JPS61148149A - Production of 2-acylamino-5-alkyl-4,6-dihalogenophenol - Google Patents

Abstract

PURPOSE:To obtain a compound useful as an intermediate for synthesizing a cyan coupler for a color photograph from easily obtainable raw materials in high yield easily, by reacting a 2-acylamino-5-alkylphenol with a halogenating agent. CONSTITUTION:A 2-acylamino-5-alkylphenol shown by the formula I (R1 is aliphatic group; R2 is aliphatic group, or aromatic group) is reacted with a halogenating agent (e.g., sulfuryl chloride) in a solvent such as dioxane, etc. at 0-100 deg.C preferably at <=40 deg.C for 0.5-4hr, to give the aimed substance shown by the formula II. The compound shown by the formula I is obtained by re arrangement reaction of an oxime compound shown by the formula III. The compound shown by the formula II is hydrolyzed by a conventional procedure, and a 2-amino-5-alkyl-4,6-dichlorophenol (or its salt) can be derived.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention relates to a 2-acylamino-5-furkyl-4,6-dihalogeno phenol compound useful as a cyan coloring agent (coupler) for color photography or an intermediate thereof. Relating to a manufacturing method.

(Prior art) 2-amino-5-alkyl-4,6-cyclophene/-
(or its hydrochloride) and 2-acylamino-5-furkyl-4,6-dichlorophenol are as follows:
Regarding 2-amino-4,6-dichloro-5-methylphenol only, U.S. Pat.
No. 4-73742, Japanese Patent Publication No. 50-39654, and Japanese Patent Application Laid-Open No. 51-95032.

(Problems to be solved by the invention) That is, US Patent No. 280,171 and Japanese Patent Application Laid-open No. 1983
The method of No. 73742 is to dichlorinate the following process formula % and then reduce the nitro group to obtain 2-amino-4,6-dichloro-5-methylphenol.

Reaction Scheme (1) However, there is no industrially easy synthesis method for 2-nitro-5-methylphenol, which is the starting material, and it is difficult to obtain the raw material using this method.

Also, Japanese Patent Publication No. 50-39654, Japanese Patent Publication No. 51-9503
In method No. 2, 4-chloro-
3-Methylphenol is sulfonated, then chlorinated, and first the sulfone group is replaced with a nitro group using nitric acid,
2-amino-4,6-dichloro-5-methylphenol is obtained by reduction of the nitro group.

Reaction Scheme (2) However, even in this method, the problem of difficulty in obtaining starting materials as described above could not be avoided. That is, the starting material 4-chloro-3-methylphenol is produced by chlorinating the 4-position of 3-methylphenol, but the regioselectivity in this case is low and therefore purification is required, resulting in a low yield. For example, using the above equation (2), 3-
Ethylphenol is added as a starting material and 2-amino-4゜6-
The total yield of dichloro-5-ethylphenol was 35%. That is, in the step of chlorinating 3-ethylphenol to obtain 3-ethyl-4-chlorophenol, selective chlorination to the 4-position is difficult, and the reaction product contains the chloroform at the 6-position and the chloroform at the 4,6-position. - Many dichloro compounds were mixed in, and as a result of rectification, the yield of the target 3-ethyl-4-chlorophenol was 53%. The yield of the step of obtaining 2-amino-4,6-dichloro-5-ethylphenol hydrochloride was 71.1%. Therefore, the method of reaction scheme (2) above cannot be said to be a generally applicable method for producing 2-amino-5-furkyl-4゜6-dichlorophenol when 3-alkylphenol is used as a starting material. Ta.

Therefore, easily available compounds can be used as starting materials, and 2-ami/-5-furkyl-4,6-dichlorophenol or 2-7-sylami-5-alkyl-4゜6-dichlorophenol can be easily carried out industrially. There is a demand for the development of a manufacturing method.

The object of the present invention is to provide 2-acylamino-5-alkyl-4
, 6-cyhalogenophenol and 2-amino-5-furkyl-4,6-cyhalogenophenol (or its hydrochloride) easily and in high yield. .

(Means for solving the problem) The present inventors have discovered the above-mentioned 2-7sil-5-alkyl-4,
As a result of various studies to overcome the drawbacks of conventional production methods for 6-dichlorophenol, we found that after acylating the 6-position of 3-alkylphenol, this acyl group was reacted with hydroxylamine to form an oxime compound. By using the process of converting the substituent of
Acylamino-5-alkylphenol can be obtained in good yield, and the 2-acylamino-5-alkylphenol can be obtained in good yield.
It was discovered that the desired 2-acyl-5-furkyl-4,6-dahaloke/phenol could be produced in good yield by halogenating alkylphenol.9 The present invention was made based on this finding. It is something.

That is, the present invention uses 2-7 sylamino-5-furkylphenol represented by the general formula (wherein R represents an aliphatic group and R2 represents an aliphatic group or an aromatic group) as a halogenating agent. 2-7, characterized in that the reaction yields a compound represented by the general formula (R and R have the same meanings as above, x1 and x2 represent halogen atoms such as chlorine, bromine, fluorine, iodine, etc.) A method for producing cylamino-5-furkyl-4,6-cyhalogenophenol is provided.

The reaction process for synthesizing 2-7 sylamino-5-furkyl-4,6-cyhalogenophenol and furthermore 2-ami7-5-furkyl-4,6-cyhalogenophenol from 3-phenol by applying the method of the present invention is It can be expressed by the following equation (3).

Reaction scheme (3) (IV) (V) , M
(1) Xl (b)
(In) (R, R, x and x2 have the same meanings as above) That is, in the method of the present invention, the compound represented by general formula CI) can be synthesized through steps 1 to 3.

In step 1, the starting material 3-alkylphenol (
R1 in IT) includes a substituted or unsubstituted aliphatic group, and is a linear, branched or cycloaliphatic group having 1 to 20 carbon atoms, such as m-cresol, 3-ethylphenol, 3- n-propylphenol, 3-isopropylphenol, 3-tart-butylphenol, 3-
Cyclohexylphenol, 3-pentadecylphenol and the like are preferably used. R2 includes a substituted or unsubstituted aliphatic group or aromatic group and has a carbon number of 1 to 18
A straight chain, branched chain, or cycloaliphatic group is preferable. When the compound of general formula (II) is directly used as a cyan coupler, it is preferable that R2 has a large number of carbon atoms. In order to introduce oil-solubilizing groups,
To form an amine (or its hydrochloride) (■), R2
Since C0- corresponds to a protecting group for an amino group, R2 is preferably a methyl group, an ethyl group, a phenyl group, or the like.

Step 1, i.e. 6 of 3-alkylphenol (IV)
Acylation at this position can be carried out by a Friedel-Crach reaction with an acid chloride or an acid anhydride in the presence of a Lewis acid such as aluminum chloride, or by Fries rearrangement of the 0-acetyl form of 3-alkylphenol. In order to maintain high regioselectivity to the 6-position, Fries rearrangement is preferred.

Fries Relocation is by Organic Reactions (Or
ganic Reactions) Volume 1, No. 342
This can be done according to the method described on page 1. That is,
As a solvent, halogenated hydrocarbons (for example, chlorobenzene, dichlorobenzene, tetrachloroethane, tetrachloroethylene, etc.), nitrobenzene, carbon disulfide, etc. can be used, but it is advantageous to carry out the reaction without a solvent.The reaction temperature is 25 Although the reaction can be carried out at a temperature in the range of .degree. C. to 200.degree. C., it is preferably carried out at a temperature of 80.degree. C. or higher, particularly 100.degree. C. or higher, from the viewpoint of reaction rate and regioselectivity. It is particularly advantageous to use aluminum chloride in a molar amount of 1 to 1.5 times the amount of 3-alkylphenol. Other reaction conditions can be appropriately determined according to conditions for general Fries rearrangement reactions.

Step 2 can be carried out by reacting compound (V) with hydroxylamine or a salt thereof, such as a hydrochloride.

Step 3 can be carried out by subjecting the oxime compound (VI) to a rearrangement reaction in the presence of a catalyst.

In this step 3, an acid such as a protonic acid or a Lewis acid, or a chloride such as an acylating agent is used as a catalyst. Preferred examples of such catalysts include sulfuric acid,
Examples include hydrochloric acid, polyphosphoric acid, formic acid, boron trifluoride, phosphorus pentachloride, phosphorus oxychloride, thionyl chloride, P-)luenesulfonyl chloride, and the like. From the viewpoint of yield, it is preferable to use phosphorus oxychloride.The reaction temperature ranges from 0°C to 1°C.
The reaction solvent is preferably a polar aprotic solvent such as, but not limited to, acetonitrile or dimethylformamide. An oxazole compound represented by the following formula (R and R2 have the same meanings as above) is produced as a by-product, which can be converted to acyl amide 7 compound (I) by hydrolysis with an acid.

In the present invention, the acyl amide 7 compound (I) thus obtained is halogenated as shown in step 4. In the present invention, as a cyan coloring agent (coupler) for color photography, X and x2 are chlorine. Atom or bromine atom is preferred, and chlorine atom is particularly preferred.

In the case of chlorination, the halogenating agent used in this case includes chlorine, sulfuryl chloride, hypochlorous acid, t-butyl hypochlorite, cupric chloride, titanium tetrachloride, and the like. Sulfuryl chloride is preferred because it is easy to handle. When sulfuryl chloride is used, the solvent may be dioxane or a halogenated hydrocarbon (for example, methylene chloride, chloroform).

carbon tetrachloride, etc.) can be used. In this case, the use of dioxane is advantageous in terms of simplifying the post-processing because it can be poured into water after the reaction is completed to produce crystals.

The halogenation reaction temperature is carried out in the range of 0°C to 100°C, but since 1 coloration tends to occur at high temperatures, it is preferable to carry out the reaction at 40°C or lower, and the reaction time is in the range of 0.5 to 4 hours. .

Further, bromine is used as the brominating agent, and the reaction can be carried out in the same manner as in the case of chlorination.

The amount of the halogenating agent used is 2 to 3 times the mole.

1° Next, in step 5, 2-acylamino-5-furkyl-4
, 6-cyhalogenopher/-le (II) by a conventional method (e.g.
2-7 minnow 5-furkyl-4,6- which is a useful intermediate for cyan color formers by hydrolysis (acid-catalyzed reaction)
It can lead to dichlorophenol (■) (or its salt).

As the acid, protonic acids such as sulfuric acid and hydrochloric acid can be used. When hydrochloric acid is used, the hydrochloride of the amino form is precipitated, so the extraction process is easy and coloration due to oxidation of the amino form can be prevented. The amount of hydrochloric acid is 1 to 10 times the mole of 2-7sil7minor-5-furkyl-4,6-cyhalogenophenol (tl), preferably 3
It is 6 times to 6 times the molar amount. The concentration of hydrochloric acid is 2 moles/apparently 1
In the range of 0 mol/cross, preferably 6 mol/! It is L or more.

Alcohols such as methanol, ethanol, and isopropanol can be used as the solvent.

The temperature is preferably 40°C or higher, more preferably the reflux temperature of the solvent used.

Incidentally, in each of the above reaction steps, the desired compound obtained may be subjected to the reaction without being isolated in any way, but it is usually isolated and purified by appropriate isolation means. Examples of such means include solvent extraction, recrystallization, filtration, and column chromatography.

(Effects of the Invention) According to the method of the present invention, 2-7 sylamino-5-furkyl-4,6-cyhalogenophenol can be obtained in high yield. Furthermore, the starting material 2-acylamino-5-
Alkylphenol can be synthesized by a simple method from readily available 3-alkylphenol. Therefore, the total yield from 3-alkylphenol, which is the first starting material, is also high.

For example, using this method, when R1 is an ethyl group in the general formula (I), the desired product can be obtained from 2-amino-5-ethyl 4,
The yield to 6-dichlorophenol hydrochloride (compound ①) exceeds 50%. Even when R1 is another alkyl group, the target product (compound ■) can be obtained in high yield using the corresponding 3-alkylphenol as a starting material, making the present invention extremely versatile compared to conventional methods. It is clear that this is a highly efficient manufacturing method.

Furthermore, since there are few by-products in each step, purification is easy and it is suitable as a method to be carried out commercially.

(Example) Next, the present invention will be explained in more detail based on examples.

Example 1 Example 1 (Synthesis of 2-acetylamino-5-ethylphenol) 1) Synthesis of 2-7cetyl-5-ethylphenol Dissolve 50g of 3-ethylphenol in 100mJL of acetonitrile and 57mM triethylamine and stir. While doing so, 46 g of anhydrous vinegar was added dropwise over 15 minutes. After 0 dropwise addition, the mixture was stirred for about 1 hour, extracted with ethyl acetate, and washed with water. After drying over anhydrous sodium sulfate, the solvent was distilled off to obtain 72 g of a colorless oil.

72 g of this oily substance was heated and stirred at an external temperature of 150° C., and 70 g of aluminum chloride was added little by little thereto. 1
After stirring for 5 minutes, the mixture was cooled from 60° C. to 70° C., and 300 mfL of ethyl acetate was added to dissolve the contents. This ethyl acetate solution was poured into ice water, extracted, washed with water, concentrated, and then evaporated under reduced pressure to obtain 2-acetyl-5-ethylphenol (b
, p, 113-115°C/9 mm Hg)
57 g was obtained (yield 85%).

2) Synthesis of 2-hydroxy-4-ditylacetophenone oxime 56 g of 2-7 cetyl-5-ethylphenol.

56 g of sodium acetate was mixed with 200 mJ1 of ethanol and dissolved in water at 150°C.

32g of hydroxylamine hydrochloride was added.

After heating under reflux in a steam bath for 2 hours, the mixture was cooled and poured into ice water to precipitate crystals. This was collected by filtration, washed with water, and dried to obtain 56 g of 2-hydroxy-4-ethylacetophenone oxime (layer, 9.88-90°C) (yield: 92
%).

3) Synthesis of 2-7cetylamino-5-ethylphenol 2-hydroxy-4-ethylacetophenone oxime 5
6 g was dissolved in 50 ml of acetonitrile and 23 mJL of dimethylacetamide, and 15.7 ml of phosphorus oxychloride was slowly added dropwise while keeping the temperature below 20°C. 1 at 25℃
After stirring for an hour, 300 mM of water and 15 mjL of concentrated hydrochloric acid were added, followed by stirring at 50°C for 4 hours. After cooling with water, the precipitated crystals were collected by filtration, washed with water, and dried to obtain 2-acetylamino-5
-Ethylphenol (m, p, 161-162°C) 2
1 g was obtained (yield 76%).

Example 2 (Synthesis of 6-amino-2,4-dichloro-3-ethylphenol hydrochloride) 1) Synthesis of 6-acetylamino-2,4-dichloro-3-ethylphenol? 15 g of -acetylamino-5-ethylphenol was mixed with 45 ml of dioxane, and 15 ml of sulfuryl chloride was slowly added dropwise to the mixture while keeping the temperature between 20 and 30°C. 1 at 25℃
．． After stirring for 5 hours, the precipitated crystals were poured into 70 ml of water and filtered, washed with water and then with chilled acetonitrile.
- 18.7 g of ethylphenol was obtained.

2) Synthesis of 6-amino-2.4-dichloro-3-ethylphenol hydrochloride 18.7 g of 6-7cetylamino-2.4-dichloro-3-ethylphenol was dissolved in 25 mft of ethanol,
To this was added 50mM of concentrated hydrochloric acid and 25ml of water. After heating in a steam bath for 2 hours, the ethanol was distilled off under reduced pressure, and when the mixture was cooled with water, hydrochloride precipitated. This hydrochloride was collected by filtration, washed with cold water, and dried to obtain 18 g of 6-7 minnow 2.4-dichloro-3-ethylphenol hydrochloride (yield:
98%).

Elemental analysis I [(I H: 4.25%. C: 39.59
%. M: 5.721 calculated value old 4.18%. C:39
-82L N: 5.78% Example 2 Example 1 (Synthesis of 2-7cetylamino-5-pentadecylphenol) ■) Synthesis of 2-acetyl-5-pentadecylphenol 30.4g of 3-pentadecylphenol was added to 150ml of acetonitrile. and triethylamine 16 were dissolved in 7 mJ1, and 11.2 g of acetic anhydride was added dropwise with stirring. After the dropwise addition, the mixture was stirred for about 2 hours and poured into water, and crystals precipitated. The crystals were collected by filtration, washed with water, and then dried. Next, the crystals were heated from 150° C. to 155° C., and 16 g of aluminum chloride was slowly added. Keep the temperature at 150℃3
After stirring for 0 minutes, the reaction mixture was poured into ice water, and the precipitated crystals were collected by filtration, washed with water, washed with acetonitrile, and dried to give 2-7 cetyl-5-pentadecylphenol (literally, p
, 38-42° C.) 24 g (yield 70%) were obtained.

2) Synthesis of 2-hydroxy-4-pentadecyl acetophenone oxime 24g of 2-7cetyl-5-pentadecylphenol and 11.4g of sodium acetate were mixed in 200mM of ethanol, and hydroxylamine hydrochloride 6 was dissolved in 30ml of water.
．． 4g was added. After heating under reflux using a steam bath for 2 hours, the mixture was cooled and poured into ice water to precipitate crystals. This was collected by filtration, washed with water and dried to obtain 2-hydroxy-4-pentadecyl 7cetophenone oxime (Peng, p. 80-82'C).
) 20g (yield 80%) was obtained.

3) Synthesis of 2-7cetylamino-5-pentadecylphenol? 17 g of -hydroxy-4-pentadecyl acetophenone oxime was dissolved in 35 mjL of acetonitrile and 17 mfL of dimethylacetamide, and 4.7 ml of phosphorus oxychloride was slowly added dropwise while keeping the reaction temperature below 20°C. After stirring at 25°C for 2 days, 10 ml of water and 4 ml of concentrated hydrochloric acid were added.

Stirring was performed at 60°C for 5 days. After cooling with water, the precipitated crystals were collected by filtration, washed with water, and dried to obtain 13 g of 2-7cetylamino-5-pentadecylphenol (107°C) (yield: 78%).

Example 2 (Synthesis of 6-7 cetylamino-2,4-dichloro-3-pentadecylphenol) 6-7 was carried out in the same manner as in Example 2, 1) of Example 1, except that 2-7 cetylamino-5-pentadecylphenol was used. Cetylamine/-2,4-dichloro-3-pentadecylphenol (m.p.l 29 -131'C) was obtained (
yield 89%).

Elemental analysis Actual value H: 8.72%, C: 84-09$
．． N: 3.20% Calculated value H: 8-681. G:84
．． 18L N: 3.251 Example 3 Example 1 (Synthesis of 2-7cetylamino-5-isopropylphenol) ■) Synthesis of 2-acetyl-5-isopropylphenol Except for using 3-isopropylphenol instead of 3-ethylphenol was reacted in the same manner as in 1) of Example 1 to obtain 2-7 cetyl-5-isopropylphenol (yield 89%).

2)? - Synthesis of hydroxy-4-isopropylacetophenone oxime The reaction was carried out in the same manner as in Example 1-2) of Example 1, except that 2-7cetyl-5-isopropylphenol was used instead of 2-acetyl-5-ethylphenol. -Hydroxy-4-isopropylacetophenone (m.p.8
0-82°C) (yield: 86%).

3) Synthesis of 2-7cetylamino-5-isopropylphenol 54g of 2- and droxy-4-isopropylacetophenone oxime, 100ml of 7cetonitrile, 7g of dimethyl
Dissolved in 50 mJL of cetamide and heated at 15°C to 28.2 mJL of phosphorus oxychloride. was slowly dripped. After dripping 2
The mixture was stirred at 5°C for 2 hours, then poured into water and extracted with ethyl acetate. After distilling off the solvent under reduced pressure, the residue was mixed with 200 ml of ethanol, 50 ml of water, and 15 moat salts.
ml was added and stirred at between 40°C and 50°C for 5 hours. After cooling, it was poured into water, and the precipitated crystals were collected by filtration, washed with water, and dried to obtain 40 g of 2-acetylamino-5-isopropylphenol (m.p. 119-120°C) (
yield 74%).

Elemental analysis Actual value N near, 80%, G: 88.40$
, N near, 28% calculated value N near, 82 $, C: 88.
37%, N near, 25% Example 2 (2-7 minnow 4,6-
Synthesis of dichloro-5-isopropylphenol hydrochloride) 2-acetylamino-5-isopropylphenol 20
g was dispersed in 50 mM dioxane, and 20 mJl of sulfuryl chloride was added dropwise over 30 minutes at 20°C or below. After the dropwise addition, the mixture was stirred at 20°C for 2 hours, poured into water, and extracted with ethyl acetate. After distilling off the solvent under reduced pressure, 25 ml of ethanol, 25% water, and 50 ml of concentrated hydrochloric acid were added to the residue.
The mixture was heated and stirred on a steam bath for 2 hours. After cooling on ice, the precipitated hydrochloride was collected by filtration, washed with cold water and acetonitrile, and then dried to obtain 16 g of 2-amino-4,6-dichloro-5-isopropylphenol hydrochloride (yield: 82%).
).

Elemental analysis Actual value H: 4.79%, G: 42.08L
N: 5.50 pieces Calculated value H: 4.71%, C: 42.
13%, N: 5.41$ Example 4 Example 1 (Synthesis of 5-ethyl-2-tetradecanoylaminophenol) 1) Synthesis of 5-ethyl-2-tetradecanoylaminophenol 13.5g of 3-ethylphenol Acetonitrile 50
The mixture was dissolved in 9.4 mJl of pyridine, and 28.6 g of tetradecanoic acid chloride was added dropwise over 20 minutes at room temperature. After stirring for 3 hours, water was added and extracted with ethyl acetate. After washing with water and drying (magnesium sulfate), the solvent was distilled off to obtain a yellow oil. Purification by silica gel column chromatography gave 32.8 g of colorless oil.

32.8 g of this oil was heated to 165° C., and while stirring, 15.8 g of aluminum chloride was added over 10 minutes. After further stirring for 15 minutes, the reaction mixture was allowed to cool, and when the temperature of the reaction mixture reached about 60°C, ethyl acetate and dilute sulfuric acid were added, followed by extraction with ethyl acetate. Wash with water and dry (ffl)
After distilling off the solvent, a yellowish brown oil was obtained, which was crystallized from acetonitrile/ethyl acetate to give 5-ethyl-2-tetradecanoylphenol (m
, p, 40-41"0) 17.8 g were obtained (yield 56.
1%).

2) Synthesis of (5-ethyl-2-hydroxyphenyl)-tridecylketone oxime 5-ethyl-2-tetradecanoylphenol 14.3
g was mixed with 15 g of sodium acetate and 60 mjL of ethanol, and 3.7 g of hydroxylamine hydrochloride dissolved in 17 ml of water was added. After heating under reflux on a steam bath for 8 hours, water was added and extracted with ethyl acetate. washing with water,
After drying, the solvent was distilled off to give a multi-colored oil. This was crystallized from acetonitrile and (5-ethyl-2-hydroxyphenyl)-tridecylketone oxime (m,p
, 38-39°C) was obtained (yield 93%) 3) Synthesis of 5-ethyl-2-tetradecanoylaminophenol 14.1 g of the oxime obtained above was dissolved in 30 ml of acetonitrile.
1. Dissolve in 14 ml of dimethylacetamide and cool with water.
6.45 g of phosphorus oxychloride was added dropwise over 40 minutes.

After stirring for an additional 45 minutes, water was added and extracted with ethyl acetate.

Add 50mJL of ethanol and 150ml of water to the resulting oil.
, 20ml of concentrated hydrochloric acid was added, and the mixture was stirred at 80°C for 7 hours. After extraction with ethyl acetate, washing with water, and drying (magnesium sulfate), the solvent was distilled off to obtain a brown oil. This is n
- Crystallization with hexane revealed that 5-ethyl-2-tetradecanoylaminophenol (Silver, p, 64-64.5
℃) 11.3 g were obtained (yield: 80%).

Elemental analysis Actual value H: 1G, 77$, C near 111.
00%, N: 3.98% Calculated value H: 10.73$,
C Near B, 03%, N: 4.03% Example 2 (Synthesis of 5-ethyl-2,4-dichloro-tetradecanoylaminophenol) 5-ethyl-2-tetradecanoylaminophenol 1
1.3 g was dissolved in 40 ml of chloroform, and 5.74 mJL of sulfuryl chloride was added dropwise over 20 minutes in an ice water bath. After further stirring for 1 hour, 1 sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate. Washing with water, drying (magnesium sulfate)
Thereafter, the solvent was distilled off to obtain a brown oil. Crystallization from n-hexane gave 12.6 g of 5-ethyl-4,6-dichloro-2-tetradecanoylaminophenol 71'C (yield 93%).

Elemental analysis Actual value H: 8.59 $. C: 83.32$
．． N: 3.45$ Calculated value H: 8.47$, G: 83
．． 45! ．． N: 3.38! Comparative example (6-amino-2,
Synthesis of 4-dichloro-3-ethylphenol hydrochloride) 1) Synthesis of 4-chloro-3-ethylphenol 300 g of 3-ethylphenol was dissolved in 720 mjL of methylene chloride, and 208 mJl of sulfuryl chloride was added dropwise at room temperature over 3 hours. ．． After the dropwise addition, the mixture was stirred for 2 hours, and then methylene chloride was distilled off under reduced pressure. removing the residue under reduced pressure; b. p. 15
The fractions at 2-154°C (36 mm Hg) were collected to yield 205 g of 4-chloro-3-ethylphenol (15153%).

2) Synthesis of 2-nitro-4,6-dichloro-5-ethylphenol 306 g of 1,2-dichloroethane and 725 g of dioxa,
2g of the solution was placed in four Lof flasks, and 42g of anhydrous sulfuric acid was added dropwise while cooling to below 525°C. Next, 68.1 g of 4-chloro-5-ethylphenol was added to the mixture in 30 m
1. Dissolved in 2-dichloroethane and added all at once. Thereafter, the mixture was stirred for 1 hour while maintaining the temperature at 50°C. When cooled to 20°C, sulfone crystals precipitated, which were dissolved in 75 ml of water. Next, while maintaining the temperature at 30°C, chlorine gas was passed in an amount approximately 1.1 times the theoretical value. After the blowing of chlorine gas was completed, the mixture was stirred for 3 hours and allowed to stand, and the mixture was poured with 220 m of water. , was added to a solution of 42.8 g of concentrated sulfuric acid at a temperature below 30°C. The lower solvent layer was removed, and 53 g of 62% nitric acid was added dropwise to the aqueous layer while stirring while keeping it at 25 to 50°C. When the mixture was cooled for 1 hour below 5°C, 2-nitro-4.6-dichloro-5-ethyl was obtained. Phenol precipitated. The crystals were collected by filtration, washed with water, and dried. Yield 77.3g (yield 75.3%) *. p. 4
6, 3-47.3°C, elemental analysis: actual value H: 3.0
3%.

3) Synthesis of 2-ami2-4,6-dichloro-5-ethylphenyl hydrochloride Isopropyl alcohol 525mM, 2-nitro4.
125 g of 6-dichloro-5-ethylphenol and 7.5 g of Raney nickel were placed in a civilian autoclave.
The initial hydrogen pressure was set to 10 kg/cm', and stirring was continued at 50°C or below until the theoretical amount of hydrogen was absorbed. The Raney nickel catalyst was filtered from the reaction mixture, 165 g of concentrated hydrochloric acid was added to the filtrate, and the mixture was stirred for 30 minutes at 40 to 50°C to precipitate white crystals. Cool for 1 hour at 5°C or below, collect the crystals by filtration, wash with 140 ml of acetone, dry, and give 2-amino-4.6
-dichloro-5-ethylphenol hydrochloride 112.5g
was obtained (yield 87.5%).

Claims (4)

[Claims] (1) 2-acylamino-5-alkylphenol represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 represents an aliphatic group, and R_2 represents an aliphatic group or an aromatic group.) is reacted with a halogenating agent to form the general formula (R_1 and R_
2 has the same meaning as above, and X_1 and X_2 represent halogen atoms. ) A method for producing 2-acylamino-5-alkyl-4,6-dihalogenophenol, which is characterized by obtaining a compound represented by: (2) An oxime compound in which the 2-acylamino 5-alkylphenol is represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R_1 represents an aliphatic group, R_2 represents an aliphatic group or an aromatic group) 2-acylamino-5- according to claim 1 obtained by rearrangement reaction of
A method for producing alkyl-4,6-dihalogenophenol. (3) Oxime compounds are 2-acyl- represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 represents an aliphatic group, and R_2 represents an aliphatic group or an aromatic group.) 2-acylamino- according to claim 2, which is obtained by reacting 5-alkylphenol with hydroxylamine or a salt thereof.
A method for producing 5-alkyl-4,6-dihalogenophenol. (4) 2-acyl-5-alkylphenol is expressed by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (R_1 represents an aliphatic group) 3-alkylphenol is O-acylated and then subjected to Fries rearrangement, or Alternatively, the method for producing 2-acylamino-5-alkyl-4,6-dihalogenophenol according to claim 3, which is obtained by directly acylating the 6-position.