Process for producing benzamidoximes

Details Process for producing benzamidoximes Process for producing benzamidoximes

2000-06-29

2001-04-03

Richter, Johann (Department: 1621)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ester doai

C564S265000

Reexamination Certificate

active

06211232

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to processes for the preparation of benzamidoximes useful as intermediates for agrochemicals and pharmaceuticals and represented by Formula (II)
(where, X is halogen, C
1-5
alkyl, C
1-3
alkoxy, C
1-3
alkylthio, hydroxyl, mercapto, amino, nitro or C
1-5
haloalkyl; and n is 0 or an integer from 1 to 5) at stable, high yields. Of the compounds produced by the processes of the present invention, 2,3-difluoro-6-trifluoromethylbenzamidoxime is particularly useful as an intermediate for agricultural and horticultural fungicides.
BACKGROUND OF THE INVENTION
It was known that amidoximes were synthesized generally by reacting nitriles and hydroxylamines (Houben-Weyl Methoden der Organischen Chemie Band VIII Sauerstoff ver Bindungen III p. 692).
It was reported that 2,3-difluoro-6-trifluoromethylbenzamidoxime, which was included in the benzamidoximes represented by Formula (II), could be produced by reacting 2,3-difluoro-6-trifluoromethylbenzonitrile with hydroxylamine hydrochloride in the presence of sodium carbonate or the like (WO 96/19442).
However, in conventional technology, if there is a very small amount of metal ions, such as iron, in a solvent or if a brown-glass or SUS vessel is used as a reaction vessel, the yield of a target amidoxime compound is strikingly reduced, and benzamides represented by Formula (III)
are produced in a large amount as byproducts.
DISCLOSURE OF THE INVENTION
It is an object of the present invention to produce a benzamidoxime represented by Formula (II) from a benzonitrile represented by Formula (I) and hydroxylamine at a stable, high yield.
The present invention is directed to processes for the preparation of benzamidoximes represented by Formula (II), characterized in that a benzonitrile represented by Formula (I) is reacted with hydroxylamine in the presence of a chelating agent. The reaction scheme of the present invention is shown below:
Representative examples of compounds to which the processes of the present invention are applicable are shown in Table 1.
TABLE 1
Major Representative Examples


No.
X
1
X
2
X
3
X
4
X
5
1
F
F
H
H
CF
3
2
F
H
H
H
CF
3
3
F
Cl
H
H
CF
3
4
Cl
F
H
H
CF
3
5
Cl
Cl
H
H
CF
3
6
F
F
F
H
CF
3
7
CF
3
H
H
H
H
8
F
H
H
H
H
9
F
F
H
H
CH
3
10
F
F
H
H
OCH
3
11
CF
3
H
H
F
NH
2
12
CF
3
H
H
F
OH
13
Cl
H
H
H
Cl
14
F
H
H
H
F
15
F
H
H
H
NO
2
16
H
F
H
H
H
17
Cl
H
H
H
H
18
H
Cl
H
H
H
19
H
H
Cl
H
H
20
H
H
H
H
H
The said reaction is carried out by reacting a benzonitrile (I) with hydroxylamine (HA) in the presence of a chelating agent. In case a reaction vessel, such as made of SUS, is used, an alkali carbonate, such as sodium hydrogencarbonate, may be present in the reaction system to protect the vessel. An amount of HA used is preferably (I):HA=1:1.5~3. HA may be used in the form of HA hydrochloride and the like in the presence of a base. It is however preferable to use free HA.
Solvents inactive to the reaction are preferably used in this invention. For example, solvents such as acetonitrile are not favorable.
Among them solvents that are highly polar and can dissolve chelating agents are preferable. For instance, a methanol-water mixed solvent is exemplified. It is more preferable to use excessive water over methanol.
Chelating agents used in the present invention are mainly those that easily form complexes with iron ions. 8-Hydroxyquinoline represented by Formula (IV) and o-phenanthroline represented by Formula (V) are preferable examples.
A quantitative ratio of a chelating agent may be a catalytic amount to benzonitrile (I), and more preferably 0.1 to 1 mol % to (I).
After the completion of the reaction, ordinary after-treatment gives a target compound. Particularly it is effective to extract with an acid, such as hydrochloric acid, in the said after-treatment, because of easy removal of benzamide byproducts.


REFERENCES:
patent: 5183828 (1993-02-01), van't Riet et al.
patent: 5621143 (1997-04-01), Pocius
Sindelar et al., “Synthesis of (2-(PhenylThio)Phenyl)Acetamidines and Related Amidoximes as Potential Antidepressants”, Collection of Czechoslovak Chemical Community, (53) 1988, p 381-387.*
Stephenson, Leslie et al., ““Reaction of some aromatic nitriles with hydroxylamine to give amides, and an alternative preparation of amidoximes” (1969),” J. Chem. Soc. C, p. 861-864, X.

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