DK149196B - PROCESS FOR THE PREPARATION OF N, N-DISUBSTITUTED 2-HALOGEN ACETAMIDES - Google Patents

Description

149196

The invention relates to a particular process for the preparation of known N, N-disubstituted 2-haloacetamides of the kind set forth in the preamble of claim 1, which compounds are useful in the agronomic field, e.g. as pesticides and plant growth regulators.

Halogen acetamides of the type described herein have been prepared using a variety of methods known in the art. By a known process described in U.S. Patent No. 2,863,752, N · -10 substituted 2-haloacetanilides are prepared by reacting a primary or secondary amine with the acid chloride of a haloacetic acid, typically in the presence of caustic soda to neutralize the hydrogen halide present as a by-product. A similar process is described in German Publication No. 1,903,198, wherein the intermediates and final products are characterized in that the N-substituent is alkoxyethyl, whereby one or two methyl groups may be attached to the ethyl radical.

By another known process described in U.S. Patent No. 3,574,746, N-substituted N-cycloalkenyl-2-haloacetamides are prepared by haloacetylation. of the corresponding N-substituted cycloalkylimine in the presence of an acid acceptor.

Another known process for the preparation of 2-halo-acetanilides is described in U.S. Patents Nos. 3,442,945 and 3,547,620, wherein a suitable starting compound, an N-halo-methyl-2-haloacetanilide, is reacted with a suitable alcohol. preferably in the presence of an acid binding agent. An analogous method is described in Canadian Patent No.

30 867 769 wherein fluoroacetylamino-trichloromethyl-chloromethane is reacted with a thio compound of the formula Me-S-R, where Me is H or an alkali metal; when the thio compound is used in the free form, it is convenient to use an acid binding agent; when the thio compound is used in the form of its salts, it is not necessary to add an acid-binding agent.

The processes of each of the above cited patents 5 '752,' 945 and '620 are described in U.S. Patent No. 3,875,228 as useful in the preparation of 2-haloacetamides (also described as acylamines) exemplified by No. chloroacetyl-N-substituted (hydrogen, alkyl, alkoxymethyl, allyloxymethyl or methoxyethyl-aminoindanes.

As relevant to the present invention involving the alcoholysis of N-haloalkyl-N-substituted 2-ha-halogenacetamide starting compounds, it is very well known (see, for example, the previously cited patents' 945, '620 and' 228 ) that the starting compound can be prepared by halogen acetylation of the phenylazomethine in question. See also U.S. Patent No. 3,637,847.

By another method described in the Journal of the Chemical Society, Volume 1, pages 2087-88 (1974) of 0.0.

Orazi et al., N-halo-N-substituted amides and imides are methylated at the nitrogen-halogen bond using diazomethane to prepare the corresponding N-halo-methyl-N-substituted amide or imide, followed by condensation with nucleophilic agents. One embodiment of this process involves the reaction of N-chloro-N-methyl-2-chloroacetamide and diazomethane to prepare the corresponding N-chloromethyl-N-methyl-2-chloroacetamide, which can then be reacted with a nucleophilic agent.

In the above patent 746, Examples 47 30 and 54 describe N-chloromethyl and N-bromomethyl-N-substituted cycloalkenyl-2-haloacetamides, respectively, which are representative of this class of compounds which can serve as starting compounds. by the method of the invention. Other known methods for preparing some starting compounds used in the invention involve the N-haloalkylation of the aniline in question followed by N-haloacylation. For example, N-2-chloroethyl or N-2-chloro-1-methylethyl-2-haloacetanilides can be prepared by reacting the corresponding aniline with 2-chloroethyl-1-p-toluenesulfonate and 2-chloro-1-methylethylene respectively. p-toluenesulfonate followed by chloroacetylation. A further process for preparing the N-haloalkyl intermediate involves reacting the halogenalkane in question, e.g. 1-chloro-2-bromethane, with the relevant aniline followed by chloroacetylation.

In processes for the preparation of N-substituted 2-haloacetanilides by alcoholising the corresponding starting compound N-haloalkyl-2-haloacetanilide, hydrogen halide is formed as a by-product, which adversely affects not only the yield of the desired product but also the harmful way affects the natural environment. As disclosed in patents' 945, '620 and' 228, it is necessary that this alcoholysis be carried out in the presence of an acid binding agent. Examples of acid-binding agents which have been used in the prior art include inorganic and organic bases such as alkali metal and alkaline earth metal hydroxides and carbonates, e.g. sodium and potassium hydroxide and sodium carbonate, tertiary amines, e.g. trimethyl and triethylamine, pyridine and pyridine bases, ammonia, quaternary ammonium hydroxides and alcoholates; metal alcoholates, e.g. sodium and potassium methylates and ethylates. Both the hydrogen halide and the acid-binding agent can promote adverse side reactions that are undesirable and, as a result, constitute a disadvantage of the known methods.

4 U9196

A significant disadvantage often encountered in the known processes described above is that the acid-binding agent reacts with the by-product hydrogen halide to form insoluble precipitates which must be separated from the reaction mixture and discarded. Separation of the desired product from the waste product often necessitates frequent distillations of any solvent used, aqueous washing, steam stripping of hydrogen halide, filtration and / or stabilization of product. Other purification methods include fractional distillation at sub- or superatmospheric pressure, solvent extraction, film distillation, recrystallization, etc. For example, in Example 4 of each of the patents '945 and' 620 disclosed, the acid binding agent, 15 ethylamine, in the preparation of N- (butoxymethyl) -2'-tert. butyl-61-methyl-2-chloroacetanilide (usually called "terbuchlor") forms a voluminous precipitate of fine needles of triethylamine hydrochloride which must be removed by aqueous washing, solvent distillation and filtration. The same problem is also described in the above-mentioned patent '746 (see column 6, lines 18-33).

When, as another example, ammonia is used as the acid-binding agent in the preparation of 2 ', 6'-diethyl-N- (methoxymethyl) -2-chloroacetanilide (usually called 25 "alachlor" and active ingredient in the commercial m / m bicid Lockso, registered trademark of Monsanto Company), ammonium chloride is formed as a solid by-product in large quantities which must be discarded.

During or after the alcoholysis of the N-haloalkyl starting compound, the majority of the hydrogen-halide by-product generated can in some cases be removed by conventional distillation. However, the hydrogen halide itself is a gaseous pollutant for the environment. In addition, distillation of the reactant alcohol and the by-product hydrogen halide in some cases results in the preparation of an alkyl halide and water, and water is detrimental to the yield of the product. Further, a certain percentage of the hydrogen halide remains in the reaction mixture and must be removed with an acid-binding agent to form solid waste products, as previously stated. In a previous work on the alachlor process, efforts were made to remove the by-product HC1 with excess methanol in conventional vacuum distillation. However, these efforts involve a prolonged exposure, namely approx. 2 hours, of the N-chloromethyl1 starting compound and the final product (alachlor) for the detrimental effect of HCl, water and other by-products, and they resulted in greatly reduced yields of ala-15 chlorine. It was then concluded that an acid-binding agent should be used during or after the distillation step, thus addressing the attendant disadvantages set forth above. In view of the energy conservation and environmental considerations affecting the disposal of process waste, it has become extremely important to find new approaches that eliminate or minimize the harmful effects of all types of waste, namely solids, liquids and / or gases from chemical processes. In some 25 cases, harmful by-products can be reused for recycling component parts. In other situations, the by-product may be purified or converted to other useful products. However, each of the treatments listed above requires additional investment and costs 30 for recycling and energy consumption. As a result, it is much more desirable to avoid the emergence of environmentally harmful products as much as possible.

6 149196

A further problem associated with known methods of preparing 2-haloacetanilides is that they are discontinuous processes with attendant disadvantages, especially on a commercial scale.

It is therefore the object of the invention to provide an improved process for the preparation of N, N-disubstituted 2-haloacetamides, which eliminates the disadvantages of the prior art process, to provide the advantages of a process requiring no acid-binding agent. and essentially does not produce any solid waste products, thus eliminating the cost of acid binding agents and problems of solid waste disposal which is unfriendly to the environment and providing one process that is continuous, simple and inexpensive to operate , conserves energy, reduces environmental pollution and yet produces yields that are as good or better than yields by known methods.

This is achieved by a method of the kind set forth in the preamble of claim 1 which is peculiar to that of the characterizing part of claim 1.

Preferred haloacetamides include those in which R is substituted pyrethyr, R 1 and R 2 are O 6 alkyl, R 4 is C 2-4 alkyl, R is monochloro or mono bromomethyl, and a is zero.

The process of the invention is particularly well suited for use in the preparation of the above-defined, N-substituted 2-haloacetanilides wherein R 1 -, R 2 and R 4 are C 1-4 alkyl, R 5 is monobromo or chloromethyl and a is zero.

7 149196

In the most preferred embodiment, the process of the invention is used to prepare alachlor (2 ', 6'-diethyl-N- (methoxymethyl) -2-chloroacetanilide) by reaction of 2', 61-diethyl-N- (chloromethyl) -2-. chloroacetanilide and methanol as described in Example 1 below.

In preferred embodiments, the above reaction / separation sequence is repeated a greater number of times to ensure complete conversion of the compound of formula II to the compound of formula I. In the most preferred embodiment, the process is effected in two steps or sequences reaction effectively. / separation, comprising: (A) reacting in a first reaction zone a compound of formula II with a compound of formula III; (B) directing an output stream of the reaction mixture from step (A) to a first separation zone, from which the major part of the by-product HX is rapidly removed as a complex with the compound of formula III and a product stream comprising mainly a compound of formula I 20, and not reacted compound of formula II; (C) directing the product stream from the first separation zone to a second reaction zone, also introducing a further amount of the compound of formula III which is to react with the unreacted compound 25 of formula II; (D) directing an outgoing stream of the reaction mixture from step (C) toward another separation zone, from which substantially all of the residual by-product HX as a complex with the compound of formula III and a product stream comprising the compound of formula I and trace impurities.

8 149196

Significant features of the method of the invention include; (1) the elimination of an added base, as used in the prior art as an acid-binding agent for released hydrogen halide, and in parallel (2) the elimination of recovery systems for neutralizing the by-product of (1), and consequently the elimination of the by-product itself from and (3) separation, preferably instantaneously and usually within 0.5 minutes of equilibrating the reaction mixture, of by-product hydrogen halide as a complex with the compound of formula III

by the operation or operations that constitute the product separation of the process.

In the process of the invention, the molar ratio of the compound of formula III to the compound of formula II in step A is greater than 1: 1, and in preferred embodiments, the ratio is usually between 2: 1 and 100: 1, in the case of the alachlor process between approx. 2: 1 and approx. 10: 1, preferably between 4: 1 and 5: 1.

The reaction temperature in step (a) will depend on the particular reactants and / or solvents or diluents used. Generally, these temperatures will be those temperatures at which mixtures of the alcohols of formula III and / or the solvents or diluents form complexes, e.g. azeotropic mixtures with by-product hydrogen halide present without significant degradation of the reactant compound of formula II or the desired product of formula I due to reaction with hydrogen halide. In general, a temperature is used within the range of approx.

30 -25 ° C and 125 ° C or higher, depending on the melting and boiling points of the reactants.

In the embodiments of the invention involving a greater number of sequences or steps of reaction / separation, the concentration of hydrogen halide is greatly reduced in successive reaction zones and, as a result, the reaction temperatures in subsequent reaction zones are generally somewhat greater than those temperatures. which is used in the first reaction zone to drive the reaction of the unreacted compound of formula II with additional alcohol to its end. Accordingly, temperatures are in the second and any subsequent reaction. zone in the interval between approx. -25 ° C and 175 ° C.

The temperatures and pressures within the separation zone or zones are, respectively, between approx. 50 and approx. 175 ° C and between approx. 1.3 and approx. 400 mbar absolute, depending on the boiling point of the compound of formula III.

In the practice of the invention, no solvent is required; however, in many cases, a solvent or diluent may be used to moderate the reaction and / or support the solution, dispersion and / or recovery of reactants, by-products and products. Suitable solvents or diluents include those which are inert under the required reaction conditions, such as petroleum ether, CCl, aliphatic and aromatic hydrocarbons, e.g. benzene, toluene and xylenes, as well as halogenated hydrocarbons, e.g. monochlorobenzene.

An advantage of the process of the invention is that the reactant of formula III can be easily separated from its complex with the by-product hydrogen halide, purified and recycled to one or more reaction steps of the process. Similarly, the hydrogen halide itself can be easily recovered for use in many useful commercial operations, e.g. yellowing of metals, oxychlorations and electrolysis for elemental chlorine and the hydrogen, or otherwise discarded without harm to the surroundings.

In a suitable raw material recovery / recycling system, exemplified as the complex methanol / HCl formed in the alachlor process described in Examples 1, 11 and 12, the methanol / HCl complex is fed from the separation step or steps to a distillation system from which purified methanol is obtained.

Although the use of the reactants, viz. If the compounds of formula II and III of technical quality are well-suited in the present process, it will be understood that the higher the quality of the compounds of formula I, the higher the purity of these reactants will be. Although in some cases it is possible to use for-15. the binders of formula III, e.g. methanol containing smaller amounts of water is much more preferred to use anhydrous compounds because water can produce hydrolysis of the reactants of formula II, resulting in a degraded product of formula I.

20 It is e.g. known that 2'-tert.-butyl-6'-ethyl-N- (chloromethyl) -2-chloroacetanilide is hydrolyzed with water in the presence of an acid binding agent to prepare the corresponding N-hydroxymethyl compound which can be used as a herbicide (see, for example, Example 1 of British patent no.

25 1 088 397). As a result, it will be appreciated that the presence of some water in certain embodiments of the invention may be detrimental to the product yields, but that this is not the case in other embodiments, depending on the reactivity of water with other reactants and final products, which will .understand by experts. Similarly, it is preferred to use reactants which are substantially free of hydrogen halides, such as HCl, because hydrogen halides exert a detrimental effect on the quality of the product.

EXAMPLE 1

This example describes the use of the process of the invention for the preparation of 21,6'-diethyl-N- (methoxymethyl) -2-chloroacetanilide (alachlor). This procedure is effectively carried out in a two-step reaction / separation sequence as follows:

Step 1: Melted (45 - 55 ° C) 2 ', 6' -diethyl-N-chloromethyl-2-chloroacetanilide is fed to an in-line mixer at a rate of 46.67 kg / h and mixed at substantially 15 ° C. anhydrous methanol fed to the mixer at a rate of 27.24 kg / h. The mixture is pumped through a thermostated tube reactor having a temperature of 40 - 45 ° C and of sufficient length to produce a standby time of at least 30 minutes. In the reaction, a yield of approx. 92¾ of 2 ', 6'-diethyl-N- (methoxymethyl) -2-chloroacetanilide (alachlor) and hydrogen chloride on the basis of the N-chloromethyl starting compound. The resulting HCl is dissolved in excess methanol. The material emanating from the reactor is directed to a descending film evaporator, operated at 100 ° C and absolute 40.0 mbar. A complex is removed, which is then fed to a methanol recovery system.

Step 2: The product stream from the evaporator in Step 1, mainly comprising alachlor and unreacted 2 ', 6'-diethyl-N- (chloromethyl) -2-chloroacetanilide, is fed to a secondary in-line mixer, to which a further amount of methanol at a rate of 27.24 kg / h. The mixture is then passed to a secondary reaction zone which also comprises a thermostated tube reactor maintained at 60-65 ° C, giving a standstill time of 30 minutes. Reaction mixture from this reactor is fed to a secondary falling film evaporator, operated at 100 ° C and 40.0 mbar 5 absolute pressure, from which a methanol complex and substantially all of the residual HCl is removed. The methanol / HCl complex from this second stage evaporator is mixed with the methanol / HCl complex from the evaporator in step 1 and fed to a methanol recovery system from which anhydrous methanol is recovered and recycled to step 1.

The product stream from the evaporator in step 2 comprises alachlor in a substantially quantitative yield and in a purity greater than 95¾ along with minor amounts of impurities. This alachlor can be effectively used as a herbicide in the condition just prepared.

It can be seen from the preceding example that the reaction / separation process step in step 1 itself gives rise to alachlor in high yield. Under optimal conditions of reactant purities and concentrations, temperatures, reactor residence times and separation zones, etc., at least one process sequence reaction / separation corresponding to the indicated step 1 would be sufficient to produce alachlor or other compounds with formula I of commercial quality.

In the non-recrystallized state, the final product has a melting point of 35.5 - 40.0 ° C. It is a light amber oil that crystallizes on standing.

EXAMPLE 2

This example describes the preparation of 2-chloro-2 ', 6'-diethyl-N- (ethoxymethyl) acetanilide.

13 149196

Ca. 5.5 g (0.02 mol) of 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) -acetanilide was dissolved in 25 ml of ethanol and the mixture was allowed to stand in a 45 ° C bath for 30 minutes. . Excess ethanol was quickly removed on a rotary vacuum evaporator at 50 ° C and 13.3 mbar. 25 ml of fresh ethanol was added to the residual oil and the mixture was maintained at 69 ° C

1 30 minutes. Again, excess ethanol was removed using a rotary evaporator. There were approx.

5.80 g of a pale amber oil containing (according to gas chromatography) 92.8% of the desired product and 1.7% 2-chloro-2 ', 6'-diethyl acetanilide ( by-product). The yield of the product was 94.5%. The desired product has a refractive index n ^ 2 ^ of 1.5220.

Example 3 Using the same method, operating conditions and amounts of reactants as in Example 2, but using isopropanol instead of ethanol, 5.92 g of product, a light amber oil containing 90.2%, was obtained. ', 6'-diethyl-N- (isopropoxymethyl) -2-chloroacetanilide (89.4% yield) and 1.8% of the secondary amide by-product, 2', 6'-diethyl-2-chloroacetanilide. The desired product had a refractive index n 1 of 1.5165.

EXAMPLE 4

Following the same method as described in Examples 2 and 25, but using 1-propanol as the reactant alcohol instead, 5.66 g of lemon yellow oil containing 92.8% (87.9%) was recovered. yield) 2 ', 6'-diethyl-N- (n-propoxymethyl) -2-chloroacetanilide and 1.2% of the corresponding secondary amide by-product. The desired product had a refractive index of 1.5175.

EXAMPLE 5

The same method as described in Examples 2-4 was used in this example, but isobutanol was used as the reactant alcohol; 6.20 g of an oil product were obtained containing 5, 96.4¾ (97¾ yield) of 2 ', 61-diethyl-N- (isobutoxymethyl) -2-chloroacetanilide and 3¾ of the corresponding secondary amide by-product. The desired product had a refractive index of 1.5151 and appears as a pale greenish yellow oil.

EXAMPLE 6

Repeating the process of Examples 2-5, but using 2-chloroethanol as the reactant alcohol, there was obtained 6.96 g of slightly amber oil containing 86.0¾ (94.0¾ yield) 2 ', 6'-diethyl -N- (chloroethoxymethyl) -2-chloroacetamide. The desired product had a refractive index n 1 of 1.5338.

EXAMPLE 7

Following the same method as described in Examples 2-6, but using n-butanol as the reactant alcohol instead, 6.18 g of pale lemon yellow oil containing 98.8¾ (99¾) was obtained. yield) 2 ', 6'-diethyl-N- (n-but-oxymethyl) -2-chloroacetanilide (namely, butachlor) and 1¾ of the corresponding secondary amide by-product.

In the above examples, NMR analysis showed that the 25 products in question had the expected chemical structure.

As further documentation of the advantages of the present invention and the surprising nature thereof, reference should be made to the following discussion and the additional experimental data in Examples 8 - 12.

15 149196

The reaction between compounds such as those identified by Formula II and Formula III above is a reversible second-order reaction. The following Reaction Scheme 1, exemplified by the reaction of Example 5 1, illustrates the reaction: C 1 H 2 0 5 C 2 H 5 0 // C _____ C-CH 2 C 1/1 J: CH 9 Cl 1 (1) fl + ch 3 OH- * f y Z + HCl —'Z ^ CH2C1 ^ '»Z ^ CH20CH3

C? H ί H

2 3 (a) (b) (c) 2 5 (d)

Since the reaction is reversible, an equilibrium state is established; this equilibrium is influenced by and is directly related to various factors, e.g. the alcohol concentration and / or the concentration of hydrogen halide present as a by-product. For example, when in Scheme (1), the concentration of alcohol (b) grows, and as a result the reactant ratio (b): (a) (to a given practical maximum), the equilibrium is shifted to the right due to further conversion of starting material (a), whereby more product (c) and by-product of the present hydrogen halide (d) are produced.

Another way to shift the equilibrium of reaction scheme (1) to the right is to remove the hydrogen halide (d), which can be done by adding an acid-binding agent, e.g.

20 tertiary amines, such as triethylamine, as disclosed in United States Patents Nos. 3,547,620 and 3,442,945 and Canadian Patent Nos.

867 769 listed above. However, the use of acid binding materials causes other disadvantages as described above.

The foregoing Canadian patent '769 suggests that the acid binding agent is unnecessary when the thio compound present as a starting material is in the form of an alkali salt; the obvious reason for this is that these salts, in themselves, provide the basic medium favorable to the particular reaction described in the particular patent. In contrast, when the thio compound as a starting material is used in the free form, it is necessary to use an acid-binding agent to bind the by-product hydrogen chloride.

Although the process described in the above patents' 620 and r945 is described such that it is preferably carried out in the presence of an acid binding agent (as exemplified in all the specific working examples), it is concluded that the same method can be exercised without the addition of an acid binding agent. However, as previously stated in the prior art section, efforts were directed to carrying out the process described in patents '945 and' 620 to obtain the preferred product alachlor without any acid-binding agent to remove as a by-product the present hydrogen halide, in greatly reduced yields of alachlor.

To further compare the results obtained by carrying out the method described in patents '945 and' 620 without an acid binding agent and the results obtained by the process of the invention, the applicant has completed the In each of these examples, the starting material N-chloro-methyl-2-chloroacetanilide was prepared by reaction of the corresponding substituted N-methylenanilide with haloacetyl halide as described in patents '945 and' 620.

EXAMPLE 8 17 149196

This example describes the preparation of 2-chloro-2 ', 6'-diethyl-N- (methoxymethyl) -acetanilide (alachlor) as set forth in Example 5 of U.S. Patent Nos. 3,547,620 and 5,442,945.

100 g of 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide having a purity of 96,050 (0.350 mol) and dissolved in ca. 70 g of benzene were added to 65.8 g (2.054 moles) of methanol. Upon addition, an exothermic reaction occurred. The reaction mixture was refluxed (at 63 ° C) and an excess (ca.

63.3 g) of triethylamine was added dropwise over 1.5 hours.

During this addition, the temperature rose to approx. 70 ° C, where it was kept for approx. 10 minutes after the addition of triethylamine. After cooling to 30 ° C, the reaction mixture was washed with two 170 ml portions of water. The product, which was present in a heavy, oily layer, was freed from solvent and dehydrated by vacuum distillation to a terminal boiler temperature of approx.

70 ° C at 1.3 mbar. The residual amber oil weighed 20 96.15 g and was found to contain 90,450 product and 4,9¾ of 2-chloro-2 ', 6'-diethylacetanilide (by-product) (gas chromatography). There was no unreacted starting material in the product. The yield of the product was 92.0¾.

EXAMPLE 9 This example describes the preparation of alachlor as set forth in Example 5 of patents '620 and' 945, but without the use of an acid binding agent.

100 g of 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide having a purity of 96.050 (0.350 mol) and dissolved in ca. 70 g of benzene was added to 66.0 g of methanol (2.059 mol). Upon addition, an exothermic reaction occurred and the reaction mixture was further heated to reflux (at 63 ° C) for 1 hour. No acid binding agent was added. After reflux, excess methanol and solvent were removed by vacuum distillation to a final boiler temperature of 70 ° C at 1.3 mbar. There were approx. 96.83 g of a pale lemon yellow oil containing (according to gas chromatographic analysis) 83.7SS product, 7.5% by-product 2-chloro-2 ', 6' diethyl acetanilide and 5.5% unreacted starting material. The yield of the product was 85.8SS.

As will be noted, omission of an acid-binding agent in this example resulted in a 6.2% yield reduction. In this approach, the reaction did not go all the way to the right. As a result, the by-product HCl 15 decreased the reaction between the starting compounds and the unreacted starting material was found to be an impurity in the product.

EXAMPLE 10

This example describes the preparation of alachlor as set forth in Example 5 of the patents '620 and' 945, 20 but without the use of an acid binding agent and under optimized temperature conditions.

100 g of 2-chloro-21,6'-diethyl-N- (chloromethyl) acetanilide of purity 96.0% (0.350 mol) and dissolved in ca. 70 g of benzene was added to 65 g (2.059 mol) of methanol. There was an exothermic reaction which raised the temperature of the reaction mixture to 45 ° C, at which value it was kept for 1 hour. No acid binding agent was added. Excess methanol and solvent were removed by vacuum distillation to a final boiler temperature of approx. 80 ° C at 1.3 mbar. There were approx. 96.20 g of oil, which by gas chromatography was found to contain 6.2% by-product, 2-chloro-2 ', 61-diethyl-acetanilide, and ca. 4.6% unreacted starting material. The yield of the product was 87.4%.

19 149195

By optimizing the reaction conditions in the absence of an acid binding agent, an increase in product quality (2.7%) and yield (1.6%) were obtained, but the basic problem, namely incomplete reaction, has not yet been solved.

EXAMPLE 11

This example describes the preparation of alachlor by the process according to the invention in accordance with the embodiment using a single stage reactor; the starting material used here was the same as that used in Examples 8-10.

10 g of 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide with a purity of 96.0% (0.035 mol) was added to ca. 6.0 g (0.1873 mol) of methanol. An exothermic reaction occurred which raised the temperature of the reaction mixture to ca. 45 ° C, where it was kept for 30 minutes. Excess methanol was rapidly removed on a rotary vacuum evaporator to a final boiler temperature of 70 ° C at 1.3 mbar. 9.80 g of pale, lemon-yellow oil was recovered which, according to gas chromatography, contained 91.0% of product, 1.7% as a by-product of 2-chloro-2 ', 6'-diethylacetanilide and 2.4% of unreacted starting material. . The yield of the product was 94.4%.

Thus, using only a single step, the quality and yield of the desired product are substantially improved in comparison to the prior art, despite the fact that the reaction was not complete (2.4% starting material in the product). Comparison with Examples 8, 9 and 10 shows an obvious improvement, although no acid binding agent was used.

. EXAMPLE 12 149196

This example describes the preparation of alachlor in the absence of an added acid binding agent according to the preferred method of the invention using a multi-stage reactor.

10 g of 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide having a purity of 96.0% (0.0360 mole) was dissolved in 6.0 g (0.1873 mole) of methanol. An exothermic reaction occurred which raised the temperature to 45 ° C, where it was kept for 10 and a half hours. Excess methanol was rapidly removed on a rotary vacuum evaporator to a final boiler temperature of 45 ° C at 1.3 mbar. A second addition of fresh methanol, 6.0 g (0.1873 mol), was made, the reaction mixture was heated to 65 ° C and held there for half a 15 hours. Excess methanol was removed as before and approx. 9.80 g of pale, lemon-yellow oil containing 95.8¾ of product, 1,4¾ of 2-chloro-2 ', 6'-diethyl-acetanilide and no starting material. The yield of the product was 99.4¾. The crude product had a melting point of 38.3 - 38.8 ° C. After recrystallization from aqueous methanol, the product appeared as a white, colorless solid having a melting point of 43.3 - 43.9 ° C.

An overview of the comparable results of the methods described in Examples 8 - 12 is shown in the following table. In this table, the "starting material" is not reacted with 2 ', 6'-diethyl-N- (chloromethyl) -2-chloroacetanilide, and' by-product 'refers to 2', 6'-diethyl-2-chloro-acetanilide, the essential acetanilide by-product of the methods of each of these examples. It is to be understood that in addition to large amounts of hydrogen halide, smaller amounts of acetanilide and other by-products are formed, and in Example 8, further is formed as neutralization by-product triethylamine hydrochloride. Percentages of product yield are here based on the 2 ', 6' - diethyl-N- (chloromethyl) -2-chloroacetanilide present as the starting material.

TABLE

Product Analysis% _

Eczema- Yield Pell Progress of Ala- Ala- Bi- Exit No. way_chlorine (¾) chlorine product material 8 Ex. 5 of the United States Pat.

3 44? 945 &3,547,620; acid 92 '° 90'4 4'9 0 binding agent added 9 The same but', 8 83.7 7.3 3.5 omitted 10 Same as Example 9 with optimized 87.4 85.8 6.2 4.6 conditions 11 Method according to the invention 94.4 91.0 1.7 2.4 Part 12 The same, multiple steps 99.4 95.8 1.4 0

An analysis of the data contained in the above table results in the following prominent features and decisive advantages of the method according to the invention, cf. Examples 11 and 12, versus the known method illustrated in Examples 8-10. : (1) a substantial increase in alachlor yield; (2) improving the purity of alachlor; (3) significantly reduced amounts of by-products; (4) increased conversion of starting material when working without added acid binding agent; and (5) the absence of the solid neutralization product present in large lengths by the method illustrated in Example 8, to which is added acid binding agent - the example illustrates the best known technique for preparing alachlor. These technical advantages are available as additional advantages in addition to the economic and ecological advantages previously stated.

EXAMPLE 13 149196 22

Preparation of 2'-methyl-6'-tert.-butyl- (N-methoxymethyl) -2-bromoacetanilide. To 15.08 g (0.040 mol) of 2'-methyl-6'-tert.-butyl (N-bromomethyl) -2-bromoacetanilide was added 25.0 5 g of anhydrous methanol. The mixture was heated to 45 ° C and let it stand for 30 minutes. Excess alcohol and HBr were removed on a rotary evaporator at 45 ° C / 13.3 mbar. The oily residue was treated twice more with 25.0 g portions of anhydrous methanol in a similar manner. After the final stripping, 13.0 g of 26 amber yellow oil (n ^ 1.5470) was obtained, which by GLC was found to contain 97.0-of 2'-methyl-6'-tert.-butyl- ) -2-bromacetanilid. The yield was 96.0¾. The NMR spectrum is consistent with the structure and is identical to the NMR spectrum of the product obtained when triethylamine is used as an HBr cleaner.

EXAMPLE 14

Preparation of 2 ', 6'-dimethyl- (N-isopropoxymethyl) -2-chloroacetanilide. Ca. 12.3 g (0.050 mol) of 2 ', 6'-dimethyl- (N-chloromethyl) -2-chloroacetanilide were dissolved in 30.0 g of anhydrous isopropanol. The reaction mixture was heated to 45 - 50 ° C for 30 minutes and excess alcohol was distilled off using a rotary evaporator at 60 ° C / 13.3 mbar. The residue was treated an additional 25 times with 30.0 g of fresh isopropanol at 45 ° C for 30 minutes.

After distilling off excess alcohol, there was 76 13.27 g of clear, lemon-pale yellow oil (n ^ 1.5245), which showed a purity of 93.9 93 by GLC. The yield was 92.5¾. The NMR assay is consistent with the structure and is identical to the NMR assay for the product prepared using other methods.

EXAMPLE 15 23 149196

Preparation of 2-chloro-2 ', 6'-diethyl-N [(2-methoxyethoxy) methyl] -acetanilide. To 13.71 g (0.050 mol) of 2 ', 6'-diethyl- (N-chloromethyl) -2-chloroacetanilide was added 38.0 g of methyl cellosolve and the mixture was allowed to stand at room temperature for 30 minutes. Excess alcohol was removed by a rotary evaporator at 65 ° C / 0.67 mbar. To the residual oil was added 38.0 g of fresh methyl celllosolve and the mixture was kept at 45 ° C for 30 minutes. Over 10 shots of alcohol were removed, as before, to give 15.46 g of lemon-pale yellow oil. The yield is 98.5¾. The oil was taken up in n-hexane and recrystallized to give a white crystalline solid, mp 31.5 - 32.5 ° C.

EXAMPLE 16

Preparation of 2'-ethyl-6'-methyl- (N-ethoxymethyl) -2-chloroacetanilide. To 10.4 g (0.040 mol) of 2'-ethyl-6'-methyl (N-chloromethyl) -2-chloroacetanilide was added 30.0 g of ethanol and heated to 45 ° C for 15-20 minutes. .

Excess alcohol was removed under vacuum on a rotary evaporator. The residual oil was treated with 30.0 g of fresh ethanol at 45 ° C for 15 minutes and excess ethanol was removed. After a third treatment, the residual oil weighed 10.73 g and at 25 GLC it was found that its purity was 96.4¾. The yield was 96.0¾. Fraction index n + = 1.5236. The NMR assay is consistent with the structure and is identical to the NMR assay for the product prepared using an acid detergent.

EXAMPLE 17

Preparation of 2'-methyl-6'-methoxy- (N-isopropoxymethyl) - 2-chloroacetanilide. To 3.30 g (12.6 mmol) of 2'-methyl-6'-methoxy- (N-chloromethyl) -2-chloroacetanilide was added 15.0 g (0.25 mol) of anhydrous isopropanol and heated to 45 °. C for 30 minutes. Excess alcohol and HCl were removed under vacuum on a rotary evaporator and replaced with 15.0 g of fresh isopropanol. The mixture was heated to 45 ° C and after 30 minutes excess alcohol was removed to give 3.10 g of light amber-26 yellow oil, np 1.5225. NMR analysis is consistent with the structure. The yield was 100? Ά.

3! / CCH2C1

<QKCh2ochO

DCH3 CH3 EXAMPLE 18

Preparation of 2 ', 6'-diethyl- (n-methoxymethyl) -2,2-dichloroacetanilide. To 15.43 g (0.050 mol) of 2 ', 6'-diethyl (N-chloromethyl) -2,2-dichloroacetanilide was added 32.0 g of anhydrous methanol. The reaction mixture was allowed to stand at 45 ° C for 30 minutes and then alcohol HCl was removed under vacuum on a rotary evaporator. The oily residue was treated twice the same way and after distilling off the excess alcohol, 26 20 15.15 g of clear, lemon-pale yellow oil (n ^ 1.5330) were obtained, which by GLC was found to have a purity of 98.3? ί. The yield was 97.9? Ό. The NMR assay is consistent with the structure and is identical to the NMR assay for the product obtained using base as a detergent for HCl.

EXAMPLE 19

Preparation of 2'-methyl-61-tert.-butyl- (N-allyloxymethyl) -2-chloroacetanilide. To 14.5 g (0.050 mol) of 2'-methyl-6'-tert.-butyl- (N-chloromethyl) -2-chloroacetanilide was added 29.0 g of allyl alcohol and heated to 45 ° C for 15 minutes. . Excess alcohol was removed during vaccum on a rotary evaporator and replaced with 29.0 g of fresh allyl alcohol. The mixture was again kept at 45 ° C for 15 minutes. After distilling off the excess alcohol, the order of reaction steps was repeated a third time.

After the third distillation, 14.45 g (93.4¾ 26 yield) of a light amber oil, n ^ 1.5338, was obtained. NMR analysis 10 was consistent with structure.

EXAMPLE 20

Preparation of N- (2,6-dimethyl-1-cyclohexen-1-yl) -N- (methoxymethyl) -2-chloroacetanilide. Ca. 5.90 g (23.5 mmol) of N- (2 ', 6'-dimethylcyclohexen-1-yl) -N- (chloromethyl) -2-chloro-acetamide were dissolved in 28.3 g of anhydrous methanol and let the mixture stand at room temperature for 30 minutes.

Excess methanol was removed under vacuum on a rotary evaporator. The above sequence of reaction steps was repeated two more times, and after the final removal of methanol, 5.50 g (94.9¾) of 26 lemon-pale pale oil (n ^ 1.5050) were obtained. Proton NMR more closely matches the structure.

EXAMPLE 21

Preparation of 2 ', 4', 6'-triethyl- (N-methoxymethyl) -2-25 chloroacetanilide. To 22.5 g (0.074 mol) of 2-chloro-2 ', 4', 6'-triethyl-N- (chloromethyl) -acetanilide in 30 ml of chlorobenzene, 25 ml (20 g) of anhydrous methanol are added and the mixture is charged stand at room temperature for 30 minutes. ' Excess methanol and some chlorobenzene were removed under a vacuum on a rotary evaporator and another 20 g portion of fresh methanol was added to the residual oil.

Again, methanol was distilled off on a rotary evaporator and the sequence of reaction steps was repeated for the third time. After the third distillation, 26 21.0 g of lemon yellow oil (np 1.5243) were obtained, which was found to be 97.7S 2 ', 4', 6'-triethyl- (N-methoxymethyl) -2-chloro-5 'acetanilide, 1.0% 2', 4 ', 6'-triethyl-2-chloroacetanilide (by-product) and 0.7% 2', 4 ', 6'-triethyl-2,2-dichloroacet-anilide (by-product) . The NMR analysis is consistent with the structure. The yield was 93.1%.

Example 22 Preparation of 21,6'-dimethyl- (N-cyclohexyloxymethyl) -2-chloroacetanilide. To 12.3 g (0.050 mol) of 2 ', 6'-dimethyl- (N-chloromethyl) -2-chloroacetanilide was added 50.0 g of anhydrous cyclohexanol and the solution was allowed to stand at room temperature overnight. Excess alcohol was distilled off on a rotary evaporator at 65 ° C / 1.3 mbar.

Fresh cyclohexanol (50.0 g) was added to the residue and the solution was heated to 45 ° C for 30 minutes.

Excess alcohol was distilled off at 65 ° C / 0.67 mbar to give 15.45 g (99.7% yield) of lemon pale pale yellow oil. By causing the oil to crystallize from cold hexane, the entire amount of oil was found to become a crystalline solid, mp 46-47 ° C. The NMR analysis is consistent with the structure.

Example 23 Preparation of 2'-methyl-6'-tert.-butyl- (N-cyclopropylmethoxymethyl) -2-chloroacetanilide. Ca. 4.77 g of 2'-methyl-6'-tert.-butyl- (N-chloromethyl) -2-chloroacetanilide (0.016 mol) is dissolved in 9.60 g (0.132 mol) of cyclopropylcarbinol. The solution is allowed to stand for one hour at room temperature and then excess alcohol is removed on a rotary evaporator at 55 ° C / 1.3 mbar. Ca. 9.6 g of fresh cyclopropyl-carbinol are added to the residual oil and the solution is heated to 45 ° C for 20 minutes. Excess alcohol is again removed under vacuum as before to give 26 a light amber, clear oil, Πρ 1.5269, weighing 5.28 g (98.9 *).

EXAMPLE 24

Preparation of 2 ', 6' -dimethyl-N- (2-methoxy-1-methylethoxy-methyl) -2-chloroacetanilide. Ca. 12.3 g (0.050 mol) of 2 ', 6'-dimethyl-N- (chloromethyl) -2-chloroacetanilide dissolved in 20 ml of ethylene dichloride are added to 22.5 g (0.25 mol) of 2-methoxy-10-methylethanol . The solution was allowed to stand for 1 hour at room temperature. Excess alcohol was removed under vacuum on a rotary evaporator. The residual oil was treated with an additional 22.5 g of fresh alcohol for 30 minutes at 60 ° C. Excess alcohol was removed as before 15 at 65 ° C / 1.3 mbar. The pale yellow oily residue weighed 14.68 g (99.1% yield). The refractive index of the oil, 26 Πρ, was 1.5263. Proton NMR is consistent with structure. EXAMPLE 25

Preparation of 2'-methyl-6'-methoxy-N- (2-methoxy-1-methyl-ethoxymethyl) -2-chloroacetanilide. Ca. 4.60 g (0.017 mol) of 2'-methyl-6'-methoxy-N-chloromethyl-2-chloroacetanilide dissolved in 15.8 g of 2-methoxy-1-methylethanol ("propasol") was heated to 45 ° C for 1 hour. 15 minutes. Excess alcohol was removed on a rotary evaporator at 55 ° C / 1.3 mbar. The residue was re-treated with 15.8 g of "propasol" for 15 minutes at 45 ° C, and excess alcohol was removed as before.

This sequence of process steps was repeated a third time at 65 ° C for 15 minutes, and after the final alcohol removal, 4.54 g (87.6 *) of a 26 30 amber oil with refractive index Πρ 1.5165 was obtained. Proton NMR was consistent with structure.

149196 28 / CH3 ° / P> n <CCH2C1 \ oy ch2ochch2och3 0CH3 ^ H3

Claims (7)

149196 A process for the preparation of N, N-disubstituted 2-haloacetamides of the general formula. Wherein R is the 2,6-dimethyl-1-cyclohexen-1-yl group or a substituted phenyl group of the general formula (* 3), - and R 2 and R is independently hydrogen or "3 is a 6 alkyl group or C 16 alkoxy group, R is a 6 alkyl group or an alkoxy group, R 4 is a C 1-4 alkyl, C 16 chloroalkyl, C 16 alkoxyalkyl or cyclopropylmethyl group or an allyl or cyclohexyl - group 10, R 1 is bromomethyl, mono or dichloromethyl group 1 2 and a is 0 or 1, at least one of the groups R and R being different from hydrogen when a is 0, when reacting between the corresponding N- halo-methyl-2-haloacetamides and alcohols, characterized in that N-halo-methyl-2-haloacetamides of the general formula 0 are 5 ° C - R? R - (II) X is chlorine or bromine and R and R 2 are as previously defined, with alcohols of the general formula R 4 - OH (III) 4 wherein R is as defined above, in the absence of 149196 acid binding agents at a temperature in the range of between -25 and 175 ° C, when the compound of formula (III) is used in excess and the reaction mixture is then discharged from the reaction zone into a separation zone where a complex mixture of by-product HX is used. and unreacted compound of formula (III) is rapidly separated from the product stream containing mainly the compound of formula (I) at a temperature between 50 and 175 ° C and a pressure between 1.3 and 400 mbar, and that this order between the reaction and - "10 separation steps, if desired, are carried out in a one-step reaction separation container or, if desired, repeated several times, if desired, the complex mixture of HX and the compound of formula (III) being conducted to a recovery system wherein the compound of formula (III) is separated from the hydrogen halide, purified and returned to the first and / or any additional reaction zones. Process according to claim 1, characterized in that the product stream from the first separation zone by a two-stage operation after reacting the N-halo-methyl-2-haloacetamide of formula (II) with the alcohol of formula (III) in a first reaction zone and separation in a first separation zone of the resulting reaction mixture in a complex mixture containing the majority of the by-product HX and the compound of formula (III) and a product stream containing mainly the compound of formula (I) and unreacted compound of formula (II) is introduced into another reaction zone wherein, if desired, an additional amount of the compound of formula (III) is introduced to react the unreacted compound of formula (II) and the reaction mixture of the a second reaction zone is introduced into a second separation zone, where a complex mixture of virtually the total residual by-product HX and the compound of formula (III) is rapidly separated. traces of impurities. 149196 Process according to claim 2, characterized in that the temperature in the first reaction zone is between -25 and 125 ° C and the temperature in the second reaction zone is between -25 and 175 ° C. Process according to claim 1, characterized in that the alcohol of formula (III) is used in an excess corresponding to between 2 and 100 times the molar amount. Process according to claim 2, characterized in that the complex mixture of HX and the compound of formula (III) from the second separation zone is introduced into a recovery system in which the compound of formula (III) is separated from the hydrogen halide, purified and returned to the first and / or the second reaction zone. Process according to claim 1 for the preparation of 2 ', 6'-diethyl-N- (methoxymethyl) -2-chloroacetanilide, characterized in that methanol is reacted with 2', 61-diethyl-N- (chloromethyl) -2 -chloroacetanilide in a molar ratio of 2: 1 to 100: 1 at a temperature between 25 and 65 ° C for 15 to 30 minutes in the absence of an acid-binding agent, and 20 introducing the reaction mixture into a separation zone in which to quickly separate a complex mixture of HCl and methanol from a product stream containing mainly the final product, whereby this consequence of reaction and separation steps may be repeated several times. 1 2 3 4 5 6 Process according to claim 6, characterized in that in a first reaction zone, methanol 3 is reacted with 2 ', 6'-diethyl-N- (chloromethyl) -2-chloroacetanilide in a 4 molar ratio of 2: 1 to 10: 1, and that the first separation zone is a short-distance distillation zone, in which 6 a temperature is maintained between 50 and 100 ° C and a pressure between 40 and 400 mbar, from which a complex mixture of methanol and most of the by-product is removed.