HRP980217A2 - Use of hydroxylamine derivatives, and method and preparations for increasing the tolerance of filed crops against weather stresses - Google Patents

Description

The field of invention

This invention relates to the use of hydroxylamine derivatives of the general formula (I), where

R1 represents a phenyl, N-heteroaryl, S-heteroaryl or naphthyl group which can be substituted with one or more halo, alkyl, alkoxy, haloalkyl or nitro, some unsubstituted or substituted phenylamino or alkylamino or lower alkoxy,

X represents halo, preferably chloro or bromo, amino or an unsubstituted or substituted phenylamino group, or an amino substituted with one or two lower alkyl or a hydroxyl group with the proviso that if R1 represents unsubstituted or substituted phenylamino, alkylamino or lower alkoxy, then X cannot represent hello,

Y represents hydrogen, hydroxy or acyloxy, preferably longer alkanoyloxy, or if Y represents hydroxy, the molecule may contain a dioxazine ring, closed at the carbon atom carrying the X group, formed by the usual XH elimination,

R 2 and R 3 , independently of each other, represent hydrogen or a lower alkyl group ensuring that R 2 and R 3 cannot be hydrogen at the same time,

R2 and R3 together with the neighboring nitrogen atom form a 5- to 7-membered saturated hetero ring,

and a method and preparation for increasing the tolerance of cultivated plants against the stresses of weather conditions.

Previous knowledge

Damage to cultivated plants due to weather stress, such as cold, frost and drought, causes significant losses for agriculture. These factors, in the scope of this invention briefly referred to as weather stresses, can occur in any period of plant growth or vegetation. Although they affect plants in different ways and plants react to them differently according to species and type, the effect is usually related to the water metabolism of plants. Protecting plants from weather stresses is even more difficult due to the wide and diverse distribution of time, intensity and length of these stresses present in most agricultural areas.

In the present invention, a temperature is considered cold if it is lower than the minimum temperature necessary for the normal physiological functioning of individuals belonging to a given plant species or type, but higher than the freezing point of water. In general, their effect does not have to be determined immediately by simple observation. Cold damage shows up later, after warming, such as reduced plant growth, drying or loss of color (chlorosis), or in the most severe cases, plant death.

Frost, i.e. temperature below zero degrees Celsius, does not necessarily cause the plant to die. Once gone, the plant can recover, but the irreversible cell damage caused by frost will stunt its development, which will ultimately reduce its yield.

While cold and frost usually appear at an early stage of plant development and hence damage germination and plant development, drought damages a fully developed plant and endangers the further stage of development. By reducing the level of evaporation, the plant can maintain a reduction in losses. For example, there is a method where the surface of the plant is covered with a polymer film with the aim of physically limiting the evaporation of the plant in case of drought. For this purpose, polyethoxylated polyoxypropylene copolymers described in US patent no. 4828602. The disadvantage of this method is that it requires the local application of a coating substance, which can only be done by investing a large amount of manual labor. Permanent prevention of evaporation is not desirable anyway; in the system, effective evaporation inhibitors are preferred considering the physiology of the plant.

Extensive research into the effects of weather stress on plants has been conducted to reduce damage from cold, frost and drought, and a large number of scientific publications deal with the physiological relationship of plant tolerance to cold, frost and drought. (bad, come up with better). Given that plants react to these weather stresses very differently according to their botanical characteristics, a theoretically satisfactory explanation of the mechanism of tolerance to cold, frost and drought has not yet been given, and hence the methods developed for practical application in order to improve the tolerance of plants against weather stresses are very they differ.

For example, it is known in the field of substances that regulate growth, which are compounds of hormonal activity, that they have a positive effect on the tolerance of plants to cold, frost and drought, and therefore they are used to treat cultivated plants. A typical example is abscisic acid, which is a growth-regulating hormone. Abscisic acid is difficult to synthesize and is therefore not used in agriculture. However, substances chemically and in terms of their action analogous to abscisic acid are used, which have the same or stronger effect than abscisic acid itself, especially when combined with other compounds, which ensures a synergistic increase in effect. For example, PCT publication WO no. 9608481 A1 describes that the plants are treated with epoxycyclohexane derivatives to make their development and yield more favorable and to increase their tolerance to cold and drought. In addition to these compounds, brasidosteroids have also been used as synergistic auxiliaries. EP no. 327309 A1 describes a compound containing a polysubstituted cyclohexenyl-acetylene derivative as an effective agent, and a differently and multiply substituted phenylbenzylurea derivative as a synergistic agent. With the help of this hormone-active substance, the plant's drought tolerance can be improved.

Compounds of hormonal activity are without any doubt significant, because they have an intense effect even when applied in small quantities, however, their disadvantage is that they affect the metabolic processes present in plants on a large scale, changing the hormonal balance of plants, which can result in unpredictable physiological changes. Therefore, such compounds and products must be used with caution in practice. Before application, it is important to carry out preliminary tests related to a given plant species or type with the aim of determining the convenience and optimal circumstances of product application in a given agricultural area, which limits their application in agricultural practice.

In order to avoid the aforementioned disadvantages of substances of hormonal activity, researchers have turned to simpler, hormonally indifferent substances to find a suitable and effective agent for improving plant tolerance to cold, frost and drought. According to PCT publication WO no. 92/08350 A1 tetrahydro-furfuryl-alcohol, tetrahydro-furfuryl-amine, or a combination of these compounds is used to improve cold tolerance of plants. These effective means do not have the mentioned disadvantages of substances with hormonal activity, their production is easier, and hence they are more profitable, but from a practical point of view they are not desirable. This is because, according to the work cited above, it is recommended to spray the plants more than once with a solution of an effective agent in order to achieve a satisfactory extent of recovery of plants affected by the cold, and to repeat the treatment after the end of the cold, and the most useful way is to spray the plants constantly. Treating the entire surface is considered important in order to ensure that the effective agent reaches the entire surface of the plant. Therefore, complete or repeated spraying is recommended. This requirement can only be met by investing a large amount of manual labor.

According to Hungarian patent no. 181241, secondary or tertiary β-hydroxyethyl-amines or corresponding quaternary ammonium salts, preferably 2-hydroxy-ethyl-amines and trimethyl-β-hydroxy-ethyl-ammonium chloride (choline chloride) and, in certain cases, a combination of these, can be used to improve plant tolerance to cold and frost. Primarily, the effective agent was applied to the plants by spraying. It can be concluded from the experimental part of the patent that the effective agent helps to change the phospholipid system of the plant cell membrane, and therefore the fluidity of the membrane. Hence, the mentioned effective means can be used to treat only fully developed plants. This is also confirmed with experimental results. Treatment of seedlings and seeds, which is mentioned in the patent, can be ineffective with these effective agents because the plants lack parts with the necessary membrane. The exception is choline chloride, whose application for seed treatment is known from publication JP no. 62161701. In that case, however, the general growth-regulating effect of the substance, as described in the above-mentioned work, was used, and this effect works, among other things, to improve the tolerance of plant shoots against cold. However, substances that regulate the growth of hormonal activity have all the disadvantages described above. Summarizing the above, we can conclude that several different attempts have been published in the patent literature with the aim of improving the tolerance of cultivated plants to weather stresses. Effective agents and products from these patents are, however, only suitable for direct agricultural application with the aforementioned limiting conditions.

Our research is aimed at finding effective agents, which increase the tolerance of plants to cold, frost and drought, but are hormonally neutral, non-toxic, the limitations of their application are the smallest possible, and which are suitable not only for treating fully developed plants, but also seedlings and seeds.

The discovery of an invention

It was found that derivatives of hydroxylamine of the general formula (I), where

R1 represents a phenyl, N-heteroaryl, S-heteroaryl or naphthyl group which can be substituted with one or more halo, alkyl, alkoxy, haloalkyl or nitro, some unsubstituted or substituted phenylamino or alkylamino or lower alkoxy,

X represents halo, preferably chloro or bromo, amino or an unsubstituted or substituted phenylamino group, or an amino substituted with one or two lower alkyl or a hydroxyl group with the proviso that if R1 represents unsubstituted or substituted phenylamino, alkylamino or lower alkoxy, then X cannot represent hello,

Y represents hydrogen, hydroxy or acyloxy, preferably longer alkanoyloxy, or if Y represents hydroxy, the molecule may contain a dioxazine ring, closed at the carbon atom carrying the X group, formed by the usual XH elimination,

R2 and R3 independently of each other represent hydrogen or a lower alkyl group ensuring that R2 and R3 cannot be hydrogen at the same time,

R2 and R3 together with the adjacent nitrogen atom form a 5- to 7-membered saturated hetero ring, show the required effect and satisfy the mentioned requirements.

These compounds work in an inductive way, that is, they increase the level of hardness if the plant is faced with environmental stresses, such as when the above-mentioned weather stresses hit the plant. Induced metabolic processes result in increased tolerance to cold, freezing and drought.

Based on these observations, the present invention relates to the use of hydroxylamine derivatives of general formula (I), where R1, X, Y, R2 and R3 are as above, for improving the tolerance of cultivated plants to weather stresses.

In the general formula (I), the lower alkyl group contains preferably 1-6 carbon atoms, most preferably 1-4 carbon atoms, and the lower alkyl group contains 1-6, preferably 1-4 carbon atoms. In the compounds of the general formula (I), where R1 is a substituted phenyl or phenylamino group, the alkyl groups attached to the phenyl ring as substituents are preferably lower alkyl groups with 1-6 carbon atoms. Alkoxyl substituents of the phenyl ring preferably contain 1-6 carbon atoms. The haloalkyl substituents of the phenyl ring preferably contain alkyl, most preferably C1-6 alkyl. The most preferred haloalkyl substituent is a trifluoromethyl group. If R1 represents alkylamino, it preferably contains a maximum of 12 carbon atoms. If R1 represents N-heteroaryl, it is preferably a pyridyl or pyrazinyl group, while if R1 represents an S-heteroaryl group, it is preferably thienyl. Finally, if Y represents a long alkanoyloxy carbon chain, it preferably contains 12-20 carbon atoms.

Some derivatives of hydroxylamine of the general formula (I) are known compounds. Those compounds of the general formula (I) in which R1 represents phenyl or pyridyl or naphthyl which may be substituted with halo or alkoxy, X represents amino and Y represents hydroxy, are known from Hungarian patent no. 177,578, which also describes procedures for the preparation of these compounds, as well as various synthesis options. These compounds, as selective beta-blocking agents, can be used in the therapy of angiopathy, primarily diabetic angiopathy. These compounds of the general formula (I) in which R1 represents phenyl or alkoxyphenyl or pyridyl or naphthyl, X represents halo and Y is hydroxy, as well as their preparation, are known from Hungarian patent no. 207,988. These compounds can also be used in the therapy of angiopathy. Those compounds of the general formula (I) in which R1 represents naphthyl or haloalkylphenyl, X is hydroxy and Y represents hydroxy, are known from the published Hungarian patent application no. 2385/92. These compounds have an anti-ischemic and anti-anginal effect, and hence they can be used especially in the treatment of heart diseases. Those compounds of the general formula (I) in which R1 represents phenyl or a phenyl group substituted with the above-mentioned substituents or a pyridyl group, X represents halo and Y is a hydrogen atom, are known from PCT publication WO no. 95/30649 A1. The same document describes the preparation of these compounds. These compounds have an anti-ischemic effect and can therefore be used in the therapy of diabetic angiopathy. Furthermore, those compounds of the general formula (I) are also known, in which R1 represents phenylamino which is unsubstituted or substituted with alkyl, alkoxy, halo, haloalkyl or nitro, or some alkoxy or alkylamino group, X represents hydroxy and Y is hydrogen, hydroxy or alkanoyloxy. Their descriptions can be found in PCT publication WO no. 97/00251, which also describes the preparation of these compounds. These compounds have an anti-ischemic effect and can therefore be used in the treatment of heart and blood vessel diseases. Note that in the known compounds R2 and R3 represent the same as defined above, and therefore these two substituents are not described in detail.

It should also be noted that tautomerism may occur in certain compounds of general formula (I), that is, they may occur in a tautomeric structure different from, but corresponding to, formula (I). Individually, this is the case when the compounds of the general formula (I) contain a hydroxyl group as X, where the more stable tautomeric form containing -(CO)-NH- is the part of the molecule that does not appear in the structural formula.

The remaining compounds of general formula (I) form the subject of our previously unpublished patent application.

The new compounds are those derivatives of hydroxylamine of the general formula (I), in which X represents halo, Y is hydroxy, and R1 represents a group different from those described in the above-mentioned Hungarian patent no. 207,988 which deals with this type of compounds, for example phenyl substituted with alkyl, haloalkyl or nitro. These substances were prepared analogously to the cited description by diazotization of the corresponding compound containing the NH2 group at position X. The necessary initial amino compounds were produced also by a known method, by the coupling reaction of the corresponding amidoxime and 3-amino-2-propanol derivative, for example according to the method described in the Hungarian patent no. 177,578.

N-substituted amidoximes of the general formula (I), where R1 represents an aromatic group and X represents a substituted amino group, are also new compounds and can be made by binding a suitable imidoyl halide of the general formula (1), where Hal represents halo and R1 is as above, while R' is a substituent of the amino group of X, and the 1-amino-3-aminooxypropane derivative of the general formula (2), where R2, R3 and Y are as above. The reaction should be carried out in a neutral solvent, for example in a chlorinated hydrocarbon, at room temperature and after separation by extraction, the product is isolated as a salt with a suitable organic or inorganic acid.

Other new compounds of general formula (I) are N-hydroxy-guanidine derivatives in which both R1 and X are substituted nitrogen atoms.

These derivatives are made by acylation of a suitable aminooxy compound of general formula (2), if the agent for acylation is haloformamidine of general formula (3), where Hal represents halogen, R1 is as above, and R' and R" are substituents of the amino group appearing as X in the product. The reaction is carried out in a two-phase system, in a mixture of an organic solvent immiscible with water and an aqueous alkali, preferably an aqueous solution of sodium carbonate. The product is isolated in this case also by separation with extraction and, if possible, as a salt .

Any of these new compounds of general formula (I), in which Y represents acyloxy, can be made by O-acylation of the corresponding compound containing hydroxy as Y. The starting compounds are either known from the literature mentioned above or can be made according to the method described.

Acid halides, active esters or other common reagents applicable for O-acylation can be used as an acylating agent. The reactions can be carried out in a neutral solvent, usually at room temperature and if necessary in the presence of a suitable acid scavenger, such as an organic or inorganic base, for example triethylamine or solid sodium carbonate. Acid chlorides are preferred as the acylating agent, where the compound itself can act as an acid-binding agent, and therefore the product can usually be easily isolated as the hydrochloride by simple ether crystallization after evaporation. When less reactive acylating agents are used, Schotten-Baumann acylation can also be used. The products are usually isolated in the form of their organic or inorganic acid salts.

With regard to the application of the invention, the following compounds of the general formula (I) are most preferred:

N-[2-hydroxy-3-(1-piperidinyl)propoxy]-benzimidoyl chloride hydrochloride (Compound 1)

N-[2-hydroxy-3-(1,1-dimethylethyl-amino)propoxy]-3-trifluoromethyl-benzamide monohydrochloride (Compound 2)

N-[2-palmitoyloxy-3-(1-piperidinyl)propoxy]-3-pyridinecarboxymidamide monohydrochloride (Compound 3)

N-[3-(1-piperidinyl)propoxy]-3-nitro-benzimidoyl-chloride monohydrochloride (Compound 4)

N-[2-hydroxy-3-(1-piperidinyl)propoxy]-2-nitro-benzimidoyl chloride monohydrochloride (Compound 5)

N[[3-(1,1-dimethylethyl)-amino]-2-hydroxypropoxy]-N'-phenyl-benzamidine hydrochloride (Compound 6)

N-N'-dimethyl-N'-phenyl-N"-[3-(1-piperidinyl)propoxy]-guanidine hydrochloride (Compound 7)

N-[3-(1-piperidinyl)propoxy]-pyrazine-carboximidoyl chloride monohydrochloride (Compound 8)

3-(3-pyridyl)-5-diethylaminomethyl-5,6-dihydro-1,4,2-dioxazine hydrochloride (Compound 9)

N-[2-hydroxy-3-(1-piperidinyl)propoxy]-1-naphthalene-carboxamide (Compound 10)

N-[2-hydroxy-3-(1-piperidinyl)propoxy]-ethylurethane (Compound 11)

N-hexyl-N'-[2-hydroxy-3-(1-piperidinyl)propoxy]-urea (Compound 12)

N,N-dimethyl-N'-phenyl-N"-[2-hydroxy-3-(1-piperidinyl)propoxy]-guanidine hydrochloride (Compound 13)

N-[3-(1-piperidinyl)propoxy]-thiophene-2-carboximidoyl chloride hydrochloride (Compound 14)

N-[3-(1-piperidinyl)propoxy]-N'-phenyl-benzamidine hydrochloride (Compound 15)

The compounds of the general formula (I) are preferred with regard to application on cultivated plants, as they are suitable for treating fully developed plants as well as seeds or seedlings. These compounds can be applied to plants using any of the usual methods widely used in plant protection.

Based on the above, the invention relates to a method for increasing the tolerance of cultivated plants against weather stresses. According to the invention, the protected plant or its seed is treated with a derivative of the general formula (I), where R1, X, Y, R2 and R3 are as above. An aqueous solution of the compound of the general formula (I) is preferably used for treatment, but alternatively, as an effective agent, a preparation containing the usual carriers and a hydroxylamine derivative of the general formula (I) can be used.

The dose and concentration of the effective agent of the general formula (I) depends on the type or type of protected plant and on the method of application.

If the method according to the invention aims at increasing the plant's tolerance to cold and frost, the seeds of the plant should preferably be treated with a hydroxylamine derivative of the general formula (I), where R1, X, Y, R2 and R3 are as above. The seed of the plant must be covered with a suitable product containing the active agent and suitable for coating, preferably as beads, in certain cases coated, or simply an aqueous solution of the active agent can be used.

The preferred method is to soak the seeds of the plant in an aqueous solution of the compound of the general formula (I). For this purpose, a 1-200 mg/l concentration of the compound of the general formula (I) was prepared as an aqueous solution.

The method according to the invention can be carried out by coating the seeds of the plant with a solution containing a hydroxylamine derivative of the general formula (I). Compounds of general formula (I) can be combined with coating agents in certain cases.

For coating the seeds, it is preferable to apply agents for the formation of beads, which contain compounds of the general formula (I) in a concentration of 0.1-10 g/l together with the usual formation of beads and auxiliary substances. Agents for forming beads may contain other effective agents than the already mentioned effective agent, such as fungicides or additives that promote germination, for example microelements. The agent for the formation of beads is applied in a small volume. For example, when treating peas, soybeans, or corn, only 1 ml or less of beading agent is used per 100 seeds, which dries evenly on the seeds with constant agitation.

Furthermore, this invention relates to a method for improving the cold tolerance of cultivated plants, where the plant is sprayed before or when the cold season begins with a spray composition containing a hydroxylamine derivative of the general formula (I) as an effective agent.

Spraying is carried out with a 1-500 mg/liter concentration of an aqueous solution of the effective agent, which may sometimes contain auxiliaries for spraying, such as a surface-active substance (detergent). In certain cases, the compounds of the general formula (I) can be combined and sprayed on the plant to be protected with other effective agents such as fungicides.

Spraying should be carried out at the beginning of the dangerous period in terms of cold temperature. If more than one period must be taken into account, the plants must be sprayed at the beginning of each such period.

According to the invention, to improve the tolerance of cultivated plants, the plant must be sprayed before or at the time of the beginning of the dry season with a spray composition containing a hydroxylamine derivative of the general formula (I) as an effective agent.

Spraying is carried out using a 1-500 mg/l aqueous solution of the active agent. The plants to be protected are sprayed before or at the beginning of the period when there is a danger of drought. In any case, the characteristics of a given plant species or type determine the applicable amount of the effective agent. If more than one dry period is taken into account, then spraying must be repeated at the beginning of each such period.

For the above-mentioned treatments, a simple aqueous solution of hydroxylamine derivatives of general formula (I) is used, but preferably such preparations are used that contain appropriate auxiliary substances in addition to the effective agent, to improve spraying, distribution and absorption of the effective agent.

The mixture of the invention for improving the tolerance of cultivated plants to weather stresses contains 0.001-95 m/m% of a hydroxylamine derivative of the general formula (I), in which R1, X, Y, R2 and R3 are as above, in addition to solid or liquid carriers and possible auxiliary substances suitable for use in agriculture.

The mixture preferably contains water as a liquid filler. The aqueous solution of the active agent is a concentrate that should be diluted before application in order to prepare the appropriate concentration mentioned above. Preferably, the aqueous solution contains surfactants, those seed treatment solutions contain auxiliaries for coating and beading, such as film forming agents. Sprays contain some agent for improving adhesion, a substance for improving dispersion, a protective agent against light, if required, a stabilizing agent and other additives in addition to detergents. ULV concentrates, emulsifiable concentrates, hydrophilic powders, soluble granules or water-dilutable microgranules can be used for spraying. These products contain anionic or non-anionic detergents to aid dilution with water. Solid products may contain kaolin, diatomite or dolomite as a filler, but may also contain any other filler widely applicable in such products. Perlite is preferably used as a filler for the production of microgranules.

Mixtures from the invention can be combined or simultaneously applied with other pesticides, if the active agent of the latter is compatible with the active agent of the mixture from the invention. In these cases, spraying the mixture from the invention does not require a special procedure, it can be carried out together with the usual pesticide treatment of cultivated plants.

The best way to carry out the invention

The invention is illustrated by the following examples without limiting the scope of the invention.

Example 1

N-[2-palmitoyloxy-3-(1-piperidinyl)propoxy]-3-pyridinecarboxymidamide monohydrochloride (Compound 3)

14.7 g (52.8 mmol) of N-[2-hydroxy-3-(1-piperidinyl)propoxy]-3-pyridinecarboxymidamide was dissolved in 160 ml of chloroform. 7.7 ml (55 mmol) of triethylamine was added, followed by dropwise addition of a solution of palmitoyl chloride (14.7 g; 56.5 mmol) in 85 ml of chloroform. The mixture was stirred overnight at room temperature. The next day, a further 3.8 ml of triethylamine and 7.4 g of palmitoyl chloride were added and stirring was continued for another day. Then the solution was extracted with water, 5 V/V% acetic acid and water, in sequence, dried over anhydrous sodium sulfate, and evaporated to dryness.

The residue (28.2 g of oil) was dissolved in ethyl acetate and the product was precipitated by adding 30 ml of 1 N HCl/ethyl acetate. The thick white precipitate was filtered, washed with ethyl acetate and dried.

Yield: 10.9 g (37%)

T.p.: 110-113°C.

Example 2

N-[2-hydroxy-3-(1-piperidinyl)propoxy]-2-nitro-benzimidoyl-chloride monohydrochloride (Compound 5)

6.0 g (16.7 mmol) of N-[2-hydroxy-3-(1-piperidinyl)propoxy]-2'-nitro-benzene-carboxymidamide monohydrochloride was dissolved in 21 ml of water and then 48 ml of concentrated hydrochloric acid. The solution was cooled to -5°C and then a cooled solution of 2.1 g (33.3 mmol) of sodium nitrite in 9 ml of water was added dropwise. The internal temperature was maintained at 0°C throughout the reaction. After the addition was complete, the mixture was stirred for a further four hours and cooled overnight. The product was filtered, washed with cold water and dried.

Yield: 3.9 g (63%). M.p.: 159-162°C

IR(KBr): 3298, 2983, 2932, 2746, 1593, 1574, 1535, 1445, 1391, 1354, 1317, 1288, 1242, 1198, 1117, 1092, 1069, 1020, 968, 947, 932, 947, 932, 914 , 756, 708, 577 cm-1.

Example 3

N[[3-(1,1-dimethylethyl)-amino]-2-hydroxypropoxy]-N'-phenyl-benzamidine hydrochloride (Compound 6)

4 g (24.7 mmol) of benzanilide-imide chloride were dissolved in 45 ml of chloroform. Then 5.32 g (24.7 mmol) of 1-aminooxy-3-[(1,1-dimethyl-ethyl)-amino]-2-hydroxy propane dissolved in 45 ml of chloroform was added to the resulting solution. The reaction mixture was stirred at room temperature for 3 hours and then washed with 25 ml of 1 M aqueous sodium carbonate solution. The chloroform portion was dried over sodium sulfate, filtered and evaporated. The residue after evaporation is crystallized with hexane. The resulting base was dissolved in (5.33 g) 50 ml of ethyl acetate and then 3.35 ml of 3.67 N hydrochloric acid/ethyl acetate was added. The isolated crystals were filtered, washed with ethyl acetate and dried.

Yield: 2.97 g (97%). T.p.: 140-143°C

1H NMR (solvent: CDCl3 [ppm]): 9.7 (m,1H) and 8.1 (m,1H,NH2+); 7.8 (s, 1H, NH-O); 6.7-7.4 (m, 10H, 2xPh); 5.7 (d,1H,OH); 4.5 (m, 1H, CH); 4.25 (d,2H,OCH2); 3.1 (m,2H,NCH2); 1.25 (s, 9H, tBu).

Example 4

N-N'-dimethyl-N'-phenyl-N"-[3-(1-piperidinyl)propoxy]-guanidine hydrochloride (Compound 7)

20 ml of 1 M aqueous sodium carbonate solution was added to 1.040 g (6.5 mmol) of 1-aminooxy-3-(1-piperidinyl)propane dissolved in 10 ml of ether. 1200 mg (6.5 mmol) of N,N-dimethyl-N'-phenyl-chloroformamidine dissolved in 10 ml of ether was added with vigorous stirring. After stirring for 2 hours, a further 20 mg (0.1 mmol) of N,N-dimethyl-N'-phenyl-chloroformamidine was added. After a further 3 hours of stirring, the phases were separated and the ethereal part was dried over sodium sulfate, filtered and evaporated. The residue (1700 mg of yellow oil) was dissolved in 10 ml of ethyl acetate and 10.5 ml of 0.54 M hydrochloric acid/ethyl acetate was added, and then the product was cooled and the isolated crystals were filtered. The crude product was crystallized from methanol-ether to give 847 mg of a white crystalline solid.

Yield: 847 mg (38%). T.p.: 138-139°C (methanol-ether)

1H NMR (solvent: CDCl3 [ppm]): 7.2 (t,2H,Ph-m); 7.1 (d,2H,Ph-o); 6.9 (t, 1H, Ph-p); 6.6 (m, 1H, NH+); 4.0 (t,2H,OCH2); 3.5 (m, 2H); 3.0 (t,2H,CH2); 2.6 (s,6H,2xNCH3); 2.2-2.5 (m, 6H, 3xNCH2); 1.8 (m,4H) and 1.3 (m,2H,piperidine).

The product crystallized from isopropanol melted at 213-216°C.

Example 5

N-[3-(1-piperidinyl)propoxy]-N'-phenyl-benzamidine hydrochloride (Compound 15)

0.8 g (5 mmol) of 1-aminooxy-3-(1-piperidinyl)propane was dissolved in 7.5 ml of chloroform, 1.08 g (5 mmol) of benzanilide-imide chloride dissolved in 7.5 ml of chloroform was added dropwise. and then the reaction mixture was stirred for 3 hours. Then it was washed twice with 10 ml of water and the chloroform part was dried over sodium sulfate, filtered and evaporated. The evaporation residue was dissolved in 20 ml of 2 N aqueous sodium hydroxide solution and the solution was extracted with 20 ml of ethyl acetate. The ethyl acetate portion was dried over sodium sulfate and filtered, and then 0.8 ml of 3.45 M hydrochloric acid/ethyl acetate was added. The isolated precipitate was filtered and dried.

Yield: 0.8 g (46%). T.t.: 164-166°C (crystallizes from ethyl acetate)

C13-NMR (solvent: CDCl3 [ppm]): 157.55 (C-amidine); 135.75 (N-Ph-ipso); 132.84 (C-Ph-ipso); 128.95 (N-Ph-m); 128.84 (C-Ph-m); 126.66 (N-Ph-p); 125.34 (N-Ph-p); 124.0 (C-Ph-p); 74.02 (OCH 2 ); 54.20 (NCH2); 53.30 (2,6 piperidine); 23.19 (CH 2 ); 22.63 (3.5 piperidine); 21.76 (4 piperidine).

Example 6

N,N-dimethyl-N'-phenyl-N"-[2-hydroxy-3-(1-piperidinyl)propoxy]-guanidine hydrochloride (Compound 13)

1150 mg (6.58 mmol) of 1-aminooxy-2-hydroxy-3-(1-piperidinyl)-propane was dissolved in 20 ml of ether and to this solution was added 20 ml of 1 M sodium carbonate solution, then 1206 mg ( 6.58 mmol) of N,N-dimethyl-N'-phenyl-chloroformamidine dissolved in 10 ml of ether. After 2 hours, 22 mg (0.11 mmol) of N,N-dimethyl-N'-phenyl-chloroformamidine was also added to the reaction mixture. After stirring for a further 3 hours, the layers were separated, the ether layer was dried over sodium sulfate, filtered and evaporated. The residue of 1800 mg of yellow oil was dissolved in 10 ml of ethyl acetate and to this solution was added 10.46 ml of 0.54 M HCl/ethyl acetate, cooled and the yellow crystals were filtered. Impurities were removed by recrystallization first in acetone and then in ethyl acetate.

Yield: 674 mg (28%) of pale yellow powder. T.t.: 127-129°C (ethyl acetate)

1 H NMR (solvent: CDCl 3 [ppm]): 7.1-7.4 (m,SH,Ph); 5.9 (m,1H,OH); 4.6 (m, 1H, CH); 4.1 (m,2H,OCH2); 3,6 (m,4H,2,6 piperidine); 3.4 (m, 2H); 3.2 (m,1 H,NH); 1,8 (m,4H,3,5 piperidine); 1,4 (m,2H,4 piperidine).

Example 7

Increasing tolerance to chilling by seed treatment

In this experiment, the cold tolerance of corn, soybean and pepper seeds treated with the active agent was tested. This test imposes the stress of temperature and lack of oxygen on the seeds and was carried out according to the Barla-Szabo and Dolinka CSVT (complex stress test). For the individual test, two hundred seeds were soaked for 48 hours at 25°C and another 48 hours at 5°C in 150 ml of distilled water containing the active agent in a concentration of 10 mg/l. After 96 hours of soaking, the seeds were further germinated between rolled wet paper for 96 hours at 25°C. There were 25 seeds in each roll, the rolls were placed vertically in containers and covered with a plastic bag to reduce evaporation. During the entire procedure, the seeds were kept in the dark.

At the end of the experiment, normally developed and ungerminated seeds were counted. The length of normal seedlings was measured and the average length of the five longest seedlings was calculated. Seedlings longer than 0.33 times the average length of the five longest seedlings were considered high vigor, and low vigor seedlings were shorter than this length.

In experiments with corn, it was found that the tested active agents did not affect the germination and development of the Mo 17 inbred corn line, which germinates under optimal conditions at 25°C. Under CSVT test conditions, however, they proved to be effective, as shown in Table 1

Table 1.

Active agent Ratio of highly potent plants (%)

Compound 1 38*

Connection 29*

Compound 33*

Junction 24

Compound 3 47*

Compound 12 23 *

Compound 4 28*

Compound 5 32*

Compound 6 35*

Compound 7 36*

Supervision 19

Results marked with * are significantly comparable to control, if P<0.05.

Using the same experimental method for HMv09 inbred maize line compounds, shown in Table 2, proved to be effective, the ratio of high strength plants increased significantly.

Table 2

Active agent Ratio of highly potent plants (%)

Compound 2 49*

Compound 10 5 2*

Compound 4 40*

Compound 6 57*

Compound 13 56*

Compound 14 45 *

Compound 15 53 *

Supervision 33

Results marked with * are significantly comparable to control, if P<0.05.

In case of further experiments with low chilling tolerance (LT) and high chilling tolerance (HT) maize crops [Citation: P. Landi, E. Frascaroli, A. Lovato; EUPHYTICA 64 21-29 (1992)], the following positive effects were found (Table 3).

Table 3

Active agent Ratio of highly potent plants (%)

HT LT

Compound 2 98* 94*

Compound 3 92* 86*

Compound 4 94* 88*

Compound 5 96* 92*

Supervision 84 74

Results marked with * are significantly comparable to control, if P<0.05.

An experiment with McCall soybeans also showed that active agents do not affect germination and development under normal conditions. When the CSVT test was applied, the following results were obtained (Table 4).

Table 4

Active agent Ratio of highly potent plants (%)

Compound 2 43*

Compound 4 46*

Compound 8 47*

Supervision 38

Results marked with * are significantly comparable to control, if P<0.05.

Compound 8 was observed to reduce the number of ungerminated seeds by 50% (control: 33%, treated: 17%, significant at P<0.05).

Experiments with green pepper similarly showed that the active agents do not work under normal conditions, they do not affect the germination of seeds and the development of plants kept at 25°C. Under CSVT test conditions, they increase the length of shoots and roots along with the proportion of highly vigorous seedlings. The proportion of ungerminated seeds dropped by 30% of the average thanks to treatment with active agents. The results are shown in Table 5.

Table 5

Active agent Ratio of highly potent plants (%)

Compound 2 47*

Compound 4 45*

Supervision 36

Results marked with * are significantly comparable to control, if P<0.05.

In order to make the results more understandable, it should be noted that the CSVT procedure was developed to predict the expected minimum ratio of germinated seeds under environmental stresses. In a given set of seeds, the ratio of those seeds that reliably germinate and germinate adequately in cool spring weather is 90% for seeds that have proven high vigor in the CSVT test, while the ratio of those seeds that reliably germinate and germinate adequately in cool spring weather is only 60% for seeds that proved to be very low in the test. Therefore, if an active agent improves seedling vigor, it ultimately improves the germination ratio under open field conditions when the soil temperature is cooler than optimal.

The above experiments prove that the compounds of the general formula (I) are able to improve the strength of seedlings and therefore improve the chances of germination, if weather stress unexpectedly occurs after sowing.

Example 8

Pearling of soybean seeds

Soybean seeds were treated with a beading agent containing 1 mg/ml of N-[3-(1-piperidinyl)propoxy]-3-nitro-benzimidoyl chloride monohydrochloride (Compound 4) in a 5% aqueous solution of polyvinyl alcohol. 100 seeds and 1 ml beading agent were filled into a glass container and while the container was rotated, the seeds were coated with the agent and then allowed to dry. For the seeds treated in this way, we obtained the following results when they were subjected to the conditions of the CSVT test described in Example 7.

Table 6

Procedure Ratio of highly vigorous plants (%)

sapling root

untreated control 47 40

beaded with PVA 52 49

beaded with PVA and Compound 4 63* 58*

Results marked with * are significantly comparable to control, if P<0.05.

PVA slightly increased the proportion of highly vigorous plants. The PVA solution containing Compound 4 proved to be such a beading agent that could significantly increase the ratio of high vigor plants under experimental conditions, increasing the length of both shoots and roots.

In the next CSVT experiment, also using the McCall strain, polyvinyl alcohol (PVA) was applied for beading the seeds. 2.5 mg dose of active agents was dissolved in 1 ml of 2.5% PVA solution, and this amount was applied to 100 pieces of seeds. Improvement in chilling tolerance was observed with significant elongation of sprouts and roots. The results are presented in Table 7.

Table 7

Active Asset Relative Length (supervision = 100)

sprout root

Compound 2 106 128

Compound 9 110 131

Compound 3 133 150

Compound 5 116 135

Connection 6 127 152

Experiments clearly show that according to the results of strength tests, the chances of plant germination increase after beading with an active agent.

Example 9

Increasing bean drought tolerance

Based on our earlier experiments, the plants were dried before applying the active agent; by withholding water for several days until the first signs of drying appeared. Then the plants are watered and the active agent is either dissolved in water or sprayed directly on the plants. After that, the plants were subjected to different periods of drought according to the given experiment, watered again and after a recovery period of one week, the survival ratio was determined.

a) The bean plantation was dried for 5 days by withholding water. After that, the plants were watered normally for two days. During that time, a solution of the active substance with a concentration of 10 mg/liter and 100 mg/liter was applied twice a day, dissolved in water or by direct injection. Water was then withheld for 7 days, and after a week of recovery, the survival ratio was determined. The results are summarized in Table 8.

Table 8

Active agent watering watering Spraying

(10 mg/l) (100 mg/l) (100 mg/l)

survival (%)

supervision 17 17 0

Compound 2 30* 41* 71*

Connection 6 25* 36* -

Results marked with * are significantly comparable to control, if P<0.05.

b) In this experiment, the bean plants (Seaway) were dried for 7 days instead of 5 days as described in procedure a. Then a solution of the active agent with a concentration of 10 mg/liter and 100 mg/liter was applied twice a day for two days. Then, after 7 days without water and after a week of recovery, the results of the experiment were evaluated. The results are summarized in Table 9.

Table 9

Active agent Survival (%)

Compound 2 14*

Compound 4 39*

Supervision 0

Results marked with * are significantly comparable to control, if P<0.05.

Example 10

Increasing soybean tolerance to drought

Bólyi 44 soybeans were dried for 6 days by water extraction. This is followed by 2 days of watering and the active agent is applied in water. The concentration of the active agent was 50 mg/liter. After 4 days of water withdrawal and one week of recovery period, the number of surviving plants was recorded. The results are listed in Table 10.

Table 10

Active agent Survival (%)

Compound 2 25*

Compound 4 33*

Supervision 18

Results marked with * are significantly comparable to control, if P<0.05.

Water was deprived for 10 days for some groups of plants in the experiment. It was observed that almost every plant died. Each of the surviving plants had previously been treated with an active agent.

Example 11

Increasing bean tolerance to frost

Seaway bean seedlings were grown under normal conditions for the first two weeks, and then they were treated with a solution of the tested active agents 2 and 1 at a concentration of 10 mg/liter and 100 mg/liter before the start of the frost tolerance experiment. In the experiment, the plants were kept at -2°C for 8 hours, then they grew under normal conditions for 1 week, and the ratio of survivors was determined. 4 trays were used for each trial and 6 seeds were planted in each tray. The compounds in Table 11 significantly increase the survival ratio.

Table 11

Active agent Procedure Survival (%)

Compound 2 injection 40*

100 mg/l

Supervision spraying 25

Compound 2 irrigation 25*

10 mg/l

Connection 4 irrigation 40*

10 mg/l

Supervision of irrigation 18

Results marked with * are significantly comparable to control, if P<0.05.

Example 12

Increasing the cooling tolerance of corn in a room with temperature control

The experiment was carried out using the Mo 17 inbred line of maize. Before germination, the seeds were coated with a 2% solution of the test compound dissolved in 2 ml of polyvinyl alcohol, where the above amount of solution was applied to 100 seeds. The seeds were germinated for 3 days wrapped in moist filter paper, then planted and grown in a room with temperature control for 6 weeks. The temperature in the room was maintained between 18 and 12°C, with differences of 1°C. This was followed by recovery for one week at a temperature of 23/20°C.

In the experiment, the length of the plants was measured 16, 31 and 43 days after planting, and at the end of the experiment, the fresh weight of the plants was measured. The experiment was conducted on 4 plants at each temperature and each treatment. The results show an increased possibility of germination of the tested corn inbred line, and an increase in the early development of seedlings compared to the untreated control. The results of the experiment are summarized in Table 12.

Table 12

Enhancement of maize chilling tolerance in a temperature controlled room with Compounds 2, 5 and 6

________________________________________________________________________________

Monitoring Connection 2 Connection 5 Connection 6

Temp. time length weight length weight length weight length weight

°C (days) (cm) (g) (cm) (g) (cm) (g) (cm) (g)

18 16 12.9 - 13.2 - 15.0 - 14.6 -

31 22.0 - 28.4 - 28.4 - 25.0 -

43 35.0 5.3 37.0 6.0 38.0 6.2 39.0 7.6

17 16 13.1 - 17.0 - 19.7 - 17.8 -

31 22.9 - 27.7 - 31.2 - 29.9 -

43 36.0 4.8 36.5 5.5 373 6.6 44.3 9.7

16 16 10.2 - 15.2 - 15.4 - 12.4 -

31 20.6 - 24.8 - 26.8 - 26.4 -

43 33.1 4.2 32.3 4.5 34.5 5.0 42.3 7.7

15 16 9.2 - 10.0 - 10.2 - 9.5 -

31 15.0 - 17.7 - 21.3 - 22.2 -

43 21.2 2.0 28.5 3.6 32.3 4.4 34.0 5.4

14 16 5.2 - 7.6 - 9.7 - 5.8 -

31 10.8 - 15.4 - 17.2 - 11.6 -

43 20.3 1.6 25.9 2.7 25.1 2.9 20.3 1.3

13 16 5.0 - 6.0 - 7.4 - 4.7 -

31 10.8 - 10.1 - 13.1 - 10.0 -

43 17.2 1.0 16.0 1.0 23.8 2.1 18.5 1.1

12 16 5.4 - 5.0 - 5.8 - 4.5 -

31 8.7 - 7.9 - 11.3 - 10.9 -

43 17.8 0.9 18.9 1.2 20.1 1.5 25.5 2.0

The following examples show the results of field experiments, which were organized with early planting in order to determine the effect of the hydroxylamine derivative from the invention on the development and yield of plants in this case under natural conditions.

Example 13

Increasing the yield of soybeans when grown in the field

The experiment was carried out using Bólyi 44 soybeans. Before sowing, the seeds were treated with Rhyzobium Japonicum, a nitrogen-fixing bacterium that forms root nodules, providing 50-70% of the plant's nitrogen requirements.

The tested compounds were applied by seed beading; 1 ml of beading agent containing 1 mg of active agent in a 5% PVA solution was used for 100 seeds.

The plants were planted after preparing the soil in autumn, using a crop rotation system, 3-5 cm deep into the soil, with 40-50 cm row spacing, 5 cm plant spacing and 450,000-500,000 plants/ha density. The date of sowing was April 15, 1997. During the development of the plant, the usual procedures were followed and the usual pesticides were used. The harvest took place from September to October, with a grain water content between 16-18%. The results are listed in Table 13.

Table 13

Active agent Crop weight (kg/m3) Improvements compared to

supervision (%)

Supervision 0.45

Compound 6 0.52 15.5

Compound 5 0.50 11.1

Compound 2 0.55 22.2

Example 14

Increasing the yield of corn when grown in the field

Experiments were conducted on Mo 17 and AMO 406 lines. Before sowing, the seeds were coated with fungicides, insecticides and rodent control agents, and at the same time, the test compounds were applied in the form of a 2.5 mg/ml solution in a 2% PVA solution; 2 ml of solution was used for 100 seeds. Plants were sown after soil preparation in autumn, using a crop rotation system, 4-8 cm deep into the soil, with 45 cm row spacing, 30 cm plant spacing and 60,000-80,000 plants/ha density. Sowing date was April 15, 1997. During plant development, standard growing practices were followed and standard pesticides were applied. The harvest was done when the water content in the grains fell below 28%. At harvest, the weight of plants and crops is determined. The results are listed in Tables 14 and 15.

Table 14

Cultivation in the field of Mo 17 maize line

Active agent Crop weight (kg/m3) Relation to supervision

(Connection no.)

Supervision 1. 1.55 100% 0.09 100%

2. 1.42 100% 0.088 100%

6 1. 2.03 130.9% 0.101 112.2%

2. 2.0 140.8% 0.11 125%

5 1. 1.97 127% 0.109 121.1%

2. 0.093 105.6%

2 1. 1.85 119.3% 0.108 120%

2. 2.0 140.8% 0.111 126.1%

Table 15

Cultivation in the field of AMO 406 corn line

Active agent Crop weight (kg/m3) Relation to supervision

(Connection no.)

Supervision 1. 1.65 100% 0.097 100%

2. 1.13 100% 0.075 100%

6 1. 2.2 133.3% 0.115 118.5%

2. 1.75 154.8% 0.097 129.3%

5 1. 1.8 109% 0.1 103.0%

2. 1.8 159.2% 0.1 133.6%

2 1. 2.35 140.6% 0.16 164.9%

2. 1.25 110.6% 0.089 118.6%

Example 15

Leaf sprayer

The leaf sprayer is prepared with the following mixtures (weight ratios):

Compound 2 20

sodium lauryl sulfate 3

sodium lignin-sulfonate 6

water 63

kaolin 8

Example 16

Leaf sprayer

The leaf sprayer is prepared with the following mixtures (weight ratios):

Connection 4 20

alkyl-aryl-sulfonate 5

water 75

Example 17

Pearling agent

The pearling agent is prepared with the following mixtures (weight ratios):

Compound 3 0.25

2% polyvinyl alcohol solution 9.75

The pearlizing agent must be applied as an active agent in a quantity of 0.01-0.02 m/m% with respect to the weight of the seed.

Example 18

Granulate

The granulate is prepared with the following mixtures (weight ratios):

Connection 13 10

limestone powder 64

ethylene glycol 3

silicic acid

high dispersion 4

sodium ligninsulfonate 4

water 15

The mixture of ingredients must be crushed in a hammer mill until a particle size of 5 microns is reached.

Example 19

Powder preparation

The powder preparation is prepared with the following mixtures (weight ratios):

Compound 6 50

polyvinyl-pyrrolidone 10

silicon dioxide 25

Chinese loam (kaolin) 15

Example 20

Powder preparation

The powder preparation is prepared with the following mixtures (weight ratios):

Connection 1 50

calcium ligninsulfonate 5

isopropyl-naphthalene-sulfonate 1

silicon dioxide 4

filler (kaolin) 40

Claims (10)

1. Hydroxylamine derivatives of the general formula (I), where R1 represents a phenyl, N-heteroaryl, S-heteroaryl or naphthyl group which can be substituted with one or more halo, alkyl, alkoxy, haloalkyl or nitro, some unsubstituted or substituted phenylamino or alkylamino or lower alkoxy, X represents halo, preferably chloro or bromo, amino or an unsubstituted or substituted phenylamino group, or an amino substituted with one or two lower alkyl or a hydroxyl group, with the proviso that if R1 represents unsubstituted or substituted phenylamino, alkylamino or rosy alkoxy, then X cannot represent hello, Y represents hydrogen, hydroxy or acyloxy, preferably longer alkanoyloxy, or if Y represents hydroxy, the molecule may contain a dioxazine ring, closed at the carbon atom carrying the X group, formed by the usual XH elimination, R2 and R3 independently of each other represent hydrogen or a lower alkyl group ensuring that R2 and R3 cannot be hydrogen at the same time, R2 and R3 together with the neighboring nitrogen atom form a 5- to 7-membered saturated hetero ring, characterized by the fact that they are used to increase the tolerance of cultivated plants against time-related stresses. 2. A method for increasing the tolerance of cultivated plants against time-related stresses, indicated by the fact that it comprises treating the plant or its seed with a hydroxylamine derivative of the general formula (I), where R1, R2, R3, X and Y are as in Claim 1. 3. A method for increasing the tolerance of cultivated plants against cold and frost, characterized in that it comprises treating the plant or its seed with a hydroxylamine compound of the general formula (I), where R1, R2, R3, X and Y are as in Claim 1. 4. The method according to Claim 3, characterized in that it comprises treating the plant seed with an aqueous solution of a hydroxylamine derivative of the general formula (I), where R1, R2, R3, X and Y are as in Claim 1. 5. The method according to Claim 4, characterized in that it comprises soaking the plant seeds with an aqueous solution of a hydroxylamine derivative of the general formula (I), where R1, R2, R3, X and Y are as in Claim 1. 6. The method according to Claim 3, characterized in that it comprises coating the plant seed with a product containing a hydroxylamine derivative of the general formula (I), where R1, R2, R3, X and Y are as in Claim 1 and optionally other active agents and/ or auxiliaries to improve germination. 7. A method for increasing the tolerance of cultivated plants against cold, characterized in that it comprises spraying the plant with a solution containing a hydroxylamine derivative of the general formula (I), where R1, R2, R3, X and Y are as in the Claim as an active agent, before or when the cold season begins. 8. A method for increasing the tolerance of cultivated plants against drought, indicated by the fact that it comprises spraying the plant with a solution containing a hydroxylamine derivative of the general formula (I), where R1, R2, R3, X and Y are as in the Claim as an active agent, before or when the dry season begins. 9. A mixture for increasing the tolerance of cultivated plants against time-related stresses, characterized by the fact that it comprises as an active ingredient a hydroxylamine derivative of the general formula (I), where R1, R2, R3, X and Y are as in Claim 1. 10. The mixture from Claim 9, characterized by the fact that it also includes solid or liquid carriers and optional auxiliary substances suitable for use in agriculture.