JP3340760B2 - Para-tert-butoxyphenyldimethylcarbinol and process for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Object of the invention]

[0001]

FIELD OF THE INVENTION The present invention relates to a novel para-tert-butoxyphenyldimethylcarbinol and a process for producing the same.

The compounds of the present invention are useful as intermediates (precursors) of para-tertiary-butoxy-α-methylstyrene, which is an intermediate for pharmaceutical synthesis and a raw material of α-methylstyrene polymer having a hydroxyl group. .

[0003]

2. Description of the Related Art Heretofore, some compounds having a chemical structure similar to the compound of the present invention are known. For example, it is known that para-n-butoxyphenyldimethylcarbinol can be obtained by reacting para-n-butoxyphenyl magnesium chloride with acetone (Chemical Abstract Vol. 106, No. 18324).
a). It is known that dimethylphenylcarbinol is obtained by a reaction between phenylmagnesium halide and acetone.

However, the compound of the present invention has not been described in the literature.

[Problems to be Solved by the Invention] Para-tert-butoxy-α-methylstyrene, which is a raw material for an α-methylstyrene polymer having a hydroxyl group, is composed of para-isopropenylphenylmagnesium halide and tertiary. Obtained by the reaction of butoxyperbenzoate.

However, this synthesis method involves a risk in the operation of the reaction and the yield is low (US Pat.
3,101).

[0007] Therefore, para-tertiary butoxy-α-
Methylstyrene on an industrial scale, without operational danger,
There is a need to develop new precursors to obtain high yields.

An object of the present invention is to provide a novel compound and a technique for synthesizing the same.

[0009]

Configuration of the Invention

Means for Solving the Problems The present inventors have made intensive studies to solve the above problems. As a result, the compound of the present invention having a tertiary butoxy group at the para-position of the phenyl group is a novel compound and can be obtained inexpensively and with high yield. Butoxydimethylcarbinol is converted to 4-hydroxyamino-2-
By treating with a dehydration catalyst such as oxalic acid or potassium hydrogen sulfate in the presence of a polymerization inhibitor such as methyl-2,5-cyclohexadien-1-one, para-tertiary butoxy-α-methylstyrene can be promptly obtained. And found to be useful as a precursor for obtaining para-tertiary-butoxy-α-methylstyrene.

That is, the gist of the first invention is that the formula (1)

Embedded image Tert-butoxyphenyldimethylcarbinol represented by the formula:

The gist of the second invention is that para-tertiary butoxyphenyl halide is reacted with metallic magnesium to obtain para-tertiary butoxyphenyl magnesium halide, which is then reacted with acetone. Thereafter, the present invention relates to a method for producing para-tertiary-butoxydimethylcarbinol, which is characterized by performing hydrolysis by adding ammonium chloride.

The process for producing para-tert-butoxyphenyldimethylcarbinol in the present invention is shown by the following reaction formula.

[0013]

Embedded image (Wherein, X represents a halogen atom)

[0014]

Embedded image (Wherein, X represents a halogen atom)

[0015]

Embedded image

The para-tert-butoxyphenyldimethylcarbinol (1) of the present invention is obtained by reacting para-tert-butoxyphenyl halide (2) with magnesium metal,
A Grignard reagent, para-tertiary-butoxyphenylmagnesium halide (3), which is reacted with acetone and then hydrolyzed by adding ammonium chloride.

Hereinafter, the method for producing the compound of the present invention will be described in more detail.

(A) Synthesis of para-tertiary butoxyphenyl magnesium halide [compound of formula (3)] The compound of formula (3), which is a Grignard reagent, is prepared by stirring activated metal magnesium in anhydrous tetrahydrofuran. It is obtained by dropping the compound of 2) at the reflux temperature of the solvent and continuing stirring for 1 to 8 hours. The metal magnesium used for the reaction is in the form of a commercially available ribbon or shaved metal in a molar amount of about 1 to 2 times the compound of the formula (2).
Prior to the reaction, stirring in a nitrogen atmosphere or under reduced pressure for the purpose of activating the metal magnesium, or reacting with a small amount of iodine, methyl iodide, methyl bromide, dibromoethane, etc., will facilitate the reaction. Is effective in Similar results can be obtained even when the solvent used in the synthesis of the compound of the formula (3) is tetrahydrofuran or diethyl ether alone or a mixed system of benzene and toluene.

(B) Synthesis of para-tertiary butoxyphenyldimethylcarbinol [compound of formula (1)] The compound of formula (1) is obtained by reacting a Grignard reagent (3) with acetone. Acetone may be used in an equimolar amount to the Grignard reagent (3). When the mixture is added dropwise at 20 to 40 ° C. and the stirring is further continued for 1 to 5 hours, the compound of formula (1) is obtained.

After the reaction, an aqueous solution of ammonium chloride is poured to separate the organic layer, which is washed with water, dehydrated with sodium sulfate and distilled off the solvent, and then the desired compound of formula (1) is obtained by distillation under reduced pressure.

Next, the present invention will be specifically described with reference to Examples 1 and 2 and Reference Production Examples.

[0022]

Example 1 29.2 g (1.2 mol) of scraped magnesium metal and 30 ml of anhydrous tetrahydrofuran were added to a 1-liter 4-diameter flask purged with nitrogen, and about 2 ml of ethyl bromide was further added and stirred. , Check the reaction by foaming,
Para-tert-butoxycyclobenzene 184.7 g
(1.0 mol) was dissolved in 400 ml of anhydrous tetrahydrofuran, and this was added dropwise at reflux temperature over 2 hours.
The mixture was further refluxed for 5 hours to obtain a Grignard reagent. When a part of this Grignard reagent was hydrolyzed and analyzed by gas chromatography, the conversion was 99.7.
%Met.

Next, in order to separate the Grignard reagent obtained by the above-mentioned operation from unreacted magnesium after cooling to 30 ° C., the supernatant was filtered through a glass filter and placed in another 1-liter 4-diameter flask. Moved. With stirring, 58.1 g of acetone was added dropwise at 25 to 35 ° C over 1 hour, and stirring was continued at the same temperature for 1 hour.

After the reaction, 300 ml of an aqueous ammonium chloride solution was added with cooling to dissolve the salt formed, and 300 ml of benzene was further added to separate an organic layer.
Dehydrated with sodium sulfate. Then, the solvent is distilled off and the crude
Tertiary butoxyphenyldimethylcarbinol was obtained.

Further, n-hexane was added thereto and recrystallized to obtain 169.3 g of para-tert-butoxyphenyldimethylcarbinol as white crystals (yield: 81.3).
%).

The melting point of this para-tert-butoxydimethylcarbinol was 60.3 ° C., and the analytical purity by gas chromatography was 99.1%. Elemental analysis values and NMR spectra were as follows.

Elemental analysis value

NMR spectrum

Embedded imageδ 1.34 (9H, S, H^a ) Δ 1.57 (6H, S, H^d ) Δ 1.76 (1H, S, H^e ) Δ 7.30 (2H, d, H^c ) Δ 6.89 (2H, d, H^b )

Example 2 In a 1-liter 4-diameter flask purged with nitrogen, 29.2 g (1.2 mol) of scraped metal magnesium and 30 ml of anhydrous tetrahydrofuran were added, and about 2 ml of ethyl bromide was further added, followed by stirring. Check the reaction by foaming,
229.1 g of para-tert-butoxybromobenzene
(1.0 mol) was dissolved in 400 ml of anhydrous tetrahydrofuran, and this was added dropwise at reflux temperature over 2 hours.
The mixture was further refluxed for 5 hours to obtain a Grignard reagent. When a part of this Grignard reagent was hydrolyzed and analyzed by gas chromatography, the conversion was 99.8.
%Met.

Then, in order to separate the Grignard reagent obtained by the above-mentioned operation from unreacted magnesium after cooling to 30 ° C., the supernatant was filtered through a glass filter and placed in another 1-liter 4-diameter flask. Moved. While stirring, 58.1 g of acetone was added dropwise at 25 to 30 ° C over 1 hour, and stirring was continued at the same temperature for 1 hour.

After the reaction, 300 ml of an aqueous ammonium chloride solution was added with cooling and stirring to dissolve the formed salt, and 300 ml of benzene was further added to separate an organic layer. The organic layer was washed with water and dehydrated with sodium sulfate. Then, the solvent was distilled off to obtain crude para-tert-butoxyphenyldimethylcarbinol.

Further, n-hexane was added to this and recrystallized, and 167.9 g of para-tertiary butoxyphenyldimethylcarbinol (yield 80.6) was obtained as white crystals.
%).

The melting point, analytical purity by gas chromatography, elemental analysis value and NMR spectrum of this para-tertiary butoxyphenyldimethylcarbinol are shown in Example 1.
Value.

Reference Production Example Para-tert-butoxy-α-
Synthesis of methyl styrene Para-tert-butoxyphenyldimethylcarbinol 2 was placed in a 1-liter 4-diameter flask equipped with a moisture meter.
08.3 g (1.2 mol) and 200 ml of toluene were added. Further, 10 g of oxalic acid as a dehydration catalyst and 4-hydroxyamino-2-methyl-2, a polymerization inhibitor,
0.2 g of 5-cyclohexadien-1-one was added. While distilling off water under reduced pressure conditions,
Stirred for hours. After the reaction is completed, cool to 30 ° C.
Wash with 1 ml of water, then add 1% aqueous sodium carbonate
After washing with 200 ml, it was dehydrated with sodium sulfate.

Then, the solvent was distilled off to obtain crude para-tert-butoxy-α-methylstyrene.

Further, tertiary butyl catechol as a polymerization inhibitor was added thereto, and the mixture was distilled under reduced pressure conditions.
167.2 g of a 75 ° C./0.2 mmHg fraction (yield 8
7.9%). The analytical purity by gas chromatography was 99.8%, and the elemental analysis value and NMR spectrum were consistent with those of the standard para-tert-butoxy-α-methylstyrene.

[0037]

The compound of the present invention is useful as an intermediate of para-tertiary-butoxy-α-methylstyrene which is a raw material for an α-methylstyrene polymer having a hydroxyl group. In addition, the compound of the present invention can be obtained in a high yield and safely by a simple operation by reacting a Grignard reagent with acetone, and is extremely industrially advantageous.

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-59-42327 (JP, A) JP-A-49-30333 (JP, A) US Patent 4,603,101 (US, A) European Patent Application Publication 465,147 (EP, A1) (58) Field surveyed (Int. Cl. ⁷ , DB name) C07C 43/23 C07C 41/26 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] (1) Formula (1) Para-tert-butoxyphenyldimethylcarbinol represented by the formula: 2. A method of reacting para-tertiary butoxyphenyl halide with metallic magnesium to obtain para-tertiary butoxyphenyl magnesium halide, which is then subjected to acetone, and then subjected to hydrolysis by addition of ammonium chloride. A process for producing para-tertiary butoxyphenyldimethylcarbinol.