JPH051024A - Sulfonamide derivative - Google Patents

Abstract

(57) [Summary] [Object] To provide a benzenesulfonylisothiourea derivative and a benzenesulfonylhydroxyguanidine derivative (hereinafter, abbreviated as the compound of the present invention) useful as an intermediate for medicines and agricultural chemicals and an organic intermediate, and a method for producing the same. [Structure] A benzenesulfonylisothiourea derivative represented by the general formula (I) and a benzenesulfonylhydroxyguanidine derivative represented by the general formula (II), wherein the benzenesulfonylisothiourea derivative represented by the general formula (I) is From the formula (III) and the general formula (IV),
The benzenesulfonylhydroxyguanidine derivative of the general formula (II) is produced from the benzenesulfonylisothiourea derivative of the general formula (I) and hydroxyamine or a salt thereof. [Wherein, X, Y and Z are the same or different from each other, a hydrogen atom, a C ₁ -C ₆ lower alkyl group, a C ₁ -C ₆ lower alkoxyl group, a halogen atom,
Represents a nitro group and an acetylamino group. R ¹ is C _{1 to} C ₃
Represents a lower alkyl group. Q represents a halogen atom. ]

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a benzenesulfonylisothiourea derivative and a benzenesulfonylhydroxyguanidine derivative (hereinafter abbreviated as the compound of the present invention) useful as an intermediate for medicines and agricultural chemicals and an organic intermediate, and a method for producing the same.

The present inventors have found that the N-oxadiazolylsulfonamide derivative obtained from the hydroxyguanidine derivative and the carboxylic acid derivative of the present invention has herbicidal activity.

[0003]

2. Description of the Related Art For example, Journal Chemical Society, 1946, page 491 (J. Chem. Soc.).
It is disclosed that the benzenesulfonylisothiourea derivative is useful as an intermediate of an antibacterial active substance. Further, for example, Japanese Patent Publication No. 38-26676 discloses that 4-acetylaminobenzenesulfonylhydroxyguanidine is useful as an intermediate for producing an antibacterial agent.

[0004]

Various sulfonamide derivatives have been known because of their antibacterial activity, but only limited benzenesulfonylisothiourea derivatives and benzenesulfonylhydroxyguanidine derivatives are known. Only.

[0005]

Means for Solving the Problems As a result of various investigations for the purpose of the use of the sulfonamide derivative other than the antibacterial activity, the present inventors have found that, in addition to those using a known compound as an intermediate, The compounds of the present invention have been found to be useful as a body.

That is, the general formula (I)

[0007]

[Chemical 5] (In the formula, X, Y, and Z are the same or different from each other and represent a hydrogen atom, a C _{1 to} C ₆ lower alkyl group, a C _{1 to} C ₆ lower alkoxyl group, a halogen atom, a nitro group, or an acetylamino group. R ¹ represents a C _{1 to} C ₃ lower alkyl group, provided that when Z is an acetylamino group or a nitro group, neither X nor Y is a hydrogen atom.), General formula (II)

[0008]

[Chemical 6] (In the formula, X, Y, and Z are the same or different from each other and represent a hydrogen atom, a C _{1 to} C ₆ lower alkyl group, a C _{1 to} C ₆ lower alkoxyl group, a halogen atom, a nitro group, or an acetylamino group. However, when Z is an acetylamino group,
Neither X nor Y is a hydrogen atom. ), A benzenesulfonylhydroxyguanidine derivative represented by the formula (1) and a method for producing the same.

X, Y and Z of the benzenesulfonylisothiourea derivative of the general formula (I) are hydrogen atom, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert. A C ₁ -C ₆ lower alkyl group such as a butyl group, a pentyl group, a hexyl group, a methoxyl group, an ethoxyl group, a propoxyl group, a C ₁ -C ₆ lower alkoxyl group such as an isopropoxyl group, a chlorine atom, Examples thereof include halogen atoms such as bromine atom, iodine atom and fluorine atom, nitro group and acetylamino group. However, when Z is an acetylamino group or a nitro group, X and Y are not hydrogen atoms at the same time. R ¹ is a C such as a methyl group, an ethyl group or a propyl group.
There may be mentioned lower alkyl groups of ₁ -C _3.

Further, as X, Y and Z of the benzenesulfonylhydroxyguanidine derivative of the general formula (II),
Hydrogen atom, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group,
C ₁ such as tert-butyl group, pentyl group and hexyl group
Lower alkyl group -C _6, methoxyl group, ethoxyl group, propoxyl group, _C 1 -C such isopropoxyl group
The lower alkoxyl group of ₆ , a halogen atom such as a chlorine atom, a bromine atom, an iodine atom and a fluorine atom, a nitro group and an acetylamino group can be exemplified. However, when Z is an acetylamino group, X and Y are not hydrogen atoms at the same time.

The benzenesulfonylisothiourea derivative of the general formula (I) has the general formula (III

[0012])

[Chemical 7] (In the formula, X, Y, and Z are the same or different from each other and represent a hydrogen atom, a C _{1 to} C ₆ lower alkyl group, a C _{1 to} C ₆ lower alkoxyl group, a halogen atom, a nitro group, or an acetylamino group. Q represents a halogen atom, provided that when Z is an acetylamino group or a nitro group, neither X nor Y is a hydrogen atom.
V)

[0013]

[Chemical 8] (R ¹ represents a C ₁ -C ₃ lower alkyl group), an isourea compound represented by the following formulas: in the presence of a solvent, in the presence of a base, under ice-cooling 1-
It can be obtained by reacting for several hours.

Examples of Q in the general formula (III) include halogen atoms such as chlorine atom, bromine atom, iodine atom and fluorine atom, but chlorine atom is preferred for reasons of reactivity and economy.

Examples of R ^{1 in the} general formula (IV) include C ₁ -C ₃ lower alkyl groups such as a methyl group, an ethyl group and a propyl group, but a methyl group is preferable from the viewpoint of reactivity. Further, isothiourea can be used in a free form, but a salt with a mineral acid such as hydrochloric acid or sulfuric acid can also be used.

As the solvent, ketones such as hydrated acetone and hydrated methyl ethyl ketone, hydrated tetrahydrofuran,
Examples include ethers such as hydrous dioxane. Aqueous acetone is preferred.

Examples of the base include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, potassium carbonate and the like, but sodium hydroxide is preferable.

It is sufficient that the amount of isothiourea is 1 equivalent or more based on the sulfonyl chloride derivative.

The benzenesulfonylhydroxyguanidine derivative of the general formula (II) is obtained by heating the benzenesulfonylisothiourea derivative of the general formula (I) and hydroxyamine or a hydrochloride thereof in an alcohol solvent such as methanol or ethanol under reflux for several hours. You can get it.

When a salt of hydroxyamine is used, it is desirable to use a base such as sodium methoxide, potassium methoxide, sodium ethoxide and potassium ethoxide. The preferred base is sodium methoxide.

The amount of base may be 1 equivalent or more with respect to the hydroxyamine, and the amount of hydroxyamine may be 1 equivalent or more with respect to the benzenesulfonylisothiourea derivative.

[0022]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.

Example 1 Preparation of S-methyl 4-chlorobenzenesulfonylisothiourea 4-chlorobenzenesulfonyl chloride 30.3 g in a 200 ml beaker containing 60 ml of acetone and 60 g of ice.
And 20 g of methylisothiourea sulfate were added sequentially with stirring. Then 10% sodium hydroxide 100
ml was added dropwise in about 40 minutes. Then, the mixture was stirred for 2 hours and left standing at room temperature for 12 hours. The precipitated solid product is collected by filtration,
It was dried under reduced pressure to obtain 22.2 g of the desired product. Yield is 5
It was 9%.

M. p. 115-118 ° C. ¹ H-NMR (DMSO-d ₆ , δppm) 2.32 (s, 3H), 7.58 (d, J = 8 Hz, 2
H), 7.70-9.12 (m, 4H) IR (KBr, cm ^-1 ) 3410, 3320, 1635, 1520, 1345,
1145, 1090, 565 Elemental analysis (%): Calculated value as C ₈ H ₉ ClN ₂ O ₂ S: C41.06, H3.92, N12.16 Measured value: C41.29, H3.89, N12.03

Examples 2 to 10 Table 1 shows benzenesulfonylisothiourea derivatives obtained in the same manner as in Example 1.

[0026]

[Table 1]

Example 11 Preparation of 4-nitrobenzenesulfonylhydroxyguanidine 5 g of metallic sodium was added and dissolved in a 100 ml eggplant-shaped flask containing 70 ml of anhydrous methanol. 15.2 g of hydroxyamine hydrochloride was added to the solution and stirred for about 10 minutes. The deposited solid is filtered and the solid is filtered to about 10
It was washed with 0 ml of methanol. S-Methyl 4-nitrobenzenesulfonylisothiourea 11.
7 g was added and the mixture was heated under reflux for about 2 hours. After cooling, the insoluble material was filtered off. The filtrate was concentrated to 60 ml and 80 ml of water was added. After the insoluble matter was filtered off, the mixture was allowed to stand overnight at room temperature and the precipitated crystals were filtered off to obtain 3.52 g of the objective yellow crystal. The yield was 32%.

118 ° C. decomposition ¹ H-NMR (DMSO-d ₆ , δppm) 7.33 (bs, 2H), 7.98 (d, J = 9 Hz,
2H), 8.35 (d, J = 9Hz, 2H), 9.50
(Bs, 1H), 10.13 (bs, 1H) IR (KBr, cm ⁻¹ ) 3400, 3325, 3200, 1645, 1570,
1520,1345,1260,1170,1140 Elemental analysis _{(%): C 7 H 8} N 4 O 5 Calculated as S: C32.06, H3.20, N21.50 Found: C32.30, H3.09 , N21.53

Examples 12 to 17 Table 2 shows benzenesulfonylhydroxyguanidine derivatives obtained in the same manner as in Example 11.

[0030]

[Table 2]

[0031]

Industrial Applicability According to the present invention, important intermediates of compounds useful as antibacterial agents and herbicides can be provided.

Claims (4)

[Claims] 1. A compound represented by the general formula (I): (In the formula, X, Y, and Z are the same or different from each other and represent a hydrogen atom, a C _{1 to} C ₆ lower alkyl group, a C _{1 to} C ₆ lower alkoxyl group, a halogen atom, a nitro group, or an acetylamino group. R ¹ represents a C ₁ -C ₃ lower alkyl group, provided that when Z is an acetylamino group or a nitro group, neither X nor Y is a hydrogen atom.). 2. A compound represented by the general formula (II): (In the formula, X, Y, and Z are the same or different from each other and represent a hydrogen atom, a C _{1 to} C ₆ lower alkyl group, a C _{1 to} C ₆ lower alkoxyl group, a halogen atom, a nitro group, or an acetylamino group. However, when Z is an acetylamino group,
Neither X nor Y is a hydrogen atom. ) A benzenesulfonylhydroxyguanidine derivative represented by: 3. A compound represented by the general formula (III): (In the formula, X, Y, and Z are the same or different from each other and represent a hydrogen atom, a C _{1 to} C ₆ lower alkyl group, a C _{1 to} C ₆ lower alkoxyl group, a halogen atom, a nitro group, or an acetylamino group. Q represents a halogen atom, provided that when Z is an acetylamino group or a nitro group, neither X nor Y is a hydrogen atom.
V) [Chemical 4] The method for producing a benzenesulfonylisothiourea derivative represented by the general formula (I) according to claim 1, which comprises reacting with an isourea compound represented by the formula (R ¹ represents a C ₁ -C ₃ lower alkyl group). . 4. A benzene represented by the general formula (II) according to claim 2 by a reaction between a benzenesulfonylisothiourea derivative represented by the general formula (I) according to claim 1 and hydroxyamine or a hydrochloride thereof. Process for producing sulfonylhydroxyguanidine derivative.