PROCESS FOR THE PRODUCTION OF 4-CHLOROACETOACETYL
CHLORIDE, 4-CHLOROACETOACETIC ACID ESTERS, AMIDES AND IMIDES
The invention relates to processes for the production of 4-chloroacetoacetyl
chloride, 4-chloroacetoaceticacid esters, amides and imides.
Background of the invention
Methods for the production of 4-chloroacetoacetyl chloride (4-chloro-3-oxobutanoyl
chloride) and esters obtained from 4-chloroacetoacetyl chloride are known in the
art. In a specific process, the 4-chloroacetoacetyl chloride is obtained by reacting
chlorine gas with diketene (4-methylideneoxetan-2-one).
The reaction takes place exothermally and therefore requires cooling. The reaction
products are relatively sensitive to heat and the formation of undesired side
products and decomposition is observed if temperature deviates locally or globally
from a given range. For example, undesired reaction products may be
regioisomers, such 2-chloroacetoacetyl chloride, or over-chlorinated products,
such as di- or tri-halogenated compounds, such as 2,4-dichloroacetoacetyl
chloride or 2,2,4-trichloroacetoacetyl chloride. Thus, it is difficult to determine
efficient production conditions by which a high yield is achieved.
JP 113 824 suggests a process in which diketene is dissolved in a solvent and
reacted in a column reaction vessel with chlorine under cooling. The chlorine gas
is fed into the column in a continuous current or counter-current manner. However,
selectivities of less than 90% are achieved.
A solvent-free process is disclosed by US 4,468,356, according to which a
diketene spray is continuously contacted with chlorine gas in a reaction zone at a
temperature between 80°C and 2 10°C. Subsequently, the intermediate product is
subjected to an esterification reaction with ethanol. However, the overall yield is
below 80% and thus relatively low, which is probably due to the exposure of the
intermediate product to relatively high temperatures. Further, the reaction is
carried out only with small amounts of starting compounds at a laboratory scale.
Reactions for the production of haloacetoacetic acids from diketene and chlorine
on laboratory scale are disclosed in US 3,950,41 2 and US 3,701 ,803. In US
4,473,508, the process of US 3,701 ,803 is discussed. The inventors conclude that
an upscale would not be possible because of problems associated with heat
transfer. In order to provide an efficient reaction on increased scale, it is suggested
to react a solution of diketene in an inert solvent with a solution of chlorine
dissolved in an inert solvent in a tube reactor. According to Example 6, the acid
chloride intermediate can be produced at a yield of 98%. However, the process is
relatively inefficient, because both starting compounds are diluted in relatively
large amounts of solvents. Thus, the overall reaction requires large amounts of
solvent and consequently large reactors and equipment and more energy for
cooling. When increasing the volume of the reactor, the yield dropped "drastically"
and the selectivity was relatively low (US 4,473,508, example 7). Thus it would be
desirable to provide a more efficient process, which requires less solvent, is more
selective and efficient on a large scale.
A laboratory process in order to produce ethyl-4-chloroacetoacetate from diketene
and chlorine is disclosed by Pan et al., Shandong Huagong 2007, 36 (10) 4-6. In
this process, it is suggested to use a relatively high concentration of diketene of
about 24 to 28 weight-%. However, the yield of the ester is only about 80% and
the reaction is carried out in a reaction flask on small scale, without any
suggestion how to resolve the heat transfer problem on increased scale.
The processes known in the art are also problematic with respect to process
safety. Especially when carried out in an industrial scale, the reaction requires high
amounts of chlorine and diketene. These substances are highly reactive and
hazardous when inhaled. When the reactor is damaged or when the process is
disturbed and gets out of control, the reactants could harm the people in the
environment and explode. Thus an industrial upscale, if at all, would only be
possible under severe safety precautions.
Problem underlying the invention
The problem underlying the invention is to provide a process for the production of
4-chloroacetoacetyl chloride and reaction products obtainable therefrom, which
overcomes the above-mentioned problems. The process shall provide the reaction
products at high yield and selectivity. The process shall be applicable on largeindustrial
scale use and as a continuous process. Specifically, the reaction
efficiency shall be high and the consumption of solvents shall be low.
It is another problem underlying the invention to provide an industrial scale
process, which is relatively safe and reduces the potential dangers associated with
the handling of high amounts of chlorine and diketene.
Disclosure of the invention
Surprisingly, the problem underlying the invention is solved by processes
according to the claims. Further inventive embodiments are disclosed throughout
the description.
Subject of the invention is a process for the production of 4-chloroacetoacetyl
chloride, comprising the steps of
(a) feeding diketene and chlorine into a thin film reactor and
(b) reacting the diketene and chlorine to obtain 4-chloroacetoacetyl
chloride.
According to the invention, it was found that a highly efficient reaction between
diketene and chlorine can be carried out in a thin film reactor. After feeding
diketene and chlorine into the thin film reactor, they react in the thin film reactor. 4-
chloroacetoacetyl chloride is formed as the reaction product and can be removed
from the reactor.
In a preferred embodiment of the invention, in step (a) the diketene is fed into the
reactor in the form of a mixture with an organic solvent. The mixture is preferably a
solution of diketene in the organic solvent.
In principle, any organic solvent may be used, in which diketene is readily
dissolved and which does not react with diketene or interfere with the reaction.
Thus the solvent should be an inert solvent. In this respect, alcohols are not
applicable, because they would react in an esterification reaction in the thin film
reactor by acetoacetate formation. Preferred inert solvents are halogenated
hydrocarbons, preferably halogenated alkanes, e.g. chloromethane,
dichloromethane, trichloromethane (chloroform), tetrachloromethane,
chloroethane, 1,2-dichlorethane, trichloroethane, tetrachloroethane,
dichloropropane, 1-chloro-2-fluoroethane, 1, 1 -dichloroethane, 1,2-dichloroethane,
methylchloroform, 1-chlorobutane, 2-chlorobutane, 1-bromobutane, ethyl bromide,
1-bromo-2-chloroethane, 1-bromo-2-fluoroethane, 1-iodobutane,
bromochloromethane, dibromomethane, 1, 1-dibromomethane,
difluoroiodomethane, 1-bromopropane, bromochlorofluoromethane, 2-
bromopropane, bromodichloromethane, bromofluoromethane,
bromotrichloromethane, dibromodifluoromethane, pentachloromethane, 1, 1 ,1 ,2-
tetrachloroethane, fluoroiodomethane, iodomethane, diiodofluoromethane, 1, 1 ,2,2-
tetrachloromethane, 1, 1 ,2-trichloroethane, 1-chloropropane, 1,2-dibromopropane,
1,2,3-trichloropropane, 1, 1 , 1 ,2-tetrachloropropane, or mixtures thereof or mixtures
comprising at least one thereof.
In a highly preferred embodiment of the invention, the solvent is dichloromethane.
It is known in the art that dichloromethane is an efficient inert solvent for the
reaction between diketene and chlorine.
According to the invention, it was found that the reaction can be carried out with
high efficiency even when the diketene is provided in the organic solvent at
relatively high concentrations. In a preferred embodiment of the invention, the
concentration of diketene in the mixture is higher than 15% (w/w). More preferably,
the concentration of diketene is higher than 20% or higher than 25% (w/w). The
concentration of diketene could be up to 80% (w/w) or up to 50% (w/w). In
preferred embodiments, the concentration of the diketene is between 15 and 80%,
between 15 and 60% or between 20 and 50% (w/w), more preferably between 25
and 50% (w/w). The concentration of diketene could also be between 2 1% and
80%, preferably between 2 1 and 60% or between 2 1 and 50% (w/w). The
relatively high concentration of diketene is advantageous, because the overall
solvent consumption is low. Further, the volume of the reaction mixture in the thin
flow reactor is kept relatively low. The contact area between the reactants is high
and a good time-space yield can be obtained. Even further, the heat removal is
more efficient if the volume is low and if thus the film thickness is also small. Thus
the process is efficient regarding energy and costs, especially when carried out on
industrial scale.
According to the invention, it is preferred that in step (a) the chlorine is fed into the
reactor in the form of gaseous chlorine. When using gaseous chlorine, the total
consumption of solvents is decreased even further. Thus, when using diketene at
a relatively high concentration dissolved in an organic solvent, preferably
dichloromethane, and using gaseous chlorine, the reaction is highly efficient for
the reasons outlined above regarding high diketene concentrations. The reaction
volume in the thin film reactor is relatively low and the time-space yield is
increased, whereas heat transfer is facilitated. Further, the use of chlorine in
gaseous form avoids a pre-dissolving step. This is advantageous, because
chlorine is aggressive and complicated to handle on large-scale industrial process.
According to the invention, it is not necessary to dilute the chlorine with an inert
gas. Thus in a preferred embodiment of the invention, no inert gas is introduced
into the thin film reactor, and/or the chlorine is not mixed with an inert gas before
or whilst being introduced into the thin film reactor. Preferably, only diketene,
chlorine and the organic solvent are introduced into the thin film reactor. Thus the
overall consumption of substances, and thus costs and energy, can be kept low.
The inventive reaction in step (a) is carried out in a thin film reactor. In such a thin
film reactor, the reaction takes place on at least one reactor surface. Usually, thin
film reactors allow a continuous renewal of the reaction surfaces. The thin films
are created on the reaction surfaces by rotating the surfaces. The reactor is thus
distinct from reactors, such as tube reactors, in which the reaction is carried out in
a spatial liquid volume. The reactor comprises means for distributing the liquid
reactants to the reaction surfaces. Further, the reactor should comprise cooling
means. Preferably, the cooling means are a heat exchanger. In the inventive
method, it is preferred that the heat, which is generated by the exothermic
reaction, is continuously removed from the reactor. Thus, the reaction temperature
can be maintained stable and relatively low, locally and globally. The thickness of
the film is adapted to the cooling system and required heat dissipation. Typically,
the average thickness of the film may be between 0.05 mm and 15 mm, more
specifically between 0.1 and 5 mm.
In a highly preferred embodiment of the invention, the reactor is a wiped film
reactor. A wiped film reactor comprises wiping means, for example blades, wipers
or rolls. Typically, such rolls or wipers are pressed against the reactor walls by
centrifugal forces. The wiping means are in contact with the films and moving,
usually by rotation. By rotating the wiping means and thus the thin films, a film
renewal and thorough and continuous mixing are achieved. The wiping means
may be arranged in columns or rows. The wiping means are usually made from an
inert material, such as PTFE (preferably available under the trademark Teflon from
DuPont), metal alloys, preferably nickel alloys (preferably those available under
the trademark Hastelloy from Haynes Int.), stainless steel, or graphite. Typically,
the number of wiper elements is between 2 and 1000, more preferably between 10
and 1000 or between 50 and 500. For example, am industrial scale reactor may
comprise 4 columns equipped with 40 rolls each. Wipers may be flat or wound,
preferably spiral-wound.
Wiped film reactors are often used in the art for distillation of thermally labile
compounds. However, the use of wiped film reactors for chemical reactions has
also been described in the art. The use in a polymerisation reaction and
adjustment of a reactor is described by Steppan et al. ("Wiped film reactor model
for nylon 6,6 polymerisation", 1990, Ind. Eng. Chem. Res. 29, 201 2-2020). The
basic considerations disclosed therein are also useful for adjusting a wiped film
reactor in the present inventive process for optimal yield. The reaction conditions
are selected and adjusted In view of the specific reactor model, considering
parameters such as number and type of wipers, liquid distribution system,
temperature, reactor volume, pressure, rotor speed, desired film thickness etc.
The area of the wiped-film reactor is preferably between 0.5 and 30 m2, preferably
between 1 and 15 m2. It is preferred that the area is at least 0.5, at least 1 or at
least 2 m2. The reactor speed may be between 10 and 2000 rpm, preferably
between 20 and 1000 rpm.
In a preferred embodiment of the invention, the process is a continuous process.
Preferably, the diketene is fed into the reactor at a rate of at least 10 kg/h. More
preferably, the diketene is fed into the reactor at a rate of at least 20 kg/h, at least
30 kg/hour or at least 75 l/hour. The diketene may be fed into the reactor at a rate
of between 10 and 500 kg/h, or between 75 to 250 kg/h. Thin film reactors are
usually adjusted for continuous processes. The reactants are fed into the reactor
at a constant speed, whereas the reaction product is withdrawn from the bottom of
the reactor at a constant speed. It was found that the inventive reaction is efficient
on relatively large scale, which is applicable for industrial production. Preferably,
the chlorine gas is fed into the reactor at a rate of at least 10 kg/hour, 20 kg/h or
50 kg/h. The chlorine may be fed into the reactor at a rate of between 250 and 500
kg/h, or between 50 to 250 kg/h. The upscale processes can still provide the
products at high yield and selectivity because of the low amounts of solvent and
the high reaction efficiency and heat transfer efficiency in the specific reactor. This
was surprising, because it was not expected that a scale-up of the reaction would
be efficient with relatively low amounts of solvent and whilst obtaining high yields.
Preferably, the volume of the thin film reactor is at least 50I, at least 1001 or at
least 5001.
In an inventive upscale process, the turnover of the starting compounds and the
reactor volume are relatively high. However, the reactants in the reactor are mostly
present in the form of thin films, and thus the effective hold-up of reactants in the
thin film reactor is significantly lower compared to a conventional batch or pipe
reactor. In view of the potential dangers of the highly reactive and hazardous
chlorine and diketene, the inventive process is thus generally safer. For example,
when the reactor is damaged, or when the reaction gets out of control, relatively
low amounts of chlorine and diketene could react in an uncontrolled manner or
leak out of the reactor. The potential consequences would be less severe
compared to a conventional reactor comprising a spatial batch volume with a high
hold-up of chlorine and diketene. Thus the inventive process solves the problem of
providing a safer process.
Moreover, it was found that the inventive reaction can be carried out with high
efficiency on a large scale at relatively low temperatures. Diketene and 4-
chloroacetoacetyl chloride are temperature-sensitive, such that the yield is
decreased at high temperatures, especially when the residence time in the reactor
is high. In a preferred embodiment of the invention, the reaction temperature is
between - 15°C and 60°C. More preferably, the reaction temperature of the first
reaction is maintained between - 15°C and 45°C or between 0°C and 30°C. Still
preferably, the reaction temperature of the first reaction is maintained between 5°C
and 45°C or between 5°C and 30°C, or between 5°C and 20°C. Preferably, the
reaction temperature is below 60°C, below 40°C, below 30°C or below 20°C. The
reaction temperature is adjusted by cooling the reactor with cooling means, such
as a heat exchanger. Preferably, the heat exchanger comprises a thermal fluid
directly on the side of the surface which is not touched by the reaction mixture.
The heat exchange can be carried out with good efficiency in a thin film reactor
even on large scale. The average residence time of the diketene in the thin film
reactor should be adjusted to be relatively low to avoid degradation and side
reactions. The average residence time may be between 2s and 500 s, or between
5 s and 250s.
The reaction in the thin film reactor can be carried out at normal pressure, but also
overpressure or sub-atmospheric or at light vacuum. The overall reaction can thus
be carried out under mild conditions.
According to the invention, it was found that in view of low amounts of solvent and
a high contact area in the reactor, even at low temperatures, the residence time of
the reactants in the thin film reactor can be set relatively low whilst obtaining high
yields. This was not expected, because at relatively low temperatures and on
large-scale, the residence time is in principle increased. However, the overall set
up, with thin film formation, preferably supported by wiping, reduces the residence
time.
As outlined above, the total amount of solvent used in the inventive process can
be kept relatively low. The consumption of solvent can be reduced even further
when the solvent is recycled. More preferably, the solvent is also reused in the
process. In a preferred embodiment of the invention, the solvent is recycled and
reused. The recycling may comprise any appropriate methods, such as distillation,
liquid-liquid extraction, reactive extraction, membrane separation technology,
chromatography or crystallisation of the solvent, or a combination of these
methods, after the esterification or amidation reaction. Subsequently, the purified
solvent is re-introduction into the process, preferably after mixing it with diketene in
the reactant stream.
In a preferred embodiment of the invention, the solvent is dichloromethane having
a purity of at least 98 weight-%. Preferably, the content of chloride, water and/or
alcohol is low.
Another subject of the invention is a process for the production of a 4-
chloroacetoaceticacid ester, a 4-chloroacetoaceticacid amide or a 4-
chloroacetoaceticacid imide, comprising the steps
(c) transferring 4-chloroacetoacetyl chloride obtained according to a
process of the invention into a second reactor and
(d) reacting the 4-chloroacetoacetyl chloride with an alcohol or amine to
obtain the 4-chloroacetoaceticacid ester, 4-chloroacetoaceticacid amide
or a 4-chloroacetoaceticacid imide.
Hence the reaction product of the initial reaction of diketene and chlorine can be
reacted further in a second reaction. Preferably, the first and second reactions are
part of one single continuous process. In such a continuous process, the 4-
chloroacetoacetyl chloride built from the first reaction is withdrawn from the first
reactor, which is the thin film reactor, and transferred directly into the second
reactor.
In the second reactor, the esterification, amidation or imidation reaction is carried
out. The reactor may be any type of reactor, which is appropriate for these
reactions. For example, the reactor may be or may comprise a vessel, tube or
column. The first and second reactors are connected by connection means, such
as a tube, pipe or hose. Thus, the overall process can be carried out in an efficient
manner without intermediate purification or isolation of the 4-chloroacetoacetyl
chloride. However, the reaction could also be carried out after intermediate
isolation of the 4-chloroacetoacetyl chloride.
The esterification, amidation or imidation reaction is a typical reaction of an acid
chloride with an alcohol or amine.
In a preferred embodiment, the alcohol is an alkyl alcohol, i.e. an alkanol, or an
aryl alcohol, such as a phenol. For example, the alcohol may be selected from the
group of methanol, ethanol, isopropanol, n-butanol, e -butanol and phenol. In
preferred embodiments, the alcohol is methanol, ethanol or phenol. In order to
obtain an amide, a primary or secondary amine is used, preferably an alkyl amine,
such as a cyclic secondary alkyl amine, or an aryl amine, such as aniline. The aryl
group of aniline may be substituted. The alkyl groups of the alcohol or amine may
have between one and 10 carbon atoms, preferably between 1 and 4 carbon
atoms.
During the second reaction, HCI is formed in virtually stoichiometric amounts. The
amount of HCI product emerging during the process is virtually equimolar to the
product (and side products). Preferably, the gaseous HCI is removed from the
offgas by neutralization, for example with a basic scrubber system. However,
usually residual amounts of HCI are dissolved in the solvents. Before reusing the
solvents, the remaining amount of HCI has to be neutralized, e.g. by extraction
with aqueous basic solution.
The reaction conditions, such as temperature and pressure, are adapted to obtain
a high yield whilst consuming relatively low amounts of energy.
In a preferred embodiment of the invention, the reaction temperature in step (d) is
between 0°C and 80°C, or preferably between 20°C and 60°C. The reaction may
be carried out at normal pressure, overpressure or negative pressure.
Preferably, the dichloromethane solvent is distilled and/or recycled after the
second reaction in step (d). In or before the recycling step, the HCI should be
removed from the solvent, preferably by neutralization. The solvent may be
purified by known means, for example using a dewatering column, molecular
sieves, membrane separation technology, liquid-liquid extraction, reactive
extraction, chromatography and/or crystallisation, or a combination of these
methods.
In a preferred embodiment of the invention, the yield of the 4-
chloroacetoaceticacid ester, 4-chloroacetoaceticacid amide or 4-
chloroacetoaceticacid imide is at least 90%, based on the total amount of ketene
provided in step (a). More preferably, the yield is above 92% or above 95%.
Preferably, the yield of 4-chloroacetoacetate chloride obtained in the first reaction
step is more than 90%, preferably more than 95% or more than 98%. Preferably,
the conversion of chlorine is at least 95%, more preferably at least 98% or at least
99.5%.
Fig. 1 shows schematically and in exemplified form a wiped film reactor
applicable in the inventive process.
Fig. 2 shows schematically and in exemplified form the top view of a possible
layout of wipers inside a thin film chlorination reactor.
Fig. 3 shows schematically and in exemplified form a set-up for an inventive
continuous process for the production of 4-chloroacetoacetate from
diketene and gaseous chlorine.
A wiped film reactor for use in the first reaction of the invention is shown in Fig. 1.
The reactor comprises means ( 1 ) and (2) for feeding the diketene and chlorine.
The reactor comprises means (3) and (4) for supplying heat exchanging fluid into
the heat exchanging means. The product is eluted through means (9), whereas
vapors and/or gas can be let out through means (5), which may comprise a valve
( 10). The reactor comprises a rotor axis (6), around which a circular movement
occurs. The reaction mixture is fed to the reactor in a manner to flow down on the
outer portions of the reactor where it is mixed and distributed. The reactor
comprises means for distributing the liquid (7) and wipers (8), on which the thin
film is formed. A top view of a thin film reactor with spiral-wound wiper plates is
shown in figure 2 .
A typical arrangement of the inventive process is illustrated by Fig. 3 . Shown is an
exemplified pathway with thin film reactor for carrying out the conversion of
diketene and gaseous chlorine, whereas the diketene is dissolved in an organic
solvent, and transfers to a second reactor unit for the production of 4-
chloroacetoaceticacid ester, 4-chloroacetoaceticacid amide or a 4-
chloroacetoaceticacid imide. The gaseous chlorine and diketene solution are fed
into the thin film reactor ( 1 1) through inlets ( 13) for diketene solution and ( 15) for
chlorine. The 4-chloroacetoacetyl chloride intermediate is eluted from reactor ( 1 1)
and combined with the alcohol or amine reagent which is fed into the reaction
stream through inlet (14). The reaction stream enters the reactor ( 12). The crude
reaction product is withdrawn to obtain a crude product ( 16), which is purified by
distillation means (17) and isolated through outlet ( 18). The solvent may be
recycled through recycling means ( 18) and returned back to the reaction of
chlorination through connection ( 19). The reactors ( 1 1) , ( 12) and means ( 16), ( 17)
are connected by connection means, such as tubes or hoses. The dimensions,
connections and positions of inlets and outlets are only shown schematically and
not to be understood as limiting.
The inventive process solves the problems underlying the invention. The invention
provides an efficient process for reacting diketene with chlorine to obtain 4-
chloroacetoacetyl chloride and reaction products obtainable therefrom. The
reactions can be carried out with high selectivity and yield. Low amounts of solvent
are used, which makes the processes more efficient. The process is efficient at
low temperatures. A scale-up is possible whilst maintaining a high yield. Overall,
the reactants in the reactor have a low residence time, high throughput and high
time-space yield, combined with good heat removal in the first reactor.
It was further observed that uniform heat removal is possible in the thin film
reactor, such that local overheating is not observed. Local overheating can lead to
partial decomposition of reactants or products. Further, the inventive chlorination
reaction provides high selectivity and only minor amounts of over-chlorinated
products, which could result in undesired side products. Dissolving of the chlorine
in solvent is not necessary, which renders the process more efficient and easier to
handle. The solvent can be recycled and re-introduced into the process.
Examples
Example 1: Production of 4-CAAMe on pilot scale
The reaction of chlorination of diketene takes continuously place on pilot scale in a
wiped-film-reactor (chlorination reactor) with 1.5 m2 area. The reactor has 20
wipers. The wipers are aligned in five rows along the reactor. Each row has four
wipers separated 90° from each other. The wipers of one row are 25° staggered in
relationship to the position of the wipers corresponding to the nearby row. The
wipers are assembled as spiral-wound Teflon plates. Figure 2 shows
schematically how the wipers are mounted inside the reactor. The reactor-rotor
speed was varied between 80 rpm and 500 rpm.
The reactants chloride gas (Cl2) and diketene are introduced at the top of the
reactor. The solvent in this reaction is dichloromethane (MeCI2) . Before diketene is
fed into the reactor, it is diluted in MeCI2. The mixture of diketene and MeCI2 is
prepared inline using a static mixer. In order to remove the heat produced by the
reaction between Cl2 and diketene, the reactor is intensively cooled with a closed
cooling system. During the reaction of Cl2 with diketene, the intermediate product
4-chloro-3-oxobutanoyl chloride (4-CAAC) is produced.
4-CAAMe is subsequently produced by adding methanol (MeOH) to the reacting
mixture leaving the chlorination reactor. MeOH is directly added into the pipeline
which connects the chlorination reactor with the esterification reactor. During the
reaction of esterification one equivalent of HCI is formed. The gases of the
reaction -mainly HCI- are sent to a scrubber system operated with an aqueous
solution of NaOH. The liquid mixture after the esterification reactor is sent to the
distilling purification steps. MeCI2 is recycled to the reaction after its corresponding
purification.
In a typical production campaign of 4-CAAMe, 27 to 30 l/h diketene together with
45 l/h MeCI2 and 25 kg/h of Cl2 gas are continuously fed into the chlorination
reactor. The speed of the reactor-rotor was controlled between 200 and 350 rpm.
In order to avoid the decomposition of diketene in the store tank, the temperature
in the diketene tank is kept at 9 to 14°C. Cl is normally dosed in a light excess ( 1
to 8%) with respect to diketene.
The temperature of the mixture leaving the chlorination reactor is 12 °C to 15°C.
The pressure in the reactor is kept under light vacuum of about -0.1 to -8 mbarg.
The esterification of the mixture is carried out adding 22 - 23 l/h MeOH. During the
reaction of esterification, the temperature of the mixture increases to 30 - 44 °C.
This material flows to a column filled with ceramic random packing, where the
esterification is completed. The reaction of esterification generates one equivalent
of HCI. The HCI is conduced to a scrubber system operated with NaOH. The liquid
phase of the esterification column overflows through a siphon in the flash
distillation of MeCI2. The MeCI2 obtained from the flash distillation is collected and
sent to a recovering process designed to recycle this MeCI2 to the reaction.
The conversion of Cl2 in the chlorination reaction is estimated to be 100%. The
selectivity to 4-CAAC is 95%, the selectivity to 2,4-CAAC is 2%, the selectivity to
other Cl-compounds is estimated to be 3%.
Example 2: Production of 4-CAAEt on pilot scale
The production of 4-CAAEt on pilot scale is carried out using the same setup as
the production of 4-CAAMe described in the example 1.
The reactants chloride gas (Cl ) and diketene are introduced at the top of the
reactor. The solvent in this reaction is dichloromethane (MeCI ) . Before diketene is
fed into the reactor, it is diluted in MeCI2. The mixture diketene and MeCI2 is
prepared inline using a static mixer. In order to remove the heat produced by the
reaction between Cl and diketene, the reactor is intensively cooled with a closed
cooling system. During the reaction of Cl with diketene, the intermediate product
4-chloro-3-oxobutanoyl chloride (4-CAAC) is formed.
4-CAAEt is produced by adding ethanol (EtOH) to the reacting mixture leaving the
chlorination reactor. EtOH is directly added in the pipeline discharging in the
esterification reactor. During the reaction of esterification 4-CAAEt and HCI are
formed. The gases of the reaction -mainly HCI- are sent to a scrubber system
operated with an aqueous solution of NaOH. The liquid mixture after the
esterification reactor is sent to the distilling purification steps. MeCI is recycled to
the reaction after its corresponding purification.
In a typical production campaign of 4-CAAEt, 39 l/h diketene together with 70 l/h
MeCI2 and 3 1 kg/h of CI2 gas are continuously fed into the chlorination reactor.
The speed of the reactor-rotor was controlled between 200 and 350 rpm. In order
to avoid the decomposition of diketene in the store tank, the temperature in tank is
kept at 9 to 14°C. Cl2 is normally dosed in a light excess ( 1 to 8%) with respect to
diketene.
The temperature of the mixture leaving the chlorination reactor is 17 °C to 19°C.
The pressure in the reactor is kept under light vacuum of about -0.1 to -8 mbarg.
The esterification of the mixture is carried out adding 27 l/h EtOH. During the
reaction of esterification, the temperature of the mixture increases to 40 - 53 °C.
This material flows to a column filled with ceramic random packing, where the
reaction of esterification is completed. The esterification reaction generates one
equivalent of HCI. The HCI is conducted to a scrubber system operated with
NaOH. The liquid phase of the esterification column overflows through a siphon in
the flash distillation of MeCI2.
The conversion of CI2 in the chlorination reaction is estimated to be 100%. The
selectivity to 4-CAAC is 95%, the selectivity to 2,4-CAAC is 2%, the selectivity to
other Cl-compounds is estimated to 3%.
Example 3: Production of 4-CAAEt on industrial scale
The reaction of chlorination of diketene takes continuously place on industrial
scale in a wiped-film-reactor (chlorination reactor) with 4 m2 area. The reactor has
160 rolls as wiper elements. The wiper elements are assembled as cylindrical
graphite rolls. The centrifugal force presses the rolls to the reactor wall. The rolls
are aligned in four vertical columns along the reactor circumference. Each column
has 40 rolls. The reactor-rotor speed was varied between 40 rpm and 200 rpm.
The reactants chloride gas (CI2) and diketene are introduced at the top of the
reactor. The solvent in this reaction is dichloromethane (MeC^). Before diketene is
fed into the reactor, it is diluted in MeCI2. The mixture diketene and MeCI2 is
prepared inline using a static mixer. In order to remove the heat produced by the
reaction between CI2 and diketene, the reactor is intensively cooled with a closed
cooling system. During the reaction of Cl2 with diketene, the intermediate product
4-chloro-3-oxobutanoyl chloride (4-CAAC) is produced.
4-CAAEt is synthesized by adding ethanol (EtOH) to the reacting mixture leaving
the chlorination reactor. EtOH is directly added in the pipeline connecting the
chlorination reactor to the esterification reactor. During the reaction of esterification
4-CAAEt and HCI are formed. The gases of the reaction -mainly HCI- are sent to a
scrubber system operated with an aqueous solution of NaOH. The liquid mixture
after the esterification reactor is sent to the distilling purification steps. MeCI2 is
recycled to the reaction after its corresponding purification.
In a typical production campaign of 4-CAAEt, 75 to 150 kg/h diketene together with
150 to 600 kg/h MeCI2 and 62 to 135 kg/h of Cl2 gas are continuously fed into the
chlorination reactor. The speed of the reactor-rotor is controlled between 70 and
120 rpm. In order to avoid the decomposition of diketene in the store tank, the
temperature in tank is kept at 9 to 14°C. Cl2 is normally dosed in a light excess ( 1
to 6%) with respect to diketene.
The temperature of the mixture leaving the chlorination reactor is -5 °C to 30°C.
The pressure in the reactor is kept under light vacuum of about -0.1 to - 10 mbarg.
The esterification of the mixture is carried out adding 40 to 80 kg/h EtOH. During
the esterification reaction the temperature of the mixture increases to 20 - 55 °C.
This material flows to a column filled with ceramic random packing, where the
esterification is completed. This reaction generates one equivalent of HCI as side
product. The HCI is conducted to a scrubber system operated with NaOH. The
liquid phase of the esterification column overflows through a siphon in the flash
distillation of MeCI2.
The conversion of Cl2 in the chlorination reaction is estimated to be 100%. The
selectivity to 4-CAAC is 95%, the selectivity to 2,4-CAAC is 2%, the selectivity to
other Cl-compounds is estimated to be 3%.
The experiments show that the inventive process can be scaled up and carried out
in an industrial scale without significant problems whilst maintaining a high yield
and selectivity.
CLAIMS
1. A process for the production of 4-chloroacetoacetyl chloride, comprising the
steps of
(a) feeding diketene and chlorine into a thin film reactor and
(b) reacting the diketene and chlorine to obtain 4-chloroacetoacetyl
chloride.
2 . The process of claim 1, wherein in step (a) the diketene is fed into the reactor
in the form of a mixture with an organic solvent.
3 . The process of claim 2, wherein the concentration of the diketene in the
mixture is higher than 15% (w/w).
4 . The process of 2 or 3, wherein the solvent is a halogenated alkane, preferably
selected from chloromethane, dichloromethane, trichloromethane (chloroform),
tetrachloromethane, chloroethane, 1,2-dichlorethane, trichloroethane,
tetrachloroethane, dichloropropane, 1-chloro-2-fluoroethane, 1, 1 -
dichloroethane, 1,2-dichloroethane, methylchloroform, 1-chlorobutane, 2-
chlorobutane, 1-bromobutane, ethyl bromide, 1-bromo-2-chloroethane, 1-
bromo-2-fluoroethane, 1-iodobutane, bromochloromethane, dibromomethane,
1, 1-dibromomethane, difluoroiodomethane, 1-bromopropane,
bromochlorofluoromethane, 2-bromopropane, bromodichloromethane,
bromofluoromethane, bromotrichloromethane, dibromodifluoromethane,
pentachloromethane, 1, 1 , 1 ,2-tetrachloroethane, fluoroiodomethane,
iodomethane, diiodofluoromethane, 1, 1 ,2,2-tetrachloromethane, 1,1 ,2-
trichloroethane, 1-chloropropane, 1,2-dibromopropane, 1,2,3-trichloropropane,
1, 1 ,1 ,2-tetrachloropropane and mixtures thereof or mixtures comprising at least
one thereof.
5 . The process of at least one of the preceding claims, wherein in step (a) the
chlorine is fed into the reactor in the form of gaseous chlorine.
6 . The process of at least one of the preceding claims, wherein the reactor is a
wiped film reactor.
7 . The process of at least one of the preceding claims, wherein the process is a
continuous process, wherein the diketene is fed into the reactor at a rate of at
least 10 kg/h, more preferably at least 75 kg/h.
8 . The process of at least one of the preceding claims, wherein the reaction
temperature is between - 15°C and 60°C.
9 . The process of at least one of the preceding claims, wherein the solvent is
recycled and reused in the process.
10 .The process of at least one of the preceding claims, wherein the solvent has a
purity of at least 98 weight %.
11.A process for the production of a 4-chloroacetoaceticacid ester, a 4-
chloroacetoaceticacid amide or a 4-chloroacetoaceticacid imide, comprising
the steps
(c) transferring 4-chloroacetoacetyl chloride obtained according to a
process of any of the preceding claims into a second reactor and
(d) reacting the 4-chloroacetoacetyl chloride with an alcohol or amine to
obtain the 4-chloroacetoaceticacid ester, 4-chloroacetoaceticacid amide
or a 4-chloroacetoaceticacid imide.
12 .The process of claim 11, wherein the alcohol is an alkanol, preferably
methanol, ethanol, isopropanol, e -butanol or phenol, or an amine, preferably
an alkyl amine, such as a cyclic secondary alkyl amine, or an aryl amine, such
as aniline.
13 .The process of at least one of claims 11 and 12, wherein the reaction
temperature in step (d) is between 0°C and 80°C.
14. The process of at least one of claims 11 to 13, wherein the yield of the 4-
chloroacetoaceticacid ester, 4-chloroacetoaceticacid amide or 4-
chloroacetoaceticacid imide is at least 90%, based on the total amount of
ketene provided in step (a).