JPS6317850A - Production of 3-phenoxycatechols - Google Patents

Abstract

PURPOSE:To obtain a compound useful as an intermediate for synthesizing a compound for photography inexpensively and in high yield, by reacting a phenolic derivative with a nitrobenzene derivative and treating the reaction product with an acid. CONSTITUTION:A compound shown by formula I (R1 and R2 are phenyl or 1-10C aliphatic group; R3 is 2-6C aliphatic oxycarbonyl; a is 0 or 1) is reacted with a compound shown by formula II (R4 is <=10C substituent group which may be replaced with benzene ring; X is halogen; b is 0-2) in the presence of a base (e.g. KOH) at 40-100 deg.C to give a compound shown by formula III (R5 is nitro, etc.; R6 is as shown for R4, etc.; R7 is as shown for R3). Then this compound is subjected to cleavage reaction by the use of an acid such as hydrochloric acid, etc., in a solvent such as methanol, etc., at 0-150 deg.C to give the aimed substance shown by formula IV.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a method for producing 3-phenoxycatechols at low cost and in high yield.

(Prior Art) 3-phenoxycatechols are compounds useful as intermediates for photographic compounds. For example, its usefulness is % Kaisho A
/-436≠It is described in No. 3. Furthermore, it is a compound that is expected to be used as an intermediate for preservatives, rust preventives, preservatives, pharmaceuticals, and dyes.

(Problem to be solved by the invention) However, there has been no concrete example of a synthesis method disclosed so far, and the development of an inexpensive manufacturing method on a particularly large scale has been desperately desired. This is the current situation.

(Means for Solving the Problems) As a result of intensive research into the synthesis method of 3-phenoxycatechols, the present inventors found that the desired product could be obtained by the method described below, and completed the present invention.

The object of the present invention is to (1) treat a compound represented by the following general formula (IV) with an acid,
A method for producing phenoxycatechols, and (2) a compound represented by the general formula NV) is produced by reacting a compound represented by the following general formula (I) and a compound represented by the following general formula (1) in the presence of a base. This was achieved by the method for producing 3-phenoxycatechos as described in (1) above, which is a reaction product or a compound derived therefrom.

General formula (1) General formula (II) General formula (I
II) General formula (IV) In the formula, R1 and R2 are each a phenyl group, carbon number/-1
0 aliphatic group or an aliphatic oxy group having -10 carbon atoms; R1 and R2 represent divalent groups and may be linked to form a ring); R3 is an aliphatic group having 2 to 2 carbon atoms; represents an oxycarbonyl group, R4 represents a substituent having a carbon number of IO or less that can be substituted on a benzene ring, X represents a halogen atom, R5 represents a nitro group or a group chemically derived from the nitro group, R6 represents the same group as R4 or a group derived from R4; R7 represents the same group as R3 or a group derived from R3; a represents Q or l; Represents an integer.

Here, when b is plural, two R4 and two R6 each represent the same or different, and two R4
and λ R6 may each represent a covalent group and form a cyclic structure.

The configuration of the present invention will be explained in detail below.

When R1 and R2 represent an aliphatic group in general formula (I), typical examples include a methyl group, an ethyl group, a propyl group, and a benzyl group. When R1 and R2 represent an aliphatic oxy group, typical examples include a methoxy group and an ethoxy group. Examples of when R and R2 each represent a divalent group and form a cyclic structure include.

Representative examples of the aliphatic oxycarbonyl group represented by R3 include methoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl group, (i) butoxycarbonyl group, and (i) inthyloxycarbonyl group.

Examples of the substituent represented by R4 in general formula (II) include aliphatic groups (e.g., methyl group, ethyl group, etc.), aliphatic oxy groups (e.g., methoxy group, ethoxy group, etc.), nitro group, norogen atom. (eg, chloro atom, bromine atom), aliphatic oxycarbonyl group (eg, methoxycarbonyl group, dodecyloxycarbonyl group, etc.), cyan group, or aliphatic carbonamide group (eg, acetamido group, pivaloylamino group).

Further, when b is 2 and two R4s represent a divalent group and are linked to form a cyclic structure, typical examples include t + 人 人 人 etc.

The compounds represented by the general formulas (1) and (It) are reacted in the presence of a base, and the resulting product is represented by the following general formula (V). The reaction scheme is shown below.

In the formula, R1, R2, R3, R4, X, a and b have the same meanings as already explained.

The compound represented by the general formula (III), which is the object of the present invention, can be obtained directly from the compound represented by the general formula (■) by chemically modifying the substituent (V) to form the derivative (IV), and then formula (II). In the formula, n is an integer from 0 to IQ, and when n is 1 or more, it means that n intermediates exist. Here, when n is plural, plural intermediates mean different structures, but they are substituents other than R and R2 (R5, (R
It means that at least one of s)b, and (R7)a) is sequentially chemically converted. Chemical conversion means, for example, conversion from nitro group to amino group to carbonamide group or from alkoxycarbonyl group to carboxylic acid.

In the above scheme, Ro, R2, R3, R4, a and b have already been explained in detail in general formulas (I) and (II). R5, R6 and R7 will be explained in detail below.

A typical example of R5 is a nitro group, an amine group derived from a nitro group, or a carbonamide group. Typical examples of carbonamide groups include acetamide, butanamide, and benzamide groups.1. z-(z,≠-Gt
-amylphenoxy)butanamide group, λ-(co, ≠-
Examples include di-t-amylphenoxy)octanamide group or tetradecanamide group.

R6 represents a group having the same meaning as R4 or a group chemically derived from R4, and the latter 'J11 is a hydroxyl group, an amine group, a carbonamide group (for example, an acetamide group, a heptafluorobutanamide group, etc.) or a group chemically derived from R4. A typical example is a carboxyl group.

R7 represents a group having the same meaning as R3 or a group derived from R3. Examples of the group derived from R3 include a carbamoyl group, a carbamoyl group, an aliphatic carbamoyl group (eg, propylcarbamoyl group, t-butylcarbamoyl group, nato), or an aromatic carbamoyl group (eg, phenyl group).

lupamoyl group), etc.

Next, reaction conditions in the manufacturing method constituting the present invention will be explained in detail.

The reaction shown in scheme (1): (where the base is a metal hydroxide (e.g., potassium hydroxide, sodium hydroxide, etc.), a metal alkoxide (e.g., sodium methoxide, t-butoxypotassium, etc.), a metal hydride ( (e.g. sodium hydride), or organic bases (e.g. /, !-diazabicyclo[3,g,0]nonene-j
, /, ≠-diazabicyclo [λ, 2.2"J octane, etc.). The amount used is O6t to 1.3 mol, preferably 0°?j per 7 mol of the compound of general formula (1).
~/, 10 mol is suitable. Examples of reaction solvents include ethers (e.g. dimethoxyethane, diglyme, etc.), amides (e.g. N=N-dimethylformamide, N +
N-dimethylacetamidonato), sulfones (e.g. dimethylsulfone, sulfolane, etc.), sulfoxides (e.g. dimethylsulfoxide), or aromatics (
For example, toluene, anisole, etc.) are used. These solvents may be used in combination. Reaction temperature is Hiro Q0C
to 2000C1 preferably 700C to ISO
It is °C. The charging molar ratio of the compound represented by general formula (1) and the compound represented by general formula (II) is (I)/
(II) = 0, j~2. O1 preferably 0. J
'-/, j is selected as appropriate.

A catalyst may be used in the reaction shown in Scheme (I).

When used, Cu is known as the Ul1mann reaction.
, Cu (e.g. CuI, Cuα, etc.), c R2+
(For example, CuCl2, CuBr2, etc.) and metal ions are selected.

In the reaction of scheme (II), NO2 group, (R4)
For the chemical conversion of the h group and the (R3)a group, generally known reactions such as a ring reaction, a hydrolysis reaction, a condensation reaction, or a substitution reaction can be used. These reactions are carried out by conventional methods.

The cleavage reaction takes place in the presence of an acid. As the acid, organic or inorganic acids can be used, such as organic sulfone [1ill
ltkf methanesulfonic acid, p-)luenesulfonic acid, etc.), organic carboxylic acids (e.g. acetic acid, formic acid, etc.), inorganic acids (e.g. sulfuric acid, hydrochloric acid, etc.), and Lewis acids (e.g. aluminum chloride, zinc chloride, etc.). selected.

Among these acids, preferred are hydrochloric acid, sulfuric acid, or organic sulfonic acids. The amount of acid used may be either a catalyst amount or a solvent amount, and the reaction time and reaction temperature will vary depending on the amount used. That is, the reaction temperature is Oo
C to 1j00C1 preferably ≠Q0C to/(7
(Selected at 70C. Reaction solvents include alcohol (e.g. methanol, ethanol, etc.), ethers U
J, tii'tetrahydrofuran, diglyme i, etc.),
halogenated hydrocarbons (e.g. dichloromethane, chloroform, etc.), nitriles (e.g. acetonitrile),
Amides (e.g. N,N-dimethylformamide,
N-methylpyrrolidone, etc.), or sulfoxides (
For example, dimethyl sulfoxide) is used.

Synthesis method of compound represented by general formula (1) and (SYN
THESIS), page 6λ6, 7925. Furthermore, a method for synthesizing a compound similar to the compound represented by the general formula (1) is described in the same publication, p./-2, teprt. The compound of general formula (1) is synthesized by methods similar to these.

Next, the present invention will be explained with specific examples. However, the present invention is not limited to these 1 (Scheme (1)
Examples of reactions shown in) ■-/ Otsu■-2 Ha.

-J I-≠ ,u,,rt) In this example! ! ,ju,! j and evaluation are each expressed by the general formula (I
V) corresponds to the intermediate (II = 4') K.

■-2 [-J ■-μ /≠ →si (hereinafter the same as [-/)-> Each corresponds to the intermediate (II=A) represented by the general formula (IV).

Specific examples of compounds synthesized in the same manner are shown below.

U02U3H7 (Example) Next, a method for synthesizing typical compounds will be specifically shown. Other compounds can be similarly synthesized.

Example (1) Synthesis of compound (jj) Compound (jj) was synthesized according to the scheme 1-/ and scheme 2-/ described above. This will be explained in detail below.

(1) First step (l+λ→3) 1, 1, 7, 7, potassium hydroxide, 2≠, 6, and water 1j- were heated to reflux with stirring for toluene/lVc'j':Q/hour. Water and toluene were distilled off azeotropically. N,N-dimethylformamide in the residue! 30m1.2 to 7
0F and cuprous chloride Q,! 1/-200C
Allowed time to react. After cooling to room temperature, salt @ / 2 yt
l, water/! 0rnl Oyo U Meta/-ru 3001
! Added t6. You can remove it by taking the precipitated crystals.3
Obtained 720y.

First step (3→u) 3 jj, pig was added to a mixed bath medium of 3 ooml of ethanol and 100ml of water, and nitrogen gas was passed through it. Add 37% of potassium hydroxide to this solution. Hiro 1 was added and the mixture was heated and refluxed for an hour. The mixture was cooled to room temperature and neutralized by adding hydrochloric acid. Ethyl acetate 5oor
rtl was added, and the mixture was transferred to a separatory funnel and washed with water. Oil 1 was separated and the solvent was distilled off under reduced pressure. The entire amount of the residue (2y) was used in the next step.

■ Third step (zt→jλ) ≠6.22 of the compound jl obtained in step ■ is converted into ethyl acetate j0
It was commonly understood as 0-. ≠7.3y of hebutafluorobutanoic anhydride was added dropwise at room temperature. After reacting at that temperature for a minute, sodium carbonate water was added to neutralize. The oil layer was transferred to a separatory funnel and washed with 9 water. The oil layer was separated, the solvent was distilled off under reduced pressure, and chloroform was added to the residue to precipitate crystals. By removing this and concentrating the 0 liquid, the j2! 2.2F
I got it.

■ No. 8 (!2→j3→zu) 29.97 of j2 is N, N-dimethylacetamide Hiroshi 0
The mixture was dissolved in a mixed solvent of 100 ytl of acetonitrile and acetonitrile, and thionyl chloride IO1≠7y was added dropwise at room temperature (λ y'C). After 10 minutes, the mixture was cooled to -sOc~-1c°C and propylamine was added dropwise. After stirring at that temperature for 3 c minutes, ethyl acetate! OQ- was added and the mixture was transferred to a separatory funnel and washed with water. Further, it was washed with dilute hydrochloric acid and then with water until it became neutral. The oil layer was taken, the solvent was distilled off under reduced pressure, and a mixed solvent of chloroform and hexane was added to the residue to crystallize it. /3. jp's μ was obtained.

■ Step J (review → zs) Add J Hiro's /3.39 to 100*l of methanol and add hydrochloric acid (
36%) was added at 7F and heated under reflux for 1 hour. After cooling to room temperature, a little water was added. By taking the precipitated crystals, F)7. I got a tf of 63.

Example (1) Compound example! Synthesis was carried out as follows according to Synthesis Scheme I-2 and Scheme ■-2 of Otsu. In the example below, two steps (≠+ko→!-, !1) were performed consecutively.

75', /P and aqueous dispersion of potassium /r, 0 were added to toluene 21 and heated to reflux with stirring.

After 1 hour, the bath medium was distilled off to give N,N-dimethylformamide!
, 00ml was added. In addition, add so, op and 1o
The reaction was carried out at o0~/10°C for 2 hours (Hiro+λ-yo).

After cooling to room temperature, add 4t of hydrochloric acid (3c%)
The reaction was carried out at o 0c for co hours (j→jA).

The mixture was cooled to room temperature, ethyl acetate/l was added thereto, and the mixture was transferred to a separating funnel and washed with water. The oil layer was taken and the solvent was distilled off under reduced pressure. By recrystallizing the residue with methanol, taro is 73.35! Obtained. The melting point is! The temperature was 228C to 236C (dec).

Example (3) Synthesis of Compound Example r It was synthesized according to the previously explained schemes I-J and 1-JK. 1roy of compound I, 7≠7 of compound O and t-butoxypotassium 37 were added to tetrahydrofuran zoo.
xlK was dissolved and reacted at room temperature (2!~27°C) for 3 hours. To this reaction bath solution, 10 ral of methanesulfonic acid and 10 rttl of water were added and reacted for 3 hours at Hiro Q-5o0c. Dichloromethane/l and water/l to the reaction mixture! was added and stirred.

The oil layer and the Dm medium were distilled off. By adding water and a small amount of methanol to the residue and taking the precipitated crystals, /23
．． Compound g of 3y was obtained. The melting point was t2-rs, joc.

Example (4) Synthesis of Compound U Compound U was synthesized according to Scheme]-7 using j2 obtained in the third step of Example (1).

■ First step (!λ→n) 12.2 of j2, reduced iron 307. ammonium chloride 3
y, and acetic acid Jvtl to isoprominol 2ror
The mixture was added to a mixed solvent of d and Mizuhiro Ogo, and heated under reflux for 1 hour. The filtrate was concentrated under reduced pressure while hot.

When crystals precipitated, the concentration was stopped and the mixture was cooled. Separating the precipitated crystals by 0 traps is a compound of tA3;, 2p! 9
I got it.

(2) Second step (9→Ao) 11F, 37 of 2-(2,Hiro-di-t-amylphenoxy)butanoyl chloride was added dropwise to the mixture under heating and reflux. 30
The reaction was carried out under reflux for a minute. Cool to room temperature and add 50 ml of ethyl acetate.
y was added and washed with water. The oil layer was separated and the solvent was distilled off under reduced pressure. The residue was recrystallized from ethyl acetate and hexane and 60.
1. ．． I got 7F.

■ 3rd process (to→6/→μ) 60 It, 7y acetonitrile 2jQ go and N.

N-dimethylacetamide 2! 2. Add thionyl chloride to the mixed solvent of Q- at room temperature. ≠1 was dropped.

After reacting for 30 minutes, it was cooled to -10oC. Propylamine 1,7,7P was added dropwise to this solution at 0°C or below. After 30 minutes, ethyl acetate was added and the mixture was washed with water. The oil layer was separated and the solvent was distilled off under reduced pressure. The residue was recrystallized from a mixed solvent of chloroform and hexane to obtain 21.

■ No. ≠ Engineering a (/, 2, AJ) g no Hiromu! , λ and methanol JOOml and hydrochloric acid/! - and heated under reflux for 1 hour. Water 2 after cooling to room temperature
By adding 00g and taking the precipitated crystals, p2r,
I got 63 of ty. The melting point is 273~2/! It was 0C.

Example (5) Synthesis of Compound Example Produced in the same manner (69) using t-butylamine instead of propylamine used in the third step of Example (4).
I got it. The melting point is 2!4cm23! It was 0C.

Example (6) Synthesis of Compound Example 70 (7Q) was obtained in the same manner using aqueous ammonia (2?Aqueous solution of steamed rice) in place of the propylamine used in the third step of Example (4). The melting point was I'19-1jloC.

Example (7) Synthesis of Compound Example 72 In the same manner as in Example (4) up to the second step, 10 was converted to 53°≠
I got 7. Part 53. Hiro's 60 was commonly interpreted as 200 tttl of N,N-dimethylacetamide. Hydrochloric acid (36%) of jO- was added and reacted at room temperature for 3 hours. Water 20, Onl
32 of Schiff 2 by adding and taking the precipitated crystals.
3'p was obtained. Further, by recrystallizing from a mixed solvent of chloroform and hexane, 31 of 72 was obtained. The melting point was 236-23r 0c (dec,).

Claims (2)

[Claims] (1) A 3- compound represented by general formula (III) characterized by treating a compound represented by general formula (IV) below with an acid.
Method for producing phenoxycatechols. (2) The compound represented by general formula (IV) is a reaction product obtained by reacting a compound represented by general formula (I) below with a compound represented by general formula (II) below in the presence of a base, or a reaction product thereof. The method for producing 3-phenoxycatechols according to claim (1), which is a derived compound. General formula (I) ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ General formula (II) ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ General formula (III) ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ General formula (IV) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In the formula, R_1 and R_2 are each phenyl group, carbon number 1
~10 aliphatic group or an aliphatic group having 1 to 10 carbon atoms (R_1 and R_2 represent divalent groups and may be linked to form a ring), and R_3 is an aliphatic group having 2 to 6 carbon atoms. represents an oxycarbonyl group, R_4 represents a substituent having 10 or less carbon atoms that can be substituted on a benzene ring, X represents a halogen atom, R_5 represents a nitro group or a group chemically derived from a nitro group, R_6 represents the same group as R_4 or a group derived from R_4, and R_7 represents R_
Represents the same group as 3 or a group derived from R_3, and a
represents 0 or 1, and b represents an integer from 0 to 2. Here, when b is plural, two R_4 and two R_
Each of 6 represents the same or different, and two R_4 and two R_6 each represent a divalent group and may form a cyclic structure.