Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-05-01
2001-07-24
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C546S329000, C548S205000
Reexamination Certificate
active
06265582
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an improved method for producing intermediates of guanidine derivatives which are useful as insecticides.
BACKGROUND ART
A guanidine derivative having an insecticidal activity and a method for producing the same are disclosed in JP-A-157308/1991. As an improved method for producing the guanidine derivative, a method for producing via an isourea derivative is disclosed in WO97/00867 as shown in the following scheme 1.
wherein R
1
and R
2
are the same or different, and each represents a hydrogen atom or an optionally substituted hydrocarbon group; R
3
represents an optionally substituted amino group; A represents a divalent hydrocarbon group which may optionally be substituted; Q′ represents an optionally substituted heterocyclic group; X represents an electron withdrawing group; Y
1
and Y
2
are the same or different, and each represents a leaving group; and n represents 0 or 1.
Among the starting materials in the above-mentioned method via the isourea derivative, for example, O-methyl-N-nitroisourea (hereinafter, sometimes abbreviated as MNI) or a salt thereof can be usually produced by nitrating O-methylisourea or a salt thereof (Recueil des Travaux Chimiques des Pays-Bas, Vol.81, pp.69, 1962).
In this method, for example, when MNI is obtained by industrially conducting nitration by using nitric acid in sulfuric acid, pouring the reaction mixture into cold water or ice, or a mixture of water and ice after the completion of the reaction, and cooling the mixture to about −15° C. to separate the resulting MNI by filtration, MNI is obtained in a low yield of about 75% at the maximum by only a post-treatment operation such as separation by filtration because of the water-solubility of MNI. Furthermore, the yield is further lowered by increasing the scale of the reaction. The yield increases to about 90% by extracting from a mother liquor for filtration. However, since the solubility of MNI in a usable extraction solvent is not so high, a large amount of an organic solvent is required and, therefore, the operation becomes complicated and is very disadvantageous from an industrial point of view. In the case of using O-methylisourea monomethyl sulfate as a starting material, this compound can be obtained by the reaction between urea and dimethyl sulfuric acid, but this reaction itself proceeds in a yield of only about 60% (Journal of Chemical Society, Vol.1955, pp.3551) and subsequent post-treatment of nitration requires extraction by solvent. Furthermore, MNI corresponds to a dangerous object V under the Jananese Fire Services Act., and has explosive properties.
DISCLOSURE OF INVENTION
Under these circumstances, an object of the present invention is to provide a method for producing an intermediate of a guanidine derivative which can be advantageously and safely practiced from an industrial point of view.
The present inventors have intensively studied methods for producing N-nitroisoureas such as NMI or a salt thereof and the reaction of subsequent steps to attain the above object.
As a result, the inventors found surprisingly that a compound represented by the formula:
wherein R
1
represents an optionally substituted hydrocarbon group; R
2
represents a hydrogen atom or an optionally substituted hydrocarbon group; and Q represents an optionally substituted heterocyclic group, or a salt thereof can be produced in a high yield by subjecting a compound represented by the formula:
wherein R
1
has the same meaning as defined above, or a salt thereof to a nitration reaction (a), and further subjecting the resulting mixture without isolating/purifying the resulting compound represented by the formula:
wherein R
1
has the same meaning as defined above, or a salt thereof to a reaction (b) with a compound represented by the formula:
Q—CH
2
—NH—R
2
[III]
wherein each symbol has the same meaning as defined above, or a salt thereof.
It is not usually expected that the compound [IV] or a salt thereof can be obtained in a high yield regardless of the assumption that by-products produced during the nitration reaction (a), starting materials and a large amount of salts of sulfate and nitrate are present in the reaction system of the reaction (b) of the present invention, that is exactly the surprising result. By means of the experimental operation of the present invention, not only industrial disadvantages of the isolation of N-nitroisoureas such as MNI or salts thereof [i.e. the yield is low only by filtration and, when the extraction is conducted to improve the yield, the post-treatment becomes very complicated] have been solved once for all, but also the safety of the operation has been improved remarkably because N-nitroisoureas such as MNI having a risk of explosion or a salt thereof are not isolated. Furthermore, the present inventors have intensively studied based on such a knowledge, thus completing the present invention.
Namely, the present invention relates to:
[1] a method for producing a compound represented by the formula:
wherein R
1
represents an optionally substituted hydrocarbon group; R
2
represents a hydrogen atom or an optionally substituted hydrocarbon group; and Q represents an optionally substituted heterocyclic group, or a salt thereof which comprises subjecting a compound represented by the formula:
wherein R
1
has the same meaning as defined above, or a salt thereof to the nitration reaction (a), and further subjecting the resulting mixture without isolating/purifying the resulting compound represented by the formula:
wherein R
1
has the same meaning as defined above, or a salt thereof to the reaction (b) with a compound represented by the formula:
Q—CH
2
—NH—R
2
[III]
wherein each symbol has the same meaning as defined above, or a salt thereof,
[2] the method as described in [1] above, wherein the nitration reaction (a) is carried out by using nitric acid in the presence of sulfuric acid,
[3] the method as described in [1] above, wherein a degassing treatment under reduced pressure is carried out after the completion of the nitration reaction (a),
[4] the method as described in [1] above, wherein the reaction mixture is diluted with water and/or ice after the completion of nitration reaction (a), and then subjected to the reaction (b),
[5] the method as described in [4] above, wherein a gas which does not interfere with the reaction is bubbled during the dilution of the reaction mixture with water and/or ice,
[6] the method as described in [5] above, wherein the gas which does not interfere with the reaction is air or nitrogen,
[7] the method as described in [4] above, wherein the reaction (b) is carried out under pH 5 to 8,
[8] the method as described in [4] above, wherein the reaction (b) is carried out under pH 6 to 7.5,
[9] the method as described in [1] above, wherein R
1
is a C
1-3
alkyl group,
[10] the method as described in [1] above, wherein the compound represented by the formula[I] or a salt thereof is O-methylisourea sulfate, O-methylisourea 1/2 sulfate or O-methylisourea monomethyl sulfate, and
[11] the method as described in [1] above, wherein R
2
is a hydrogen atom and Q is a 6-chloro-3-pyridyl group or a 2-chloro-5-thiazolyl group.
BEST MODE FOR CARRYING OUT THE INVENTION
In the above formulas, the hydrocarbon group in the optionally substituted hydrocarbon group for R
1
or R
2
, includes a saturated or unsaturated aliphatic hydrocarbon group or an aromatic hydrocarbon group.
The saturated or unsaturated hydrocarbon group includes a C
1-15
alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl or pentadecyl; a C
2-10
alkenyl group such as vinyl, allyl, 2-methylallyl, 2-butenyl,
Kamiya Yasuo
Konobe Masato
Uneme Hideki
Yamada Junji
Takeda Chemical Industries Ltd.
Vollano Jean F.
Wenderoth , Lind & Ponack, L.L.P.
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