DE3021579A1 - Fungicidal tri:morfamide prodn. - by reaction of morpholine with 1,2,2,2-tetra:chloro-ethyl-formamide in an aq. two=phase system - Google Patents

Abstract

In the prodn. of N-(1-formamide-2,2,2-trichloroethyl) morpholine (I) by reaction of 1,2,2,2-tetrachloroethyl formamide (II) with morpholine, the reaction is carried out at -2 to ca 60 deg.C and at pH 3-14 in a 2-phase system one phase of which is water. (I) is the known fungicide trimorfamide. Carrying out the reaction in a 2-phase system gives improved yields of (I) (ca 90% or, in the presence of a phase-transfer catalyst, up to 97%). Despite the known sensitivity of (II) to water, the reaction is carried out in an aqueous 2-phase system without marked hydrolysis. The reaction is pref. carried out at a pH of greater than 7 by adding alkaline cpds. The reaction is advantageously carried out in the presence of a phase-transfer catalyst.

Description

Process for the preparation of N- (l-formylamido-2,2,2-

-trichloroethyl) -morpholine Among the compounds of the general formula described so far There are two that are fungicidal agents, namely Triforine (DE-OS 19 01 421) and trimorfamid (DE-OS 24 39 610) The preparation of compounds of formula I was the first time F. Feist in Chem. Ber. 47, 1173 (1914).

Another series of examples was provided by H. Böhme et al.

in Arch. d. Pharm. 66, 307 (1961).

Both authors used 1,2,2,2 - tetrachloroethylformamide as starting material, that in all cases in water free medium with the corresponding Amine was implemented.

In further literature (DE-OS 19 01 421 and 19 46 112) the implementation mainly described in organic medium.

It has now been found that trimorfamide can be obtained with improved yield obtained when tetrachloroethylformamide with morpholine at temperatures from -2 to about 600C in the pH range 3 to 14 in a two-phase system, of which the one phase is water.

This result is surprising and could not have been foreseen because the authors mentioned the starting material tetrachloroethylformamide as a very describe unstable and easily hydrolyzable compound.

F. Feist mentions loc.cit on p. 1177. Tetrachloroethylformamide very much inconsistent and completely decomposed after a short time, extremely decomposable on p. 1180. - on the same page it is mentioned that the one chlorine atom (in the 1-position) Can be titrated "sharply" with n / 10 potassium hydroxide solution, which means for the expert that it is easily hydrolyzable.

H. Böhme reports on p. 307 loc.cit. That tetrachloroethylformamide is characterized by the reactive chlorine atom in preparation, which is easily subject to hydrolysis. Also the homologous compound with one more CH2 group in the molecule, the 1,2,2,3-tetrachloropropylformamide of the formula below will be in the Journ. f. Prakt. Chemie Vol. 316, p. 63 (1974) by H. Zimmer et al., namely that the chlorine in the 1-position should be very reactive and particularly sensitive to water, so that, for example, the air humidity is sufficient for hydrolysis to cause.

With this sensitivity of tetrachloroethylformamide to water it was not to be expected that the reaction with morpholine would be in a two-phase system would be possible without noticeable hydrolysis and the yield compared to literature data is still increased considerably, with 96 to 97% of theory. practically quantitative. In addition the purity of the compound thus obtained is very high.

Practically suitable as the organic phase in the two-phase system all solvents that are not or only sparingly soluble in water and one have a certain solubility for tetrachloroethylformamide, e.g. aromatic hydrocarbons and chlorinated aromatic hydrocarbons such as benzene, toluene, xylene, cumene, Chlorobenzene, dichlorobenzene, or nitrobenzene, as well as aliphatic compounds, such as methylene chloride, chloroform, carbon tetrachloride, ethyl acetate, isobutyl acetate, Diethyl ether, anisole, acetophenone, cyclohexane. Also mixtures of such solvents can be used.

The reaction temperature is between -2 and about 60 ° C., advantageously between 0 and 300 ° C., preferably between 20 and 0-25 ° C. Since the reaction is exothermic is, it is appropriate to maintain the intended temperature by cooling to care.

Advantageously within the marked pH range from 3 to 14 is the neutral to alkaline pH range, especially between 8 and 10, preferably between 8.5 and 9. If you submit the morpholine, it is sufficient to adjust the pH range if desired to regulate only when about half of the morpholine by implementation is used up. To then the pH value is set by the free Morpholine a. Alkaline compounds can be used for regulation, e.g. caustic soda, Sodium carbonate, sodium acetate, potassium hydroxide, potassium carbonate. It is expedient on in this way to adjust the pH range to higher than pH 7 in the course of the reaction and hold.

For an economical use of the reactants, it is advisable to the molar ratio of tetrachloroethylformamide: morpholine between 0.5: 1 and 2 : 1 to choose, advantageously between 0.8: 1 and around 1.2: 1, preferably 0.95: 1 up to 0.98: 1.

The tetrachloroethylformamide can be added to the reaction mixture in solid form as a suspension or, because of the easier handling, as a solution. If you use a solvent in which tetrachloroethylformamide is difficult or does not dissolve completely, it may be advantageous to keep the solution at an elevated temperature to keep.

It is not necessary to use pure raw materials. One can also use, for example, an unpurified tetrachloroethylformamide, which can be obtained by chlorination obtained from chloralformamide with thionyl chloride without loss of yield or purity of the compound obtained decrease noticeably.

The yield is usually 90%, but can be achieved with the help of a Phase transfer catalyst can be increased up to 97%. Suitable catalysts are the common onium compounds, preferably quaternary ammonium compounds, such as tetraethylammonium bromide, triethylbenzylammonium chloride, tetrabutylammonium hydrogen sulfate. They are generally used in the usual amounts, namely 0.1 to 50 mol percent, based on morpholine.

The response time is relatively short since the implementation is smooth and runs quickly. It is in the range from 5 to 180 minutes, generally at 30 minutes.

The end of the reaction can easily be seen from the fact that the pH remains constant in the desired range without adding further base.

The method of this connection can be carried out, for example, as follows are: morpholine, optionally part of the solvent and water, optionally In addition, a phase transfer catalyst are presented and the tetrachloroethylformamide in solid form, as a suspension in a solvent or dissolved in a solvent admitted. By adding a base, the most economical caustic soda, the During the reaction, the pH is kept in the slightly alkaline range, the pH can most easily be checked with a pH electrode. After the end of the When a solvent is used, the reaction will be the trimorfamide under the reaction conditions completely dissolves, the phases separated and the solvent by distillation of Trimorfamide separated. When using a solvent, which the resulting Trimorfamid has only partially dissolved, the resulting suspension is treated with a the usual isolation devices, such as filters or centrifuges, in solids and Filtrate separated.

In the filtrate the phases are separated and the organic phase becomes optionally also worked up for isolation. An additional extraction the aqueous phase is usually unnecessary, since trimorfamide is very difficult in water is soluble.

In a preferred form of the process that is particularly economical first stir chloral and formamide several hours in Toluene at elevated temperature and sets without isolation of the chloralformamide formed Thionyl chloride too. The mixture is again stirred for a few hours at an elevated temperature and heated to remove excess thionyl chloride, the reaction solution under reduced Pressure until about one twentieth of the volume is distilled off.

The solution thus obtained is immersed in an aqueous solution of morpholine run in, whereby by adding caustic soda it is ensured that the initially pH at 11.4 does not fall below 8.5. One obtains in this way with high economic efficiency Trimorfamide with a total yield, based on the formamide used, of 88 %.

In the following examples, parts by volume are related to parts by weight how liters to kilograms.

Example 1 In a stirred tank equipped with a pH electrode is, 90 parts by weight of morpholine, 3 parts by weight of tetraethylammonium bromide Submitted 50 parts by volume of toluene and 1000 parts by volume of water.

A template is left at 0 50 ° C. in the course of 30 minutes maintained solution of 211 parts by weight of tetrachloroethylformamide in 350 parts by volume Toluene run in, whereby the temperature is cooled to 20 to 25 0C and through Addition of sodium hydroxide solution (25 Zig) keeps the pH value at 8.5.

'After 30 minutes of stirring time, the suspension obtained is filtered off with suction, washes chloride-free with water and, after drying, contains 254 parts by weight of trimorfamide, which is uniform by thin layer chromatography and has a melting point of 113.50C owns. This corresponds to a yield of 97% of theory, based on tetrachloroethylformamide.

Example 2 If the implementation of Example 1 is carried out without the addition from phase transfer catalysts, the yield is 88%.

Example 3 If the implementation of Example 1 is carried out in the form that the toluene is dispensed with, i.e. no toluene is initially charged, and the tetrachloroethylformamide enters as a powder, the yield is 55%. This will take advantage of the two-phase system especially clear.

Claims (4)

Claims 1. A process for the preparation of N- (l-formylamido-2,2,2 - trichloroethyl) morpholine by reacting 1,2,2,2-tetrachlorathyiformamide with morpholine, characterized in that that the reaction at temperatures from -2 to about 600C in the pH range 3 to 14 in a two-phase system, one phase of which is water. 2. The method according to claim 1, characterized in that one during the implementation of the pH range by adding alkaline compounds to a higher pH 7 sets. 3. The method according to claim 1 or 2, characterized in that one used in the implementation of a phase transfer catalyst. 4. The method according to claim 1, 2 or 3, characterized in that the reaction with a 1,2,2,2 - tetrachloroethylformamide is carried out without Isolation of the intermediates from chloral and formamide was made.