JPH0338350B2 - - Google Patents

Description

[Detailed description of the invention]

"Industrial Application Field" The present invention relates to a method for producing 2-(nitrophenyl)ethanols. More specifically, the present invention relates to a method for producing 2-(nitrophenyl)ethanol by reacting a nitrotoluene compound with a reduction product obtained by electrolytically reducing paraformaldehyde. "Prior Art" 2-(nitrophenyl)ethanols are compounds useful as intermediates for polymeric substances, dyes, agricultural chemicals, polymeric stabilizers, photosensitive materials, fragrances, and pharmaceuticals. However, no industrially advantageous method for its production has been found. That is, for example, nitrotoluene and paraformaldehyde are combined with sodium ethoxide or potassium tertiary-
A method of reacting in the presence of an alkali metal alcoholate such as butoxide [Acta Chemica
Scandinavica, Vol. 21, p. 718 (1967);
Volume 21, page 1967 (1967)] has been proposed by B. Wesselen et al. However, this method uses an alkali metal alcoholate, which is a strong base, as a catalyst, and since this catalyst is easily decomposed by moisture in the air, special care must be taken in its preparation and storage. For these reasons, it is difficult to say that this is a practically advantageous manufacturing method. On the other hand, improved methods have been proposed, including a method using an alkali metal salt of phenol as a catalyst (Japanese Unexamined Patent Publication No. 52-108941), a method using caustic alkali (Japanese Unexamined Patent Publication No. 52-122330), and DBU (1,8-
Diazobicyclo(5.4.0)-7-undecene)
Alternatively, B.
Similar to the method of Wesselen et al., it has disadvantages such as using an expensive catalyst as a base and requiring special care in handling, and requiring a high reaction temperature to increase the conversion rate. These methods are generally not advantageous from an industrial standpoint. "Problems to be Solved by the Invention" There is a desire to develop a method for producing 2-(nitrophenol)ethanols in good yields without using alcoholate catalysts that are difficult to handle. "Means for Solving the Problems" The present inventors have conducted intensive research on a method for efficiently producing 2-(nitrophenol)ethanol by improving the above-mentioned drawbacks of conventional production methods, and have developed this book. This is an invention. That is, in the present invention, in an aprotic polar solvent or a mixed solvent of an aprotic polar solvent and another solvent,
First, polaformaldehyde is electrolytically reduced in the presence of a supporting electrolyte (electrolytic reaction), and then the resulting reduction product is given the formula (1). [In formula (1), R is at the ortho or para position to the nitro group or methyl group, and R is hydrogen, a halogen atom, a nitro group, a hydroxyl group, a C _1-4 alkyl group, or a C _1-4 alkoxy group. React the nitrotoluene compound represented by (condensation reaction) formula (2) [In formula (2), R represents the same meaning as above, and the nitro group is
The method is to produce 2-(nitrophenyl)ethanols represented by CH _3-o (CH ₂ OH ₎ in the ortho or para position relative to the o group, where n represents 1 or 2. The nitrotoluenes represented by formula (1) used in the method of the present invention are ortho or para-nitrotoluenes, and specific examples include 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-xylene
-cymene, 4-nitro-m-cymene, 2-nitro-p-cymene, 4-nitro-m-cresol, 2-nitro-m-cresol, 3-nitro-
p-cresol, 4-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-nitrotoluene, 3-butoxy-p-nitrotoluene,
Examples include 2,4-dinitrotoluene. As the supporting electrolyte used in the present invention, salts that are subjected to ordinary electrolytic reactions can be used, but preferred ones are those of the following formula: [In the formula, R ¹ , R ² , R ³ , and R ⁴ are the same or different unsubstituted or substituted alkyl groups or unsubstituted or substituted phenyl groups, and X is

[Formula] CIO ₄ , halide ion, HSO ₃ , CN or BF ₄
It means an anion that forms a quaternary ammonium salt by pairing with an ammonium ion such as. ]
Specific examples of quaternary ammonium salts include the following. Quaternary ammonium paratoluenesulfonic acid esters such as tetramethylammonium paratoluenesulfonate, tetraethylammonium paratoluenesulfonate, and tetrabutylammonium paratoluenesulfonate; tetramethylammonium perchlorate, tetraethylammonium perchlorate, tetrabutyl perchlorate Perchloric acid quaternary ammonium salts such as ammonium; tetramethylammonium bromide, tetraethylammonium bromide, tetraethylammonium chloride, tetrabutylammonium bromide, n-dodecyltrimethylammonium bromide, cetyltrimethylammonium bromide, tetraethylammonium iodide, benzyltetraethylammonium Halogenated quaternary ammonium salts such as iodide; quaternary ammonium salts such as tetramethylammonium cyanide, tetraethylammonium cyanide, and tetrabutylammonium cyanide; quaternary ammonium salts such as tetraethylammonium tetrafluoroborate. Other compounds used as the supporting electrolyte include alkali metal perchlorates such as sodium perchlorate and potassium perchlorate; alkali metal halides such as sodium iodide and potassium iodide. However, ammonium salts such as ammonium chloride, ammonium perchlorate, ammonium paratoluenesulfonate, etc. are not suitable for the purposes of the present invention. The amount of these supporting electrolytes to be used varies depending on the reaction medium, the shape of the reaction vessel, etc., but is usually in the range of 0.01 to 30 times, preferably 0.1 to 10 times, the weight ratio of paraformaldehyde. The amount of paraformaldehyde used is usually in the range of 0.1 to 10 times the mole, preferably 0.5 to 3.0 times the mole of the nitrotoluene compound added in the condensation reaction. As the aprotic polar solvent used in the method of the present invention, dimethylformamide, dimethylsulfoxide, tetrahydrofuran, hexamethylphosphorotriamide, dimethylacetamide, dioxane, dimethoxyethane, acetonitrile, propionitrile, etc. are used. If necessary, a mixed solvent of these and an aliphatic alcohol such as methanol, ethanol, isopropyl alcohol, tertiary-butyl alcohol, etc. can also be used. Particularly preferred is dimethylformamide or a mixed solvent containing dimethylformamide as the main solvent. The amount of these solvents to be used is 5 to 1000 times, preferably 10 to 1000 times the weight of paraformaldehyde.
100x range. For the electrolytic reaction of the present invention, ordinary electrodes for electrolysis, ie, electrodes made of materials such as platinum, carbon, nickel, lead, copper, stainless steel, zinc, aluminum, etc., and titanium electrodes surface-treated with platinum, can be used. In the present invention, a single cell or a separate cell with separate anode and cathode chambers is used, but a separate cell is preferred. At this time, the diaphragm that separates the anode and cathode chambers is not particularly limited, but glass filters, unglazed magnetic materials, ion exchange membranes, etc. are used. In addition, the reaction temperature during the electrolytic reaction and its subsequent reaction (condensation reaction) is usually 0 to 100°C, preferably 10 to 100°C.
40℃, reaction time is usually 1 to 10 hours, preferably 2 hours.
~3 hours. In the electrolytic reaction, a constant potential electrolysis method or a constant current electrolysis method can be adopted. Current density is 0.1-100mA/ ^cm2
In addition, the amount of electricity applied is usually 0.01 to 2 F, preferably 0.1 to 1.0 F per mole of nitrotoluene added later, so that active reactive species are generated.
In the subsequent reaction with a nitrotoluene compound, 2-
(Nitrophenyl)ethanol is efficiently produced. The concentration for the cathode reaction solution is usually expressed as % by weight.
It ranges from 0.1 to 50%, preferably from 1 to 25%. As described above, in the method of the present invention, paraformaldehyde is electrolytically reduced in the presence of an electrolyte, and then a nitrotoluene compound is added to the catholyte for reaction, or the catholyte is transferred to another reactor and the nitrotoluene compound is added thereto. By adding and reacting, it is possible to obtain 2-(nitrophenyl)ethanols in high yield without producing by-products. The present inventors first prepared nitrotoluenes and paraformaldehyde in an aprotic polar solvent.
We proposed a method for producing 2-(nitrophenyl)ethanols by electrolytic reduction in the presence of ammonium salts. (Patent Application No. 59-56142) Patent Application No. 59-56142
The method of the present invention involves electrolytic reduction in the coexistence of nitrotoluenes, so depending on the compound, the nitro group may be reduced, resulting in a slight decrease in yield, but the method of the present invention does not contain nitrotoluenes as a starting material. Electrolytic reduction in the system has the advantage of improving the yield. The produced 2-(nitrophenyl)ethanols can be easily separated and purified from the reaction mixture by known methods such as distillation and extraction. The present invention will be specifically explained below with reference to Examples. "Example" Example 1 260 mg of paraformaldehyde (8.67 mmol as formaldehyde) in the cathode chamber of the positive and cathode separation cell
430 mg (1.43 mmol) of tetraethylammonium paratoluene sulfonate (Et ₄ NOTs) and 6 ml of N,N-dimethylformamide (DMF) are added as supporting electrolytes. on the other hand,
Add 430 mg of Et ₄ NDTs and 6 ml of DMF to the anode chamber.
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 sufficiently soaking them in the reaction solution. The reaction temperature was maintained at 25 to 29° C., and electrolysis was carried out under the conditions of a current density of 3.3 mA/cm ² and a terminal voltage of 9 to 10 V, and the electrolysis was stopped when an amount of electricity of 0.3 F/M was passed. Next, add 300 g of o-nitrotoluene to the cathode chamber.
mg (2.2 mmol) was added, and the reaction temperature was maintained at 25 to 29°C and stirred for 2 hours. Next, pour the reaction solution in the cathode chamber into saturated saline, and adjust the pH to 4 with 5% hydrochloric acid aqueous solution.
I gave it ~5. It was extracted several times with ethyl acetate, and the extract was washed with water, dried, and concentrated. The obtained crude product was filtered with benzene using a silica gel column, and further filtered with n
-2-(2-nitrophenyl)ethanol when developed with a mixed solvent of hexane-ethyl acetate (2/1)
32.7mg (8.9%), 2-(2-nitrophenyl)-
217.8 mg (87.0%) of 1,3-propanediol was obtained. The conversion rate of this reaction was 96.3%. Physical properties of 2-(2-nitrophenyl)ethanol IR (neat) 3350, 2930, 2890, 1608, 1580,
1530, 1350, 1050, 861, 795, 745, 703cm ^-1 NMR (CDCl ₃ ) δ 2.47 (br.s, 1H, −OH) δ 3.12 (t, 2H, −CH ₂ −) δ 3.90 (t, 2H , _-CH2- ) δ 7.25-8.00 (m, 4H, Ar-H) Physical properties of 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 ) δ 3.55 (br.s, 2H, OH) δ 3.45~3.70 (m, 1H, −′CH−) δ 3.90 (d, J=5.0Hz, 4H, −CH ₂ -) δ 7.17 to 7.85 (m, 4H, Ar-H) Examples 2 to 8 Table 1 shows the results of reactions conducted in substantially the same manner as in Example 1, but with different types of cathodes.

[Table] Reaction conditions Raw material o-nitrotoluene; 300 mg (2.2 mmol),
Positive electrode; platinum electrode (1.0×1.5cm ² ), supporting electrolyte:
Et ₄ NOTs; 420 mg×2, DMF; 6.0×2 ml, paraformaldehyde; 260 mg (8.7 mmol), reaction temperature; 25 to 29°C, current; 5 mA, quantity of electricity; 0.3 F/M Examples 9 to 35 Example 1 Table 2 shows the results obtained by performing almost the same procedure as above 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 (1.0×1.5cm ² ), DMF;
6.0×2ml, paraformaldehyde; 260mg (8.7
mmol), reaction temperature: 25-29°C, current: 5 mA,
Electricity: 0.3F/M In the table, Me is methyl, Et is ethyl, Bu is n
-Butyl, ph represents phenyl.

【table】

[Table] Reaction conditions Raw material o-nitrotoluene; 300 mg (2.2 mmol),
Paraformaldehyde; 260 mg (8.7 mmol),
DMF; 6.0×2ml, positive electrode; platinum electrode (1.0×1.5
cm ² ), reaction temperature: 20 to 25° C., current: 5 mA, quantity of electricity: 0.3 F/M. In the table, Ts represents a tosyl group. Examples 36 to 44 Table 4 shows the results obtained by performing almost the same operation as in Example 1 but changing the solvent.

[ ^* In the case of THF, Bu ₄ NClO ₄ (0.9 mmol) was used. ]

Reaction temperature: 20-29℃, current: 5mA, quantity of electricity;
0.3F/M Example 45 Using p-nitrotoluene instead of o-nitrotoluene as a raw material
When the reaction was carried out using nitrotoluene and other conditions were almost the same as in Example 1, 84.3 ml (22.9%) of 2-(4-nitrophenyl)ethanol, 2-(4-
Nitrophenyl)-1,3-propanediol
257.0 mg (59.3%) was obtained. Furthermore, 2-(4-
2-(4-nitrophenyl), which is thought to be produced by dehydration of 1,3-diol (nitrophenyl)
44.5 mg (11.3%) of allyl alcohol was obtained. The conversion rate of this reaction was 97.0%. Physical properties of 2-(4-nitrophenyl)ethanol IR (CHCl ₃ ) 3590, 3400, 2940, 2875, 1605,
1520, 1350, 1320, 1180, 1113, 1040, 1020,
860, 835, 692cm ^-1 NMR (CDCl ₃ ) δ 1.76 (br.s, 1H, −OH) δ 2.98 (t, 2H, −CH ₂ −) δ 3.95 (t, 2H, −CH ₂ −) δ 7.27 ~8.36 (m, 4H, Ar-H) Physical properties of 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 ) δ 3.00-3.40 (m, 1H,

[Formula]) δ 3.83 (br.s, 2H, −CH ₂ −) δ 3.92 (br.s, 2H, −CH ₂ −) δ 3.96 (br.s, 2H, −CH −) δ 7.40 to 8.20 ( m, 4H, Ar-H) Physical properties of 2-(4-nitrophenyl) allyl alcohol IR (nujol) 3280, 1700, 1680, 1600,
15151378, 1347, 1110, 1040, 1025, 1010,
855, 708cm ^-1 NMR (Acetone-d ⁶ ) δ 4.53 (br.s, 2H, −CH ₂ −) δ 4.70 (br.s, 1H, −OH) δ 5.54 (br.s, 1H, C=CH -) δ 5.64 (br.s, 1H, C=CH-) δ 7.60-8.30 (m, 4H, Ar-H) Example 46 2, instead of o-nitrotoluene as a raw material
Using 4-dinitrotoluene, the amount of electricity is 0.1F/
When the reaction was carried out in the same manner as in Example 1 except that M was used, 2-(2,4-dinitrophenyl)-
522 mg (98.0%) of 1,3-propanediol was obtained as yellow crystals. (mp: 88-90℃) Physical properties of 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 ) δ 2.93 (br.s, 2H, -OH) δ 3.30-3.90 (m, 1H,

[Formula]) δ 4.00 (d, J = 4.0Hz, 4H, -CH ₂ -) δ 8.00 (d, J = 9.0Hz, 1H, -CH = C) δ 8.45 (d, d, J = 9.0Hz, 2.0Hz, 1H, −
CH=C) δ 8.60 (d, J=2.0Hz, 1H, -CH=C) Example 47 Weigh out 250 mg (8.3 mmol) of paraformaldehyde in the cathode chamber of an anode-cathode separation cell and add tetraethylammonium bromide as a supporting electrolyte.
Add 450 mg and 5.5 ml of DMF. Meanwhile, add 450 mg of tetraethylammonium bromide and 5.5 ml of DMF to the anode chamber. Stirrer, thermometer and stainless steel electrode (1.0
×1.5cm ² ) sufficiently soaked in the reaction solution and attached.
Keep the reaction temperature at 20-29℃ and keep the current density at 3.3m.
Electrolysis is carried out under the conditions of A/cm ² and terminal voltage of 9 to 12 V.
Electrolysis was stopped when an amount of electricity of 0.27F/M was passed. Next, add 3-nitro-o-xylene to the cathode chamber.
300 mg (2.0 mmol) was added and the reaction temperature was maintained at 20 to 29°C and the reaction was carried out for 2 hours. 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, then dried and concentrated. The obtained crude product was extracted with benzene using a silica gel column, and then developed with a mixed solvent of n-hexane-ethyl acetate (2/1) to obtain 351.5 mg of 2-(6-methyl-2-nitrophenyl)ethanol.
(97.1%) was obtained. The conversion rate of this reaction was 100%. Physical properties of 2-(6-methyl-2-nitrophenyl)ethanol IR (neat) 3320, 2950, 2870, 1604, 1530,
1455, 1355, 1092, 1040, 898, 797, 739cm ^-1 NMR (CDCl ₃ ) δ 2.45 (s, 3H, −CH ₃ ) δ 2.70 (br.s, 1H, −OH) δ 3.07 (t, 2H, -CH ₂ -) δ 3.86 (t, 2H, -CH ₂ -) δ 7.05 to 7.67 (m, 3H, Ar-H) Examples 48 to 59 Raw materials, electrodes, and supporting electrolyte were prepared in almost the same manner as in Example 47. Table 5 shows the results obtained by changing the parameters.

[Table] Reaction conditions Raw materials; 2.0 mmol, paraformaldehyde; 250
mg (8.3 mmol), supporting electrolyte; 1.0-1.5 mmol,
DMF; 6.0×2ml, positive electrode; platinum electrode (1.0×1.5
cm ² ), reaction temperature: 20 to 27°C, current: 5 mA, quantity of electricity: 0.5 F/M In the table, products 2 to 2 are 2-(nitrophenyl)ethanols in which one molecule of formaldehyde is added to the raw material nitrotoluenes. and 3~ is 2-(nitrophenyl)-1,3-propanediol in which two molecules of formaldehyde are added to nitrotoluene as a raw material. "Effects of the Invention" 2-(nitrophenyl)ethanols can be obtained efficiently without using alcoholate catalysts that are difficult to handle.

Claims (1)

[Claims] 1. Paraformaldehyde is first electrolytically reduced in an aprotic polar solvent or a mixed solvent of an aprotic polar solvent and another solvent in the presence of a supporting electrolyte, and then the resulting reduction product is Formula (1) [In formula (1), R is at the ortho or para position to the nitro group or methyl group, and R is hydrogen, a halogen atom, a nitro group, a hydroxyl group, a C _1-4 alkyl group, or a C _1-4 alkoxy group. Formula (2) characterized by reacting a nitrotoluene compound represented by [R in formula (2) has the same meaning as above, the nitro group is at the ortho or para position to the CH _3-o (CH ₂ OH) _o group, and n represents 1 or 2] A method for producing 2-(nitrophenyl)ethanol.