JP3376481B2 - Method for producing hexahydropyridazine - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a process for producing hexahydropyridazine, which is useful as an intermediate for benzothiazine pesticides (herbicides). [0002] Hitherto, the production of hexahydropyridazine has been carried out by isolating a hexahydropyridazine-1,2-dicarboxy derivative and then decarboxylating it. A method for producing a 2-dicarboxy derivative by performing a decarboxylation reaction without isolation has not been known. [0003] An object of the present invention is to provide a method for producing hexahydropyridazine industrially simple and inexpensively. [0004] As a result of intensive studies on a method for producing hexahydropyridazine to solve the conventional problems, the present inventor surprisingly found that a method for producing hexahydropyridazine was used in the presence of an aprotic polar solvent. Decarboxylation using alkali metal hydroxide without isolation of hexahydropyridazine-1,2-dicarboxy derivative obtained by reacting hydrazine dicarboxy derivative with dihalogenobutane in the presence of alkali metal hydroxide It was recognized that hexahydropyridazine can be obtained by a simple operation of reacting, and the present invention was completed based on this finding. That is, the present invention relates to a compound represented by the general formula: R ¹ OOC-NH-NH-COOR ² (wherein R ¹ and R ² are each independently represented by an aprotic polar solvent) And a hydrazine dicarboxy derivative represented by the formula: ## STR5 ## and X ¹ --CH ₂ CH ₂ CH ₂ CH _2- X ² (wherein X ¹ and X ² each independently represent a halogen atom). A dihalogenobutane represented by the following formula is reacted in the presence of an alkali metal hydroxide to obtain a compound represented by the general formula: ] (In the formula, R ¹ and R ² have the same meanings as described above.)
Provided is a method for producing hexahydropyridazine, which comprises obtaining a 1,2-dicarboxy derivative and decarboxylating it without isolation in the presence of an alkali metal hydroxide and a hydrogen-donating compound. Things. Hereinafter, the present invention will be described in detail. The process of the present invention relates to hexahydropyridazine-1, which is obtained by reacting a hydrazine dicarboxy derivative (formula 4) or dihalogenobutane (formula 5) with an alkali metal hydroxide in the presence of an aprotic polar solvent. A method for producing hexahydropyridazine, comprising decarboxylating in the presence of an alkali metal hydroxide and a hydrogen-donating compound without isolating a 2-dicarboxy derivative (Formula 6). In the method of the present invention, first, a hydrazine dicarboxy derivative (Formula 4) is used in the presence of an aprotic polar solvent.
And dihalogenobutane (Chem. 5) in the presence of an alkali metal hydroxide to give hexahydropyridazine-1,2
And performing a reaction to obtain a dicarboxy derivative (Formula 6). The hydrazine dicarboxy derivative (Chemical Formula 4) used as a raw material in this reaction includes R ¹ ,
R ² is each independently an alkyl group, specifically, for example, an alkyl group having a linear, branched, or alicyclic structure having 1 to 8 carbon atoms, more specifically, for example, a methyl group, an ethyl group,
Propyl, isopropyl, butyl, pentyl,
Alkyl group such as hexyl group, cyclohexyl group, heptyl group, octyl group; or a group having 1 to 1 carbon atoms including, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, pentyl group, hexyl group, cyclohexyl group, etc.
6 lower alkyl groups having a straight-chain, branched-chain or alicyclic structure (hereinafter, lower alkyl groups are synonymous) and / or halogen atoms including chlorine, bromine, fluorine, and iodine atoms (hereinafter, referred to as the following) , These atoms may be simply referred to as halogen atoms.) Any compound may be substituted at one or more positions, for example, an aryl group including a phenyl group or a naphthyl group. Examples thereof include dimethylhydrazine dicarboxylate, diethyl hydrazine dicarboxylate, dibutyl hydrazine dicarboxylate, diphenyl hydrazine dicarboxylate and the like. R ¹ and R ² having the same substituent are suitable because raw materials are easily available. Further, compounds in which both R ¹ and R ² are lower alkyl groups are particularly easily available and are preferred. Two or more hydrazine dicarboxy derivatives (Chemical Formula 4) may be used as desired. The dihalogenobutane (Chemical Formula 5) used in this reaction is a compound wherein X ¹ and X ² are each independently a halogen atom, specifically a chlorine atom, a bromine atom, a fluorine atom or an iodine atom. Those which are chlorine atoms or bromine atoms are easily available and suitable. Examples of such compounds include 1,4-dichlorobutane, 1,4-dibromobutane, 1-bromo-4-chloro-butane, and the like. Two or more dihalogenobutanes (Chem. 5) may be used as desired. As the alkali metal hydroxide used in the present reaction, any of those usually referred to as such may be used without any limitation, and specific examples thereof include sodium hydroxide and potassium hydroxide. Two or more alkali metal hydroxides may be used as desired. In this reaction, the molar ratio of the hydrazine dicarboxy derivative (Chem. 4), dihalogenobutane (Chem. 5) and alkali metal hydroxide used is 1: (1 to 1).
0) :( 1-20), preferably 1: (1-2) :( 2
To 4) can be exemplified. As the aprotic polar solvent used in the present reaction, any solvent which is usually referred to as an aprotic polar solvent may be used.
Amide aprotic polar solvents represented by N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAc), N, N-diethylacetamide (DEAc), etc., tetrahydrothiophen-1,1-dioxide (sulfolane) ), N, N-dimethylsulfoxide (DMSO) and other aprotic polar solvents containing a sulfur atom, other 1,3-dimethylimidazolidinone (DMI), N, N-dimethylpropyleneurea (DM
PU) and the like. One or more aprotic polar solvents may be used in combination. The amount of the aprotic polar solvent to be used is not particularly limited as long as it can be stirred or more, but usually 500 ml to 2000 ml per 1 mol of the hydrazine dicarboxy derivative (Formula 4) is suitable. This reaction is carried out at a temperature of 10 ° C. to 80 ° C., preferably 40 ° C.
The reaction is usually carried out at a temperature in the range of from 70 ° C. to 70 ° C. under normal pressure, and the reaction time is usually 30 minutes to 24 hours, preferably 1 to 5 hours. In this reaction, for example, a compound capable of functioning as a phase transfer catalyst such as a quaternary phosphonium salt, a quaternary ammonium salt, a crown ether, or a polyethylene glycol may be allowed to coexist. The hydrazine dicarboxy derivative (Chemical Formula 4) used as a starting material for this reaction is obtained from Organic Synthesis Col.
l. , Vol. III, 375, can be easily obtained. In the method of the present invention, the hexahydropyridazine-1,2-dicarboxy derivative (Chem. 6) obtained by the above reaction is decarboxylated in the presence of an alkali metal hydroxide and a hydrogen-donating compound without isolation. The target product, hexahydropyridazine, is obtained by subjecting it to the reaction. As the alkali metal hydroxide used in this reaction, the same ones as in the above reaction, specifically, for example, sodium hydroxide and potassium hydroxide can be exemplified.
The alkali metal hydroxide used here is the above-mentioned hexahydropyridazine-1,2-dicarboxy derivative (Formula 6)
May be different from that used in the reaction for producing The hydrogen-donating compound used in this reaction is, for example, a compound having a hydroxyl group, more specifically, water;
Linear, branched chains having 1 to 6 carbon atoms such as methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, n-pentanol, i-pentanol, n-hexanol and cyclohexanol; Alternatively, alcohols having a ring structure can be exemplified. Generally, water is easy to obtain and handle, and is preferably used. The amounts of the alkali metal hydroxide and the hydrogen-donating compound used in the present reaction are, as molar ratios, the hydrazine dicarboxy derivative (formula 4) used in the previous reaction: alkali metal hydroxide: hydrogen-donating compound = 1: (2-2
0) :( 2-20), preferably 1: (4-8) :( 2
To 8). In this reaction, a reaction solution for the production of the above-mentioned hexahydropyridazine-1,2-dicarboxy derivative (Chemical Formula 6) is used, so that it is usually unnecessary to add a solvent. A polar solvent, specifically, for example, N, N-dimethylformamide (DM
F), N, N-dimethylacetamide (DMAc),
Amide-based aprotic polar solvents such as N, N-diethylacetamide (DEAc), tetrahydrothiophen-1,1-dioxide (sulfolane), N, N-
Sulfur atom-containing aprotic polar solvents such as dimethyl sulfoxide (DMSO) and the like, 1,3-dimethylimidazolidinone (DMI), N, N-dimethylpropylene urea (DMPU) and the like may be added. When the aprotic polar solvent is added, the aprotic polar solvent to be added may be the same as or different from the one used in the reaction for producing the above-mentioned hexahydropyridazine-1,2-dicarboxy derivative (Formula 6). Is optional.
The amount of addition may be any amount as long as the reaction system can be stirred or more, but the total amount of the solvent is hexahydropyridazine-1,2.
It is appropriate that the amount is in the range of 500 ml to 2000 ml per 1 mol of the hydrazine dicarboxy derivative (formula 4) used in the reaction for producing the dicarboxy derivative (formula 6). The reaction is carried out at 80 ° C. to 160, preferably 9
In the temperature range of 0 ° C. to 120 ° C., the reaction is usually performed at normal pressure, but may be performed under pressure. The reaction time is 1 to 24 hours, preferably 2 to 8 hours. The isolated hexahydropyridazine-
The 1,2-dicarboxy derivative (Formula 6) was used to carry out a decarboxylation reaction in an aprotic polar solvent in the presence of an alkali metal hydroxide and a hydrogen-donating compound. No formation of certain hexahydropyridazine was observed. According to the method of the present invention, a hexahydropyridazine-1,2-dicarboxy derivative (formula 6) produced from a hydrazine dicarboxy derivative (formula 4) and a dihalogenobutane (formula 5) is isolated. Hexahydropyridazine can be produced by a simple operation of subjecting to a decarboxylation reaction without performing. Therefore, it is not only suitable for industrial production of hexahydropyridazine due to its simple operation, but also important as a method for producing a useful intermediate of a benzothiazine herbicide (described in JP-A-63-264489). The present invention will be specifically described below with reference to examples and comparative reference examples. Example 1 Production of Hexahydropyridazine A four-diameter flask equipped with a reflux condenser, a stirrer, and a thermometer was prepared.
176 g of diethyl hydrazine dicarboxylate (1.
0 mol), 129.5 g of 1,4-dichlorobutane (1.
02 mol), 1 l of 1,3-dimethylimidazolidinone and 112.4 g (2.0 mol) of potassium hydroxide,
The mixture was gradually heated to 50 ° C to 60 ° C, and reacted for 3 hours in this temperature range. After the reaction, the reaction solution was cooled and filtered, and 224.4 g (4.0 mol) of potassium hydroxide and 72 g (4.0 mol) of water were added to the obtained filtrate, and the temperature was raised to 100 ° C to 110 ° C. After aging for 4 hours in the same temperature range, cooling and filtration to remove inorganic salts, the filtrate was rectified to obtain 53 g of hexahydropyridazine having a boiling point of 38 ° C./8 mmHg. The yield was 61.
6%. Example 2 Preparation of hexahydropyridazine Instead of 1 l of 1,3-dimethylimidazolidinone, N,
Except for using 1 l of N-dimethylpropylene urea,
It carried out similarly to (Example 1). As a result, 44.5 g of hexahydropyridazine was obtained. The yield was 51.7%. Comparative Reference Example 1 Decarboxylation reaction using isolated diethyl hexahydropyridazine-1,2-dicarboxylate. 50 ml of 3-dimethylimidazolidinone,
Diethyl hexahydropyridazine-1,2-dicarboxylate [produced, isolated and purified according to the method of (Example 1)] 5.05 g (0.025 mol), potassium hydroxide 5.61 g ( 0.1 mol), 0.9 g of water
(0.05 mol), and the mixture was stirred for 1.5 hours in a temperature range of 100 to 110 ° C., and the reaction mixture was analyzed. As a result, hexahydropyridazine, which was the target substance, was not detected. In this analysis, the peak of diethyl hexahydropyridazine-1,2-dicarboxylate added as a raw material had disappeared.

Claims (1)

(57) [Claims] [Claim 1] In the presence of an aprotic polar solvent, R ¹ OOC-NH-NH-COOR ² (wherein R ¹ and R ² are each A hydrazine dicarboxy derivative represented by the formula: X ¹ -CH ₂ CH ₂ CH ₂ CH ₂ -X ² (in which the alkyl group or the aryl group which may have a substituent may be independently represented); Wherein X ¹ and X ² each independently represent a halogen atom.)
Is reacted with a dihalogenobutane represented by the following formula in the presence of an alkali metal hydroxide to obtain a compound represented by the general formula: (Wherein R ¹ and R ² have the same meanings as described above) represented by the formula ( ¹ ), which is further isolated without isolation of an alkali metal hydroxide and A process for producing hexahydropyridazine, comprising decarboxylation in the presence of a hydrogen-donating compound.