Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
  • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
  • C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
  • C07C49/782—Ketones containing a keto group bound to a six-membered aromatic ring polycyclic
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
  • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
  • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation

Definitions

• the present invention relates to a process for the synthesis of beta-dicarbonyl compounds on an industrial scale from at least two carbonyl compounds such as esters or ketones in the presence of a strong base or a mixture of bases strong by Claisen condensation, in particular beta-diketones from at least one ketone and at least one ester.
• This process comprises reacting at least two carbonyl compounds such as esters or ketones in the presence of a strong base or a mixture of strong bases by Claisen condensation, in particular at least one ketone and at least one ester according to reaction R 1 -CO-CH 2 -R 2 + R 3 -CO-O-R 4 -> R 1 -CO-CHR 2 -CO-R 3 + R 4 -OH
• Beta-diketones correspond to industrial additives which are widely used especially as stabilizing agents for plastics and cosmetics, in particular because of their anti-UV and anti-oxidant properties.
• stabilizers based on tin will also be banned in the near future.
• beta-diketones which are distinguished by a series of advantages, in particular from the point of view of ecology and the preservation of the environment.
• beta-diketones The classical synthesis process of beta-diketones is the Claisen condensation which has been extensively described in the literature and consists in reacting at least one ketone and at least one ester in the presence of a strong base or a mixture of bases. strong.
• the base generally consisting of an alkoxide and, if appropriate, a solvent.
• the ketone is introduced into the reactor over several hours, and the alcohol formed is generally removed from the reaction mixture by distillation throughout the course of the reaction.
• a complement of solvent may optionally be added during the reaction.
• reaction mixture After completion of the addition of the ketone and a finishing and resting time, the reaction mixture is acidified, washed, stripped of solvent and purified.
• This article also describes the synthesis of beta-diketones substituted from salts of beta-diketones and alkyl halides.
• the titles are relatively low, from 30 to 56%, and moreover the cycle times can reach forty hours to obtain the best titles.
• the ketone, the ester and the lime were introduced together into the reactor and heated to a high temperature close to 200 ° C., with a ketone / ester ratio of 1: 1 to 1: 1 to 1: 10, and the reaction lasted from 3 to 16 hours.
• Titres ranging from 0 to 86% were obtained; the extreme case of 0% of titre was obtained for a too low temperature and when the reaction took place the titles varied between 32 and 86%.
• This publication mainly concerns the synthesis of dibenzoylmethane, which is known to correspond to an extremely favorable reaction, although some examples also relate to the synthesis of relatively close molecules; in particular an example relates to the synthesis of stearoylbenzoylmethane for which the title was only 45%.
• this additional step has a very negative environmental balance in that it requires the use of large amounts of solvent and a lot of energy and where it leads to the formation of purification residues which must be destroyed.
• the separation of the impurities involves a loss of 20% of the product in order to obtain a 95% pure product.
• the reaction medium with sufficient energy per unit volume, which poses no particular problem at the laboratory but is difficult to achieve at the scale.
• the reactors are large and generally equipped with a jacket in which circulates a heat transfer fluid and a stirrer: in fact, the volume of such a reactor increases as the cube of its diameter whereas the heating surface increases as the square of this diameter; consequently the ratio surface / volume which quantifies the flow of energy supplied per unit volume of the reactor evolves inversely proportional to the diameter thereof.
• the volumetric energy supplied on an industrial scale is ten times lower than the volumetric energy supplied to the laboratory scale.
• This situation is related to the fact that the heating of the reaction medium is carried out by thermal conduction through the wall of the synthesis reactor or a heat exchanger, then by forced convection so that there is a significant temperature gradient between the fluid located in the center of the reactor and that located near its walls.
• an increase in the temperature difference between the heat transfer fluid and the reaction medium causes a strong local heating at the reactor walls likely to degrade the reactants and cause parasitic reactions.
• the presence of a coil in the reactor significantly modifies the flow characteristics within the reaction medium, which is likely to impair its renewal at the reactor surface, and therefore the evaporation of alcohol, resulting in an increase in side reactions.
• the first of these reasons is related to safety problems because if the speed of the reaction medium in the lines of the external recirculation loop is too high, there is a risk of explosivity by accumulation of electrical charges.
• the second reason is related to the hydrodynamic conditions in the reactor: in fact beyond a dozen recirculation of the volume thereof per hour, the flow caused by the stirrer is disturbed.
• the object of the present invention is to remedy this drawback by proposing a process for the industrial synthesis of beta-dicarbonyl compounds, in particular beta-diketones by Claisen condensation, which makes it possible to guarantee the homogeneity of the reaction medium in terms of temperature and concentration, and at the same time very rapid evaporation of the alcohol as it is formed.
• this process thus makes it possible to significantly increase the titre of the reaction and the purity of the final product, and in particular to obtain a titre greater than 95%, in particular a titre greater than 98%, and therefore a titre never reached for this type of reaction, so as to avoid having to purify the final product.
• the process according to the invention is therefore particularly advantageous both from an economic point of view and from an ecological point of view.
• this method is characterized by the following steps:
• a synthesis reactor preferably a double jacket, is mounted surmounted by a separation column provided with a condenser with variable reflux controlled by the temperature in this column and equipped with at least one microwave generator, as well as a stirring system,
• the microwave generator (s) is turned on
• the reactor is stopped and the reaction mixture is acidified and washed.
• the reactor can be equipped with at least one microwave generator directly mounted for example on flanges at its inner part, in particular at the sky thereof and / or especially in the event of insufficient space at this level, at least one external microwave generator connected thereto by a waveguide for channeling the microwaves in the reaction medium, and / or still be equipped with an external recirculation loop equipped with a recirculation pump and a microwave generator.
• the essential characteristic of the process according to the invention is thus linked to the use of microwaves to heat the reaction medium.
• the use of microwaves makes it possible to significantly reduce the reaction time, in particular by at least a factor of two compared to the conventional method, and in parallel to increase to a large extent the productivity by a factor easily up to 5.
• the process according to the invention is therefore particularly advantageous from an economic and ecological point of view due to the lower use of raw materials and also in terms of safety and investment due to the reduction in the size of the equipment. ments and cycle times.
• the microwaves act in fact mainly at two levels, the first of which is linked to the way in which the calories are supplied to the reaction mixture while the second is bound to the vibratory effect of microwaves.
• the heating mode of the reaction medium by the microwaves differs totally from the conventional method insofar as the energy is brought to the heart of this medium and where the temperature at the heating point is only very slightly greater than the average temperature of the reactor.
• the reactions that occur in the entire volume of the reactor are homogeneous and can be optimized to obtain a higher titre.
• the second mode of action of microwaves is due to their vibrational effect: in fact, the intermediate polar activated complexes forming during the Claisen condensation induce a significant energy barrier that must be overcome to allow the reaction.
• the products to be tested are conventionally introduced into pressure-resistant test tubes which are then transferred to a microwave enclosure so as to accelerate the reactions.
• microwaves are perfectly adapted in the context of the present invention according to which the energy and investment extra cost is largely offset by the possibility of obtaining a very high title and to avoid having to implement steps. subsequent purification.
• the first step of the process according to the invention therefore consists in mounting the synthesis reactor in which the Claisen condensation will be implemented.
• the synthesis reactor 1 is constituted by a jacketed enclosure 2 equipped with an agitator 3 and against blades.
• This reactor 1 is surmounted by a separation column 5 to which is connected a condenser 7 and a reflux line 8.
• the separation column 5 is equipped with a temperature sensor 6 which controls a valve / control valve 9 so as to allow to adjust the fraction of the condensed liquid returning to the column 5 by the reflux line 8 or withdrawn through a discharge pipe 10 depending on the temperature.
• the synthesis reactor 1 is also equipped with a recirculation loop 1 1 provided with a recirculation pump 12 and a microwave generator 13.
• the carbonyl compounds are constituted by at least one ketone and at least one ester
• reaction can selectively be carried out with a stoichiometric proportion of these two reagents, or with a molar excess of ester or with a molar excess of ketone, each time obtaining a beta betetone yield greater than 95%.
• the process according to the invention makes it possible to operate under operating conditions in which the ketone is in molar excess with respect to the ester, which allows a quasi-total conversion of the latter compound while at the same time resulting in only a slight decrease in the purity of the final product.
• the process according to the invention makes it possible to obtain an economic gain added to the use of an excess of ketone with respect to the ester.
• a strong base is used, the conjugate acid of which is volatile under the reaction conditions, such as an alcoholate, especially a sodium alkoxide and in particular sodium methoxide.
• the operating conditions can vary to a large extent depending on the starting materials and the nature of the beta-dicarbonyl compounds, in particular beta-diketones that are to be synthesized.
• the process according to the invention may in particular be carried out in the absence of a solvent or in the presence of a pure solvent or in a mixture, in particular a solvent containing an aromatic nucleus.
• the reaction may also be carried out under vacuum or at any pressure, especially at atmospheric pressure, or at a pressure below atmospheric pressure of from 0 to 1 absolute atmosphere, preferably from 0.1 to 0.5 absolute atmosphere, or at a pressure above atmospheric pressure of 0 to 5 relative atmospheres, preferably 0 to 2 relative atmospheres.
• the temperature of the reaction can be in a range from 60 ° C. to 180 ° C., preferably in a range from 90 ° C to 140 ° C.
• Example 1 Synthesis of Stearoylbenzoylmethane (SBM) by the "classical" method.
• SBM Stearoylbenzoylmethane
• a conventional 1-liter chemical glass reactor double wrapped and equipped with high-performance stirring, 450 ml of xylene, 178.79 g of molten methyl stearate and 34.05 g of sodium methoxide powder are introduced.
• the reactor is inerted by a slight flow of nitrogen continuously.
• the mixture is then boiled and refluxed at the top of the separation column.
• Acetophenone is introduced into the reactor at a rate of 68.42 g in 5 hours.
• the productivity obtained during the reaction phase in SBM is. of 30.3 kg / h / m3.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W.
• 68.39 g of acetophenone are introduced in one hour. At the end of the introduction the mixture continues to react for 15 minutes. During all this time the methanol produced is removed from the reaction medium. After 15 minutes of completion, the microwave generator is stopped, the heating also and the mixture is acidified and washed.
• the SBM titre of the process according to the invention is more than 15 points higher than that of the conventional process.
• the productivity obtained during the SBM reaction phase is 172.6 kg / h / m3, which is 5.7 times the productivity of the conventional process.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with a double wrapped recirculation loop fitted with a gear pump. The temperature of the double envelopes is greatly increased to obtain the heat transfer as close as possible to the overall heat transfer of Example 2.
• the organic phase is very strongly colored. Its analysis by gas chromatography shows that the conversion of acetophenone is almost complete and that the titre in SBM is 71.8%. A peak forest is present on the chromatogram showing that there have been numerous parasitic reactions.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W. 560 ml of xylene, 81.59 g of methyl benzoate and 34.03 g of sodium methoxide powder are introduced. Once the reactants have been introduced, the reactor is inerted by a slight flow of nitrogen continuously. The mixture is recirculated in the outer loop at a rate of 15 kg / h. It is boiled to total reflux and the microwave generator is turned on.
• the productivity obtained during the reaction phase in DBM is 101.4 kg / h / m3.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W. It is also equipped with a vacuum pump allowing a vacuum up to about 100 mbar in the system.
• the productivity obtained during the reaction phase in DBM is 101.8 kg / h / m3.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W.
• the productivity obtained during the SBM reaction phase is 173.2 kg / h / m3.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W. 550 ml of xylene, 94.78 g of methyl octanoate and 34.05 g of sodium methoxide powder are introduced. Once the reactants have been introduced, the reactor is inerted by a slight flow of nitrogen continuously. The mixture is recirculated in the outer loop at a rate of 15 kg / h. It is heated to full reflux and the microwave generator is turned on.
• the productivity obtained during the reaction phase in OBM is 1 10.3 kg / h / m3.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column provided with a condenser with variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W.
• the productivity obtained during the SBM reaction phase is 180.6 kg / h / m3.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux, it is also equipped with a recirculation loop provided with a gear pump and a microwave generator with a power of 600 W.
• 68.40 g of acetophenone are introduced in one hour. At the end of the introduction, the mixture continues to react for 15 minutes. During all this time the methanol produced is removed from the reaction medium. After 15 minutes of completion, the microwave generator is stopped, the heating also and the mixture is acidified and washed.
• the productivity obtained during the reaction phase in PBM is 168.4 kg / h / m3.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W. 490 ml of xylene, 145.22 g of methyl myristate and 33.98 g of sodium methoxide powder are introduced. Once the reactants have been introduced, the reactor is inerted by a slight flow of nitrogen continuously. The mixture is recirculated in the outer loop at a rate of 15 kg / h. It is boiled to total reflux and the microwave generator is turned on.
• the productivity obtained during the MBM reaction phase is 155.4 kg / h / m3.
• Example 1 1 Synthesis of LauroylBenzoylMethane (LBM) by the process according to the invention.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W.
• 68.45 g of acetophenone are introduced in one hour. At the end of the introduction the mixture continues to react for 15 minutes. During all this time the methanol produced is removed from the reaction medium. After 15 minutes of completion, the microwave generator is stopped, the heating also and the mixture is acidified and washed.
• the productivity obtained during the reaction phase in DEBM is 129.3 kg / h / m3.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column provided with a condenser with variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W.
• the productivity obtained during the reaction phase in BpMBM is 1 12.9 kg / h / m3.
• the experimental setup consists of a conventional one-liter chemical reactor, made of glass, double-wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with a recirculation loop equipped with a gear pump and a microwave generator with a power of 600 W.
• the industrial tool consists of a conventional 1000 liter chemical engineering reactor, made of stainless steel, double wrapped and equipped with high performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with microwave sources with a total power of 30 kW.
• the industrial tool consists of a conventional 10.000 liter chemical engineering reactor, made of stainless steel, double wrapped and equipped with high-performance stirring. It is surmounted by a separation column equipped with a condenser with a variable reflux. It is also equipped with microwave sources with a total power of 120 kW.

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• 2010
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  • 2011-09-19 WO PCT/FR2011/052143 patent/WO2012038648A1/fr active Application Filing
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