivatives
exhibit a normalizing effect on skin metabolism and
have a significant effect on hair. For example, they are
used in preparations to treat excess skin lipid production (seborrhoea) and acne, in anti-dandruff shampoos
and, especially in Japan, as a substitute for thioglycolic
acid for less damaging cold wave preparations.
The pharmaceutical industry requires L-cysteine to
produce
N-acetyl-r_-cysteine,
S-carboxymethyl-r_-cysteine and L-cysteine methyl ester, which are used as
mucolytic agents in the treatment of bronchitis and
nasal catarrh. Many other derivatives are employed in
the treatment of hepatitis, respiratory disorders, dermatitis and radiation damage. L-Cysteine is itself required as an antidote to snake venom. The application
areas and uses of L-cysteine have been extensively
reviewed elsewhere [4,5].
2. Alternative synthesis routes
There are a number of alternative synthesis routes
to r_-cysteine in addition to the electrochemical reduction of L-cysteine, but none compete for large-scale
manufacture.
2.1. Microbial production
A fermentation method for r_-cysteine has not been
established but enzymatic methods have recently been
developed in the laboratory [6]. These procedures are
still some years away from evaluation as industrial
processes but they are of interest since the L-isomer is
produced in a one-step reaction.
2.2. Chemical synthesis
Many chemical routes to r_-cysteine are available
[7-91. With the exception of the chemical reduction of
L-cystine, however, all are expensive, multi-step processes which produce a racemic mixture that must be
optically resolved to give the desired L-isomer and the
b-isomer for racemization and recycling. The addi-
TABLE 1. A typical product specification for L-cysteine hydrochloride [11,12]
Minimum assay
Specific rotation at [crlD at 25°C
(20gdm-3in5moldm-3HCI)
Other amino acids
Loss on drying
Residue on ignition (as sulphate)
Heavy metals
98.5% w/w
+ 5.50 to + 6.50
< 1% w/w
< 0.5% w/w
< 0.1% w/w
< 10 ppm
tional processes represent a significant economic disincentive.
Chemical reduction of L-cystine is normally performed by catalytic hydrogenation, usually with tin in
hydrochloric acid [lo]:
RSSR + 2M-H,,,,
-
2RSH + 2M
(1)
The process compares favourably with electrochemical
reduction for laboratory preparations but is inferior for
industrial production. Toxic waste must be disposed of
and the metal recycled.
3. Electroreduction of L-cystine
Several hundred tonnes per annum of L-cysteine, as
the hydrochloride or less frequently the sulphate salt,
are produced by the electrochemical reduction of Lcystine in the corresponding mineral acid catholyte.
The resultant acid salt, which is produced by simply
evaporating the catholyte, may be converted into the
free base in a separate electrodialysis step with an
anion-exchange membrane. The major manufacturers
include Degussa, Diamalt, Ajinomoto, Tanabe, Takeda,
Nipon Chemical and Drug and Isochem.
The reactant, L-cystine, is obtained by extraction
from acid hydrolysates of keratines from hair, feathers,
hooves, horn and wool. Extraction is based on the low
solubility of the disulphide at neutral pH. This technology suffers from a high energy requirement, objectionable odours and intractable wastes. Consequently, raw
material costs are significant, being around f15 kg-’ at
present [2]. Together with the high value of r_-cysteine
and the high product purity demanded by the application areas for the thiol (e.g. a typical product specification is shown in Table 1 [11,12]), this places an essentially quantitative material yield and selectivity as the
most important performance criteria.
Tables 2 and 3 summarize the available electrosynthesis conditions cited in the literature for the reaction
RSSR + 2H++ 2e- -
2RSH
(2)
As early as 1955, Rambacher [13] patented the electrochemical reduction of r_-cystine hydrochloride to
L-cysteine hydrochloride in almost quantitative yield at
tin and copper cathodes. With copper cathodes tin
chloride was added to the catholyte.
Suzuki and Karube [14] investigated the reduction at
a series of cathodes at all of which L-cystine was readily
reduced to L-cysteine. Zinc gave a quantitative chemical yield and the highest current efficiency (100%). The
cathode corroded in the acidic catholyte, however,
contaminating the product with zinc(H) ions. There
was a suggestion that adsorbed, atomic hydrogen, produced during the corrosion process, aided the reduc-
Pt
Pb
Pb
Pb
cu
Stainless
steel
Unspecified
type of threedimensional
carbon
High area
carbon felt
6F-S6
(Electrosynthesis
Company)
Parallel plate
batch recycle
Parallel plate
batch recycle
DSA
0.42 M RSSR
8.6 M aq. NH,
0.42 M RSSR
2.3 M HCl
0.7 M RSSR
2.7 M HCl
0.1-0.4 M RSSR
1.0-1.5 M HCl
0.24 M RSSR
lMHC1
0.25 M RSSR
3Maq.NH3
0.75 M (NH,),CO,
0.25 M RSSR
1.5 M HCl
0.1 M RSSR
lMHC1
0.5 M RSSR
2.7 M HCl
Catholyte
3 M H,SO,
4 M H,SO,
0.05 M H *SO4
2.7 M HCl
1 M H,SO,
1.5 M HCl
3.35 M (NH,),CO,
1.4 M HCl
lMHC1
Anolyte
1.5
0.5
0.4
0.2
0.1
0.2
78
17
N/A
N/A
80-670 N/A
150
50
40
20
10
N/A
Not applicable
Not applicable
Not applicable
Not applicable
ms-’
0.4
78
17
600
(cell voltage
4.4-4.8 V)
1500
(cell voltage
6.4-7.8 V)
2500
(cell voltage
6.2-8.4 V)
5000
100-400
(cell voltage
3v
700
600-900
(cell voltage
5 V)
700
(cell voltage
2.5 V to 3.5 V)
250
500
300-600
j/
Ame
96.6
96.5
94.6
96.5
94.5
92
591
60-70
50-60
93.5
92.4
87.8
81.5
76.1
46
N/A
100
50
19
14
12
N/Ah
%4”
96.6
94
< 91
95.6
95.0
90.4
84.0
78.4
99.8
92
100
100
70
65
58
100
%f?pa
31,32
30
28
20-2?
18,19
17
16
14
13
Ref.
amount of L-cysteine reduced). See Table 3 for
N/A
N/A
80-670 N/A
N/A
30
1.55
Not applicable
Not applicable
Not applicable
Not applicable
10-6
m’s_l
10-s
m3sm1
ms-’
Anolyte
Catholyte
Flow rate
of r_-cysteine reduced); % 4 = 100 (amount of L-cysteine formed/theoretical
Cationic
membrane
Cationic
membrane
Cationic
membrane
Cationic
membrane
Cationic
membrane
Anionic
membrane
Porcelain
diaphragm
Porcelain
diaphragm
Diaphragm
Separator
a % 0p = 100 (amount of L-cysteine formed/amount
definitions of figures of merit. j = current density.
b N/A: data not available.
Electrocell AB
parallel plate
batch recycle
(100 cm2)
3-D
carbon
Pb
Pb
Parallel plate
batch recycle
(500 cm21
Parallel plate
batch recycle
(20 cm’)
Stainless
steel
Stainless
steel
Pt
Pt
Graphite
Anode
Tank cell
(80 cm21
Beaker cell
(120 cm21
Sn. Cu
Tank cell
(2 cm21
Beaker cell
(120 cm2)
Zn
Pb
Ag
CU
Pb
Cathode
Cell design
(cathode area)
TABLE 2. Synthetic studies of the electrochemical reduction of L-cystine to L-cysteine
T.R. Ralph et al. / Electrochemistry of L-cystine and L-cysteine: Part 2
20
tion. Corrosion of lead, silver and copper cathodes was
not reported during the short duration (typically 6 h)
experiments. Current losses were attributed exclusively
to hydrogen evolution, with higher current efficiencies
being obtained at high hydrogen overpotential cathodes such as lead. During electrolysis, L-cystine reduction and hydrogen evolution consumed protons. The
resultant decrease in the acid concentration of the
catholyte was promoted by the use of an anion-exchange membrane, which prevented protons being
transferred from the anolyte to the catholyte. It was
claimed this lowered the time required for product
work-up. Suzuki and Karube [14] examined alkaline
electrolytes but there was a considerable loss of both
amino acids, due not only to oxidation and decomposition reactions (see Part 1 of this review ‘1 but also
from migration and diffusion of the negatively charged
amino acid molecules into the anolyte compartment.
The poor performance in alkaline media was confirmed by Hasaka 1151 and Mizuguchi [16]. Hasaka
found for electrolysis at a lead cathode at a low current
density of 100-300 A me2 the yield of L-cysteine was
only approximately 75% in various alkaline media.
Similarly, Mizuguchi, using a lead cathode at a current
TABLE 3. Cumulative figures of merit for reduction of L-cystine at various cathodes
Cell design
Parallel plate
Batch recycle
(100 cm’) a
Cathode
Mercury-plated
copper
Pb
Ti
Sll
C
18% Cr-8% Ni
stainless steel
cu
Ni
MO
DEM
batch recycle
(1750 cm2) b
Parallel plate
batch recycle
(20 cm*) ’
Ti
Porous,
three-dimensional
carbon
i/
A m-’
Xd
%e,e
%f#Jf
PST
g/
kg mm2 h-’
100
0.26
0.26
0.99
0.26
0.24
0.99
0.29
0.26
0.99
0.23
0.24
0.99
0.28
0.24
0.98
0.24
0.25
0.99
0.26
0.24
0.98
0.22
0.26
0.26
0.22
0.97
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
1.00
94
97.6
65.0
39.0
95.4
58.9
37.0
72.5
65.0
30.7
81.4
38.6
17.6
74.9
32.2
14.6
64.2
33.2
14.7
54.9
32.2
14.6
33.6
10.0
23.2
5.0
73.0
92
-‘A
h/
Ref.
kWhkg-’
2.20
5.82
3.48
2.20
5.26
3.32
1.62
5.82
2.76
1.82
3.46
1.58
1.68
2.88
1.30
1.44
2.98
1.32
1.24
2.98
1.30
0.76
0.90
0.52
0.44
8.32
0.59
1.61
2.88
0.60
1.77
3.03
0.77
1.50
3.27
0.65
2.51
5.58
0.70
2.93
6.64
0.79
2.77
6.46
0.93
2.85
6.49
1.41
8.88
2.08
17.98
0.91
29.17
1.04
24-26
26-27
29
a Platinized titanium anode. Catholyte, 0.7 M RSSR in 2.0 M HCI (Hg/Cu, Pb, Ti) and 0.25 M RSSR in 2.0 M HCl (other cathodes), both at
25°C. Anolyte, 2.0 M HCI. Catholyte and anolyte linear velocities 0.123 m s-l. Expamet PV876 turbulence promoting mesh in the catholyte
channel.
b Platinized titanium anode. Catholyte, 0.77 M RSSR in 2.0 M HCI at 30-40°C. Anolyte, 1.2 M HCl. Catholyte and anolyte linear velocities 0.3 m
s-1.
Three-dimensional carbon anode. Catholyte, 1.0 M RSSR in 2.3 M RSSR in 2.3 M HCl at 45°C. Anolyte, 4 M H,SO,. Catholyte and anolyte
flow rates 1.67 x 10m5 m3 s-r.
d Fractional conversion, X= 1 - (moles r,-cystine consumed/initial moles r_-cystine).
e Material yield, 8, = ((moles of L-cysteine formed/moles of t_-cystine reduced) x 100).
f Current efficiency, 4 = ((moles of L-cystine reduced/theoretical
moles of L-cystine reduced) X 100).
g Space-time yield, p ST = (3.6 X lo3 ZM+/nFA) where Z (A) is the current, M (kg mol-‘) the molar mass and A (mZ) the active electrode area.
h Specific energy consumption for electrolysis, Es = ( -~FE,,,/IU&J),
where E,,, is the cell voltage.
’
T.R. Ralph et al. / Electrochemistry
density of 250 A m-‘, obtained a product yield of only
58% with a current efficiency of 12%. The catholyte
was aqueous 3 mol dmw3ammonia with added ammonium carbonate.
Wong and Wang [17] described the electrochemical
reduction of L-cystine hydrochloride to L-cysteine hydrochloride at stainless-steel electrodes. The process is
not suitable, however, for large-scale manufacture. The
anode would soon corrode and the chlorine (or
hypochlorite) generated at the electrode would tend to
attack and degrade the type of anion-exchange membrane used (i.e. Selemion AMV, Asaki Glass). The
acid salt was converted into the free base by dissolving
in ethanol and adding ammonia solution to pH 6.2.
This simple neutralization procedure gave a product
yield of only 80%. Clearly this purification route is not
competitive with electrodialysis.
A series of Japanese patents [18,19] for Showa
Denko dealt with the manufacture of L-cysteine hydrochloride in a parallel plate electrochemical
reactor
operated in the batch recycle mode. Lead was the
preferred cathode giving at best a chemical yield of
95.6% and a current efficient of 93.5%. From liquid
chromatography, a product purity of better than 99%
was claimed. The importance of catholyte flow rate on
both the chemical yield and current efficiency was
stressed. A high flow rate minimized side-reactions. At
lead electrodes the cathode potential was monitored
during electrolysis and a sharp rise from about - 0.6 V
(vs. SCE) to more negative potentials was associated
with increased hydrogen evolution. Monitoring of the
cathode potential was proposed as a method of determining the moment to terminate electrolysis. Excessive
electrolysis times not only resulted in wastage of energy
but also in reduced chemical yields with the pungent
smell of hydrogen sulphide being noted.
Several papers [20-231 in the Chinese literature
consider essentially the system patented by Showa
Denko. No improvement on lead as a cathode was
reported. At lead electrodes, increasing the electrolyte
flow rate and the current density reduced electrolysis
times.
More recently, the present authors have investigated
the production of r_-cysteine hydrochloride at a wide
range of cathode materials (i.e. mercury plated copper,
lead, titanium, tin, stainless steel, carbon, copper, nickel
and molybdenum) using constant-current
batch electrolysis in a small, divided, parallel plate reactor operated in the batch recycle mode [24-261 (Fig. 1). This
reactor was used rather than small glass “H” cells
which are typically employed in the initial evaluation of
reactor materials for a new electrosynthesis, for two
main reasons. First, it provided conditions, particularly
with regard to rates of mass transport, more closely
ofwzystine and myteine: Part 2
21
resembling those in an industrial scale-reactor, and
second, it allowed long-term tests on electrodes, electrolytes, membranes and other reactor materials to be
made. At each cathode a parametric study of the major
process variables (i.e. current density and catholyte
flow rate) was performed. A simple model was used to
predict the reactant concentration decay during batch
electrolysis. At high reactant levels (short times) the
rate of reduction was under current control and at low
reactant levels (long times) pure mass transport control
ensued. The model was used to characterize the electrosynthesis conditions at each cathode (Table 3).
For all cathodes, the material yield and selectivity
were essentially quantitative, all current losses being
ascribed to hydrogen evolution. Consequently, the effect on the electrosynthesis of varying the current density was well defined. For example, Fig. 2 shows the
performance of a lead cathode and Table 3 provides
data for a range of cathode materials. As the current
density was increased, batch processing times were
reduced (Fig. 2(a)), as reflected by the higher spacetime yields (Fig. 2(b)), although this was partly offset by
a reduction in the current efficiency (Fig. 2(c)), due to
increasing rates of hydrogen evolution which, together
with an increased cell voltage, resulted in a larger and
less favourable specific energy consumption for electrolysis (Fig. 2(d)). The exception to this behaviour was
shown by titanium electrodes, where only a small decrease in current efficiency was observed as the current
density was increased. Consequently, at 500 A rnM2,
Fig. 1. Expanded view of a laboratory parallel plate reactor [25]
showing (a) cell housing (PVC), (b) disc spring compressors, (c)
cathode, (d) glass reservoir containing SCE, (e) PTFE tube salt
bridge for reference electrode, (0 catholyte compartment frame
(PVC), (g) anolyte cell frame (PVC), (h) electrolyte inlet ports, (i)
electrolyte outlet ports, (j) PTFE flexible seal, (k) expanded plastic
mesh turbulence promoter, (1) plastic mesh spacer, (m) Nafion 324
cation exchange membrane, (n) nylon mesh, (0) anode, (p) end-plate,
(q) screw to compress assembly.
T.R. Ralph et al. / Electrochemistry of L-cystine and L-cysteine: Part 2
22
high hydrogen overpotential mercury-plated copper and
lead cathodes were the most efficient substrates but, at
the industrially useful current density of 2000 A rnm2,
titanium was just as proficient. At all three of these
cathodes batches of product met the specification listed
in Table 1. For routine industrial manufacture, however, none was satisfactory. With prolonged usage all
showed stability problems [24] in the acidic catholyte.
The mercury-plated
copper cathode slowly amalgamated, the lead electrode corroded with lead chloride
film formation and, in the case of titanium, hydride
was formed. The net result was a drastic decrease in
current efficiency at all of the electrodes, due to enhanced rates of hydrogen evolution, and at mercuryplated copper and lead cathodes there was also product contamination by toxic heavy metal ions.
The model also made clear the great importance of
efficient rates of mass transport for the process economics. Since the mass transport of r_-cystine hydrochloride controlled the rate of reduction towards the
end of an electrolysis, the use of high catholyte flow
rates and the inclusion of plastic mesh turbulence
promoters in the catholyte channel significantly reduced electrolysis times, thereby improving the cumulative figures of merit at high reactant conversion. For
example, at lead (Fig. 31, increasing the catholyte flow
rate from 0.033 to 0.123 m s-l, in the presence of a
F
turbulence promoter, significantly reduced electrolysis
times (Fig 3(a) and (b)). The result was an increase in
the current efficiency (Fig. 3(c)) and space-time yield
(Fig. 3(d)) values whilst the specific energy consumption for electrolysis was reduced (Fig. 3(e)) at high
reactant conversions. Table 4 shows the cumulative
figures of merit for these electrolyses at a lead electrode, with a fractional conversion close to 99%, such
high conversions being necessary to avoid costly product work-up. The benefit of the higher catholyte flow
rate and the use of an Expamet PV 876 turbulence
promoter in the catholyte channel is clear. At an
electrolyte velocity of 0.033 m s-r, the reactant conversion was below 95% over the duration of the experiments.
The importance of efficient mass transport was highlighted, on a larger pilot scale, by the performance of
titanium cathodes in a dished electrode membrane
(DEM) reactor (Fig. 4) [26,27]. Much improved figures
of merit were obtained at high reactant conversion in
the DEM reactor compared with the small parallel
plate cell using titanium cathodes (see Table 31, because of the higher rates of mass transport in this unit.
This study highlighted [12] that product work-up is
costly and the obvious purification method (dissolution
of the acid salt in water, followed by filtration to
remove undissolved disulphide and evaporation of the
A$:1
0 60
a
'ij
0.45
E
,
0.30 -
0.15 -
'q.;;r.,,
'-7..
“y.,
"~,_
,.
'.
'Lb_
(a>
'9
'P
t “T,,,
08
200
600
Nxl
I
I
t/n%
5.0 ,
0
I
I
I
I
400
200
t /
I
6(X1
I
xtn,
min
Fig. 2. Effect of current density on the reduction of L-cystine hydrochloride at a lead cathode in 2 M HCI [24] in the presence of a plastic mesh
turbulence promoter at a linear catholyte velocity of 0.123 m s-l, showing the time dependence of (a) reactant concentration, (b) space-time
yield, (c) cumulative current efficiency and (d) specific electrolytic energy consumption. Current density: (0) 2000; (m) 1000; (v) 500 A m-‘. (0)
(t,rit, c,,~~), i.e. the point at which the reaction changes from charge transfer to mass transport control. Dashed lines, predicted by model.
T.R. Ralph et al. / Electrochemistry of L-cyst& and L-cysteine: Part 2
”
200
23
8M)
600
t / min
ci,*/ mol dmm3
5.0
0
I
I
Ci,t /
mol dmm3
I
I
I
I
0.2
Ci,t /
0.4
0.6
0.8
mol dme3
Fig. 3. Effect of catholyte flow rate on the reduction of L-cystine hydrochloride at a lead cathode in 2 M HCI in the presence of a plastic mesh
turbulence promoter at 2000 A me2 [24], showing the time dependence of (a) reactant concentration, (b) natural logarithm of reactant
concentration, (c) cumulative current efficiency, (d) space-time yield and (e) specific electrolytic energy consumption. Flow rate: (0) 0.123; (m)
0.066; (v) 0.033 m s- t. (0) (tcrif, c._,~~).
i.e. the point at which the reaction changes from charge transfer to mass transport control. Dashed lines,
predicted by model for flow rates of (1) 0.123, (2) 0.066 and (3) 0.033 m s-l.
TABLE 4. Effect of mass transport on the cumulative figures of
merit a at high reactant conversion for the reduction of r_-cystine
hydrochloride to L-cysteine hydrochloride at a lead cathode [24-261
Catholyte
Empty channel,
u =0.123 ms-’
Expamet PV 876,
u=O.l23ms-’
Expamet PV 876,
u=O.O66ms-l
%X
%8,
%4
psr/
ES/
kg mm2 h-t
kW h kg-’
98
100
28.2
2.52
3.95
99
100
33.8
3.02
3.33
99
100
28.5
2.56
3.92
Basis: parallel plate reactor (100 cm2 active electrode area) operated
in the batch recycle mode; catholyte, 0.7 M RSSR in 2.0 M HCl at
25°C; platinized titanium anode; anolyte, 2.0 M HCl. Current density
2000 A m-‘.
a Figures of merit are defined in Table 3.
filtrate to give pure product) results in oxidation of
L-cysteine hydrochloride to L-cystine hydrochloride.
Workers from Taiwan [28] have also described a
divided parallel plate reactor, operating in the batch
recycle mode, for electrosynthesis of L-cysteine in hydrochloric acid solution. The reactor employed a lead
plate cathode and platinum net anode, with a CMV
(Asahi Glass) cation-exchange membrane. Copper and
stainless steel were examined as alternative cathode
materials but both showed an inferior current efficiency to lead. At lead cathodes, the authors reported
a current efficiency of 91.5% at a current density of
200 A m-*. However, the material yield was only 91%
and a significant level of unreacted L-cystine was found
in the product. No conversion data or concentration vs
T.R. Ralph et al. / Electrochemistry of L-cystine and L-cysteine: Part 2
24
time curves were presented and the cathode area was
not stated. Following concentration and crystallization,
the product was found to contain an average lead
content of 15 ppm, which was slightly higher than the
13 ppm contained in the L-cystine starting material.
However, the authors noted that, by controlling the
start-up and shut-down procedure and ensuring that
the cathode always operated at a reasonably high current density, no significant lead pickup by the product
occurred.
The problems of traditional electrode materials for
the electrosynthesis of the acid hydrochloride and the
problems of chlorine evolution at the anode in hydrochloric acid anolytes have encouraged
alternative
CATHOLYTE
OUT
ANOLYTE
n
OUT
MEMBRANE
CATHODE
ANODE
TURBULENCE
PROMOTER
CATHOLYTE
IN
ANOLYTE
IN
DISHED
ANOLYTE
CATHOLYTE
ANODE
FRAME
FRAME
I
I
I
TURBULENCE
PROMOTER
MEMBRANE
D&ED
CATHODE
(b)
Fig. 4. The DEM cell used for electrosynthesis of L-cysteine hydrochloride, showing the construction of a divided cell. (a) Sectional
view; (b) exploded view.
TABLE 5. Electrosynthesis of L-cysteine at planar and porous
three-dimensional carbon cathodes in a flow-through parallel plate
cell [29]
Type of cathode
%XB
%e,a
%4a
Planar carbon
(in the presence of a
turbulence promoter)
RVC
(40 pores per linear cm)
99
100
38
99
100
91
Catholyte linear velocity 0.12 m s-l. Other conditions as in Table 4.
a Figures of merit are defined in Table 3.
strategies. For example, Walsh et al. [29] have recently
incorporated high surface area carbon cathodes (projected area 1 dm2) into a laboratory filter press cell
which utilizes a Nafion 324 cation-exchange membrane
and an oxygen-evolving DSA type anode. In the case of
a 100 ppi (pores per inch) RVC (reticulated vitreous
carbon) electrode, batch electrolysis times were considerably reduced whilst maintaining high materials yield
and current efficiency values (Table 5).
Sanchez-Can0 et al. [30] have also found that threedimensional carbon electrodes (type unspecified) were
highly efficient for reduction of the disulphide in an
acid environment using a reactor operating in the
batch recycle mode. At a current density of 5000 A
me2 (based on the geometric area) a very high spacetime yield of 29 kg mm2 h-’ was achieved with a
material yield of 94% and a current efficiency of 92%
at 100% conversion. The 6% of reactant not accounted
for is a concern. The low material yield was not addressed by the authors, although prolonged batch electrolysis may have reduced the loss.
The Electrosynthesis Company have explored the
direct electrosynthesis of L-cysteine free base by reduction of L-cystine in an Electrocell AB MP flow cell
[31,32] (Fig. 5). Using a proprietary high surface area
carbon felt cathode and an aqueous ammonia catholyte,
which was nitrogen purged, they claimed, based on the
determination of the L-cysteine concentration, a chemical yield of 94.6% and a current efficiency of 94.6% at
a high current density of 2500 A me2 (Table 6). Evaporation of the solvent under pressure yielded the crude
product (at a maximum purity of approximately 98%
L-cysteine). As discussed, this is not sufficiently pure
for many applications. In contrast with attempts to
purify the acid salt, however, dissolution of the free
base in demineralized water followed by filtration to
remove insoluble material, it was claimed, gave L-cysteine with a purity of 99.6 wt.%. This, however, may
represent an additional costly process step. Moreover,
the more stable hydrochloride salt is easily stored and
is favoured for many applications.
T.R. Ralph et al. / Electrochemistry of L-cystine and L-cysteine: Part 2
In agreement with the findings of Walsh et al. [29]
and Sanchez-Cano et al. [30], the Electrosynthesis
Company have found that the use of three-dimensional
25
TABLE 6. Effect of current density on the electrosynthesis of
L-cysteine free base at a carbon felt cathode in the Electrocell AB
MP flow cell [31]
j/
%X
%dJ
96.6
99.2
96.5
94.6
86.5
95.6
99.2
94.6
94.6
86.5
Ame
600
1000
1500
2500
4000
Projected cathode area 100 cm2, catholyte, 0.42 M L-cystine in 8 M
ammonia solution; catholyte flow rate, 0.28 m3 s-‘; mean linear
catholyte velocity, 0.16 m s-t; cathode-membrane
gap, 5 mm; anode, DSA-0,; anolyte, 3 M H,S04.
100
Q (%I
*
II
a
80 60 .‘1?*...
fluid distrlbutor
!
20
I
0
I
1000
I
I
2000
t
3000
j I A me2
Fig. 6. Current efficiency as a function of current density for L-cystine
reduction at planar and high surface area (felt) carbon electrodes
[31-341. The current efficiencies for the felt and the planar electrodes are reported at 100% and 75% theoretical fractional conversion, respectively. (0) Carbon felt; (01 planar carbon.
(a)
Turbulence Pro
Graphkc Backplate
(b)
Fig. 5. (a) MP model of Electrocell reactor used with (b) a three-dimensional carbon felt cathode for electrosynthesis of L-cysteine free
base.
cathodes (based on carbon felt) resulted in much higher
current efficiencies for reduction of the disulphide
(Fig. 6). This was at least partly due to the much
enhanced rates of mass transport to the cathodes compared with the corresponding planar cathodes [34].
Care must be exercised over the stability of both
L-cystine and r_-cysteine in alkaline catholyte, based
upon previous experience [14-161, even if the electrolyte was nitrogen purged. The specific energy consumption of the Electrosyntheis Company process is
also much higher than typical values for production of
L-cysteine hydrochloride. Cell voltages of 6.2-8.4 V
were measured for production of the free base at a
current density of 2500 A m-*. This contrasts with cell
voltages of 3.8-4.2 V for L-cysteine hydrochloride production from 2.0 mol dme3 hydrochloric acid using a
titanium cathode at a current density of 2000 A m-*.
Much of this difference is due to the lower conductivity
of the alkaline catholyte. On the other hand, ammonia
solution facilitates efficient catholyte evaporation to
yield the free base directly.
26
T.R. Ralph et al. / Electrochemistry of L-cystine and L-cysteine: Part 2
4. Conclusions
Both the free base and acid salt processes are capable of generating r_-cysteine in high purity by simple
evaporation of the catholyte following electrolysis of
the disulphide. The majority of applications require the
hydrochloride salt, but local markets or speciality processes may demand the free base; for storage and
transportation, the acid salt is much more stable.
It is clear from the recent literature that porous,
three-dimensional carbon cathodes have significant potential for the commercial electrosynthesis being electrocatalytic, offering good stability and avoiding product contamination by toxic metals from the cathode.
Such high surface area electrodes are becoming increasingly used, within plate-and-frame
cells, to improve the performance of many existing electrosyntheses and to investigate novel syntheses [33,34]. The
usual drawback of non-uniform potential and currrent
distributions over three-dimensional
electrodes does
not appear to affect the electrosynthesis adversely under the reported conditions as the only side-reaction is
hydrogen evolution.
Of the remaining cathode materials investigated for
the production of the acid salt, lead with its high
hydrogen overpotential is amongst the most proficient
and remains the choice for many industrial processes.
During prolonged use, or stop/start operation, however, there are concerns regarding cathode stability in
acid electrolytes and some lead contamination of the
product can result.
The common reactor choice is a parallel plate design operating in the batch recycle mode. Such operation allows the rate of mass transport to be readily
enhanced by increasing the catholyte flow rate and by
incorporation
of turbulence
promoters within the
catholyte channel. The significance of maximizing mass
transport rates of L-cystine supply to the cathode is
clearly shown by much improved figures of merit towards the end of a batch electrolysis, coupled with the
requirement for a near quantitative reactant conversion to avoid costly product work-up. Selection of the
other major process variable, the current density, is a
trade-off between use of the highest value to maximise
the space-time yield whilst avoiding losses due to
hydrogen evolution and the attendant increase in specific energy consumption for the product.
Concerning the other major reactor components, a
choice exists between the generation of chlorine or
oxygen gas at the anode. Platinized titanium in hydrochloric acid and a DSA oxygen-evolving anode in sulphuric acid have, respectively, been the two common
strategies The use of an oxygen-evolving anode has the
attraction of avoiding the need to handle toxic chlorine
gas if it cannot be used on-site. Cation membranes are
currently favoured owing to their greater stability when
compared with their anion counterparts. In a recently
developed free base process, the cation membrane
prevents the loss of negatively charged reactant and
product molecules into the anolyte. There is no evidence of such loss of the positively charged analogues
in the case of the acid salt process.
Acknowledgements
The academic authors are grateful to EA Technology, Capenhurst, for fruitful collaboration, to the SERC
for the provision of a CASE award studentship (to
T.R.R.) and the University of Portsmouth Science Faculty for research support (to F.C.W.).
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