JPS6228782B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel nitro compound and a method for producing the same. More specifically, the present invention relates to a novel nitro compound represented by the following general formula (), which is a useful intermediate for agricultural chemicals and medicines, and a method for producing the same. [In the formula, R ₁ is

[Formula] (where R ₄ represents a hydrogen atom, a lower alkyl group or a halogen atom), and R ₂ represents a lower alkyl group, a lower alkenyl group or a lower alkynyl group. _R3
represents a hydrogen atom or a lower alkyl group. ] Allethrin is known as a useful pesticide.
Invented by MS Schechter in 1949, it is widely used throughout the world due to its excellent insecticidal activity and low toxicity, and various studies have been conducted on its synthesis methods. Among these, various proposals have been made regarding methods for synthesizing the alcohol component of allethrin, some of which have been incorporated into actual production. However, these methods are not necessarily industrially satisfactory in terms of yield, operation, environmental problems, etc. For example, the method for synthesizing allethrone that is currently practiced industrially is a slight improvement on the method first carried out by MS Schechter et al., and consists of the following steps. However, in this method, the final step from compound (4) to allethrone (5) has a low yield, and methylglyoxal (used in the synthesis of compound (4) from compound (3) ) 6) is not easy to synthesize and is expensive, so it is not always a satisfactory method industrially. In addition, as a method for synthesizing arethrolone using the Michael reaction, there is a method by RH Schlessinger et al. This method uses methylthioacetone (7) and ketene thioacetal monooxide (8) as raw materials and consists of the following steps. . However, the method of Schlessinger et al. also has the following major problems as an industrial method. After the Michael reaction, allyl iodide, which is highly reactive and expensive, is used to introduce an allyl group into the α-position of the sterically crowded ketone. (Process of compound (9) → (10) ) In the reaction from compound (11) to arethrolone (5) ,
For industrial use, potassium t-butoxy is used, which is highly dangerous and difficult to handle. Therefore, this method is not necessarily satisfactory as an industrial manufacturing method. Against this background, the present inventors have conducted intensive studies on the production method of cyclopentenolones, which are used as intermediates for insecticidal compounds, and have discovered a novel and extremely advantageous method for producing the same. Based on this, the present invention was completed by conducting various studies on the important intermediate and its manufacturing method. That is, the present invention provides a novel nitro compound represented by the general formula () and a method for producing the same, which is represented by the general formula (). (In the formula, R ₁ and R ₂ have the same meanings as above.) In the presence of a base, a compound represented by the general formula () R ₃ −CH=CH−NO ₂ () (in the formula, R ₃ is The present invention provides a method for producing a novel nitro compound represented by the general formula (), which is characterized by reacting a nitroolefin represented by the formula () with the same meaning as above. The compound of the present invention represented by the general formula () can be easily and efficiently prepared by the method shown below, for example, by the general formula (), which is a useful intermediate for agricultural chemicals. (In the formula, R ₂ and R ₃ have the same meanings as above.) It is an extremely useful intermediate that can lead to the cyclopentenolones shown below. That is, after reacting the compound of the present invention represented by the general formula () with a base, an acid is reacted in an alcohol represented by the general formula () R ₅ OH () (wherein R ₅ represents a lower alkyl group). This is then treated with acid in the presence of water to give the general formula () (In the formula, R ₁ , R ₂ and R ₃ have the same meanings as above.) By obtaining an aldehyde compound represented by the formula and further treating the aldehyde compound with a base, a cyclopentenolone represented by the general formula () is obtained. or in the above method, the general formula ()
Without isolating the aldehyde compound represented by, the compound of the present invention represented by the general formula () is reacted with a base, and then reacted with an acid in the alcohol represented by the general formula (), and then, where A method for obtaining a cyclopentenolone represented by the general formula () by subjecting the obtained compound to an acid treatment and a base treatment, or a method in which the compound of the present invention represented by the general formula () is reacted with a base, and then water The aldehyde compound represented by the general formula () is directly obtained by reacting with an acid in the presence of cyclopentenolone, and then the aldehyde compound is treated with a base to lead to a cyclopentenolone represented by the general formula (). Furthermore, the compound of the present invention represented by the general formula () can also be an intermediate for prostaglandins, which are known as pharmaceuticals, in addition to the above-mentioned cyclopentenolones, and its role as an intermediate is extremely important. is important. In addition, the compound represented by the general formula (), which is the starting material of the present invention, is a known compound represented by the following general formula (). (In the formula, R ₁ has the same meaning as above.) Nitroolefin, which is easily obtained by alkylating and represented by the general formula (), can be obtained by combining an aldehyde represented by the following general formula () and nitromethane. It can be easily obtained by reacting and then dehydrating. R ₃ CHO () (In the formula, R ₃ has the same meaning as above.) In the compound of the present invention represented by the general formula (), specific examples of R ₂ include a methyl group, an ethyl group,
Alkyl groups such as propyl, allyl, alkenyl groups such as 2-butenyl, 2-propargyl, 2
Examples of R 3 include alkynyl groups such as -butyn-1-yl, and specific examples of R ₃ include hydrogen atoms, methyl groups,
Examples include alkyl groups such as ethyl group and propyl group. Specific examples of R ₄ include a hydrogen atom, a methyl group, a chlorine atom, and a bromine atom.
Further, in the general formula (), specific examples of R ₅ include a methyl group, an ethyl group, and a propyl group. Examples of bases used in the production of the compound () of the present invention include alcoholates such as sodium methylate, sodium ethylate, potassium t-butoxide, sodium, sodium hydride, potassium hydride, dimsyl sodium, sodium fluoride, and sodium fluoride. Potassium chloride, etc. can be given. In addition, as a solvent, methanol,
Lower alcohols such as ethanol and t-butanol, tetrahydrofuran, dioxane, dimethylformamide, dimethyl sulfoxide, ether, benzene, toluene, etc. can be used. The reaction temperature is not particularly limited, but -
Range of boiling point of solvent from 50℃, preferably -30℃~
It can be carried out at a temperature of 40°C. Using the compound of the present invention represented by the general formula (),
In the method described above to lead to cyclopentenolones, substituents are added before the Michael reaction.
Since R ₂ can be introduced, it has the advantage that the substituent R ₂ can be introduced extremely easily. Furthermore, in the process of treating the compound represented by the general formula () with a base to synthesize the final target cyclopentenolone represented by the general formula (), a general-purpose base such as sodium ethylate can be used with good yield. The desired product can be obtained, and it is advantageous as an industrial production method compared to the method of RH Schlessinger et al., and it is not carried out industrially today, such as the high yield of the ring-closing reaction step and the fact that methylglyoxal is not used. It has many advantages compared to the method of MSSchechter et al. As described above, the present invention relates to a novel intermediate extremely useful in the production of agricultural chemicals and medicines, and a method for producing the same, and is useful for industrial production of these products by reducing the number of steps and facilitating operation. Its contribution, such as good yield, is very large. EXAMPLES Next, in order to make the present invention more clear, the present invention will be explained in detail using the following examples, but it goes without saying that the present invention is not limited to these examples. Example 1 0.58 g of sodium hydride was added to 150 ml of dimethylformamide, and 3-phenylthio-5 was prepared at room temperature.
- A solution of 5.0 g of hexen-2-one dissolved in 10 ml of dimethylformamide is added dropwise. After stirring at room temperature for 1 hour, the reaction solution was cooled to -5°C, and a solution of 2.0 g of 1-nitro-1-propene dissolved in 5 ml of dimethylformamide was added dropwise over 10 minutes while stirring. After stirring at -5°C for 1 hour, 3 ml of acetic acid was added dropwise while maintaining the temperature at -5°C. It was poured into 100 ml of water and extracted with ether. The ether layer was washed successively with water and brine, and then dried over magnesium sulfate. After distilling off the ether, it was purified by silica gel column chromatography to obtain 1-nitro-2
-Methyl-3-acetyl-3-phenylthio-5
- 5.7 g of hexene were obtained as a pale yellow oil. Yield 81.2% Refractive index n ¹⁷ . ⁶ _D 1.5572 NMR data ( _CCl4 , internal standard TMS) δ1.04(d), 1.26(d)(3H) δ2.16(s), 2.30(s)(3H) δ2.3~2.5(2H, m ) δ2.8~3.0 (1H, m) δ4.1~4.5 (1H, m) δ5~6 (3H, m) δ7.3 (5H) Example 2 Prepare 1.176 g of sodium hydride in 150 ml of dimethylformamide and bring to room temperature. 3-phenylthio-5
- A solution prepared by dissolving 10.0 g of hexin-2-one in 15 ml of dimethylformamide is added dropwise. After stirring at room temperature for 1 hour, the reaction solution was cooled to -5°C, and a solution of 4.26 g of 1-nitro-1-propene dissolved in 10 ml of dimethylformamide was added dropwise over 15 minutes while stirring. After stirring at -5°C for 1 hour, 6 ml of acetic acid was added dropwise while maintaining the temperature at -5°C. The ether layer was poured into 100 ml of water and extracted with ether. The ether layer was washed with water and brine in that order. After drying over magnesium sulfate, the ether was distilled off and purified by silica gel column chromatography. 10.86 g of 3-acetyl-3-phenylthio-5-hexyne was obtained as a pale yellow oil. Yield 76.1% Refractive index ⁿ¹⁹ . ⁵ _D 1.5660 NMR data (CCl ₄ , internal standard TMS) δ1.11(d), 1.32(d) (3H) δ2.18(t) (1H) δ2.41(s) (3H) δ4.3~5.3 (m) (2H) δ7.21 (5H) Example 3 In the same manner as in Example 2, 3-phenylthio-
6-methyl- instead of 5-hexyn-2-one
3-phenylthio-5-hepten-2-one 4.68
g, and the amount of sodium hydride used is
0.50g, the amount of 1-nitro-1-propene used is
By the same operation as in Example 2 except that the amount was changed to 1.74 g, 4.62 g of 1-nitro-2,6-dimethyl-3-acetyl-3-phenylthio-5-heptene was obtained as a pale yellow oil. Yield 72.0% NMR data (CCl ₄ , internal standard TMS) δ1.15(d), 1.40(d)(3H) δ1.70(m)(6H) δ2.30(s), 2.35(s)(3H ) δ2.55~2.65(d)(2H) δ2.70~3.00(m)(1H) δ4.20~4.40(m)(2H) δ7.20~7.40(m)(5H) Reference example 1 Sodium 0.086 Dissolve g in 5 ml of methanol and stir at -5℃ to dissolve 1-nitro-2-
Methyl-3-phenylthio-3-acetyl-5-
A solution prepared by dissolving 1.0 g of hexene in 3 ml of methanol was added dropwise. This liquid was added dropwise over 1 hour to a sulfuric acid-methanol mixture (8 ml of concentrated sulfuric acid, 30 ml of methanol) cooled to -5°C while stirring vigorously. After dropping, pour the reaction solution into 150ml of dichloromethane, then add to ice water.
It was washed sequentially with 100 ml of 2% caustic soda water and saline. After drying the dichloromethane layer with magnesium sulfate, the solvent was distilled off to obtain 0.98 g of pale yellow oil. This oil is almost pure from NMR, 1.1
-dimethoxy-2-methyl-3-phenylthio-
It was 3-acetyl-5-hexene. Refractive index n ¹⁷ . ⁷ _D 1.5615 Reference example 2 0.98 g of 1,1-dimethoxy-2-methyl-3-phenylthio-8-acetyl-5-hexene
The mixture was poured into 10 ml of 1N hydrochloric acid and stirred vigorously at 55°C for 1.5 hours. Add 20 ml of ether to the reaction solution for extraction, wash the ether layer with deuterated water, water, and brine in sequence, and then dry over anhydrous magnesium sulfate. After distilling off the ether, purification was performed using silica gel column chromatography to obtain 0.60 g of 2-
Methyl-3-phenylthio-3-acetyl-5-
Hexene-1-al was obtained as a pale yellow oil. Yield 72.2% Refractive index n ¹⁷ . ⁷ _D 1.5634 NMR data (CDCl ₄ , internal standard TMS) δ1.20(d), 1.40(d) (3H) δ2.44(s, 3H) δ2.5~3.4(m, 3H) δ5~6(m , 3H) δ7.3 (s, 5H) δ9.5 (s), 9.8 (s) (1H) Reference example 3 Dissolve 0.174 g of sodium in 10 ml of methanol and stir at -5°C to dissolve 1-nitro-2-
Methyl-3-phenylthio-3-acetyl-5-
A solution of 2.0 g of hexine dissolved in 6 ml of methanol was added dropwise. This liquid was added dropwise over 30 minutes to a sulfuric acid-methanol mixture (16 ml of concentrated sulfuric acid, 60 ml of methanol) cooled to -5°C while stirring vigorously. After dropping, pour the reaction solution into 150ml of dichloromethane, then add 100ml of ice water.
ml, 2% soda carbonate, water, and saturated saline in this order. After drying the dichloromethane layer with magnesium sulfate, the solvent was distilled off to obtain 1.98 g of pale yellow oil. This oil is almost pure 1.1 from NMR.
-dimethoxy-2-methyl-3-phenylthio-
It was 3-acetyl-5-hexyne. Yield 94.3% Refractive index ⁿ¹⁹ . ⁵ _D 1.5442 Reference example 4 1.90 g of 1,1-dimethoxy-2-methyl-3-phenylthio-3-acetyl-5-hexyne
The mixture was poured into 20 ml of % hydrochloric acid water and stirred vigorously at 55°C for 1.5 hours. Add 50ml of ether to the reaction solution and extract.
The ether layer is washed successively with heavy water, water, and brine, and then dried over magnesium sulfate. After distilling off the ether, the residue was purified by silica gel column chromatography to obtain 1.54 g of 2-methyl-3-phenylthio-3-acetyl-5-hexyn-1-al as a pale yellow oil. Yield 95.4% Refractive index ⁿ²³ . ⁰ _D 1.5728 NMR data (CCl ₄ , internal standard TMS) δ1.15(d), 1.32(d) (3H) δ2.1(m) (1H) δ2.36(s), 2.41(s) (3H) δ2.52(d), 2.62(d)(2H) δ2.60-3.0(m)(1H) δ7.2(5H) δ9.50(s), 9.85(s)(1H) Reference example 5 Sodium 0.086 Dissolve g in 5 ml of methanol and stir at -5°C to dissolve 1-nitro-2-
Methyl-3-phenylthio-3-acetyl-5-
A solution prepared by dissolving 1.0 g of hexene in 3 ml of methanol was added dropwise. This liquid was added dropwise to 50 ml of a 20% sulfuric acid aqueous solution cooled to -5°C while stirring vigorously. After stirring at -5°C for 3 hours, the reaction solution was extracted with dichloromethane. Dichloromethane layer in ice water
It was washed successively with 100 ml, 2% caustic soda water, and saline. After drying the dichloromethane layer with magnesium sulfate, the solvent was distilled off. The obtained pale yellow oil was purified by silica gel chromatography,
0.54 g of 2-methyl-3-phenylthio-3-acetyl-5-hexen-1-al was obtained as a pale yellow oil. Yield 60.4% Refractive index n ¹⁹ _D 1.5642 NMR (CDCl ₄ , internal standard TMS) δ1.20(d), 1.40(d) (3H) δ2.44(s, 3H) δ2.5~3.4(m, 3H ) δ5~6 (m, 3H) δ7.3 (s, 5H) δ9.5 (s), 9.8 (s) (1H) Reference Example 6 Stir 0.044g of sodium dissolved in 8ml of absolute ethanol at room temperature. Meanwhile, a solution prepared by dissolving 0.50 g of 2-methyl-3-phenylthio-3-acetyl-5-hexen-1-al in 2 ml of absolute ethanol was added dropwise. After stirring at room temperature for 15 minutes,
After adding 5 ml of 5% hydrochloric acid, ethanol was distilled off under hydraulic pressure. After adding ether to the reaction solution for extraction, the ether layer was washed successively with water and brine, and dried over magnesium sulfate. After distilling off the ether, the residue was purified by silica gel column chromatography to obtain 0.20 g of arethrolone as a pale yellow oil. Yield 68.0% NMR (CDCl ₄ , internal standard TMS) δ2.1 (s, 3H) δ2.35(d), 2.60(d) (2H) δ2.90 (d, 2H) δ3.1 (bs, 1H) ) δ4.5-6.0 (m, 4H) Reference Example 7 Dissolve 2.50 g of 2-methyl-3-phenylthio-3-acetylhexane-1-al in 20 ml of toluene, and add 20 mg of benzyltriethylammonium chloride and 3 g of 50% caustic potassium aqueous solution. was added and stirred at room temperature under a nitrogen stream for 5 hours. The reaction solution was poured into water, saturated with sodium chloride, and then extracted twice with ether. The ether layer was washed twice with brine and then dried over magnesium sulfate. After evaporation of the solvent, silica gel column chromatography was performed to obtain the pale yellow oil 2-methyl-3-
Propyl-cyclopent-2-en-4-one-
0.73 g of 1-ol was obtained. Yield 52% NMR (CCl ₄ , internal standard TMS) δ0.93 (t, 3H) δ1.98 (s, 3H) δ2~3 (m, 4H) δ4.43 (d, 1H)

Claims (1)

[Claims] 1. General formula [In the formula, R ₁ represents the formula (herein, R ₄ represents a hydrogen atom, a lower alkyl group, or a halogen atom], and R ₂ represents a lower alkyl group, a lower alkenyl group, or a lower alkynyl group. _R3
represents a hydrogen atom or a lower alkyl group. ] A nitro compound represented by 2 General formula [In the formula, R ₁ represents the formula (herein, R ₄ represents a hydrogen atom, a lower alkyl group, or a halogen atom], and R ₂ represents a lower alkyl group, a lower alkenyl group, or a lower alkynyl group. ] The compound represented by is reacted with a nitroolefin represented by the general formula R ₃ -CH=CH-NO ₂ (wherein R ₃ represents a hydrogen atom or a lower alkyl group) in the presence of a base. Featured general formula (In the formula, R ₁ , R ₂ and R ₃ have the same meanings as above.) A method for producing a nitro compound represented by the following.