GB1561695A - Chloroacetyl-phenylamino-acetamides for the regulation of plant growth - Google Patents

Description

(54) N-CHLOROACETn-PHENYLAMINO-ACETAMIDES FOR THE REGULATION OF PLANT GROWTH (71) We, CIBA-GEIGY AG, a body corporate organised according to the laws of Switzerland, of Basle, Swtzerland, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The present invention relates to novel sub stituted N - chloroacetyl - phenylamino - acetamides possessing for practical application the particularly favourable property of retarding plant growth, the preparation of these compounds, and compositdons containing them as active ingredients.

According to the present invention there are provided compounds of the general formula I

wherein R1 represents a chlorine atom, or a methyl or ethyl group, and R represents an n-propyl, allyl, methoxy ethyl, cyclopropyl or methylcyclopropyl group.

Phenylaminoacetic acid esters and phenyl aminoacetamides are already known from the literature 2,6-Dialkylphenylaminoacetic acid esters are suggested in United States Patent Specifica tion No. 3,780,090 as herbicides.

Similar compounds and substituted phenyl aminoacetamides are suggested also in German Offenlegungsschrift No. DT4S 2,311,897 as agents for combating weeds.

Benroylated phenylaminopropionic acid esters and -amides are described in United States Patent Specification No. 3,712,805 as herbicides.

Compounds closely related to the active ingredients of the present invention are the benzoylated or in some other way acylated phenylaminoacetamides suggested in United States Patent Specification No. 2,676,188 as therapeutic agents (local anaesthetics, analgesics or sedatives).

None of these references provides any pointers to the possibility of effecting specific phytomorphological changes of practical significance by application of the respective groups of active ingredients suggested. It has furthermore been shown that the nearest comparable compounds disclosed in the literature do not in any way possess the properties of the active ingredients of formula I according to the invention, or that they produce a change cf plant growth only in the sense of herbicidal activity, that is to say, of activity harmful to plants.

It has been found that the property of retarding plant growth, which is advantageous in practice, is surprisingly confined in this class of compounds essentially to the compounds of formula I. Compounds which structurally are bordering directly on the outer limits of the range of compounds embraced by formula I likewise possess in some cases these properties that are described in more detail in the following, but they do not possess them to the extent that would render them sufficiently effective for practical application, or to the extent that they could be used without damaging the plants.

Unlike a herbicidal effect, such as that of compounds given in the aforementioned literature, the effect that a substance retarding plant growth has on the plants has to be of such a nature that the treated plants suffer no damage. The compounds of formula I satisfy this requirement to a high degree in the case of application to emerged plants. Particularly grasses growing wild and also cereals are retarded in growth. By use of these compounds in practice it is possible both to prevent weed infestation of railway embankments, of strips bordering highways, of slopes of river banks, of factory installations, etc., and to maintain intact the turf necessary for consolidation of the soil. Unlike after application of a herbicide, there occurs after use of the compounds of formula I no destruction of the plants and hence no erosion of the soil.Keeping the vegetation short renders unnecessary the otherwise regularly required grass-cutting operations, which are problematic at difficultly accessible places, such as embankments, and which increase the risk of accidents where road traffic is circulating. Compounds of formula I also inhibit however the growth of shrubs such as privet, and the growth of lignifying plants such as blackberry; in both cases species of plants the proliferation of which frequently contributes towards the undermining of the foundations of railway tracks. In the case of varieties of cereals, such as in particular rye and barley and also wheat, the reduction in height (shortening of the internodal spacing) results in a desired increase of the stem's resistance to breaking or kinking.Crop losses often occurring as a result of flattening of the cereals owing to continuous rain or to hailstorms can to a great extent be avoided. One compound which is excellently suitable as growth inhibitor on grasses is N - n - propyl [N' - (2,6 - dimethylphenyl) - N' - chloro acetylammoj - acetamide.

In the case of soya plants, the vegetative growth of the plants is retarded in favour of the generative growth (fruit setting) by treatment with the active ingredients. This is particularly surprising because as a rule a retardation of growth automatically results in a reduction of fruit setting. A smaller distance between rows of plants treated with the present active ingredients and therefore having a reduced breadth of growth leads to noticeably higher hectare yields. Especially suitable active ingredients in this case are, inter alia, the compounds N - n - propyl - [N' - (2,6 - dimethylphenyl) - N' - chloroacetylamino] - acetamide, and N - methoxyethyl - [N' - (2,6- dimethylphenyl) - N' - chloroacetylamino] - acetamide.

A number of the compounds of the present invention result also in the inhibition of the growth of side shoots on tobacco plants, which is very effective in practice, as well as in interesting morphological changes in the case of ornamental plants and flowers.

The active ingredients of formula I are stable compounds and have a duration of action extending over at least two months; however, in the cultivation of, for example, soya beans, cereals or tobacco, they are decomposed before the end of the cultivation season.

The mounts applied are generally between 0.1 and 10 kg, preferably between 2.5 and 5 kg, of active ingredient per hectare.

The invention also provides a method of retarding plant growth, particularly growth of plants of the aforementioned species, which method comprises applying to plants or the locus in which they are growing an effective amount of a compound of formula I.

The plants to be treated may be located on the verge of a road, railway, waterway or lake.

The invention in particular provides a method of reducing the overall size of soybean plants which method comprises applying to plants or the locus in which arey are growing an effective amount of a compound of formula I.

The compounds of formula I possess in the pre-emergence process good herbicidal properties against Gramineae such as millet and millet-like plants, and hence have to a certain extent also the effects which are known from the literature to be the effects of the chloroacetanilide class of active ingredients.

Compounds of formula I wherein 4 represents methyl or ethyl have a growth-retarding action which fundamentally is particularly suitable in practice.

Compounds to be emphasised are: N - n - propyl - [N' - (2,6- dimethylphenyl) N' - chloroacetylamino] - acetamide, N - allyl - [N' - -(2;6- dimethylphenyl) - N' chloroacetylaminoj - acetamide, N - methosyethyl - [N' - - dimethyl- phenyl) - N' - chloroacetylamino] - acet amide, N - methylcyclopropyl - [N' - (2,6 - di methyiphenyl) - N' - chloroacetylamino] acetamide, and N - cyclopropyl - [N' - (2 - methyl - 6 ethylpheny) - N' - chloroacetylamino] acetamide The compounds of formula r may be prepared, for example, by reacting a phenylamino-acetamide of formula II

with a chloroacetylating agent, preferably with the anhydride or a halide of chloroacetic acid.

The symbols R1 and R in formula II have the meanings given under formula I.

Conversely, it is also possible firstly to chloroacetylate a corresponding N-phenylaminoacetic acid (or, e.g., its lower alkyl ester) and to then amidate tbe resulting product with an appropriate amine, i.e. reaction of the compound of formula III

with an amine of the formula (IV) NH2R (IV) Again the symbols R1 and R have the meanings given under formula I.

The reactions can be performed in the presence or absence of solvents or diluents inert to the reactants. Those suitable are, for example, aliphatic, aromatic or halogenated hydrocarbons, ethers and ethereal compounds, ethyl acetate, acetonitrile and alcohols, as well as mixtures of these solvents with each other.

As suitable chloroacetylating agents there are preferably used chloroacetic acid anhvdride and chloroacetic acid halides, such as chloroacetyl chloride or chloroacetyl bromide. The reaction temperatures are generally between 0 and 200"C, preferably between 200 and 100"C. With the use of chloroacetyl halides, the reaction can be performed in the presence of an acid-binding agent The reaction is usually performed at normal pressure, if necessary however at a pressure of up to 20 bars.

There may be mentioned as condensation agents for some reactions dicyclohexyl-carbo diimide, chloroformic acid ester and oxalyl chloride.

Some starting materials are known; the production of for example 2,6-dimethylanilinoacetic acid and of its ethyl ester is known from J. Org. Them. 23, 186 (1958) or Farmaca 16, 701 (1961). Starting materials not hitherto described, or intermediates thereof, can be produced analogously, e.g. by reaction of the corresponding aniline of the formula

with the haloacetamide of the formula HaCH,3CO--NHH-R in the presence of a base. See also the method from "J. Org. Chem., Vol. 22, 1099 [1957]" for the production of anilino-acetic acid from the aniline by way of N-phenylaminomethanesulphonic acid and N-phenylaminoacetonitrile.

The acetamides of formula II can be advantageously obtained also from the cyanomethyl ester.

The following Examples illustrate the method of manufacture. Temperature values are in degrees Centigrade.

A.) Manufacture of some starting materials.

2,6-Dimethylanilinoacetic acid N-n-propylamide 28.8 g of 2,6-dimethylanilinoacetic acid methyl ester (Farmaca 16, 701 (1961)1 and 49 ml of n-propylamine in 250 ml of abs.

methanol are refluxed for 15 hours. The reaction mixture is cooled and the readily volatile constituents are then removed in vacuo to leave 32.1 g of 2,6-dimethylanilinoacetic acid N-n-propylamide, which can be directly further processed (see Example 1).

N-Chloroacetyl-2,6-dimethylanilino acetic acid 36 g (0.2 mole) of 2,6-dimethylanilinoacetic acid, 400 ml of methylene chloride and 200 ml of 1N NaOH (0.2 mole) are placed into a flask with stirrer, and there is then slowly added dropwise, with stirring, 17.5 ml (0.22 mole) of chloroacetic acid chloride, whereby the temperature is held at 20"25 by cooling with ice water. During the dropwise addition, a white precipitate commences to form; stirring is maintained for 30 minutes, and the reaction mixture is subsequently filtered. The precipitate is washed with cold water, well pressed out and then dried over P,O5 in a desiccator.There is obtained 44 g (86% of theory) of N - chloroacetyl - 2,6 - dimethylanilinoacetic acid, m.p. 1600 (decomposition) (recrystallization from ethylacetate).

B.) Manufacture of final products.

Example 1.

N-n-propyl- [N'-( 2,6dimethylphenyl) -N' chloroacetylamino] -acetamide 24 ml of chloroacetyl chloride is added dropwise, with vigorous stirring, to 60 g of crude 2,6 - dimethylanilinoacetic acid - N propylamide and 31.8 g of sodium carbonate in 300 ml of benzene. The temperature rises to 490C. After 3 hours' stirring at room temperature, the inorganic constituents are filtered off and the filtrate is concentrated by evaporation. The crvstalline residue is recrystallised from ethyl acetate to thus obtain 71.5 g of N - n - propyl - [N' - (2,6 - dimethyiphenyl)- N' - chloroacetylamino] - acetamide, m.p.

111112 .

In addition other compounds of formula I are prepared by analogous procedure to the above or to one of the following Examples.

These compounds and the product of Example 1 are listed in the following Table.

Example 2.

N-Cyclopropylmethyl- [N'- (2,6-dimethyl phenyl) -N'-chloroacetylamino] -acetamide 25.6 g of N-chloroacetyl - 2,6 - dimethylanilinoacetic acid is dissolved in 200 ml of tetrahydrofuran and the whole is cooled to 150C. There is then added, with stirring, 26.18 ml of tri-n-butylamine; the solution is cooled to 0 C and 10.8 ml of 97% chloroformic acid ethyl ester is slowly added dropwise. After 30 minutes' stirring at O-SC an addition is made dropwise, at the same tem- perature, of 7.8 g of cyclopropylmethylamine dissolved in 20 ml of tetrahydrofuran, whereby the evolution of 02 occurs.Stirring is continued firstly for 30 minutes at room temperature and then for 30 minutes at 30--35"C.

The reaction mixture is subsequently concentrated by evaporation; the residue is taken up in ethyl acetate and processed in the normal manner. After drying over sodium sulphate, the ethyl acetate is distilled off in vacuo, and the residue is crystallised from diisopropylether with the addition of a small amount of ethyl acetate. There is obtained 14.2 g of N cyclopropylmethyl- [N' - (2,6 - dimethylphenyl) - N' - chloroacetylaminoj - acetamide, m.p. 120-121 C.

Example 3.

NJy-chloropropyl- [N'- (2,6-dimethylphenyl ) - N'-c:hloroacetylamino] -acetamide 25.6 g of N - chloroacetyl - 2;6 - dimethylanilinoacetic acid is suspended in 200 ml of benzene (abs.); 0.3 ml of pyridine and 10 ml of oxalyl chloride are added, and the whole is stirred overnight at room temperature. In order to complete the reaction, stirring is then carried out for 15 minutes at 50 C. The almost clear solution is filtered, and quickly concentrated in a rotary evaporator. The solid residue is dissolved in 100 ml of methylene chloride, and the solution is added dropwise at 5-100C to a solution of 13 g of Wy-chloro- propylamine hydrochloride and 28 ml of tri ethylamine in 150 ml of alcohol. After 30 minutes the reaction mixture is allowed to warm up to room temperature and is then evaporated to dryness in a rotary evaporator.

The residue is taken up in ethyl acetate and processed in the normal manner. After drying over Na2SO4, the ethyl acetate is distilled off in vacuo, and the crystalline residue is re crystallised from diisopropyl ether with the addition of ethyl acetate. There is obtained in this manner 14.8 g of N - y - chioropropyl- [N - (2,6 - dimethylphenyl) - N' - chloro acetylamino] - acetamide, m.p. 6990C.

TABLE

&verbar; Physical No. Rl R characteristics 1.1 CH3 n-C3H7 m.p. 1111120 1.2 CH3 -CH2-CH--cH2 m.p. 123125 1.3 CH3 CH, ; m.p. 146--1480 1.4 CH3 ACH3 [ m.p. 121123 1.5 CH3 -CH2-CH2-O-CH3 m.p. 6972 2.1 C2Hs n-C3H7 m.p. 7376 2.2 C2H5 -CH,-CH=CH2 m.p. 8183 2.3 C2H5 < m.p. 104106C 2.4 C2H5 CH m.p. 78800 2.5 C,Hs -CH2-CH2-O-CH3 viscous oil 3.1 Cl n-C,H7 m.p. 717 4 3.2 Cl - -CH,-CH=CH2 m.p. 83-840 3.3 Cl < - m.p. 105107 3.4 Cl < LCH3 m.p. 78-800 3.5 Cl -CH2-CH2-O-CH oil The invention provides solid compositions for retarding plant growth which compositions comprise, as active ingredient, a compound of formula I, together with a solid extender and, optionally, a surface active agent.

The invention also provides liquid composi tions for retarding plant growth which compositions comprise the active ingredient together with a liquid diluent and a surface active agent Plant growth retarding compositions containing compounds of formula I may be manufactured in a manner known per se e.g. by mixing and grinding the active ingredients with carriers and/or distributing agents, optionally with the addition of anti-foaming agents, cross-linking agents, dispersing agents and/or solvents all inert to the active ingredients. The active ingredients can be worked up into the form of the following preparations and can be applied as such: solid preparations: dusts, scattering agents or granulates; water-dispersible concentrates of active in gredients: wettable powders, pastes and emulsions; liquid preparations: solutions.

The concentration of active ingredient in the compositions according to the invention is generally 1 to 80 percent by weight; the activeingredients can however be applied also at a low concentration, for example at a concentration of about 0.05 to 1%.

Wettable powder The following constituents are used to prepare a 50% wettable powder: 50 parts of an active ingredient of formula 1 5 parts of sodium dibutylnaphthyl sulphon ate, 3 parts of naphthalenesulphonic acid/ pleenolsulphonic acid/fonnaldehyde con densate 3:2:1, 20 parts of kaolin, and 22 parts of Champagne chalk.

The active ingredient is dissolved, e.g., in acetone, and the solution is absorbed onto the corresponding carriers (kaolin and chalk). By grinding there is obtained wettable powders, from which are produced, by dilution with water, suspensions containing 0.1-8% of active ingredient These are particularly suitable for application to plants.

Biological Examples.

Growth retardation in the case of grasses Seeds of the grasses Lolium perenne, Poa pratensis, Festuca ovina and Dactylis glomer ata were sown in plastic trays containing a soil/peat/sand mixture (6:3:1) and watered in the usual manner. The emerged grasses were cut back weekly to a height of 4 cm; and 40 days after sowing and 1 day of the last cutting they were sprayed with aqueous spray liquors of the active ingredients of formula I. The amount of active ingredient was equivalent Lo 5 kg of active substance per hectare. The growth of the grasses was evaluated 10 and 21 days after application of the active ingredients, according to the following linear scale of values: 1.=severe retardation (no further growth from time of application, 0%), 9=no retardation (growth as in the case of the untreated control specimens, 100%).

The active ingredients of formula I effected a pronounced reduction of growth to 70% or less. The compounds Nos. 1.1, 1.2, 1.3, 2.1, 2.3, 3.1, 3.2, 3.3 and others reduced growth to 50% or less.

In contrast to these compounds of formula I, the structurally similar compound Nbenzoyl - 4 - methylanilinoacetic acid N' - diethylamide (United States Patent Specification No. 2,676,188, Example 3) produced with 80N-100% growth in height of the grasses practically no reduction; with the resulting 100% growth in height of the grasses, the compound N - chloroacetylanilinoacetic acid - N',N' - diethylamide (United States Patent Specification No. 2,676,18B, Example 11) and the compound N-chloroacetyl-anilino- butyrmide (DT4S 2,311,897, No. 61) produced no reduction in growth.

Retardation of growth in the case of cereals Spring wheat-(Tridcum aestivum), spring barley (IHordeum vulgare) and rice (Oryza sativa) are sown in plastic bowls containing sterilised soil, and grown in a greenhouse. The wheat and barley are treated with spray liquors of the active ingredients 5 days after sowing, and the rice 12 days after sowing. The application to the leaves corresponds to 6 and 2 kg, respectively, of active substance per hectare (soil application=500 and 100 ml of liquor per pot). After application of the active in gradients, the rice bowls are covered with water up to 3 cm above the soil.

An evaluation is carried out 7 and 21 days after application. All the compounds of formula I, especially the compounds 1.2, 1.4, 1.5, 2.1, 2.3, 2.5, 3.1, 3.2, 3.3 and 3.5, produced a distinct shortening and simultaneous strengthening of the stems.

Regulation of growth of soya bean plants (Growth retardation, branching, pod setting).

Soya beans of the variety "Hark", "Grosskorn" or "Lee 68" were sown in a soil/peat/ sand mixture (6:3:1) in 11 cm pots with 4-5 seeds per pot m a greenhouse at about 250C.

After emergence, the plants were thinned out down to the strongest 2 plants per pot, which were then tied up.

As soon as the plant had developed 3 unfolded trifoliate leaves, the preparation of active ingredient was sprayed on until the surface of the leaves was uniformly wetted. The concentrations of active ingredient were 1000, 500, 100 and 50 ppm of active ingredient After being placed into an air-conditioned chamber, the plants were watered with a sprinkling tube and subsequently received a nutriment solution once weekly.

An evaluation was made 14 and 28 days after application. The compounds of formula I produced a pronounced retardation of vegetative growth.

There was observed in particular with application of the active ingredients 1.1, 1.5 and 2.1 also normal branching as well as normal pod setting in the case of the treated plants.

WHAT WE CLAIM IS: 1. A compound of the general formula

wherein R1 represents a chlorine atom, or a methyl or ethyl group, and R represents an n-propyl, allyl, methoxyethyl or cydopropyl group, 2. A compound of the general formula

wherein R1 represents a chlorine atom, or a methyl or ethyl group, and R represents a methylcyclopropyl group.

3. A compound according to claim 1 wherein R1 represents a methyl or ethyl group.

4. A compound according to daim 2 wherein R1 represents a methyl or ethyl group.

5. N - n - propyl - [N' - (2,6 - dimethylphenyl) - N - chloroacetylamino] - acetamide.

6. N - allyl - [N' (2,6 - dimethyiphenyl) N' - chloroacetylamino] - acetamide.

7. N - methoxyethyl - [N' - (2,6 - dimethylphenyl) - N' - chloroacetylamino]acetamide.

8. N - methylcyclopropyl - [N' - (2,6 - di- methylphenyl) - N' - chloroacetylamino]acetamide.

9. N - cycloproBl - [N' - (2 - methyl - 6ethylphenyl) - N' - chloroacetylamino] - acetamide.

10. A process for preparing a compound as claimed in claim 1 which process comprises reacting a compound of the formula

in which R1 and R are as defined in claim 1, with a chloroacetylating agent.

11. A process according to claim 10, wherein the anhydride or a halide of chloroacetic acid is used as chloroacetylating agent.

12. A process for preparing a compound as claimed in claim 1 which process comprises reacting a compound of the formula

(wherein Rl is as defined in claim 1) with an amine of the formula NH2R (wherein R is as defined in claim 1).

13. A process for preparing a compound as claimed in claim 2 which process comprises reacting a compound of the formula

in which Rl and R are as defined in claim 2, with a chloroacetylating agent.

14. A process according to daim 13, wherein the anhydride or a halide of chloroacetic acid is used as chloroacetylating agent 15. A process for preparing a compound as claimed in claim 2 which process comprises reacting a compound of the formula

(wherein R1 is as defined in claim 2) with an amine of the formula NH2R (wherein R is as defined in claim 2).

16. A compound according to claim 1 prepared by the process claimed in any one of

Claims (1)

1. claims 10 to 12.

   17. A compound according to claim 2 prepared by the process claimed in any one of claims 13 to 15.

   18. A solid composition for retarding plant growth which composition comprises, as active ingredient, a compound as claimed in any one of claims 1, 3 and 5 to 7 together with a solid extender and, optionally, a surface active agent.

   19. A liquid composition for retarding plant growth which composition comprises, as active ingredient, a compound as claimed in any one of claims 1, 3 and 5 to 7 together with a liquid diluent and a surface active agent.

   20. A solid composition for retarding plant growth which composition comprises, as active ingredient, a compound as claimed in any one of claims 2, 4, 8 or 9 together with a solid extended and, optionally, a surface active agent

   21. A liquid composition for retarding plant growth which composition comprises, as active ingredient, a compound as claimed in any one of claims 2, 4, 8 or 9, together with a liquid diluent and a surface active agent

   22. A method of retarding the growth of plants which method comprises applying to plants or the locus in which they are growing an effective amount of a compound as claimed in any one of claims 1, 3 and 5 to 7.

   23. A method according to claim- 22 wherein the compound is applied to grass.

   24. A method according to claim 22 wherein.

   the compound is applied to cereal.

   25. A method according to claim 22 wherein the plants to be treated are located on the verge of a road, railway, waterway or lake.

   126. A method of reducing the overall size of soybean plants which method comprises applying to the plants or the locus in which they are growing an effective amount of a compound as claimed in any one of claims 1, 3 and 5 to 7.

   27. A method of retarding the growth of plants which method comprises applying to plants or the locus in which they are growing an effective amount of a compound as claimed in any one of claims 2, 4, 8 or 9.

   28. A method according to claim 27 wherein the compound is applied to grass.

   29. A method according to claim 27 wherein the compound is applied to cereal.

   30. A method according to claim 27 wherein the plants to be treated are located on the cerge of a road, railway, waterway or lake.

   31. A method of reducing the overall size of soybean plants which method comprises applying to the plants or the locus in which they are growing an effective amount of a compound as claimed in any one of claims 2, 4, 8 or 9.