Process for preparing 3,4-dihydroxy benzonitrile

Abstract

3,4-Dihydroxybenzonitrile, which is used as a starting compound in the synthesis of pharmaceuticals and agrochemicals, is produced in high yield by chlorination with sulfuryl chloride or a mixture of molecular chlorine and a chlorination accelerator 3,4-methylenedioxybenzonitrile to give 2-chloro-benzo[1,3]dioxole-5-carbonitrile, wherein the chlorination accelerator comprises phosphorus trichloride , phosphorus pentachloride, sulfuryl chloride, thionyl chloride and / or nitrosyl chloride; 2-chloro-benzo[1,3]dioxole-5-carbonitrile is contacted with water to make it hydrolyzed 3,4-Dihydroxybenzonitrile is obtained.

Description

technical field

[0001] The present invention relates to a kind of method for preparing 3,4-dihydroxybenzonitrile. More particularly, the present invention relates to a process for preparing 3,4-dihydroxybenzonitrile from 3,4-methylenedioxybenzonitrile.

[0002] The target product 3,4-dihydroxybenzonitrile is used as a starting material in the synthesis of drugs and agrochemicals, in particular, the compound is used as a starting material in the synthesis of quinazolines as anticancer drugs. Background technique

[0003] As a conventional method for preparing 3,4-dihydroxybenzonitrile from 3,4-methylenedioxybenzonitrile, for example, "Journal of Organic Chemistry" (J.Org.Chem.), 62 , 4097 (1977) discloses a kind of by 3,4-methylenedioxybenzonitrile and lithium diisopropylamide reaction preparation 3,4-dihydroxy The method of benzonitrile, the reaction is carried out at a high temperature of 185 ° C in a reaction medium composed of 1,3-dimethyl-2-imidazolidinone, wherein the...

Examples

Embodiment 1

[0055] 10.00 g (67.97 mmol) of 3,4-methylenedioxybenzonitrile and 50 ml of toluene were added to a 200 ml internal capacity flask equipped with a stirrer, thermometer, dropping funnel and airway under nitrogen atmosphere. Then, 0.96 g (6.99 mmol) of phosphorus trichloride was added to the mixture through a dropping funnel while stirring the resulting mixture in the flask. The resulting mixture was heated to 50°C, and then chlorine gas was continuously introduced into the mixture at this temperature for 3.5 hours through a gas duct.

[0056] After the chlorination reaction, the resulting reaction mixture was cooled to room temperature and then concentrated under reduced pressure to remove toluene.

[0057] The concentrated reaction mixture was then mixed with 50 ml of water, the resulting reaction was heated to 50°C and stirred at this temperature for 30 minutes. After completion of the hydrolysis reaction, the reaction system was cooled to 50°C and stirred at this temperature...

Embodiment 2～5

[0059] In each case in Examples 2 to 5, except that the toluene used as the reaction medium was replaced by the compounds shown in Table 1, and the time of the chlorination reaction was changed as shown in Table 1, 3,4-dihydroxybenzonitrile The preparation methods are all the same as in Example 1.

[0060] The conversion rate of 3,4-methylenedioxybenzonitrile (MDBN) and the selectivity of generating 3,4-dihydroxybenzonitrile (DHBN) are analyzed by the high performance liquid chromatography (absolute calibration curve method) result of gained product Sure. The results are shown in Table 1.

[0061] implement

Example number

reaction medium

when reacting

time (hour)

Transformation of MDBN

Rate (mol%)

Choice of DHBN

Sex (mol%)

2

Xylene

1

99

96

3

tert-butylbenzene

1

99

88

4

ethyl acetate

4

91

81

5

benzene

2

100

...

Embodiment 6

[0066] Under a nitrogen atmosphere, add 1.00 g (6.8 mmol) of 3,4-methylenedioxybenzonitrile and 5 ml of toluene to a glass flask with an internal capacity of 25 ml equipped with a stirrer, a thermometer and a dropping funnel, and stir The mixture was heated to 50° C., and then 3.67 g (27.2 mmol) of sulfuryl chloride were gradually mixed into the heated mixture. The resulting reaction mixture was stirred at 50°C for 8 hours to chlorinate 3,4-methylenedioxybenzonitrile.

[0067] After completion of the chlorination reaction, the reaction mixture containing the chlorination product was mixed with 15 g of ice water and heated to 50° C., at which temperature the hydrolysis reaction of the chlorination product was carried out for one hour.

[0068] After the hydrolysis reaction was completed, the resulting reaction mixture was mixed with 250 ml of acetonitrile to obtain a homogeneous solution. Analyze this solution with high-performance liquid chromatography (absolute calibration c...

technical field

[0001] The present invention relates to a kind of method for preparing 3,4-dihydroxybenzonitrile. More particularly, the present invention relates to a process for preparing 3,4-dihydroxybenzonitrile from 3,4-methylenedioxybenzonitrile.

[0002] The target product 3,4-dihydroxybenzonitrile is used as a starting material in the synthesis of drugs and agrochemicals, in particular, the compound is used as a starting material in the synthesis of quinazolines as anticancer drugs. Background technique

[0003] As a conventional method for preparing 3,4-dihydroxybenzonitrile from 3,4-methylenedioxybenzonitrile, for example, "Journal of Organic Chemistry" (J.Org.Chem.), 62 , 4097 (1977) discloses a kind of by 3,4-methylenedioxybenzonitrile and lithium diisopropylamide reaction preparation 3,4-dihydroxy The method of benzonitrile, the reaction is carried out at a high temperature of 185 ° C in a reaction medium composed of 1,3-dimethyl-2-imidazolidinone, wherein the...

Examples

Embodiment 1

[0055] 10.00 g (67.97 mmol) of 3,4-methylenedioxybenzonitrile and 50 ml of toluene were added to a 200 ml internal capacity flask equipped with a stirrer, thermometer, dropping funnel and airway under nitrogen atmosphere. Then, 0.96 g (6.99 mmol) of phosphorus trichloride was added to the mixture through a dropping funnel while stirring the resulting mixture in the flask. The resulting mixture was heated to 50°C, and then chlorine gas was continuously introduced into the mixture at this temperature for 3.5 hours through a gas duct.

[0056] After the chlorination reaction, the resulting reaction mixture was cooled to room temperature and then concentrated under reduced pressure to remove toluene.

[0057] The concentrated reaction mixture was then mixed with 50 ml of water, the resulting reaction was heated to 50°C and stirred at this temperature for 30 minutes. After completion of the hydrolysis reaction, the reaction system was cooled to 50°C and stirred at this temperature...

Embodiment 2～5

[0059] In each case in Examples 2 to 5, except that the toluene used as the reaction medium was replaced by the compounds shown in Table 1, and the time of the chlorination reaction was changed as shown in Table 1, 3,4-dihydroxybenzonitrile The preparation methods are all the same as in Example 1.

[0060] The conversion rate of 3,4-methylenedioxybenzonitrile (MDBN) and the selectivity of generating 3,4-dihydroxybenzonitrile (DHBN) are analyzed by the high performance liquid chromatography (absolute calibration curve method) result of gained product Sure. The results are shown in Table 1.

[0061] implement

Example number

reaction medium

when reacting

time (hour)

Transformation of MDBN

Rate (mol%)

Choice of DHBN

Sex (mol%)

2

Xylene

1

99

96

3

tert-butylbenzene

1

99

88

4

ethyl acetate

4

91

81

5

benzene

2

100

...

Embodiment 6

[0066] Under a nitrogen atmosphere, add 1.00 g (6.8 mmol) of 3,4-methylenedioxybenzonitrile and 5 ml of toluene to a glass flask with an internal capacity of 25 ml equipped with a stirrer, a thermometer and a dropping funnel, and stir The mixture was heated to 50° C., and then 3.67 g (27.2 mmol) of sulfuryl chloride were gradually mixed into the heated mixture. The resulting reaction mixture was stirred at 50°C for 8 hours to chlorinate 3,4-methylenedioxybenzonitrile.

[0067] After completion of the chlorination reaction, the reaction mixture containing the chlorination product was mixed with 15 g of ice water and heated to 50° C., at which temperature the hydrolysis reaction of the chlorination product was carried out for one hour.

[0068] After the hydrolysis reaction was completed, the resulting reaction mixture was mixed with 250 ml of acetonitrile to obtain a homogeneous solution. Analyze this solution with high-performance liquid chromatography (absolute calibration c...

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