SUBSTITUTED PYRIDAZINES, PROCESSES FOR MAKING THEM, THEIR USE AS PLANT GROWTH REGULATORS, AND PLANT GROWTH REGULATING COMPOSITIONS CONTAINING THEM

Abstract: Novel substituted pyridazines are provided which ex­ hibit plant growth regulating activity on gramineous plants such as cereals. The novel compounds are of Formula (I) below: wherein R¹ is (C₁-C₄) alkyl, phenyl or naphthyl each of the last two groups being optionally substituted with up to three of the same or different substituents selected from halogen, trihalomethyl, (C₁-C₄) alkoxy, (C₁-C₄) alkyl and cyano; R³ is hydrogen or a group as defined below for R⁵; R⁵ is a carboxy (-COOH) group or agronomically acceptable alkali metal salt thereof, an alkoxycarbonyl (-COOR) group or a substituted carbamoyl (-CONR′R″) group, wherein R represents (C₁-C₄) alkyl, R′ represents hydrogen or (C₁-C₄) alkyl and R″ represents (C₁-C₄) alkyl; and R⁶ is a (C₁-C₄) alkyl group or an optionally substituted phenyl or naphthyl group as defined for R¹ above. Also provided are agronomically acceptable acid addi­ tion salts of compounds of Formula (I).

Description: SUBSTITUTED PYRIDAZINES, PROCESSES FOR MAKING THEM, THEIR USE AS PLANT GROWTH REGULATORS, AND PLANT GROWTH REGULATING COMPOSITIONS CONTAINING THEM. This invention concerns novel substituted pyridazines and their use as plant growth regulators, particularly as chemical sterilants for producing hybrid seed of cereal grain plants; also concerned are processes for making the new compounds and plant growth regulating compositions containing them. In Belgian Patent specification No.864,704 and its foreign equivalents: French No.2,392,980, W.German No.2,808,795,Egyptian No.13401, Australian No.78/33980 and New Zealand No.186,596 there are described l-aryl(or substituted aryl)-1,4-dihydro-4-oxo-3-carboxy-6alkylpyridazines and derivatives thereof. These compounds are disclosed as having utility as plant growth regulators particularly as chemical hybridizing agents for the production of hybrid cereal seed. The present invention provides novel substituted pyridazines which bear some resemblance to those of the prior art compounds noted above but which are principally characterized in that they contain a carboxy group, or derivative thereof, in the 5-position and, in some cases, in the 3position as well. Representative compounds of the new substituted pyridazines are unexpectedly safer chemical hybridizing agents as compared with the cited prior art compounds in that they have significantly reduced adverse effects as regards hybrid seed quality or amount of plant injury at doses above those required to produce maximum male sterility thus allowing for higher yields of hybrid seed. The-pyridazine compounds concerned in this invention are those of Formula (I) below. EMI2.1 wherein R1 is (C1-C4)alkyl, phenyl or naphthyl each of the last two groups being optionally substituted with up to three (preferably one or two) of the same or different substituents selected from halogen(viz. chlorine, bromine, fluorine and iodine), trihalomethyl (e.g. trifluoromethyl or trichloromethyl), (C1-C4)alkoxy, (C1-C4)alkyl and cyano; R3 is hydrogen or a group as defined below for R5; ; 5 is a carboxy (-COOH) group or agronomically acceptable alkali metal salt thereof (particularly a salt of Na, K or Li), an alkoxycarbonyl (-COOR) group or a substituted carbamoyl (-CONR R )group, wherein R represents (C1-C4)alkyl, R represents hydrogen or (C1-, C4) alkyl and R" represents (C1-C4) alkyl; and R6 is a (Cl-C4)alkyl group or an optionally substituted phenyl or naphthyl group as defined for R1 above. Compounds of Formula (I) meriting particular attention are those wherein, when R3 is hydrogen, R1 is halophenyl, particularly 4halophenyl, R5 is -CO2Na or CO2K and R6 is methyl or ethyl and those wherein, when R is other than hydrogen, R1 is halphenyk, particularly 4-halo-. phenyl, R3 is -CO2Na, -CO2K or -CO2(C1-C3) alkyl, R5 is -CO2CH3 and R6 is methyl or ethyl. The term alkyl used in this specification includes both straight and branched chain alkyl groups and, where unqualified, alkyl means n-alkyl. Also included within the scope of the invention are agronomically acceptable acid addition salts of compounds of Formula (I). Typical acid addition salts are those formed with strong acids such as hydrochloric, hydrobromic, sulfuric and nitric acids. Typiucal compounds ofFormula (I) wherein R is hydrogen are: LIST A l-phenyl-1,4-dihydro-4-ozo-6-methylpyridazine-5-carboxylic acid l-phenyl-1,4-dihydro-4-oso-6-ethylpyridazine-5-c2rboxylic acid, l-phenyl-1,4-dihydro-4-oxo-6-propylpyrid2zine-5-c2rboxylic acid, 1-phenyl-1,4-dihydro-4-oxo-6-butylpyridazine-5-carboxylc acid 1-methyl-1,4-dihydro-4-oxo-6-butylpyridazine-5-carboxylc acid 1-phenyl-1,4-dihydro-4-oxo-6-butylpyridazine-5-carboxylc acid 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-6-butylpyridazine-5 carboxylic acid 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-6-butylpyridazine-5 carboxylic acid, 1-(3,4-dichloropheyl)-1,4-dihydro-4-oxo-6-butyl-pyridazine-5 -5-carboxylic acid, 1-(4-iocophenyl)-1,4-dihydro-4-oxo-6-butylpyri 2zine-5- carboxylic acid, 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-6-butylpyridazine-5 carboxylic acid; 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-6-butylpyridazine-5 carboxylic acid, 1-(3-chlorophenyl)-1,4-dihydro-4-oxo-6-butylpyridazine-5 carboxylic acid', 1-(2-c:qlorophenyl)-1,4-dihydro-4-ozo-ó-ethylpyrid22ine-5- carboxylic acid1 1-(3-bromophenyl)-1,4-dihydro-4-oxo-6-propylpyridazine-D- carboxylic acid, 1-(2-bromphenyl)-1,4-dihydro-4-oxo-6-butylpyridazine-5 carboxylic acid, 1-(2,4-trichlorphenyl)-1,4-dihydro-4-oxo-6-butyl pyridazine-5-carboxylic acid 1-(4-methylphenyl)-1,4-dihydro-4-oxo-6-butylpyridazine-5 carboxylic acid 1-(4-trifluromthylphenyl)-1,4-dihydro-4-oxo-6-methyl pyridazine-5-carboxylic acid 1-(3-ethOxyphenyl)-1,4-dihydro-4-oxo-6-ethylpyrid2zine-5- carboxylic acid 1-butyl-1,4-dihydro-4-oxo-6-propyl pyridamine-5-carboxy acid 1-(3-cyaqnophenyl)-1,4-dihydro-4-oxo-6-butylpyridazine-5 carboxylic acid 1-(2-chloro-4-methylphenyl)-1,4-dihydro-4-oxo-phenyl pyridazine-5-carboxylic acid 1-(2-trifluoromethyl-4-chlorophenyl)-1,4-dihydro-4-oxo-6 metylpyridazine-5-czrbaylic acid 1-(2-trifluormethyl-4-bromophenyl)-1,4-dihydro-4-oxo-6 ehtyklpyridazijne-5-carboxylic acid 1-(2-chloro-; ;-tritluorsmethylphenyl)-1,4-dihy -o-4-oxo-6- ethylpyridazine-5-carboxylic acid 1-(2-naphthyl)-1,4-dihydro-4-oxocarboxylic acid and the sodium,potassium and lithium carboxy salts and the inethyl,ethyl,n-propyl, isopropyl and butyl (all isomers) carboxy esters of each of the above compounds and the acid addition salts of all the above 'listed compounds including the carboxy salts and carboxy esters. Typical compounds of Formula (I) wherein 3. R is carboxy, or a derivative thereof, are: LIST z z B 1-phenyl-1,4-dihydro-4-oxo-6-methylpyridazine-3,5-dicarboxylic acid, 1-phenyl-1,4-dihydro-4-oxo-6-methylpyridazine-3,5dicarboxylic acid, l-phenyl-1,4-dihydro-4-oxo-6-propylpyridazine-3,5-dicarboxylic acid, l-phenyl-1,4-dihydro-4-oxo-6-butylpyridazine-3,5-dicarboxylic acid, l-phenyl-1,4-dihydro-4-oxo-6-phenylpyridazine-3,5-dicarboxylic acid, 1-(4-chiorophenyl)-l,4-dihydro-4-oxo-6-methylpyridazine-3,5-di carboxylic acid) 1-(4-bromophenyl)-1,4-dihydro-4-oxo-6-ethylpyridazine-3,5-di- carboxylic acid, 1-(3,4-dichlorophenyl)-1,4-dihydro-4-oxo-6-propylpyridazine 3,5-dicarboxylic acid. 1- ( 4 - iod ophenyl ) -1, 4-dihydro-4-oxo-6-butylpyridazine-3,5- dicarboxylic acid, 1-(4-flurophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3,5dicarboxylic acid, 1-(4-chlorophenyl) -l,4-dihydro-4-oxo-6-phenylpyridazine-3,5- dicarboxylic acid, 1-(3-chlorophenyl-1,4-dihydro-4-oxo-6-methylpyridazine-3,5dicarboxylic acid, 1-(2-chlorphenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3,5dicarboxylic acidi 1-(3-bromophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3,5dicarboxylic 1-(2-bromophenyl)-1, -dihydro-4-oxo-6-butylpyridazine-3,5- dicarboxylic acid, 1-(2,4,6-trichlorophenyl)-1,4-dihydro-4-oxo-6-benzyl pyr idazine-3 , 5-dicarboxylic acid, 1-(4-methylphenyl)-1,4-dihydro-4-oxo-6-phenylpyridazine-3,5dicarboxylic -acidj 1-(4-triEluoromethylphenyl)-1,4-dihydro-4-oxo-6-methyl- pyridazine-3 ,5-dicarboxylic acid, 1-(3-ethOxyphenyl)-1,4-dihydro-4-oxo-6-ethylpyridazine-3,5- dicarboxylic acid, l-methyl-1,4-dihydro-4-oxo-6-proyl- pyridazine-3,5-dicarboxylic acid, 1-(3-cyanophenyl)-1,4-dihydro-4-oxo-6-butylpyridazine-3,5- dicarboxylic acid, l-butyl-1,4-dihydro-4-oxo-6-methylpyridazine-3,5-dicarboxylic acid, 1-(2-trifluoromethyl-4-chlorophenyl)-1,4-dihydro-4-oXo-6- methylpyridazine-3,5-dicarboxylic acid, 1-(2-trifluoromethyl-4-bromophenyl)-1,4-dihydro-4-oXo-6- ethyklpyridazine-3,5-dicarboxylic acid, 1-(2-chloro-5-trifluoromethylphenyl)-1,4-dihydro-4-oXo-6- ethylphydridazine-3,5-carboxylic acid, 1-(2-naphthyl)-1,4-dihydro-4-oxo-6-butylpyridazine-3,5dicarboxylic acid, and derivatives of each of the above listed compounds wherein the hydrogen atom in one or both carboxy groups is replaced by a group or atom selected from sodium, potassium, lithium, methyl, ethyl, n-propyl isopropyl and butyl (all isomers). There should also be listed the acid addition salts of all the preceding compounds in List B. The following is a sequence utilized to prepare the compounds concerned in this invention. EMI8.1 The synthetic secuence outlined above is unique in its ability to produce (V) and (VI). No directed syntheses of either of these classes of compounds has been reported in the literature. The reactions involving the sodium hydride and acetyl chloride can be carried out in an inert solvent at a temperature from about O0,'to about 10 C; the reaction of the pyrone with the diazonium salt can be carried out at a temperature from about 0 to about 50 C; and the decarboxylation using sulfuric acid can be carried out in an inert atmosphere from about 200 to 25O0C. In the above reaction sequence a 3-oxoglutarate is first reacted with sodium hydride thereby replacing a hydrogen atom from the active methylene group followed by reaction with acetyl chloride to form the intermediate of Formula II which then rearranges under acid conditions to form the pyrone of Formula III. The pyrone is then reacted with a diazonium salt to form a hydrazone of Formula IV. The hydrazone is then rearranged in the presence of a base to form the dícarboxypyridazine of 'Formula V which is then decarboxylated under acidic conditions to form the 5- carboxypyridazine of Formula VI. A more preferred synthetio route to compounds of Formula (I) is outlined below. EMI9.1 In this approach the 3-oxoglutarate is first reacted with a diazonium salt to form the hydrazone of Formula VII which is then reacted with isopropyl magnesium chloride followed by reaction with acetyl chloride to form the dicarboxypyridazine ester of Formula VIII which is then hydrolyzed to the corresponding acid of Formula IX. Decarboxylation under strongly acidic conditions as described above will again form the monocarboxy pyridazine of Formula VI. The following preparations are provided to illustrate the processes for preparing the compounds of Formula I. There may also be used other processes described in the literature for the preparation of analagous compounds such as processes described in Belgian Patent No.864,704 and its foreign equivalents cited earlier. In the following preparations temperatures are in degrees Celsius and percentages are on a weight basis unless otherwise specified. Synthesis of 6-methyl-5-methoxycarbonyl-4-hydroxy-2-pyrone Via dimethyl-2-acetyl-3-oxoglutarate A 3-liter, three necked, round bottomed flask was equipped with addition funnel, paddle stirrer and thermometer. The flask was charged with 300 ml dry toluene and sodium hydride (50% as a dispersion in mineral oil, 82.8 g, 1.72 moles). The addition funnel was charged with dimethyl-3-oxoglutarate (dimethyl ester of acetone-l, 3-dicarboxylic acid, 300 g, 1.72 moles). The flask was cooled to 50 in an ice-water bath. The diester was added dropwise to the sodium hydride slurry, not allowing the reaction temperature to exceed 100. Complete addition required 3 hrs. The resulting mixture was stirred 30 mien. at 5 . Acetyl chloride (135 g, 1.72 moles) was then added dropwise through the addition funnel, being careful to maintain the pot temperature at 5-10 . After complete addition; the resulting slurry was .stirred a further 30 min., then poured slowly into 500 ml water saturated with ammonium chloride. The resulting mixture showed a pE of 6. The layers were separated. The aqueous phase was extracted with methylene chloride (3 x 100 ml). The combined organic layers were taken to dryness in vacuo to leave a yellow oil. Vacuum distillation of this oil (at 0.5 mm Hg) gave fractions boiling from 50-120 . A major fraction, bp 85-110 (97g) contained the desired acetylated diester, along with some 'starting material, as inferred by NMR. The- impure acetylated diester (97 g) obtained above, was dissolved in 300 ml dry xylene, along with p-toluenesulfonic acid (100 mg). This mixture was refluxed into a Dean-Stark trap for 12 hr. The resulting dark solution was cooled in an ice-water bath. The desired pyrone crystallizes out as fine needles (28.1 g, 10% yield based on dimethyl 3-oxoglutarate). An analytical sample was crystallized from ethyl acetate. NMR (CDC13): 5.6 ppm- (S. lE); 4.1 (S, 3E); 2.7 (S, 3H). IR (CH2Cl2): 5.75)#, 5.95 6.90, 9.10. mp 104-106 . Elemental Analvsis Calculated: C: 52.18; H: 4.38 Found: C: 52.30; H: 4.44 Synthesis fo 1-(p-Chlorophenyl)-1,4-dihydro-4-oxo-3carboxy-5-methoxycarbonyl-6-methylpyridazine A 250 a1, three necked, round bottomed flask was equipped with addition tunnel, paddle stirrer and thermometer. The flask was charged with 50 ml methanol, sodium acetate (16.0 g, 0.198 mole), and the above pyrone (8.0 g, 0.043 mole).. p-Chlorobenzenediazonium chloride was prepared on the side by the dropwise addition of sodium nitrite (3.3 g, 0.047 mole)- in 10 ml water to a cooled (5t) slurry containing p-chloroaniline (5.6 g, 0.043 mole) in aaueous hydrochloric acid (16.5 ml 12N RCl t0.198 mole) plus 10 ml water). The diazonium chloride solution was added dropwise to the solution containing the pyrone. This addition was carried out during 10 min. with no noticeable exotherm. After complete addition, the resulting orange slurry was stirred for 40 min. at room temperature. Suction filtration gave an orange filter cake which was washed repeatedly with water, then sucked dry during 2 hr. The filter cake thus obtained was placed back into the three necked flask used above. Methanol (200 ml) was added to give a slurry. Morpholine (lO-Og.,0.115 mole) was added in one portion. A mildly exothermic reaction occurred, and a dark, homogeneous solution was obtained. After stirring 10 min., the solution was poured into 3b0 ml water.. This was extracted with methylene chloride (3 x 100 ml). The combined organic extracts were extracted repeatedly with, dilute aqueous sodium hydroxide (pH 8). The combined aaueous basic layers were acidified with 6N hydrochloric acid. With cooling and scratching, a solid crystallized from solution. Suction filtration gave the product.as.a licht brown powder (8.2 g, 60% yield based on the pyrone NMR (CDCl3): 7.5 ppm (multiplet, 4H); 4.0 (S, 3H); 2.3 (5, 3H). IR (CHC12): 5.75 , 6.22, 6.90. mp 203-204 (dec.). An analytical sample was crystalized from methanol. Elemental Analvsis Calculated: C: 52.10; E: 3.44; N: 8.68 Found. C: 52.06; H: 3.43: N: 8.89 Synthesis of 1-(p-Chlorophenyl)-1,4-pihydro-4-oxo-5-carboxy-6- methpyridazine carbonyl-6-methyl 1-(p-chlorophenyl-1.4-dihydro-4-oxo-3-carboxy-5-methoxy-/ pyridazine (2,0-g, 6.2 mmoles)was dissolved in 10 ml, con centrated sulfuric acid, in an atmosphere of dry nitrogen. This was warmed rapidly'to 2000 and maintained there for 40 min. The resulting dark solution was cooled, then poured into cold water (50 ml). A brown precipitate formed immediately. Sutio: filtration and thorough washing with water gave the desired acid (1.0 g 63% yield), pure by NMR. NRM (CDCl3): 8,5 ppm (S, 1H); 7,5 (AB quartet, 4H); 2.8 ppm (S, 3E). IR (Nujol): 5.81 . mp 207-208 (dec.). An analytical sample was obtained by crystallization from methanol. Elemental Analysis Calculated : C: 54.45; R: 3.43 ; N: 10.59 Found: C: 54.45; H: 3.52; N: 10.16 Synthesis of Dimethol-2 ,3-dioxyglutarate, 2-UChloro- phenylhydrazone: A 10-Firter widemouthed polyethylenen container was fitted with a stirrer paddle and addition funnel. This container was charged with dimethyl-3-oxoglutarate (1 kg, 5.75 moles), 'methanol (1.5 1), and sodium acetate (1 kg, 12.19 moles). p-Chlorobenzenediazonium chloride (5.75 moles) was generated on the side in seven equal portions, by combining p-chloroaniline 7 x 104 g, 5..75 moles), hydroric acid (7 x 314 ml 12N, 26 moles), water (7 x 200 ml) and sodium nitrite (7 x 65..6 g in 100 ml H2O, 6.66 moles). The diazonium salt was added dropwise, rapidly to the reaction kettle. The pE was monitored periodically and maintained at 5 during the course of the reaction by adding sodium acetate via a spatula. At the end of the procedure, another 800 g of sodium acetate had been added. The resulting mixture was allowed to stand overnight, then suction filtered and the filter cake washed thoroughly with water. The brick-red filter cake was air dried to give 1.4 kg of the desired product (80% yield). NMR (CDC13) 7.5 ppm (S, 6s); 3.9 ppm (S, 6H); 3.7 ppm (S, 2E). 'This compound is known to the literature. See: Bulow and Hopfner, Berichte, 34, 71 (1901); ibid, 44, 2835 (1911). Synthbesis of Dimethyl-1-(p-chlorophenyl)-1,4-dihydro4-oxo-pyridazone-3,5-dicarboxylate A dry 1-l;iter, four-necked round bottomed flask was fitted with stirrer, thermometer, nitrogen inlet and rubber septum. The flask was charged with dimethyl-2,3- dioxyglutarate, 2-p-chlorophenyl hydrazone (50 g, 0.16 mole) in dry tetrahydrofuran (170 ml). This solution was maintained under an atmosphere of dry nitrogen while cooling to 50 C. Isopropyl magnesium chloride (72 ml, 2.25 N in ethyl ether, 0.16 mole) was added dropwise via syringe, maintaining the pot temperature at 5-10 C. After complete addition, the mixture was stirred for 15 min. in the cold, then acetyl chloride (12 ml, 13.0 g, 0.16 mole) was added dropwise, rapidly, keeping the temperature of the reaction mixture below 10 C. The resulting dark solution was allowed to warm to toom temperature during 2 hrs. Water (200-ml) was added. This mixture was stirred for 30. min., then extracted with ethyl acetate. The extracts were dried over MgSOn, then filtered and reduced, in volume in vacuo. The resulting dark oil was dissolved in ethyl ether, and cooled in an ice bath. The desired diester crystallized out to give Z2.1 g yellow powder (42% yield), mp 153-540C. NMR (CDC13): 7.6 ppm (multiplet, 4R); 4.0 ppm (S, 6n);' 2.3 ppm (S,. 3H)- IR (CH2Cl2): 5.75 , 6.12 , 9.15 Table I below gives the structure, melting point and elemental analysis for some of representative compounds of Formula (I) wherein R3 is hydrogen and which were prepared by the processes disclosed above. In Table I and in later Table III the figures first appearing for elemental analysis are those calculated and those immediately thereafter are those found. TABLE I EMI15.1 TABLE I (continued) Elemental Analysis(a) Compound No. X Y R6 mp ( C)(a) C H N 1 4-Cl Na n-Butyl 157-58 58.73 4.93 9.13 58.91 4.@4 9.25 2 4-Cl Na n-Propyl 171-72 57.44 4.48 9.57 57.43 4.33 9.30 3 3,4-diCl Na ethyl 202-03 49.86 3.22 8.95 50.12 3.27 9.32 4 H Na ethyl 163-64 63.92 4.95 11.47 63.90 4.89 11.81 5 4-Cl Na ethyl 190-191 56.02 3.98 10.05 55.93 3.98 9.96 6 4-Br Na ethyl 220 (dec) 48.32 3.43 8.67 48.71 3.45 8.66 7 H Na methyl 204 (dec) 62.60 4.38 12.17 63.05 4.47 11.94 8 4-Cl ethyl methyl 175-77 57.44 4.48 9.57 57.17 4.66 9.55 9 4-F Na methyl 211-12 50.06 3.65 11.29 57.69 3.70 11.11 TABLE I (continued) Elemental Analysis(a) Compound No. X Y R6 mp ( C)(a) C H N 10 4-Cl ethyl methyl 140-42 56.02 3.98 10.05 55.78 4.06 10.00 11 3,4-diCl Na methyl 213-14 48.18 2.69 9.37 47.52 2.72 4.74 12 4-Br Na methyl 200-10 (dec) 46.62 2.93 9.06 46.74 2.91 9.32 13 4-Cl Na methyl 207-08 54.45 3.43 10.59 54.45 3.52 10.16 14 4-Cl ethyl ethyl 129-131 58.73 4.93 9.13 58.61 5.12 9.26 15 4-Cl methyl ethyl 119-20 57.44 4.48 9.57 57.18 4.49 9.76 16 4-I Na ethyl 185-86 43.35 3.08 7.78 41.40 2.94 7.59 17 2-Cl Na ethyl 174-75 56.02 3.98 10.05 55.99 3.91 10.43 (a) Melting Points and Elemental Analyses recorded are for the parent acid of the sodium salts and carboxylic acid esters. Table II and III below give the structure, melting point in degrees Celsius and the elemental analysis of representative compounds of Formula (I), wherein R3 is a carboxy derivative, and which were prepared by the processes disclosed above. EMI19.1 TABLE II - Compound No. X Y R6 18 4-1 Na CH3CH2 19 2-C1 CH3 CH3CH2 20 4-1 CH3 CH3CH2 21 4-C1 Na n-C7H15 22 2,5-diCH3 CH3 CH3 23 2,5-diCH3 Na CH3CH2 24 2,5-diCH3 Na CH3 25 4-C1 Na C6H5 26 4-C1 CH3 C6H5 27 4-C1 Na CH3CH2CH2CH2 28 4-C1 CH3 CH3CH2CH2CH2 29 4-C1 Na CH3CH2CH2 30 3,4-diCl CH3 CH3CH2 31 4-C1 CH3 n-propyl 32 H Na Isopropyl 33 H CH3 Isopropyl 34 H Na CH3CH2 35 H CH3 CH3CH2 36 4-CF3 Na CH3 37 4-F Na CH3 38 4-CH3 Na z CH3 39 4-C1 NH-CH2CH2CH2CH3 CH3CH2 40 4-Br Na CH3 41 4-1 Na CH3 42 3,4-diC1 Na CH3 TABLE II (Continued) Compound No. X Y R6 43 H Na CH3 44 4-C1 Na CH3 45 4-Br CH3CH2CH2 CH3 46 4-Br CH3 CH3 47 4-Br CH3CH2 CH3 48 H CH3 CH3 49 4-Br Na CH3CH2 50 4-Br CH3 CH3CH2 51 4-C1 CH3 CH3CH2 52 4-C1 Na CH3CH2 53 2-C1 Na CH3CH2 54 4-C1 CH3 CH3 TABLE III Compound (a) Elemental Analysis (a) No. mp( C) C H N 18 225-300(dec) 42.07 3.06 6.54 42.48 3.01 7.11 19 130-31 54.78 4.31 7.99 54.57 4.15 8.39 20 -210-11 43.45 3.42 6.34 43.57 3.39 6.66 21 138-39 59.04 5.70 6.89 59.53 5.87 7.25 22 157-58 61.81 5.49 8.48 61.73 5.52 8.85 23 221-22 61.81 5.t9 8.48 62.04 ' 5.69 8.74 24 205-207 60.75 5.10 8.86 60.72 5.23 9.26 25 193-94 59.31 3.41 7.28 59.37 3.45 7.03 26 216-17 60.23 3.79 7.03 60.19 3.77 6.75 27 153-54 55.97 4.70 7.68 55.74 4.66 7.33 28 109-11 57.07 5.06 7.40 56.86 5.03 7.21 29 <RTI ID=21.4> 2056o 54.78 4.31 7.99 54.79 4.24 7.96 30 154-55 50.15 3.68 7.31 50.03 3.55 7.58 31 141-420 55.97 4.69 7.68 56.01 4.75 7.54 TABLE III (Continued) Compound Elemental Analysis No. mp( C) C H N 32 209-11 (dec) 60.75 5.09 8.86 61.30 5.21 9.40 33 158-59 61.81 5.49 8.48 61.61 5.51 8.30 34 194-95 59.59 4.67 9.27 58.93 4.58 9.78 35 187-88 60.75 5.09 8.86 60.46 5.14 8.78 36 206-08 50.57 3.11 7.87 50.40 3.03 8.18 37 209-10 54.90 3.62 9.15 54.90 3.67 9.13 38 216-18 59.60 4.67 9.27 59.43 4.78 9.17 39 127-28 57.22 5.33 11.12 57.28 5.31 10.66 40 215-17 45.79 3.02 7.63 45.71 3.02 7.58 41 228-31 40.59 2.68 6.77 40.60 2.68 6.70 42 218-19 47.08 2.82 7.85 47.22 2.93 7.98 43 223-27 58.33 4.20 9.72 58.05 4.21 9.59 '44 203-4 52.10 3.44 8.68 52.06 3.43 8.89 45 122-24 49.89 4.19 6.85 50.10 4.33 6.85 46 163-65 47.26 3.44 7.35 47.26 3.40 7.49 47 151-32 48.62 3.83 7.09 48.82 3.77 7.47 TABLE III (Continued) Compound Elemental Analysis No. mp( C) C B N 48 183-84 - 59.60 4.67 9.27 59.87 4.72 9.24 49 199-200 47.26 3.44 7.35 47.52 3.41 7.56 50 155-57 48.6'2 3.83 7.09 48.79 3.87 6.94 51 138-39 54.78 4.31 7.99 55.36 4.36 8.20 52 219-20 53.49 3.89 8.32 53.65 3.88 8.54 (a) As in Table I above, melting points and elemental analyses recorded are for the parent acid where Y is hydrogen. The compounds of Formula (I) are particularly useful as chemical hybridization agents in gramineous crops, such as wheat, barley, maize, rice, sorghum, millets, oats, rye, triticale, forage crops and the like. When used as chemical hybridization agents, the compounds induce a selective male sterility without also inducing unacceptable female sterility in the treated plants and without causing unacceptable phytotoxicity towards the treated plants. As used herein, the term male sterility includes both actual male sterility, as evidenced by a lack of male flower parts or by sterile pollen, and functional male sterility, in which the male flower parts are unable to cause pollination. The compounds also cause other plant growth regulatory responses, such as, for example, control of flowering, control of fruiting and inhibition of seed formation in non-cereal species and other related growth regulatory responses. Where, in the compounds of Formula (I), male sterility is accompanied by some female infertility and/or phytotoxicity, the compounds are still of utility in producing new plant hybrids or in the production of ergot for which see French Published Patent Application No.2400832. The compounds of Formula (I) may be used as plant growth regulators in the manner and at doses described in Belgian Patent No.864,704 and its foreign equivalents listed earlier. The compounds of Formula I may also be formulated, with such changes as are dictated by the solubities and other characteristics of the compounds in question, as described in the Belgian Patent or its equivalents. The compounds of Formula (I) may be used singly or in admixture or may be used in conjunction with other types of plant growth regulators or with different types of agricultural chemicals as described in the Belgian patent and its equivalents. Formulations usually include one or more of the compounds of Formula (I), e.g. in an amount from 1-99% by weight, and an agronomically acceptable carrier or diluent. Of course, reference in the last three paragraphs - and elsewhere in this specification unless the context requires otherwise - to compounds of Formula (I) includes the acid addition salts. In the biological data given later units are expressed in U.S. units, the metric equivalents of which are given below together with other explanatory information. 6 inches = 15.24 cm. Parts are parts by weight. Fertilizer (16-25-16) = (16-25-16 by wt. NPK). 1 tsp/gal = 1.3 ml/l. Isotox = benzenehexachloride Feekes' scale is described by W. Feekes, Vers.17 Tech. Tarwe Comm, Groningen, pp 560,561,1941. 50 gal/A (acre) = 467.5 1/aha. 2 oz/5O gal = 56.7g/189.25 1 Dose = dose of active ingredient lbs/acre = kg./ha lbs/acre = kg/ha 1/128 0.009 1/2 0.561 1/64 0.017 1 1.121 1/32 0.035 2 2.242 1/16 0.07 4 4.484 1/8 0.140 8 8.968 1/4 0.280 Chemical Hybridization Activity The following procedures are used to evaluate the activity of the compounds of the invention for inducing male sterility in cereals. An awned variety (Fielder) and an awnless variety (Mayo-64) of spring wheat are planted at the rate of 6 to 8 seeds per 6 inch pot containing a sterile medium of 3 parts soil and 1 part humus. The plants are grown under short-day (9 hour) conditions for the first 4 weeks to obtain good vegetative growth before flower initiation. The plants are then moved to long-day (16 hour) conditions which are provided by high intensity lights in the greenhouse. The plants are fertilized at 2,4, and 8 weeks after planting with a water soluble fertilizer (16-25-16) at the rate of 1 tsp/gal of water, and are frequently sprayed with isotox for aphid control and dusted with sulfur for powdery mildew control. Test compounds are foliarly applied to the awned female plants when these plants reach the flag leaf emergence stage (stage 8 on Feekes' scale). All compounds are applied in various concentrations.in an aqueous carrier (containing if necessary, an organic solvent and conventional surfactant). The carrier volume is 50 gal/A (acre) in all cases. A typical usable surfactant is that sold as TRITON XlOO used at a rate of 2oz/gal of carrier. After spike emergence but before anthesis, 4 to 6 spikes per pot are bagged to prevent outcrossing. At the first signs of flower opening, two spikes per pot are cross pollinated, using the approach method, with the awnless male parent. As soon as the seeds become plainly visible, spike length is measured and seeds per spike let counted in boh bagged and crossed spikes. Male sterility can then be calculated as percent inhibition of seed set in bagged spikes of treated plants, and female fertility in crossed spikes can be calculated as percent of control seed set. After maturity the seed on crossed spikes can be planted for determination of percent hybridization. Where applicable,percent sterility, percent fertility, and percent height inhibition are calculated from the following formulas: a. % Sterility = (Sc - St/Sc) x 100 5c = seeds/spikelet in bagged spikes of control plants. St = seeds/spikelet in bagged spikes of treated plants. b. % Fertility = (Ft/FC) x 100 Ft = seeds/spikelet in approach crossed spikes of treated plants F = seeds/spikelet in unbagged spikes of c control plants c. % Height inhibition = (Hc - Ht/Hc) x 100 Hc = Height of control plants Ht= Height of treated plants Table IV summarizes typical results obtained in the evaluation of compounds of Formula (I) wherein R3 is hydrogen. TABLE IV EMI28.1 TABLE IV (continued) Dose Male Plant Compound (1b/acre) Sterility % Injury (0-9) No. 1 1/8 0 0 1/4 24.4 0 1/2 74.2 0 1 91.0 0 2 99.1 0 2 1/8 0 0 1/4 29.4 0 1/2 75.1 0 1 99.1 0 2 100 0 3 1/8 5.7 0 1/2 ' 57.9 0 2 99.1 0 8 100 0 4 1/8 3.1 0 1/2 26.6 0 2 46.9 0 8 55.3 0 5 1/8 77.0 1/2 98.0 0 1/2 98.0 0 2 100.0 0 8 100.0 0 1/8 20.0 6 1/8 20.0 1/2 82.0 2 99.0 0 0 8 100.0 0 7 1/8 0 0 1/2 28.0 0 2 100.0 0 8 100.0 0 8 1 66.0 0 2 72.0 0 4 100.0 0 8 100.0 0 TABLE IV (Continued) Com Dose Male Plant pound (lb/acre) Sterility t; Injury (0-9) No. 9 1/2 1.0 0 1 0 0 2 0 0 4 - 57.0 0 10 1 99.0 0 2 100.0 0 4 100.0 0 8 100.0 0 11 1/4 10.8 0 1/2 39.4 0 1 90.8 0 2 100.0 12 1/4 19.9 0 1/2 41.2 0 1 90.5 0 2 93.2 0 Representative compounds of Formula (I) wherein R3 is hydrogen exhibit an improved margin of safety while maintaining high levels of activity, as compared to the known compound l(p-chlorophenyl) 1 ,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid sodium salt, as shown in Table V below TABLE V EMI31.1 TABLE V (continued) EMI32.1 <tb> <SEP> 6 <SEP> Slb/acre) <SEP> ¯ <SEP> ttale <SEP> Plant <tb> <SEP> x <SEP> p <SEP> .2 <SEP> 51b/acre) <SEP> * <SEP> v <SEP> InjurvInurv <tb> <SEP> Z <SEP> ,O <SEP> - <SEP> 1/8 <SEP> 3.1: <SEP> 0 <tb> <SEP> 1/2 <SEP> 26 <SEP> 0 <tb> <SEP> 7 <SEP> 46.9= <SEP> 0 <tb> <SEP> B <SEP> 55.3= <SEP> 0 <tb> 3, <SEP> 4 <SEP> ! <SEP> Cr <SEP> 7/9 <SEP> Its <SEP> T <SEP> /8 <SEP> ;, <SEP> 7: <SEP> 0 <tb> <SEP> 1/2 <SEP> 57.9: <SEP> 0 <tb> <SEP> 2 <SEP> -09.2: <SEP> 0 <tb> <SEP> 8 <SEP> 00.0: <SEP> 0 <tb> <SEP> c-.1,c---: <SEP> r/s <SEP> 77.C: <SEP> 0 <tb> <SEP> = <SEP> 1/2 <SEP> 98.t= <SEP> 0 <tb> <SEP> 2 <SEP> 7C <SEP> -C- <SEP> 0 <tb> <SEP> S <SEP> ics.c: <SEP> 0 <tb> <SEP> 4-B: <SEP> 3C::. <SEP> Ts8 <SEP> 20.0: <SEP> 0 <tb> <SEP> 7/2 <SEP> S2.0: <SEP> 0 <tb> <SEP> 2 <SEP> 99.0: <SEP> 0 <tb> <SEP> 8 <SEP> . <SEP> 200.0: <SEP> o <tb> <SEP> L: <SEP> C <SEP> 2/s <SEP> o <SEP> 0 <tb> <SEP> 2/2 <SEP> 2 .cm <SEP> 0 <tb> <SEP> 2 <SEP> 200.0: <SEP> 0 <tb> <SEP> 8 <SEP> lOO.C- <SEP> O <tb> <SEP> a <tb> <SEP> CO:Na <tb> <SEP> 1 <SEP> 1/4 <SEP> xS.C7: <SEP> O <tb> <SEP> C <SEP> 7/2 <SEP> gr <SEP> O <tb> <SEP> 2 <SEP> 1 <SEP> 200.0: <SEP> 1 <tb> <SEP> 2 <SEP> /O0-C= <SEP> S <tb> <SEP> tl <tb> Table VI summarizes typical results obtained in the evaluation of compounds of Formula I wherein R3 is carboxy derivative. A dash indicates that no determination of value was made. TABLE VI EMI33.1 Compound X Y R6 Dose Percent Percent Plant No. lb/A Male Female Injury -Steril- Steril- 0-9 ity ity 18 4-I Na CH3CH2 1/32- 100 - trace 1/8 100 - trace 1/2 100 - 2 2 100 - 5 19 2-C1 CH3 CH3CH2 1/8 57.0 - 0 1/2 100 - 0 2 100 - 1 8 100 - 4 20 4-1 CH3 CR3CH2 1/32 84.3 - 0 1/8 100 - 1 1/2 100 - 3 2 100 - 5 28 4-C1 CH3 n-butyl 1/8 19.0 - 0 1/2 16.0 - 0 2 32.7 620 0 8 87.8 7.6 trace 29 4-C1 Na n-CR - 1/8 80.2 - 3 CH2CH2 1/2 100 - 5 2 100 - 7 8 100 - 8 30 3,4- CH3 CH3CH2 1/128 0 - 0 diCl 1/64 9.8 23.9 0 1/32 42.7 56.3 0 1/16 87.5 63.5 0 32 H Na Iso- 1/8 4.4 - 0 propyl 1/2 99.6 - 0 2 100 - 0 8 100 - 4 Compound X Y R6 Dose Percent Percent Plant No. lb/A Male Female Injury Steril- Steril- 0-9 ity ity 33 H CH3 Isopro- 1/8 21.8 - 0 pyl 1/2 79.9 40.2 0 2 100 0.43 0 8 100 0 2 34 H Na CH3CH2 1/8 71.1 - 0 1/2 100 - 2 2 100 - 6 8 - - 8 35 H CH3 CH3CH2 1/8 84.6 - 1/2 100 - 2 100 - 8 36 4-CF3 Na CH3 1 3.0 - 0 2 5.0 - 0 4 53.0 - 0 8 62.0 - 0 37 4-F Na CH3 1/8 0 - 0 1/4 0 - 0 1/2 7.0 - 0 1 83.0 - 0 39 4-Cl NH CH (CH2)3- 3CH2 1/8 4.0 3 2 CH3 1/2 4.4 - 0 2 86.7 69.4 0 8 100 - trace 40 4-Br Na CH3 1/2 22.0 - 0 1 87.0 - trace 2 100 - 3 4 100 - 5 Compound X Y R6 Dose Percent Percent Plant No. lb/A Male Female Injury Steril-. Steril- 0-9 ity ity 41 4-1 Na CH3 1/2 0 - 0 1 72.0 - 0 2 99.0 - 0 4 100 - 2 42 3,4 Na CH3 1/2 3.0 - 0 diCl 1 2.0 - 0 2 43.0 - trace 4 70.0 - 3 43 H Na CH3 1/2 12.0 - 0 1 77.0 - 0 2 92.0 - 0 4 100 - 0 44 4-C1 Na CH3 1/2 4.0 - 0 1 84.0 - 0 2 100 - 0 4 94.0 - 1 45 4-Br CH3- CH3 1 10.0 - 0 CH2CH2 2 57.0 - 0 4 93.0 - 1/2 8 100 - 2 46 4-Br CH3 CH 1/8 0 - 0 3 1/4 27.0 - 0 1/2 80.0 - 0 1 100 - 1/2 47 4-Br CH3CH2 CH3 1 9.0 - 0 2 64.0 - 0 4 99.0 - 2 8 100 - 3 Compound X Y R6 Dose Percent Percent Plant No. lb/A Male Female Injury Steril- Steril- 0-9 ity - ity 48 H CH3 CH3 1/8 0 - 0 1/2 80 - 0 2 100 - 0 8 100 - 1 49 4-Br Na CH3CH2 1/32 11.4 - 0 1/16 69.3 - 0 1/8 99.1 - 0 1/4 100 - 2 50 4-Br CH3 CH3CH2 1/32 91.2 - 0 1/16 85.1 - 0 1/8 100 - 0 1/4 100 - 0 51 4-C1 CH3 CH3CH2 1/32 40.9 - 0 1/16 92.2 - 1 1/8 94.6 - 2 1/4 95.5 - 3 52 4-C1 Na CH3CH2 1/32 36.4 - 1 1/16 100 - 2 1/8 91.3 - 1 1/4 100 - 2 53 2-Cl Na C2H6 1/8 100 - 0 1/2 100 - trace 2 100 - 3 8 100 - 4 54 4-C1 CH3 CH3 1/8 4 1/4 0 - 1/2 53 - 1 69 - 2 92 - Table VII below gives comparative field test data on winter wheat (variety Newton) using potassium 1-(4 -chlorophenyl) -1, 4-dihydro-4-oxo-6-methyl- pyridazine-3-carboxylate (Compound A) with a compound of the invention, potassium 1-(4 -chlorophenyl)-1,4-dihydro-4-oxo-6-ethyl-pyridazine-5carboxylate (Compound B). TABLE VII Male Plant Dose Sterility Seed Yield Plant Height Injury (lbs/A) (%) (% of Nontreated) (%Inhibition) (0-9) Compound A 1/4 24 87 1 0 1/2 65 61 1 0 1 99 29 3 0.3 2 100 15 14 1.3 Compound B 1/2 - 11 1Q8 0 '0 1 18 88 0 0 2 39 81 . 0. 0 4 85 75 0 0 Table VIII gives comparative field test data on winter wheat using sodium 1-(4 -chlorophenyl)-l,4 dihydro-4-oxo-6-methyl-pyridazine-3-carboxylate (Com pound C) with a'compound of the present invention, sodium 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-6-methyl pyridazine-5-carboxylate (Compound D). TABLE VIII 1 2 3 4 Wheat Variety ED95 Seed Seed Plant Compound (lb/A) Yield Quality Injury C Abe 0.6 59% 0.1 0 Hart 1.5 54% 1.1 0 Centurk 0.9 69% 0.7 0.3 Cloud 0.9 57% 2.2 0.7 D Abe 8.0 83% - 0 0 Hart - 15.0 73% 0 0 Centurk 18.0 72% 0 0 Cloud 17.0 78% 0 0 @@dose of active ingredient required to effect 95% male sterility (0.6 lb/A = 0.67 Kg/ha, 0.9 lb/A = 2 Kg/ha, 1.5 lb/A = 1.7 Kg/ha, 8 lb/A = 8.97 Kg/ha, 15 lb/A = 16. 8 Kg/ha, 17 lb/A = 19.06 Kg/ha and 18 lb/ha = 20.18 Kg/ha). 2. As a percent of untreated control. 3. 0-5. 0 denotes a normal seed; 5 denotes a very shriveled seed. 4. 0-10. 0 denotes no injury; 10 denotes plant kill.

Claims: Claims: 1. A compound of Formula (I) below, or an agronomically acceptable acid addition salt thereof, EMI40.1 wherein R1 is (C1-C4) alkyl, phenyl or naphthyl each of the last two groups being optionally substituted with up to three of the same or different substituents selected from halogen, trihalomethyl, (C1-C4) alkoxy, (C1-C4) alkyl and cyano; R3 is hydrogen or a group as defined below for R5; S R is a carboxy (-COOH) group or agronomically acceptable alkali metal salt thereof, an alkoxycarbonyl (-COOR) group or a substituted carbamoyl (-CONR R group, wherein R represents (C1-C4) alkyl, R represents hydrogen or (C1-C4) alkyl and R" represents (C1-C4) alkyl; and R6 is a (C1-C4) alkyl group or an optionally substituted phenyl or naphthyl group as defined for R1 above. 2. A compound as claimed in Claim 1, wherein R1 is halo substituted phenyl, R3 is hydrogen, R5 is CO2Na, CO2K or CO2CH3 and R6 is methyl or ethyl. 3. A compound as claimed in Claim 2, wherein R1 is 4-chloro- or 4-bromo-phenyl, R5 is CO2Na or CO2K and R6 is ethyl. 4. A compound as claimed in Claim 1, wherein R1 is halo-substituted phenyl, R is CO2Na, CO2K or CO2CH3, R5 is CO2CH3 and R6 is methyl or ethyl. 5. A compound as claimed in Claim 4, where R1 is 4-chloro- or 4-bromo-phenyl, R3 is CO2Na or CO2K, R5 is CO2CH3 and R6 R is ethyl. 6. A plant growth regulating composition containing at least one compound as claimed in any preceding claim and an agronomically acceptable carrier there for. 7. A method of regulating the growth of a gramineous crop plant which comprises applying to the growing plant, or to seeds thereof, a growth regulating amount of one or more compounds as claimed in any one of Claims 1-5. 8. A method as claimed in Claim 7 as applied to the production of hybrid seed by using at least one growth regulating compound which induces male sterility without destroying female fertility. 9. A method as claimed in Claim 8 wherein the plant is maize, barley, wheat, sorghum or a forage crop plant.

Inventors: PATTERSON, DENNIS RAY
Applicants: ROHM AND HAAS COMPANY
Application year: 1981
Main classification: C07D237
IPC codes: A01H1, C07D237, A01N43