Some examples of phase-transfer catalysis application in organochlorine chemistry

Article abstract of DOI:10.1021/op990041j

Kinetics of phase-transfer catalysed (PTC'd) dehydrochlorination of the α-isomer of hexachlorocyclohexane in the presence of proton donors was investigated. Carboxylic acids and picric acid act as inhibitors. Benzyl alcohol strongly promotes the reaction. The plots of observed rate constants vs phenol and pentachlorophenol concentration have a bell-shaped form that was not observed before. An example of long-chain quats application in the synthesis of the ketamine anaesthetic intermediate by dehydrochlorination in dilute alkali is shown. Another application of phase-transfer catalysis (PTC) in organochlorine chemistry is the aqueous (sodium hypochlorite) chlorination of alkyl aromatic compounds. The results of m-phenoxytoluene chlorination and reaction kinetics in the presence of the polymeric crown are described.

Full text of DOI:10.1021/op990041j

Organic Process Research & Development 1999, 3, 437−441
Some Examples of Phase-Transfer Catalysis Application in Organochlorine
Chemistry
Felix S. Sirovski*
N.D. Zelinsky Institute of Organic Chemistry of RAS, 47 Leninsky pr., Moscow, 117913, Russia
Abstract:
1. Alkaline Dehydrochlorination in Dilute Alkali and
Proton Donor Influence in PTC’d Dehydrochlorination.
The topic of synergetic additives to PTC has become quite
fashionable. This was caused by the recent work of Savy-
olova5 who showed that in the hydrolysis of nitroaromatic
esters by solid sodium hydroxide a 50:50 mixture of
quaternary ammonium salt and crown ethers gives the highest
reaction rates. Much earlier the analogous effect was
demonstrated by Szabo6 in the alkylation of malonic ester.
However, from the viewpoint of a process chemist, the use
of such a mixture in an industrial medium- or even small-
scale process is hardly feasible due to large costs. The same
effect can be obtained in a rather simpler and cheaper way
using cocatalytic acid additives.4,7,8 As indicated earlier, the
role of proton-donating substances in PTC’d reactions is still
debated. Thus, in PTC’d displacement of chloride from hexyl
chloride by sodium formate the introduction of acid additives
(such as phenol) resulted in the retardation of the reaction.9
Conversely, in PTC’d dehydrobromination of dibromoethyl-
benzene the addition of phenol resulted in acceleration of
the reaction.10 Makosza has also shown that addition of weak
H-acids strongly promotes alkaline dehydrobromination in
concentrated NaOH using Bu4NBr as the catalyst,7 but no
kinetic dependencies were obtained in either cases. It was
therefore, interesting to investigate the effect of addition of
proton donors on kinetics of PTC alkaline elimination.
As the model reaction we chose the dehydrochlorination
of the R-isomer of hexachlorocyclohexane (HCCHX). The
kinetics of this reaction in the presence of different quats
was studied earlier in considerable detail,11,12 thus making it
possible to avoid some preliminaries. For the proton donor
additive we have used phenol (I), pentachlorophenol (II),
benzyl alcohol (III), picric acid (IV), caproic acid (V), and
R-methyl substituted fatty acids (fraction C7-C9) (VIK-1)
(VI), whilst the phase-transfer catalyst was Katamin AB
(PhCH2(Me)2N(C16-C18)Cl). The reaction in the presence
and absence of additives is satisfactorily described by a first-
order kinetics, that is shown in Figure 1.
Kinetics of phase-transfer catalysed (PTC’d) dehydrochlorina-
tion of the r-isomer of hexachlorocyclohexane in the presence
of proton donors was investigated. Carboxylic acids and picric
acid act as inhibitors. Benzyl alcohol strongly promotes the
reaction. The plots of observed rate constants vs phenol and
pentachlorophenol concentration have a bell-shaped form that
was not observed before. An example of long-chain quats
application in the synthesis of the ketamine anaesthetic inter-
mediate by dehydrochlorination in dilute alkali is shown.
Another application of phase-transfer catalysis (PTC) in organo-
chlorine chemistry is the aqueous (sodium hypochlorite) chlo-
rination of alkyl aromatic compounds. The results of m-phe-
noxytoluene chlorination and reaction kinetics in the presence
of the polymeric crown are described.
Introduction
Many industrial processes are based on the various
reactions of organochlorine compounds. It is quite natural
that phase-transfer catalysis has attracted a great interest of
chemists working in the field. The well-known advantages
of PTC answer best to the current challenge for the chemical
industry, that is, the development of safer and more
environmentally benign processes.1 PTC is in many aspects
nearly an ideal tool for retrofitting organochlorine chemistry
processes based on dehydrochlorination or chlorination
reactions.
Earlier the author had published the summary of results
obtained in his laboratory.2,3 This work is devoted to two
problems, namely, alkaline dehydrochlorination in dilute
alkali and the effect of proton donors in it and PTC’d
chlorination. These problems have both applied and scientific
importance. The use of cocatalysts in PTC had been first
described by Dehmlow more than 10 years ago.4 Neverthe-
less, so far there were significant discrepancies concerning
the role of acidic additives in PTC reactions.
PTC’d chlorination is quite advantageous as it allows the
use of large amounts of hypochlorite solutions formed as
the side-products in many industrial processes. Until now
this was performed using soluble catalysts; we have studied
this chemistry using a solid catalyst.
(5) Savelova, V. V.; Vakhitova, N. N.; Magasinski, A. N.; Rybak, V. V.
MendeleeV Commun. 1995, 123.
(6) Szabo, G. T.; Aranyosi, K.; Csiba, M. Synthesis 1987, 565.
(7) Makosza, M.; Lasek, W. Tetrahedron 1991, 47, 2843.
(8) Sirovskii, F. S.; Mochalov, V. N.; Panova, M. V. Russ. Chem. ReV. 1991,
60, 345.
* Author for correspondence. Fax: +7 (095) 135-5328. E-mail: sirovski@gol.ru.
(1) Sheldon, R. A. J. Mol. Catal. 1996, 107, 75.
(2) Sirovsky, F. S. Russ. Chem. Bull. 1995 44.
(9) Zahalka, H. A.; Sasson, Y. J. Chem. Soc., Chem Commun. 1984, 1581.
(10) Kurginyan, K. A. Arm. Khim. Zhurn. [Armenian J. Chem.] 1985, 38, 223.
(11) Sirovskii, F. S.; Velichko, S. M.; Panova, M. V.; Chimishkyan, A. L. Kinet.
Catal. 1986, 27, 731 (Engl. Trans.).
(3) Sirovski, F. S. In Phase Transfer Catalysis. Mechanisms and Syntheses;
Halpern, M., Ed.; ACS Symposium Series No. 659; American Chemical
Society: Washington, DC, 1996; p 68.
(4) Dehmlow, E. V.; Thieser, R.; Sasson, Y.; Neumann, R. Tetrahedron 1986,
42, 3569.
(12) Sirovskii, F. S.; Skibinskaya, M. B.; Berlin, E. R.; Treger, Yu. A.; Stepanova,
N. N.; Molodchikov, S. I. Kinet. Katal. 1986, 27, 614 (Russian).
10.1021/op990041j CCC: $18.00 © 1999 American Chemical Society and The Royal Society of Chemistry
Published on Web 10/26/1999
Vol. 3, No. 6, 1999 / Organic Process Research & Development
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437

Figure 4. Dependence of kobs on phenol concentration;
points: experiment, line: least-squares fit.
Figure 1. Kinetic curves of HCCHX dehydrochlorination at
20 °C, [HCCHX]0 ) 5.1 × 10-2 M, [cat] ) 1.78 × 10-4 M, [I]
) 7.0 × 10-4 M, [II] ) 1.0 × 10-5 M, [III] ) 4.0 × 10-4 M,
[IV] ) 4.7 × 10-5 M, [V] ) 1.5 × 10-5 M, [VI] ) 1.8 × 10-4
M.
Figure 5. Dependence of kobs on pentachlorophenol concentra-
tion; points: experiment, line: least-squares fit.
The results obtained in the presence of carboxylic and
picric acids are quite fairly described by the well-known com-
petitive inhibition scheme.13 Makosza in his work on cocata-
lysts in â-elimination reactions7 proposed a following scheme:
Figure 2. Dependence of kobs on VIK-1 and picric acids
concentration.
where YH is a proton donor, Q is the quaternary ammonium
cation, subscripts “o”, “aq”, and “if” denote respectively the
organic phase, the aqueous phase, and the interface. Unfor-
tunately, it was not supported by kinetic data.
Figure 3. Dependence of kobs on benzyl alcohol concentration.
The possible competing reaction
Figures 2-5 show the dependencies of the observed first-
order rate constants on cocatalyst concentration. It is seen
that addition of carboxylic acid inhibits the reaction, the effect
being more pronounced the more lipophilic is the acid. Picric
acid also acts as the inhibitor.
(13) Schmid, R.; Sapunov, V. N. Nonformal Kinetics, Verlag Chemie: Weinheim,
1982.
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is less probable as Dehmlow14 showed that the distribution
coefficient of Q+Cl- is 5 orders of magnitude larger than
that of Q+OH-. It is evident that in the absence of the
promoter the reaction proceeds either at the interface or in
the third phase, that is the liquid border film.
It is easy to show that the rate of product formation for
the above scheme is expressed by the following differential
rate equation:15
basicity). Thus, with very stable (low pKa) anions (from the
very acidic Y-H), these anions Y- are too weak to act
effectively as base (associated with Q+ in the organic phase)
but nevertheless largely tie up Q+ with ineffective Y- thereby
preventing Q+ from associating with more reactive hydroxide
HO- due to the greater organophilicity of Y- than HO-.
Hence, increasing the concentration of strongly acidic Y-H
inhibits the reaction by reducing Q+ availability. Far less
acidic Y-H acts as by being more easily solubilised into
the organic phase than hydroxide, whilst Y- is still a strong
enough base to catalyse the E2 elimination. As regards the
phenol and pentachlorophenol results, a possible rationali-
sation for the kinetics observed is that at low additive
concentration (less than that fully occupying the quat Q+),
increasing additive concentration increases the reactive QY
base concentration. However, as additive concentration
increases above that of quat concentration, then further
additive can associate with QY by hydrogen bonding to give
QY-HY in which the basic phenoxide is stabilised by
hydrogen bonding to another phenol, thereby reducing its
reactivity. Hence increasing additive HY concentration
beyond that fully occupying quat Q+ gradually decreases the
reactivity of the basic species QY. It is quite plausible, as
Brandstrom proved the formation of Y-Q+, Y-Q+(Y-H),
Y-Q+(Y-H)2, and higher complexes on addition of the quat
and base to the solution of phenol or carboxylic acid in
methylene chloride.18 This scheme is also described by the
above equation. The obtained results can well explain the
discrepancies concerning the action of phenol additives
obtained by different authors [compare refs 9 and 10]. It is
interesting to note also that even strong inhibitors, such as
VI do not fully stop the reaction. That confirms our previous
findings on dual catalytic character of long-chained quats
and some of their advantages over short-chained ones.2,3 It
is that the long-chained quats are both micellar and phase
transfer catalysts, and only the phase-transfer function is
inhibited.
d[C ) C]org
)
dτ
k1k2k3[Q+X-]org[NaOH]aq[Y - H]org[HCCX]org
k-1k-2[X-]aq + k-1k-3[HCCX]org + k2k3[HCCX]org[Q+X-]org
This equation validly describes the action of promoters (Y-
H), such as fatty alcohols, amines, and benzyl alcohol. Benzyl
alcohol acts as the promoter, confirming the results on PTC-
elimination in the presence of alcohols obtained by Dehmlow
and co-workers.4 It should be noted that the distribution of
quaternary ammonium hydroxides between aqueous and
organic phases in the presence of alcohols was already
studied by Agarwall and Diamond in 1963.16 They showed
that in benzene solution quaternary hydroxide exists as an
ion pair linked with three alcohol molecules. In a more polar
organic phase, such as nitrobenzene, quaternary hydroxide
exists as a free ion also linked with three alcohol molecules.
In the author’s opinion it is most probable that the alcohol
molecules are bonded with the hydroxyl ion rather then with
the quaternary cation. So Makosza’s scheme is not very
accurate.
The most peculiar results are obtained in the presence of
phenol and pentachlorophenol (Figures 4 and 5). The
obtained dependence is best described by the equation of
the type
kobs ) kCadd/(1 + K1Cadd)(1 + K2Cadd
)
We have used the advantage of the long-chained quats,
that is their ability to catalyse elimination at low alkali
concentrations, in the solution of the following practical task.
One of the steps in the synthesis of the short-time anaesthetic
ketamine includes dehydrochlorination. This reaction is
usually carried out in the presence of an amine base.
where Cadd is the concentration of the cocatalyst and k, K1,
and K2 are some reaction constants. This equation implies
the mechanism where the cocatalyst forms complexes with
both the reacting species. This kind of equation is common
for micellar and acid catalysis. In the framework of existing
views on PTC elimination mechanism that would mean that
in this case not only does the catalyst form a complex with
the additive but the substrate does so also. However, this is
hardly plausible in this case, as it is difficult to conceive of
a HCCHX complex with the quaternary salt or a proton
donor. The species Y- is effectively the major source of base
in the organic phase (by virtue of the greater organophilicity
of complex QY than that of QOH when the Y-H concentra-
tion is greater than that of QX, so that Q+ is almost wholly
associated with Y- in place of HO-), then the reactivity of
Y- as base in E2 elimination is going to be inversely
proportional to the stability of Y- (e.g., as measured by its
This is a bottleneck step as the yield is about 70%. It
seemed interesting to try PTC in this reaction but the use of
concentrated alkalis was ruled out as it would result in
numerous side-processes involving the keto group. The usual
catalysts (TEBA or Bu4NBr) do not work in diluted alkali.
Therefore, we had to apply our usual long-chained catalyst
(14) Dehmlow, E.; Slopianka, M.; Heider, J. Tetrahedron Lett. 1977, 2361.
(15) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase-Transfer Catalysis.
Fundamentals, Applications and Industrial PerspectiVes; Chapman &
Hall: New York, London, 1994.
(17) Sirovski, F. S.; Berlin, E. R.; Mulyashov, S. A.; Bobrova, E. A.; Batrakova,
Z. I.; Dankovskaya, D. F. Org. Process Res. DeV. 1997, 1, 253.
(18) Brandstrom, A. AdV. Phys. Org. Chem. 1977, 15, 267.
(16) Agarwall, B. R.; Diamond, R. M. J. Phys. Chem. 1963, 67, 2785.
Vol. 3, No. 6, 1999 / Organic Process Research & Development
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439

Table 1. Dehydrochlorination of VII in the presence of
NaOH, catalystsKatamin AB, t ) 20 °Ca
Table 3. Chlorination of m-phenoxytoluene by aqueous
NaOCl, t ) 20 °C, [PhOC6H4Me]0 ) 0.5 M, solvent CHCl3,
[[(C7-C9)3NMe]2SO4]0 ) 1.6 % w/w, [C7H9COOH]0 ) 3.2 %
w/w, NaOCl/PhOC6H4Me ) 3:1
[NaOH]0,
M
Ccat,
% mol.
reaction
time, h
chromatographic
yield, % theor.
reaction
yield
[NaOCl]0,
M
time, conversion of X, ring-chlorinated
0.44
1.06
3.57
6.92
10.86
0.6
0.6
0.047
0.1
0.1
2
2
3
5
4
93
86
15.1
10.2
22.1
pH
min
of IX, % % theor.
products, %
0.98
0.98
1.65
1.65
1.65
1.65
1.65a
1.65a
1.65a
1.65a
8
3
7
7
6
7
7
7
7
7
170
30
90
20
40
70
20
35
50
95.0
54.0
67.6
12.1
16.1
26.4
25.0
41.2
66.6
92.8
74.8
14.5
51.4
8.9
12.4
21.8
23.4
38.8
63.5
88.8
20.2
39.5
16.2
3.2
3.7
4.6
1.4
2.4
3.1
4.0
a In all of the experiments the conversion was 100%.
Table 2. Dehydrochlorination of VII in the presence of
KOH, t ) 20 °C
reaction chromatographic
130
[KOH]0,
M
Ccat,
% mol
time,
h
yield,
% theor.
catalyst
a The catalyst was XI preliminary swelled in CHCl3.
0.28 dibenzo-18-crown-6 1.04
0.3 dibenzo-18-crown-6 1.2
0.63 dibenzo-18-crown-6 1.04
1.14 dibenzo-18-crown-6 1.6
1.85 dibenzo-18-crown-6 1.6
3
3
3
4
3.5
4
2
3
3
1
1
2.5
1
84
85
84
85
82
86
0
84
84
97
94
94
94
2.1
3.2
0.3
0.7
dibenzo-18-crown-6 1.25
dibenzo-18-crown-6 1.65
Katamin AB
Katamin AB
0.12
0.12
0.22 [(C7-C9)3NMe]2SO4 0.08
0.27 [(C7-C9)3NMe]2SO4 0.06
0.66 [(C -C9)3NMe]2SO4 0.1
0.74 [(C7-C9)3NMe]2SO4 0.2
7
a
In all of the experiments the conversion was 100%.
PhCH2(Me)2N+(C16-C18)Cl-.17 The results are listed in
Tables 1 and 2. It is seen that the increase in alkali
concentration results in a sharp decrease in the product yield.
At quite moderate concentration of 3.0 M the yield falls
practically to zero. At the lower base concentrations the yield
is much higher than in the presence of an amine base. Thus,
PTC dehydrochlorination is one solution to the problem.
PTC Chlorination. The use of PTC for the chlorination
of alkylaromatic compounds has some significant advantages.
First, it is very selective as only side chain is chlorinated.19
Second, it allows one to use large quantities of sodium
hypochlorite solutions that are obtained as side-products in
many industrial processes. Nevertheless, the use of the
soluble catalyst is not very advantageous for the large-scale
processes as it necessitates the purification of the final
product from the catalyst or the products of its decomposi-
tion. The use of polymeric phase-transfer catalysts is widely
known,15 but till now they were not applied in chlorination
reactions. We decided to test triphase catalysis in the
chlorination of m-phenoxytoluene.
Figure 6. Dependence of the observed rate constant on the
catalyst amount.
The resulting compound, m-phenoxybenzyl chloride is
used in the synthesis of pyrethroid insecticides. For the
catalysts we used the mixture of [(C7-C9)3NMe]2SO4 with
heptanoic acid that proved perfect in the bromination of
cyclopentadiene3 and polymeric dibenzo-18-crown-6 (XI) of
the following structure:
The results are listed in Table 3. It is seen that the
polymeric crown is much more selective then soluble quats.
At the low pH values mostly ring-chlorinated products are
formed.
These results made it worthwhile to investigate the
kinetics of this reaction. The reaction was investigated at
room temperature. Some of the obtained results are shown
in Figures 6-8.
It should be noted that all experiments were carried out
at stirring rates above 2000 rpm, that is, when it did not
(19) Fonouni, H. E.; Krishnan, S.; Kurtis, D.; Hamilton, J. J. Am. Chem. Soc.
1983, 105, 7672.
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The obtained results show that use of triphase catalysis
for the chlorination of alkylaromatics is rather promising.
The problem lies in obtaining the catalyst in the form suitable
for industrial use.
Experimental Section
Materials. Solvents and reagents were commercial grade.
The R-isomer of hexachlorocyclohexane was isolated from
the mixture of isomers by the known methods.20 The product
used had mp 157-158° (159-160°20).
Product Identification and Analysis. Reaction products
of m-phenoxytoluene chlorination were determined by GLC,
using a TSVET gas chromatograph, model 152 with FI
detector. Analyses were performed on a 3 m SE-30 column.
Reaction products of VII dehydrochlorination were deter-
mined by GLC, using a Chrom-5 gas chromatograph with
FI detector. Analyses were performed on a 1 m OV-17
column. Product identification was performed using GLC-
MS spectroscopy. GLC-MS spectra were recorded on a
Varian-MAT spectrometer, model CH7A with chromato-
graph model 2740 and a data treatment module SS-100.
Kinetic Experiments. Kinetics of the R-hexachlorocy-
clohexane dehydrochlorination was studied using NaOH
concentration 2.5 M, by the methods described in ref 11.
Kinetics of m-phenoxytoluene chlorination was investigated
in a three-necked jacketed 150 mL glass reactor with baffles,
equipped with high-speed stirrer and thermometer. The
reaction was studied at about 1800-2000 rpm where stirring
speed did not influence the reaction rate. The reaction was
monitored by taking samples of the organic phase and
analysing them by GLC. The polymeric catalyst XI was
soaked in CHCl3 for at least 5 h before its use until it
increased its volume 3-fold.
Figure 7. Dependence of the initial rate on the hypochlorite
concentration.
Figure 8. Dependence of the observed rate constant on the
catalyst particle size.
Acknowledgment
This paper is dedicated to Professor Eckehard Volker
Dehmlow on his 65th birthday.
influence the reaction rate. The reaction was first-order on
catalyst amount and NaOCl concentration. The reaction rate
was strongly dependent on the size of catalyst granules (see
Figure 8). The obtained dependence is typical for reactions
proceeding in the internal diffusion region. The catalyst was
rather strongly cross-linked, thus resulting in internal diffu-
sion limiting the overall reaction rate. Also it worked only
in swelled state after soaking for several hours in CHCl3.
Received for review May 5, 1999.
OP990041J
(20) Besobrazov, Yu.; Molchanov, A.; Gar, K. Geksakhloran, ego sVoistVa,
poluchenie I primenenie [Hexachloran, its properties, manufacture and
uses]; Goskhimizdat: Moscow, 1958.
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