GB2169290A - Pyrono-3-carboxamide derivatives - Google Patents

Abstract

Pyrone-3-carboxamide derivatives of the general formula:- <IMAGE> wherein R1 is an alkyl radical and R2 is an alkyl radical or halogen atom, have plant growth-inhibiting activity.

Description

SPECIFICATION Pyrone-3-carboxamide derivatives The present invention is concerned with new pyrone-3-carboxamide derivatives and, more particularly, with 2,6-dimethyl-4-oxo-4H-pyran-3-carboxamides, these compounds having a growth-inhibitory activity on plants and also being useful as intermediates for preparing pharmaceutical or agricultural chemicals.

Certain 2,6-dimethyl-4-oxo-4H-pyran-3-carboxamides have already been mentioned in the literature.

Thus, it is known that the treatment of o-haloaceto-anilides (2-chloro, 2-bromo-, 2,4-dichloro or 2,5-dichloro compounds) with polyphosphoric acid for one hour at 140"C. gives the corresponding halogen derivatives of 2,6-dimethyl-4-oxo-N-phenyl-4H-pyran-3-carboxamide (see A.K. Mallams & S.S. Islaeistam, J.

Org. Chem., 29, 3548/1964 and A.K. Mallams, J. Org. Chem., 29, 3555/1964). This method using polyphosphoric acid was applied on other acetoaceto-anilides, for example the 2-fluoro, 2-piperidino, 2-hexahydroazepinyl, 2-morpholino, 2-pyrrolidinyl and the like compounds, to give the corresponding 2,6-dimethyl-4-oxo-4H-pyran-3-carboxamide compounds (see R. Garner & H. Suschitzky, J. Chem. Soc. (C), 186/ 1966).

The formation of 2,6-dimethyl-N-(4-nitrophenyl)-4-oxo-4H-pyran-3-carboxamide was identified as the reaction product between p-nitroaniline and diketene (see Kato & Kubota, Yakugakuzassi, 87, 1212/1967). N (2-chlorophenyl)-2,6-dimethyl-4-oxo-4H-pyran-3-carbox-amide was also obtained by treating 2,6-dimethyl 4-oxo-4H-pyran-3-carboxylic acid with thionyl chloride, followed by reaction with o-chloroaniline or by heating the p-nitrophenyl ester of 2,6-dimethyl-4-oxo-4H-pyran-3-carboxylic acid and o-chloroaniline for 4.3 hours at 110 C. (see Toda, Yakugakuzassi, 87, 1351/ 1967). This literature also disclosed pyrone-3carboxamide compounds which were obtained by the reaction of 4-aminotropolones with diketene.

Japanese Patent Specification No. 45.31663 (1970) discloses a process for preparing 2,6-dimethyl-4oxo-4H-pyran-3-carboxamides which comprises reacting iso-cyanates and diketene in the presence of an acid catalyst and specifically mentions in the working examples 2,6-dimethyl-4-oxo-N-phenyl-4H-pyran-3carbox-amide, 2.6-dimethyl-N-(2-methyl phenyl )-4-oxo-4H-pyran-3-carboxa mide, N-(2-chlorophenyl)-2,6-dimethyl-4-oxo-4H-pyran-3-carboxamide, 2,6-dimethyl-N-(2-n itrophenyl )-4-oxo-4H-pyran-3-carboxamide, N (2,5-dich lorophenyl)-2,6-dimethyl-4-oxo-4H-pyran-3-carboxam ide, oxo-4H-2,6-dimethyl-N-(3-nitrophenyl)-4 oxo-4H-pyran-3-carbox-amide and 2,6-dimethyl-N-(4-methyl ph enyl)-4-oxo-4H-pyran-3-carboxa mide.

Furthermore, 2,6-dimethyl-4-oxo-N-phenyl-4H-pyran-3-carboxamide, N-(4-methoxyphenyl )-2,6-dimethyl4-oxo-4H-pyran-3-ca rboxamide and N-(4-chlorophenyl)-2,6-di methyl-4-oxo-4H-pyran-3-carboxamide have been disclosed as the reaction products between 3-morpholinocrotonanilide compounds and diketene (see Kato etal., Yakugakuzassi, 101, 43/1981).

There have been described pyrone-3-carboxamide compounds which correspond to aminotropones (see H. Toda & S. Seto, Chem. Pharm. Bull., 19, 1477/1971.), aminopyridines (see T. Kato petal., Chem.

Pharm. Bull., 20, 133/1972; ibid. 28, 2129/1980; and H.L. Yale petal., J. Heterocyclic Chem., 14, 637/1977) and 2-amino-1,3,4-thiadiazoles (see R.F. Lauer et al., J. Heterocyclic Chem., 13, 291/1976), respectively.

In the above-mentioned Japanese Patent Specification No. 45.31663, it is disclosed that 2,6-dimethyl-4oxo-4H-pyran-3-carboxamides are useful as agricultural chemicals, for example as control agents for sheath blight in rice, as nematicides and as acaricides, ans also as antiviral agents or the like, but without any data supporting such utility.

However, there have been no reports of pyrone-3-carboxamide compounds of the following general formula (I) or of a suggestion of their plant growth-inhibitory activity.

Thus, according to the present invention, there are provided compounds of the general formula:

wherein R, is an alkyl radical and R2 is an alkyl radical or halogen atom, and the salts thereof.

The term "alkyl radical" preferably means one containing up to 5 carbon atoms and "halogen" in the definition of R2 preferably means a fluorine, chlorine or bromine atom.

Preferred alkyl radicals R, and R2 include the methyl, ethyl and isopropyl radicals and the halogen atom is preferably a chlorine atom.

The compounds of general formula (I) can be obtained in good yield by reacting a butyrylanilide derivative of the general formula:

wherein R, and R2 have the same meanings as above, with diketene or with its addition product with acetone, i.e. 2,2,6-trimethyl-4H-1 ,3-dioxin-4-one.

The butyrylanilide derivatives of general formula (II) can be easily prepared by reacting the corresponding acetoacetanilide derivative with N,N-dimethylhydrazine under dehydro-condensation conditions in accordance with conventional methods. The intermediate of general formula (II) is desirably used after isolation and purification but may be used directly as the reaction mixture obtained.

The reaction of compounds of general formula (II) with diketene or with 2,2,6-trimethyl-4H-1,3-dioxin-4one is carried out in an appropriate solvent with heating. The solvent used is preferably one in which the products are not very soluble at a low temperature. Aromatic hydrocarbons, such as benzene, soluene, xylene and the like, are advantageously used as solvents. The reaction temperature is in the range of from 60 to 1300C. when using diketene and in the range of from 100 to 14000. when using 2,2,6-trimethyl4H-1,3-dioxin-4-one.

In addition to the compounds described in the Examples, preferred compounds according to the present invention include the following: N-(3-chloro-2-methylphenyl-)-2,6-dimethyl-4-oxo-4H-pyran-3-carboxamide, 2,6-dimethyl-N-(2,4-dimethylphenyl)-4-oxo-4H-pyran-3-carboxamide, 2,6-dimethyl-N-(2,5-dimethyl phenyl )-4-oxo-4H-pyran-3-carboxamide.

The following Examples are given for the purpose of illustrating the present invention: Example 1.

N- (2, 6-Dieth ylphen yI)-2, 6-dimethyi-oxo-4Thp yran-3-carboxamide.

A mixture of 25.0 g. (90.8 mmol) N-(2,6-diethyl-phenyl)-3-(N,N-dimethylhydrazono)-butyrylamide (m.p.

107 - 108.5"C., recrystallised from hexane) and 130 ml. toluene was heated under reflux, a solution of 28.4 g. (200 mmol) 2,2,6-trimethyl-4H-1,3-dioxin-4-one in 70 ml. toluene being added dropwise thereto over the course of 30 minutes, whereafter the mixture was further refluxed for 2 hours. After distilling off the solvent, 200 ml. diethyl ether were added to the residue. The mixture was well mixed and filtered to remove unsoluble material and the filtrate was concentrated. The residue obtained was subjected to chromatography to remove highly polar impurities. The resultant product was recrystallised from hexane to give 20.2 g. (yield 74% of theory) of the title compound. Its physical properties are given in the following Table 1. The "evaluation" values also given in Table 1 were obtained as follows.

A carrier was prepared by mixing, by weight, 50 parts talc, 25 parts bentonite, 2 parts of Solpole -9047 (Toho Chemical Co., Ltd., Japan) and 3 parts of Solpole -5039 (Toho Chemical Co., Ltd, Japan). 50 parts of a test compound and 200 parts of the carrier were mixed to give a 20% wettable powder, followed by dispersing the powder in distilled water to make dispersions of definite concentrations.

Seeds of Oryza sativa L., Echinochloa crus-galli L., and Raphanus sativus L. were germinated in a laboratory dish, to which the dispersion was added. After growing for 7 days in a thermostatic box kept at 25"C. and illuminated with fluorescent tubes, the growth of plants was observed. In the "Evaluation" column of Table 1, 1 means no influence, 2 means 25% growth inhibition, 3 means 50% growth inhibition, 4 means 75% growth inhibition and 5 means 100% growth inhibition.

Example 2.

N-(2,3-Dimethylphen yI)-2, 6-dimeth yl-4-oxo-4H-pyran-3-carboxamide.

A mixture of 10.3 g. (50 mmol) N-(2,3-dimethyl-phenyl)-3-oxo-butanamide, 4.50 g. (75 mmol) N,N-dimethylhydrazine and 60 ml. toluene was stirred for 8 hours at 600C. Unreacted N,N-dimethylhydrazine and the resultant water, together with about 10 ml. of toluene, were distilled off from the reaction mixture.

10.5 g. (125 mmol) of diketene were added dropwise to the remaining solution over a period of 5 minutes, while refluxing. The mixture was further refluxed for 2 hours and cooled to ambient temperature.

The resultant crystals were filtered off, washed and dried to give 8.63 g. (yield 64% of theory) of the title compound.

Example 3.

N-(2-Chloro-6-methylphenyl)-2, 6-dimethyl-4-oxo-4ll-p yran-3-carboxamide.

The title compound was prepared from N-(2-chloro-6-methylphenyl)-3-oxo-butanamide and N,N-dimethyl-hydrazine as starting materials in a manner analogous to that described in Example 2. Yield: 45 iO of theory.

Example 4.

N- (2, 6-dim eth ylphen yl)-2, 6-dim ethyl-4-oxo-4H-p yran-carboxamide.

The title compound was prepared from N-(2,6-dimethylphenyl)-3-oxo-butanamide and N,N-dimethyl-hydrazine as starting materials in a manner analogous to that described in Example 2. Yield: 63% of theory.

Example 5.

N-(2-Ethyl-6-methylphenyl)-2, 6-dimethyl-4-oxo-4H-pyran-3-carboxamide.

The title compound was prepared from N-(2-ethyl-6-methylphenyl)-3-oxo-butanamide and N,N-dimethyl-hydrazine in a manner analogous to that described in Example 2. Yield: 58% of theory. TABLE 1 Example substit- NMR (CDCl3) value IR(cm-1) m.p. evaluation No. uent c=0 ( C) R1, R2 CH3 H NH substituent (KRr) con. plants used at 2,6- at 5- on the phe- (ppm) position position nyl radical x y x 2-C2H5 2.80 (s) 6.24 (s) 1.17 (t,6H) 1655 83.5- 20 1 2 3 1 11.00 84.5 6-C2H5 2.29 (s) 2.61 (q,4H) 1675 100 2 4 4 2-CH3 2.83 (s) 2.28 (s,6H) 1645 174.5- 20 1 1 3 2 6.23 (s) 11.66 175.5 3-CH3 2.28 (s) 1675 100 1 2 4 2-Cl 2.80 (s) 2.28 (s,3H) 1655 145.0- 20 1 1 2 3 6.24 (s) 11.40 148.0 6-CH3 2.28 (s) 1678 100 1 2 4 2-CH3 2.79 (s) 2.24 (s,6H) 1650 111.5- 20 1 1 1 4 6.22 (s) 11.18 112.0 6-CH3 2.28 (s) 1678 100 1 1 3 2-C2H5 2.80 (s) 1.18 (t,3H) 1653 20 1 4 1 5 6.23 (s) 10.97 2.24 (s,3H) 58.5 6-CH3 2.28 (s) 2.63 (q,2H) 1683 100 1 1 1 compar- 2,6-dimethyl-4-oxo-N-phenyl-4H-pyran-3-carboxamide 20 1 1 1 ative 100 1 1 1 Example (known compound) x : Oryza sativa L.

y : Echinochloa crus-galli L.

z : Raphanus sativus L.

Claims (11)

1. Pyrone-3-carboxamide derivatives of the general formula:

wherein R, is an alkyl radical and R2 is an alkyl radical or halogen atom.

2. Compounds according to claim 1, wherein the alkyl radicals R, and R2 contain up to 5 carbon atoms.

3. Compounds according to claim 1, wherein the halogen atom R2 is a fluorine, chlorine or bromine atom.

4. Compounds according to claim 1, wherein the alkyl radicals R, and R2 are methyl, ethyl or isopropyl radicals.

Compounds according to claim 1, wherein the halogen atom R2 is a chlorine atom.

6. Compounds according to claim 1 which are hereinbefore described and exemplified.

7. Process for the preparation of compounds according to claim 1, wherein a butyrylanilide derivative of the general formula:

in which R, and R2 have the same meanings as in claim 1, is reacted with diketene or with the addition product thereof with acetone in a solvent.

8. Process according to claim 7, wherein the reaction with diketene is carried out at a temperature of from 60 to 130"C. and the reaction with the diketene-acetone addition product is carried out at a temperature of from 100 to 140"C.

9. Process for the preparation of compounds according to claim 1, substantially as hereinbefore described and exemplified.

10. Compounds according to claim 1, whenever prepared by the process according to any of claims 7 to 9.

11. Plant growth-inhibiting compositions containing at least one compound according to claim 1 and an appropriate carrier or diluent.