HU181460B - Process for preparing halo-acylamide derivatives - Google Patents

Description

The present invention relates to a novel process for the preparation of haloacylamide derivatives, in particular haloacetanilides, which are agriculturally useful compounds, such as pesticides, as active ingredients of plant growth regulators.

Several processes for preparing the haloacylamides and haloacetanilides of the invention are described in the literature.

According to U.S. Patent No. 2,863,752, N-substituted 2-haloacetanilides can be prepared by reaction of the acid chloride of primary or secondary amines with haloacetic acid in the presence of caustic soda to neutralize the hydrogen halide formed as a by-product. A similar procedure is described in German Patent Publication No. 1,903,198, wherein the intermediates and end products are N-substituted lower alkoxyethyl derivatives wherein the ethyl radical may have one or two methyl groups.

According to U.S. Patent 3,574,746, N-substituted-N-cycloalkenyl-2-haloacetamides can be prepared by haloacetylation of the corresponding N-substituted-cycloalkylimine in the presence of an acid acceptor.

According to U.S. Patent Nos. 3,442,945 and 3,547,620, 2-haloacetanilide derivatives can be prepared by reacting the corresponding intermediate N- (halomethyl) -2-haloacetanilide with the appropriate alcohol, preferably in the presence of an acid scavenger. .

Canadian Patent No. 867,769 discloses a similar method of reacting a fluoroacylaminotrichloromethylchloromethane with a thio compound of the formula Me-S-R wherein Me is hydrogen or an alkali metal ion when the thio- If the thio compound is used in its free form, it is advisable to use an acid scavenger, whereas when the thio compound is used as a salt, an acid scavenger is not required.

U.S. Pat. No. 3,875,228 uses the above processes to prepare 2-haloacetamides. Examples of such compounds are N-chloroacetyl-N-substituted-aminoindan derivatives. The alcoholysis of the N-haloalkyl-N-substituted 2-haloacylamide or 2-haloacetanilide intermediate is described, for example, in U.S. Patent No. 3,637,847.

According to another method, [Ο. O. Orazi et al., Journal of the Chemical Society, Volume 1, pages 2087-88 (1974)] methylate the nitrogen-halogen bond of N-halogen-N-substituted amides and imides with diazomethane to yield the corresponding N-halomethyl-N -substituted amide or imide which is condensed with a nucleophilic compound. One way of doing this is by reacting N-chloro-N-methyl-2-chloroacetamide with diazomethane to give the corresponding N- (chloromethyl) -N-methyl-2-chloroacetamide. This is then reacted with a nucleophilic compound.

Examples 47 and 54 of U.S. Pat. No. 3,574,746 mention N- (chloromethyl) and N- (bromomethyl) -N-substituted cycloalkenyl-2-haloacetamides, which are the process of the present invention. intermediates. The intermediates of the present invention may be prepared, for example, by N-haloalkylation of the corresponding aniline followed by N-haloacylation. Thus, N- (2-chloroethyl) or N- (2-chloro-1-methylethyl) -2-haloacetanilide can be prepared from the corresponding aniline and 2- (chloroethyl) p-toluene. sulfonate and 2-chloro-1-methylethyl p-toluenesulfonate followed by chloroacetylation.

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Another process for the preparation of N-haloalkyl intermediates is the reaction of the corresponding haloalkane such as 1-chloro-2-bromoethane with the corresponding aniline followed by acetylation.

When the N-substituted 2-haloacetanilide is prepared by alcoholysis of the corresponding N-haloalkyl-2-haloacetanilide intermediate, halogen hydrogen is produced as a by-product which reduces the yield of the desired product. Therefore, as mentioned in the aforementioned U.S. Patent Nos. 3,442,945, 3,576,620 and 3,875,228, alcoholysis must be carried out in the presence of an acid scavenger.

Suitable acid scavengers in the literature include inorganic and organic bases such as alkali metal and alkaline earth metal hydroxides and carbonates such as sodium and potassium hydroxide, sodium carbonate and the like. tertiary amines such as trimethyl and triethylamine, pyridine and pyridine bases, ammonium and quaternary ammonium hydroxides and alcoholates; metal alcoholates, sodium and potassium methylates, ethylates, etc. Both the halogenated hydrogens and the acid scavenger both promote opposite side reactions, which are undesirable.

A significant disadvantage of each of the processes described above is that the acid scavenger reacts with the by-product in the form of a halogen-insoluble precipitate, which must be separated from the reaction mixture. Separation of the desired product from the waste by-product is usually accomplished by solvent evaporation, aqueous washing, steam distillation of the hydrogen halide, dewatering, filtration and / or product stabilization. Other methods include fractional distillation at low or above atmospheric pressure, extraction, film distillation, recrystallization, and the like. For example, Example 4 of U.S. Patent Nos. 3,442,945 and 3,547,620 describes the preparation of N- (butoxymethyl) -2'-t-butyl-6'-methyl-2-chloroacetanilide (commonly known as terbuclor). the acid acceptor, triethylamine, forms a voluminous precipitate of fine needles of triethylamine hydrochloride, which must be removed by washing with water, distillation of the solvent and filtration.

When ammonia is used as an acid acceptor in the preparation of 2 ', 6'-diethyl-N-methoxymethyl-chloroacetanilide (commonly known as "alachlor" and the herbicide active ingredient Lasso ^R ), a large amount of solid ammonium chloride is formed, which must be removed.

In some cases, during or after alcoholysis of the N-haloalkyl intermediate, most of the halogen hydrogen by-product formed can be removed by simple distillation, but the halogen hydrogen is a gaseous environmental pollutant. In addition, in some cases, the halogen hydrogen distillation of the alcohol reagent and by-product results in the formation of alkyl halide and water, which impairs the yield. In addition, a few percent of the halogen hydrogen remains in the reaction mixture, which has to be removed with an acid binder, which, as mentioned above, forms a large amount of solid precipitate. In our experiments for the production of alachlor, we tried to remove the hydrochloric acid by-product with excess methanol by standard vacuum distillation. In the meantime, however, the N-chloromethyl intermediates and the final product (alachlor) are exposed to the opposite effect of hydrochloric acid, water and other by-products for a longer period of time, approximately two hours, resulting in significantly lower alachlor yield. From this, it was concluded that the acid scavenger should be used during or after the distillation step to avoid these accompanying disadvantages.

Disposal of by-products from the process is crucial for environmental reasons as well as energy conservation, and we had to find a new process that eliminates or minimizes the adverse effects of by-products such as precipitation, liquids and / or gases during the chemical process. In some cases, harmful by-products can be recycled back into the process. In other cases, purification or conversion of the by-products may yield another useful product. However, each of these treatments requires additional investment, increased processing costs and energy use. It is therefore desirable to minimize the generation of by-products which are harmful to the environment.

Another problem with the 2-haloacetanilide production methods described in the literature is that they are not continuous. It is therefore an object of the present invention to provide an improved process for the preparation of 2-haloacylamides and 2-haloacetanilides which overcomes the drawbacks of the aforementioned processes. The object of the present invention is to provide a process which does not require an acid scavenger, does not produce large quantities of solid by-products, thus reduces the need for raw materials and equipment, eliminates separation costs and hassle disposal problems.

Another object of the invention is that the process is continuous, simple, does not run costly, is energy efficient, reduces environmental pollution, and at the same time, its yield and purity is at least equal to or greater than the processes used hitherto.

The invention thus relates to a novel process for the preparation of compounds of formula I, preferably continuous, wherein:

R is phenyl substituted with two or three C 1-6 alkyl groups, or di (C 1-4 alkyl) C 3-7 cycloalkenyl;

R ⁶ is C 1-6 alkyl, C 2-4 alkenyl, (C 1-4 alkoxy) (C 1-4 alkyl), haloC 1-4 alkyl), C 3-6 cycloalkyl, ( C 3 -C 6 cycloalkyl) (C 1 -C 4 alkyl) or furyl (C 1 -C 4 alkyl); and

R ⁷ is C 1 -C 4 mono- or dihaloalkyl.

According to the invention, the compounds of formulas II and III are reacted - R, R ⁶ and R ¹ are as defined above and X is halogen, and the reaction is carried out at a temperature of -20 to 4160 ° C in the absence of an acid scavenger. 1 to 100 mol of alcohol (ΠΙ) per mole of the compound of formula (II) and the mixture of by-product HX and alcohol (EH) is continuously separated from the compound of formula (I), preferably 50 - by distillation at 175 ° C and 1.0 to 300 mm Hg.

A preferred product is alachlor prepared by reaction of 2 ', 6'-diethyl-N-chloromethyl-2-chloroacetanilide with methanol as in Example 1.

Preferably, the above reaction and separation process is repeated several times so that the compound of formula (II) can be completely converted to the compound of formula (I). Most preferably, the process can be carried out in two steps, as follows:

(A) reacting the compound of formula (II) with the compound of formula (ΠΙ) in the first reaction zone;

(B) Feeding the reaction mixture from step (A) in a constant stream to the first separation zone, where most of the HX by-product 2181460 can be rapidly removed as it complexes with the compound of formula (III); and stream (C) from the first partitioning zone, mainly consisting of the compound of formula (I) and the unreacted compound of formula (II), into the second reaction zone, where an additional amount of the compound of formula (III) is fed. reacting with an unreacted compound of formula II; and (D) introducing the reaction mixture from step (C) in a constant stream into a second separation zone from which substantially all of the remaining by-product HX can be removed in the form of a complex with the compound of formula (III). contains.

The main advantages of the process according to the invention are:

1. the use of a base used in the literature procedures is unnecessary, together with it

2. the recovery system required to neutralize the by-product becomes redundant and the dust-polluting effect of the by-product can be avoided,

3. The complex of the by-product halogen hydrogen with the compound of formula (III) can be separated immediately after the reaction mixture is equilibrated, usually within half a minute during the product separation step of the process.

According to an embodiment of the invention, in step A, the compound of formula (III) and the compound of formula (II) are used in a molar ratio higher than 1: 1, generally from 2 to 100: 1, preferably from 2 to 10 for alachlor. and preferably (4-5): 1.

The reaction temperature in Step (A) depends on the reagents used and / or solvents or diluents. Generally, it is a temperature at which the alcohols of formula (III) and / or mixtures of solvents or diluents form a complex or azeotropic mixture with the halogen hydrogen and the product of the formula (I) does not suffer damage by reaction with the halogen hydrogen . In general, temperatures of from -25 ° C to 125 ° C are preferred and, depending on the melting point or boiling point of the reagents, higher temperatures may be used.

In the multistep embodiments of the invention, the concentration of halogen hydrogen in the successive reaction zones is greatly reduced, so that the reaction temperature may be raised above the temperature used in step (A) to displace the reaction to the compound of formula (II). Accordingly, temperatures in the reaction zones are generally in the range of -25 to 175 ° C, or higher if necessary.

Preferably, the temperature and pressure values in the separation zones are between 50 and 175 ° C and between 1.0 and 300 mmHg, depending mainly on the boiling point of the compound of formula (III).

The process according to the invention does not require the use of a solvent; however, in many cases, a solvent or diluent may be used to reduce the reaction rate and / or to facilitate dissolution, dispersion and / or recovery of reagents, by-products, and products. Suitable solvents and diluents which are inert under the reaction conditions include petroleum ether, carbon tetrachloride, aliphatic and aromatic hydrocarbons such as hexane, benzene, toluene, xylenes or halogenated hydrocarbons such as monochlorobenzene.

The process according to the invention has the advantage that the reagent of formula (III) can be readily separated from the complex of the by-product with halogen hydrogen, can be purified and can be traced back to one or more reaction steps. Similarly, halogen hydrogen is readily recovered and can be used in a number of useful operations such as pickling metals, oxychlorination, elemental chlorine and hydrogen electrolysis, and the like. or another operation without polluting the environment.

One suitable recovery / recycling system for the methanolic hydrochloric acid complex formed in the alachlor process is described in Examples 1, 11 and 12. Thus, the methanolic hydrochloric acid complex is passed from your separation step to a distillation system to obtain purified methanol.

Example 1

The example illustrates the two-step process of the present invention for alachlor production.

Step 1: Melting (45-55 ° C) 46.67 kg / h of 2 ', 6'-diethyl-N- (chloromethyl) -2-chloroacetanilide was fed to an in-line mixer and mixed with anhydrous methanol. The methanol mass flow rate in the mixture was 27.24 kg / h. The mixture is pumped into a tube reactor thermostated at 40-45 ° C for a residence time of at least 30 minutes. The reaction yields 92% of 2 ', 6'-diethyl-N-methoxymethyl-2-chloroacetanilide (alachlor) and hydrochloride from the N-chloromethyl intermediate. The hydrochloric acid formed is soluble in excess methanol. The material leaving the reactor was transferred to a drop film evaporator operating at 100 ° C and an absolute pressure of 30 mm Hg. The complex is removed and introduced into a methanol recovery apparatus.

Stage 2: The stream from the evaporator of Stage 1, consisting mainly of alachlor and unreacted 2 ', 6'-diethyl-N- (chloromethyl) -2-chloroacetanilide, is fed to a second "inline" mixer, into which a further 27, Methanol (24 kg / h) was also added. The mixture is then passed into a second reaction zone, a tube reactor thermostated at 60-65 ° C with a residence time of 30 minutes. The product leaving the reactor is directed to a second drop film evaporator operating at 100 ° C and 30 mmHg absolute pressure, where substantially all of the methanolic hydrochloric acid complex is removed. The methanolic hydrochloric acid complex from this second evaporator is also fed into a methanol recovery system from where the recovered anhydrous methanol is recycled to Step 1.

The yield of alachlor in the material stream leaving the Stage 2 evaporator is essentially quantitative and has a purity of greater than 95%. This formulation can be used immediately after preparation as a herbicidal active ingredient. 35.5-40 ° C (crude product).

As shown in the example, the first-stage operation already yields high alachlor yields. Therefore, at an optimum value for the purity and concentration of the reagents, temperatures, residence time in the reactor, and separation time, at least one set of operations consisting of the reaction / separation operations of Step 1 will already result in a satisfactory commercial grade form.

Example 2

Preparation of 2-chloro-2 ', 6'-diethyl-N- (ethoxymethyl) acetanilide

5.5 g (0.02 mol) of 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide are dissolved in 25 ml of ethanol and the solution is stirred for 30 minutes at 45 ° C.

Allow to stand in a water bath at -3181460 ° C. Excess ethanol is rapidly removed in a rotary evaporator at 50 ° C and 10 mm Hg. To the residual oil was added 25 ml of fresh ethanol and the mixture was heated at 65 ° C for 30 minutes. Excess ethanol was removed by rotary evaporation. 5.80 g of a pale amber oil are obtained, which according to gas chromatography is 92.8% by weight of the desired product and the by-product is 2-chloro-2 ', 6'-diethylacetanilide.

Contains 1.7% by weight. Yield 94.5%. n ²⁴ = 1.5220.

Example 3

Example 2 was followed, but ethanol was replaced with isopropanol. 5.92 g of a light amber oil are obtained, 90.2% by weight of 2-chloro-2 ', 6'-diethyl-N- (isopropoxymethyl) -acetanilide (89.4% yield); Contains 1.8% by weight of 2-chloro-2 ', 6'-diethylacetanilide.

n * = 1.5165.

Example 4

The procedure described in Examples 2 and 3 was followed, but using 1-propanes as the alcohol to give 5.66 g of a lemon yellow oil, 92.8% (yield 87.9%) of 2 ', 6'-diethyl-N. (n-propoxymethyl) -2-chloroacetanilide and 1.2% by weight of the corresponding secondary amide by-product.

ηθ = 1.5175.

Example 5

Figures 2-4. The same procedure as in Examples 1 to 2, but using isobutanol as the alcohol, gave 6.20 g of oily product, which was 96.4% (97% yield) of 2 ', 6'-diethyl-N- (isobutoxymethyl) -acetanilide. 3% by weight of a mixture of suitable secondary amide by-products.

ηθ = 1.5151.

Example 6

Repeat steps 2-5. Example 2 but using 2-chloroethanol as the alcohol gave 6.96 g of a light amber oil which was 86.0% (94.0% yield) of 2 ', 6'-diethyl-N. - (chloro-ethoxymethyl) -2-chloroacetanilide.

n "= 1.5338

Example 7

2-6. EXAMPLE 1 N-Butanol was used as the alcohol to give 6.18 g of a light lemon yellow oil, which was found to be 98.8% (yield 99%) of 2 ', 6'-diethyl-N- (n-butoxy). -methyl) -2-chloroacetanilide (butachlor) and 1% by weight of the corresponding secondary amine by-product.

In the above examples, NMR analysis showed that the products obtained had a constant chemical structure.

The reactions between the compounds of formula (II) and (III) are reversible secondary reactions. Scheme 1, which illustrates the reaction of Example 1, illustrates this type of reaction. The reaction is reversible and the equilibrium is influenced and controlled by a number of factors, such as the alcohol concentration and / or the halogen hydrogen concentration of the by-product. For example, in equation 1, the concentration of alcohol (b), i.e. the ratio of reagents [(b): (a)], as the equation increases, shifts to the right due to further conversion of starting material (a), resulting in more products (c) and a halogen-hydrogen by-product (d) is formed.

Another way to better equilibrate Equation 1 is by removing the halogen hydrogen (d); this can be done by adding an acid binding agent such as tertiary amines such as triethylamine in U.S. Pat. No. 3,547,620,3,442,945 and Canadian Patent No. 867,679. However, the use of acid scavengers has the disadvantages mentioned above.

According to the aforementioned Canadian Patent No. 867,769, when the starting thio compound is in the form of an alkali metal salt, the acid scavenger is unnecessary; the reason for this is that said salts are also basic. In contrast, when the parent compound is used in free form, it is necessary to use an acid acceptor to bind the halide to the by-product.

Although the processes of the aforementioned U.S. Patent Nos. 3,547,620 and 3,442,945 are preferably carried out in the presence of an acid acceptor, they may be carried out without the use of an acid acceptor, but in very low yields.

To further illustrate the comparative advantages of the process of the present invention over the acid-free process of U.S. Patent Nos. 3,442,945 and 3,547,620, the following Examples 8-12. Examples 1 to 4 show the results of comparative procedures using known methods. In each of the examples, the N-chloromethyl-2-chloroacetanilide starting material was prepared by reacting the corresponding substituted N-methylene aniline with haloacetyl halide in U.S. Patent Nos. 3,442,945 and 3,547,620.

Example 8

Preparation of 2-chloro-2 ', 6'-diethyl-N- (methoxymethyl) -acetanilide (alachlor) according to Example 5 of U.S. Patents 3,547,620 and 3,442,945.

100 g of 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide (96%, 0.350 mol) were dissolved in 70 g of benzene and 65.8 g (2.054 mol) of methanol were added. . When methanol is added, the reaction becomes exothermic. The reaction mixture was refluxed at 63 ° C and further (ca.

63.3 g) triethylamine was added dropwise over one and a half hours. During the dropwise addition, the reaction temperature rises to about 70 ° C, which is maintained for about 10 minutes after completion of the dropwise addition. The reaction mixture was then cooled to 30 ° C and washed twice with 170 ml of water each time. The product, which is a heavy, oily layer, is dewatered from the solvent by vacuum distillation (final temperature: 70 ° C / 1 mm Hg). The ma55 radish was an amber oil weighing 96.15 g, according to analysis

90.4% by weight of product and 4.9% by weight of 2-chloro-2 ', 6'-diethylacetanilide by-product (gas chromatography). The product contains no unreacted starting material. Yield: 92.0%.

Example 9

Preparation of alachlor according to Example 5 of U.S. Patents 3,547,620 and 3,442,945 but without the use of an acid scavenger

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100 g of 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) -acetanilide (96%, 0.350 mol) were dissolved in 70 g of benzene and 66.0 g of methanol (2.059 mol) was added. When methanol is added, the reaction becomes exothermic and the reaction mixture is heated at reflux for 1 hour (63 ° C). The excess methanol and solvent were then removed by vacuum distillation at a final temperature of 70 'C / 1 mm Hg. The product is 96.83 g of a pale lemon yellow oil, which (by gas chromatography) is 83.7% by weight of the product,

7.5% by-product contains 2-chloro-2 ', 6'-diethylacetanilide and 5.5% by weight of unreacted starting material. The extraction

85.8%.

In the example, abandonment of the acid scavenger resulted in a decrease in yield (6.2%). In this procedure, the reaction did not shift completely to the right. As a result, the hydrochloric acid byproduct reduced conversion and the unreacted starting material proved to be harmful to the product.

Example 10

Preparation of alachlor according to Example 5 of U.S. Patents 3,547,620 and 3,442,945, but without an acid acceptor and under optimum temperature conditions.

2-Chloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide (100 g, 96.0%, 0.350 mol) was dissolved in benzene (70 g) and 66 g (2.059 mol) was added. methanol. Due to the exothermic reaction, the temperature of the reaction mixture rises to 45 ° C for one hour. The excess methanol and solvent were removed by vacuum distillation (about 80 ° C / 1 mm Hg final temperature). Gas chromatography analysis of the resulting product (96.20 g) showed 85.8% by weight of the desired product, 6.2% by-product of 2-chloro-2 ', 6'-diethylacetanilide and about 4.6% by weight of unreacted starting material. Yield 87.4%.

In the absence of an acid acceptor, optimizing the reaction conditions resulted in a 2.7% improvement in product quality and a 1.6% increase in yield, but did not resolve the overall shift in the reaction.

Example 11

Production of alachlor according to the process of the invention in a one-step reactor. The starting materials are the same as in

8-10. In Examples 1 to 6 g (96%, 0.035 mol) of methanol was added to 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide (6.0 g, 0.1873 mol). The exothermic reaction raises the temperature of the reaction mixture to about 45 ° C for 30 minutes. Excess methanol was rapidly removed in a rotary evaporator (final temperature 70 'C / 1 mm Hg). This gave 9.80 g of a pale lemon yellow oil, 91.0% by weight, 1.7% by-product of 2-chloro-2 ', 6'-diethylacetanilide, and 2.4% of unreacted starting material (by gas chromatography). according to the study). Yield 94.4%.

Thus, even in one-step production, the quality and yield of the desired product are significantly improved, although the reaction is not complete (2.4% by weight of starting material in the product). Compared to Examples 8, 9 and 10, this is an obvious improvement, although no acid scavenger has been used.

Example 12

Preparation of alachlor without an acid acceptor by the process of the present invention in a multistage reactor g 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide (96.0%, 0.350 mol) 6.0 g (0.1783 mol) dissolved in methanol. The exothermic reaction raises the temperature to 45 ° C and the reaction mixture is maintained at this temperature for 1.5 hours. The excess methanol was removed rapidly in a rotary evaporator (final temperature 45 'C / lHgmm). An additional 6.0 g (0.1873 mole) of fresh methanol was then added to the reaction mixture which was kept at 65 ° C for 1.5 hours. Excess methanol was removed as above to give 9.80 g of a pale lemon yellow oil containing 95.8% by weight of product, 1.4% by weight of 2-chloro-2 ', 6'-diethylacetanilide, leaving no unreacted starting material. . Yield: 99.4%.

8-12. The results of the Examples are summarized in the table below. In the table, the term "starting material" refers to unreacted 2 ', 6'-diethyl-N- (chloromethyl) -2-chloroacetanilide, a by-product of the main acetanilide in each example. Naturally, in addition to the high amount of halogen hydrogen, small amounts of acetanilide and other by-products are formed, in addition to triethylamine hydrochloride in Example 8. Yield percentages refer to 2 ', 6'-diethyl-N- (chloromethyl) -2-chloroacetanilide starting material.

Mp: 38.3-38.8 (crude product)

M.p. 43.3-43.9 (recrystallized from methylene chloride).

Spreadsheet

The example number Type of procedure Alachlor extraction, 7th Product Analysis (%) alachlor Annexes product starting material 8 3,442,945 and U.S. Patent 3,547,620. Description Example 5, with base 92.0 90.5 4.9 0 9 same without base 85.8 83.7 7.5 5.5 10 same as Example 9 under optimal conditions 87.4 85.8 6.2 4.6 11 The process according to the invention is one-step 94.4 91.0 1.7 2.4 12 same, multistage 99.4 95.8 1.4 0

The table above shows that the process according to the invention is more advantageous to the process of FIGS. in the Examples. These advantages are: (shown in Examples 11-12)

1. a significant increase in alachlor production

2. Improved purity of alachlor

3. Significant reduction in by-products

4. increase in conversion of starting material when no base is used.

5. Absence of a solid product resulting from the neutralization which is produced in large amounts in the base addition process of Example 8.

Example 13

Preparation of 2-bromo-2'-methyl-6'-tert-butyl-N-methoxymethylacetanilide

15.08 g (0.040 mol) of 2-bromo-2'-methyl-6'-tert-butyl-N-bromomethylacetanilide are added to 25.0 g of anhydrous methanol. The

The mixture was heated to 45 ° C and allowed to stand for 30 minutes. The excess alcohol and hydrogen bromide were evaporated on a rotary evaporator at 45 ° C / 10 mm Hg. The oily residue was treated twice with 25.0 g of anhydrous methanol in a similar manner. After the final evaporation, 13.0 g of pure amber oil (n = 1.5470) are obtained, which is 97.0%

2-Bromo-2'-methyl-6'-tert-butyl-N-methoxymethylacetanilide (by gas chromatography). Yield 96%. The structure of the compound was consistent with that of the NMR spectrum.

Example 14

2-chloro-2 ', 6'-dimethyl-N-isopropoxymethyl-acetanilidelőállítása

12.3 g (0.050 mol) of 2-chloro-2 ', 6'-dimethyl-N-chloromethylacetanilide are dissolved in 30.0 g of anhydrous isopropanol. The reaction mixture is heated at 45-50 ° C for 30 minutes and the excess alcohol is evaporated on a rotary evaporator at 60 ° C / 10 mm Hg. The residue was again treated with 30 g of fresh isopropanol at 45 ° C for 30 minutes. The excess alcohol was evaporated to give 13.27 g of a clear pale yellow oil (n ²⁶ = 1.5245) which was 93.9% pure by gas chromatography. Yield: 92.5%.

Example 15

Preparation of 2-Chloro-2 ', 6'-diethyl-N - [(2-methoxyethoxy) methyl] acetanilide

To 13.71 g (0.050 mol) of 2-chloro-2 ', 6'-diethyl-N-chloromethylacetanilide is added 38.0 g of methylcellosolve and the? the mixture was allowed to stand at room temperature for 30 minutes. The excess alcohol was then evaporated on a rotary evaporator at 65 ° C / 0.5 mm Hg and 38.0 g of fresh methylcellulose was added to the residual oil and the mixture was allowed to stand at 45 ° C for 30 minutes. The excess alcohol was evaporated again to give 15.46 g of a pale yellow oil. Yield 98.5%. The oil was taken up in n-hexane and recrystallized to give a white, crystalline solid, m.p. 31.5-32.5 ° C.

Example 16

Preparation of 2-Chloro-2'-ethyl-6'-methyl-N- (ethoxymethyl) acetanilide

To 2-chloro-2'-ethyl-6'-methyl-N-chloromethylacetanilide (10.4 g, 0.04 mol) was added 30 g of ethanol and the mixture was heated at 45 ° C for 15-20 minutes. heated. The excess alcohol was evaporated in a rotary evaporator in vacuo. The resulting oil was treated with fresh ethanol (30.0 g) for 15 minutes at 45 ° C and the excess ethanol removed. After the third treatment, the oil obtained weighed 10.73 g and was 96.4% pure by gas chromatography. Yield: 96.0%.

= 1.5236.

Example 17

Preparation of 2, -2-dichloro-2 ', 6'-diethyl-N- (methoxymethyl) acetanilide

To 15.43 g (0.050 mol) of 2,2-dichloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide was added 32.0 g of anhydrous methanol. · ⁶ The reaction mixture was allowed to stand for 30 minutes at 45 ° C and the alcohol-hydrochloric acid were removed in vacuo on a rotary evaporator. The oily residue was treated twice more as described above, and the alcohol was distilled off to give 15.15 g of pure pale yellow oil (n = 1.5330) which was 98.3% pure by gas chromatography. Yield: 97.9%.

Example 18

Preparation of 2-Chloro-2'-methyl-6'-tert-butyl-N- (allyloxymethyl) acetanilide

Allyl alcohol (29.0 g) was added to 2'-methyl-6'-tert-butyl-2-chloro-N-chloromethylacetanilide (14.5 g, 0.05 mol) and the mixture was stirred for 15 minutes. Heat at 45 ° C. The excess alcohol was evaporated in a rotary evaporator in vacuo and fresh allyl alcohol (29.0 g) was added to the residue. After a further 15 minutes at 45 ° C, the excess alcohol was distilled off and the procedure was repeated once more. The third distillation gave 14.45 g (93.4% yield) of a pale amber oil, ηθ = 1.5338.

Example 19

Preparation of 2-Chloro-2'-ethyl-6'-methyl-N- (tetrahydrofurfuryloxymethyl) acetanilide

10.4 g (0.040 mol) of 2-chloro-2'-ethyl-6'-methyl-N- (chloromethyl) acetanilide are dissolved in 40.8 g (0.40 mol) of tetrahydrofurfuryl alcohol and the leave at room temperature overnight. The excess alcohol was evaporated on a rotary evaporator at 65-70 ° C / 0.4 mmHg. An additional 40 g of fresh alcohol was added and the mixture was heated at 45 ° C for 30 minutes. The excess alcohol was then removed as above and the light yellow oil remaining weighed 13.0 g (99.7%).

n ^ ⁵ = 1.5327.

Example 20 Preparation of α-Chloro-N- (2,6-dimethyl-1-cyclohexen-1-yl) -N- (methoxymethyl) acetamide

2.90 g (23.5 mmol) of 2-chloro-2 ', 6'-dimethylcyclohexen-1-yl-N-chloromethylacetanilide are dissolved in 28.3 g of anhydrous methanol and then at room temperature for 30 minutes. let it stand. Excess methanol was removed on a rotary evaporator in vacuo. The above procedure was repeated two more times and the final methanol was removed to give 5.50 g (94.9%) of a pale yellow oil (m.p. = 1.5050).

Example 21

Preparation of 2-chloro-2 ', 4', 6'-triethyl-N- (methoxymethyl) acetanilide

To a solution of 22.5 g (0.074 mol) of 2-chloro-2 ', 4', 6'-triethyl-N- (chloromethyl) acetanilide in 30 ml of chlorobenzene is added 25 ml (20 g) of anhydrous methanol and the mixture is stirred for 30 minutes. leave to stand at room temperature for one minute. The excess methanol and a portion of the chlorobenzene were evaporated in vacuo on a rotary evaporator and an additional 20 g of fresh methanol was added. The mixture was allowed to stand at room temperature for an additional 30 minutes. The methanol is then redistilled on a rotary evaporator and the procedure is repeated once more. After the third distillation, 21.0 g of a yellow oil are obtained (n = 1.5243).

97.7% by weight of 2-chloro-2 ', 4', 6'-triethyl-N- (methoxymethyl) -acetanilide, 1.0% by weight of 2-chloro-2 ', 4', 6'- triethylacetanilide (by-product) and 0.7% by weight of 2,2-dichloro-2 ', 4', 6'-triethylacetanilide (by-product). Yield: 93.1%.

Example 22

Preparation of 2-Chloro-2 ', 6'-dimethyl-N- (cyclohexyloxymethyl) acetanilide

To 2 ', 6'-dimethyl-2-chloro-N-chloromethylacetanilide (12.3 g, 0.050 mol) was added 50.0 g of anhydrous cyclohexanol and the solution was allowed to stand overnight at room temperature. The excess alcohol was then distilled on a rotary evaporator at 65 ° C / 1 mm Hg. To the residue was added 50.0 g of fresh cyclohexanol and the solution was heated at 45 ° C for 30 minutes. The excess alcohol was removed by distillation at 65 ° C / 0.5 mm Hg to give 15.45 g (99.7%) of a pale yellow oil. The oil was recrystallized from cold hexane to give a crystalline solid, m.p.

Example 23

Preparation of 2-Chloro-2'-methyl-6'-tert-butyl-N- (cyclopropylmethoxymethyl) acetanilide

2.77 g of 2-chloro-2'-methyl-6'-tert-butyl-N- (chloromethyl) acetanilide (0.016 mol) are dissolved in 9.60 g (0.132 mol) of cyclopropyl alcohol. The solution was allowed to stand at room temperature for one hour and then the excess alcohol was distilled off on a rotary evaporator at < 55 > C / 1 mm Hg. To the residual oil was added about 9.6 g of fresh cyclopropyl alcohol and the solution was heated at 45 ° C for 20 minutes. The excess alcohol was removed in vacuo to give a pale amber, clear oil. n '= 1.5280, yield: 5.28 g (98.9%).

Example 24

Preparation of 2-Chloro-2 ', 6'-dimethyl-N- (2-methoxy-1-methyl-ethoxymethyl) -acetanilide

2-Chloro-2 ', 6'-dimethyl-N-chloromethylacetanilide (12.3 g, 0.050 mol) was dissolved in ethylene dichloride (20 ml) followed by 2-methoxy (22.5 g, 0.25 mol). -1-Methylethanol is added. The solution was allowed to stand at room temperature for 1 hour. The excess alcohol was then evaporated in vacuo using a rotary evaporator. The residual oil was treated with additional 22.5 g of fresh alcohol at 60 ° C for 30 minutes. The excess alcohol was distilled as above at 65 ° C / 1 mm Hg. 14.86 g (99.1%) of a light yellow oil are obtained.

ηθ = 1.5263.

Example 25

To 25.0 g (0.78 mole) of anhydrous methanol at -20 to -25 ° C, 2.15 g (0.0078 mole) of 2-chloro-2 ', 6'-diethyl- (N-chloromethyl) acetanilide (purity 96.0%) was added with stirring. After 30 minutes, all acetanilides were dissolved. After a further 1 hour at -20 to -25 ° C, the excess methanol was rapidly distilled off in vacuo. The residual oil had a NMR spectrum of 60.8% alachlor conversion. The residue was treated with additional 25 g of fresh methanol at -20 to -25 ° C for 1 hour. After rapid vacuum distillation of the excess methanol, the NMR spectrum showed a 91.6% alachlor conversion. A third third of the residue was treated with 25 g of fresh methanol at -20 to -25 ° C for 2 hours, followed by rapid vacuum distillation of the excess methanol to give 2.11 g of a clear pale yellow oil. The NMR spectrum showed complete conversion to alachlor. Gas chromatography showed 94.7% 2-chloro-2 ', 6'-diethyl-N-methoxymethylacetanilide (alachlor), 2.1% 2-chloro-2', 6'-diethylacetanilide. (by-product). Yield: 98.7%.

Example 26

To 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) -acetanilide (11.70 g, 0.041 mol) (96.0% purity) was added 25 ml of anhydrous methanol and the mixture was stirred for 5 minutes. heat at 65 ° C for 1 minute. The excess alcohol and hydrochloric acid were rapidly evaporated on a rotary evaporator at 65 ° C / 10 mm Hg. To the residual oil was added another 15 ml of fresh methanol, heated to 85 ° C over 2 minutes, and the excess alcohol was distilled off in vacuo as above. After repeated treatment with 15 ml of fresh methanol for 2 minutes at 100 ° C, the excess alcohol was distilled off in vacuo to give 14.33 g of a yellow oil, 96.0% by weight of 2-chloro-2 ', 6'-diethyl ether. Contains N-methoxymethyl-acetanilide and 0.9% by weight of 2-chloro-2 ', 6'-diethylacetanilide (by-product). Yield: 95.4%.

Example 27

To 2-chloro-2 ', 6'-diethyl-N- (chloromethyl) acetanilide (11.17 g, 0.0391 mol) was added 25 ml of anhydrous n-butanol. The solution was immediately heated to 120 ° C in an oil bath for 2 minutes and then the excess alcohol was distilled off under vacuum on a rotary evaporator at 60 ° C / 10 mm Hg. The residual oil was treated a third time with 25 ml of n-butanol at 160 ° C for 5 minutes and then the excess alcohol was removed on a rotary evaporator as above. This gives 12.45 g of a clear yellow oil which is 94.9% by weight of 2-chloro-2 ', 6'-diethyl-N-butoxymethyl-acetanilide (butachlor) and 0.9% by weight of 2 contains chloro-2 ', 6'-diethylacetanilide (by-product). Yield: 96.9%.

Claims (8)

Patent claims A process for the preparation of a compound of formula (I): R is phenyl substituted with two or three C 1-6 -alkyl or di (C 1-4 -alkyl) - (C 3-7 -cycloalkenyl) -, R ⁶ is C 1-6 alkyl, C 2-4 alkenyl, (C 1-4 alkoxy) (C 1-4 alkyl), haloC 1-4 alkyl), C 3-7 -7181460 cycloalkyl, (C3-C7 cycloalkyl) -C1-4 alkyl) or furyl (C1-C4 alkyl), R ⁷ is C 1-4 mono- or di-alkyl - (II) and (III) of the formula reacting compound - halo 5 wherein R, R ⁶ and R ⁷ are as defined above and X - wherein to carry out the reaction at -20 to + 160 ° C in the absence of an acid scavenger, using 1-100 mol of alcohol (III) per mole of the compound of formula (II) and then reacting the by-product HX and (III) the alcohol mixture of formula I is continuously separated from the resulting compound of formula I, preferably 50- By distillation at 175 ° C and 1.0-300 mm Hg. 2. The process of claim 1, wherein the reaction and separation step is repeated several times. 3. A process according to claim 2, wherein the process is carried out in two steps, as follows: (A) reacting the compound of formula (II) with the compound of formula (III) in the first reaction zone; (B) transferring the reaction mixture from step (A) to a first separation zone where the complex of by-product HX and alcohol (III) is rapidly separated, (C) predominantly the compound of formula (I) and A stream of material comprising the unreacted portion of a compound of formula II is introduced from the first separation zone into the second reaction zone, the unreacted compound of formula II being reacted again with an alcohol of formula III; and (D) introducing the reaction mixture from step (C) into a second separation zone where a residual mixture of by-product HX and alcohol (III) is separated. The process of claim 3 wherein the temperature in step (A) is between -25 and 125 ° C. 5. The process of claim 3 wherein the temperature in step (C) is -25. 15 to 175 ° C. 6. A process according to claim 3 wherein the complex of the compound of formula III and HX is fed from step (D) to a recovery unit from which the halogen hydrogen is separated. The compound of formula (III) is recycled back to steps (A) and / or (C). 7. The process of claim 3, wherein the temperature in the steps (B) and (D) is between 50 and 175 ° C and the pressure is between 1.0 and 300 mmHg. 8. The process of claim 3, wherein the residence time of the reaction mixture in the distillation zones (B) and (D) is less than 0.5 minutes.