AU748367B2

AU748367B2 - Use of hydroxylamine derivatives, and method and preparations for increasing the tolerance of field crops against weather stresses

Info

Publication number: AU748367B2
Application number: AU70703/98A
Authority: AU
Inventors: Mihaly Barabas; Tamas Berzy; Zita Csakai; Gabor Galiba; Andrea Jednakovits; Gabor Kocsy; Ede Marvanyos; Laszlo Stehly; Jeno Szilbereky; Magdolna Torok; Laszlo Urogdi
Original assignee: Biorex Kutato Fejleszto Kft
Current assignee: Biorex Kutato Fejleszto Kft
Priority date: 1997-04-22
Filing date: 1998-04-21
Publication date: 2002-06-06
Anticipated expiration: 2018-04-21
Also published as: HUP9702365A2; JP2002514216A; AU7070398A; HRP980217A2; AR012482A1; NZ500579A; ID20187A; WO1998047362A1; HU9702365D0; CA2288075A1; HUP9702365A3; CO5040008A1; EP1018876A1; IL132509A0; BR9808976A

Description

WO 98/47362 PCT/HU98/00039 Use of Hydroxylamine Derivatives, and Method and Preparations for Increasing the Tolerance of Field Crops against Weather Stresses TECHNICAL FIELD This invention relates to the use of hydroxylamine derivatives of general formula wherein

R

1 represents phenyl, N-heteroaryl, S-heteroaryl or a naphthyl group which may be substituted with one -or more halo, alkyl, alkoxy, haloalkyl or nitro, an 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 amino substituted with one or two lower alkyl or a hydroxy group provided that if R1 represents unsubstituted or substituted phenylamino, alkylamino or lower alkoxy, then X may not represent halo, 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 formal XH elimination,

R

2 and R 3 independently from each other, represent hydrogen or lower alkyl group provided that R 2 and R 3 may not represent hydrogen simultaneously,

R

2 and R 3 along with the adjacent nitrogen atom form a 5 to 7membered saturated hetero ring, and the method and preparation for increasing the tolerance of cultivated plants against weather condition stresses.

-2- BACKGROUND ART Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.

Damages to cultivated plants by weather stresses, such as cold, frost and drought cause significant losses for the agriculture. These factors, within this invention briefly referred to as weather stresses, may occur in any period of the growth or vegetation of the plant. Although they affect the plants in various ways and the plants react to them differently according to species and type, the effect is usually connected to the water 10 metabolism of the plants. The protection of plants against weather stresses is made more •difficult by the widely varied distribution of the time, strength and length of these stresses present at most agricultural regions.

In the present invention a temperature is considered cold if it is less than the o o, minimum temperature necessary for normal physiological functioning of the individuals 15 belonging to a given plant species or type, but greater than the freezing point of the water. Generally its effect may not be determined immediately by simple observation.

The damage caused by the cold appears later, after warming up, such as the decrease in plant growth, the withering or fading (chlorosis), or in the most severe cases, death of the plant.

The frost, i.e. the temperature below zero degree centigrade does not necessarily cause the plant to perish. After it is gone, the plant may be regenerated but the irreversible cell damages caused by the frost will strain its development, which will decrease its yield in the end.

2a- While the cold and the frost usually appears at an early stage of plant development and hence damages the germinating or developing plant, the drought damages the fully developed plant and endangers the further stage of development. Decreasing the evaporation level of "In OR 17AAI7 3 LI/U9Zn U UUUS9 the plant may render the reduction of the losses. For example there exists a method, when the surface of the plant is coated with a polymer film in order to physically limit the transpiration of the plant in the case of drought. For this purpose polyetoxylated polyoxypropylene copolymers described in the US Patent No. 4828602 are applied. The disadvantage of the method is that it requires a local application of the coating material, which may be done only by investing a great amount of manual labour. A durable transpiration inhibition is not desirable anyway; the system-effect transpiration inhibitors are more favourable with respect to plant physiology.

Thorough research related to the effects of the weather stresses on plants has been performed to reduce the damages of the cold, frost and drought, and a great number of scientific publications deal with the plant physiological relevance of cold, frost and drought tolerance.

Since plants react to these weather stresses very differently according to their botanical characteristics, a theoretically satisfactory explanation of the mechanism of the cold, frost and drought tolerance has not yet been given, and hence the methods developed for application in practice to improve the tolerance of plants against weather stresses are very diverse.

For example, it is known in the art that growth. regulating materials, which are compounds of hormonal activity, affect the cold, frost and drought tolerance of plants positively, and therefore they are applied for the treatment of cultivated plants. A typical example is abscisic acid, which is a growth regulating hormone. Abscisic acid itself is difficult to synthesise and hence it is not applied in agriculture.

However, materials analogous to abscisic acid chemically and in their effect are used, which have identical or stronger effect than the abscisic acid itself especially when combined with other compounds, which WO 98/47362 DPIT/IU TOQ /nnn0n WO 98/.7362 IDIt Ti I/A4OlUUU.J 4 ensures a synergetic increase in the effect. For example, the PCT publication WO No. 9608481 Al describes that plants are treated with epoxycyclohexane derivatives so as to make their development and yield more favourable and to increase their tolerance against cold and drought. Besides these compounds, brassidosteroids are also used as synergetic auxiliarys. The EP No. 327309 Al describes a compound that contains a poly-substituted cyclohexenyl-acetylene derivative as effective agent, and a diversely and multi-substituted phenyl-benzylurea derivative as synergetic auxiliary. With the help of this substance of hormonal activity, the tolerance of the plant against drought may be improved.

Compounds of hormonal activity are without any doubt significant, because they have an intense effect even when applied in small quantity, however their disadvantage is that they affect the metabolic processes taking place in the plants to a large extent, modify the hormnonal equlibrium of the plants, which may result in unpredictable physiological changes. Therefore such compounds and products must be applied with care in practice. Before application, it is essential to perform preliminary experiments related to a given plant species or type in order to determine the suitability and optimal application circumstances of the product in a given agricultural region, which limits their use in agricultural practice.

To avoid the above mentioned disadvantages of substances of hormonal activity, researchers turned to simpler, hormonally indifferent substances to find a suitable effective agent to improve the tolerance of plants against cold, frost and drought. According to the PCT publication WO No. 92/08350 Al tetrahydro-furfuryl-alcohol, tetrahydro-furfuryl-amine, or the combination of these compounds is applied to improve the tolerance of plants against cold. These effective agents WO 98/d73f2 ~T*rFn~mn r~~~?rr WO 98736..2 5 I/nl uysiuuuy lack the mentioned disadvantages of substances of hormonal activity, their production is easier, and hence they are more economical, but in view of the practice they are not favourable. This is because, according to the paper cited above, it is recommended to spray the plants more than once with the solution of the effective agent in order to achieve a satisfactory extent of regeneration of the cold-effected plants, and to repeat the treatment after the cold is gone, but the most expedient way is to spray the plants regularly. A treatment of the whole surface is considered important to ensure the contact of the effective agent on the entire surface of the plant. Therefore, thorough or repeated spraying is recommended. This requirement may be fulfilled only by investing a great amount of manual labour.

According to Hungarian Patent No. 181241, secondary or tertiary P-hydroxyethyl-amines or respective quaternary ammonium salts, preferably 2-hydroxy-ethyl-amines and trimethyl-p-hydroxy-ethylammonium-chloride (choline-chloride) and, in certain cases, combinations of these may be applied to improve the tolerance of plants against cold and frost. Primarily, the effective agent is applied to the plant by spraying. It may be concluded from the experimental section of the Patent that the effective agent is aimed at changing the phospholipid composition of the membrane of plant cells, and thus the fluidity. of the membrane. Hence the mentioned effective agents may be applied for the treatment of fully developed plants only. This was supported by the experimental results as well. The treatment of seedlings and seeds, which is mentioned in the Patent may not be effective with these effective agents since the plants lack the parts with the necessary membrane. An exception of is the choline-chloride, the application of which for treatment of seeds is known from the publication JP No.

62161701. In this case, however, the general growth regulating effect of -6the substance is utilised, as described in the above mentioned paper, and this effect causes among others the improved tolerance of the sprouting plant against cold.

However, the growth regulating substances of hormonal activity possess all of the disadvantages described above.

To sum up the above, we may conclude that several different attempts have been published in Patent literature aimed at improving the tolerance of cultivated plants against weather stresses. The effective agents and products of these Patents are, however, suitable for direct agricultural application only with the mentioned limiting conditions.

10 Our research was aimed at finding effective agents, which increase the cold, frost and drought tolerance of plants but are hormonally neutral, non-toxic, the limits of their application being the smallest possible, and which are suitable not only for the treatment of fully developed plants but also of seedlings and seeds, or at least overcome or 0 ameliorated at least one of the aforementioned disadvantages.

*o **00 15 DISCLOSURE OF INVENTION In accordance with a first aspect of the invention there is provided the use of hydroxylamine derivatives of general formula x R C Y R-

(I)

wherein R represents phenyl, N-heteroaryl, S-heteroaryl or a naphthyl group which may be substituted with one or more halo, alkyl, alkoxy, haloalkyl or nitro, an unsubstituted or substituted phenylamino or alkylamino or lower alkoxy, 6a X represents halo, preferably chloro or bromo, amino or an unsubstituted or substituted phenylamino group, or amino substituted with one or two lower alkyl or a hydroxy group provided that if R1 represents unsubstituted or substituted phenylamino, alkylamino or lower alkoxy, then X may not represent halo, 9 **o -7- 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 formal XH elimination,

R

2 and R 3 independently from each other, represent hydrogen or lower alkyl group provided that R 2 and R 3 may not represent hydrogen simultaneously, or

R

2 and R 3 together with the adjacent nitrogen atom form a 5 to 7membered saturated hetero ring, to increase the tolerance of cultivated plants against weather condition stresses.

These compounds act in an inductive manner, i.e. they increase the level of hardiness if the plant faces environmental stresses, as when the above mentioned weather stresses affect the plant. The inducted 15 metabolic processes result in an improved tolerance against cold, frost and drought.

Based on this observation, this invention relates to the use of 2 2 hydroxylamine derivatives of general formula where R 1 X, Y, R and 3 R are as above, for the improvement of the tolerance of cultivated S* 20 plants against weather stresses and a method of achieving that effect comprising treating the plant or its seed with such a derivative.

In general formula a lower alkyl group contains preferably 1-6 carbon atoms, most preferably 1-4 carbon atoms, and a lower alkoxy group contains 1-6, preferably 1-4 carbon atoms. In compounds of general formula where R 1 is a substituted phenyl or phenylamino group, the alkyl groups attached to the phenyl ring as substituents are preferably lower 1-6 carbon atom alkyl groups. The alkoxy substituents Sof the phenyl ring preferably contain 1-6 carbon atoms. The haloalkyl 0 substituents of the phenyl ring contain preferably alkyl, most preferably 125AUPOO.DOC -8-

C

1 6 alkyl. Most preferable haloalkyl substituent is the trifluoro-methyl group. IfR 1 represents alkylamino, it preferably contains at most 12 carbon atoms. If R 1 represents Nheteroaryl, it is preferably pyridyl or pyrazinyl group, while ifR 1 represents an Sheteroaryl group, it is preferably tienyl. Finally, ifY represents a long carbon chain alkanoyloxy, it preferably contains 12-20 carbon atoms.

In accordance with a second aspect, the invention provides a method for increasing the tolerance of cultivated plants against weather condition stresses, comprising treating the *3 plant or its seed with a hydroxylamine derivative of general formula where R 1

R

2

R

3 X and Y are as in the first aspect.

In accordance with a third aspect, the invention provides a method for increasing the tolerance of cultivated plants against cold and frost, comprising treating the seed of the .2 plant with a compound of general formula where R 2

R

3 X and Y are as in the first aspect.

In accordance with a fourth aspect, the invention provides a method for increasing 15 the tolerance of cultivated plants against cold, comprising spraying the plant with a solution containing a hydroxylamine derivative of general formula where R 2

R

3

X

and Y are as in the first aspect as active agent, before or when the cold season sets in.

In accordance with a fifth aspect, the invention provides a method for increasing the tolerance of cultivated plants against drought, comprising spraying the plant with a solution containing a hydroxylamine derivative of general formula where R 2

R

3 X and Y are as in the first aspect, as active agent, before or when the drought period sets in.

In accordance with a sixth aspect, the invention provides a composition for S increasing the tolerance of cultivated plants against weather stresses, comprising as active 3 ingredient a hydroxylamine derivative of general formula -8a-

R-C

C

N

Y Rwherein R 1 represents phenyl, N-heteroaryl, S-heteroaryl or a naphthyl group which may be substituted with one or more halo, alkyl, alkoxy, haloalkyl or nitro, X represents unsubstituted or substituted phenylamino group, or amino substituted with 5 one or two lower alkyl, Y represents hydrogen, hydroxy or acyloxy, or if Y represents hydroxy, the molecule may contain a dioxazine ring closed at the carbon atom carrying the X group formed by formal XH elimination, o2 3 R and R independently from each other, represent hydrogen or lower alkyl group 2 3 10 provided that R and R may not represent hydrogen simultaneously, 2 3 R and R along with the adjacent nitrogen atom form a 5 to 7-membered saturated hetero ring.

In accordance with a seventh aspect the invention provides hydroxylamine derivatives of the general formula (I)

X

N--CH -CH-CH--N

R

Swherein R' is phenyl which is unsubstituted or substituted with one or more selected from halo, alkyl, alkoxy, haloalkyl and nitro, from halo, alkyl, alkoxy, haloalkyl and nitro, 8b X is unsubstituted or substituted phenylamino, Y is hydrogen, hydroxy or acyloxy,

R

2 and R 3 independently from each other are H or lower alkyl provided that at least one of them is not hydrogen, or

R

2 and R 3 together with the nitrogen adjacent thereto, form a 5 to 7-membered saturated hetero ring, and the salts thereof.

In accordance with an eighth aspect, the invention provides N-{[3-(1,1-dimethylethyl)-amino] -2-hydroxy-propoxy} -N'-phenyl-benzamidine hydrochloride.

In accordance with a ninth aspect, the invention provides N-[3-(1-piperidinyl)propoxy]-N'-phenyl-benzamidine hydrochloride.

Unless the context clearly requires otherwise, throughout the description and the claims, the words 'comprise', 'comprising', and the like are to be construed in an o* S* inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense 15 of "including, but not limited to".

Some of the hydroxylamine derivatives of general formula are known compounds. Those compounds of general formula in which R 1 represents phenyl or pyridyl or naphtyl 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 the process of preparation of these compounds, as well as the different possibilities for synthesis. These compounds, as selective beta-blocking agents, may be applied in the therapy of angiopathy, primarily diabetic angiopathy. Those compounds of general formula in which R 1 represents phenyl or alkoxyphenyl or pyridyl or 'f naphtyl, X represents halo and Y is hydroxy, as well as their preparation are known from 8c Hungarian Patent No. 207.988. These compounds may also be applied in the therapy of angiopathy. Those compounds of general formula in which R 1 represents naphtyl or haloalkylphenyl, X is hydroxy and Y represents hydroxy, are known from published Hungarian Patent Application No. 2385/92. These compounds have antiischemic and antianginal effect, and hence may be applied particularly in the therapy of heart diseases.

Those compounds of general formula in which R 1 represents phenyl or phenyl group substituted by the above listed substituents or a pyridyl group, X represents halo and Y is S. a hydrogen atom, are known from the PCT publication WO No. 95/30649 Al. The same document describes the preparation of these compounds. These compounds have 10 antiischemic effect and hence may be applied in the therapy of diabetic angiopathy.

Furthermore, those compounds of

S

55

•.S

WO 98/47162 ~FTl/T'/TTr /ArtAn r 9 general formula are also known, in which R 1 represents phenylamino which is unsubstituted or substituted with alkyl, alkoxy, halo, haloalkyl or nitro, or an alkoxy or alkylamino group, X represents hydroxy and Y is hydrogen, hydroxy or alkanoyloxy. Their description may be found in the PCT publication WO No. 97/00251, which describes the preparation of these compounds as well. These compounds have antiischemic effect and hence may be applied in the therapy of heart and blood vessel diseases. Note that in the known compounds R 2 and R 3 represent the same as defined above, and therefore these two substituents are not described in detail.

It should also be noted that in certain compounds of general formula tautomery may occur, i.e. they may appear in a tautomeric structure different from but corresponding to the formula In particular, this is the case when compounds of general formula (I) contain a hydroxy group as X, where the tautomeric version containing a molecule part not appearing in the structural formula is more stable.

The remaining compounds of general formula form the subject matter of our pendin patent application.

New compounds are those hydroxylamine derivatives of general formula in which X represents halo, Y is hydroxy, and R. represents a group that is different from the ones described in the above mentioned Hungarian Patent No. 207.988 dealing with these kinds of compounds, for example phenyl substituted with alkyl, haloalkyl or nitro. These substances are prepared analogously to the cited description by diazotating the corresponding compound containing a NH2 group in the place of X. The necessary starting amino compounds are produced also by known method, by the coupling reaction of the corresponding amidoxime and a 3-amino-2-propanol derivative, for WO 98/473f2 f Tr T I rrvvfrr if\flr\- 0 rLi/IUVjIU/UU3y example according to the method described in the Hungarian Patent No. 177.578.

N-substituted amidoximes of general formula where R 1 represents an aromatic group and X represents a substituted amino group, are also novel compounds, and may be produced by the coupling reaction of a suitable imidoyl-halide of general formula wherein Hal represents a halo and R 1 is as above, while R' is the substituent of the amino group of X, and a 1-amino-3-aminooxypropane derivative of general formula where R 2

R

3 and Y are as above. The reactions should be performed in a neutral solvent, for example in chlorinated hydrocarbon, at room temperature and after extraction separation, the product is isolated as a salt with a suitable organic or inorganic acid.

Other novel compounds of general formula are N-hydroxyguanidine derivatives in which both R1 and X are substituted nitrogen atoms. These derivatives are produced by the acylation of a suitable aminooxy compound of general formula if the acylating agent is haloformamidine of general formula where Hal represents halogen,

R

1 is as above, and R' and R" are substituents of the amino group appearing as X in the product. The reaction is performed in a two phase system, in the mixture of some organic solvent not mixable.with, water and a aqueous base, preferably aqueous sodium-carbonate solution.

The product is isolated in this case also by extraction separation and, if possible, by salt-formation.

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

W OQ/A4736'2 11 PCT/HU98/00039UUUJY As acylating agent, acid halides, active esters or other usual reagents applicable for O-acylation may be used. The reactions can be performed in a neutral solvent, usually at room temperature and if necessary in the presence of a suitable acid-binding agent, such as an organic or inorganic base, for example triethylamine or solid sodiumcarbonate. For acylating agent, the acid chlorides are preferable, where the compound itself may behave as acid-binding agent, and hence usually the product may be easily isolated in the form of hydrochloride by simple ethereal crystallisation after evaporation. When using less reactive acylating agents, Schotten-Baumann acylation may also be applied. The products are generally isolated in the form of their salt with a organic or an inorganic acid.

With respect to the application of the invention, most preferable compounds were the following ones of general formula N-[2-hydroxy-3-(1-piperidinyl)propoxy]-benzimidoyl-chloride hydrochloride (Compound 1) N-[2-hydroxy-3-(1,1 -dimethylethyl-amino)propoxy]-3-trifluoromethylbenzamide monohydrochloride (Compound 2) N-[2-palmitoyloxy-3-(1-piperininyl)propoxy]-3-pyridinecarboximidamide monohydrochloride (Compound 3) -piperidinyl)propoxy]-3-nitro-benzimidoyl-chloride monohydrochloride (Compound 4) N-[2-hydroxy-3-(1-piperidinyl)propoxy]-2-nitro-benzimidoyl-chloride monohydrochloride (Compound -dimethylethyl)-amino]-2-hydroxypropoxy]-N'-phenylbenzamidine hydrochloride (Compound 6) N-N'-dimethyl-N'-phenyl-N"-[3-( 1 -piperidinyl)propoxy]-guanidine hydrochloride (Compound 7) Wn O/A716 12 PCrT/HU98/00039 -piperidinyl)propoxy]-pirazine-carboximidoylchloride monohydrochloride (Compound 8) 3-(3-piridyl)-5-diethylaminomethyl-5,6-dihydro- 1,4,2-dioxazine hydrochloride (Compound 9) N-[2-hydroxy-3-(1-piperidinyl)propoxy]- 1-naphtalene-carboxamide (Compound N-[2-hydroxy-3-(l-piperidinyl)propoxy]-ethylurethane (Compound 11) N-hexyl-N'-[2-hydroxy-3-( -piperidinyl)propoxy]-urea (Compound 12) N,N-dimethyl-N'-phenyl-N"-[2-hydroxy-3-( 1 -piperidinyl)propoxy]guanidine hydrochloride (Compound 13) -piperidinyl)propoxy]-tiophene-2-carboximidoylchloride hydrochloride (Compound 14) -piperidinyl)propoxy]-N'-phenyl-benzamidine hydrochloride (Compound Compounds of general formula are favourable with respect to application in the cultivation of plants because they are suitable for treating both the fully developed plant and the seed or the seedling.

These compounds may be applied to the plants using any of the usual procedures widely used in plant-protection.

Based on the above, the invention relates to a procedure to increase the tolerance of cultivated plants against weather stresses.

According to the invention, the protected plant or its seed is treated with a hydroxylamine derivative of general formula where R 1 X, Y,

R

2 and R 3 are as above. Preferably an aqueous solution of the compound of general formula is used for the treatment, but alternatively a preparation containing the usual carriers and the hydroxylamine derivative of general formula as effective agent may be applied.

The dose and the concentration of the effective agent of general formula is dependent on the protected plant species or type and on WO 98/47362 WO 9.7362 13 CTl/U98/IUO39 the method of the application.

If the procedure according to the invention is aimed at improving the tolerance of the plant against cold and frost, preferably the seed of the plant should be treated with a hydroxylamine derivative of general formula where 1 X, Y, R 2 and R 3 are as above. The seed of the plant must be covered with the proper product containing the active agent and suitable for coating, preferably pearled, in certain cases dressed, or the aqueous solution of the effective agent may simply be used.

The preferable method is to soak the seed of the plant in an aqueous solution of a compound of general formula For this purpose a 1-200 mg/1 concentration of the compound of general formula in aqueous solution is prepared.

The procedure according to the invention may be performed by coating the seed of the plant with a solution containing a hydroxylamine derivative of general formula The compounds of general formula may be combined with dressing agents in certain cases.

For the coating of the seeds preferably pearling agents are applied, which contain compounds of general formula in a concentration of 0.1-10 g/1 along with the usual pearling and auxiliary materials. The pearling agents may contain other effective agents beside the mentioned effective agent as well, such as fungicides or additives promoting germination, for example microelements. The pearling agent is applied in a small volume. For example, when treating bean, soybean or maize seeds, only 1 ml or less amount of pearling agent is used for 100 seeds, which is dried on the seeds uniformly while constantly stirring.

Furthermore, this invention relates to a procedure for improving the tolerance of cultivated plants against cold, where the plant is WO 98/47362 14 PCT/HU98/00039 sprayed before or at the time when the cold season sets in with a spray preparation containing a hydroxylamine derivative of general formula (I) as effective agent.

The spraying is performed with a 1-500 mg/litre concentration aqueous solution of the effective agent, which may occasionally contain spraying auxiliary materials, such as surface active material (detergent). In certain cases, compounds of general formula may be combined and sprayed to the plant to be protected with other effective agents such as fungicides.

The spraying is to be performed at the beginning of the period hazardous in terms of cold temperature. If more than one period is to be taken into consideration, then 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 when the dry season sets in with a spray preparation containing a hydroxylamine derivative of general formula as effective agent.

The spraying is performed 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 risk of drought. In every case, the characteristics of the given plant species or type determine the applicable quantity of the active agent. If more than one drought period is to be taken into consideration, then the spraying must be repeated at the beginning of each such period.

For the above listed treatments, a simple aqueous solution of the hydroxylamine derivatives of general formula but preferably such preparations are used which contain proper auxiliary materials beside the active agent, for improving the spraying, distribution and the absorption of the active agent.

Wn OQ/A'714') PCT/HU98/00039 The composition of the invention for improving the tolerance of cultivated plants against weather stresses contains 0.001-95 m/m% hydroxylamine derivative of general formula in which R 1 X, Y, R 2 and R 3 are as above, beside the solid or liquid carriers and possible s auxiliary materials suitable for agricultural application.

The composition preferably contains water as liquid vehicle agent. The aqueous solution of the active agent is a concentrate, which should be diluted before application in order to prepare the proper concentration mentioned above. Preferably, the aqueous solutions contain surfactants, those solutions for treating the seed contain dressing and pearling auxiliary materials, such as film forming materials. The sprays contain an adhesion improving agent, a substance to improve spreading, light protecting agent, if required, a stabilising agent and other additives beside the detergents. For spraying purposes ULV concentrates, emulsifiable concentrates, hydrophyl powders, soluble granulates or microgranulates dilutable with water may be applied. These products contain anionic or non-anionic detergents in order to help the dilution with water. The solid products may contain kaolin, diatomite or dolomite as vehicle, but may also contain any other solid vehicle agent widely applied in such products. Preferably, perlite is used as vehicle agent for the production of microgranulate.

The compositions of the invention may be combined or simultaneously applied with other pesticides, if the active agent of the latter is compatible with the active agent of the composition of the invention. In these cases, the spraying of the composition of the invention does not require a separate process, it can be performed along with the usual pesticide treatment of the cultivated plants.

wn oQi/47A6 16 PCT/HU9U8/0003 BEST MADE OF CARRYING OUT THE INVENTION The invention is demonstrated by the following examples without limiting the scope of the invention.

Example 1: N-[2-palmitoyloxy-3-( -piperidinyl)propoxy]-3pyridinecarboximidamide monohydrochloride (Compound 3) 14.7 g (52.8 mmol) of N-[2-hydroxy-3-(1-piperidinyl) propoxy]-3pyridine-carboximidamide is dissolved in 160 ml of chloroform. 7.7 ml mmol) of triethylamine is added, followed by the dropwise addition of a solution of palmitoyl chloride (14.7 g; 56.5 mmol) in 85 ml of chloroform. The mixture is stirred overnight at room temperature. The next day, a further 3.8 ml of triethylamine and 7.4 g of palmitoylchloride are added, and the stirring is continued for one more day. Then the solution is extracted with water, 5 V/V% acetic acid and water, successively, dried over anhydrous sodium sulphate, and evaporated to dryness.

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

Yield: 10.9 g (37%) Mp.: 110-113 °C Example 2: N-[2-hydroxy-3-( 1-piperidinyl)propoxy]-2'-nitrobenzenecarboximidoyl chloride monohydrochloride (Compound Wn OR/'7'i 17 r/PCTIU9/0U039 g (16.7 mmol) of N-[2-hydroxy-3-(1-piperidinyl) propoxyj-2'nitro-benzene-carboximidamide monohydrochloride is dissolved in 21 ml of water, then 48 ml of concentrated hydrochloric acid is added. The solution is cooled to -5 OC, then a cold solution of 2.1 g (33.3 mmol) of sodium nitrite in 9 ml of water is added dropwise. Throughout the reaction the internal temperature is maintained at 0°C. When the addition is completed, the mixture is stirred for a further four hours and cooled overnight. The product is filtered off, washed with cold water and dried.

Yield: 3.9 g Mp.: 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, 914, 852, 793, 756, 708, 577 cm- 1 Example 3 -dimethylethyl)-amino]-2-hydroxypropoxy]-N'-phenylbenzamidine hydrochloride (Compound 6) 4 g (24.7 mmol) of benzanilide-imide-chloride is dissolved in ml of chloroform. Then 5.32 g (24.7 mmol) of 1-aminooxy-3-[(1,1dimethyl-ethyl)-amino]-2-hydroxy-propane dissolved in 45 ml of chloroform is added dropwise to the resulting solution. The reaction mixture is stirred at room temperature for 3 hours, and then washed with 25 ml of 1 M aqueous sodium-carbonate solution. The chloroform phase is dried over sodium-sulphate, filtered and evaporated. The evaporation residue is cristallysed with hexane. The resulting base is dissolved in (5.33 g) 50 ml of ethyl-acetate and then 3.35 ml of 3.67 N hydrochloric acid/ethyl-acetate is added. The isolated crystals are WO98/ Q94d7 18 PCT/HU98/00039 filtered off, washed with ethyl-acetate and dried.

Yield: 2.97 g 140-143 °C IH-NMR (solvent: CDCla; reference: CDC1 3 9.7 (m,lH) and 8.1 (m,1H,NH 2 7.8 (s,1H,NH-O); 6.7-7.4 (m,10H,2xPh); 5.7 (d,lH,OH); (m,lH,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) ml of 1 M aqueous sodium-carbonate solution is added to 1,040 g (6.5 mmol) of l-aminooxy- 3 -(l-piperidinyl)propane dissolved in ml of ether. While intensely stirring, 1200 ml (6.5 mmol) of N,Ndimethyl-N'-phenyl-chloroformamidine dissolved in 10 ml of ether is added. After 2 hours of stirring, further 20 mg (0.1 mmol) of N,Ndimethyl-N'-phenyl-chloroformamidine is added. After further 3 hours of stirring, the phases are separated and the ethereal phase is dried over sodium-sulphate, filtered and evaporated. The residue (1700 mg of yellow oil) is dissolved in 10 ml of ethyl acetate. 10.5 ml of 0.54 M hydrochloric acid/ethyl-acetate is added, and then the product is cooled and the isolated crystals are filtered off. The raw.product is crystallised from methanol-ether mixture to give 847 mg of white crystalline material.

Yield: 847 mg 138-139 °C (methanol-ether) 'H-NMR (solvent: CDCl 3 reference: CDCl 3 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,OCH 2 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).

WO 98/47362 PCT/HU98/00039 The product crystallised from isopropanol melts at 213-216 0

C.

Example -piperidinyl)propoxy]-N'-phenyl-benzamidine hydrochloride (Compound 0.8 g (5 mmol) of 1-aminooxy- 3 -(l-piperidinyl)propane is dissolved in 7.5 ml of chloroform. 1.08 g (5 mmol) of benzanilide-imidechloride dissolved in 7.5 ml of chloroform is added dropwise and then the reaction mixture is stirred for 3 hours. Then it is washed with two times 10 ml of water, and the chloroform phase is dried over sodiumsulphate, filtered and evaporated. The evaporation residue is dissolved in 20 ml of 2 N aqueous sodium-hydroxide solution and the solution is extracted with 20 ml of ethyl-acetate. The ethyl-acetate phase is dried over sodium-sulphate and filtered, and then 0.8 ml of 3.45 M hydrochloric acid/ethyl acetate is added. The isolated precipitate is filtered and dried.

Yield: 0.8 g 164-166 °C (crystallised from ethyl-acetate)

C

13 -NMR (solvent: CDC13; reference: CDC1 3 157.55 (C-amidine); 135.75 (N-Ph-ipso); 132.84 (C-Ph-ipso); 128.95 128.84 (C-Ph- 126.66 125.34 124.0 74.02 (O.CH2); 54.20 (NCH 2 53.30 (2.6 piperidine); 23.19 (CH 2 22.63 piperidine); 21.76 (4 piperidine).

Example 6 N,N-dimethyl-N'-phenyl-N"-[2-hydroxy-3-(1-piperidinyl)propoxy]guanidine hydrochloride (Compound 13) WOn ORI/471 ~rrm rrrl r~rr r~llnl rL II'IUYV/UUU3Y 1,150 mg (6.58 mmol) 1-aminooxy-2-hydroxy-3-(1-piperidinyl)propane] is dissolved in 20 ml of ether and to this solution 20 ml of 1 M sodium carbonate solution is added, then 1,206 mg (6.58 mmol) of N,Ndimethyl-N'-phenyl-chloroformamidine dissolved in 10 ml of ether is added. After two hours, 22 mg (0.11 mmol) of N,N-dimethyl-N'-phenylchloroformamidine is also added to the reaction mixture. After stirring for further 3 hours, the layers are separated, the ether layer is dried over sodium-sulphate, filtered and evaporated. The residual 1,800 mg of yellow oil is taken in 10 ml of 'ethyl acetate, and to this solution 10.46 ml of 0.54 M HCl/ethyl acetate is added, cooled and the yellow crystals are filtered off. Impurities are removed by recrystallization first in acetone, then in ethyl acetate.

Yield: 674 mg pale yellow powder. Mp.: 127-129 °C (ethyl acetate) 1 H-NMR (solvent: CDCl3; reference: CDCl3 7.1-7.4 5,9 (m,1H,OH); 4.6 (m,lH,CH); 4,1 (m,2H,OCH2); 3.6 (m,4H,2-6 piperidine); 3.4 3.2 (m,1H,NH); 1.8 (m,4H,3-5 piperidine); 1.4 (m,2H,4 piperidine) Example 7 Increasing chilling tolerance by treating seeds In this experiment the tolerance of maize, soybean and pepper seeds treated with the active agent against cold was tested. This test imposed temperature and oxygen deficiency stresses on the seeds and was carried out according to Barla-Szab6 and Dolinka CSVT (Complex Stressing Vigour Test). For a single test, two hundred seeds were soaked for 48 hours at 25°C and another 48 hours at 5°C in 150 ml distilled water containing the active agent in 10 mg/l concentration.

WO oiTIt'lf 21 P'CT/HU98/00039 Following the 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 into containers and covered with a plastic bag in order to reduce evaporation. During the whole procedure the seeds were kept in darkness.

At the end of the experiment the number of normally developing and ungerminated seeds were recorded. The length of the 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 to be of high vigour, and low vigour seedlings were shorter than this length.

In experiments with maize, it was found that the tested active agents did not influence the germination and development of the Mo 17 inbred maize line germinated in optimal circumstances, at 25°C. Under the circumstances of the CSVT test, however, they proved to be effective, as it is shown in Table 1.

Table 1. Active agent Ratio of high vigour plants Compound 1 38* Compound 2 29* Compound 9 33* Compound 11 24 Compound 3 47* Compound 12 23* Compound 4 28* Compound 5 32* Compound 6 Compound 7 36* Control 19 WO 98/47362 PrC n 0039nnn 22 /IL UOIVUUU.

Results marked with are significant compared to the control, if P<0.05.

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

Table 2.

Active agent Ratio of high vigour plants Compound 2 49* Compound 10 52* Compound 4 Compound 6 57* Compound 13 56* Compound 14 Compound 15 53* Control 33 Results marked with are significant compared to the control, if P<0.05.

In the case of a further experiment with maize of low chilling tolerance (LT) and high chilling tolerance (HT) populations [Ref: P.

Landi, E. Frascaroli, A. Lovato; EUPHYTICA 64 21-29 (1992)], the following positive effects were found (Table WO 98/47362 PCT[HU98/00039 Active agent Compound 2 Compound 3 Compound 4 Compound 5 Control Table 3.

Ratio of high vigour

HT

98* 92* 94* 96* 84 plants

LT

94* 86* 88* 92* 74 Results marked with are significant compared to the control, if P<0.05.

Experiments with McCall soybeans also showed that the active agents have no effect on the germination and development of the plants under normal conditions. When applying the CSVT test, the following results were obtained (Table Table 4.

Active agent Compound 2 Compound 4 Compound 8 Control Ratio of high vigour plants 43* 46* 47* 38 Results marked with are significant compared to the control, if.

It was further observed that Compound 8 decreased the number of ungerminating seeds by 50% (control: 33%, treated: 17%, significant at P<0.05).

WO 98/47362 ~~lm rn lmn r~nn? n WO. 24 r.II IUVY IUU 3Y Experiments with green peppers showed similarly that the active agents have no effect under normal circumstances, do not influence the germination of the seeds and the development of the plants kept at Under the circumstances of the CSVT test, they increased the length of the sprouts and the roots along with the proportion of the high vigour seedlings. The ratio of the ungerminating seeds decreased by 30% on average due to the treatment with the active agents. The results are demonstrated in Table Table Active agent Ratio of high vigour plants Compound 2 47* Compound 4 Control 36 Results marked with are significant compared to the control, if P<0.05.

In order to make the results more comprehensible, it should be noted that the CSVT procedure is developed to predict the expected minimal ratio of sprouting seeds under environmental stresses. In a given set of seeds, the ratio of those seeds that safely sprout and properly germinate in cold spring weather is 90% for seeds which proved to be of high vigour in the CSVT test, while the ratio of those seeds which safely sprout and properly germinate in cold spring weather is only 60% for seeds that proved to be of low vigour in the test. Hence, if an active agent improves the vigour of the seedlings, it in the end improves the sprouting ratio under open field conditions in the case of ground temperature colder than optimal.

WO Q/ld7362 1'11U92Ir/u/UJ9 The above experiments prove that the compounds of general formula are able to improve the vigour of the seedlings and hence improve the chance of sprouting, if unexpectable weather stresses occur after the sowing.

Example 8 Pearling of soybean seeds Soybean seeds are treated with a pearling agent, which contains 1 mg/ml of N-[3-(1-piperidinyl)propoxy]- 3 -nitro-benzimidoyl-chloride monohydrochloride (Compound 4) in a 5% aqueous polyvinylalcohol solution. 100 seeds and 1 ml of pearling agent are filled into a glass vessel and while the vessel is rotated, the seeds are coated with the agent and then it is left to dry. For seeds treated this way, we obtained .the following results when placed under the conditions of the CSVT test described in Example 7.

Table 6.

Treatment Ratio of high vigour plants sprout root untreated control 47 pearled with PVA 52 49 pearled with PVA and 63* 58* Compound 4 Results marked with are significant compared to the control, if P<0.05.

Wn ORIA/471 Rr-r~rr rrr~~ rn 26 VL IJLLnIUUU3Y PVA slightly increased the ratio of high vigour plants. The PVA solution containing Compound 4 proved to be such a pearling agent which was able to increase the ratio of high vigour plants significantly under the experimental conditions, increasing the length of both the sprouts and the roots.

In a further CSVT experiment also using McCall soybeans, polyvinylalcohol (PVA) was applied for pearling the seeds. The 2.5 mg doses of the active agents were dissolved in 1 ml of 2.5% PVA solution, and this quantity was applied to 100 pieces of seeds. The improvement of the chilling tolerance is observed by the significant elongation of the germ and the roots. The results are demonstrated in Table 7.

Table 7.

Active agent Relative length (control= 100) germ root Compound 2 106 128 Compound 9 110 131 Compound 3 133 150 Compound 5 116 135 Compound 6 127 152 The experiments show clearly that, according to the results of the vigour test, the chances of sprouting of the plants increased after pearling with the active agent.

WO 98/47362 ID"T' rvi Tn 0 /nnrkI n 27 IllJ I Example 9 Increasing the drought tolerance of beans Based on the experiences of our preliminary experiments, the plants were hardened before the application of the active agent; by withholding the water for a few days, until the first signs of withering appeared. Then the plants were watered and the active agent was either dissolved in the water, or sprayed to the plants directly. Afterwards, the plants were subjected to different periods of drought according to the given experiment, watered again, and after a week-long regeneration period, the survival ratio was determined.

a) Seaway bean cultivar was hardened for 5 days by withholding the water. Afterwards the plantlets were watered for two days normally. During this time, a 10 mg/litre and 100 mg/litre concentration solution of the active agent was applied two times a day dissolved in water or by direct spraying. Then the water was withheld for 7 days, and after a week-long regeneration period, the survival ratio was determined. The results are summarised in Table 8.

Table 8 Active agent Watering (lOmg/l) Watering (100mg/1) Spraying (100mg/1) survival Control 17 17 0 Compound 2 30* 41* 71* Compound 6 25* 36* WO 98/47362 ID/-T'r Tn0 nn'n 28 I.U7OIUUJ 7 Results marked with are significant compared to the control, if P<0.05.

b) In this experiment, bean plants (cv. Seaway) were hardened for 7 days instead of the 5 days described in Part a. Then a 10 mg/litre and 100 mg/litre concentration solution of the active agent was applied two times a day for two days. Then 7 days without water followed, and after a week-long regeneration period, the results of the experiment were evaluated. The results are summarised in Table 9.

Table 9.

Active agent Survival Compound 2 14* Compound 4 39* Control 0 Results marked with are significant compared to the control, if P<0.05.

Example Increasing the drought tolerance of soybeans Soybeans of soybean cv. B61yi 44 were hardened for 6 days by withholding the water. This was followed by two days of watering, and the active agent was applied in the water. The concentration of the solution of the active agent was 50 mg/litre. After a 4-day-long cease of watering and a one week regeneration period, the number of surviving plants was recorded. The results are listed in Table WO 9S/47362 'T'/iT I oInno WO 98 -7362 Sr.1XT1h Tito Infaffl2a 29 17 r IuooUvuJ.

Table Active agent Survival Compound 2 Compound 4 33* Control 18 Results marked with are significant compared to the control, if P<0.05.

Watering was ceased for 10 days for a certain group of plants in the experiment. It was observed that almost every plant perished. Each of the 4 surviving plants had previously been treated with the active agent.

Example 11 Increasing the frost tolerance of beans Seedlings of bean cv. Seaway were cultivated under normal conditions for the first two weeks, then they were treated with mg/litre and 100 mg/litre concentration solutions of the examined active agents 2 and 1 days before the initiation of the frost tolerance experiments. In the experiment, the plants were kept at -2 0 C for 8 hours, then grew under normal conditions for 1 week, and the survival ratio was determined. 4 trays were used for each experiment and 6 seeds were planted in each tray. The compounds in Table 11. significantly increased the survival ratio.

WO 98/47362 Table 11.

PCTHU98/00039 Active agent Compound 2 Control Compound 2 Compound 4 Control Results marked Treatment Survival spraying, 100 mg/i spraying watering, 10 mg/i watering, 10 mg/i watering 18 with are significant compared to the control, if P<0.05.

Example 12 Increasing the chilling tolerance of maize in a gradient chamber The experiment was performed using the Mo 17 maize inbred line. The seeds were coated with a 2% solution of the examined compound dissolved in 2 ml polyvinylalcohol before germination, where the above quantity of solution is applied for 100 seeds. The seeds were germinated for 3 days wrapped in wet filter paper, they were sown and then cultivated in gradient chamber for 6 weeks. In the gradient chamber, the temperature was maintained on a scale between 18 and 12'C, with differences of 1IC. This was followed by a one week regeneration at 23/20'C temperature.

In the experiment, the length of the plants was measured 16, 31 and 43 days after the sowing, and at the end of the experiment the fresh weight of the plants was measured. The experiment was performed on 4 plants at each temperature and by each treatment. The results demonstrate the increased germination potential of the examined maize inbred line, and the imrovement of the early development of WO 98/47362 TT^^m rnnr rrn v 31 PCIU9Y00UU3Y the seedlings compared to the untreated control. The experimental results are summarized in Table 12.

Table 12.

Increasing the chilling tolerance of maize in gradient chamber with Compounds 2, 5 and 6 Control Length (cm) Compound 2 Compound 5 Compound 6 Temp. Time (days)

FW

(g) Length (cm) 18 °C 16 31 43 17 °C 16 31 43 16 °C 16 31 43 °C 16 31 43 14 °C 16 31 43 13 °C 16 31 43 12 °C 16 31 43 12.9 22.0 35.0 13.1 22.9 36.0 10.2 20.6 33.1 9.2 15.0 21.2 5.2 10.8 20.3 5.0 10.8 17.2 5.4 8.7 17.8 13.2 28.4 5.3 37.0 17.0 27.7 4.8 36.5 15.2 24.8 4.2 32.3 10.0 17.7 2.0 28.5 7.6 15.4 1.6 25.9 6.0 10.1 1.0 16.0 5.0 S 7.9 0.9 18.9 FW Length (cm) 15.0 28.4 6.0 38.0 19.7 31.2 5.5 37.3 15.4 26.8 4.5 34.5 10.2 21.3 3.6 32.3 9.7 17.2 2.7 25.1 7.4 13.1 1.0 23.8 5.8 11.3 1.2 20.1 FW Length (cm) S 14.6 25.0 6.2 39.0 S 17.8 29.9 6.6 44.3 12.4 26.4 5.0 42.3 22.2 4.4 34.0 5.8 11.6 2.9 20.3 4.7 10.0 2.1 18.5 10.9 1.5 25.5

FW

(g) 7.6 9.7 7.7 5.4 1.3 1.1 WO 98/47362 D r'1'irmo mnn n WO 98.473 .32 f'I I sr/ ,lduuuj In the following examples, results of field experiments are shown, which were arranged with early sowing in order to determine the effect of the hydroxylamine derivatives of the invention on the development and yield of the plants in this case under natural conditions.

Example 13 Increasing the yield of field soybean cultivation The experiment was performed using soybean cv. B61lyi 44. Before sowing, the seeds were treated with Rhyzobium Japonicum nitrogenbinding bacterium, which forms a root nodule providing 50-70% of the nitrogen demand of the plant.

The examined compounds were applied by pearling the seeds; 1 ml of pearling agent containing 1 mg of active agent in a 5% aqueous PVA solution was used for 100 seeds.

The plants were sown after soil preparation in the autumn, using a crop rotation system, 3-5 cm deep in the ground, with a 45-50 cm row distance, a 5 cm plant distance and 450,000-500,000 plant/ha density. The date of sowing was April 15, 1997. During the development of the plant, the usual cultivation procedures were followed and the usual pesticides were used. The harvest took place in September October, with the water content of the grains being between 16-18%.

The results are listed in Table 13.

WO 98/47362 ID' r lr n 33 lln~blIU U,, Table 13.

Active agent Weight of the crop (kg/m 2 Improvement compared to the control Control 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 maize in field cultivation The experiments were perfomed on the Mo 17 and AMO 406 lines. Before sowing, the seeds were dressed with fungicides, insecticides and rodent-control agents, and, at the same time, the tested compounds were applied in the form of a 2.5 mg/ml concentration solution in a 2% PVA solution; 2 ml of solution was used for 100 seeds.

The plants were sown after soil preparation in the autumn, using a crop rotation system, 4-8 cm deep in the ground, with a 45 cm row distance, a 30 cm plant distance and 60,000-80,000 plant/ha density.

The date of the sowing was April 15, 1997. During the development of the plant, the usual cultivation procedures were followed, and the usual pesticides were applied. Harvest took place when the water content of the grains decreased below 28%. At harvest, the weight of the plants and of the crop were determined. The results are listed in Table 14. and WO 98/47362 34 PCT/HU98/00039 Table 14.

Field cultivation of the Mo 17 maize line Active agent (Compound No.) Control 1st 2nd 6 1st 2nd 1st 2nd 2 1st 2nd Weight of the crop (kg/m 2 Ratio to the control 1.55 1.42 2.03 2.0 1.97 1.85 2.0 100% 100% 130.9% 140.8% 127% 119.3% 140.8% 0.09 0.088 0.101 0.11 0.109 0.093 0.108 0.111 100% 100% 112.2% 125% 121.1% 105.6% 120% 126.1% Table Field cultivation of the AMO 406 maize line Active agent (Compound No.) Control 1st 2nd 6 1st 2nd 1st 2nd 2 1st 2nd Weight of the crop (kg/m 2 Ratio to the control 1.65 1.13 2.2 1.75 1.8 1.8 2.35 1.25 100% 100% 133.3% 154.8% 109% 159.2% 140.6% 110.6% 0.097 0.075 0.115 0.097 0.1 0.1 0.16 0.089 100% 100%.

118.5% 129.3% 103.0% 133.3.6% 164.9% 118.6% WO 98/47362 'FRlT/lTT, n IIIeUYIU r •i.I UUY l Example Foliar spray The foliar spray is prepared with the following composition (proportions by weight): Compound 2 sodium-lauryl-sulphate sodium-lignine-sulphonate water kaolin Example 16 Foliar spray Foliar spray is prepared with the following composition (proportions by weight): Compound 4 alkyl-aryl-sulphonate water Example 17 Pearling agent Pearling agent is prepared (proportions by weight): Compound 3 2 aqueous solution of polyvinylalcohol with the following composition 0.25 9.75 WO 98/47362 'P /H.iT'l O ni n 36 ,'lsnu ,osuuuJ The pearling agent must be applied as active agent in a quantity of 0.01-0.02 m/m% with respect to the weight of the seed.

Example 18 Granulate Granulate is prepared with the following composition (proportions by weight): Compound 13 limestone-powder 64 ethylene-glykol 3 high dispersity silicic acid 4 sodium-ligninesulphonate 4 water The mixture of the components must be ground in a hammer mill until it reaches the particle size of 5 micron.

Example 19 Powder preparation Powder preparation is prepared with the following composition (proportions by weight): Compound 6 poly-vinyl-pyrrolidon silicon-dioxide china-clay (kaolin) WO 98/47362 PCrTO«/ 0nnno 37 Example Powder preparation Powder preparation is prepared with the following composition (proportions by weight): Compound 1 calcium-ligninesulphonate isopropyl-naphtalene-sulphonate 1 silicon-dioxide 4 filler (kaolin)

Claims

1. The use of hydroxylamine derivatives of general formula X R C N -O--CH-CH CH-- N Y R wherein R 1 represents phenyl, N-heteroaryl, S-heteroaryl or a naphthyl group which may *S 5 be substituted with one or more halo, alkyl, alkoxy, haloalkyl or nitro, an unsubstituted or substituted phenylamino or alkylamino or lower alkoxy, X represents halo, amino or an unsubstituted or substituted phenylamino group, or amino S.. substituted with one or two lower alkyl or a hydroxy group provided that ifR 1 represents unsubstituted or substituted phenylamino, alkylamino or lower alkoxy, then X may not represent halo, Y represents hydrogen, hydroxy or acyloxy, or if Y represents hydroxy, the molecule may contain a dioxazine ring closed at the carbon atom carrying the X group formed by formal XH elimination, 2 3 R and R 3 independently from each other, represent hydrogen or lower alkyl group provided that R 2 and R 3 may not represent hydrogen simultaneously, or R 2 and R 3 together with the adjacent nitrogen atom form a 5 to 7-membered saturated hetero ring, to increase the tolerance of cultivated plants against weather condition stresses.

2. The use as claimed in claim 1 wherein in the derivative of general formula X F O represents chloro or bromo. -39-

3. The use as claimed in claim 1 or claim 2 wherein in the derivative of general formula Y is longer alkanoyloxy.

4. Method for increasing the tolerance of cultivated plants against weather condition stresses, comprising treating the plant or its seed with a hydroxylamine derivative of general formula where R 2 R 3 X and Y are as in Claim 1. Method for increasing the tolerance of cultivated plants against cold and frost, comprising treating the seed of the plant with a compound of general formula where R 2 R 3 X and Y are as in Claim 1. 0

6. Method according to Claim 5, comprising treating the seed of the plant with an to aqueous solution of a hydroxylamine derivative of general formula where R' R 2 R 3 .o So**o X and Y are as in Claim 1.

7. Method according to Claim 6, comprising soaking the seed of the plant in an *3 *aqueous solution of a hydroxylamine derivative of general formula where R 2 R 3 00°* X and Y are as in Claim 1. i* 0 15 8. Method according to Claim 5, comprising coating the seed of the plant with a 'u product containing a hydroxylamine derivative of general formula where R R 2 R 3 X and Y are as in Claim 1 and optionally other active agents and/or germination improving auxiliary materials as well.

9. Method for increasing the tolerance of cultivated plants against cold, comprising spraying the plant with a solution containing a hydroxylamine derivative of general formula where R 2 R 3 X and Y are as in Claim 1 as active agent, before or when the cold season sets in. Method for increasing the tolerance of cultivated plants against drought, y comprising spraying the plant with a solution containing a hydroxylamine derivative of general formula where R 2 R 3 X and Y are as in Claim 1, as active agent, before or when the drought period sets in.

11. Composition for increasing the tolerance of cultivated plants against weather stresses, comprising as active ingredient a hydroxylamine derivative of general formula X i I N-0-CH- CH-CH- N l Y R wherein R 1 represents phenyl, N-heteroaryl, S-heteroaryl or a naphthyl group which may be substituted with one or more halo, alkyl, alkoxy, haloalkyl or nitro, X represents unsubstituted or substituted phenylamino group, or amino substituted with one or two lower alkyl, Y represents hydrogen, hydroxy or acyloxy, or if Y represents hydroxy, the molecule may contain a dioxazine ring closed at the carbon atom carrying the X group formed by formal XH elimination, R 2 and R 3 independently from each other, represent hydrogen or lower alkyl group provided that R andR 3 may not represent hydrogen simultaneously, R 2 and R 3 along with the adjacent nitrogen atom form a 5 to 7-membered saturated hetero ring.

12. The composition of claim 11 wherein Y represents longer alkanoyloxy.

13. The composition of claim 11 or claim 12 which also comprises solid or liquid carriers and optionally auxiliary materials suitable for agricultural use. -41

14. The composition according to claim 11 wherein R 1 is unsubstituted or substituted phenyl, X is unsubstituted or substituted phenylamino and R 2 R 3 and Y are as defined in claim 1. The composition according to claim 14 which comprises N-{[3-(1,1-dimethyl- ethyl)-amino]-2-hydroxy-propoxy}-N'-phenyl-benzamidine hydrochloride as active compound.

16. The composition according to claim 14 which comprises N-[3-(1-piperidinyl)- S propoxy]-N'-phenyl-benzamidine hydrochloride as active ingredient.

17. Hydroxylamine derivatives of the general formula (I) R N- 0- CH,-CH- CH, N y R Y r 10 wherein R' is phenyl which is unsubstituted or substituted with one or more selected from halo, alkyl, alkoxy, haloalkyl and nitro, X is unsubstituted or substituted phenylamino, Y is hydrogen, hydroxy or acyloxy, R 2 and R 3 independently from each other are H or lower alkyl provided that at least one of them is not hydrogen, or R 2 and R 3 together with the nitrogen adjacent thereto, form a 5 to 7-membered saturated hetero ring, and the salts thereof.

18. Hydroxylamine derivatives as claimed in claim 17 wherein Y is longer Salkanoyloxy. -42-

19. N- {[3-(1,1-dimethyl-ethyl)-amino]-2-hydroxy-propoxy} -N'-phenyl-benzamidine hydrochloride. N-[3-(1-piperidinyl)-propoxy]-N'-phenyl-benzamidine hydrochloride.

21. A hydroxylamine derivative for increasing the tolerance of a cultivated plant against weather condition stress substantially as herein described with reference to any one of the embodiments of the invention illustrated in the accompanying examples.

22. A method for increasing the tolerance of a cultivated plant against weather condition stress substantially as herein described with reference to any one of the embodiments of the invention illustrated in the accompanying examples.

23. A plant or its seed when treated by a method as claimed in any one of claims 4 to DATED this 22nd Day of March 2002 BIOREX KUTATO ES FEJLESZTO RT. Attorney: DENIS E. TUFFERY 15 Registered Patent Attorney Sof BALDWIN SHELSTON WATERS