WO2009129939A2

WO2009129939A2 - Use of 5-amino-1,2,4-thiadiazole for inhibiting or controlling nitrification

Info

Publication number: WO2009129939A2
Application number: PCT/EP2009/002676
Authority: WO
Inventors: Ute Radics; Hans-Joachim Niclas; Carola Schuster; Michael Fuchs
Original assignee: Skw Stickstoffwerke Piesteritz Gmbh
Priority date: 2008-04-25
Filing date: 2009-04-09
Publication date: 2009-10-29
Also published as: DE102008020785A1; WO2009129939A3; DE102008020785B4

Abstract

Disclosed is the use of 5-amino-1,2,4-thiadiazole, the salts, metal complexes, and simple derivatives thereof according to formulas (I) and (II) as a substance for inhibiting or controlling nitrification.

Description

Use of 5-amino-1,2,4-thiadiazole for inhibiting or controlling the nitrification

The present invention relates to the use of 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives as well as fertilizer compositions comprising them for inhibiting nitrification.

Nitrification inhibitors inhibit the microbial conversion of ammonium nitrogen to nitrate nitrogen in the soil over a period of time, thereby resulting in improved nitrogen utilization by the plant as the risk of nitrate shift is significantly reduced. At the same time, nitrous oxide emissions can be reduced by more than 50%.

The use of nitrogen fertilizers combined with nitrification inhibitors allows both economic and ecological advantages due to their mode of action. Due to the inhibition of microbial oxidation of the fertilized ammonium nitrogen to nitrate over a period of 4 to 12 weeks, the nitrogen is predominantly in the form of ammonium (available to the plants) and N losses due to nitrate leaching and nitrous oxide emissions are reduced. The reduction of the loss potential, combined with certain advantages of an ammonium-emphasized plant nutrition, allows a reduction of the N-effort with a consistently high yield level as well as a combination of operations, which leads to economic advantages.

The use of N-stabilized fertilizers can contribute to the reduction of nitrogen surpluses in agriculture. This is an environmental demand that must increasingly meet agricultural production. It has been proven that the use of nitrogen fertilizers provided with nitrification inhibitors has a particularly advantageous effect in water protection zones since the delayed nitrate formation can considerably reduce the entry of this N form into water.

As effective nitrification inhibitors, inter alia, nitrogen-containing heterocyclic compounds, preferably from the series of 1 H-pyrazoles and the 1, 2,4-triazoles, have been proposed, for. In US 3,635,690, US 4,969,946, US 4,523,940, EP-A 166 420, US 3,697,244.

A major disadvantage of the pyrazole derivatives, which generally have very good nitrification-inhibiting activity, is their relatively high volatility or, especially in the case of compounds substituted at the N-1 nitrogen atom, their sensitivity to hydrolysis, as a result of which effective but again volatile derivatives are formed. For these reasons, an application in solid fertilizers, especially in combinations with urea, can not be realized easily. To overcome this deficiency, proposals for the chemical modification of the 1-N-unsubstituted base pyrazoles are known (DE-OS 27 45 833, EP-A 508 191, DD 292 232, DE-OS 40 18 395, EP-A 160 804, DE-OS. OS 37 04 359, SU 1 470 737, DE-OS 44 46 194, EP-A 808 297). However, the decline in volatility due to derivatization usually also involves a decrease in the effect of nitrification inhibitor. Moreover, such approaches are coupled with an overhead of synthetic steps, which almost always lead to a cost burden, so that their application is no longer economically useful.

Other solutions for reducing the volatility of nitrification-inhibiting pyrazoles consist in the utilization of the actually known principle of salt formation with acids (EP-A 529 473, WO 98/05607, DE-OS 4018 395).

Both the mineral acid salts of the nitrified base pyrazoles and nitrified pyrazoles, which carry hydrophilic groups on the 1-N-nitrogen, can be used as nitrifying agents. cation inhibitors are not yet fully satisfactory, since they have too low hydrolytic stability, whereby the duration of action in the soil and the storage stability is reduced. This concerns z. B. N-Glyoxylpyrazole (DE-A 37 04 359) or N-hydroxymethylpyrazoles (SU-A 1 470 737). With the introduction of various lipophilic groups in 1-N position (DE-OS 101 17 821 A1, DE-OS 101 35 423 A1), although the hydrolysis of these pyrazole derivatives could be eliminated, but these nitrification inhibitors are no longer at low concentrations sufficiently powerful.

DE-OS 102 24 823 A1 describes pyrazole derivatives which contain acylated methylol groups. Since in the application of these compounds as nitrification inhibitors, a release of formaldehyde in the course of degradation by the soil organisms can not be completely excluded, there is a need for compounds from which an improved ecotoxicological behavior can be expected.

Another shortcoming is the manufacturing process for these agents. For example, in the preparation of N- (1H-azolylmethyl) amides (DE-OS 103 43 277 A1), mixtures of isomers with respect to the position of the substituents on the azole ring are obtained as products. The subsequent separation of the individual isomers increases the synthesis effort considerably.

The present invention has for its object to find or to develop agents for inhibiting or controlling the nitrification of ammonium nitrogen, which due to their low volatility and their hydrolytic stability all application methods, but also all possibilities for incorporation in or application to mineral nitrogen-containing fertilizer and regardless, also allow an application to organic fertilizers. At the same time, the structural elements of the active ingredients should be selected so that the greatest possible environmental compatibility can be assumed. The active ingredients should be produced by an economically meaningful synthesis in a simple way. The object is achieved by the use of 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives.

Of the sulfur-containing heterocycles, only the 1,2,4-thiadiazoles have gained some importance as the nitrification inhibiting compounds.

As a precondition for an effect, however, the presence of electron-withdrawing substituents, in particular in the 3-position, has hitherto been considered on thiadiazole. Thus, the trichloromethyl group in the 3-position causes the nitrifiziden properties in contact fungicide Etridiazol. The use of substances with trichloromethyl groups is, however, to be rejected because of their toxicological and ecotoxicological properties.

The 1,2,4-thiadiazoles claimed in US Pat. No. 4,226,609 also contain a trichloromethyl group in the 3-position. In addition, a cyclic amine must be present in the 5-position for the desired effect to occur. With primary amines and with an unsubstituted amino group in the 5-position, a much weaker effect or even inefficiency is stated under the selected test conditions.

Although DD 229 396 A1 also claims substances having an alkyl substituent in the 3-position, an effect inhibiting the nitrification is found only with compounds substituted by chlorine, amino or alkylthio in the 3-position. In the 5-position of these thiadiazoles are either mercapto, alkyl (aryl) thio or alkyl or Arylalkylsulfonylgruppen.

In DE 103 32 288 A1, which describes 1, 2,4-thiadiazoles as urease inhibitors, which also act as nitrification inhibitors, for the first time a hydrogen atom is also permitted as a substituent in the 3-position, a prerequisite for the substances which can be used as active substances But here is a thio group in the 5-position. Due to the severe limitations of the prior art for the substituent pattern of 1, 2,4-thiadiazoles which can be used as nitrification inhibitors, it was not foreseen that with 5-amino-1, 2,4-thiadiazoles. thiadiazole a compound is found which shows an extremely good, the nitrification inhibitory effect. Surprisingly, this effect occurs not only at the application rates of 16 to 1% N-described in the prior art, but already at 0.5% N-bez. in the floor model test. This was not foreseeable because in the 3-position with aryl- or alkyl-substituted 5-amino-1, 2,4-thiadiazoles under the same conditions in the soil model test show no effect.

The very good effect of the inventively used 5-amino-1, 2,4-thiadiazole could also be confirmed by the corresponding vascular and field experiments.

The 5-amino-1,2,4-thiadiazole used according to the invention per se is a known compound for which many different applications have been described. For example, WO 2005 019 816 A1, the use as a hardener component for dispersants in WO 2003 027 162 A1, the use as active ingredient for immunosuppressants in EP 455356 A1 or as starting material for the synthesis of pharmaceutical preparations in WO 2003 019 816 A1 WO 2007 0775895 A2 reports.

The preparation of 5-amino-1, 2,4-thiadiazole is known from the literature. For example, formamidine can be reacted with bromine or chlorine and the intermediate product subsequently reacted with potassium thiocyanate to give the thiadiazole (Goerdeler et al., Chem. Ber. 87 (1954) 57-68, DE 842 346 B). Another variant consists in the monoimino-formulation of thiourea with DMF-acetal, followed by the reaction of the intermediate with hydroxylamine-O-sulfonic acid (C. Landreau, D. Deniaud, A. Reliquet, J. Meslin Phosphorus, Sulfur Silicon Relet. Elements 177 (2002) 2651). 5-Amino-1,2,4-thiadiazole is a readily crystallizing compound melting at 119 ^° C. In contrast to the pyrazoles, which are partly volatile, such as 3-methyl- and 3,4-dimethyl-pyrazole, it is a heavy-volatile, stable substance that can be handled well even in industrial processes.

The 5-amino-1, 2,4-thiadiazole used according to the invention can also be used in the form of its salts, metal complexes or simple derivatives.

Simple derivatives are to be understood as meaning the 5-N-hydroxymethyl-amino-1, 2,4-thiadiazole I or the diol II.

5-Amι

Derivatives I and II are new compounds.

The 5-N-hydroxymethyl-amino-1, 2,4-thiadiazole I can by reaction of 5-amino-1, 2,4-thiadiazole with paraformaldehyde at temperatures of 100 to 200 ⁰ C, z. B. 125 to 145 ° C, without solvent in the melt and with a molar ratio of 5-amino-1, 2,4-thiadiazole to formaldehyde of 1: 1 to 2.5: 3 are prepared according to Equation 1.

The reaction can also be carried out at temperatures of 40 to 110 ^° C. in water as solvent and with a molar ratio of 5-amino-1,2,4-thiadiazole to formaldehyde of 1: 1 to 2.5: 3. Optionally, an alcohol or acetonitrile can be added as a solubilizer.

I The 1, 2-bis - [[1,2,4] thiadiazol-5-ylamino) ethane-1,2-diol II is prepared by reaction of 5-amino-1,2,4-thiadiazole with glyoxal at temperatures of 10 to 200 ⁰ C ₁ z. B. 10 to 80 ⁰ C, in a solvent selected from the group of alcohols (such as methanol or ethanol) and the halogenated hydrocarbons (such as chloroform or methylene chloride) and water and with a molar ratio of 5-amino-1,2 4-thiadiazole to glyoxal of 1, 0: 1, 0 to 2.2: 1, 0 synthesized according to Equation 2.

The novel compound II can also be prepared by reacting at temperatures of 20 ^° C. to 80 ^° C. in water as solvent and with a molar ratio of 1: 1 of 5-amino-1,2,4-thiadiazole to glyoxal to 2.2: 1, 0 performs. Optionally, an alcohol can be added as a solubilizer.

Another object of the present invention is the use of 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) for inhibiting or regulating the nitrification, wherein the compounds proposed by the invention in a known manner as nitrification inhibitors with solid ammonium and / or amide-containing fertilizers can be combined. As nitrogen fertilizers are preferably ammonium salts, such as. B. Kalkammonsalpe- ter, ammonium sulfate nitrate, ammonium nitrate, ammonium sulfate or urea used. Also possible is the use of 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) in combination with organic and liquid fertilizers. Application rates of 0.01 to 10.0 wt .-%, z. Example, 0.01 to 5.0 weight percent, in particular 0.01 to 3.0 weight percent, calculated on the reduced nitrogen content of the fertilizer, ie on ammonium and carbamide nitrogen, are sufficient for practical use. Of course, the 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) optionally be used in combination with other conventional nitrification inhibitors. Active ingredient formulations, solutions and concentrates which comprise 5-amino-1,2,4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) are a further subject of the invention.

The manner in which the nitrification inhibitors proposed by the invention are combined with the fertilizer is not particularly limited. All methods known in the prior art are suitable. Thus, the 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) preferably alone or in admixture with other additives as a solution or together with a suitable conditioning agent, for example with a hydrophobically effective paraffinic Conditioning agents are applied to the surface of the fertilizer granules, wherein the solvent (preferably aprotic solvents such as esters, oils, ketones, ethers, etc.) z. B. is removed by drying.

Alternatively, 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) alone or in admixture with other additives for homogeneous distribution in the fertilizer in the fertilizer melt or slurry during the molding process, eg , B. for the production of granules are introduced. Liquid and organic fertilizers, the compounds of the invention are preferably added in the form of a suitable formulation.

It is clear that for formulation customary and known in the art auxiliaries, carriers and extenders or a combination of these agents, or surfactants, for. As a wetting, dispersing, emulsifying or suspending agent can be used. The respective formulation methods correspond to the prior art and are known to the person skilled in the art.

The following examples are intended to illustrate the invention without limitation. Examples:

5-N-hydroxymethyl-amino-1,2,4-thiadiazole I

Option A:

General Synthesis Instructions:

0.01 mol of 5-amino-1, 2-4-thiadiazole and 0.01 mol of paraformaldehyde are intimately mixed. The mixture is heated gently to 140 ⁰ C and the clear melt stirred for 15 to 75 minutes at this temperature. The reaction mixture is allowed to solidify and optionally purified by column chromatography.

Variant B:

General Synthesis Instructions:

0.01 mol of 5-amino-1, 2,4-thiadiazole are introduced into 20 ml of methanol and 0.01 mol

37% aqueous formaldehyde solution was added dropwise. It is heated for two hours

Reflux and follow the reaction by thin layer chromatography. You can do that

Cool reaction mixture and the solvent is evaporated off under vacuum.

Variant C:

General Synthesis Instructions:

0.011 mol of paraformaldehyde and 80 mg of potassium hydroxide are placed in 25 ml of ethanol and heated to 50 ⁰ C until everything is dissolved. Now, 0.01 mol of 5-amino-1, 2,4-thiadiazole added. The mixture is heated for 30 minutes at 50 ⁰ C and the reaction is monitored by thin layer chromatography. The reaction mixture is allowed to cool, the solvent is evaporated off under vacuum, and the resulting oil is purified by column chromatography if necessary.

5-N-hydroxymethyl-amino-1,2,4-thiadiazole I

R _F = 0.12 (ethyl acetate / dichloromethane 1: 4) ¹ H-NMR (DMSO) δ [ppm]: 4.70-4.91 (m, 2H); 5.97-6.20 (m, IH); 8.00-8.10 (m, IH); 9.06

(m, 0.5H)

¹³ C-NMR (DMSO) δ [ppm]: 68.5 (CH ₂ ); 73.4 (CH ₂ ); 160.0; 183.6

1, 2-bis - ([1, 2,4] thiadiazol-5-ylamino) ethane-1,2-diol II

Option A:

General Synthesis Instructions:

To a mixture of 0.05 mol of 5-amino-1, 2,4-thiadiazole and 70 ml of water are added dropwise at room temperature 0.025 mol of 40% glyoxal solution. It is heated to 70 ⁰ C for one hour. The mixture is stirred at room temperature, allowed to stand overnight and the precipitate is filtered off with suction. The product is washed thoroughly with water and dried.

Variant B:

General Synthesis Instructions:

Analog variant A, but 0.0275 mol 40% glyoxal solution are added dropwise.

Variant C:

General Synthesis Instructions:

Analog variant A, but the 5-amino-1, 2,4-thiadiazole is presented in 50 ml of methanol.

1, 2-bis - ([1, 2,4] thiadiazol-5-ylamino) ethane-1,2-diol II

Mp 140-2 ⁰ C.

Elemental analysis:

C in%: calculated: 27.7 F .: 27.5

H in%: calculated: 3.10 found: 3.16

N in%: calculated: 32.3 months: 31, 9

¹ H-NMR (DMSO) δ [ppm]: 5.21 (s, 2H); 6.50 (d, 2H); 7.94 (s, 2H); 8.30 (d, 2H) ¹³ C-NMR (DMSO) δ [ppm]: 79.4; (CH); 159.6; 160.2; 182.4; 183.5

Determination of the nitrification-inhibiting effect

Testing of the 1, 2,4-thiadiazoles was carried out in the concentrations shown in Table 1. The nitrification-inhibiting effect was determined in such a manner that 100 g of air-dry soil was adjusted to 50% of the maximum water capacity. For this purpose, in each case 10 mg of urea-N and the amount of active substance stated were added with as homogeneous a distribution as possible. Thereafter, the thus prepared vessels are stored under standardized conditions at 20 ⁰ C in the dark climatic chamber. From the time-dependent determination of the conversion of ammonium-N to nitrate nitrogen compared to the variant without inhibitor, the percentage inhibition to day X is determined. The K value used below embodies a value independent of the biological fluctuations of the soil activity, since it is relativised by the quotient formation to the effect of a standard, in this case 3-methylpyrazole with an inhibitor concentration of 0.2% N-. The calculation of the K value is preceded by the calculation of the T ₅₀ value. This value expresses the time in days when the nitrification inhibition for a single substance decreased to 50%. From this, the K value is derived as follows:

K = t ₅ o value of the test substance / 1 ₅₀ value standard

Table 1: Nitrification-inhibiting effect of selected 1, 2,4-thiadiazoles at a drug concentration of 0.5 ppm

¹ dihydrogen phosphate ² hydrochloride ³ 1% N-based

K values by a factor of 1 correspond to the effect of the standard substance. From this aspect, it can be seen from Table 1 that the compounds according to the invention have an excellent nitrification-inhibiting action.

Claims

claims

1. Use of 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives according to the formula I and II as an agent for inhibiting or controlling the nitrification:

5-amino-1,2,4-thiadiazole

2. Composition comprising 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) according to claim 1 and optionally further nitrification inhibitors and / or urease inhibitors in combination with solid and liquid ammonium and / or or amide-containing fertilizers.

3. The composition according to claim 2, characterized in that the 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) and optionally further nitrification inhibitors and / or urease inhibitors in a total application amount of 0 , 01 to 10.0 weight percent, calculated on the reduced nitrogen content of the amide and / or ammonium-containing fertilizer used.

4. The composition according to claim 3, characterized in that the 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) are used in an application rate of 0.01 to 3.0 weight percent ,

5. Composition according to claims 2 to 4, characterized in that 5-amino-1, 2,4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) alone or in admixture with other additives in the Fertilizer melt or slurry have been introduced during the molding process and distributed homogeneously in the fertilizer in this way.

6. Composition according to claims 2 to 4, characterized in that the 5-amino-1, 2-4-thiadiazole, its salts, metal complexes and simple derivatives (I and II) optionally with further additives in the form of a solution or together with a suitable conditioning agent have been applied to the surface of the fertilizer granules and, optionally, then the solvent has been removed by drying.

7. 5-N-hydroxymethyl-amino-1, 2-4-thiadiazole I

8. A process for the preparation of 5-N-hydroxymethyl-amino-1, 2,4-thiadiazole I, characterized in that reacting 5-amino-1, 2-4-thiadiazole with formaldehyde according to equation (1).

I

9. The method according to claim 8, characterized in that the reaction with paraformaldehyde at temperatures of 100 to 200 ⁰ C without solvent in the melt and with a molar ratio of 5-amino-1, 2,4-thiadiazole to formaldehyde of 1: 1 to 2.5: 3.

10. The method according to claim 9, characterized in that one carries out the reaction at 125 to 145 ⁰ C.

11. The method according to claim 8, characterized in that the reaction at temperatures of 40 to 110 ⁰ C in water as a solvent and with a molar ratio of 5-amino-1, 2,4-thiadiazole to formaldehyde of 1: 1 to 2 , 5: 3.

12. The method according to claim 11, characterized in that one adds an alcohol or acetonitrile as a solubilizer.

13. 1, 2-bis - ([1, 2,4] thiadiazol-5-ylamino) ethane-1,2-diol II

14. A process for the preparation of 1, 2-bis - [[1, 2,4] thiadiazol-5-ylamino) ethane-1, 2-diol II, characterized in that 5-amino-1, 2,4 -thiadiazole reacts with glyoxal according to equation (1).

15. The method according to claim 14, characterized in that the reaction at temperatures of 10 to 200 ⁰ C in a solvent selected from alcohols, halogenated hydrocarbons and water and having a molar ratio of 5-amino-1, 2,4-thiadiazole to glyoxal from 1, 0: 1, 0 to 2.2: 1, 0 performs.

16. The method according to claim 15, characterized in that methanol or ethanol is used as the alcohol and chloroform or methylene chloride as the halohydrocarbon.

17. The method according to claim 15 or 16, characterized in that one carries out the reaction at 10 to 80 ⁰ C.

18. The method according to claim 15, characterized in that the reaction at temperatures of 20 ⁰ C to 80 ⁰ C in water as a solvent and with a molar ratio of 5-amino-1, 2,4-thiadiazole to glyoxal of 1: 1 to 2.2: 1, 0 performs.

19. The method according to claim 18, characterized in that one adds an alcohol as a solubilizer.