DK156607B - PROCEDURE FOR INFLUENCING STRAIGHT STERILITY IN A CEREAL CEREAL PLANT - Google Patents

Description

DK 156607 B

The present invention relates to a free-throw method for inducing selective male constancy in a cereal grain plant.

Cereals of cereals, such as corn, wheat, rye, barley, millet, sorghum 5 and teff (Epagrostis abyssinica) are among the largest food crops in the world. This significance has prompted extensive exploration to improve the productivity and nutritional value of these crops. One of the most significant approaches to improving the quality and yield of cereal kernels has been the hybridization series.

While hybridization has been an effective technique for some crops, especially maize, there have been numerous problems 15 with the current techniques. Eg. For example, hybridization of maize requires a time-consuming removal of male flowers by hand or an ineffective mechanical removal of male flowers which may damage the maize plant. Hybridization of maize, barley and wheat by cytoplasmic male-sterile varieties can only be carried out with a limited genetic basis requiring a lineage and a rebuild line. In addition, male-barley cytoplasmic sterile and wheat cytoplasmic techniques provide a highly refined method for coping with the genetic complexities of these crops, and to date no greater success has been achieved in developing a suitable method. Since induction of selective male sterility by chemical means would avoid many of the problems faced by current hybridization techniques, new compounds which produce the desired sterility would be highly desirable in a reliable and unconstitutional manner. to provide the male-sterile plants necessary for hybridization. In accordance with the present invention, there is provided a method for inducing male constancy in cereal cereal plants, which is characterized in that it comprises treating the plant prior to meiosis with an amount effective for to induce him-

DK 156607 B

2 plant sterility of at least one compound of formula (I):

ISLAND

R4 1 rI

5 Y | R2 represents a carboxy group, or an agronomically acceptable site thereof, or alkoxycarbonyl having up to 12 carbon atoms in the alkoxy moiety, R2 represents phenyl optionally substituted with up to 15 to three substituents having a total of 0 to 6 carbon atoms, the substituent or the substituents are selected from (1) alkyl, (2) C 4 H 4 to form a naphthyl group, (3) alkoxy, (4) halogen, (5) nitro, (6) trifluoromethyl, (7) alkanoyloxy and (8) alkylthio, R3 represents (C1-4 J alkyl, and r4 represents hydrogen, (C1-4) alkyl or halogen.

In a preferred embodiment, R 1 represents a carboxy group or an alkali metal salt thereof, R 3 is a methyl group, R 4 is a hydrogen atom and R 2 is a 4-chloro-substituted phenyl group.

When R 1 represents a site of a carboxy group, an alkali number, alkaline earth metal or transition metal can deliver the cation. The cation may 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, cupri, cupro, ferric, ferrous, titanium and aluminum. To the ammonium salts are salts wherein the ammonium cation has the formula NZlz2Z3Z4, wherein Z1, Z2, Z3 and Z4 (which may be the same or different) represent hydrogen, hydroxy, (C1-4) alkoxy, (0 ^ -20) - alkyl, (C3-8) -alkenyl, (C3-8) -alkynyl, (C2-8) -hydroxyalkyl,

DK 156607 B

3 alkoxyalkyl having from 2 to 8 carbon atoms, (C2-6) -alinoalkyl, (C2-6) 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, two conditions of Z1, Z2, Z3 and Z4 may be joined to form, together with the nitrogen atom, a 5- or 6-membered heterocyclic ring, optionally containing up to one additional heterooxygen, nitrogen or sulfur atom. ring, and which is preferably saturated as in a piperidine, morpholine, pyrrolidine or piperazine ring. Another alternative is that three conditions of z1, Z2, Z3 and Z * may be linked 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 usually be selected from halogen, (C1-8) alkyl # (C1-4) alkoxy, hydroxy, nitro, trifluoromethyl, cyano, amino and (Cx_4) alkylthio. Preferably, such substituted phenyl groups have up to two such substituents. Representative ammonium cations include ammonium, dimethylammonium, 2-ethylhexylammonium, bis (2-hydroxyethylammonium, tris (2-hydroxyethylammammonium, dicyclohexylammonium, jt-octylammonium, 2-hydroxyethylammonium, morpholinium, morpholinium, morpholinium) monium, 2-methylbenzylammonium, n-hexylammonium, triethylammonium, trimethyl 1 ammonium, tri (n-butyl Jammonium, methoxyethylammonium, diisopropylammonium, pyridinium, diallylammonium, pyrazole, propargylammonium, dimethylhydrazinium, dimethylhydrazinium , dodecylammonium, octadecylammonium, 4-dichlorophenyl ammonium, 4-nitrobenzylammonium, benzyltrimethylammonium, 2-hydroxyethyldimethyloctadecylammonium, 2-hydroxyethyl diethyl octylammonium, decyltrimethylammonium, decyltrimethylammonium, decyltrimethylammonium

Representative embodiments of R 2 include a phenyl group 35 substituted with (1) alkyl, preferably with up to 4 carbon atoms, (2) C 4 H 4 to form a naphthyl group, (3) alkoxy, preferably with up to 4 carbon atoms, (4) halogen, such as fluorine, chlorine, bromine and iodine, (5) nitro, (6) trifluoromethyl, (7)

DK 156607 B

4 alkanoyloxy, preferably with up to 4 carbon atoms and (8) alkylthio, preferably with up to 4 carbon atoms. The phenyl group may also be substituted to form a condensed ring. The most preferred substituents on the phenyl group are 5 1 or 2 halogen atoms, a (C 1-4) alkyl, preferably methyl group, a (C 1-4) alkoxy, preferably methoxy group or a trifluoromethyl group.

Typical compounds within the scope of the invention include: 1-phenyl-1,4-dihydro-4-oxo-6-methylpyridazine n-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-di hydro-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-di hydro-4-oxo-6-methylpyridazine-3-carboxylic acid, 1- (3-chlorophenyl) -1,4-di hydro-4-oxo-6 -methylpyridazine-3-carboxylic acid, 1- (3-bromophenyl) -1,4-dihydro-4-oxo-5-methylpyridazine-3-carboxylic acid, 1- (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-methylpyric acid -sin-3-carboxylic acid, 1- (3-trifluoromethylphenyl) -1,4-dihydro-4-oxo-6-methyl pyrisazi n-3-carboxylic acid, 1-phenyl-1,4-di hydro-4-oxo-6-ethylpyridazine n-3-carboxylic acid, 1- (4-chlorophenyl) -1,4-di hydro-4- oxo-6-ethylpyridazin-3-carboxylic acid, 1- (4-fluorophenyl) -1,4-dihydro-4-oxo-6-ethylpyridazine-3-carboxylic acid, 1- (3, 4-dichlorophenyl) -1,4-di hydro-4-oxo-6-ethylpyridazine n-3-5 carboxylic acid, 1-phenyl-1,4-dihydro-4-oxo-6-propylpyridazine n-3-carboxylic acid, 1-Phenyl-1,4-di-hydro-4-oxo-5,6-dimethylpyridazin-3-carboxylic acid, 1- (4-chlorophenyl) -1,4-dihydro-4-oxo-5,6-carboxylic acid dimethylpyridazine-3-10 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-methylpyrisa-z in n-3-carboxylic acid, 1- (2,4,6-trichlorophenyl) -1,4-dihydro-4-oxo-6-methyl-pyridazine 3-carboxylic acid, 1- (3-ethoxyphenyl) -1,4-di hydro-4-oxo-6-ethylpyridazine-3-carboxylic acid, 1- (4-methylthiophenyl) 1,4-dih ydro-4-oxo-6-methylpyridazine-3-carboxylic acid, 2,5-1-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, 1- (4-chlorophenyl) -5-bromo-1,4-dihydro-4-oxo-6-ethylpyridazine n-30 3-carboxylic acid, as well as the salts and esters of the above acids.

The compounds may be prepared by analogous compounds known per se or other methods devised for the purpose. In a convenient process, a 4-hydroxy-2-pyrone of the formula is reacted:

DK 156607 B

6 <x | (II) r3 / ° A0 5 wherein R6 represents a hydrogen atom or an alkyl group and R3 has the meaning defined above, or a site of a pyrone of formula (II) (prepared by treating the pyrone with an equivalent of a suitable aqueous base, such as potassium 10 or sodium hydroxide, acetate or carbonate), usually at a temperature of from -10 to 50 ° C, in a polar solvent, such as water, methanol, ethanol, glyme or dimethylformamide. amide, with a diazonium salt, such as diazonium chloride, prepared by conventional diazotizing technique from an amine of formula R 2 - NH 2 (III) wherein R 2 has the meaning defined above. The obtained hy-20 drone having the formula: | (IV) wherein R 2, R 3 and R 4 have the meaning defined above are 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 of 20 to 150 ° C, and preferably 40 to 100 ° C, to produce (by a rearrangement) a pyridazine of the formula: 35

DK 156607 B

7 VST * 5 R2 where r2, r3 and g6 have the meaning defined above.

Esters of the pyridazine of formula (V) are prepared by esterification with a suitable alcohol, preferably a (Cj_)) alkanol.

A convenient technique is a Fischer esterification using anhydrous hydrochloric acid or sulfuric acid as a catalyst and the alcohol as a solvent. This esterification is usually carried out at a temperature of from 35 to 150 ° C, optionally using an inert co-solvent such as methylene chloride, ethylene chloride, diethyl ether, toluene or xylene.

Salts of the pyridazines of formula (V) and their 5-halo analogous compounds can be prepared by conventional techniques, such as by neutralization with a suitable inorganic or organic base in a solvent such as water or methanol.

The compounds wherein R 4 represents a halogen atom can be prepared by reacting the corresponding pyridazines wherein R 4 represents a hydrogen atom, with an equivalent of a halogenating agent, such as bromine, chlorine, sufuryl bromide or sulfuryl chloride or the like. in a suitably inert solvent such as hexane, benzene, ethylene dichloride or methanol, usually at a temperature of from 0 to 50 ° C, and preferably at room temperature.

Typical compounds for use in the process of the invention, their melting points and elemental analysis are listed in the following Table I. The following examples of embodiments show the synthesis of compounds 10, 12, 14, 35 and 16 of Table I, and in these examples all temperatures are in ° C and parts and percentages by weight unless otherwise indicated.

DK 156607 B

8

TABLE I

1-Aryl-1,4-dihydro-4-oxo-pyridazines 5

N

CH3 ^^ à

X

. R Compound No. 15 R No. X Mp ° C% C * H% N% Ha3-1 H 3-F 213-5 Calculated 58.06 3.65 11.29 7.65

Found 58.07 3.60 11.33 7.68 2 H 4-CH2 3-Cl 202-3 56.22 3.63 10.09 12.77 3 55.92 3.84 10.90 13, 36 3 H 4-1 241-2 40.47 2.55 7.87 35.64 20 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-CF, 234-5 52.35 3.04 9.40 19.11 3 51.99 2.97 9.13 18.94 6 H 4-NO- 244-5 52.37 3.30 15.27 ----- 25 3 52.76 3.33 15.69 -----. 0 Calculated 63.92 4.95 11.47 ----- 7 H 4-CH3 162-3 pounds 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-OCHo 169-70 59.94 4.64 10.77 ----- 30 3 60 , 14 4.62 10.82 -----] _q 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-diCl 220-2 48.18 2.69 9.37 23.71 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-Cl 192-3 ~

DK 156607 B

9 TABLE I (continued) 5 -

Connect.

else No. χ X Mp. C% C% H% N% Hal

14. H H 173 "III

Br 4-CH-, 241 48.31 3.43 8.67 24.73 iD ür 3 49.37 3.59 9.25 23.65 µg Br 4-F 219-20 44.06 2, 46 8.57 24.43 44.50 2.52 9.00 24.26 77 Br 4-Br>? Ππ 37'14 2'08 7'22 41.19 17 Br B 250 36.73 1.93 7 , 35 40.33 15 19 t »T. H ion 46.62 2.93 9.06 25.85 15 18 46.63 2.33 9.25 25.62 ia Cl 4 — Br 255—9 41.95 2.3o 8.16 23.26 19 ci 4 Br. 3. 4lf6S 2.31 7.74 23.17 *% Br; % P: calculated 5.81; found 5.83 20 # *% Br; % F; calculated 10.17; found 9.91 25 30 35

DK 156607 B

10

Example 1 (Compound 10 / Table I)

Preparation of 1- (4-fluorophenyl) -1,4-dihydro-4-oxo-6-methylpyridazin-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 are added to the suspension to effect dissolution of the pyrone.

In a separate flask, mix 7/22 g of 4-fluoroaniline with 25 ml of concentrated hydrochloric acid and 31 ml of water. The resulting solution is kept at approx. 5 to 10 °, and a solution of 4/75 g of sodium nitrite in 16 ml of 10 water is added. The obtained solution of 4-fluorophenyl diazonium chloride is added dropwise to the stirred pyrone solution, keeping the temperature at ca. 5 to 10 ° and the pH of approx. 8 to 9 by adding small amounts of aqueous sodium hydroxide.

The obtained hydrazone is refluxed for approx. 2 hours with 500 ml of concentrated hydrochloric acid. Cooling and filtration give 10/2 g of 1- (4-fluoro-phenyl) -1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid, which is recrystallized from chloroform / ether (mp 185-187 ° C).

Example 2 (Compound 12, Table I)

Preparation of 1- (4-chlorophenyl) -1,4-dihydro-4-oxo-6-methylpyridazine carboxylic 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 is added a solution of 7.6 g of sodium nitrite with a temperature between 0 and 5 °. The diazotized aniline is added under ice-cooling to a pre-prepared solution of 12.6 g of 4-hydroxy-6-methyl-2-pyrone and 55 g of sodium carbonate in 500 ml of water.

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

The acid (5.0 g) is converted to the sodium salt by treatment with

DK 156607 B

11 0.7β g of sodium hydroxide in 200 ml of anhydrous methanol. The solvent is removed and the solid washed with ether and dried in vacuo at 90 ° C.

Analysis for C 12 H 22 N 2 O 8 H 2 O: 5 Calculated: 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.

Example 3 (Compound 14, Table I)

Preparation of 1-phenyl-1,4-dihydro-4-oxo-6-methylpyridazine-3-1Q carboxylic acid In 375 ml of water, 11.8 g of 4-hydroxy-6-methyl-2-pyrone are suspended and 9.95 g of anhydrous sodium carbonate is added to effect the solution of the pyrone.

In a separate flask, mix 9.08 g of aniline with 37.5 ml of concentrated hydrochloric acid and 47 ml of water. The resulting solution is maintained at ca. 5 to 10 °, and a solution of 7.13 g of sodium nitrite in 24 ml of water is added. The resulting solution of phenyl diazonium chloride is added dropwise to the stirred pyrone solution, keeping the temperature at ca. 5 to 10 °. The pH value is kept at approx. 8 to 9 by adding small amounts of sodium hydroxide solution.

After the addition is complete, the obtained hydrone (18 g) is isolated by filtration and resuspended in 500 ml of concentrated hydrochloric acid. The mixture is refluxed for 2½ hours and then cooled. The 1-phenyl-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid precipitates as brownish crystals which are recrystallized from water. Yield 7.0 g; mp. 173 °.

Example 4 (Compound 16, Table I)

Preparation of 1- (4-Fluorophenyl) -5-bromo-1,4-dihydro-4-oxo-methylpyridazine-3-carboxylic acid 1- (4-Fluorophenyl) -1,4-dihydro-4-oxo 6-methylpyridazine-3-carboxylic acid (1.5 g) is suspended in 100 ml of 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 give 1, 4 g of 1- (4-fluorophenyl) -5-bromo-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid. (Mp 219-220 °).

DK 156607 B

12

The compounds are particularly useful as chemical hybridizers in cereal crops, such as wheat, barley, corn, rice, durra, millet, oats and rye. When the compounds are used in chemical hybridizers, they effectively induce a high degree of selective male sterility and without also causing female sterility of importance in the treated plants and without inducing significant inhibition in the treated plants. As the term male sterility is used herein, both actually include male sterility, evidenced by a deficiency of male flower parts or by sterile pollen, and functional male sterility at which the male flower is unable to produce pollination. The compounds also induce other plant growth regulating reactions, such as e.g. flowering control, fructification control and inhibition of free formation by non-cereal species and other related growth regulating reactions.

Used as hybridizers, the compounds are fed in any amount that will be sufficient to induce the individual plant reaction without eliciting any unwanted or phytotoxic reaction. The compounds are usually fed to the crops to be treated in an amount of 0.035 to 22.42 kg per day. per hectare, and preferably 0.14 to 11.21 kg per hectare. acres. The amount of feed will vary depending on the crop being treated, the compound used for the treatment, and the corresponding factors.

In order to obtain hybrid seeds, the following procedure is usually used. The two stem plants that are to be crossed are planted in alternating rows. Female stem growth is treated with a compound for use in the process of the invention. The thus-produced male-sterile female stem growth will be pollinated with pollen from the second male-fertile male stem growth, and the frees produced by the female stem growth will be hybrid free, which can then be hosted in a conventional manner.

A preferred method of administering one of the compounds as a chemical hybridizer is by leaf blending.

DK 156607 B

13 growth figures. When this method is used, selective male sterility is most effectively induced when the connection between flower initiation and rowing is made. The compounds can also be applied to a free treatment by blending the frees into a liquid composition containing the active component or by coating the frees with the connection. In the case of freebies, the compounds are usually fed in an amount of approx. 1/4 to 10 kg per 100 kg fre. The compounds are also effective when applied to the soil or water surface 10 by rice crops.

The compounds can be used as hybridizers together, e.g. in admixture, with other plant growth regulators, such as auxins, gibberellins, ethylene releasing agents such as ethylene, pyridones, cytokinins, maleic acid hydrazide, succinic 2,2-dimethylhydrazide, choline and its salts, (2-chloroethyl) trimethyl thylammonium chloride, triiodobenzoic acid, tributyl-2,4-dichlorobenzylphosphonium chloride, polymeric N-vinyl-2-oxazolid ions, tri (dimethylamonethylethyl phosphate and its salts), and N-dimethyl-20 amino-1,2,3,6-tetrahydrophthalamic acid Under certain conditions, the compounds may advantageously be used in connection with agricultural pesticides, such as herbicides, fungicides, insecticides and plant bactericides.

One or more of the compounds can be applied to the culture medium or plants to be treated either alone or as it usually does, as a component of a liquid control preparation or composition which also comprises an agronomically acceptable carrier, such as e.g. a carrier which is agronomically acceptable but pharmaceutically unacceptable. By "agronomically acceptable carrier" is meant any material which can be used to read, disperse or distribute a compound in the composition without adversely affecting the effectiveness of the compound and which itself has no detrimental effect on soil, apparatus, crops or agronomic environment. The growth regulating compositions may be of either solid or liquid composition or may be solutions. Eg. For example, the compounds can be designed as wettable

DK 156607 B

14 powders, emulsifiable concentrates, powders, granules, aerosols or lightly liquid emulsion concentrates. In such preparations, the compounds are stretched with a liquid or solid carrier and, if desired, suitable surfactants are incorporated.

It is usually desirable, especially in leaf growth batches, to include auxiliaries such as wetting agents, spreading agents, dispersing agents, adhesives, adhesives and the like in accordance with agricultural practice. Examples of auxiliaries commonly used in the field can be found in the John W. McCut-Cheon publication. Inc. "Detergents and Emulsifiers Annual".

The compounds can be dissolved in any suitable solvent. Examples of solvents useful in the practice of the invention include water, alcohols, ketones, aromatic hydrocarbons, halogenated hydrocarbons, dimethylformamide, dioxane and dimethyl sulfoxide. Mixtures of these solvents may also be used. The concentration of the solution may vary from approx. 2 to approx. 98 wt.% With a preferred range between approx. 20% and approx. 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 emulsifier. or surfactant which allows dispersion in water. Suitable emulsifiers include e.g. the ethylene oxide derivatives of alkyl phenols or long chain alcohols, mercaptans, carboxylic acids as well as reactive amines and partially esterified polyhydroxy alcohols. Solvent-soluble sulfates or sulfonates, such as the alkaline earth salts or amine salts of alkyl benzene sulfonates and the fatty alcohol sodium sulfates with surfactant properties, can be used as emulsifiers either alone or in conjunction with an ethylene oxide reaction product. Easy-flowing emulsion concentrates

DK 156607 B

15, in a similar manner to the emulsifiable concentrates, and includes, in addition to the above components, water and a stabilizer, such as a water-soluble cellulose derivative or a water-soluble site of a polyacrylic acid. The concentration of the active ingredient in emulsifiable concentrates is usually about 10 to 60% by weight, and in light liquid emulsion concentrates it is usually about 10 to 60% by weight or even as high as 75% by weight.

Wettable powders suitable for spraying can be prepared by mixing the active compound with a finely divided solid, such as clays, inorganic silicates and carbonates and silicas, and the addition of wetting agents, adhesives and / or dispersants to such mixtures The concentration of active components in such wettable powders is usually in the range of from about. 20 to 98% by weight, preferably approx. 40 to 75% by weight.

A dispersant can usually comprise about 0.5 to approx. 3 wt. Of the wettable powder and a wetting agent can usually comprise from 0.1 to approx. 5% by weight of the composition.

Powders can be prepared by mixing the active compounds with finely divided inert solids which may be of an organic or inorganic nature. Materials suitable for this purpose include e.g. botanical melt types, silicas, silicates, carbonates and clays. A convenient way of making a powder is to dilute a wettable powder with a finely divided carrier. Powder concentrates containing approx. 20 to 80% of the active component is frequently prepared and then diluted to a use concentration of approx. 1 to 10% by weight.

Granular formulations may be prepared by impregnating a solid such as granulated whey soil, vermiculite, ground corn flasks, seed shells, including bran or other grain shells or similar material. A solution of one or more of the compounds in a volatile organic solvent may be sprayed or mixed with the granular solid and the solvent may then be removed by evaporation. The granular material may have any suitable size with a preferred size range from 16 to 60 mesh (US Standard Sieve Series). The active compound will usually constitute approx. 2 to 15% by weight of the granulated composition.

DK 156607 B

16

Salts of the compounds can be formed and treated as aqueous solutions. The salts will typically form approx. 0.05 to approx. 50% by weight, preferably approx. 0.1 to approx. 10% by weight of the solution. These preparations can also be further diluted with water, if required, if desired. In certain applications, the activity of these compositions may be enhanced by incorporating into them an adjuvant such as glycerine, methyl ethyl cellulose, hydroxyethyl cellulose, polyoxyethylene sorbitan monooleate, polypropylene glycol, polyacrylic acid, polyethylene sodium malate and polyethylene oxide. The excipient will usually amount to approx. 0.1 to approx. 5% by weight, preferably approx. 0.5 to approx. 2% by weight of the composition. Such compositions may also, if desired, contain an agro- nomically acceptable surfactant.

The compounds can be treated as spraying agents by the commonly used methods, such as conventional hydraulic spraying agents, sprained spraying agents and powders. For low volume transport, a jointing of the joint is usually used. The dilution and volume added will usually depend on such factors as the type of equipment used, the method of treatment, the area to be treated, and the type and stage of development of the crop to be treated.

The following example, by which it is not intended to limit the invention in any way, illustrates the growth-regulating activity of the compounds.

Application Example 1 Chemical hybridization activity

The following methods are used to assess the activity of the compounds to induce male cancer mortality in cereals.

35 A stacked variety (Fielder) and a stack of varieties (Mayo-64) of wheat flour are placed in an amount of 6 to 8 grains per 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 for a short period of time (9 hours).

DK 156607 B

17 things over the first 4 weeks to achieve good vegetative growth for flower initiation. The plants are then transferred to long-day (16 hours) conditions, which are provided with high-intensity light in the greenhouse. The plants are fertilized 2, 4 and 8 weeks after plant 5 with a water-soluble fertilizer (nitrogen-phosphorus-potassium = 16% -25% -16%) in an amount of 1.3 ml per liter of water and is frequently sprayed with a suitable insecticide, such as that sold under the trade mark "Isotox", "for the control of leaf lice and powdered with sulfur for the control of mold.

10

Experimental compounds are fed to the leaf growth of the degenerate female plants when these plants reach the flag leaf stage of growth (step 8 on Feekes' scale). All compounds are supplied in a carrier volume of 468 liters per hectare containing a surfactant such as that sold under the trademark "Triton X-100" at an amount of 0.3 g per liter.

After the axis emergence for anthesis, 4 to 6 axis per pot is closed inside a bag to prevent outcrossing. At the first 20 signs of flower opening, two axes per pot are crossed with the homeless male stem growth using the approximation method. As soon as the seeds become clearly visible, the length of the axis is measured and the number of seeds per taste is counted in both enclosed and crossed axes. Male consistency can then be calculated as percent inhibition of fertilization in enclosed axis on treated plants, and female consistency in crossed axis can be calculated as percent of control prediction. After ripening, the seeds are seeded from crossed axis to determine hybridization percentage. The above "approximation method" implies that the axes to be cross-pollinated are brought close together or in contact.

Percent sterility, percent fertility, and percent shaft length inhibition are calculated from the following formulas: 35

DK 156607 B

18 s - st a)% sterility = --- X 100

sc

Sc = fr0 / small axis in enclosed axis on control plants S = fr0 / small axis in enclosed axis on treated plants * 5 ^ b)% fertility = Ffc X 100

TT

Ft = fr0 / small axis in approximate crossed axis on treated plants F = fr0 / small axis on non-enclosed axis on control plants lu c

c)% axis inhibition = -—-- X

hc

Hc = shaft length of control plants Ht = shaft length of treated plants.

Table II summarizes typical results obtained by examining compounds for use in the process of the invention. A dash indicates that no provision was made.

20

TABLE II

Gametocid activity

i T

CH3 30

X

35 19% Sterility (at kg / ha) X_ R 8.96 4.48 2.24 1.12 0.56 0.28 3F HH --- 100 94 72 46+ 7+ 5 74 83 3F H Na - 100 100 100 100 81 4-CH3,3-Cl HH 16 3 10 14 10 --- 4-CH3,3-Cl H Na 0 14 2 13 6 --- 4-1 HH --- 100 100 100 99 10 4 -1 H Na 100 100 100 100 100 97+ 82 4-Br HH ---- 100 100 100 100 --- 4-Br H Na 100 100 100 100 100+ 98+ 86 73 4-CF3 HH --- 100 97 100 96 15 4-CF3 H Na 100 100 100 100 97+ 99+ 90 80 4-NO2 HH 9 18 --- --- --- --- 4-NO2 H Na 9 16 8 16 8 4-CH3 HH 73 41 20 4-CHH Na 100 98+ 92+ 38 12 --- 100 100 4-C1 HH 33 15 --- --- --- --- (naphthyl) 4-C1 H Na 0 5 4 4 9 --- (naphthyl) 25 4-OCH3 HH 100 94 --- --- --- --- 4-0CH-, H Na 100 100+ 99+ 83+ 43+ --- J 100 98 100 100 4-FHH 100 --- --- --- --- 4-FH Na 100 100 100 100 95 66+ 88 30 3,4-diCl HH 100 --- --- --- --- - - 3,4-diCl H Na 100 98 92 16 --- --- 4-C1 HH 100 100 96 --- --- --- 4-C1 H Na 100 100 100+ 100+ 100+ 100+ 45 34 90 72 35 3-Cl H Na 86 --- --- --- --- --- 3-C1 H Na 100 100 74 64+ 94 --- 73 DK 156607 B '20 TAB EL II (continued) 5% Sterility (at kg / ha) x_ R 8.96 4/48 2/24 1/12 0/56 0/28 HHH 75 --- --- --- --- - - in HH Na 100 100 100 100 97+ 40+ 10 90 97 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 15 65 73 4-Br Br H --- --- --- 82 48 32 ± 4-Br Br Na --- --- --- --- --- --- H Br H --- --- --- --- --- --- H Br Na - - --- --- 100 88 18 ii 20 4-Br Cl Na --- 100 100 92 55 --- 4-Cl H CH3 ++ 100 ++ --- 100 --- *** 4- C1H C2H5 100 --- 100 --- 100 --- **** + multiple results, so that multiple separate attempts are performed.

25 in 35 at 0/14 kg / ha fcfe 0 at 0/14 kg / ha 96 at 0.14 kg / ha 99 at 0.14 kg / ha ++ axis yield inhibited at 2.24 and 8.96 kg / ha .

30 35 DK 156607 B '

Table III

21

Table III below shows additional compounds which have been prepared.

VV * (i) A "

R I

10

Qr x 15 Example_Rf_R ^ _X_R * _ AH CH3 4-Br CO2-n-C4H9 BH CH3 4-1 CO2CH3 CH CH3 4-1 CO2-n-C4Hg DH CH3 4- € 1 CO2- (1 / 2CU ++) 20 EH CH3 4-CH3S CO2CH3 FH CH3 4 ~ CH3CO2 CO2Na 6 H CH3 4 ~ CH3S CO2Na H n-C3H7 CH3 4-C1 CO2CH3 IH n-C4Hg 4-C1 C02CH3 25 JH CH3 4 ~ C1 CO2CH3 KH CH3 4-C1 C0 C6H13 LH CH3 4-C1 CO2CH2C6H13 MH CH3 4-Cl CO2CH3 NH CH3 4-Cl CO2CH3 30 0 H CH3 4-C1 CO2C2H5 PH C2H5 4 — C1 C02CH3 QH C2H5 4-C1 C02Na R CH3 C2H5 4-C1

Table IV

Table IV below provides physical characteristics and / or elemental analysis for the compounds shown in Table III.

DK 156607 B

22 5

Example Melting Point (° C) _% C% H% H% Hal A 85.5-88 Calculated: 52.61 4.69 7.67

Found: 52.25 4.70 7.90 10 B 186-189 42.18 3.00 7.57 41.95 2.91 7.16 C 134-137 46.61 4.16 6.80 46.84 4.26 6.95 D 263-265 41.24 4.02 8.02 10.15) 39.55 3.40 7.62 9.35 E 157-159 57.91 4.86 9.65 57 , 98 4.88 9.66 F 300 51.22 3.99 8.54 &) 51.32 3.73 8.68 20 G 310 .......... .....

H Semi-solid 59.90 5.34 8.74 60.13 5.45 8.57 I Oil 59.90 5.34 8.74 25 59.85 5.61 9.11 J 183-193 49.54 3, 84 8.89e) 50.12 3.69 9.29 K 62.33 5.52 8.08 62.45 5.75 8.45 30 L 125-127 63.24 5.87 7.77 63.44 5, 97 7.48 H 154-156 52.97 3.76 9.51e *) 52.45 3.89 9.48 N 200-202 56.02 3.98 10.05 12.72 56.15 4.06 10, 10 12.71 3 5 0 143 57.44 4.48 9.57 12.11e) 57.37 4.51 9.56 12.06 P 110-114 57.44 4.48 9.57 57.20 4 , 34 9.60

DK 156607B

23 Q 48.93 3.80 8.79f) 48.22 3.56 9.22 R 165 50.53 4.24 8.492) 5 50.39 3.86 8.41 a)% Cl; Cu: Calculated: 9.09 Found: 10.60% H 2 O: Calculated: 15.47 Found: 15.96 b)% Na ·. calculated: 7.01 found: 8.19 c) Analysis for hydrochloride salt d)% S ·. Found: 10.88 Found: 12.25 20 e)% Cl: f)% Na: Calculated: 7.22 Found: 7.40% H 2 O Calculated: 5.65 Found: 4.74 (monohydrate) g)% Na calculated: 6.91 found: 6.1% H 2 O calculated: 5.42 Found: 4.31 (monohydrate)

Table V below shows male constancy data for the compounds of Table III obtained by the method used to obtain the results listed in Table II.

35

DK 156607 B

24

Table V

% Male sterility (at kg / ha) 5 Ex. 8.96 4.48 2.24 1.12 0.56 0.28 0.14 0.07 A --- --- --- --- 100 100 90 90 B --- ..... . --- 100 100 98 97 C ......... --- 100 100 100 94 D --- --- 100 +++ 100 +++ 91 +++ 63 +++ - - --- 10 E 100 --- 96 --- 56 --- 16 --- F --- 4 3 --- 0 ... ......

G --- --- --- 19 8 7 55 H --- 100 100 100 89 72 I --- --- --- 49 7 0 0 15 J ++ --- ++ --- 100 --- 96 --- K --- --- --- 31 12 2 0 L --- --- --- 63 9 1 0 M 100 --- 99 --- 67 --- 9 N ......... 100 100 100 98 20 0 100 --- 100 --- 100 --- 99 --- P ......... 100 100 100 98 Q 100 --- 100 100 100 98 95 --- R 100 --- 100 88 37 2 0 --- 25 ++ Inhibitor's inhibition at 2.24 and 8.96 kg / ha +++ Soil bleeding sample, not leaf spray

Particular mention may be made among the compounds of a novel class of compounds, namely the compounds of the previously mentioned formula (I) wherein R 4 is different from hydrogen, e.g. halogen.

The invention is of particular importance in that it provides a method of enhancing, by hybridization, the commercial value of free to produce cereal grains, including (1) fattening a mechanical spreading agent with a hybridization composition containing a compound of formula (I). ) and an agronomically acceptable carrier therefore, (2) that

Claims (3)

10 Patent Claims. A method of inducing male sterility in a cereal grain plant, characterized in that it comprises treating the plant prior to meiosis with an amount effective to produce male sterility in the plant of at least one compound of the formula: ll / ^ 1 11 (I), yv. .n k1 in which r! represents a carboxy group, or an agronomically acceptable site thereof, or alkoxycarbonyl having up to 12 carbon atoms in the alkoxy moiety, R 1 represents phenyl optionally substituted with up to 30 to three substituents having a total of 0 to 6 carbon atoms, (1) alkyl, (2) C R 2 represents (C 1-4) alkyl, and R * represents hydrogen, (C 1-4) alkyl or halogen. A process according to claim 1, characterized in that R 1 has a tonor and anionic allele of an allied metal rl - DK 156607 B of, R 2 represents 4-chlorophenyl, R 3 represents methyl and R 4 represents hydrogen. 5 10 15 20 25 30 35