JPS62202091A - Production of 2-(nitrophenyl)-1-substituted-ethanol - Google Patents

Abstract

PURPOSE:To industrially and efficiently produce 2-(nitrophenyl)-1-substd.-ethanols by electrolyzing specific nitrotoluenes and prescribed aldehydes in the presence of a supporting electrolyte. CONSTITUTION:The nitrotoluenes such as O-nitrotoluenes expressed by formula I and the aldehydes such as isobutyl aldehydes expressed by formula II are electrolyzed in the presence of a supporting electrolyte such as alkaline halide metallic salt or the like such as KI to obtain the above-mentioned ethanols expressed by formula III. In formula I, a nitro group is substd. with the ortho position or para position relative to a methyl group, R denotes hydrogen; nitro group; hydroxyl group; substd. or unsubstd. amino group; halogen atom; alkyl group, alkoxy group of 1-4C; aryl group; aryloxy group or aralkyl group. In formula II, R1 and R2 denote an alkyl group of 1-9C, and may form a ring with R1 and R2. This compd. is useful as an intermediate raw material in production of dyes, agricultural chemicals, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The industrial field of application M relates to a process for the production of 2-trophenyl)-1-substituted ethanols. More specifically, the present invention relates to a method for producing 2-trophenyl)-1-11-converted ethanols, which comprises electrolyzing nitrotoluenes and aldehydes in the presence of a supporting electrolyte.

Prior Art 2-Trophenyl)-+-mm-ethanol is an important compound as an intermediate raw material for the production of polymeric compounds, dyes, agricultural chemicals, photosensitive materials for polymeric stabilizers, fragrances, and pharmaceuticals. However, an industrially efficient manufacturing method has not yet been found.

2-trophenyl)-1-ff-substituted-ethyls are generally synthesized by reacting nitrotoluenes and aldehydes in the presence of a base, but KOH, NaO
When a normal base-catalyzed reaction is carried out using a base such as Me or t-BuOK, self-aldol condensation of aldehydes occurs preferentially and the desired addition reaction proceeds only slightly.

Problem 2 to be Solved by the Invention: It is desired to develop a method for efficiently producing trophenyl)-1-[converted-ethanols].

Means for Solving the Problems 2 The present invention was achieved as a result of intensive research to find a method for efficiently producing 1-(nitrophenyl)-1-substituted ethanols. That is, the present invention provides formula (1) [in formula (1), the nitro group is substituted at the ortho or para position with respect to the methyl group, and R is hydrogen; -nitro group; hydroxyl group; substituted or unsubstituted Amino group; halogen atom;
It represents a C1-4 alkyl group; a C1-4 alkoxy group; an aryl group; an aryloxy group or an aralkyl group. ] Nitrotoluenes represented by formula (2) [in formula (2),
R1 and R2 represent a C1-9 alkyl group, and R1 and R2 may form a ring. [In formula (5), R, R1 and R2 have the same meanings as above and are substituted at the ortho or para position. The present invention provides a method for producing ethanols by replacing trophel with 2-i as shown in the following.

As mentioned above, in the condensation of nitrotoluenes and aldehydes using a normal base catalyst, self-aldol condensates are mainly produced, and the desired product f
Compared to certain 2-trophenyl)-1-substituted ethanols that can only be obtained in low yields, the method of the present invention efficiently and selectively converts the desired 2-trophenyl) to the desired 2-trophenyl) using a simple electrolytic method. -1-Substituted-ethanols can be obtained.

The nitrotoluenes represented by the general formula (1) are ortho or baranitrotoluene wire conductors, and specific examples include 0-nitrotoluene, P-nitrotoluene, 2
-Nitro-m-xylene, 26-nitro-m-cresol, 3-nitro-P-cresol, 5-nitro-F-toluidine, 5-nitro-m-toluidine, 3-nitro-
〇-Toluidine, 4-ethylamino-2-nitrotoluene, 2-methylamino-4-nitrotoluene, 4-dimethylamino-2-nitrotoluene, 4-chloro-2-nitrotoluene, 6-talol-0- Nitrotoluene, 4-
Bromo-2-nitrotoluene, 5-chloro-2-nitrotoluene, 5-iodo-2-nitrotoluene, 5-fluoro-2-nitrotoluene, 4-fluoro-2-nitrotoluene, 2- Chloro-4-nitrotoluene, 2-7'
Romo-4-nitrotoluene, 2-iodo-4-nitrotoluene 2-nitrotoluene, 5-phenoxy/-2-nitrotoluene, 5-methoxy-4-nitrotoluene, 3-butquine-4-nitrotoluene, 2,4-dinitrotoluene, 2-nitro-a-(4 '-methylphenyl)toluene, 2-nitro-4-phenyltoluene, 4-benzyl-2-nitrotoluene, 4-(a'-nitrobenzyl)
-2-nitrotoluene, 4-7enether-2-nitrotoluene, and the like.

Further, specific examples of aldehydes represented by formula (2) used in the method of the present invention include isobutyraldehyde, 2-methylbutyraldehyde, 2-ethylbutyraldehyde,
Cyclohexanecarboxaldehyde, 2-methyl-n-
Valeraldehyde.

2.5-Dimethylvaleraldehyde% 2-ethylhexylaldehyde, 2-methylundecanal, etc. are mentioned.

As the supporting electrolyte used in the present invention, salts used in ordinary electrolytic reactions can be used, but preferred ones include the following formula [wherein R1, R2 and R4 are the same or different substituted or unsubstituted alkyl groups, xe is CH , ()-058, C104e, Hara(to(on, Hso, e.

Refers to an anion that forms a quaternary ammonium salt with ammonium ions such as cNe or BF4e.] Examples of the quaternary ammonium salts are as follows. Tetramethylammonium valatoluene sulfonate.

Tetraethylammonium valatoluene sulfonate,
Quaternary ammonium salts such as tetrabutylammonium varatoluenesulfonate para-toluenesulfonic acid ester #14 = Quaternary ammonium perchlorate salts such as tetramethylammonium perchlorate, tetraethylammonium perchlorate, and tetrabutylammonium perchlorate : Tetraethylammonium chloride, tetramethylammonium bromide, tetraethylammonium bromide, n
- Halogenated quaternary ammonium salts such as dodecyltrimethylammonium bromide, cetyltrimethylammonium bromide, and tetraethylammonium iodide: tetramethylammonium cyanide, tetramethylammonium cyanide.

Quaternary ammonium salts such as tetrabutylammonium cyanide and tetraethylammonium tetrafluoroborate.

Other examples used as supporting electrolytes include alkali metal perchlorates such as sodium perchlorate, potassium perchlorate; sodium iodide, potassium iodide, etc.
Examples include alkali metal salts. The amount of these supporting electrolytes to be used varies depending on the type of solvent and the shape of the reaction tank, but is usually 0% by weight relative to nitrotoluene.
．． It is in the range of 1 to 30 times, preferably 0.3 to 10 times. The amount of aldehyde used is usually in the range of O,S to 10 times the mole, preferably 1 to 5 times the mole relative to the nitrotoluene. The method of the present invention is conveniently carried out in an organic solvent, and as the organic solvent, an aprotic polar solvent or a mixed solvent of an aprotic polar solvent and another solvent can be used. Dimethylformamide is an aprotic polar solvent.

Dimethyl sulfoxide, tetrahydrofuran, hexamethylphosphotriamide, dimethylacetamide, dioxane, dimethoxyethane, acetonitrile, propionitrile, etc. are used. If necessary, add methanol, ethanol, inopropyl alcohol, 5th class 7'
A mixed solvent with an aliphatic alcohol such as chill alcohol can also be used. In particular, it is preferable to use dimethylformamide or a mixed solvent containing dimethylformamide as the main solvent. The amount of these solvents to be used is in the range of 1 to 100 times, preferably 3 to 30 times, the weight of the nitrotoluenes.

In the electrolytic reaction of the present invention, electrodes for ordinary electrolysis are used, such as electrodes made of materials such as platinum, carbon, nickel, lead, copper, stainless steel, zinc, and aluminum, and electrodes whose surfaces are treated with platinum.
@Koku 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 separating the corner and cathode chamber 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 is usually 0-100°C, preferably 5-100°C.
The temperature is 40°C.

In the electrolysis method of the present invention, a constant potential method or a constant current method can be adopted. The current density is in the range of 0.1 to 100m to -2, and the amount of electricity applied varies depending on the shape of one reaction tank and the type of nitrotoluene, but it is usually o, o o s to 2F per mole of nitrotoluene. , preferably 0.01
~1. It is sufficient to energize OF. The concentration of nitrotoluenes in the cathode chamber is usually 1 to 50% by weight, preferably 5 to 50%.
50% range (solution concentration).

As described above, the method of the present invention uses an electrolytic reaction to react ortho- or para-nitrotoluenes with aldehydes in the presence of a supporting electrolyte, and selectively and efficiently reacts <2- without producing by-products. trophenyl)-1-substituted-
The 2-(trophenyl)-1-fif-converted ethanols produced by the reaction mixture that make it possible to obtain ethanols can be easily separated from the reaction mixture by known methods such as distillation and extraction.

The compound of formula (5) obtained by the method of the present invention is used, for example, by subjecting it to a ring-closing reaction to form an indole metal conductor in the production of medicines, dyes and pigments, agricultural chemicals, and the like.

Example The present invention will be explained in more detail with reference to Examples.

Example 1 0-Nitrotoluene 507 in the cathode chamber of the positive and cathode separation cell
19 (2.2 mmol), (7 Weighed 500 μ (4.2 mmol) of buteraldehyde, dissolved 400 μ of tetraethelammonium paratoluenesulfonate (B7aHOTtx), and dissolved 9 N,N-dimethylformamide ( DMF) 6a# was added.Meanwhile, anode f
iK]! :DMF6d in which t4NOTs 4007719 was dissolved was added. Stirrer, thermometer, and platinum electrode (size, 1.0 x 1.
s,,@2) was fully immersed in the reaction bath solution and attached. Reaction temperature 1FI: kept at 25-26℃, current density 3-S
mA/cm2. Electrolysis was carried out under the conditions of a terminal voltage of 7-IQv, and the electrolysis was stopped when an amount of electricity of 0.5 F/mol was passed. Next, the catholyte was poured into a saturated saline solution, and the pH was adjusted to pH 4.5 with a 5% aqueous hydrochloric acid solution. Ethyl acetate (AQ
The extract was washed with water, dried over Glauber's salt, and then concentrated. The obtained crude product was developed with a mixed solvent of n-hexane-AcOEe using a 7-layer gel column to obtain 505 μl of 2-(2-nitrophenyl)-1-inogumivir ethanol (yield: 65.1 %) obtained. The conversion rate of this reaction was 71.5 h.

Engineering R (neae) 3395. 2960. 28
70. 15! So, 1!550°1050,79
0.740 Demand-1 HMR (CDCl, ) δ0.96 ((1, J=6.QHz, 6H,
CH5) 61.46-1.90 (m, + H, CH
) δ+, 96 (br, e, +H,OH) δ2.
73 (d, d, J=i sHz, J=10Hz
, l) (, Ar-CH) δS, 14 ((1, d,
J=15Hz, J==L4Hz, IH, Ar-C
H) 62.10-7.90 (m, aH, Ar-H
) Comparative Example 1 Q −= ) ator: r-n s 17rqC2,3m
mol).

Inobutyraldehyde 551719 (4.6 mmol
).

Add 20μ of potassium hydroxide to the mixture of DMF6d (
0.4 mmol) was added and stirred at room temperature (25°C) for 2 hours. The reaction mixture was poured into saturated brine and neutralized with 5% aqueous hydrochloric acid.

Extraction was performed with ethyl acetate, and the extract was thoroughly washed with water and concentrated to dry (mirabilite)%. When the obtained crude product was developed using a silica gel column with a mixed solvent of n-hexane-AcOEt (1°:1), 2-(2-=)lophenyl)-1-inogumivir ethanol was obtained in 11 μg (yield). 2.2%) 1,1- which is a self-aldol condensate of inbutyraldehyde
Dimethyl-2-hydroxy-5-methylvaleraldehyde was obtained. The conversion rate of this reaction was 15%.

Examples 2 to B Table 1 shows the results of reactions conducted in the same manner as in Example 1, but with different types of cathodes.

Table 1 Reaction conditions 0-=)cxtorxn;3oorng(2,
2 mmol).

Inobutyraldehyde; 25o■ (5-5 mmol)
Supporting electrolyte Ice4NOT8; 400 +#X 2
.

DMF; 6. Ox 2a/, reaction temperature '+ 23-
27℃.

Current i5mA, Wt volume; o-5F/mol electrode; platinum electrode (1, ox 1.s, 2) Example? ~24 Table 2 shows the results of a reaction conducted in the same manner as in Example 1 with different supporting electrolytes.

Table 2 Reaction conditions 0-Nitrotoluene; 300 μ (2.2 mmol).

Inbutyraldehyde; 250η (5.5 mmol)
.

DMII′i 6.0alX 2. Anode and cathode; platinum electrode (
1,5x1, Or: 1n2), reaction temperature '+25~2
6°C, electric current m is mA.

Electricity: 0.2-0.5 F/mol, 1Mθ in the table
represents methyl, E7 represents ethyl, Bu represents butyl, and Ph represents phenyl group.

Examples 25 to 55 Table 5 shows the results obtained by performing the same operation as in Example 1 but changing the solvent.

Reaction conditions 0-Nitrotoluene 8500η (2.2 mmol)
.

Inobutyraldehyde i 250 mf (L5 mm
ol).

Anode/cathode; platinum electrode (t, ox +, 5/2).

Et4NOTs (cathode chamber); 1a ~ 13mmo
x ("For THF Bu4NC104 (0-? mm
ol) t-used. ]Reaction temperature i 23-25℃,
Current: 5mA.

Electricity io, s F/mol Example 34 0-Nitrotoluene 253T in the cathode chamber of the anode-cathode separation cell
Ig (1.8 mmol) and 265 mmol of cyclohexanecarboxaldehyde (2.4 mmol) were weighed out, and 5 ml of DMF' in which ICt4NOTs 400719f was dissolved was added. Meanwhile, E in the anode chamber
DMF5d containing 400 mf of t4NOTs was added. A stirrer, a thermometer, and a stainless steel electrode (thick g, 1.OXl, 5c+++) were fully immersed in the reaction solution and attached to the anode and cathode compartments.

The reaction temperature was kept at 25-27°C, and the current density was 3.3 mA.
/crn2. Eleven solutions were carried out under conditions of a terminal voltage of 9 to 1 tV, and the electrolysis was stopped when an amount of electricity of 0.a F/mol was passed. Next, the catholyte was poured into a saturated saline solution, and the pH of the solution was adjusted to 5 with a 5% aqueous hydrochloric acid solution. The extract was extracted with Ac OE t;, and the extract was washed with water, dried (mirabilite), and concentrated.

When the obtained crude product was used as an eluent in a mixed solvent of n-hexane-AcO[t (3:1) using a silica gel column, 2-(2-nitrophel)-j-7 chlorohexylethanol was obtained in an amount of 280 μ(62 , 0%) was obtained as yellow crystals. (Melting point 197-99°C) The conversion rate of this reaction was 69.5%.

Engineering R (CHCL3) 3580,2920.284
L 152s.

+450.1350.865cm-1 HMR (CD(J,) δ+, 15-4.14 (m, + I H, Cycl
ohexyl) δ2.7B (d, d, J=13
Hz, J=? H2, IH, CH) δ3.22 (d,
d, :f=1sHz, J=7! , 4Hz, +H
, CH) δ3.45-5.77 (m, 1H, CH-
0)67.25-7.94 (m, 4H, Ar-H
) Example 35 Using 2,4-dinitrotoluene gold instead of 0-nitrotoluene as the raw material and carrying out the same conditions as in Example 1, 2-(2,4-dinitrophenyl)-1-isopropylethanol was obtained. 313 (56.0%) was obtained. The conversion rate of this reaction was 70.0%.

Engineering R (neat) 3550.3380.2950.
2B60.1605.1605°1550, +345.
1040,910. B55,735 demand NMR (CDCl
5) δ1.00 (d, , r==6.2I(Z, 6H
,CH,)δ1.3~1-9 (m+ IH,CH)δ
2.00 (br, a, +H,OH)δ2.95
(L d, I=13Hz, J=:10Hz, I
H, Ar-CH) δ3.27 (d, a, :f=1
5Hz; J=5. aHz, tH, Ar-CH)J
S48-41.77 (m, IH, CH-0) δ7.6
4 (d, J=8,4HJ IH, Ar-I()δ8
．． 31 (6, (1, J=8.JHz, J=2.OH2
, I H, Ar-H) δB, 65 (eL, J=2
．． 0Hz, 1H, Ar-H) Example 36 305 m of 0-nitrotoluene was placed in the cathode chamber of the anode-cathode separation cell.
fC2,2 mmol) and 350 g (z・y mmol) of 2-ethylhexylaldehyde were weighed, and to this was added tetraethylammonium bromide sso.
5 ml of DMI' in which my was dissolved was added. - DM F 5 R1 in which 550 μm of tetraethelammonium bromide was dissolved was added to the barrier electrode chamber. A stirrer in the anode and cathode compartments.

Thermometer and carbon electrode (size, 1.o x 1-
5 cm2) was fully immersed in the reaction solution. The reaction temperature was maintained at 20-25°C, and the current density was 5.3 mA/(g
, Electrolysis was carried out under the conditions of terminal pressure 10 to 1zv and 0.2
Electrolysis was stopped when 5F/mol of electricity was applied.

Next, the catholyte was poured into a saturated saline solution, and the pH was adjusted to 4 with a 54HC1 aqueous solution. The extract was extracted with AeOEl:, and the extract was washed with water, dried over Glauber's salt, and concentrated. The obtained crude product was purified using a silica gel column, and n-hexane-AcDK
When developed with a mixed solvent of e, 5-ethyl-2-hydroxy-+ -(,2-nitrophenyl)heptane is 355μ
(58.0%) was obtained. The conversion rate of this reaction is 65.0%
Met.

Engineering R (neae) 540012940.2920.
1525. +345゜865, 780.755 saw-1 HMR (CDCl5) δO-70~L60 (m, 15 H, CH2CH3
, (CH2) 3CJ , CH) δ2.50 (br
, s, 1H,OH)δ2.86(a, (1,J=
=13H? , J=10Hz, IH, Ar-CH)δ
3.16 (a, a, J==t3Hz, , r=5
．． 8HJ IH, A, r-CH) δS, 7a-4. oo
(m, 1H, CH-0) 57.16-7.93 (
m, aH, Ar-H) Example 37 O-nitrotoluene 510 in the cathode chamber of the positive and cathode separation cell
■(2,s mmol), 2-ethylbutyraldehyde 2851 nI! Weigh out (2.8 mmol) and add tetrabutyl ammonium (tetrabutyl ammonium).
Add DM F 5 JIl in which o a rng was dissolved, and add 4007 nI of tetrabutylammonium bromide to the barrier chamber. DMF S tgt in which was dissolved was added. 1, a stirrer 3 thermometer and a lead electrode (size +, ox 1-5 am) were fully immersed in the reaction solution and attached to the negative electrode chamber. The reaction temperature was maintained at 24-26°C, and the current density was 5-3 mA/cm2. Terminal voltage 10-1
Electrolysis was carried out under the conditions of 27, and the electrolysis was stopped when an amount of electricity of 0.35 F/mol was passed.

Next, the catholyte was poured into a saturated saline solution, and the pH of the solution was adjusted to 5 with a 5% HCI aqueous solution. The extract was extracted with Ac0Itit, and the extract was washed with water, dried over Glauber's salt, and concentrated. The obtained crude product was developed using a silica gel column with a mixed solvent of n-hexane, AcO: [3-ethyl-2-hydroxy-1
-(2-nitrophenyl)pentane 555 mg (61
, 4%) was obtained.

The conversion rate was 73.0%.

Engineering R (neat) 3400, 2945.2860.17G5.1605.
1525°1350, 870.785.735tan-1N
MR (CDC13) δ0.80~1.50 (m, 10H, CH2C
H,)δ2,0low2.5o(m, 1H,CH)δ
2.83 (d, (L, J=i3Hz, J=10
H2, +H, Ar-CH) δs, 1b (d, d,
J=13H2, :J=s, bHz, 1H, Ar-CH
) δ3.60 (br, S, ta, OH) δ! 1.65-4.00 (m, IH, CH-0) δ
7. t7-7.95 (m, 4H, Ar-H) Example 38 0-Nitrotoluene 300W in the cathode chamber of the anode-cathode separation cell
9 (2.2 mmol), 2-Melfba l/ /l/
7 Lua'hito 274■ (5.9 mmol) T-Weigh and add 4 o of tetraethylammonium perchlorate to this.
aytq'tfflWj DM F 5 ite
t-Add, -Tetrabutylammonium perchlorate aaamg@dissolved DM' in the barrier electrode chamber! '5 ml was added.

A stirrer, a thermometer, and an aluminum electrode (size, 1.OX i.5-) were attached to the anode and cathode side chambers by fully immersing them in the reaction solution. Electrolysis was carried out under the conditions of a current density of 5-S mA/rR2 and a terminal voltage of 9-12 V while the reaction temperature was maintained at 23 to 26°C, and the electrolysis was stopped when an amount of electricity t- of 0.5/mol was flowed. Next, the catholyte was poured into a saturated saline solution, and the pH was adjusted to pH 4 with a 5% HCI aqueous solution. Ac0
After extraction with Et, the extract was washed with water, dried over Glauber's salt, and concentrated. The obtained crude product was subjected to n-
When developed with a mixed solvent of hexf7-AcoEt (1o:1), 2-hydroxy-3-methyl-+-(2
-nitrophenyl)hexane is 3s1rnIi(6a,
3%) was obtained.

The conversion rate of this reaction was 68.0%.

Engineering R (neat,) 55BO, 2960, 29+0.2855.1520.
1340°857, 780.730cm-' NMR (CDCl, ) δ0.70~2.00 (m, 11H, CH3, (C
H2)2CH3,OH)δ2.50 (br, e
, 1H,0R)62.82~5.52(m, 2H,
CH2) δ5.5a ~ 3.82 (m, 1H, CH-
0) δ7.25-7.90 (m, 4H, Ar-H
) Examples 39 to 60 Table 4 shows the results of reactions conducted in substantially the same manner as in Example 58, but with different raw materials, negative electrodes, and supporting electrolytes.

Reaction conditions Nitrotoluene W4; 2. Ommol, Artehi)
"[i2.2~3.5mm01. Supporting electrolyte; 1.0~
1.5mm0IX 2. DMF i 5m1X 2. Positive electrode; platinum electrode (size, i, ox+, 5 parts) 1 reaction temperature: 23-27°C.

Current i5mA, 1i air volume i 0-2~0.5F/mo
1 Effect of the invention 2-(2-nitrophenyl) -1-1! An efficient electrolytic method for producing ethanols has been established.

Claims (1)

[Claims] 1.Formula (1) ▲Mathematical formulas, chemical formulas, tables, etc.▼(1) (In formula (1), the nitro group is substituted at the ortho or para position with respect to the methyl group. R is hydrogen; nitro group; hydroxyl group;
Substituted or unsubstituted amino group; halogen atom; C_1_~
_4 alkyl group; ), R_1 and R_2 represent an alkyl group of C_1_ to_9, and R_1 and R_2 may form a ring.) A formula characterized by electrolyzing an aldehyde represented by () in the presence of a supporting electrolyte. (3) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (3) (In formula (3), R, R_1 and R_2 have the same meanings as above, and the nitro group is a group ▲There are mathematical formulas, chemical formulas, tables, etc.) A method for producing 2-(nitrophenyl)-1-substituted ethanol represented by the formula (substituted at the ortho or para position).