JP3246984B2 - Tertiary butoxyphenethyl chloride and process for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[Object of the invention]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel tertiary butoxyphenethyl chloride and a method for producing the same. The compound of the present invention is useful as a raw material for synthesizing hydroxyphenethyl chloride, which is an intermediate for synthesizing drugs, agricultural chemicals and liquid crystals having a hydroxyphenyl group.

[0002]

2. Description of the Related Art It is conventionally known that phenethyl chloride is obtained by a chlorination reaction of phenethyl alcohol. However, the compound of the present invention has not been described in the literature, and the compound of the present invention is not known.

[0003]

The compounds having a chemical structure similar to that of the tertiary butoxyphenethyl chloride of the present invention include methoxyphenethyl chloride and n-butoxyphenethyl chloride. However, in order to obtain hydroxyphenethyl chloride by dealkylating the aliphatic alkoxyphenethyl chloride such as methoxyphenethyl chloride, it is necessary to use a strong acid such as hydrobromic acid, hydroiodic acid or trifluoroacetic acid. Requires treatment under conditions, and yield and purity are low. In particular, the debutylation reaction of n-butoxyphenethyl chloride is extremely difficult, as shown in Reference Test Examples below. Therefore, development of a raw material and a production method capable of easily producing hydroxyphenethyl chloride is desired. An object of the present invention is to provide tertiary butoxyphenethyl chloride which is useful as a precursor for obtaining hydroxyphenethyl chloride in good yield.

[0004]

Configuration of the Invention

Means for Solving the Problems The present inventors have made intensive studies to solve the above problems. As a result, they have found that tertiary butoxyphenethyl chloride having a tertiary butyl group as a protecting group for a hydroxide group is useful as a raw material for producing hydroxyphenethyl chloride.

That is, the gist of the first invention is that the formula

Embedded image Tert-butoxyphenethyl chloride represented by the formula: A second aspect of the present invention is to produce tertiary butoxyphenethyl chloride (I), which comprises reacting tertiary butoxyphenethyl chloride (II) with thionyl chloride in the presence of a base. About the law.

The method for producing the tertiary butoxyphenethyl chloride (I) of the present invention can be represented by the following reaction formula.

Embedded image

The method for producing the compound of the present invention will be described below. The compound of formula (I) of the present invention can be obtained by reacting with thionyl chloride in the presence of a base. The compound of formula (II) can be obtained, for example, by reacting tertiary butoxyphenyl halide with metal magnesium to form tertiary butoxyphenyl magnesium halide, and reacting it with ethylene oxide (JP-A-1-156939). Can be The compound of formula (II) thus obtained may be used for the reaction with thionyl chloride. The amount of thionyl chloride used is 1.0 to 1.0 of tertiary butoxyphenethyl alcohol.
The molar amount is 1.2 times, preferably 1.2 times. As the solvent, halogenated hydrocarbon solvents such as dichloromethane and dichloroethane are preferable. Examples of the base include trimethylamine, triethylamine and pyridine. This addition amount is preferably 1.5 times the mol of the tertiary butoxyphenethyl alcohol. Reaction temperature is 50-60
° C, preferably 55 to 60 ° C. By setting the temperature in this range, the yield of the compound of the formula (I) is increased.

[0008]

Next, the present invention will be described more specifically with reference to examples and reference examples. Example 1 (Synthesis of p-tert-butoxyphenethyl chloride) A stirrer and a reflux condenser were attached, and 388.5 g (2.0 mol) of p-tert-butoxyphenethyl alcohol was placed in a 2-liter 4-neck flask purged with nitrogen. ), 237.3 g (3.0 mol) of pyridine, 400 ml of methylene chloride
Add. While the mixture was heated to 60 ° C. with a mantle heater and refluxed, 285.6 g (2.4 mol) of thionyl chloride diluted with 200 ml of dichloromethane was added dropwise over 3 hours. Stirring is continued at the same temperature for 6 hours. Next, 800 ml of water is dropped into the reaction solution while cooling the reaction solution, and the mixture is stirred. After mixing, the organic solvent layer is separated. This is neutralized by adding 800 ml of a 5% aqueous sodium carbonate solution. This was dehydrated with anhydrous sodium sulfate, and the solvent was distilled off. The residue was distilled under reduced pressure to obtain 361.6 g (yield: 85.0%) of a liquid having a boiling point of 150 ° C./20 mmHg.

The analytical purity, elemental analysis value and NMR spectrum of this product by gas chromatography were as follows. (1) The analytical purity by gas chromatography is 99.
1%. (2) Elemental analysis value Calculated value C 67.8% H 8.1% Analysis value C 67.5% H 8.0% (3) NMR spectrum

Embedded image δ 1.33 (9H, S, H ^a ) δ 3.00 (2H, T, H ^c ) δ 3.67 (2H, T, H ^d ) δ 6.85 to 7.19 (4H, m, H ^b ) It was identified as tertiary butoxyphenethyl chloride.

EXAMPLE 2 (Synthesis of p-tert-butoxyphenethyl chloride) A 2-liter 4-neck flask equipped with a stirrer and a reflux condenser and purged with nitrogen was charged with 388.5 g of p-tert-butoxyphenethyl alcohol (2 3.0 mol), 303.6 g (3.0 mol) of triethylamine and 400 ml of dichloromethane. This was heated to 55 ° C. with a mantle heater and refluxed, and 285.6 g (2.4 mol) of thionyl chloride diluted with 200 ml of methylene chloride was added dropwise over 3 hours. Stirring is continued at the same temperature for 6 hours. Next, 800 ml of water is dropped into the reaction solution while cooling the reaction solution, and the mixture is stirred. After mixing, the organic solvent layer is separated. This is neutralized by adding 800 ml of a 5% aqueous sodium carbonate solution. This was dehydrated with anhydrous sodium sulfate, and the solvent was distilled off. The residue was distilled under reduced pressure to give a liquid fraction of 358.
2 g (84.2% yield) were obtained. Analytical purity of this product by gas chromatography, elemental analysis value and NMR
The spectrum was consistent with the values of Example 1.

Example 3 (Synthesis of m-tert-butoxyphenethyl chloride) A stirrer and a reflux condenser were installed, and 388.5 g of m-tert-butoxyphenethyl alcohol (28.5 g) was placed in a 2-liter 4-neck flask purged with nitrogen. 2.0 mol), pyridine 237.3 g (3.0 mol), methylene chloride 400 ml
Add. While the mixture was heated to 60 ° C. with a mantle heater and refluxed, 285.6 g (2.4 mol) of thionyl chloride diluted with 200 ml of dichloromethane was added dropwise over 3 hours. Stirring is continued at the same temperature for 6 hours. Next, 800 ml of water is dropped into the reaction solution while cooling the reaction solution, and the mixture is stirred. After mixing, the organic solvent layer is separated. This is neutralized by adding 800 ml of a 5% aqueous sodium carbonate solution. This was dehydrated with anhydrous sodium sulfate and the solvent was distilled off, and distilled under reduced pressure to obtain 350.1 g (yield: 82.3%) of a liquid as a fraction having a boiling point of 146 ° C./19 mmHg.

The analytical purity, elemental analysis value and NMR spectrum of this product by gas chromatography were as follows. (1) The analytical purity by gas chromatography is 99.
1%. (2) Elemental analysis value Calculated value C 67.8% H 8.1% Analysis value C 67.5% H 8.0% (3) NMR spectrum

Embedded image δ 1.33 (9H, S, H ^a ) δ 3.01 (2H, T, H ^c ) δ 3.67 (2H, T, H ^d ) δ 6.61 to 7.20 (4H, m, H ^b ) It was identified as tertiary butoxyphenethyl chloride.

[Reference Production Example] In a 300 ml flask equipped with a stirrer, 106.4 g (0.5 mol) of p-tert-butoxyphenethyl chloride was added, and 150 g of concentrated hydrochloric acid was added dropwise at 20 to 30 ° C. Continue stirring for 2 hours. After the reaction,
This was neutralized with a 5% aqueous sodium carbonate solution, extracted with 300 ml of methylene chloride, and the solvent was distilled off to obtain crude crystals of p-hydroxyphenethyl chloride. Then, distillation was carried out under reduced pressure conditions to obtain 99.5 g of a fraction having a boiling point of 160 ° C./10 mmHg (gas chromatography purity: 99.3%, yield: 93.6%). The melting point of the target product was 56 to 57 ° C, and the infrared absorption spectrum was completely identical to that of the standard p-hydroxyphenethyl chloride.

On the other hand, 21.3 g (0.1 mol) of pn-butoxyphenethyl chloride and 30 g of concentrated hydrochloric acid (0.1 mol) were used.
3 mol) in a 100 ml flask
Stirring was continued for hours, but no change was observed. There was no change even if stirring was continued at the reflux temperature for 5 hours.
Similarly, 30 g of concentrated hydrobromic acid was added, and stirring was continued at the reflux temperature for 5 hours, but no change was observed.

[0015]

Industrial Applicability The compound of the present invention is an intermediate for synthesizing a drug, a pesticide and a liquid crystal having a hydroxyl group, since the tertiary butyl group of the compound of the present invention is easily removed under mild acidic conditions. -Or useful as a raw material for producing p-hydroxyphenethyl chloride. Further, the compound of the present invention can be produced in high yield using tertiary butoxyphenethyl alcohol as a starting material.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-4-173756 (JP, A) JP-A-2-117681 (JP, A) JP-A-1-156939 (JP, A) JP-A-60-1985 149540 (JP, A) JP-A-5-271226 (JP, A) JP-A-5-287022 (JP, A) JP-A-57-181050 (JP, A) JP-A-63-233974 (JP, A) JP-A-63-233975 (JP, A) JP-A-2-134377 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 43/225 C07C 41/22 REGISTRY (STN) CA (STN)

Claims (2)

(57) [Claims] (1) Formula (1) Tertiary butoxyphenethyl chloride represented by the formula: 2. A process for producing tert-butoxyphenethyl chloride, which comprises reacting tert-butoxyphenethyl alcohol with thionyl chloride in the presence of a base.