HK1192878B - Process for the production of 4-chloroacetoacetyl chloride, 4-chloroacetoacetic acid esters, amides and imides - Google Patents

Description

Process for the preparation of 4-chloroacetoacetyl chloride, 4-chloroacetoacetate, 4-chloroacetoacetamide and 4-chloroacetoacetamide

Technical Field

The present invention relates to processes for the preparation of 4-chloroacetoacetyl chloride, 4-chloroacetoacetate, 4-chloroacetoacetamide and 4-chloroacetoacetamide.

Background

Methods for preparing 4-chloroacetoacetyl chloride (4-chloro-3-oxobutanoyl chloride) and esters derived from 4-chloroacetoacetyl chloride are known in the art. In a specific process, 4-chloroacetoacetyl chloride is obtained by reacting chlorine gas with diketene (4-methyleneoxetan-2-one).

The reaction occurs exothermically and therefore requires cooling. The reaction products are relatively sensitive to heat, and if the temperature deviates locally or globally from the given range, the formation of undesired by-products and decomposition are observed. For example, the undesired reaction products may be regioisomers (e.g., 2-chloroacetoacetyl chloride) or over-chlorinated products (e.g., di-or tri-halogenated compounds, such as 2, 4-dichloroacetoacetyl chloride or 2,2, 4-trichloroacetoacetyl chloride). Therefore, it is difficult to determine efficient preparation conditions for obtaining high yields.

JP 113824 proposes a process wherein diketene is dissolved in a solvent and reacted with chlorine in a column reaction vessel with cooling. Chlorine gas is fed to the column in a continuous flow or counter-current manner. However, less than 90% selectivity was obtained.

A solvent-free process is disclosed by US4,468,356, according to US4,468,356, diketene spray is contacted continuously with chlorine gas in a reaction zone at a temperature between 80 ℃ and 210 ℃. Subsequently, the intermediate product was subjected to an esterification reaction using ethanol. However, the overall yield is lower than 80% and is therefore relatively low, probably due to the relatively high temperature to which the intermediate product is exposed. Furthermore, the reaction is only carried out on a laboratory scale using small amounts of starting compounds.

Reactions for the preparation of chloroacetoacetic acid on a laboratory scale from diketene and chlorine are disclosed in US3,950,412 and US3,701,803. In US4,473,508, the method of US3,701,803 is discussed. The inventors concluded that scale-up was not possible due to problems associated with heat transfer. In order to provide an efficient reaction on an increased scale, it is proposed to react a solution of diketene in an inert solvent with a solution of chlorine dissolved in an inert solvent in a tubular reactor. The acid chloride intermediate can be prepared in 98% yield according to example 6. However, the process is relatively inefficient because both starting compounds are diluted in a relatively large amount of solvent. Therefore, the entire reaction requires a large amount of solvent, and thus a large reactor and equipment and more energy for cooling are required. When the reactor volume was increased, the yield decreased "significantly" and the selectivity was relatively low (US 4,473,508, example 7). It would therefore be desirable to provide a more efficient process that requires less solvent and is more selective and efficient on a large scale.

A laboratory process to prepare ethyl-4-chloroacetoacetate from diketene and chlorine is disclosed by Shandong Huagong 2007, 36(10), 4-6 to Pan et al. In this process, it is proposed to use a relatively high concentration of diketene of about 24 to 28 wt.%. However, the yield of ester was only about 80% and the reaction was carried out in a reaction flask on a small scale without any suggestion on how to solve the heat transfer problem on an increased scale.

JP 62-053940-a relates to a process for the preparation of 4-chloroacetoacetyl chloride wherein diketene and chlorine are reacted in a thin film reactor on a laboratory scale wherein the chlorine is diluted with an inert gas.

JP 60-25955-a relates to a process for the preparation of gamma-chloroacetoacetate on a laboratory scale from chlorine and diketene in a batch reactor.

JP 60-259591-a relates to a process for the preparation of gamma-chloroacetoacetyl chloride in a rotating thin film reactor, wherein diketene is reacted with a solution of chlorine in dichloroethane on a laboratory scale.

The methods known in the art are also problematic in terms of process safety. Especially when carried out on an industrial scale, the reaction requires large amounts of chlorine and diketene. These substances are highly reactive and dangerous when inhaled. When the reactor is damaged or when the process is disturbed and out of control, the reactants can harm people in the environment and explode. Thus, industrial upscaling (if any) is only possible under strict safety precautions.

The fundamental problem of the invention

The problem underlying the present invention is to provide a process for the preparation of 4-chloroacetoacetyl chloride and reaction products obtainable therefrom, which process overcomes the above-mentioned problems. The process should provide the reaction product in high yield and selectivity. The process should be applicable as a continuous process on a large industrial scale. In particular, the reaction efficiency should be high and the solvent consumption should be low.

Another problem underlying the present invention is to provide an industrial scale process which is relatively safe and which reduces the potential risks associated with handling large amounts of chlorine and diketene.

Disclosure of Invention

Surprisingly, the problem underlying the present invention is solved by a method according to the claims. Additional embodiments of the invention are disclosed throughout the specification.

The subject of the present invention is a process for the preparation of 4-chloroacetoacetyl chloride, comprising the steps of:

(a) feeding diketene and chlorine to a membrane reactor, and

(b) diketene is reacted with chlorine to obtain 4-chloroacetoacetyl chloride.

According to the present invention it was found that a highly efficient reaction between diketene and chlorine can be carried out in a thin film reactor. After diketene and chlorine are fed into the thin film reactor, they react in the thin film reactor. 4-chloroacetoacetyl chloride is formed as a reaction product and can be removed from the reactor.

In a preferred embodiment of the present invention, in step (a), diketene is fed to the reactor as a mixture with an organic solvent. The mixture is preferably a solution of diketene in an organic solvent.

In principle, any organic solvent in which diketene is readily soluble and which does not react with or interfere with diketene may be used. Therefore, the solvent should be an inert solvent. In this connection, alcohols are unsuitable since they will react in the esterification reaction in a thin film reactor by acetoacetate formation. Preferred inert solvents are halogenated hydrocarbons, preferably halogenated alkanes, for example methyl chloride, methylene chloride, chloroform (chloroform), tetrachloromethane, ethyl chloride, 1, 2-dichloroethane, trichloroethane, tetrachloroethane, dichloropropane, 1-chloro-2-fluoroethane, 1-dichloroethane, 1, 2-dichloroethane, methylchloromethane, 1-chlorobutane, 2-chlorobutane, 1-bromobutane, ethylbromide, 1-bromo-2-chloroethane, 1-bromo-2-fluoroethane, 1-iodobutane, bromochloromethane, dibromomethane, 1-dibromomethane, difluoroiodomethane, 1-bromopropane, bromochlorofluoromethane, 2-bromopropane, bromodichloromethane, bromofluoromethane, bromotrichloromethane, dibromodifluoromethane, bromodifluoromethane, 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 a mixture thereof or a mixture comprising at least one of the same.

In a highly preferred embodiment of the invention, the solvent is dichloromethane. Methylene chloride is known in the art as an effective inert solvent for the reaction between diketene and chlorine.

According to the present invention, it was found that the reaction can be carried out with high efficiency even when diketene is provided in an organic solvent at a relatively high concentration. 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 may be at most 80% (w/w) or at most 50% (w/w). In preferred embodiments, the concentration of 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 may also be between 21% and 80%, preferably between 21 and 60% or between 21 and 50% (w/w). A relatively higher concentration of diketene is advantageous because the overall solvent consumption is lower. In addition, the volume of reaction mixture in the thin film reactor is kept relatively low. The contact area between the reactants is high and good space-time yields can be obtained. Furthermore, heat removal is more efficient if the volume is smaller and if therefore also the film thickness. Thus, the process is efficient in terms of energy and cost, especially when performed on an industrial scale.

According to the present invention, it is preferred that chlorine is fed to the reactor in step (a) in the form of gaseous chlorine. When gaseous chlorine is used, the total consumption of solvent is reduced even further. Therefore, when diketene dissolved in an organic solvent (preferably dichloromethane) at a relatively high concentration is used, and gaseous chlorine is used, the reaction is highly efficient due to the reasons described above with respect to the high diketene concentration. The reaction volume in thin-film reactors is relatively low and the space-time efficiency is increased, while the heat transfer is promoted. Furthermore, the use of chlorine in gaseous form avoids the pre-dissolution step. This is advantageous because chlorine is aggressive and complex to handle in large scale industrial processes.

According to the invention, it is not necessary to use an inert gas for diluting the chlorine. Thus, in a preferred embodiment of the invention, no inert gas is introduced into the membrane reactor and/or chlorine is not mixed with the inert gas before or at the time of introduction into the membrane reactor. Preferably, only diketene, chlorine and organic solvent are introduced into the thin film reactor. Thus, the overall consumption of material, and therefore the cost and energy, can be kept low.

The reaction in step (a) of the present invention is carried out in a thin film reactor. In such a thin film reactor, the reaction takes place on at least one reactor surface. Typically, thin film reactors allow for continuous renewal of the reaction surface. The thin film is produced on the reaction surface by rotating the surface. Thus, the reactor is different from a reactor in which the reaction is carried out in a spatial liquid volume, such as a tubular reactor. The reactor comprises means for distributing the liquid reactants to the reaction surface. Furthermore, the reactor should comprise cooling means. Preferably, the cooling device is a heat exchanger. In the process of the present invention, it is preferred that the heat generated by the exothermic reaction is continuously removed from the reactor. Thus, the reaction temperature can be kept stable and relatively low locally and globally. The thickness of the film is adapted to the cooling system and heat dissipation is required. Typically, the average thickness of the film may be between 0.05mm and 15mm, more particularly between 0.1 and 5 mm.

In a highly preferred embodiment of the invention, the reactor is a wiped film reactor. The wiped film reactor comprises wiping means such as blades, scrapers or rollers. Typically, such rolls or scrapers are pressed against the reactor wall by centrifugal force. The scraping device is in contact with the film and is typically moved by rotation. By rotating the scraping device and thus by rotating the film, a film renewal and a complete and continuous mixing are achieved. The scraping means may be arranged in columns or rows. The scraping device is typically made of an inert material such as PTFE (preferably available under the trademark Teflon from DuPont), a metal alloy, preferably a nickel alloy (preferably those available under the trademark Hastelloy from haynesint), stainless steel or graphite. Typically, the number of scraping elements is between 2 and 1000, more preferably between 10 and 1000 or between 50 and 500. For example, a commercial scale reactor may comprise 4 rows each equipped with 40 rolls. The blade may be straight or wound, preferably spirally wound.

Wiped film reactors are commonly used in the art for distilling thermally unstable compounds. However, wiped film reactors have also been described in the art for chemical reactions. The use in polymerization reactions and the regulation of the reactor are described by Steppan et al ("Wiped film reactor model for nylon 6,6 polymerization", 1990, Ind. Eng. chem. Res.29, 2012-. The basic considerations disclosed therein can also be used to adjust the wiped film reactor in the process of the present invention to obtain the best yield. The reaction conditions are selected and adjusted according to the specific reactor model taking into account parameters such as the number and type of blades, liquid distribution system, temperature, reactor volume, pressure, rotor speed, desired film thickness, etc.

The area of the wiped film reactor is preferably 0.5 to 30m²Preferably 1 to 15m²In the meantime. Preferably the area is at least 0.5, at least 1 or at least 2m². The reactor speed may be between 10 and 2000rpm, preferably between 20 and 1000 rpm.

In a preferred embodiment of the invention, the process is a continuous process. Preferably, diketene is fed to the reactor at a rate of at least 10 kg/h. More preferably, diketene is fed to the reactor at a rate of at least 20kg/h, at least 30kg/h or at least 75 l/h. Diketene may be fed to the reactor at a rate of between 10 and 500kg/h, or between 75 and 250 kg/h. Thin film reactors are generally tuned for continuous processes. The reactants are fed into the reactor at a constant rate, while the reaction products are withdrawn from the bottom of the reactor at a constant rate. It has been found that the reaction of the present invention is effective at a relatively large scale, which is applicable to industrial production. Preferably, chlorine is fed to the reactor at a rate of at least 10 kg/hour, 20 kg/hour or 50 kg/hour. Chlorine may be fed to the reactor at a rate of between 250 and 500kg/h, or between 50 and 250 kg/h. The scale-up process can still provide products in high yield and selectivity due to the low amount of solvent and high reaction and heat transfer efficiency in a particular reactor. This is unexpected because it was not expected that scale-up reactions would be efficient and at the same time achieve high yields using relatively low amounts of solvent. Preferably, the volume of the thin film reactor is at least 50l, at least 100l or at least 500 l.

In the scale-up process of the present invention, the turnover of starting compounds and the reactor volume are relatively large. However, the reactants in the reactor are mostly present in the form of a thin film, and thus the effective hold-up of the reactants in the thin film reactor is significantly reduced compared to a conventional batch reactor or tubular reactor. The process of the invention is therefore generally safer in view of the high reactivity and the potential danger of the dangerous chlorine and diketene. For example, when the reactor is damaged, or when the reaction runs away, relatively small amounts of chlorine and diketene may react or leak out of the reactor in an uncontrolled manner. The potential consequences are less severe than in conventional reactors comprising a space batch volume with a high hold-up of chlorine and diketene. The method of the present invention thus solves the problem of providing a more secure method.

Furthermore, it has been found that the reaction of the present invention can be carried out at relatively low temperatures and with high efficiency on a large scale. Diketene and 4-chloroacetoacetyl chloride are temperature sensitive, so that the yield decreases 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 ℃ and 60 ℃. More preferably, the reaction temperature of the first reaction is maintained between-15 ℃ and 45 ℃ or between 0 ℃ and 30 ℃. Also preferably, the reaction temperature of the first reaction is maintained between 5 ℃ and 45 ℃ or between 5 ℃ and 30 ℃, or between 5 ℃ and 20 ℃. Preferably, the reaction temperature is 60 ℃ or less, 40 ℃ or less, 30 ℃ or less, or 20 ℃ or less. The reaction temperature is adjusted by cooling the reactor using a cooling device such as a heat exchanger. Preferably, the heat exchanger comprises a hot fluid directly on the surface side, which is not in contact with the reaction mixture. Heat exchange can be carried out with good efficiency in a thin film reactor even on a large scale. The mean residence time of diketene in the membrane reactor can be adjusted to be relatively low to avoid degradation and side reactions. The average residence time may be between 2s and 500s, or between 5s and 250 s.

The reaction in the thin film reactor may be carried out at normal pressure, or may be carried out at overpressure or sub-atmospheric pressure or under slight vacuum. Therefore, the whole reaction can be carried out under mild conditions.

According to the present invention, it was found that the residence time of reactants in a thin film reactor can be set relatively low even at low temperatures, and at the same time high yields are obtained, taking into account the low solvent amount and the high contact area in the reactor. This was not expected, since the residence time increased in principle at relatively low temperatures and on a large scale. However, the overall device with a film construction preferably supported by scraping reduces the residence time.

As mentioned above, the total amount of solvent used in the process of the invention can be kept relatively low. When the solvent is recycled, the solvent consumption can be reduced even further. More preferably, the solvent may also be reused in the process. In a preferred embodiment of the invention, the solvent is recycled and reused. After the esterification or amidation reaction, recycling may include any suitable method, such as distillation, liquid-liquid extraction, reactive extraction, membrane separation techniques, chromatography, or crystallization of a solvent, or a combination of these methods. The purified solvent is then preferably reintroduced into the process after mixing the purified solvent with the diketene in the reactant stream.

In a preferred embodiment of the invention, the solvent is dichloromethane having a purity of at least 98% by weight. Preferably, the content of chlorine, water and/or alcohol is low.

Another subject of the present invention is a process for the preparation of 4-chloroacetoacetate, 4-chloroacetoacetamide or 4-chloroacetoacetamide, comprising the steps of:

(c) transferring the 4-chloroacetoacetyl chloride obtained according to the process of the invention into a second reactor, and

(d) reacting 4-chloroacetoacetyl chloride with an alcohol or an amine to obtain 4-chloroacetoacetate, 4-chloroacetoacetamide or 4-chloroacetoacetamide.

Thus, the reaction product of the initial reaction of diketene and chlorine can be further reacted in a second reaction. Preferably, the first and second reactions are part of a single continuous process. In this continuous process, the 4-chloroacetoacetyl chloride formed by the first reaction is withdrawn from the first reactor, which is a thin film reactor, and transferred directly to the second reactor.

In the second reactor, an esterification reaction, an amidation reaction, or an imidization reaction is performed. The reactor may be any type of reactor suitable for these reactions. For example, the reactor may be or may include a vessel, tube, or column. The first and second reactors are connected by a connecting means such as a pipe, tube or hose. Thus, the overall process can be carried out in an efficient manner without intermediate purification or isolation of 4-chloroacetoacetyl chloride. However, the reaction can also be carried out after an intermediate isolation of 4-chloroacetoacetyl chloride.

Esterification, amidation, or imidization reactions are typical reactions of acid chlorides with alcohols or amines.

In a preferred embodiment, the alcohol is an alkyl alcohol (i.e., an alkanol) or an aryl alcohol (e.g., phenol). For example, the alcohol may be selected from methanol, ethanol, isopropanol, n-butanol, t-butanol, and phenol. In preferred embodiments, the alcohol is methanol, ethanol or phenol. To obtain the amides, primary or secondary amines are used, preferably alkylamines (such as cyclic secondary alkylamines) or arylamines (such as anilines). The aryl group of the aniline may be substituted. The alkyl group of the alcohol or amine may have between 1 and 10 carbon atoms, preferably between 1 and 4 carbon atoms.

During the second reaction, HCl is formed in an almost stoichiometric amount. The amount of HCl product formed during the process is nearly equimolar to the product (and by-products). Preferably, gaseous HCl is removed from the off-gas by neutralization, for example, using an alkaline scrubbing system. However, residual amounts of HCl are typically dissolved in the solvent. The remaining amount of HCl must be neutralized, for example, by extraction with an aqueous alkaline solution, before the solvent is reused.

The reaction conditions (e.g. temperature and pressure) are adapted to obtain high yields while consuming relatively low amounts of energy.

In a preferred embodiment of the present invention, the reaction temperature in step (d) is between 0 ℃ and 80 ℃, or preferably between 20 ℃ and 60 ℃. The reaction can be carried out at normal pressure, overpressure or underpressure.

Preferably, the dichloromethane solvent is distilled and/or recycled after the second reaction in step (d). In or before the recycling step, the HCl should preferably be removed from the solvent by neutralization. The solvent may be purified by known means, for example using dehydration columns, molecular sieves, membrane separation techniques, liquid-liquid extraction, reactive extraction, chromatography and/or crystallization, or a combination of these methods.

In a preferred embodiment of the present invention the yield of 4-chloroacetoacetate, 4-chloroacetoacetamide or 4-chloroacetoacetamide is at least 90% based on the total amount of ketene provided in step (a). More preferably, the yield is 92% or more or 95% or more. Preferably, the yield of 4-chloroacetoacetyl 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%.

Drawings

FIG. 1 shows a schematic view of aA wiped film reactor suitable for use in the method of the invention is shown schematically and by way of example.

FIG. 2A top view of a possible arrangement of the scrapers inside the membrane chlorination reactor is shown schematically and by way of example.

FIG. 3The present invention is shown schematically and by way of example for the preparation of 4-chloroacetoacetate from diketene and gaseous chlorineAn apparatus for a continuous process is disclosed.

Detailed Description

A wiped film reactor for use in the first reaction of the present invention is shown in figure 1. The reactor comprises means (1) and (2) for feeding diketene and chlorine. The reactor comprises means (3) and (4) for supplying a heat exchange fluid to the heat exchange means. The product is eluted through means (9) and the vapour and/or gas can be vented through means (5), said means (5) may comprise a valve (10). The reactor comprises a rotor axis (6), the circular motion occurring around said rotor axis (6). The reaction mixture is fed to the reactor in a manner that flows down on the outside of the reactor where it is mixed and distributed. The reactor comprises means for distributing the liquid (7) and a doctor blade (8), on which doctor blade (8) a film is formed. A top view of a thin film reactor with spirally wound doctor blades is shown in fig. 2.

A typical setup of the method of the invention is shown by figure 3. An exemplary route is shown using a thin film reactor for carrying out the conversion of diketene and gaseous chlorine, while diketene is dissolved in an organic solvent and transferred to a second reactor unit for the preparation of 4-chloroacetoacetate, 4-chloroacetoacetamide or 4-chloroacetoacetamide. Gaseous chlorine and diketene solution are fed into the membrane reactor (11) through an inlet (13) for diketene solution and an inlet (15) for chlorine. The 4-chloroacetoacetyl chloride intermediate is eluted from reactor (11) and combined with an alcohol or amine reagent fed into the reaction stream through inlet (14). The reaction stream enters the reactor (12). The crude reaction product is removed to obtain a crude product (16), said crude product (16) being purified by a distillation device (17) and separated via an outlet (18). The solvent can be recycled by means of a recycling device (18) and returned to the chlorination reaction via connection (19). The reactors (11), (12) and the devices (16), (17) are connected by connecting means, such as pipes or hoses. The size, connection and location of the inlet and outlet ports are shown schematically and are not to be construed as limiting.

The method of the present invention solves the fundamental problem of the present invention. The present invention provides an efficient process for reacting diketene with chlorine to obtain 4-chloroacetoacetyl chloride, and reaction products obtainable therefrom. The reaction can be carried out with high selectivity and yield. A low solvent amount is used, which makes the process more efficient. The method is effective at low temperatures. Scale-up is possible while maintaining high yields. Overall, the reactants have a low residence time in the reactor, a high flux and a high space-time yield, and a good heat removal in the first reactor.

It was further observed that uniform heat removal in the thin film reactor was possible, so that no local overheating was observed. Local overheating can lead to partial decomposition of the reactants or products. Furthermore, the chlorination reaction of the present invention provides high selectivity and only small amounts of over-chlorinated products, which may produce undesirable by-products. It is not necessary to dissolve chlorine in the solvent, which makes the process more efficient and easier to handle. The solvent may be recycled and reintroduced into the process.

Examples

Example 1: preparation of 4-CAAMe at Pilot Scale

The chlorination reaction of diketene is carried out at the concentration of 1.5m²The operation in the wiped-film reactor (chlorination reactor) of the area was carried out continuously on a pilot scale. The reactor had 20 scrapers. The scrapers were arranged in five rows along the reactor. Each column has four blades separated from each other by 90 °. The blades of one row are staggered by 25 deg. with respect to the position corresponding to the blades of the adjacent row. The blades were assembled in the form of a spiral wound Teflon sheet. Figure 2 shows schematically how the scraper is mounted inside the reactor. The reactor rotor speed was between 80rpm and 500 rpm.

Reactant chlorine (Cl)₂) And diketene is introduced at the top of the reactor. The solvent in this reaction was dichloromethane (MeCl)₂). Diketene is in MeCl before it is fed to the reactor₂And (4) diluting. On-line preparation of diketene and MeCl using static mixer₂A mixture of (a). To discharge Cl₂The heat generated by the reaction with diketene is intensively cooled by a closed cooling system in the reactor. In Cl₂In the process of reacting with diketene, the intermediate product 4-chloro-3-oxobutyryl chloride (4-CAAC) is prepared.

4-CAAMe was then prepared by adding methanol (MeOH) to the reaction mixture leaving the chlorination reactor. MeOH was added directly to the line connecting the chlorination reactor and the esterification reactor. During the esterification reaction, one equivalent of HCl is formed. The gas of reaction (mainly HCl) was sent to a scrubber system operating with aqueous NaOH. The liquid mixture after the esterification reactor is sent to a distillation purification step. In MeCl₂After the corresponding purification, it is recycled to the reaction.

In a typical 4-CAAMe preparation activity, 27 to 30l/h diketene are combined with 45l/hMeCl₂And 25kg/h Cl₂Gas is continuously fed to the chlorination reactor. The speed of the reactor rotor was controlled between 200 and 350 rpm. To avoid decomposition of the diketene in the storage tank, the temperature in the diketene tank is maintained at 9 to 14 ℃. Cl₂Usually in slight excess (1 to 8%) relative to diketene.

The temperature of the mixture leaving the chlorination reactor is from 12 ℃ to 15 ℃. The pressure in the reactor was maintained under a slight vacuum of about-0.1 to-8 mbarg. The esterification of the mixture was carried out by adding 22-23l/h MeOH. During the esterification reaction, the temperature of the mixture increased to 30-44 ℃. The material flows to a column packed with ceramic random packing where esterification is completed. The esterification reaction produces one equivalent of HCl. HCl was introduced into the scrubber system operated with NaOH. Liquid phase of esterification column in MeCl₂In the flash evaporation ofThe overflow passes through the siphon. MeCl obtained by flash evaporation₂Collected and sent to a recovery process designed to recycle the MeCl₂And recycled to the reaction.

Cl in chlorination reaction₂The conversion of (a) was estimated to be 100%. The selectivity to 4-CAAC was 95%, the selectivity to 2,4-CAAC was 2%, and the selectivity to the other Cl components was estimated to be 3%.

Example 2: preparation of 4-CAAEt at Pilot Scale

The preparation of 4-CAAEt on a pilot scale was carried out using the same apparatus as the preparation of 4-CAAMe described in example 1.

Reactant chlorine (Cl)₂) And diketene is introduced at the top of the reactor. The solvent in this reaction was dichloromethane (MeCl)₂). Diketene is in MeCl before it is fed to the reactor₂And (4) diluting. On-line preparation of diketene and MeCl using static mixer₂A mixture of (a). To discharge Cl₂The heat generated by the reaction with diketene is intensively cooled by a closed cooling system in the reactor. In Cl₂During the reaction with diketene, 4-chloro-3-oxobutanoyl chloride (4-CAAC) is formed as an intermediate.

4-CAAEt was prepared by adding ethanol (EtOH) to the reaction mixture leaving the chlorination reactor. EtOH was added directly to the line discharging into the esterification reactor. During the esterification reaction, 4-CAAEt and HCl are formed. The gas of reaction (mainly HCl) was sent to a scrubber system operating with aqueous NaOH. The liquid mixture after the esterification reactor is sent to a distillation purification step. In MeCl₂After the corresponding purification, it is recycled to the reaction.

In a typical 4-CAAEt preparation activity, 39l/h diketene are combined with 70l/h MeCl₂And 31kg/h Cl₂Gas is continuously fed to the chlorination reactor. The speed of the reactor rotor was controlled between 200 and 350rpm. To avoid decomposition of diketene in the storage tank, the temperature in the tank is maintained at 9 to 14 ℃. Cl₂Usually in slight excess (1 to 8%) relative to diketene.

The temperature of the mixture leaving the chlorination reactor is between 17 ℃ and 19 ℃. The pressure in the reactor was maintained under a slight vacuum of about-0.1 to-8 mbarg. The esterification of the mixture was carried out by adding 27l/h EtOH. During the esterification reaction, the temperature of the mixture increased to 40-53 ℃. The material flows to a column packed with ceramic random packing where the esterification reaction is completed. The esterification reaction produces one equivalent of HCl. HCl was introduced into the scrubber system operated with NaOH. Liquid phase of esterification column in MeCl₂Overflows through a siphon.

Cl in chlorination reaction₂The conversion of (a) was estimated to be 100%. The selectivity to 4-CAAC was 95%, the selectivity to 2,4-CAAC was 2%, and the selectivity to the other Cl components was estimated to be 3%.

Example 3: preparation of 4-CAAEt on an industrial scale

The chlorination reaction of diketene has a reaction pressure of 4m²The continuous operation on an industrial scale in an area wiped-film reactor (chlorination reactor). The reactor had 160 rolls as the scraper elements. The blade elements are assembled in the form of cylindrical graphite rolls. Centrifugal force presses the rolls to the reactor wall. The rollers are arranged in four vertical columns along the circumference of the reactor. Each column has 40 rollers. The reactor rotor speed was between 40rpm and 200 rpm.

Reactant chlorine (Cl)₂) And diketene is introduced at the top of the reactor. The solvent in this reaction was dichloromethane (MeCl)₂). Diketene is in MeCl before it is fed to the reactor₂And (4) diluting. On-line preparation of diketene and MeCl using static mixer₂A mixture of (a). To discharge Cl₂The heat generated by the reaction with diketene is intensively cooled by a closed cooling system in the reactor. In Cl₂And is twoIn the ketene reaction process, an intermediate product 4-chloro-3-oxobutyryl chloride (4-CAAC) is prepared.

4-CAAEt was synthesized by adding ethanol (EtOH) to the reaction mixture leaving the chlorination reactor. EtOH was added directly to the line connecting the chlorination reactor to the esterification reactor. During the esterification reaction, 4-CAAEt and HCl are formed. The gas of reaction (mainly HCl) was sent to a scrubber system operating with aqueous NaOH. The liquid mixture after the esterification reactor is sent to a distillation purification step. In MeCl₂After the corresponding purification, it is recycled to the reaction.

In a typical 4-CAAEt preparation activity, 75 to 150kg/h diketene are added together with 150 to 600kg/h MeCl₂And 62 to 135kg/h Cl₂Gas is continuously fed to the chlorination reactor. The speed of the reactor rotor was controlled between 70 and 120 rpm. To avoid decomposition of diketene in the storage tank, the temperature in the tank is maintained at 9 to 14 ℃. Cl₂Usually in slight excess (1 to 6%) relative to diketene.

The temperature of the mixture leaving the chlorination reactor is between-5 ℃ and 30 ℃. The pressure in the reactor was maintained under a slight vacuum of about-0.1 to-10 mbarg. The esterification of the mixture was carried out by adding 40 to 80kg/h EtOH. During the esterification reaction, the temperature of the mixture was increased to 20-55 ℃. The material flows to a column packed with ceramic random packing where esterification is completed. The reaction produces one equivalent of HCl as a by-product. HCl was introduced into the scrubber system operated with NaOH. Liquid phase of esterification column in MeCl₂Overflows through a siphon.

Cl in chlorination reaction₂The conversion of (a) was estimated to be 100%. The selectivity to 4-CAAC was 95%, the selectivity to 2,4-CAAC was 2%, and the selectivity to the other Cl components was estimated to be 3%.

Experiments have shown that the process of the present invention can be scaled up and carried out on an industrial scale without significant problems, while maintaining high yields and selectivities.

Claims (14)

1. A process for preparing 4-chloroacetoacetyl chloride, comprising the steps of:

(a) feeding diketene and chlorine to a wiped film reactor, and

(b) reacting diketene with chlorine to obtain 4-chloroacetoacetyl chloride,

wherein in step (a) diketene is fed to the reactor in a mixture with the organic solvent, wherein the concentration of diketene in the mixture is higher than 15% (w/w),

wherein in step (a) chlorine is fed to the reactor as gaseous chlorine, wherein the chlorine is not diluted with an inert gas,

the process is a continuous process wherein diketene is fed to the reactor at a rate of at least 10 kg/h.

2. The method of claim 1, wherein the solvent is a halogenated alkane selected from the group consisting of: methyl chloride, methylene chloride, chloroform (chloroform), tetrachloromethane, ethyl chloride, 1, 2-dichloroethane, trichloroethane, tetrachloroethane, dichloropropane, 1-chloro-2-fluoroethane, 1, 1-dichloroethane, 1, 2-dichloroethane, methylchloroform, 1-chlorobutane, 2-chlorobutane, 1-bromobutane, ethylbromide, 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, trichlorobromotrichloromethane, bromodifluoromethane, pentachloromethane, 1,1,1, 2-tetrachloroethane, trichloromethane, 1-bromobromobromobromobromobromobromomethane, 1, 2-bromo, 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 of the same.

3. The process according to claim 1, wherein diketene is fed into the reactor at a rate of at least 75 kg/h.

4. The process of claim 1, wherein the reaction temperature is between-15 ℃ and 60 ℃.

5. The process of claim 1, wherein the solvent is recycled and reused in the process.

6. The method of claim 1, wherein the solvent has a purity of at least 98 wt.%.

7. A process for preparing 4-chloroacetoacetate, 4-chloroacetoacetamide, or 4-chloroacetoacetamide, comprising the steps of:

(c) preparing 4-chloroacetoacetyl chloride according to the method of any of the preceding claims, transferring it to a second reactor, and

(d) reacting 4-chloroacetoacetyl chloride with an alcohol or a phenol or an amine to obtain 4-chloroacetoacetate, 4-chloroacetoacetamide or 4-chloroacetoacetamide.

8. The method of claim 7, wherein the alcohol is an alkanol.

9. The process according to claim 7 or 8, wherein the reaction temperature in step (d) is between 0 ℃ and 80 ℃.

10. The process according to claim 7, wherein the yield of 4-chloroacetoacetate, 4-chloroacetoacetamide or 4-chloroacetoacetamide is at least 90% based on the total amount of ketene provided in step (a).

11. The process according to claim 1, wherein diketene is fed into the reactor at a rate of at least 30 kg/h.

12. The method of claim 8, wherein the alkanol is methanol, ethanol, isopropanol, or tert-butanol.

13. The method of claim 7, wherein the amine is an alkyl amine or an aryl amine.

14. The method of claim 13, wherein the alkyl amine is a cyclic secondary alkyl amine or wherein the aryl amine is aniline.