DE4016076A1 - Process for carrying out sonochemical reactions - with continuous flow through ultrasonic appts. - Google Patents

Abstract

Chemical reactions are performed by continuously passing the reaction mixt. past a sound wave source to sonicate the reaction mixt. USE/ADVANTAGE - The process may be applied to a wide range of reactions, the exemplified reaction being the prodn. of ethyl 3-hydroxyhexanoate (I) from butyraldehdye (II) and ethyl bromoacetate (III). Unlike known batch processes, the continuous process can be scaled up without the need for very large sonication baths.

Description

The present invention relates to a device for continuous production of chemical Ultrasonic connections.

The application of ultrasound in the chemical Process engineering is known per se.

So the effect of cleaning baths in the Metal surface treatment through the use of Ultrasound can be increased significantly.

In biotechnology, ultrasound sources become Used for disinfection. Here, in Water cells of bacteria and algae torn. Milk can, for example, in this way can be sterilized within a few seconds.

In addition, the oil yield can be extracted from the oil with hexane to about 90% compared to 32% Increase non-radiation [E. Henglein, lexicon Chemical technology, Verlag Chemie, Weinheim 1988, p. 615 and quot. Lit.].

Although the phenomena of ultrasound have been around since 1927 are known is the use of ultrasound in the only recently synthetic organic chemistry to break through, for which the leaps and bounds increasing number of publications on this topic provides impressive evidence [K. S. Suslick, Ultrasound in Synthesis in H. Schef Folg (Ed.): Modern Synthetic Methods 4 (1986), Springer-Verlag, Berlin 1986; C. Einhorn and J. Einhorn, J.-L. Luche, Sonochemistry - The Use of Ultrasonic Waves in Synthetic Organic Chemistry, Synthesis (1989) 787; T. J. Mason, Use of ultrasound in chemical synthesis, Ultrasonics (1986) 245].  

During ultrasonic vibrations initially only to do so were used to cleave organic molecules (Sonolysis) - for example to polymerize depolymerize - could subsequently Applying ultrasound to a full range of - constructive - organic synthesis methods be successfully expanded.

It was discovered that ultrasonic vibrations were not can only be used to control the Reaction rate and / or the yield of desired reaction product to increase - which at numerous heterogeneous reaction systems successfully could be carried out - but that the The course of the reaction with this method is sustainable can be influenced.

The use of ultrasound in chemical reactions is basically in homogeneous as well as heterogeneous Systems possible.

In the past, however, this type of A comparative sonochemistry for heterogeneous systems significantly more important than for homogeneous systems.

With the heterogeneous systems between liquid / liquid systems and solid / liquid systems distinguished.

The latter group can be divided into again Reactions involving metals or Organometallic compounds run off (e.g. Grignard or Reformatzky reactions) and all other reaction types.

Considered from the multitude for sonochemistry the following reactions are exemplary picked out:

• 1. Oxidations and reductions of inorganic Compounds in aqueous solution [K. S. Suslick, Ultrasound in Synthesis in H. Schef Folg (Ed.): Modern Synthetic Methods, 4 (1986), Springer-Verlag, Berlin 1986].
• 2. Reactions of metal carbonyls - in particular Ligand exchange reactions and Clustering reactions [K. S. Suslick, J. Am. Chem. Soc. 105 (1983) 5781].
• 3. Radical fragmentation of organic Connections - such as B. thymine, uracil or cytosine in aqueous solution [R. E. Verrall et al., Can. J. Chem. 53 (1975) 2394; ibid. 58 (1980) 1909; ibid. 65 (1987) 1162].
• 4. Solvolysis of haloalkanes - such as. B. from 2-chloro-2-methylpropane in water alcoholic solution [T. J. Mason et al., Tetrahedron 41 (22) (1985) 5201].
• 5. Two-phase saponification of esters [p. Moon et al., Tetrahedron Lett. 20 (1979) 3917; D. S. Kristol et al., Tetrahedron Lett. 22 (1981) 907] or from Nitriles [J. Elguero et al., C.R. Acad. Sc. Paris, II, 298 (1984) 877].
• 6. Synthesis of Organometallic Compounds - for example lithium organylene - in situ and their Use in subsequent reactions - such as B. in the Barbier reaction [J. L. Luche and J.C. Damiano, J. At the. Chem. Soc. 102 (1980) 7926; B. M. Trost and B. P. Coppola, J. Am. Chem. Soc. 104 (1982) 6879; J.L. Luche and J. Einhorn, Tetrahedron Lett. 27 (1986) 501].  
• 7. Grignard reactions [W. Oppolzer and P. Schneider, Tetrahedron Lett. 25 (1984) 3305; J.L. Luche and J.C. Damiano, J. Am. Chem. Soc. 102 (1980) 7926], being activated even in damp Reaction media (diethyl ether) is possible [J. D. Sprich and G. S. Lewandos, Inorg. Chim. Acta 76 (1982) 1241].
• 8. Reformatzky reactions [P. Boudjouk and B. H. Han, U.S. Patent 4,476,870; J. Org. Chem. 47 (1982) 5030].
• 9. Preparation of dichlorocarbenes [p. L. Regen and A. Singh, J. Org. Chem. 47 (1982) 1587] and their Use in the so-called Simmons-Smith reaction [O. Repic and S. Vogt, Tetrahedron Lett. 23 (1982) 2729].
• 10. Clemmenson reduction type reactions [P. Boudjouk, Nachr. Chem. Techn. Lab. 31 (1983) 798].
• 11. Lithiations without the use of organolithium compounds as well in situ representation of butyllithium and Lithium diisopropylamide [J. L. Luche and J. Einhorn, J. Org. Chem. 52 (1987) 4124].
• 12. Bouveault-Blanc type reactions [J. L. Luche and J. Einhorn, Tetrahedron Lett. 27th (1986) 1791; ibid. 27 (1986) 1793; J.L. Luche et al., ibid. 23 (1982) 3361].
• 13. Reductive silylations of dicarbonyl compounds in the presence of metals - such as B. Zinc [P. Boudjouk and Jeung Ho So, Synth. Commun. 16 (1986) 775].  
• 14. Representation of organosilicon compounds from the corresponding dihalosilanes [P. Boudjouk and B. H. Han, U.S. Patent 4,476,870].
• 15. Ullmann type reactions [T. J. Mason, Ultrasonics 24 (1986) 292].
• 16. Hydrogenation of alkenes and alkynes [P. Boudjouk and B. H. Han US-PS 44 76 870] and reductive opening of cyclopropane rings [P. Boudjouk and B. H. Han, J. Catal. 79 (1983) 489].
• 17. Reductions of the type of B'champ reduction and reductions of nitro groups by means of the system Fe / N ₂ H ₄ .H ₂ O / "C" [BH Han et al., Bull. Korean Chem. Soc. 6 (1985) 320].
• 18. Hydrogenation of carbon-carbon Double bonds with hydrogen in the presence of a Catalyst - such as B. Palladium.
• 19. Aldol condensations e.g. B. by means of aluminum oxide [B. C. Barot et al., Synth. Commun. 14 (1984) 397].
• 20. Oxidations of alcohols - for example with Potassium permanganate [J. Yamawaki et al., Chem. Lett. 1983, 379].
• 21. Conversion of amides into thioamides using Phosphorus sulfides - such as B. with dimers Disphosphorus Pentasulfide [p. Raucher and P. Klein, J. Org. Chem. 46 (1981) 3558].
• 22. Production of aromatic acylcyamides by Implementation of the corresponding acyl halides with Alkali cyanides [T. Ando et al., Synthesis 1983, 637].  
• 23. Production of alkali metal suspensions - e.g. B. for use in Dieckmann cyclization [J. L. Luche et al., Tetrahedron Lett. 25 (1984) 753].
• 24. Production of alkenes based on Wittig-Horner reaction - e.g. B. in the presence of Alkaline earth metal hydroxides such as barium hydroxide [J. V. Sinisterra et al., J. Org. Chem. 52 (1987) 3875].
• 25. Production of Sugar Acetals [J. L. Luche and C. Unicorn, carbohydr. Research 155 (1986) 258].
• 26. Reduction of aryl halides with complex Alkaline aluminum hydrides [P. Boudjouk and B. H. Han, Tetrahedron Lett. 23 (1982) 1643].
• 27. Preparation of trialkylboranes via the Intermediate stage of the corresponding Alkyl aluminum sesquibromide - for example that Manufacture of triethylborane via Ethyl aluminum sesquibromide [Kou Fu Liou et al., J. Organomet. Chem. 294 (1985) 145].
• 28. Implementations based on the Michael addition [K. Shibata, Chem. Letters 1987, 519].
• 29. N-alkylations of amines [R. S. Davidson et al., Tetrahedron Lett. 24 (1983) 5907].
• 30. Implementations based on the Cannizzaro reaction [J. V. Sinisterra and A. Fuentes, Tetrahedron Lett. 27 (1986) 2967].  
• 31. Strecker syntheses to represent 2-aminonitriles [J. Menedez et al., Tetrahedron Lett. 27 (1986) 3285].
• 32. Hydrosilylations [P. Boudjouk and B. H. Han, Organometallics 2 (1983) 769].
• 33. Hydroalkylations [T. Kitazume and N. Ishikawa, J. Am. Chem. Soc. 107 (1985) 5186].
• 34. Cycloadditions [G. Mehta and H. S. P. Rao, Synth. Commun. 15 (1985) 991].
• 35. Friedel-Crafts acylations [B. M. Trost and B. P. Coppola J. Am. Chem. Soc. 104 (1982) 6879; P. Boudjouk et al., Synth. Commun. 16 (1986) 401].

Although the reactions mentioned are sustainable End pressure from the wide range of applications with Convey ultrasound-assisted reactions only a few - especially for such implementations designed - devices have been developed. How to get there usually commercially available ultrasonic cleaning baths for Commitment. The use of a reaction apparatus in one Enlarged laboratory scale is only in the literature a case (Simmons-Smith reaction) known [O. Repic et al., Org. Preps and Procedures Int. 16 (1984) 25]. To carry out this reaction on a 22 liter scale however, an ultrasonic bath with a 220 l capacity required!  

In general, there are two fundamentally different ones Possibilities of energy in the form of the reaction system Feed ultrasound:

• a) The reaction vessel is placed in a liquid submerged - usually water - which in turn is sonicated as z. B. in the mentioned Cleaning baths is the case.
• b) An ultrasound probe is placed inside the Reaction medium placed. The one from the Ultrasonic probe will be outgoing vibrations via a resonator into the sound system Substance initiated.

Regardless of the choice of method, it is necessary both the temperature and the so-called To be able to control the sound intensity.

Regarding the choice of temperature, it should be noted that the Response speed supported by ultrasound Reactions generally with increasing temperature decreases. The reason for this is likely to be that with increasing temperature the vapor pressure in the cavities increases so that the vesicular collapse less is more energetic than with implosion highly evacuated cavities [s. a .: K. S. Suslick, the chemical effects of ultrasound in: spectrum of Science 1989, 60]. That's why it is beneficial to those solvents to resort to the lowest possible Have vapor pressure.  

The intensity of the sound reinforcement primarily depends on the reaction apparatus intended for use. While the power density in an ultrasonic bath is only in the range of approx. 0.1 to 1 W / cm ² , power outputs of 10-1000 W / cm ² can be achieved when using ultrasonic probes.

A far less influence - compared to the mentioned reaction parameters sonication intensity and reaction temperature - comes the Sound frequency too - as long as they are in one The area causing cavitation is (approx. 1 kHz to 1 MHz).

In addition to the low power density, which in Ultrasonic baths can be achieved Use of this apparatus with others Disadvantages connected:

• - effective control of radiation intensity can not;
• - only a part of the total floor area of the Bades radiated energy gets into that Reaction vessel;
• - one favorable for energy transmission Positioning the reaction vessel is difficult (the standing waves forming in the bathroom point so-called knots - there is no knot at these points Energy transfer);
• - a temperature control is difficult - u. U. must the entire bath contents can be circulated;  
• - A continuous reaction leads to no acceptable sales results; a appropriate modification of the equipment would be additional with a comparatively high expenditure on equipment connected;
• - for larger approaches there are none commercially available ultrasonic baths.

It is the object of the present invention that to overcome the disadvantages mentioned and a process as well as to provide a reaction apparatus, that in particular enables ultrasound-assisted reactions continuously perform.

It is another object of the present invention to provide a reaction apparatus that the implementation beyond the laboratory scale Orders of magnitude of reactants in a simple manner and allowed with the help of commercially available devices.

According to the invention, the above objects solved in that one containing the reactants Reaction mixture or solution continuously on one passed sound wave emitting source and is sonicated.  

For the implementation of this method, for. B. a so-called loop reactor, in which one Solution containing reactants on a Ultrasound source, which is in a corresponding designed flow cell is located continuously passed and sonicated.

The above-mentioned objects are achieved, for example, by the reaction apparatus shown schematically in FIG. 1. Various, other and further features, configurations and the like which are associated with the present invention will become apparent to those skilled in the art from the present description and can be better understood in conjunction with the drawing, in which the presently preferred embodiment of the invention is shown by way of example. However, it is expressly pointed out that the drawing and the description associated with it are provided only for the purpose of explanation and description and should not be regarded as a limitation of the invention.

Description of the drawing

Fig. 1 embodies the schematic representation of the reaction apparatus according to the invention. The reactor 10 serves primarily for taking up and mixing and storing the reactants or starting materials and is provided with devices 11 for mixing the reaction mixture and for determining the temperature or, if appropriate, other characteristic properties of the reaction mixture 12 or for introducing inert gas 13 . Depending on the requirements that make the respective reaction types necessary, the reactor 10 can also be equipped with devices for metering individual components - such as. B. a dropping funnel 14 - and devices for condensing (cooler) 15 or cooling or heating the reaction mixture 16 in the reactor. The reaction mixture is fed to the pump 30 from the reactor 10 . The feed line 20 is provided with a device for heat exchange 21 as well as devices which allow the removal of reaction solution 22 or the addition of reactants 23 and possibly devices for determining the temperature 24 or other devices for detecting further characteristic properties of the reaction mixture .

The reaction solution is pump 30 - z. B. a metering pump 30 - via the pulsation damper 31 and the feed line 32 of the flow cell 40 , in which the ultrasound source 41 is located and in which the sonication is carried out.

After passing through the flow cell 40 , the reaction solution is returned to the reactor 10 via the feed line 42 , wherein devices for determining the temperature 43 or other characteristic properties of the reaction mixture of the reaction solution and devices for heat exchange 44 can be provided after exiting the flow cell 40 .

After being fed into the reactor 10 , the reaction solution can, if necessary, be mixed with new reactants and the flow cell 40 and thus the ultrasound source 41 can be fed again in the manner described.

Reference symbol list

10 reactor
11 Mixing device
12 Device for determining the temperature
13 Device for introducing inert gas
14 dropping funnels
15 coolers
16 Device (s) for cooling or heating the reaction contents
20 supply line
21 Heat exchange device
22 Device for removing reaction solution
23 Device for adding reactants
24 Device for determining the temperature
30 pump
31 pulsation dampener
32 supply line
40 flow cell
41 Ultrasound source
42 supply line
43 Device for determining the temperature
44 Heat exchange device.

The operation of the apparatus described above will in the Reformatzky reaction described below explained without the breadth of application to this reaction or restrict this type of reaction.

example 1 Preparation of 3-hydroxyhexanoic acid ethyl ester

After purging the equipment with inert gas 600 ml of dioxane placed in the reactor and after Commissioning of the dosing pump (type: Prominent exotronic type BX Li / 0267 T / 671 / h with pulsation damper and pressure gauge) while stirring with 114.3 g zinc dust transferred. After commissioning the Ultrasonic generator (type: Branson Sonifier 250 with Flow cell without ceramic disc) are used in a Performance display of 72% with a dropping funnel Pressure equalization about a third of a mixture of 64.9 g butyraldehyde and 185.0 g ethyl bromoacetate within a period of about 5 minutes dripped. After a sonication time of approx. 10 Minutes the reaction starts, whereby the Reaction temperature or heat exchanger in the Reaction cell from 45 ° C to 70 ° C and in the reactor from 33 ° C to 40 ° C increases (start-up of the cooler). To The remaining mixture intensifies the cooling from butyraldehyde and ethyl bromoacetate Added dropping rate of 5 ml per minute. The output of the ultrasound source kept constant in a range of 50 to 55% and the output of the dosing pump to a value of 10 l set per hour. The cooling is like this regulates that the temperature in the cell in one Range from approx. 40 ° C to 50 ° C and that in the reactor in an interval of approx. 30 ° C to approx. 40 ° C.  

After the butyraldehyde / Ethyl bromoacetate mixture is the Reaction mixture over a period of approx. 15 Minutes.

After the cell temperature has dropped (end of Reaction) is allowed to result Reaction suspension in the reactor to a temperature of cool down at approx. 25 ° C.

Then the mixture from the reactor away. The reaction apparatus is with 200 ml of dioxane rinsed. The combined mixtures become slow with stirring in a mixture of approx. 700 g ice and Poured 500 ml of 45% by weight sodium hydroxide solution. Subsequently add about 400 ml to the hydrolysis mixture Methyl tert-butyl ether and stirred for about 5 minutes to. The reaction mixture is with a Vacuumed K2 Seitz filter and Clarcel-coated suction filter.

The filter material is washed with 100 ml of methyl tert-butyl ether. The organic phase is separated from the combined filtrates. The aqueous phase is extracted with 300 ml of methyl tert-butyl ether. The combined organic phases are washed neutral with water. The combined aqueous phases are extracted with 200 ml of methyl tert-butyl ether. The combined organic phases are dried with 150 g of calcium chloride and after filtering off the drying agent at a temperature in the range from 25 ° C. to 70 ° C. i. Vac. constricted. 114 g (79.1% of theory, based on butyraldehyde) of the 3-hydroxyhexanoic acid ethyl ester with a refractive index n _D 25 = 1.4283 (GC: 95% strength) are obtained.

Claims (2)

1. A process for carrying out sonochemical reactions, characterized in that a reaction mixture or solution containing the reactants is continuously guided past a sound wave emitting source and sonicated. 2. Device for performing sonochemical Reactions, characterized in that they essentially from at least one Ultrasound source and at least one device for passing the reaction mixture or solution is built up at the ultrasound source and optionally other devices for Detection of properties of the reaction mixture and / or treating the reaction mixture.