JPH033748B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing 2-(nitrophenyl)ethanols. For more details, please refer to the general formula [In the formula, the nitro group is substituted at the ortho or para position with respect to the methyl group, and R is hydrogen, a nitro group, a halogen atom, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms. , means hydroxyl group. A general formula characterized by electrolyzing nitrotoluenes represented by ] and paraformaldehyde in the presence of a quaternary ammonium salt in an aprotic polar solvent [In the formula, the nitro group is substituted at the same position as above, R has the same meaning as above, and n means an integer of 1 to 2. ] It is related with the manufacturing method of 2-(nitrophenyl) ethanol shown by this. 2-
(Nitrophenyl)ethanol is a polymer substance,
It is a compound useful as an intermediate raw material in the production of dyes, agricultural chemicals, polymer stabilizers, photosensitive materials, fragrances, and pharmaceuticals. However, little research has been conducted on its production method, and no industrially advantageous production method has been found. For example, a method in which nitrotoluene and paraformaldehyde are reacted in the presence of an alkali metal alcoholate such as sodium ethoxide or potassium t-butoxide [Chemica UcTa.
Scandinavica. Volume 21, page 718 (1976), same magazine,
Volume 21, page 1967 (1967) was proposed by B. Wesselen et al., and only a few examples of improved methods have been reported [JP-A-52-108941, JP-A-52-122330. , JP-A-52-139035, JP-A-Sho
No. 52-156825]. However, the method of B. Wesselen et al. requires the use of an alkali metal alcoholate, which is a strong base, as a catalyst, and also requires special handling for preparation and storage because it is easily decomposed by moisture in the air. Care must be taken, and it is difficult to say that this is a practical manufacturing method. On the other hand, the method proposed as an improved method is
Methods using alkali metal salts of phenols as catalysts (Japanese Patent Application Laid-open No. 52-108941), methods using caustic alkali (Japanese Patent Application Laid-Open No. 122330-1982), methods using DBU or quaternary ammonium hydroxides (Japanese Patent Application Laid-open No. 1982-122330), Showa 52
-139035), and a method using a complex formed from an alkali metal alcoholate and a crown ether (Japanese Patent Application Laid-open No. 156825/1983). However, like the method of B. Wesselen et al., these methods use expensive catalysts as bases and require special care in handling, and also require high reaction temperatures to increase the conversion rate. There are drawbacks such as. Furthermore, in general, the yield is not very good, and it is difficult to say that it is an advantageous method from the viewpoint of practical application. The present inventors have conducted intensive research on a method for economically and efficiently producing 2-(nitrophenyl)ethanol by overcoming these drawbacks of conventional production methods, and have found that 2-( The present inventors discovered that (nitrophenyl) ethanols can be easily obtained in high yields and completed the present invention. Compared to conventional methods that use chemical reagents, various efforts are made to increase the conversion rate and yield.
With a simple electrolytic reaction like the method of the present invention,
Moreover, it is surprising that 2-(nitrophenyl)ethanols can be easily obtained at a reaction temperature around room temperature. The nitrotoluenes represented by the general formula (1) used in the method of the present invention are ortho- or para-nitrotoluenes, and more specifically, o-nitrotoluene, p-nitrotoluene, 2-nitro-
m-xylene, 4-nitro-m-xylene, 2-
Nitro-p-xylene, 3-nitro-o-xylene, 4-nitro-o-xylene, 2-nitro-m
-cymene, 4-nitro-m-cymene, 2-nitro-p-cymene, 4-nitro-m-cresol, 2-nitro-m-cresol, 3-nitro-
p-Cresol, 4-chloro-o-nitrotoluene, 4-bromo-o-nitrotoluene, 5-chloro-o-nitrotoluene, 5-iodo-o-nitrotoluene, 4-fluoro-o-nitrotoluene, 6-chloro-o- Nitrotoluene, 2-chloro-p-nitrotoluene, 2-bromo-p-nitrotoluene, 2-iodo-p-nitrotoluene,
5-methoxy-o-nitrotoluene, 5-propoxy-o-nitrotoluene, 3-methoxy-p-
Examples include nitrotoluene, 3-butoxy-p-nitrotoluene, and 2,4-dinitrotoluene. The quaternary ammonium salt used in the present invention has the following general formula: [In the formula, R ¹ , R ² , R ³ , R ⁴ are the same or different unsubstituted or substituted alkyl groups, and X is

[Formula] means an anion that forms a quaternary ammonium salt that pairs with ammonium ions such as ClO ₄ , halide ion, HSO ₃ and BF ₄ to form a salt. ] is preferred.
More specifically, quaternary ammonium para-toluenesulfonic acid esters such as tetramethylammonium paratoluenesulfonate, tetraethylammonium paratoluenesulfonate, and tetrabutylammonium parasulfonate; tetramethylammonium perchlorate, tetraethylammonium perchlorate, Quaternary ammonium perchlorate salts such as tetrabutylammonium perchlorate; tetramethylammonium bromide, tetraethylammonium bromide, tetraethylammonium chloride, tetrabutylammonium bromide, n-dodecyltrimethylammonium bromide, cetyltrimethylammonium bromide, benzyltriethylammonium Bromide, tetraethylammonium iodide,
Examples include halogenated quaternary ammonium salts such as benzyltetraethylammonium iodide; quaternary ammonium salts such as tetraethylammonium tetrafluoroborate. The amount of quaternary ammonium salt used in the present invention is:
Although it varies depending on the reaction medium and the shape of the reaction tank, it is usually in the range of 0.1 to 30 times, preferably 0.3 to 10 times, relative to nitrotoluene. The amount of paraformaldehyde used is usually 0.1 to 10 times the mole of nitrotoluene, preferably 0.5 to 3.0 times the mole. Examples of the aprotic polar solvent used in the electrolytic reaction of the present invention include N,N-dimethylformamide,
Dimethyl sulfoxide, tetrahydrofuran, hexamethylphosphortriamide, dimethylacetamide, dioxane, dimethoxyethane, acetonitrile, propionitrile, etc. are used.
If necessary, a mixed solvent system with an aliphatic alcohol such as methanol, ethanol, isopropyl alcohol, and butyl alcohol can also be used. Particularly preferred is dimethylformamide or a solvent containing dimethylformamide as the main solvent. The amount of these solvents to be used is 5 to 1000 times, preferably 5 to 100 times, the weight of the nitrotoluenes. For the electrolytic reaction of the present invention, ordinary electrodes for electrolysis, that is, electrodes made of materials such as platinum, carbon, nickel, lead, copper, stainless steel, zinc, etc., and titanium electrodes surface-treated with platinum can be used. In the present invention, a single cell or a separated cell with separate cathode and anode chambers is used, and a separated cell is preferred. At this time, the diaphragm is not particularly limited, but glass filters, unglazed magnetic materials, ion exchange membranes, etc. are used. The concentration of nitrotoluenes in the cathode chamber is usually in the range of 1 to 50%, preferably 3 to 15% by weight. In addition, the reaction temperature during the electrolytic reaction is usually 0 to 100℃, preferably 15 to 100℃.
It is in the range of 40℃. Conventional methods generally require reactions to be carried out at high temperatures;
It is noteworthy that according to the present invention, the desired product can be obtained in high yield at about room temperature. As the electrolytic reaction method, constant potential electrolysis or constant current electrolysis method can be adopted. Current density is 0.1~100mA/
When carried out in the cm ² range, 2-(nitrophenyl)ethanol can be efficiently produced with a preferable yield. The amount of electricity applied is usually 0.1 to 1 F per mole of nitrotoluene, but preferably 0.2 to 0.5 F to substantially complete the reaction. As described above, the method of the present invention uses an electrolytic reaction to efficiently add one molecule or more than one molecule of formaldehyde to nitrotoluenes in a high yield without producing by-products. When applied to o-nitrotoluene, the reaction product is 2-(2-nitrophenyl)- with two molecules of 2-(2-nitrophenyl)ethanol and formaldehyde added.
It is 1,3-propanediol. Furthermore, when the method of the present invention is applied to p-nitrotoluene, the reaction product is 2-(4-nitrophenyl)ethanol and 2 molecules of formaldehyde added.
-(4-nitrophenyl)-1,3-propanediol, and 2-(4-nitrophenyl) allyl alcohol, which is thought to be produced by further dehydration, is obtained as a by-product. Furthermore, when the method of the present invention is applied to 2,4-dinitrotoluene, the reaction product is mainly 2-(2,4-dinitrophenyl)-1,3-propanediol to which two molecules of formaldehyde have been added. It is. 2-(nitrophenyl) produced
Ethanols can be easily separated and purified from the reaction mixture using known methods such as distillation and extraction. The present invention will be specifically explained below with reference to Examples. Example 1 O-nitrotoluene in the cathode chamber of the anode-cathode separation cell
304.1mg (2.23mmol), paraformaldehyde
Weigh out 139.0 mg (4.63 mmol as formaldehyde) and add 650 mg of tetraethylammonium para-toluene sulfonate as a supporting electrolyte.
(2.16mmol), N,N-dimethylformamide 6.5
Add ml. Meanwhile, in the anode chamber, 650 mg of tetraethylammonium paratoluene sulfonate and N,
Add 6.5 ml of N-dimethylformamide. Attach a stirrer, a thermometer, and a platinum electrode (size 1.5 x 1.0 cm ² ) to both the anode and cathode chambers by thoroughly soaking them in the reaction solution. Keep the reaction temperature at 18-20℃ and reduce the current density
Electrolysis was performed under the conditions of 3.3 mA/cm ² and a terminal voltage of 7.0 to 12 V, and the electrolysis was stopped when an amount of electricity of 0.25 F/mol was passed. Next, the reaction solution in the cathode chamber was poured into saturated saline, and the pH was adjusted to 4 to 5 with a 5% aqueous hydrochloric acid solution. It was extracted several times with ethyl acetate, and the extract was washed with water, dried, and concentrated. Using a silica gel column, the obtained crude product was extracted with benzene and then developed with a mixed solvent of hexane and ethyl acetate (2/1), yielding 74.3 mg of 2-(2-nitrophenyl)ethanol.
(20.0%), 2-(2-nitrophenyl)1,3-
306.2 mg (70.1%) of propanediol was obtained.
The conversion rate of this reaction was 95.0%. 2-(2-nitrophenyl)ethanol IR (neat) 3350, 2930, 2890, 1608, 1580,
1530, 1350, 1050, 861, 795, 745, 703 cm ^-1 NMR (CDCl ₃ ) δ2.47 (br s, 1H, OH) δ3.12 (t, 2H, -CH ₂ ) δ3.90 (t, 2H , _-CH2 ) δ7.25-8.0 (m, 4H, Ar-H) 2-(2-nitrophenyl)-1,3-propanediol IR (neat) 3350, 2955, 2945, 2895, 1608,
1582, 1530, 1360, 1040, 985, 858, 790,
750, 710cm ^-1 NMR (CDCl ₃ ) δ3.55 (br s, 2H, 2×OH) δ3.45~3.70 (m, 1H,

[Formula]) δ3.90 (d, J=5.0Hz, 4H, 2×−CH ₂ −) δ7.15 to 7.85 (m, 4H, Ar−H) Examples 2 to 9 Same operation as Example 1 Table 1 shows the results obtained by changing the type of cathode.

[Table] Raw material o-nitrotoluene; 300 mg (2.2 mmol),
Positive electrode; platinum electrode (1.5 x 1.0 cm ² ), supporting electrolyte;
Tetraethylammonium paratoluenesulfonate 300 x 2 mg, solvent: DMF, 6.5 x 2 ml, paraformaldehyde: 136 mg (4.5 mmol), reaction temperature: 15-30°C, current: 5 mA, quantity of electricity: 0.25 F/m Examples 9-28 Table 2 shows the results obtained by performing the same operation as in Example 1 but changing the supporting electrolyte. Table 3 also shows the results of changing the type of negative electrode and supporting electrolyte.

[Table] Raw material o-nitrotoluene; 300 mg (2.2 mmol),
Positive and negative electrodes: platinum electrode (1.5×1.0cm ² ), solvent: DMF,
6.5×2ml, paraformaldehyde; 136mg
(4.5mmol), reaction temperature: 15-25℃, current: 5mA,
Electricity: 0.25F/M In the table, Et represents ethyl, Bu represents butyl, Me represents methyl, and Ph represents phenyl.

[Table] Raw materials o-nitrotoluene; 300 mg, paraformaldehyde; 136 mg (4.5 mmol), positive electrode; platinum electrode (1.0 x 1.5 cm ² ), solvent: DMF, 6.5 ml x 2, reaction temperature: 15-25°C, current ;5mA, electricity quantity;0.25F/
M Examples 29 to 36 Table 4 shows the results obtained by performing the same operation as in Example 1 but changing the solvent.

[Table] Raw materials o-nitrotoluene; 300 mg, paraformaldehyde; 136 mg (4.5 mmol), positive and negative electrodes; platinum electrode (1.0 x 1.5 cm ² ), supporting electrolyte; Et ₄ NOTs, 1.0
~1.3 mmol [*Bu ₄ NClO ₄ (0.9 mmol) was used in the case of THF. [Reaction temperature: 15 to 25°C, current: 5 mA, quantity of electricity: 0.25 F/M In the table, Ts represents tosyl. Example 37 Using p-nitrotoluene as a raw material instead of o-nitrotoluene
When nitrotoluene was used and the other conditions were the same as in Example 1, 2-(4-nitrophenyl)ethanol, 55.5 mg (15.1%), and 2-(4-nitrophenyl)-1,3-propanediol, 227.5 mg.
(52.4%) was obtained. Furthermore, 2-(4-nitrophenyl), which is thought to be produced by dehydration of 2-(4-nitrophenyl)-1,3-propanediol,
41.3 mg (10.5%) of allyl alcohol was obtained.
The conversion rate of this reaction was 90.0%. 2-(4-nitrophenyl)ethanol IR (CHCl ₃ ) 3590, 3400, 2940, 2875,
1605, 1520, 1350, 1320, 1180, 1113, 1040,
1020, 860, 835, 692 cm ^-1 NMR (CDCl ₃ ) δ1.76 (br, s, 1H, OH) δ2.98 (t, 2H, −CH ₂ −) δ3.95 (t, 2H, −CH ₂ -) δ7, 27 ~ 8.36 (m, 4H, Ar-H) 2-(4-nitrophenyl)-1,3-propanediol IR (nujol) 3200, 1610, 1600, 1518, 1379,
1360, 1040, 1033, 1010, 973, 855, 840,
750, 720, 700cm ^-1 NMR (Acetone-d ₆ ) δ3.00-3.40 (m, 1H, -CH-) δ3.83 (br, s, 2H, -CH ₂ -) δ3.92 (br, s , 2H, -CH ₂ -) δ3.96 (br, s, 2H, 2XOH) δ7.40~8.20 (m, 4H, Ar-H) 2-(4-nitrophenyl) allyl alcohol IR (nujol) 3280, 1700 , 1680, 1600, 1515,
1378, 1347, 1110, 1040, 1025, 1010, 855,
708cm ^-1 NNR (Acetone-d ₆ ) δ4.53 (br, s, 2H, -CH ₂ -) δ4.70 (br, s, 1H, OH) δ5.54 (br, s, 1H, C=CH -) δ5.64 (br, s, 1H, C=CH-) δ7.60-8.30 (m, 4H, Ar-H) Example 38 Instead of o-nitrotoluene as a raw material,
Using 2,4-dinitrotoluene, the quantity of electricity is
When electrolysis was carried out in the same manner as in Example 1 except that the setting was 0.1F/M, 2-(2,4-dinitrophenyl)-
525.3 mg (98.7%) of 1,3-propanediol was obtained as yellow crystals. (mp: 88-90℃) 2-(2,4-dinitrophenyl)-1,3-propanediol IR (nujol) 3230, 1608, 1540, 1533, 1375,
1360, 1100, 1058, 1045, 988, 920, 908,
845, 833, 780, 730cm ^-1 NMR (Acetone-d ₆ ) δ2.96 (br, s, 2H, 2X-OH) δ3.30-3.90 (m, 1H, -CH-) δ4.00 (d, J=4.0Hz, 4H, 2X−CH ₂ −) δ8.00 (d, J=9.0Hz, 1H, −CH=C) δ8.45 (d, d, J=9.0Hz, 2.0Hz, 1H, − CH＝
C) δ8.60 (d, J = 2.0 Hz, 1H, -CH = C) Example 39 In the cathode chamber of the anode-cathode separation cell, 381.5 mg (2.22 mmol) of 4-chloro-o-nitrotoluene and 140 mg of paraformaldehyde (formaldehyde as
4.67 mmol) and add 450 mg of tetraethylammonium bromide as a supporting electrolyte.
(2.14 mmol), N,N-dimethylformamide 6.5
Add ml. Meanwhile, 450 mg of tetraethylammonium bromide and 6.5 ml of N,N-dimethylformamide are added to the anode chamber. Stirrer in positive and negative polarity chamber,
Thermometer and stainless steel electrode (size, 1.5×
1.0cm ² ) sufficiently soaked in the reaction solution and attached. The reaction temperature was kept at 18-20℃ and the current density was 6.6mA/
cm ² and a terminal voltage of 10 to 12 V to conduct electrolysis at 0.5F/
Electrolysis was stopped when M amount of electricity was passed. Next, the reaction solution in the cathode chamber was poured into saturated saline, and the pH was adjusted to 4 to 5 with 5% aqueous hydrochloric acid. It was extracted several times with ethyl acetate, and the extract was washed with water, dried, and concentrated. Using a silica gel column, the obtained crude product was extracted with benzene and then developed with a mixed solvent of hexane-ethyl acetate (2/1) to obtain 188.3 mg of 2-(4-chloro-2-nitrophenyl)ethanol.
(42.1%), 2-(4-chloro-2-nitrophenyl)-1,3-propanediol 236.2 mg (46.0
%)was gotten. The conversion rate of this reaction was 92.3%. Examples 40 to 50 Table 5 shows the results obtained by performing the same procedure as in Example 40 but changing the raw materials, electrodes, and supporting electrolytes.

[Table] Reaction conditions Raw materials; 2.2 mmol, paraformaldehyde; 136
mg (4.5 mmol), positive electrode; platinum electrode (1.0 x 1.5 cm ² )
Reaction temperature: 15-20℃, current: 5mA, quantity of electricity;
0.5F/MProduct 2 is 2-(nitrophenyl)ethanol with one molecule of formaldehyde added to the raw material, and product 3 is 2-(nitrophenyl)ethanol with formaldehyde added to the raw material.
These are 2-(nitrophenyl)-1,3-propanediols with added molecules.

Claims (1)

[Claims] 1. General formula [In the formula, the nitro group is substituted at the ortho or para position with respect to the methyl group, and R is hydrogen, a nitro group, a halogen atom, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms. , means hydroxyl group. A general formula characterized by electrolyzing nitrotoluenes represented by ] and paraformaldehyde in the presence of a quaternary ammonium salt in an aprotic polar solvent [In the formula, the nitro group is substituted at the same position as above, and R has the same meaning as above. n means an integer from 1 to 2. ] A method for producing 2-(nitrophenyl)ethanol.