HU188596B - Process for preparing n-dichlor-acetyl-1-oxa-4-aza-spiro-/4,5/-decane - Google Patents

Abstract

The essence of the process is that of monoethanolamine and cyclohexanone is a solvent in a near stoichiometric ratio without reaction at a temperature of 128-132 ° C, the resulting 1-oxa-4-aza-spiro (4,5) -decane is below 100 ° C boiling point water-immiscible with 1.3-1.6 g / cm3 water diluted with a solvent and formed with an acid scavenger in a dispersion with dichloroacetyl chloride - 2 and + 2 ° C acylate between them. After acylation the product contains from the organic phase, the salts are washed with water and the organic phase bar from the target product of the present invention with the introduction of water or steam distil.

Description

The present invention relates to an improved preparation of N-dichloroacetyl-1-oxa-4-aza-spiro (4,5) decane which is economically feasible on a large scale.

The preparation of the target compound is an important technical task as the compound is used as an antidote for herbicides in plant protection.

Several processes for the preparation of analogue dichloroacylated heterocyclic compounds have become known in the literature and in the patent literature. An example of these methods is disclosed in U.S. Patent No. 165,736. in the Hungarian patent. According to known methods, aliphatic ketones or aldehydes are reacted with amines such as monoethanolamine, 2-amino-thioethanol or ethylenediamine in a water-immiscible solvent while the water formed is removed by azeotropic distillation. The resulting intermediate is subjected to Schotten-Baumann acylation with dichloroacetyl chloride in the presence of an acid binder such as triethylamine or sodium hydroxide. The precipitate of triethylamine hydrochloride or sodium chloride from the product formed during the acylation is removed by filtration or washing with water, the solvent is distilled off from the system by atmospheric or vacuum distillation and the crude product is subsequently purified by recrystallization.

No. 176,784. Hungarian Patent Publication No. 4,198,015 discloses a laboratory formulation for the preparation of N-dichloroacetyl-1-oxa-4-aza-spiro (4,5) decane, wherein the 1.3: 1 molar mixture of cyclohexanone and monoethanolamine is boiled in benzene solution until the formation of water is eliminated. To the cooled solution is added 40% sodium hydroxide solution and then acylated by the dropwise addition of dichloroacetyl chloride. After the reaction, the mixture is washed neutral with water and the crude product is recrystallized from ethanol.

Known processes can be used to produce a chemically pure product, but when reproduced on an industrial scale, it can be observed that each operation requires a great deal of effort. Distil the water formed in the ring closure reaction! should be removed while yielding the target product and waxing phenomena occur. The Schotten-Baumann acylation operation can be carried out efficiently only when the mixing is very intensive, thus limiting the potential for further industrial growth. Significant losses also occur in the subsequent purification and drying of the resulting crude product.

SUMMARY OF THE INVENTION The object of the present invention is to provide a continuous process for the preparation of the target product which can be carried out more economically than known processes, it is possible to increase the reaction rate, partially eliminate the solvent and produce a purer product.

The preparation of the N-dichloroacetyl-1-oxa-4-aza-spiro (4,5) decane of the present invention is accomplished by the ring closure reaction of monoethanolamine with cyclohexanone followed by dichloroacylation to give monoethanolamine and cyclohexanone 1: 1. , 1 molar ratio at atmospheric pressure of 128-132 ° C, the water formed is removed by distillation. The resulting 1-oxa-4-aza-spiro (4,5) -decane is diluted with 8 to 12 times the weight of a water-immiscible solvent having a boiling point below 100 ° C and 1.3-1.6 g / cin ³ . Thus, crystals of the product formed do not precipitate at the temperature of the acylation reaction. The solution is dispersed in aqueous sodium hydroxide solution and the pH 10-12 solution is reacted with dichloroacetyl chloride at a temperature between -2 ° C and + 2 ° C. The salts from the solvent phase containing the crude product are washed and, after separation of the organic phase, the product obtained in the solvent phase is distilled by adding 0.4 to 1.5 times the weight of the solution with water or steam to remove the solvent and condense into the system. optionally recycled and the melt recovered in known manner. The solvent used may be toluene, xylene, carbon tetrachloride, dichloroethane or trichlorethylene.

The purity of the product obtained by the above procedure is 94-99%. The advantages of the process according to the invention over the prior art are summarized as follows:

- no solvent is used in the ring closure reaction, with intensive contact and at higher temperatures it is possible to increase the reaction rate by 50 to 100 times;

- the formation of by-products can be suppressed in the ring closure reaction;

- the final product does not require any subsequent cleaning, which results in significant time and energy savings;

conducting the ring closure and acylation reaction and solvent deprotection of the reaction mixture can be carried out continuously on a large scale.

Conducting the process of the invention in the absence of solvent and at higher temperatures without the formation of by-products was not anticipated, since at higher temperatures than the batch process, the need for resinization and purification of the final product could not be eliminated. The rate of the ring closure reaction according to the invention can be increased to such an extent that no adverse side reactions are detectable and the finished product is free of resinous impurities.

In the process, monoethanolamine and cyclohexanone are generally reacted in stoichiometric molar ratios in a continuous apparatus for distillation of the water formed during the reaction.

Λ experience has shown that a stoichiometric molar ratio is advisable, since otherwise unreacted materials are discharged, which reduces the yield.

It is expedient to use a rotary film reactor to conduct the ring closure reaction and to quench the water formed. The water vaporized intermediates and starting materials are either returned to the film reactor by deflegmation or separated from the water by settling after total condensation and fed back to the film reactor at a constant rate. The organic phase is fed back to the film reactor at the rate at which it would leave the settler with free discharge. The local excess of cyclohexinone in the reactor can be generated by filling the settler with water and cyclohexanone prior to continuous start-up and starting to feed back the pure cyclohexanone as the organic phase. Cyclohexanone is significantly more volatile than monoethanolamines and 1-oxa-4-aza-spiro (4,5) -decane, so that the bulk of the organic content of the condenser is also cyclohexanone, which circulates through the filine reactor.

The resulting 1-oxa-4-aza-spiro (4,5) -decane is acylated in the presence of a solvent. The solvent used is immiscible with water and does not enter into contact with dichloroacetyl chloride

188,596 such as benzene, toluene, xylene, dichloroethane, trichlorethylene. In addition to the solubility of the target product in said solvent, the boiling point, density and freezing point below -2 ° C are important selection criteria for solvent selection. The preferred boiling point is below 100 ° C and its density is 1.3-1.6 g / cm ³ . The degree of dilution is determined by the solubility of the target product in said solvent.

In Schotten-Baumann acylation, 20% to 40% by weight of sodium hydroxide is added as an acid binder, and the organic intermediate is dispersed in the alkali, and dichloroacetyl chloride is added to the resulting emulsion.

Because acylation is an extremely vigorous exothermic reaction, it is desirable to introduce the reaction components after passing through the deep-freezing apparatus to the continuously operating acylation reactor. Thus, after preheating, both the intermediate product and dichloroacetyl chloride and an excess of sodium hydroxide solution are added. In acylation, the reaction partners are suitably reacted in a 1: 1 molar ratio.

Acylation below pH 10-12 results in a more impure emulsion of the resulting product which is difficult to decompose at too high a pH, which degrades the efficiency of the settling-decanting required after washing with water. An excess of aqueous ammonium hydroxide or triethylamine in anhydrous medium may also be used as the acid binder.

From a technological point of view, the use of an aqueous solution of sodium hydroxide is preferred. Temperatures below −2 ° C increase the stability of the emulsion formed, but at higher temperatures above + 2 ° C, hydrolysis is increased during acylation, which in any case causes loss of product.

Thus, in order to increase the reaction rate for acylation, it is highly desirable that the contact partners be as intimate as possible. This requires that the 1-oxa-4-aza-spiro (4,5) -decane emulsify with sodium hydroxide at the interface to form the formed hydrochloric acid so that the preferred acylation reaction can be carried out efficiently. At the given acylation temperature, the rate of the acylation reaction is substantially higher than the reaction rate of hydrolysis. The bulk of dichloroacetyl chloride enters the organic phase since only the products of hydrolysis are soluble in water. The density of the solvent used for acylation also plays a role, since using a solvent having a specific gravity close to the specific gravity of the sodium hydroxide solution and dichloroacetyl chloride facilitates the formation of the emulsion.

The acylation was carried out in a vigorously stirred, high-cooled apparatus. The material leaving the acylation reactor is transferred to an aqueous washer, from where it is transported, together with the wash water, to a separator from which, in the case of sodium hydroxide acid binder, the aqueous solution of sodium chloride and excess alkali are discharged.

The separated organic phase in the separator is added to a continuous distillation apparatus, which is simultaneously fed with water or steam. The amount of water added is controlled to protect the thermosensitive product from overheating while at the same time washing the water-soluble impurities from the product. The solvent is removed by evaporation along with a portion of the feed water and, after condensation and settling, is returned to the process.

The melt leaving the distillate is separated from the hot water in a small separator.

The product is plated or granulated while the separated hot water is returned to the first aqueous washer separator.

Alternatively, the product can be recovered by suspending the melt leaving the distillate in cold water, filtering or centrifuging the resulting slurry, and drying the wet product. With the latter solution we can obtain 1-2% more pure terrine, but the operating costs increase,

The process of the present invention is illustrated in more detail by the following embodiments:

Example 1

In a film reactor with a useful surface area of 0.15 m ² , 1.832 kg / h of monoetarolamine and 2.944 kg / h of cyclohexanone were added at a temperature of 100 ° C. The temperature of the liquid film is adjusted to 13 ° ± 2 ° C. The vapors leaving the film reactor are passed through a single-fill column, in which the head temperature is cooled by approx. After being cooled to 100 ° C and drained off as waste water, the liquid dripping from the charge, predominantly cyclohexanone, is returned to the film reactor. The 1oxa-4-aza-spiro (4,5) -decane continuously leaving the fdm reactor was cooled to 20 ° C and diluted with trichlorethylene (40 kg / h). The organic phase is cooled to -10 ° C with a vigorous stirrer and introduced into a 7 liter acylation reactor equipped with an internal cooling coil, containing 4.45 kg / h of dichloroacetyl chloride and 6.6 kg / h pre-cooled to -10 ° C. Sodium hydroxide (20 falcons) was added.

The acylation reactor is maintained at a temperature of -1 to +1 ° C. The reaction mixture in the emulsion leaving the overflow was washed in a washing injector with a flow rate of 100 liters / hour, and the organic phase was separated from the washing water in a separator.

The solvent from the target product in the organic phase is removed in a film distiller having a useful surface area of 0.25 m ² , and 50 l / h of water preheated to 96-98 ° C are simultaneously introduced into the film distiller. The added water is approx. 10% by weight of the captured trichlorethylene, after condensation and separation from water by sedimentation, is recycled to dilute 1-oxa-4-aza-spiro (4,5) -decane for the acylation reaction. The temperature of the solvent evaporation liquid film was maintained at 98-100 ° C, the effluent was separated from the water in a 3 liter hydrocyclone and the product was plated. The structure of the target product was confirmed by infrared spectroscopy and quantified by gas chromatography. 6.4 kg / h and 95.1% purity were produced in the above apparatus.

Example 2

The procedure was carried out as in Example 1, except that the acid acceptor was 20% by weight.

Instead of 188,596 sodium hydroxide triethylamine (3.38 kg / h) was added during acylation. Accordingly, a product with a purity of 92.8% is produced at 6.8 kg / h.

Example 3

The procedure was carried out as in Example 1 except that 2.8 kg / h of 20% aqueous ammonia was used as acid binder instead of 20% by weight of sodium hydroxide. 5.5 kg / h was obtained with a purity of 94.5%.

Example 4

The procedure of Example 2 was repeated except that benzene was used as a solvent instead of trichlorethylene. The benzene solution was cooled to + 5 ° C before being introduced into the acylation reactor. 6.3 kg / h of 94.9% pure product are thus obtained.

Example 5

The procedure of Example 1 was performed except that the ring closure reaction was carried out at a pressure of 20 kPa at a liquid film temperature of 90-92 ° C. 5.5 kg / h and 94.8% purity were obtained.

Example 6

The procedure was carried out as in Example 1, except that the cyclohexanone was used in the ring closure at 3.091 kg / h. The cyclohexanone-containing trichlorethylene, separated from the water by road construction, is purified through a rectifying column of 1500 mm long and 10 mm diameter filled with 5 x 5 mm Raschig rings, since the l-oxa-4,5-aza-spiro formed in the ring closure reaction ) -decane is slightly degraded by both acid and alkali, such as cyclohexanone. The product enters the trichlorethylene circulating, where it is enriched and reduced in purity after prolonged operation. The cyclohexanone recovered as a bottom product can be reused as a reaction partner. As a further exception, 3.5 kg of water vapor, reduced to 1.8 bar pressure, is introduced into the bottom of the film distiller to aid distillation and to provide thermal protection, and the melt from the film distiller is fed to an intense mixer with 10 liters of overflow. Water at temperature C is added. The slurry leaving the overflow of the aqueous washing reactor is introduced into a trough of a vacuum suction filter with a useful surface area of 0.2 m ² . The filtrate collected with the peeling knife was dried at a temperature below 95 ° C. 6.2 kg / h of 98.2% product are obtained.

EXAMPLE 7 Cyclohexanone (kg / h) and monoethanolamine (42.8 kg / h) are added to a static mixer which is fed to a 0.32 m ² rotary film actor. The heating of the film reactor is controlled so that the temperature of the bottom outlet fluid is maintained at 130-132 ° C. The vapors formed are one

It is condensed on a 3 m ² condenser and separated into a 60 liter separator at 50-55 ° C for aqueous and organic fesh. The aqueous phase is discharged as waste water and the organic phase is returned to the mixer at a rate of 20 kg / h.

The 1-oxa-4-aza spiro (4,5) -decine effluent from the film reactor was cooled in an aqueous cooler to 30-35 ° C, diluted with 3 x 630 kg / h trichloroethylene, and the solution was cooled at 0 ° C. below 380 liters, with an intense low-slit acylation reactor with a cooling surface of 10 m ² . Dichloroacetyl chloride (101 kg / h) and 20% (w / w) aqueous sodium hydroxide solution (140 kg / h) were also charged to the acylation reactor at a temperature below -2 ° C and + 2 ° C.

The trichloroethylene solution of the resulting product was washed with industrial water and then with cation exchanged water to neutral pH and added to a 4.5 m ² rotary film distiller. To provide heat protection and to facilitate distillation, 60 kg of water vapor reduced to 1.8 bar is injected into the bottom of the film distiller. The distilled solvent is condensed with water vapor and then separated from the water by settling back to the acylation reaction to dilute 1-oxa-4-aza-spiro (4,5) -decane.

The fluid spill from the film distillate was resuspended in 1500 liters / hour of water in a 70 liter vigorously stirred apparatus, the suspension was dried in a vacuum drum filter, and the filtrate dried in a flow-dryer. 125 kg / h yield 96-99% purity.

Claims (3)

Claims 1. Process N-dichloroacetyl-1-oxa-4-aza-spiro (4,5) -decane 40 for cyclization of monoethanolamine and cyclohexanone and acylation of the resulting product with dichloroacetyl chloride, characterized in that the monoetancylamine and cyclohexanone were 1: 1-1.1 molar at atmospheric pressure at 128-132 ° C. reacting while removing the water formed, 8 to 12 times the weight of l-oxa-4-aza-spiro (4,5) -decane formed at a boiling point below 100 ° C, Dilute with a water-immiscible solvent of a density of 1.3 to 1.6 g / cm ³ , and the resulting solution is diluted with aqueous sodium hydroxide. Dispersed with 50 solution and acylated at pH 10-12 with dichloroacetyl chloride at -2 to + 2 ° C, the organic phase containing the crude product was washed with water and separated by weight of the organic phase. By introducing 0.4 to 1.5 times the amount of water or steam, the solvent is distilled off, the distilled solvent is recycled, if desired, to the acylation reaction, and the product is recovered from the melt in a known manner. The method of claim 1, wherein Toluene, xylene, carbon tetrachloride, dichloroethane or trichlorethylene are used as the 60 tip solvent. Process according to claims 1 and 2, characterized in that the ring closure reaction and solvent removal are continuously conducted in a film reactor.