GB1596611A

GB1596611A - 1,4-dihydro-4-oxo-6-alkyl-pyridazine-3-carboxylic acid derivatives thereof and their use as plant growth regulants

Info

Publication number: GB1596611A
Application number: GB7638/78A
Authority: GB
Original assignee: Rohm and Haas Co
Current assignee: Rohm and Haas Co
Priority date: 1977-03-10
Filing date: 1978-02-27
Publication date: 1981-08-26
Also published as: AR219522A1; FR2383605A1; JPS62265204A; IL54122A0; CH629077A5; NL171118C; IT7867511A0; DK156607C; BG34901A3; ZA781424B; EG13401A; PL115813B1; JPS53133633A; PL205233A1; IL54122A; SE8503365L; NZ186596A; DK156607B; GR64069B; TR20326A

Abstract

Agents for regulating the growth of plants are described which correspond to the formula: <IMAGE> where R<1> represents a carboxy radical or a corresponding salt suitable in agriculture, or an alkoxycarbonyl radical, R<2> represents an optionally substituted phenyl radical, R<3> represents an alkyl radical, and R<4> represents a hydrogen atom or an alkyl or halo radical. These compounds can be used in particular for the production of hybrid cereals by induction of male sterility.

Description

(54) 1 ,4-DIHYDRO-4-OXO-6-ALKYL PYRIDAZINE 3-CARBOXYLIC ACID, DERIVATIVES THEREOF, AND THEIR USE AS PLANT GROWTH REGULANTS (71) We, ROHM AND HAAS COMPANY, a Corporation organized under the laws of the State of Delaware, United States of America, of Independence Mall West, Philadelphia, Pennsylvania 19105, United States of America, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention concerns compounds which show activity as plant growth regulants, particularly as chemical hybridization agents, to growth regulant compositions which contain these compounds, and to methods of regulating the growth of plants, particularly by inducing selective male sterility, with these compounds and compositions.

The cereal grains, such as corn (i.e. maize), wheat, rice, rye, barley, millets, sorghum, and teff are among the major food crops throughout the world. This importance has led to extensive research to improve both the productivity and food value of these crops. One of the most important approaches taken to improve the quality and yield of the cereal grains has been hybridization. While hybridization has been an effective technique for some crops, most notably corn, there have been a number of problems, with present techniques. For example, corn hybridization requires time-consuming hand detasseling or inefficient mechanical detasseling, possibly injuring the corn plant. Corn, barley, and wheat hybridization by means of cytoplasmic male sterile varieties can only be done with a limited genetic base, requiring a maintainer line and a restorer line. Furthermore, cytoplasmic male sterile techniques with barley and wheat necessitate a highly sophisticated approach to deal with the genetic complexities of these crops, and great success has not yet been achieved in developing a suitable approach. Since the induction of selective male sterility by chemical means would obviate many of the problems confronting the present hybridization techniques, new compounds which selectively produce the desired sterility would be extremely desirable in dependably and economically supplying the male sterile plants needed for hybridization.

In accordance with this invention, there is provided a method of inducing male sterility in a cereal grain plant which comprises treating the plant prior to meiosis with an amount, which is effective to produce male sterility in the plant, of at least one 4-pyridazone having the formula

wherein R' is a carboxy group (-COOH), or an agronomically-acceptable salt thereof, or alkoxycarbonyl, preferably having up to 12 carbon atoms in the alkoxy moiety, most preferably up to 4 carbon atoms in the alkoxy moiety, R2 is phenyl or substituted phenyl having up to 3 substituents collectively having a total of zero to 6 carbon atoms, the substituent(s) being selected from (1) alkyl, (2) C4H4= forming a naphthyl group, (3) alkoxy, (4) phenoxy, (5) halogen, (6) nitro, (7) perhaloalkyl, (8) alkoxyalkyl, (9) alkoxyalkoxy, (10) amino, (11) alkyl- or dialkylamino, (12) cyano, (13) alkoxycarbonyl, (14) carbamoyl, (15) alkyl- or dialkyl-carbamoyl, (16) sulfo, (17) sulfonamide, (18) alkylcarbonyl, (19) carboxyalkyl, (20) alkanoyloxy, (21) haloalkyl, (22) alkanoylamino, (23) alkylthio, (24) alkylsulfinyl and (25) alkylsulfonyl, R3 is alkyl, preferably having up to 4 carbon atoms, and R4 is hydrogen, alkyl, preferably having up to 4 carbon atoms, or halogen, preferably a bromine or a chlorine atom.

In a preferred embodiment of the invention, R' is a carboxy group or a salt thereof, R3 is a methyl group, R4 is a hydrogen atom or a halogen atom, and R2 is a substituted phenyl group.

When R' is a salt of a carboxy group, an alkali metal, alkaline earth metal, or transition metal can provide the cation. The cation can also be an ammonium or substituted ammonium group. Representative metal salt cations include alkali metal cations, which are preferred, such as sodium, potassium and lithium; alkaline earth metal cations, such as calcium, magnesium, barium and strontium, or heavy metal cations, such as zinc, manganese, cupric, cuprous, ferric, ferrous, titanium and aluminum. Among the ammonium salts are those in which the ammonium cation has the formula NZ1Z2Z3Z4, wherein Z1, Z2, z3 and Z4 (which may be the same or different) represent hydrogen, hydroxy, (C1-C4)alkoxy, (C1-C20)alkyl, (C3-C8)alkenyl, (C3-Ca)alkynyl, (C2-C8)hydroxyalkyl, alkoxyalkyl having from 2 to 8 carbon atoms, (C2-C6)aminoalkyl, (C2-C6)haloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenylalkyl having up to 4 carbon atoms in the alkyl moiety, amino or alkyl-substituted amino. Alternatively, any two of z, Z2, z3, or Z4 can be joined together to form, with the nitrogen atom, a 5- or 6-membered heterocyclic ring which optionally has up to one additional hetero oxygen, nitrogen, or sulfur atom in the ring and which is preferably saturated as in a piperidine, morpholine, pyrrolidine, or piperazine ring. Another alternative is that any three of Z1, Z2, z3, or Z4 can be joined together to form, with the nitrogen atom, a 5- or 6-membered aromatic heterocyclic ring, such as a pyrrole or pyridine ring. When the ammonium group contains a substituted alkyl, substituted phenyl, or substituted phenylalkyl group, the substituents will generally be selected from halogen, (C1-C8)alkyl, (C1-C4)alkoxy, hydroxy, nitro, trifluoromethyl, cyano, amino and (C1-C4)alkylthio. Such substituted phenyl groups preferably have up to two such substituents. Representative ammonium cations include ammonium, dimethylammonium, 2-ethylhexylammonium, bis(2hydroxyethyl)ammonium, tris(2-hydroxyethyl)ammonium, dicyclohexylammonium, t-octylammonium, 2-hydroxyethylammonium, morpholinium, piperidinium, 2-phenethylammonium, 2-methylbenzylammonium, n-hexylammonium, triethylammonium, trimethylammonium, tri(nbutyl)ammonium, methoxyethylammonium, diisopropylammonium, pyridinium, diallylammonium, pyrazolium, propargylammonium, dimethylhydrazinium, hydroxyammonium, methoxyammonium, dodecylammonium, octadecylammonium, 4-dichlorophenylammonium, 4-nitrobenzylammonium, benzyltrimethylammonium, 2-hydroxyethyldimethyloctadecylammonium, 2 hydroxyethyldiethylQctylammonium, decyltrimethylammonium.

hexyltriethylammonium and 4-methylbenzyltrimethylammonium.

Representative embodiments of R2 include a phenyl group substituted with alkyl having up to 4 carbon atoms; alkoxy having up to 4 carbon atoms; fluorine, chlorine, bromine or iodine; trifluoromethyl; alkoxyalkyl having up to 6 carbon atoms; alkoxyalkoxy having up to 6 carbon atoms; alkyl- or dialkyl-amino groups having not more than 4 carbon atoms in each alkyl substituent; alkoxycarbonyl having up to 4 carbon atoms in the alkoxy moiety; alkyl- or dialkyl-carbamoyl groups having not more than 4 carbon atoms in each alkyl substituent; alkylcarbonyl or carboxyalkyl each having up to 4 carbon atoms in the alkyl moiety; alkanoyloxy having up to 4 carbon atoms; alkanoylamino having up to 4 carbon atoms; alkylthio having up to 4 carbon atoms; alkylsulfinyl having up to 4 carbon atoms; and alkylsulfonyl having up to 4 carbon atoms. The most preferred substituents on the phenyl group are 1 or 2 halogen atoms, a (C1-C4)alkyl, preferably methyl, group, a (C1-C4)alkoxy, preferably methoxy group, or a trifluoromethyl group.

Typical compounds within the scope of this invention include: - - phenyl - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, 1 - (4 - chlorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 carboxylic acid, 1 - (4 - fluorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, 1 - (4 - bromophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 carboxylic acid, 1 - (4 - iodophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, 1 - (3 - fluorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, 1 - (3 - chlorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 carboxylic acid, 1 - (3 - bromophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, I - (3,4 - dichlorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, 1 - (2 - fluorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, 1 - (2 - chlorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, 1 - (4 - trifluoromethylphenyl) - 1,4 - dihydro - 4 - oxo - 6 methylpyridazine - 3 - carboxylic acid, 1 - (3 - trifluoromethylphenyl) - 1,4 - dihydro - 4 - oxo - 6 methylpyridazine - 3 - carboxylic acid, I - phenyl - 1,4 - dihydro - 4 - oxo - 6 - ethylpyridazine - 3 - carboxylic acid, 1 - (4 - chlorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - ethylpyridazine - 3 - carboxylic acid, 1 - (4 - fluorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - ethylpyridazine - 3 carboxylic acid, I -(3,4 - dichlorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - ethylpyridazine - 3 carboxylic acid, I - phenyl - 1,4 - dihydro - 4 - oxo - 6 - propylpyridazine - 3 - carboxylic acid, 1 - phenyl - 1,4 - dihydro - 4 - oxo - 5,6 - dimethylpyridazine - 3 - carboxylic acid, 1 - (4 - chlorophenyl) - 1,4 - dihydro - 4 - oxo - 5,6 - dimethylpyridazine - 3 - carboxylic acid, 1 - phenyl - 1,4 - dihydro - 4 - oxo - 5 - ethyl - 6 - methylpyridazine - 3 - carboxylic acid, 1 - phenyl - 1,4 - dihydro - 4 - oxo - 5,6 - diethylpyridazine - 3 - carboxylic acid, 1 - (4 - methylphenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, 1 - (2 - chloro - 4 - methylphenyl)- 1,4 - dihydro - 4 - oxo - 6- methylpyridazine - 3 - carboxylic acid, 1 - (2,4,6 - trichlorophenyl) - 1,4 - dihydro - 4 - oxo - 6 methylpyridazine - 3 - carboxylic acid, I - (3 - ethoxyphenyl) - 1,4 - dihydro - 4 - oxo - 6 - ethylpyridazine - 3 - carboxylic acid, I - (4 - methylthiophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, 1 - (3 - cyanophenyl) - 5 - bromo - 1,4 - dihydro - 4 - oxo - 6 ethylpyridazine - 3 - carboxylic acid, 1 - phenyl - 5 - bromo - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid, 1 - (3 - chlorophenyl) - 5 - chloro - 1,4 - dihydro - 4 - oxo - 6 methylpyridazine - 3 - carboxylic acid, - - (4 - chlorophenyl) - 5 - bromo - 1,4 - dihydro - 4 - oxo - 6- ethylpyridazine - 3 - carboxylic acid, and the salts and esters of the above acids.

The compounds concerned in the invention can be prepared by methods known per se for analogous compounds or other methods devised for the purpose.

In one convenient method, a 4 - hydroxy - 2 - pyrone of the formula

wherein R6 is a hydrogen atom or an alkyl group and R3 is defined above, or a salt of a pyrone of Formula II (prepared by treating the pyrone with an equivalent of a suitable aqueous base such as potassium or sodium hydroxide, acetate, or carbonate), is reacted, usually at a temperature from -10 to 500C, in a polar solvent, such as water, methanol, ethanol, glyme or dimethylformamide, with a diazonium salt, such as diazonium chloride, prepared by conventional diazotization technique from an amine of the formula R2--NH, (III) wherein R2 is as defined above. The product hydrazone, which has the formula

wherein R2, R3 and R6 are as defined above, is then treated with either an aqueous acid, such as hydrochloric acid, trifluoroacetic acid, sulfuric acid, methanesulfonic acid or nitric acid, or an aqueous base, such as sodium carbonate, or sodium hydroxide, usually at a temperature from 20 to 1500C and preferably 40 to 100"C, to yield (by a rearrangement) a pyridazine of the formula

wherein R2, R3 and R6 are as defined above.

Esters of the pyridazine of Formula V are prepared by esterification with a suitable alcohol, preferably a (C1-C4)alkanol. One convenient technique is a Fischer esterification, using anhydrous hydrochloric acid or sulfuric acid as a catalyst and the alcohol as the solvent. This esterification is generally carried out at a temperature from 35 to 1500C, optionally using an inert cosolvent such as methylene chloride, ethylene chloride, diethyl ether, toluene or xylene. Salts of the pyridazines of Formula V and their 5-halo analogues can be prepared by conventional techniques, such as by neutralization with an appropriate inorganic or organic base, in a solvent such as water or methanol.

The compounds concerned in the invention in which R4 is a halogen atom can be prepared by reacting a pyridazine of Formula V in which R6 is a hydrogen atom with one equivalent of a halogenating agent such as bromine, chlorine, sulfuryl bromide or sulfuryl chloride in a suitable inert solvent such as hexane, benzene, ethylene, dichloride or methanol, usually at a temperature from 0 to 50 C and preferably at room temperature.

Table I following lists typical compounds concerned in the invention and their melting points and elemental analyses. The working preparations which follow Table I show the synthesis of Compounds 10, 12, 14 and 16 in Table I and in these preparations all temperatures are in degrees Celsius and parts and percentages are by weight, unless otherwise indicated.

TABLE I 1-Aryl-1,4-dihydro-4-oxo-pyridazines

Compound No. R4 X m.p.( C) %C %H %N %Hal Calc. 58.06 3.65 11.29 7.65 H H 3-F 213-5 Found 58.07 3.60 11.33 7.68 2 H 4-CH3, 202-3 56.22 3.63 10.09 12.77 3-C1 55.92 3.84 10.90 13.36 3 H 4-I 241-2 40.47 2.55 7.87 35.64 41.20 2.46 8.05 35.67 4 H 4-Br 243 46.62 2.93 9.06 25.85 47.45 3.14 9.26 25.64 5 H 4-CF3 234-5 52.35 3.04 9.40 19.11 51.99 2.97 9.13 18.94 6 H 4-NO2 244-5 52.37 3.30 15.27 - 52.76 3.33 15.69 - 7 H 4-CH3 162-3 63.92 4.95 11.47 - 63.66 4.89 11.52 - 8 H 2,3-benzo- 218-20 61.06 3.52 8.90 11.27 4-C1 61.07 3.42 8.86 11.00 9 H 4-OCH3 169-70 59.94 4.64 10.77 - 60.14 4.62 10.82 - 10 H 4-F 185-7 58.06 3.65 11.29 7.65 58.73 3.64 11.74 7.47 11 H 3,4- 2202 48.18 2.69 9.37 23.71 diCI 48.03 2.73 9.21 23.96 12 H 4-C1 229-30 54.45 3.43 10.59 13.39 54.49 3.44 10.44 13.59 13 H 3-C1 192-3 - - - 14 H H 173 - - 15 Br 4-CH3 241 48.31 3.43 8.67 24.73 49.37 3.59 9.25 23.65 16 Br 4-F 219-20 44.06 2.46 8.57 24.43 44.50 2.52 9.00 24.26 Compound No. R4 X m.p. ("C) %C %H %N %haul Calc.

17 Br 4-Br > 25 Found 37.14 2.08 7.22 41.19 36.78 1.98 7.35 40.83 18 Br H 22 46.62 2.93 9.06 25.85 46.68 2.88 9.25 25.62 19 Cl 4-Br 255-9 41.95 2.35 8.16 23 26** 41.65 2.31 7.74 23.17 *"/ Br; % F: Cal. 5.81; found 5.83.

**% Br; F: calc. 10.37; found 9.91.

Preparation 1 (Compound 10, Table I) Preparation of 1 -(4-Fluorophenyl)- 1 ,4-dihydro-4-oxo-6- methylpyridazine-3-carboxylic Acid 4 - Hydroxy - 6 - methyl - 2 - pyrone (7.88 g) is suspended in 250 ml water and 6.63 g of anhydrous sodium carbonate is added to the suspension to effect solution of the pyrone.

In a separate flask, 7.22 g of 4-fluoro aniline is mixed with 25 ml concentrated hydrochloric acid and 31 ml water The resulting solution is maintained at about 5 to 100 and a solution of 4.75 g of sodium nitrite in 16 ml of water is added. The resulting solution of 4-fluorophenyldiazonium chloride is added dropwise to the stirred pyrone solution, while maintaining the temperature at 5 to 100, and the pH at 8 to 9 by adding small amounts of aqueous sodium hydroxide.

The resulting hydrazone is refluxed for about 2 hours with 500 ml of concentrated hydrochloric acid. Coating and filtration yields 10.2 g of 1 - (4 fluorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid which is recrystallized from chloroform/ether (mp -- 185--7").

Preparation 2 (Compound 12, Table I) Preparation of 1 -(4-Chlorophenyl)- 1 ,4-dihydro-4-oxo-6- methylpyridazinecarboxylic Acid and its Sodium Salt p-Chloroaniline (12.75 g) is dissolved in 40 ml of concentrated hydrochloric acid and cooled to 0 and to the solution thus obtained there is added a solution of 7.6 g sodium nitrite temperature between 0 and 5". The diazotized aniline is added under ice cooling to a previously prepared solution of 12.6 g 4 - hydroxy - 6 methyl - 2 - pyrone and 55 g sodium carbonate in 500 ml of water.

The resultant slurry is heated at reflux overnight. When complete reaction is not observed, the pH is adjusted to 12 and refluxing is continued. The dark solution is neutralized to pH 6-7 with acetic acid and treated with activated charcoal. The filtrate is acidified to pH 2 with concentrated hydrochloric acid under ice cooling to precipitate product. The acid is recrystallized from acetone/hexane yielding 10.5 g (39%) 1 - (4 - chlorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine 3 - carboxylic acid (mp -- 229--230"C).

The acid (5.0 g) is converted to the sodium salt by treatment with 0.76 g sodium hydroxide in 200 ml of anhydrous methanol. The solvent is removed and the solid is washed with ether and dried in vacuo at 90"C. Analysis calculated for Cl2H8CIN2ONa 112 H2O: C, 48.75; H, 3.07; N, 9.48; Cl, 11.99; Na, 7.78. Found: C, 48.11; H, 2.80; N, 9.24; Cl, 12.37; Na, 7.62.

Preparation 3 (Compound 14, Table I) Preparation of 1 -Phenyl- 1 ,4-dihydro-4-oxo-6-methylpyridazine 3-carboxylic Acid In 375 ml of water is suspended 11.8 g of 4 - hydroxy - 6 - methyl - 2 pyrone, and 9.95 g of anhydrous sodium carbonate is added to effect solution of the pyrone.

In a separate flask; 9.08 g of aniline is mixed with 37.5 ml of concentrated hydrochloric acid and 47 ml of water. The resulting solution is maintained at about 5 to 10 and a solution of 7.13 g of sodium nitrite in 24 ml of water is added. The resulting solution of phenyldiazonium chloride is drop-added to the stirred pyrone solution, while maintaining a temperature of about 5 to 10 . The pH is maintained at about 8 to 9 by the addition of small amounts of sodium hydroxide solution.

After the addition is complete, the resulting hydrazone (18 g) is isolated by filtration and resuspended in 500 ml of concentrated hydrochloric acid. The mixture is refluxed for 2-1/2 hours, and then cooled. The 1 - phenyl - 1,4 dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic acid precipitates out as brownish crystals which are recrystallized from water. Yield - 7.0 g; mp - 1730.

Preparation 4 (Compound 16, Table I) Preparation of 1 (4-Fluorophenyl)-5-bromo- 1 ,4-dihydro-4-oxo- methylpyridazine-3-carboxylic Acid - - (4 - Fluorophenyl) - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine - 3 - carboxylic (1.5 g) is suspended in 100 ml of dry methanol, and 0.242 g of sodium hydroxide is added. To the solution is added dropwise 1.038 g of bromine dissolved in 50 ml of methanol. The solvent is removed leaving a white solid, which is taken up in dilute base and the solution acidified with hydrochloric acid. The resulting precipitate is filtered and recrystallized from chloroform/ether to yield 1.4 g of 1 (4 fluorophenyl) - 5 - bromo - 1,4 - dihydro - 4 - oxo - 6 - methylpyridazine 3 - carboxylic acid. (mp -- 219--20").

The compounds concerned in the invention are particularly useful as chemical hybridization agents in cereal crops, such as wheat, barley, maize, rice, sorghum, millets, oats and rye. When used as chemical hybridization agents, the compounds effectively induce a high degree of selective male sterility, that is without also inducing significant female sterility, in the treated plants and without causing significant growth inhibition of 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 of the invention 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.

When used as hybridization agents, the compounds are applied in any amount which will be sufficient to effect the desired plant response without causing any undesirable or phytotoxic response. The compounds are generally applied to the crops to be treated at a rate of from 0.035 to 22.42 kg per hectare and preferably 0.14 to 11.21 kg per hectare. The rate of application will vary depending on the crop being treated, the compound being used for treatment, and related factors.

- To obtain hybrid seed, the following procedure is generally employed. The two parents to be crossed are planted in alternate strips. The male/female parent is treated with a compound concerned in the invention. The male-sterile parent thus produced will be pollinated by pollen from the other male-fertile parent, and the seed produced by the male-sterile parent will be hybrid seed which can then be harvested by conventional means.

A preferred method of applying a compound of the invention as a chemical hybridization agent is by foliar application. When this method is employed, selective male sterility is most effectively induced when the compound is applied between flower initiation and the meiosis. The compounds of the invention may also be applied as a seed treatment by soaking the seed in a liquid formulation containing the active compound or by coating the seed with the compound. In seed treatment applications, the compounds of the invention will generally be applied at a rate of from 1/4 to 10 kg per hundred kg of seed. The compounds of the invention are also effective when applied to the soil or to the water surface in rice crops.

The compounds concerned in this invention can be used as hybridization agents together, e.g. in admixtures, with other plant growth regulators, such as auxins, gibberellins, ethylene-releasing agents such as ethephon, pyridones, cytokinins, maleic hydrazide, succinic acid 2,2-dimethylhydrazide, choline and its salts, (2-chloroethyl)trimethylammonium chloride, triiodobenzoic acid, tributyl 2,4 - dichlorobenzylphosphonium chloride, polymeric N - vinyl - 2 oxazolidinones, tri(dimethylaminoethyl)phosphate and its salts, and Ndimethylamino - 1,2,3,6 - tetrahydrophthalamic acid and its salts. Under some conditions the compounds concerned in the invention may be used advantageously with agricultural pesticides such as herbicides, fungicides, insecticides, and plant bactericides.

One or more of the compounds concerned in the invention can be applied to the growth medium or to plants to be treated either by itself or themselves or, as is generally done, as a component in a growth regulant composition or formulation which also comprises an agronomically acceptable carrier such as, for example, a carrier which is agronomically acceptable but pharmaceutcally unacceptable. By "agronomically acceptable carrier" is meant any substance which can be used to dissolve, disperse, or diffuse a compound in the composition without impairing the effectiveness of the compound and which by itself has no significant detrimental effect on the soil, equipment, crops, or agronomic environment. The growth regulant compositions can be either solid or liquid formulations or solutions. For example, the compounds can be formulated as wettable powders, emulsifiable concentrates, dusts, granular formulations, aerosols, or flowable emulsion concentrates. In such formulations, the compounds are extended with a liquid or solid carrier and, when desired suitable surfactants are incorporated.

It is usually desirable particularly in foliar applications to include adjuvants, such as wetting agents, spreading agents, dispersing agents, stickers and adhesives in accordance with agricultural practices. Examples of adjuvants which are commonly used in the art can be found in the John W. McCutcheon, Inc.

publication "Detergents and Emulsifiers Annual".

The compounds concerned in the invention can be dissolved in any appropriate solvent. Examples of solvents which are useful in the practice of this invention include water, alcohols, ketones, aromatic hydrocarbons, halogenated hydrocarbons, dimethylformamide, dioxane and dimethyl sulfoxide. Mixtures of these solvents can also be used. The concentration of the solution can vary from 2% to 98% by weight with a preferred range being from 20% to 75%.

For the preparation of emulsifiable concentrates, the compound can be dissolved in organic solvents, such as benzene, toluene, xylene, methylated naphthalene, corn oil, pine oil, o-dichlorobenzene, isophorone, cyclohexanone or methyl oleate, or in mixtures of these solvents, together with an emulsifying agent or surfactant which permits dispersion in water. Suitable emulsifiers include, for example, the ethylene oxide derivatives of alkylphenols or long-chain alcohols, mercaptans, carboxylic acids, and reactive amines and partially esterified polyhydric alcohols. Solvent-soluble sulfates or sulfonates, such as the alkaline earth salts or amine salts of alkylbenzenesulfonates and the fatty alcohol sodium sulfates, having surface-active properties can be used as emulsifiers either alone or in conjunction with an ethylene oxide reaction product. Flowable emulsion concentrations are formulated similarly to the emulsifiable concentrates and include, in addition to the above components, water and a stabilizing agent such as a water-soluble cellulose derivative or a water-soluble salt of a polyacrylic acid.

The concentration of the active ingredient in emulsifiable concentrates is usually from 10% to 60% by weight and in flowable emulsion concentrates is usually from 10% to 60%, or even as high as 75%, by weight.

Wettable powders suitable for spraying, can be prepared by admixing the active compound with a finely divided solid, such as clays, inorganic silicates and carbonates, and silicas and incorporating wetting agents, sticking agents, and/or dispersing agents in such mixtures. The concentration of active ingredients in such wettable powder is usually in the range of from 20% to 98% by weight, preferably from 40% to 75%. A dispersing agent may generally constitute from 0.5% to 3% by weight of the wettable powder, and a wetting agent may generally constitute from 0.1% to 5% weight of the composition.

Dusts can be prepared by mixing the active compounds with finely divided inert solids which may be organic or inorganic in nature. Materials useful for this purpose include, for example, bot hydroxyethylcellulose, polyoxyethylenesorbitan, monooleate, polypropylene glycol, polyacrylic acid, polyethylene sodium malate or polyethylene oxide. The adjuvant will generally comprise from 0.1 to 5% by weight, preferably from 0.5 to 2 ó of the composition. Such compositions can also optionally include an agronomically-acceptable surfactant.

The compounds concerned in the invention can be applied as sprays by methods commonly employed, such as conventional hydraulic sprays, aerial sprays, and dusts. For low-volume applications a solution of the compound is usually used.

The dilution and volume of application will usually depend upon such factors as the type of equipment employed, the method of application, the area to be treated and the type and stage of development of the crop being treated.

The following example illustrates the growth regulatory activity of the compounds concerned in the invention but is not intended to limit the invention in any way.

Example 1 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 I 15.25 cm pot containing a sterile medium of 3 parts by weight of soil and 1 part by weight of 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 (nitrogen - phosphorus - potassium=16%-25%-16%) at the rate of 1.3 ml per litre of water, and are frequently sprayed with an appropriate insecticide, such as that sold under the trade mark 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 state (stage 8 on Feekes' scale). All compounds are applied in a carrier volume of 468 1/ha containing a surfactant, such as that sold under the trade mark Triton X-100, at the rate of 0.3 g/l.

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 became plainly visible, spike length is measured and seeds per spikelet counted in both 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 are planted for determination of percent hybridization. The "approach method" referred to above involves bringing the spikes to be crosspollinated into close proximity or contact.

Percent sterility, percent fertility, and percent spike length inhibition are calculated from the following formulas: ScSt a) % Sterility x 100 Sc Sseeds/spikelet in bagged spikes of control plants, St=seeds/spikelet in bagged spikes of treated plants, Ft b) % Fertility=-x 100 c Fseeds/spikelets in approach crossed spikes of treated plants, Fseeds/spikelet in unbagged spikes of control plants, HcHt c) % Spike inhibition x 100 Hc Hc=Spike length of control plants, HSpike length of treated plants.

Table III summarizes typical results obtained in the evaluation of compounds concerned in the invention. A dash indicates that no determination of value was made.

TABLE III Gametocidal Activity

% Sterility (at Kg/ha) X R4 R 8.96 4.48 2.24 1.12 0.56 0.28 3F H H - 100 94 72 46+ 7+ 74 83 3F H Na - 100 100 100 100 81 4-CH3, 3-Cl H H 16 9 10 14 10 - 4-CH3, 3-Cl H Na 0 14 2 13 6 4-I H H - 100 100 100 99 - 4-I H Na 100 100 100 100 100 97+ 82 4-Br H H - 100 100 100 100 4-Br H Na 100 100 100 100 100+ 98+ 86 73 4-CF3 H H - 100 97 100 96 - 4-CF3 H Na 100 100 100 100 97+ 99+ 90 80 4-NO2 H H 9 18 - - - - 4-NO2 H Na 9 16 8 16 8 4-CH3 H H 73 41 - - - -4-CH3 H Na 100 98+ 92+ 38 12 100 100 4-Cl H H 33 15 - - - - (naphthyl) 4-Cl H Na 0 5 4 4 9 (naphthyl) 4-OCH3 H H 100 94 - - - - 4-OCH3 H Na 100 100+ 99+ 83+ 43+ 100 98 100 100 4-F H H 100 - - - - - 4-F H Na 100 100 100 100 95 66+ 88 3,4-diCl H H 100 - - - - - 3,4-diCI H Na 100 98 92 16 - 4-Cl H H 100 100 96 - - - 4-Cl H Na 100 100 100+ 100+ 100+ 100+ 45 34 90 72 3-Cl H Na 86 - - - - - 3-Cl H Na 100 100 74 64+ 94 73 H H H 75 - - - - - H H Na 100 100 100 100 97+ 40+ 90 97 TABLE III (contd.) 4-CH3 Br H - 6 2 10 7 4-CH3 Br Na 9 3 - 8 7 4-F Br H - - - - - 4-F Br Na 100 100 100 100+ 84+ 15 65 73 4-Br Br H - - - 82 48 32* 4-Br Br Na - - - - - H Br H - - - - - H Br Na - - - 100 88 18** 4-Br Cl Na - 100 100 92 55 4-C1 H CH3 ++ - ++ - 100 4-C1 H C2H 100 100 100 --*** + multiple results so that multiple separate tests were carried out.

* 35 at 0.14 kg/ha.

** 0 at 0.14 kg/ha.

*** 96 at 0.14 kg/ha.

**** 99 at 0.14 kg/ha.

++ spike emergence inhibited at 2.24 and 8.96 kg/ha.

Amongst the compounds concerned in this invention, there may be singled out for mention a novel class of compounds, namely compounds of Formula I given earlier wherein R2 is halophenyl and R4 is other than hydrogen. Some compounds of Formula I are known (vide U.K. Patent Specifications Nos. 634,236 and 762,141 and Helvetica Chimica Acta, Vol. 39, 1956 at page 1750).

The invention is of particular utility in providing a method of improving, by hybridization, the commercial value of seeds for the production of cereal grain (1) which comprises charging to a mechanical dissemination device a hybridization composition containing a compound of Formula I and an agronomically acceptable carrier therefor, (2) using the mechanical dissemination device to apply, as a dust or liquid spray, the hybridization composition to the foliage of a male and female cereal grain plant prior to meiosis whereby male sterility is induced, (3) causing the thus treated parent to be pollinated with pollen from a male parent of the cereal grain, (4) allowing the pollinated parent to mature until seed formation and (5) harvesting the mature seeds.

WHAT WE CLAIM IS: 1. A method of inducing male sterility in a cereal grain plant which comprises treating the plant prior to meiosis with an amount, which is effective to produce male sterility in the plant, of at least one compound of the formula

wherein R1 is carboxy, or an agronomically acceptable salt thereof, or alkoxycarbonyl, R2 is phenyl or substituted phenyl having up to 3 substituents collectively having a total of zero to 6 carbon atoms, the substituent(s) being selected from (1) alkyl, (2) C4H4=forming a naphthyl group, (3) alkoxy, (4) phenoxy, (5) halogen, (6) nitro, (7) perhaloalkyl, (8) alkoxyalkyl, (9) alkoxyalkoxy, (10) amino, (11) alkyl- or dialkylamino, (12) cyano, (13) alkoxycarbonyl, (14) carbamoyl, (15) alkyl- or dialkylcarbamoyl, (16) sulfo, (17) sulfonamide, (18) alkylcarbonyl, (19) carboxyalkyl, (20)

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **.

TABLE III (contd.) 4-CH3 Br H - 6 2 10 7 4-CH3 Br Na 9 3 - 8 7 4-F Br H - - - - - 4-F Br Na 100 100 100 100+ 84+ 15

65 73 4-Br Br H - - - 82 48 32* 4-Br Br Na - - - - - H Br H - - - - - H Br Na - - - 100 88 18** 4-Br Cl Na - 100 100 92 55 4-C1 H CH3 ++ - ++ - 100 4-C1 H C2H 100 100 100 --*** + multiple results so that multiple separate tests were carried out.

* 35 at 0.14 kg/ha.

** 0 at 0.14 kg/ha.

*** 96 at 0.14 kg/ha.

**** 99 at 0.14 kg/ha.

++ spike emergence inhibited at 2.24 and 8.96 kg/ha.

Amongst the compounds concerned in this invention, there may be singled out for mention a novel class of compounds, namely compounds of Formula I given earlier wherein R2 is halophenyl and R4 is other than hydrogen. Some compounds of Formula I are known (vide U.K. Patent Specifications Nos. 634,236 and 762,141 and Helvetica Chimica Acta, Vol. 39, 1956 at page 1750).

The invention is of particular utility in providing a method of improving, by hybridization, the commercial value of seeds for the production of cereal grain (1) which comprises charging to a mechanical dissemination device a hybridization composition containing a compound of Formula I and an agronomically acceptable carrier therefor, (2) using the mechanical dissemination device to apply, as a dust or liquid spray, the hybridization composition to the foliage of a male and female cereal grain plant prior to meiosis whereby male sterility is induced, (3) causing the thus treated parent to be pollinated with pollen from a male parent of the cereal grain, (4) allowing the pollinated parent to mature until seed formation and (5) harvesting the mature seeds.

WHAT WE CLAIM IS: 1. A method of inducing male sterility in a cereal grain plant which comprises treating the plant prior to meiosis with an amount, which is effective to produce male sterility in the plant, of at least one compound of the formula

wherein R1 is carboxy, or an agronomically acceptable salt thereof, or alkoxycarbonyl, R2 is phenyl or substituted phenyl having up to 3 substituents collectively having a total of zero to 6 carbon atoms, the substituent(s) being selected from (1) alkyl, (2) C4H4=forming a naphthyl group, (3) alkoxy, (4) phenoxy, (5) halogen, (6) nitro, (7) perhaloalkyl, (8) alkoxyalkyl, (9) alkoxyalkoxy, (10) amino, (11) alkyl- or dialkylamino, (12) cyano, (13) alkoxycarbonyl, (14) carbamoyl, (15) alkyl- or dialkylcarbamoyl, (16) sulfo, (17) sulfonamide, (18) alkylcarbonyl, (19) carboxyalkyl, (20)

alkanoyloxy, (21) haloalkyl, (22) alkanoylamino, (23) alkylthio. (24) alkylsulfinyl and (25) alkylsulfonyl, R3 is alkyl, and R4 is hydrogen, alkyl or halogen.
2. A method according to Claim 1, wherein (a) R1 is alkoxycarbonyl containing up to 12 carbon atoms in the alkoxy moiety, (b) R3 is (C1-C4)alkyl, and (c) R4 is chlorine or bromine.
3. A method according to Claim 1, wherein R1 is carboxy or an agronomically acceptable salt thereof.
4. A method according to Claim 3, wherein R2 is unsubstituted phenyl or phenyl substituted with one or two halogen atoms, a methyl group, a methoxy group, or a trifluoromethyl group.
5. A method according to Claim 4, wherein R4 is hydrogen.
6. A method according to Claim 5, wherein R3 is methyl.
7. A method according to Claim 6, wherein R2 is halophenyl.
8. A method according to Claim 7, wherein R2 is 4-halophenyl.
9. A method according to Claim 8, wherein R2 is 4-chloro- or 4-bromo-phenyl.
10. A method according to Claim 7, wherein R2 is 3-halophenyl.
11. A method according to Claim 6, wherein R2 is trifluoromethylphenyl.
12. A method according to Claim 4, wherein R3 is methyl and R4 is halogen.
13. A method according to Claim 12, wherein R2 is halophenyl and R4 is bromine.
14. A method according to any one of the preceding claims, wherein the cereal grain is wheat, barley, maize or rice.
15. A method according to any one of the preceding claims as applied to the production of hybrid cereal grain seed, the method comprising treating a male/female parent of the cereal grain with said compound, causing the thus treated parent to be pollinated with pollen from a male-fertile parent of the cereal grain, allowing the pollinated parent to mature until seed formation is substantially complete, and harvesting the mature seed.
16. A method according to Claim 15, wherein the amount sufficient to produce male sterility in the female parent is from 0.035 to 22.42 kg per hectare.
17. Hybrid cereal grain seed produced by a method according to Claim 15 or 16.
18. A compound of Formula I, in Claim 1, wherein R1 is as defined in any one of Claims 1-3; R2 is halophenyl; R3 is as defined in any one of Claims 1,2 and 12 and R4 is as defined in any one of Claims 1, 2 and 13 but is other than hydrogen.
19. A compound according to Claim 18 which is any one of those individual compounds specified in the foregoing descriptive portion of the specification.
20. A compound according to Claim 19 when prepared by any one of the general methods given in the foregoing descriptive portion of the specification.
21. A method according to Claim 1, wherein the compound employed is any one of those individual compounds specified in the foregoing descriptive portion of the specification.