JPS62212368A - Manufacture of heterocyclic compound - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to the preparation of certain substituted dihydropyridine and pyridine compounds and to the novel dihydropyridine compounds themselves. The compound is useful as an intermediate for producing herbicidal pyridylimidazolinone compounds.

Pyridylimidacillin compounds have been disclosed in various publications as herbicides and plant growth regulators.

For example, EP-A-≠7623 discloses a wide range of such compounds and their use as herbicides;
-A-! /4.2≠ disclose their use as plant growth regulators. Among the compounds, each of these specifications specifically mentions 2-(j-ingropyruyo-monomethyl-hiro-oxo-2-imidazoline-choyl)-J-ethyl-nicotinic acid and ethyl-(j-ingropyru-! −
Methyl≠-oxo-2-imidacillin-λ-yl]-
Termethylnicotine et-disclosed.

EP-A-10J discloses that the pyridylimidacilline compound is synthesized from 2,3-pyridinecarboxylic anhydride, and that the dicardexy compound itself which readily provides the anhydride is a quinoline compound. It is known that scales are produced by exposure to fully oxidizing conditions.

EP-A-/6/22/ discloses that a compound of formula A R1 is reacted with a hydrazone of formula B and a maleic acid derivative of formula C to form a compound of formula H-
NR7R,. It is claimed that the scales are produced by removing the scales. There is no base R1! A wide range of possibilities are claimed for R1°.

The group X of the compound of formula C is a dihydropyridyl compound Dt-
For the reaction that produces, it is a chlorine or bromine atom. To absorb the hydrochloric acid or hydrobromic acid that forms,
The presence of a base is stated as preferred and is used in all examples.

Deamination has been carried out using acids in dioxane.

In the compounds of the examples of EP-A-/Ot/, 2.2/, the radicals R3 and R4 always represent a bonding group, which is usually of the formula; is an alkyl group).

In the /t embodiment, the bonding group is an oxygen atom. EP-A
-/Otsu/, 2.2/ further relates to providing 3-pyridinecargonic acid anhydride for synthesizing a pyridylimidacillin compound. According to IP-A-/Otsu/2.2/, the method for producing the anhydride is to deaminate a compound of the formula in which R3 and R4 combine to represent a group of the formula R to form a compound R-NH2. ? It involves ring-opening of a pyridyl compound induced by loss to form a dicarboxylic compound, followed by dehydration.

EP-A-/1. The 20 compounds required for the reaction disclosed in /22/ have to be synthesized themselves, and this is done by treating maleic anhydride with a compound of formula R-NH2 and then with acetic anhydride. , followed by halodanization (see EP-A-≠/I2.2≠).

The present invention relates to a simple method for producing a dihydropyridine compound by which such co-,3-pyridine caldicic anhydride can be easily produced.

According to the present invention, the general formula (wherein R1 represents a hydrogen atom or an optionally substituted alkyl or cycloalkyl group, and R2 represents an optionally polysubstituted alkyl or cycloalkyl group) each of R3 and R4 independently represents an optionally substituted alkyl group;
and each of R5 and R6 independently represents an optionally polysubstituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl or aralkyl group. There is provided a method for the preparation comprising reacting a dicarboxylate compound of the general formula II (IfD).

The prior art involves the formation of a ring compound containing a sieving group'; Whereas the present invention provides a route to 2,3-pyridinecarboxylic acid anhydride from maleic anhydride that requires multiple steps including ring-opening, the present invention
provides a simple and direct route to compounds that does not require conjugation, the use of bases, or ring-opening steps that involve loss of material.

According to the process of the invention, an alkyl, alkenyl or alkynyl group preferably has 1 to 2, especially 1 to 1,000 carbon atoms, whereas a cycloalkyl group preferably has 3 to 5 carbon atoms. The aryl group is preferably phenyl, and the aralkyl group is preferably benzyl. If the group is substituted, possible substituents are, for example, a halogen atom% C1-4 alkoxy or haloalkoxy group, hydroxy, cyan, amino, alkylamino, phenyl, phenoxy, cal? Can include xy and alkoxycarbonyl groups. In general, however, it is preferred that each substituent R2 to R6 is an unsubstituted group, and is preferably an unsubstituted c1-4 alkyl group, with methyl and ethyl being the most preferred groups, while R1 is preferably hydrogen. It is an atom.

Preferably the reaction is carried out in an inert organic solvent such as tetrahydrofuran, acetonitrile or dioxane, suitably an alkylated benzene such as toludine or xylene. The reaction may be carried out at a temperature ranging from 0°C to reflux temperature (this may suitably range from 70°C to L/≠θ°C depending on the solvent used) and advantageously in the range from 50°C to reflux temperature, most preferably at reflux temperature. It is done at temperature.

Preferably, the hydrazone is in molar excess over the dicarboxylate. However, even if this is not the case, the reaction can proceed satisfactorily. Generally, the preferred ratio of hydrazone to dicarboxylate is in the range /:l to 2:/particularly /:/ to /, J''2/.

In another aspect the invention relates to the compounds of formula 1 as such.

Compounds of general formula (1) can be converted to pyridine compounds of general formula under deamination conditions. Preferably the reaction is carried out in an inert organic solvent such as benzene, toluene or xylene in the presence of a catalyst such as palladium or platinum, which may conveniently be supported on a charcoal substrate. Preferably, the reaction is carried out at elevated temperature, suitably in the range of 50°C to reflux temperature, most preferably at reflux temperature.

In another aspect, the invention relates to the novel pyridine compounds themselves, excluding j-methyl-2,3-pyridinecardoic acid diethyl ester.

Compounds of general formula IV can be converted to acid anhydrides, for example by converting them to the corresponding dicarginic acids in aqueous sodium hydroxide and refluxing the acids, suitably in the presence of acetic anhydride. and can then be used to produce herbicidal pyridylimidazolinyl compounds by the method disclosed in EP-A-TA 5ios.

The invention will be further described with reference to the following examples.

Example/ Production of stell acetylene dicargen a2 dimethyl CI7.3P; 0,
/ u comol) and 2-methylderopoucoenal dimethylhydrazone (lyooy: o, 13tt
% #) t [added to 20-20% of dry toluene. The reaction mixture was refluxed for 7 hours under nitrogen atmosphere. Evaporate the solvent. 3j-≠0tsCma/ma)ethyl acetate/n- as eluent
Column chromatography on silica using hexane gave the title compound as a yellow oil (Otsu, Ri 1) which crystallized upon freezing (melting point C050°C).

Required value for analysis (chi) Ta, 7C7/H//, ON measurement value (%
) jOtsuJC7jH//, ONNCoco-H-/-tumethylamino-2,3-dicardiacetylenedicarboxylate dimethyl (,2o, st; O0/≠Homole) and 2-ethylprodeλ-dinal dimethylhydrazone ( ,2o,o P: o, istamol) in dry toluene 2! Added to r-. The reaction mixture was refluxed for t-7 hours. The solvent was removed by evaporation. Column chromatography on silica using 4/lo, sti(v/ma) ethyl acetate/n-hexane as eluent yielded the title compound as an orange oil (7,754).

Required value for analysis (H) J″1.2C7, fH10, lAN measurement value (*) j B, fc7.7H9,6N Example 3 Production example of methyl ester/Title compound 1.J″? ) t-dry toluene som
t and j % w/w mother radium charcoal CO,
Otsu? ) was added as a gold catalyst. The reaction mixture was refluxed with catalyst replenishment every 2 hours/≠ hours. The reaction was carried out and the solvent was evaporated leaving a reddish-brown color (7.0P). Column chromatography on silica using 'i' 0% v/ethyl acetate/n-hexane as eluent yielded the title compound <3.3! rP) as a solid (melting point J''
The temperature was θ°C).

Required values for analysis (%) Measured values for C3, fH and N (%)
jg, 7c 3.7 HION Example 2 Add dry toluene 7.5 to the title compound (Z≠Jl)'
'' - dissolved in and %w/v palladium on charcoal C0,7!
;P) k Added as a catalyst. The reaction mixture was refluxed under a nitrogen atmosphere for 21 hours with catalyst replenishment after 7 and 1 hours. The reaction mixture was filtered and the solvent was evaporated. Of the obtained oil (Otsu?), 3j-4tO% (v/v
) Column chromatography on silica using ethyl acetate/n-hexane gave the title compound a pre-orange color (3,41).
Arose as.

Required value for analysis (%) jg, 2c, ifH6,3N Measured value (chi) Yo ZtC Yo fH Otsu jN When the above procedure is repeated, Hirotsu? From the starting material of 3, ≠ 7
The title compound 1 was obtained.

The following example shows that the compound of formula IV is EP-A-ta! 10!
We will explain how it can be converted into an acid anhydride compound that can be used for the synthesis of pyridylimidazolinyl compounds.

For example, λ, 3-cal? Kissy! -Title compound of Preparation Example 3 of methylpyridine anhydride (ZRIjP)k/0%
Added W/W aqueous sodium hydroxide (Jjm/). The reaction mixture was refluxed for an hour and cooled. Hydrochloric acid was added until the - of the reaction mixture became 2. The light brown precipitate formed upon cooling was dried by stirring (2./j?). −
Further hydrochloric acid was added until . Furthermore, the formed precipitate (OoIff) was filtered and dried.

, 2. Precipitation of ist (2,3-dical?xyj-methylgiridine) t-acetic anhydride (Jj-: density/, 0♂2?
It was dissolved in /ri. The reaction mixture was refluxed for 2A hours. The acetic anhydride was first evaporated and then separated by hot water bath and vacuum pump to give a pale gray solid.

analysis

Claims (8)

[Claims] (1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) (In the formula, R^1 represents a hydrogen atom or an optionally substituted alkyl or cycloalkyl group, and R^2 represents a hydrogen atom or optionally substituted alkyl or cycloalkyl group. represents an optionally substituted alkyl or cycloalkyl group, each of R^3 and R^4 independently represents an optionally substituted alkyl or cycloalkyl group, and R^5 and R^ (Each of 6 independently represents an optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl or aralkyl group) In the method for producing compounds of the general formula ▲ mathematical formulas, chemical formulas, tables, etc. ▼(II) The above manufacturing method includes reacting the hydrazone compound with the dicarboxylate compound of the general formula ▲ (which includes mathematical formulas, chemical formulas, tables, etc.) (III). (2) R^1 represents a hydrogen atom, and R^2 to R
2. The method of claim 1, wherein each ^5 independently represents a C_1_-_4 alkyl group. (3) The method according to claim 2, wherein each of R^3 to R^6 represents a methyl group and R^2 represents a methyl or ethyl group. (4) The method according to any one of claims 1 to 3, wherein the hydrazone is in molar excess relative to the dicarboxylate. (5) The method according to any one of claims 1 to 4, wherein the reaction is carried out in an inert organic solvent at a temperature ranging from 50°C to reflux temperature. (6) The method according to any one of claims 1 to 5, in which the compound of the general formula I is subsequently deaminated to produce the compound of the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (IV) . (7) A compound of general formula I as defined in any one of claims 1 to 3. (8) A compound of general formula IV as defined in claim 6 (but not 5-methyl-2,3-pyridinecarboxylic acid, diethyl ester).