USE OF SUBSTITUTED 2-THIAZOLINES AS NITRIFICATION INHIBITORS

Abstract

The invention relates to novel nitrification inhibitors of formula I, which are substituted 2-thiazoline compounds. Moreover, the invention relates to the use of compounds of formula I as nitrification inhibitors, i.e. for reducing nitrification, as well as agrochemical mixtures and compositions comprising the nitrification inhibitors of formula I.

Claims

1. A substituted 2-thiazoline compound of formula I ##STR00021## or a salt, stereoisomer, tautomer, N-oxide, or S-oxide thereof for use as a nitrification inhibitor, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently of each other selected from H, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.1-C.sub.4-alkylsulfonyl, benzyl, hetaryl, and phenyl, wherein said groups are unsubstituted or substituted by one or more, same or different substituents R.sup.x; or R.sup.1 and R.sup.2 or R.sup.3 and R.sup.4 together form ═O, or ═CR.sup.C1R.sup.C2, wherein R.sup.C1 and R.sup.C2 together form a 5- or 6-membered saturated, partially or fully unsaturated, or aromatic carbocyclic or heterocyclic ring, wherein said heterocyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and/or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or heteroatom in the aforementioned cyclic moieties is independently unsubstituted or substituted with one or more, same or different substituents R.sup.x; and wherein R.sup.S is H, C.sub.1-C.sub.2-alkyl, C.sub.3-C.sub.6-cycloalkyl, allyl, propargyl, or phenyl, wherein said groups are unsubstituted or substituted by one or more, same or different substituents R.sup.y; CHR.sup.aC(═O)OR.sup.b, CHR.sup.aC(═O)O.sup.−Q.sup.+, CHR.sup.aC(═O)R.sup.d, CHR.sup.aC(═O)NR.sup.bR.sup.c, C(═O)R.sup.d, C(═O)OR.sup.b, C(═O)NR.sup.bR.sup.c, CHR.sup.aOR.sup.b, C(═O)(CH.sub.2).sub.2C(═O)OR.sup.b, or CSNR.sup.bR.sup.c; R.sup.a is H, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, phenyl, or phenyl-C.sub.1-C.sub.2-alkyl; R.sup.b is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.3-C.sub.6-cycloalkyl, aryl, phenyl, or phenyl-C.sub.1-C.sub.2-alkyl; R.sup.c is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.3-C.sub.6-cycloalkyl, aryl, phenyl, or phenyl-C.sub.1-C.sub.2-alkyl; R.sup.d is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, phenyl, phenyl-C.sub.1-C.sub.2-alkyl, hetaryl, or hetaryl-C.sub.2-C.sub.3-alkenyl, wherein these groups are unsubstituted or substituted by one or more, same or different substituents selected from halogen, OH, OCH.sub.3, and CH.sub.3; R.sup.x is halogen, OH, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-alkylcarbonyl, or C.sub.1-C.sub.6-alkylcarboxy; R.sup.y is halogen, OH, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, or C.sub.1-C.sub.6-haloalkoxy; and Q.sup.+ is selected from the group consisting of Na.sup.+, K.sup.+, Ca.sup.2+, and NH.sub.4.sup.+.

2. The compound of claim 1, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently of each other selected from H, halogen, and C.sub.1-C.sub.4-alkyl; R.sup.S is H, C.sub.1-C.sub.2-alkyl, allyl, propargyl, or phenyl, wherein phenyl is unsubstituted or substituted with one or more, same or different substituents R.sup.y; CHR.sup.aC(═O)OR.sup.b, C(═O)NR.sup.bR.sup.c, CHR.sup.aC(═O)O.sup.−-Q.sup.+, CHR.sup.aC(═O)R.sup.d, or C(═O)R.sup.d; R.sup.a is H, or C.sub.1-C.sub.4-alkyl; R.sup.b is H, C.sub.1-C.sub.4-alkyl, or phenyl; R.sup.c is H, C.sub.1-C.sub.4-alkyl, or phenyl; R.sup.d is C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, phenyl, phenyl-C.sub.1-C.sub.2-alkyl, hetaryl, or hetaryl-C.sub.2-C.sub.3-alkenyl, wherein these groups are unsubstituted or substituted by one or more, same or different substituents selected from halogen, OH, OCH.sub.3, and CH.sub.3; R.sup.y is halogen, or C.sub.1-C.sub.4-alkyl; Q.sup.+ is selected from the group of Na.sup.+, K.sup.+, Ca.sup.2+, and NH.sub.4.sup.+.

3. The compound of claim 1, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently of each other selected from H, and C.sub.1-C.sub.4-alkyl; R.sup.S is H, C.sub.1-C.sub.2-alkyl, propargyl, or phenyl, wherein phenyl is unsubstituted or substituted with one or more, same or different substituents R.sup.y; CHR.sup.aC(═O)OR.sup.b, C(═O)NR.sup.bR.sup.c, or CHR.sup.aC(═O)R.sup.d; R.sup.a is H, or C.sub.1-C.sub.4-alkyl; R.sup.b is H, C.sub.1-C.sub.4-alkyl, or phenyl; R.sup.c is H, C.sub.1-C.sub.4-alkyl, or phenyl; R.sup.d is C.sub.1-C.sub.4-alkyl, or phenyl; R.sup.y is F, Cl, Br, or C.sub.1-C.sub.3-alkyl.

4. The compound of claim 1, wherein the substituted 2-thiazoline compound of formula I is present in the form of a salt with different acids, selected from the group consisting of H.sub.3PO.sub.4, H.sub.2SO.sub.4, HNO.sub.3, HBr, and HCl.

5. A substituted 2-thiazoline compound of formula I ##STR00022## wherein the compound of formula I is selected from ##STR00023##

6. A composition for use in reducing nitrification comprising at least one compound of formula I as defined in claim 1 and at least one carrier.

7. An agrochemical mixture comprising (i) at least one fertilizer; and (ii) at least one compound of formula I as defined in claim 1.

8. The method of claim 10, wherein said compound of formula I is used in combination with a fertilizer.

9. The method of claim 10, wherein said reduction of nitrification occurs in or on a plant, in the root zone of a plant, in or on soil or soil substituents and/or at the locus where a plant is growing or is intended to grow.

10. A method for reducing nitrification, comprising treating a plant growing on soil or soil substituents and/or the locus or soil or soil substituents where the plant is growing or is intended to grow with at least one compound of formula I as defined in claim 1.

11. The method of claim 10, wherein the plant and/or the locus or soil or soil substituents where the plant is growing or is intended to grow is additionally provided with a fertilizer.

12. The method of claim 10, wherein the application of said compound of formula I and of said fertilizer is carried out simultaneously or with a time lag.

13. A method for treating a fertilizer or a composition, comprising applying a nitrification inhibitor as defined in claim 1 to the fertilizer or the composition.

14. The agrochemical mixture of claim 7, wherein said fertilizer is a solid or liquid ammonium-containing inorganic fertilizer; a solid or liquid organic fertilizer.

15. The method of claim 10, wherein said plant is an agricultural plant; a vegetable; sorghum; a silvicultural plant; an ornamental plant; or a horticultural plant, each in its natural or in a genetically modified form.

16. The method of claim 12 wherein the time lag is an interval of 1 day, 2 days, 3 days, 1 week, 2 weeks or 3 weeks.

17. The agrochemical mixture of claim 7 wherein the fertilizer comprises an NPK fertilizer, ammonium nitrate, calcium ammonium nitrate, ammonium sulfate nitrate, ammonium sulfate or ammonium phosphate, liquid manure, semi-liquid manure, biogas manure, stable manure, straw manure, worm castings, compost, seaweed, guano, urea, formaldehyde urea, anhydrous ammonium, urea ammonium nitrate (UAN) solution, urea sulphur, urea based NPK-fertilizers, or urea ammonium sulfate.

18. The method of claim 15 wherein the plant is wheat, barley, oat, rye, soybean, corn, potatoes, oilseed rape, canola, sunflower, cotton, sugar cane, sugar beet, rice, spinach, lettuce, asparagus, or cabbages.

Description

EXAMPLES

[0605] The compounds of the invention have been tested as follows in terms of the inhibition of nitrification:

[0606] 100 g soil is filled into 500 ml plastic bottles (e.g. soil sampled from the field) and is moistened to 50% water holding capacity. The soil is incubated at 20° C. for two weeks to activate the microbial biomass. 1 ml test solution, containing the compound in the appropriate concentration (usually 0.3 or 1% of nitrogen N), or DMSO and 10 mg nitrogen in the form of ammoniumsulfate-N is added to the soil and everything mixed well. Bottles are capped but loosely to allow air exchange. The bottles are then incubated at 20° C. for 0 and 14 days.

[0607] For analysis, 300 ml of a 1% K.sub.2SO.sub.4-solution is added to the bottle containing the soil and shaken for 2 hours in a horizontal shaker at 150 rpm. Then the whole solution is filtered through a filter (Macherey-Nagel Filter MN 807%). Ammonium and nitrate content is then analyzed in the filtrate in an autoanalyzer at 550 nm (Merck, AA11).

[0608] The inhibition (NI® a specified concentration) is calculated as follows:

[00001]$\mathrm{inhibition}\mathrm{in}\%=\frac{\left(\begin{array}{c}\mathrm{NO}3-N_{wi\mathrm{thout}\mathrm{NI}\mathrm{at}\mathrm{end}\mathrm{of}\mathrm{incubation}}-\\ \mathrm{NO}3-N_{\mathrm{with}\mathrm{NI}\mathrm{at}\mathrm{end}\mathrm{of}\mathrm{incubation}}\end{array}\right)}{\left(\begin{array}{c}\mathrm{NO}3-N_{wi\mathrm{thout}\mathrm{NI}\mathrm{at}\mathrm{end}\mathrm{of}\mathrm{incubation}}-\\ \mathrm{NO}3-N_{\mathrm{at}\mathrm{beginning}}\end{array}\right)}\times 100$

[0609] The following compounds of general formula I, wherein R.sup.1 and R.sup.2 are in each case H, have been tested.

##STR00020##

TABLE-US-00005 NI* NI* NI* @ @ @ No. R.sup.3 R.sup.4 R.sup.S 3% 1% 0.3% 1 H H CH.sub.3 88 90.2 60.1 2 H H propargyl 76.3 — — 3 H H H 83.5 47 — 4 CH.sub.3 CH.sub.3 H 57.5 — — 5 H H C(═O)NH(phenyl) 55 — — 6 H H CH.sub.2C(═O)(phenyl)H.sup.+Br.sup.− 53.9 31 21   7 H H 2-methyl-4-chloro-phenyl 48.8 25.7 — 8 H H C(═O)NH(CH.sub.2CH.sub.3) 43.1 — — 9 H H CH.sub.2CH.sub.3 — 22 — 10 H H CH.sub.2C(═O)OCH.sub.3 — 21.5 — 11 H H C(═S)N(CH.sub.3).sub.2 58.4 31.2 —

Synthesis of Tested Compounds

[0610] Cmpd 1: 2-(Methylthio)-2-thiazoline, CAS-No. 19975-56-5. This substance is commercially available and has been purchased.

[0611] Cmpd 2: 2-(Propynylthio)-2-thiazoline, CAS-No. 1750-41-0. This compound has been prepared as described in Journal of Chemical Research (2016), 40(11), 674-677.

[0612] Cmpd 3: 2-Mercapto-2-thiazoline, CAS-No. 96-53-7. This substance is commercially available and has been purchased. It exists in equilibrium with its tautomer 1,3-Thiazolidine-2-thione.

[0613] Cmpd 4: 4,4-Dimethyl-2-mercaptothiazoline, CAS-No. 1908-88-9. This compound has been prepared as described in Tetrahedron, 67(41), 7971-7976; 2011. It exists in equilibrium with its tautomer 4,4-Dimethyl-2-thiazolidinethione.

[0614] Cmpd 5: 2-(Phenylaminocarbonylthio)-2-thiazoline. New compound. The synthesis of this compound is described in the following:

[0615] To a solution of 1.79 g (0.015 mol) of 2-Mercapto-2-thiazoline (Cmpd. 3) in 25 ml of tetrahydrofuran was added 1 drop of Borchi® Kat 315 (Borchers GmbH, Germany). To the stirred solution were added 2.03 g (0.017 mol) phenyl isocyanate and the solution was stirred at 60° C. for 4 h and then evaporated. The solid residue (3.73 g) was recrystallized from 30 ml of ethyl acetate to afford 2.55 g of compound 5 as a white solid. .sup.1H-NMR in CDCl.sub.3 (ppm): 3.32 (t, 2H), 4.80 (t, 2H), 7.1-7.6 (m, 5H).

[0616] Cmpd 6: 2-(2-Thiazolin-2-ylthio)-acetophenone, hydrobromide, CAS-No. 17385-77-2. This compound has been prepared via addition of 1 equivalent of hydrobromic acid to the 2-(2-thiazolin-2-ylthio)-acetophenone, CAS-No. 17385-78-3. The latter has been prepared as described in Journal of Sulfur Chemistry, 32(1), 71-84; 2011.

[0617] Cmpd. 7: 2-(4-Chloro-2-methylphenylthio)-2-thiazoline. New compound. This compound has been prepared by CuI promoted coupling of 2-Mercapto-2-thiazoline (Cmpd. 3) with 4-Chloro-1-iodo-2-methylbenzene using the method described in Journal of Organic Chemistry, 2010, 75(11), 3626-3643.

[0618] Cmpd. 8: 2-(Ethylaminocarbonylthio)-2-thiazoline. New compound. The synthesis of this compound is described in the following:

[0619] To a solution of 1.79 g (0.015 mol) of 2-mercapto-2-thiazoline (Cmpd. 3) in 25 ml of tetrahydrofuran was added 1 drop of Borchi® Kat 315 (Borchers GmbH, Germany). To the stirred solution were added 2.28 g (0.032 mol) ethyl isocyanate and the solution was stirred at 65° C. for 12 h and then evaporated to afford 2.9 g of compound 8 as a light yellow oil. .sup.1H-NMR in CDCl.sub.3 (ppm): 1.18 (t, 3H), 3.25 (t, 2H), 3.35 (m, 2H), 4.70 (t, 2H), 9.8 (bs, NH).

[0620] Cmpd. 9: 2-(Ethylthio)-2-thiazoline, CAS-No. 23994-89-0. This compound has been prepared as described in the Chinese patent application CN 104292222 A.

[0621] Cmpd. 10: (2-Thiazolin-2-ylthio)-acetic acid, methyl ester, CAS-No. 22623-64-9. This compound has been prepared as described in Tetrahedron Letters, (31), 2677-80; 1977.

[0622] Cmpd. 11: 4,5-dihydro-3H-thiazol-2-yl N,N-dimethylcarbamodithioate, CAS-No. 140652-77-3. This compound has been prepared as described in Archiv der Pharmazie (Weinheim, Germany), 325(3), 173-5; 1992.