JP2000095748A - New intermediate for producing tetrahydrofuranyl derivative having insecticidial activity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new compound not containing a sulfur atom and useful as a new intermediate for producing tetrahydrofuranyl derivatives having insecticidal activities instead of isothiourea derivatives which by-produce malodor- releasing mercaptan compounds. SOLUTION: A compound of formula I (X1-X7 are each H or a 1-4C alkyl; R1 is H, a 1-4C alkyl or benzyl; R2 is a 1-4C alkyl or benzyl; R3 and R4 are each H, a 1-4C alkyl or benzyl). For example, o-methyl-N-(tetrahydrofuran-3- ylmethyl)-N'-nitroisourea of formula II. The compound of formula I is obtained by reacting an O-substituted-N-nitrosoisourea compound of formula III with an amine compound of formula IV preferably in an amount of 0.5-2 equivalents per equivalent of the compound of formula III in a solvent such as water, an alcohol, an aprotic polar solvent, an ether compound or a ketone compound at pH 6-8 preferably at -20 to 200 deg.C for 0.01-50 hr.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel intermediate for producing a tetrahydrofuranyl derivative having insecticidal activity.

[0002]

2. Description of the Related Art A method for producing a tetrahydrofuranyl derivative having insecticidal activity is described in, for example, Japanese Patent Publication No. 276.
Some of them have been disclosed to date, as represented by 6848 and the like. However, isothiourea derivatives, which are widely used as intermediates for their production, contain a sulfur atom in their molecules and produce by-products mercaptans that emit a bad smell by exchange reaction with amines. In some cases, it was not always the most suitable production intermediate.

[0003]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a novel intermediate for producing a tetrahydrofuranyl derivative having insecticidal activity, in place of an isothiourea derivative which is a by-product of mercaptans which give offfensive odor. And

[0004]

The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, as a production intermediate of a tetrahydrofuranyl derivative, a mercaptan which does not contain a sulfur atom in its molecule and therefore emits an odor. N which does not produce by-products
-A nitroisourea derivative was found, and the present invention was completed.

That is, the present invention is as follows.

The general formula (1)

[0007]

Embedded image [Wherein X ₁ , X ₂ , X ₃ , X ₄ , X ₅ , X ₆ and X ₇ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₁ represents a hydrogen atom, a carbon atom R ₂ represents an alkyl group or a benzyl group having 1 to 4 carbon atoms; R ₃ and R ₄ each independently represent a hydrogen atom; an alkyl group having 1 to 4 carbon atoms; Represents a benzyl group or a benzyl group. ] The N-nitroisourea derivative represented by these.

[0008]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.
In the N-nitroisourea derivative represented by the general formula (1) and the method for producing the same, specific examples of the alkyl group having 1 to 4 carbon atoms include methyl, ethyl, propyl, i
-Represents a propyl group, a butyl group, an i-butyl group, a t-butyl group or the like. The N-nitroisourea derivative represented by the general formula (1) is a novel compound, and can be produced by the method shown in Reaction formula (1) (Chem. 3) (Reference: JP-A-10-120666).

[0009]

Embedded image Wherein X ₁ , X ₂ , X ₃ , X ₄ , X ₅ , X ₆ , X ₇ , R ₁ , R
₂ , R ₃ and R ₄ have the same meanings as in formula (1) (formula 2). In the reaction formula (1), the O-substituted-N-nitroisourea represented by the general formula (3) is reacted with the amine represented by the general formula (2) or a salt thereof in a solvent at a pH of 6 to 8. The N-nitroisourea derivative represented by the general formula (1) can be produced by performing the reaction as described above.

In the reaction formula (1), the acid forming a salt with the amine represented by the general formula (2) includes hydrochloric acid, sulfuric acid,
Examples thereof include mineral acids such as phosphoric acid, sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid, and carboxylic acids such as formic acid, acetic acid and propionic acid.

Solvents used in the reaction represented by the reaction formula (1) include water, alcohols such as methanol and ethanol, N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO) · 1,3- Dimethyl-
Examples include aprotic polar solvents such as 2-imidazolidinone (DMI), ethers such as tetrahydrofuran (THF) and 1,4-dioxane, nitriles such as acetonitrile and propionitrile, and ketones such as acetone. it can.

PH in the reaction represented by reaction formula (1)
Is adjusted by combining acids represented by mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid with bases represented by alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, and sodium borate -General buffer solution such as hydrochloric acid or Tris-
A buffer represented by a special buffer such as hydrochloric acid or triethanolamine-hydrochloric acid can be used.

In the reaction formula (1), the equivalents of the amines represented by the general formula (2) and the salts thereof are 0.1 to 0 with respect to the O-substituted-N-nitroisoureas represented by the general formula (3). 5
~ 2 equivalents are preferred, and more preferably 0.9-1.1 equivalents.

The reaction temperature and reaction time of the reaction represented by the reaction formula (1) can be varied over a wide range. Generally, the reaction temperature is preferably −20 to 200 ° C., more preferably 0 to 100 ° C., and the reaction time is preferably 0.01 to 50 hours, more preferably 0.1 to 15 hours.

In the reaction formula (1), the amines represented by the general formula (2) can be produced by the method described in Japanese Patent Publication No. 2766848 or the like. Further, the O-substituted-N-nitroisoureas represented by the general formula (3) include, for example, when R ₂ is a methyl group, as shown in JP-A-10-120666, etc. It can be manufactured by chemical conversion.

Using the N-nitroisourea derivative represented by the general formula (1) obtained by the reaction formula (1), the reaction formula (2)
As shown in Chemical formula 4, a tetrahydrofuranyl derivative having insecticidal activity can be produced.

[0017]

Embedded image Wherein X ₁ , X ₂ , X ₃ , X ₄ , X ₅ , X ₆ , X ₇ , R ₁ , R
₂ and R ₃ R ₄ have the same meaning as in the general formula (1) (Formula 2),
R ₅ and R ₆ are independently hydrogen, carbon 1-4
Represents an alkyl group and a benzyl group]

Next, the present invention will be described specifically with reference to Examples and Reference Examples, but the present invention is not limited to the following description.

Example 1 Preparation of O-methyl-N- (tetrahydrofuran-3-ylmethyl) -N'-nitroisourea (Compound No. 1)

[0020]

Embedded image (Tetrahydro-3-furanyl) methylamine 12.5
4 g (0.124 mol) was suspended in 50.0 g of distilled water while stirring, and 12.54 g (0.124 mol) of 35% hydrochloric acid was added under ice cooling.
l) was slowly added dropwise. 14.49 g of salt (0.24
8 mol), O-methyl-N-nitroisourea 14.7
6 g (0.124 mol) and 50.1 g (0.005 mol) of a 0.1 N aqueous sodium hydroxide solution were sequentially added to adjust the pH of the reaction solution to 7.01. The reaction system was stirred at room temperature for 18 hours while controlling the pH (pH 7.0 to 7.2) of the reaction system with a 1.0 N aqueous sodium hydroxide solution using an automatic pH controller. After completion of the reaction, the mixture was extracted three times with 100 g of dichloromethane and dried over anhydrous sodium sulfate. The crude product obtained by evaporating the solvent under reduced pressure was recrystallized from a mixed solvent of n-hexane: ethyl acetate = 1: 1 (v / v) to obtain 21.41 g of the title compound (0.105 mol).
1) was obtained as white crystals (yield 85%). Melting point 62.4-63.3 ° C ¹ H-NMR (CDCl ₃ , 270 MHz) δ: 1.59-1.68 (1H, m), 2.08-2.16 (1
H, m), 2.50-2.60 (1H, m), 3.33-3.47 (1H, m), 3.55-3.60 (1H, m
m), 3.73-3.86 (2H, complex-m), 3.90-3.96 (1H, m), 3.98 (3
H, s), 9.2 (1H, br) .IR ν ^KBr _max 3274,2982,2883,1603cm ^-1

Example 2 Preparation of O-ethyl-N- (tetrahydrofuran-3-ylmethyl) -N'-nitroisourea (Compound No. 13)

[0022]

Embedded image (Tetrahydro-3-furanyl) methylamine 25.0
8 g (0.248 mol) was suspended in 150.0 g of a tris (hydroxymethyl) aminomethane-hydrochloric acid buffer aqueous solution (Tris-hydrochloric acid buffer solution, 1.0 M, pH = 7.5) with stirring, and O-ethyl- N-nitroisourea 33.0
0 g (0.248 mol) was added and the mixture was stirred at room temperature for 20 hours. After completion of the reaction, the mixture was extracted three times with 150 g of dichloromethane and dried over anhydrous sodium sulfate. The crude product obtained by evaporating the solvent under reduced pressure was subjected to silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 2:
1 (v / v)) to give 36.62 g of the title compound.
(0.169 mol) was obtained as a pale yellow oil (yield 68%). ¹ H-NMR (CDCl ₃ , 270 MHz) δ: 1.36 (3H, t, J = 7.2 Hz), 1.60-1.6
8 (1H, m), 2.08-2.16 (1H, m), 2.50-2.60 (1H, m), 3.29-3.44
(1H, m), 3.55-3.60 (1H, m), 3.73-3.86 (2H, complex-m), 3.9
0-3.96 (1H, m), 3.88 (3H, q, J = 7.2Hz), 9.2 (1H, br) .IR ν ^film _max 3276,2990,2888,1607cm ^-1

Example 3 Synthesis of O-benzyl-N- (tetrahydrofuran-3-ylmethyl) -N'-nitroisourea (Compound No. 20)

[0024]

Embedded image (Tetrahydro-3-furanyl) methylamine 8.36
g (0.083 mol) in tris (hydroxymethyl)
The suspension was stirred and suspended in 50.0 g of an aminomethane-hydrochloric acid buffer aqueous solution (Tris-hydrochloric acid buffer solution, 1.0 M, pH = 7.5), and O-benzyl-N-nitroisourea 16.1 was added under ice cooling.
3 g (0.248 mol) was added, and the mixture was stirred at room temperature for 15 hours. After the completion of the reaction, the mixture was extracted three times with 50 g of dichloromethane and dried over anhydrous sodium sulfate. The crude product obtained by evaporating the solvent under reduced pressure was subjected to silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 3: 1).
(V / v)) to give 16.62 g of the title compound.
(0.060 mol) as a pale yellow oil (yield 72%). ¹ H-NMR (CDCl ₃ , 270 MHz) δ: 1.59-1.67 (1H,
m), 2.07-2.16 (1H, m), 2.50-2.60 (1H, m), 3.33-3.47 (1H,
m), 3.57-3.62 (1H, m), 3.73-3.86 (2H, complex-m), 3.90-3.
96 (1H, m), 4.50 (1H, AB, J = 11.7Hz), 4.65 (1H, AB, J = 11.7H
z), 7.03-7.52 (5H, m), 9.2 (1H, br) .IR ν ^film _max 3272,2988,2885,1604cm ^-1

Example 4 O-methyl-N-methyl-N-
Production of (tetrahydrofuran-3-ylmethyl) -N'-nitroisourea (Compound No. 7)

[0026]

Embedded image 5.00 g (0.043 mol) of N-methyl (tetrahydro-3-furanyl) methylamine was added to methanol 15.
The solution was stirred and dissolved in 0 g, and 15.83 g (0.043 mol) of a 10% hydrochloric acid-methanol solution was slowly added dropwise with ice cooling. 5.1 g (0.087 mol) of common salt, O-methyl-
5.17 g (0.043 mol) of N-nitroisourea,
17.4 g of 0.1N aqueous sodium hydroxide solution (0.0
02 mol) was added successively to adjust the pH of the reaction solution to 7.10. Using an automatic pH controller, control the pH of the reaction system with 1.0N aqueous sodium hydroxide solution (pH
The mixture was stirred at room temperature for 18 hours while performing (7.0 to 7.2). After completion of the reaction, methaneol was distilled off under reduced pressure, the residue was dissolved in 100 g of dichloromethane, washed three times with 30 g of water, and dried over anhydrous sodium sulfate. The crude product obtained by evaporating the solvent under reduced pressure was subjected to silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 4: 1).
(V / v)), and 7.26 g (0.2%) of the title compound was obtained.
033 mol) as a pale yellow oil (yield 77).
%). ¹ H-NMR (CDCl ₃ , 270 MHz) δ: 1.58-1.68 (1H, m), 2.08-2.16 (1
H, m), 2.50-2.60 (1H, m), 3.31-3.46 (1H, m), 3.57-3.62 (1H, m
m), 3.70-3.86 (5H, complex-m), 3.90-3.96 (1H, m), 3.98 (3
H, s) .IR ν ^film _max 2981,2880,1609cm ^-1

Example 5 O-methyl-N-ethyl-N-
Production of (tetrahydrofuran-3-ylmethyl) -N'-nitroisourea (Compound No. 25)

[0028]

Embedded image 4.00 g (0.031 mol) of ethyl (tetrahydro-3-furanyl) methylamine was added to 40.0 g of a tris (hydroxymethyl) aminomethane-hydrochloric acid buffer aqueous solution (Tris-hydrochloric acid buffer solution, 1.0 M, pH = 7.5). Under ice-cooling and O-methyl-N-nitroisourea 3.6
9 g (0.031 mol) was added, and the mixture was stirred at room temperature for 17 hours. After completion of the reaction, the mixture was extracted three times with 40 g of ethyl acetate,
Dry over anhydrous sodium sulfate. The crude product obtained by evaporating the solvent under reduced pressure was subjected to silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 5: 1 (v
/ V)) and purified with the title compound (4.08 g, 0.01
8 mol) as a pale yellow oil (yield 57).
%). _{^{1 H-NMR (CDCl 3,}} 270MHz) δ: 1.23 (3H, t, J = 7.2Hz), 1.58-1.6
8 (1H, m), 2.08-2.16 (1H, m), 2.50-2.60 (1H, m), 3.31-3.46
(1H, m), 3.57-3.62 (1H, m), 3.70-3.86 (5H, complex-m), 3.9
0-3.96 (1H, m), 4.00 (3H, s) .IR ν ^film _max 2988,2885,1604cm ^-1

The N-nitroisourea derivatives prepared by the same procedures as in Examples 1 to 5 are shown in Table 1 (Table 1).

[0030]

[Table 1] In the table, H represents a hydrogen atom, Me represents a methyl group, Et represents an ethyl group, nPr represents a normal propyl group, isoPr represents an isopropyl group, nBu represents a normal butyl group, and Bn represents a benzyl group.

[0031]

[Table 2] In the table, H represents a hydrogen atom, Me represents a methyl group, Et represents an ethyl group, nPr represents a normal propyl group, isoPr represents an isopropyl group, nBu represents a normal butyl group, and Bn represents a benzyl group.

Reference Example 1 Preparation of 1-{(tetrahydro-3-furanyl) methyl} -2-nitro-3-methylguanidine

[0033]

Embedded image O-methyl-N- (tetrahydrofuran-3-ylmethyl) -N'-nitroisourea 10.00 g (49.2 m
mol) was suspended and stirred in 50.0 g of distilled water, and stirred under ice-cooling.
7.61 g (98.0 mmol) of a 25% aqueous methylamine solution
Was slowly added dropwise, followed by stirring at room temperature for 3 hours. After adjusting the pH to 6.5 with dilute hydrochloric acid, 30.0 g of dichloromethane was added to the mixture.
Extracted times. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained crude product was recrystallized from ethyl acetate: methanol = 50: 1 (v / v) to give the title compound 9.
06 g (44.8 mmol) were obtained as white crystals (yield 91%). ¹ H-NMR (CDCl ₃ , 270 MHz) δ: 1.62-1.74 (1 H, m), 2.09-2.22 (1
H, m), 2.59-2.79 (1H, m), 2.96 (3H, d, J = 5.1Hz), 3.35 (2H, t,
J = 5.1Hz), 3.66-3.80 (3H, m), 3.92-4.08 (1H, m), 6.04 (1H, b
r), 9.35 (1H, br) .IR ν ^KBr _max 3339,3280,1618,1316,1231,1169cm ^-1 mp.99.5-100.7 ℃

Reference Example 2 1-{(tetrahydro-3-furanyl) methyl} -2-nitro-3-n-butyl-3-
Production of methylguanidine

[0035]

Embedded image 7.50 g of O-ethyl-N- (tetrahydrofuran-3-ylmethyl) -N'-nitroisourea (34.5 mm
ol) in 30.0 g of tetrahydrofuran and stirred,
6.10 g of N-methylbutylamine (70.0 m
mol) was slowly added dropwise. 1 hour at room temperature, 40 ° C
After stirring for 1 hour, the mixture was concentrated under reduced pressure. Distilled water 5 for residue
0.0 g and 50.0 g of dichloromethane were added, and the mixture was adjusted to pH 6.5 with dilute hydrochloric acid with stirring to carry out liquid separation. The aqueous layer was re-extracted with 50.0 g of dichloromethane, and the combined organic layers were dried over anhydrous sodium sulfate. The crude product obtained by evaporating the solvent under reduced pressure was subjected to silica gel column chromatography (developing solvent: n-hexane: ethyl acetate = 2: 1 (v /
v)) and 7.76 g (30.0 g) of the title compound
mmol) as a pale yellow oil (yield 87).
%). _{^{1 H-NMR (CDCl 3,}} 270MHz) δ: 0.95 (3H, t, J = 7.3Hz), 1.22-1.4
2 (2H, m), 1.58-1.77 (3H, m), 2.07-2.18 (1H, m), 2.50-2.62
(1H, m), 3.05 (3H, s), 3.29-3.46 (4H, m), 3.65-3.77 (3H, m),
3.94 (1H, dt, J = 5.1,8.1Hz), 6.51 (1H, br) .IR ν ^film _max 3285,1626,1307cm ^-1

Reference Example 3 Production of 1-{(tetrahydro-3-furanyl) methyl} -2-nitro-3,3-dimethylguanidine

[0037]

Embedded image O-benzyl-N- (tetrahydrofuran-3-ylmethyl) -N'-nitroisourea 5.00 g (17.9 m
mol) was dissolved in 20.0 g of methanol and stirred.
4.04 g (35.8 mmol) of dimethylamine aqueous solution
Was added and stirred at room temperature for 5 hours. After concentration under reduced pressure, 25.0 g of toluene was added to the residue, and azeotropic dehydration under normal pressure was performed.
The crystals precipitated by cooling the reaction solution were collected by filtration to obtain 2.90 g (13.4 mmol) of the title compound as white crystals (yield: 75%). ¹ H-NMR (CDCl ₃ , 270 MHz) δ: 1.55-1.78 (1H, m), 2.06-2.23 (1
H, m), 2.48-2.65 (1H, m), 3.10 (6H, s), 3.29-3.50 (2H, m), 3.
58-3.82 (3H, m), 3.85-4.00 (1H, m), 6.77 (1H, br) .IR ν ^KBr _max 3274,2940,1637,1387,1075cm ^-1 mp.127.1-128.8 ℃

Reference Example 4 1,3,3-trimethyl-1-
Production of {(tetrahydro-3-furanyl) methyl} -2-nitroguanidine

[0039]

Embedded image O-methyl-N-methyl-N- (tetrahydrofuran-
3-ylmethyl) -N'-nitroisourea 6.00 g
(27.6 mmol) was dissolved in 50.0 g of ethyl acetate and stirred, and 15.56 g of a 40% aqueous dimethylamine solution (13.
8.0 mmol) and heated under reflux for 2 hours. After allowing to cool, the layers were separated, and the aqueous layer was re-extracted with 25.0 g of ethyl acetate. The organic layers were combined, washed with diluted hydrochloric acid and water, and dried over anhydrous sodium sulfate. The crude product obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (developing solvent: n-hexane: ethyl acetate = 3: 1 (v / v)), and 4.32 g of the title compound (18. 8 mmol) as a pale yellow oil (68% yield). ¹ H-NMR (CDCl ₃ , 270 MHz) δ: 1.50-1.62 (1H, m), 1.95-2.10 (1
H, m), 2.56-2.69 (1H, m), 2.96 (6H, s), 2.99 (3H, s), 3.26-3.
40 (2H, m), 3.47 (1H, dd, J = 5.1,8.8Hz), 3.70-4.02 (3H, m) .IR ν ^film _max 1439,1244cm ^-1

Reference Example 5 Production of 1-ethyl-1-{(tetrahydro-3-furanyl) methyl} -2-nitroguanidine

[0041]

Embedded image O-methyl-N-ethyl-N- (tetrahydrofuran-
7.00 g of 3-ylmethyl) -N'-nitroisourea
(30.0 mmol) in 50.0 g of 1,4-dioxane
And stirred with 28% aqueous ammonia 9.21 g (15%
1.5 mmol) and stirred at 50 ° C. for 1 hour.
After concentration under reduced pressure, the residue was subjected to silica gel column chromatography (developing solvent: ethyl acetate: methanol = 5: 1 (v /
v)) to give 5.43 g (25.1 g) of the title compound.
mmol) as a pale yellow oil (yield 83).
%). _{^{1 H-NMR (CDCl 3,}} 270MHz) δ: 1.20 (3H, t, J = 7.3Hz), 1.55-1.7
1 (1H, m), 1.97-2.08 (1H, m), 2.58-2.70 (1H, m), 3.32 (1H, d
d, J = 8.1,14.7Hz), 3.42-3.50 (3H, s), 3.56 (1H, dd, J = 5.1,
8.1Hz), 3.71-3.83 (2H, m), 3.93 (1H, dt, J = 5.1,8.1Hz), 8.2
4 (2H, br) .IR ν ^film _max 3385,1616,1575,1263cm ^-1

[0042]

By using an N-nitroisourea derivative represented by the general formula (1) as a novel production intermediate,
It is possible to produce a tetrahydrofuranyl derivative having insecticidal activity without by-producing malodorous mercaptans. Further, the use of the intermediate of the present invention makes it possible to produce a tetrahydrofuranyl derivative more easily than in the conventional method.

Claims (3)

[Claims] 1. A compound represented by the general formula (1): [Wherein X ₁ , X ₂ , X ₃ , X ₄ , X ₅ , X ₆ and X ₇ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₁ represents a hydrogen atom, a carbon atom R ₂ represents an alkyl group or a benzyl group having 1 to 4 carbon atoms; R ₃ and R ₄ each independently represent a hydrogen atom; an alkyl group having 1 to 4 carbon atoms; Represents a benzyl group or a benzyl group. ] The N-nitroisourea derivative represented by these. 2. R₁ Is a hydrogen atom or an atom having 1 to 4 carbon atoms.
Represents a alkyl group; _Two Represents an alkyl group having 1 to 4 carbon atoms.
Then R_Three And R_Four Are each independently a hydrogen atom or charcoal
The N-nitro according to claim 1, which represents an alkyl group having a prime number of 1 to 4.
Loisoureas derivatives. 3. R ₁ represents a hydrogen atom, and R ₂ has 1 carbon atom.
The N-nitroisourea derivative according to claim 1, wherein each of R ₃ and R ₄ represents a hydrogen atom.