KR860001310B1 - Process for preparing 2,3-dihydro-2,2-dimethyl-7-benzofuranol - Google Patents

Abstract

The prodn. of 2,3-dihydro-2,2-dimethyl-7-benzofuranol of formula (I) comprises (a) reacting t-butyl catechol or catechol with isobutyraldehyde in the presence of an oxide, hydroxide, alcoholate or carboxylate of a metal of Gps. IA, IIA, IIB, or VIIB of the Periodic Table; (b) rearranging the prods., opt. after removing low boiling components, by contact with an acidic compd.; and (c) recovering (I), opt. after further treatment. (I) is used for the prodn. of the pesticide 'Carbofurn'.

Description

2, 3-bihydro-2, 2-dimethyl-7-benzofuranol

The present invention relates to a process for the preparation of 2, 3-bihydro-2, 2-dimethyl-7-benzofuranol.

The compounds of this 2, 3-bihydro-2, 2-dimethyl-7-bendofuranol are 2, 3-bihydro-2, 2-dimethyl-, a potent pesticide known under the trade name CARBOFURAN. It is an especially useful intermediate for the synthesis of 7-bendofuranyl catamate.

Many methods are known in the art for the preparation of 2, 3-bihydro-2, 2-dimethyl-7-bendofuranol.

For example, as described in US Pat. No. 3,320,286, the reaction of 0-nitrophenol and metalyl chloride is followed by the resulting phenolic etherol clatirene potential reaction and the nitro group being a hydroxyl group. It is known to convert to.

However, this process is complicated and the raw material is expensive. Another method is to react catechol with metalyl chloride to yield 2-oxymetall-phenol, and then to Klyzen transpose of the 2-oxymetall-phenol in the presence of an acidic catalyst. 932, 458 and European Published Application Nos. 40 and 400. This method has the drawbacks of low selectivity of useful reaction products and expensive metalryl chlorides.

Another method is to react catechol with isobutyraldehyde to give 2-isopropyl-1,3-benzodioxol as intermediates, which then undergo isomerization on a catalyst of magnesium chloride and pd / C. , 118, 400. While this method has a relatively good selectivity of useful reaction products, it is not satisfactory because the second reaction step is complex and the conversion rate is low.

Accordingly, an object of the present invention is to provide a method for preparing 2, 3-bihydro-2, 2-dimethyl-7-benzobutanol, which overcomes the above-mentioned drawbacks.

The process according to the invention is carried out in catechol or 4-tert. By preliminary reaction between butylcatechol and isobutyraldehyde, the product obtained therefrom is reacted with the catalyst amount of at least one acidic compound and optionally subjected to final treatment to obtain the desired product.

According to the present invention, a method for preparing 2, 3-bihydro-2, 2-dimethyl-7-benzobutanol is used as a starting material of 4-tert. There are various processes depending on whether butyl catechol or catechol is selected.

Therefore 4-tert. When butylcatechol and isobutyraldehyde are reacted together, the method can be divided into the following steps:

4-tert for isobutyraldehyde in the first reaction step. The molar ratio of butyl catechol is at least 0.3: 1 and the reaction temperature range is 80-200 ° C. in the group consisting of oxides, hydroxides, alcoholates and carboxylates of the metals belonging to the IA, IIA, IIB and VIIB groups of the periodic table. 4-tert. In a liquid inert organic solvent, optionally in the presence of a catalytic amount of at least one compound selected, that does not react with other components in the reaction medium. Butylcatechol and isobutyraldehyde were reacted to produce intermediates 1, 1-bis (2, 3-bihydroxy-5-tert. Butylbenzene) -dimethylmethane and 4-tert. A mixture of butyl-6-isobutenylcatechol is obtained;

In the second reaction step, the inert solvent and the unreacted isobutyraldehyde are optionally removed from the reaction mixture produced in the first step, and then the mixture is subjected to a catalytic amount of at least one compound of an organic acid or an inorganic acid and a temperature of 180-250 ° C. The reaction was carried out under reduced pressure at a temperature to give 2, 3-nonhydro-2, 2-dimethyl-5-tert. Butyl-7-benzofuranol and 4-tert. Vaporization products such as butylcatechol are vaporized. 2, 3-bihydro-2, 2-dimethyl-5-tert. Butyl-7- benzofuranol is recovered separately;

-2, 3-bihydro-2, 2-dimethyl-5-tert in the third step. Butyl-7-benzofuranol is dealkylated under catalyst to afford nonhydro-2, 2-dimethyl-7-benzofuranol.

The reactions that produce the desired reaction product can be summarized in the following reaction forms.

First step:

Second step:

Third step:

First step

According to the invention, in the first reaction step 4-tert. The molar ratio of butylcatechol and isobutyraldehyde is used in the range of 0.3: 1-2: 1, but the preferred molar ratio is 0.4: 1-1: 1.

In addition, the most preferred types of catalysts in the first reaction stage include oxides such as sodium, calcium, magnesium, zinc, and manganese, hydroxides, alcoholates, and carboxylates. Examples of such catalysts include sodium methylate and calcium oxide. These catalysts are 4-tert. It shows activity in an amount of 0.3-1-% relative to butylcatechol, but a suitable range is 0.5-9 wt.%. The reaction temperature is generally 80-180 ° C, with a suitable range of 110-160 ° C. The relative reaction time depends on the temperature or catalyst chosen, typically 1-10 hours.

The first reaction step is carried out without the addition of an organic solvent to obtain a high yield for the effective volume of the reactor.

According to another specific example of the present invention, the first reaction step is carried out using an inert organic solvent which is active under the reaction conditions. Suitable solvents include hydrocarbons, alcohols, ethers, nitriles, and the like.

In the first reaction step, the mole produced as the main product is continuously removed from the reaction mixture. According to a suitable embodiment, the water is continuously removed for azeotropic distillation together with the organic solvent used as the reaction medium.

The reaction mixture produced in the first reaction stage can be used for the potential reaction in the second stage. According to a preferred example, the desired compound is obtained from the mixture by removing the isobutyraldehyde remaining without solvent or reaction by distillation in advance.

Second step

In the second reaction step, the reaction mixture which raises the compound stated as obtained in the first step is contacted with the catalytic amount of at least one base compound of acidic organic or inorganic quality. Catalysts suitable for this purpose can be selected from sulfuric acid, phosphoric acid, potassium hydrogen sulfate, acid alumina, acid zeolite, P-toluenesulfonic acid. Of all these, phosphoric acid (H ₃ PO ₄ ) is suitable or 50-100% of the concentration of liquid phosphoric acid with high stability under reaction conditions is used.

The amount of catalyst added should be more stoichiometric than the amount of catalyst used in the first reaction step. The amount of catalyst used in the second stage includes 1-10% by weight of the reaction intermediate produced in the first stage in addition to the amount used to neutralize the catalyst of the first stage. Preferred values for the catalysts of the second stage are 2-5% by weight of the intermediate as described above. The reaction temperature range of the second stage is 180-250 ° C, but a suitable range is 200-250 ° C.

An important point of the process according to the invention is 2, 3-bihydro-2, 3-dimethyl-5-tert. Butyl-7-benzofuranol and 4-tert. Potential reaction products, such as butylcatechol, are produced, which are subsequently removed in the form of a vapor.

Therefore, the reaction is carried out under reduced pressure to ensure complete removal as possible. Due to the temperatures given above, the suitable pressure range for this purpose is 5-50 mmHg.

Third step

2, 3-bihydro-2, 3-dimethyl-5-tert. 4-tert butyl-7-benzofuranol. It is preferable to carry out the dealkylation reaction for this compound after separation from butylcatechol.

In particular, the dealkylation reaction is carried out in 2, 3-bihydro-2, 3-dimethyl-5-tert. Butyl-7-benzofuranol is carried out by heating to about 200 ° C. in the presence of 3-10 wt.% Of a catalyst for dealkylation selected from acidic alumina and phosphoric acid.

In fact, this operation is carried out by distilling 2, 3-bihydro-2, 3-dimethyl-7-benzofuranol continuously in a medium that affects the dealkylation reaction.

If catechol is used as a starting product, the preparation of 2, 3-bihydro-2, 3-dimethyl-7-benzofuranol is divided into the following steps.

In the first reaction step, the mole ratio of catechol to isobutyraldehyde is at least 1: 1 in the reaction temperature range of 80-180 ° C., with oxides, hydroxides and alcoholates of metals belonging to groups IA, IIA, IIB and VIIB of the periodic table. In the presence of a catalytic amount of at least one compound of the carboxylate, catechol and isobutyraldehyde are reacted in a liquid organic solvent which is inert to the other components of the reaction medium to react with intermediates 1, 1-bis (2, 3-bihydroxybenzene Dimethyl ethanol;

-Separate one or more low boiling compounds from the reaction mixture of the first stage, if necessary;

The intermediate obtained in the first step vaporizes the reaction mixture in which the reaction mixture from which one or more low boiling point compounds have been removed as necessary and at least one catalytic amount of an acidic organic or inorganic compound is reacted under reduced pressure at 180-250 ° C. under a reduced pressure. ;

-2, 3-nonhydro-2, 3-dimethyl-7-benzofuranol is separated and recovered from the vaporized dislocation product;

The production reaction of 2, 3-bihydro-2, 3-dimethyl-7-benzofuranol according to the present invention can be summarized by the following scheme.

First step

In the first reaction step according to the present invention, the molar ratio of catechol to isobutatealdehyde is in the range of 1: 1-3: 1 and the preferred mole ratio is about 2: 1.

The most suitable catalysts for the first stage of reaction are oxides, hydroxides, alcoholates, carboxylate compounds such as sodium, calcium, magnesium, zinc, manganese. Examples of such catalysts are calcium oxide, sodium methylate and zinc acetate. These catalysts are added in amounts of 0.2% to 5% by weight to catechol, with a preferred range of 0.3-2.5% by weight.

The reaction temperature is generally in the range of 80 ° C to 180 ° C and the preferred temperature range is 110 ° C to 160 ° C.

The relative reaction time, which is a function of the preselected catalyst and temperature, generally ranges from 1 hour to 10 hours.

The reaction of the first step is carried out without the addition of the organic solvent, so that a high yield can be obtained for the reactor of the same volume.

Another specific example of the present invention is that the first reaction step is carried out in the presence of an inert organic solvent in which no reaction occurs under the reaction conditions.

Examples of solvents used for this purpose are hydrocarbons, alcohols, ethers and nitriles and the like.

Water produced as a by-product from the first reaction stage is removed from the reactants as it is produced. The most suitable specific method is to remove water continuously by azeotropic distillation together with the organic solvent which is a reaction medium.

The reaction mixture from the first stage may be used for the second stage of potential reaction or the catechol is pre-separated with one or more low boiling compounds such as water, solvents and unreacted isobutyraldehyde.

Second step

In the second reaction stage, the reaction mixture from one or more low boiling point compounds, obtained from the first stage, is reacted with at least one catalytic amount of organic and inorganic acid compounds. Suitable catalysts for the purpose are selected from sulfuric acid, phosphoric acid, potassium hydrogen sulfate, acid alumina, acid zeolite and P-toluene sulfonic acid. Above all, phosphoric acid is suitable, or aqueous phosphoric acid is suitable for the concentration of 50% -100% since it shows remarkable stability under the reaction conditions.

The amount of catalyst deposited is more stoichiometric than the amount of catalyst used in the first step. In particular, the second stage catalyst should be added in an amount necessary for the neutralization of the first stage catalyst, in an amount of about 1-10 wt.% Relative to the intermediate produced in the first stage. Suitable catalyst concentration values range from 2% to 5% for the intermediates described above.

The reaction temperature of the second stage is in the range of 180 ° C. to 250 ° C., and a suitable range is between 200 ° C. and 250 ° C.

An important point of the process according to the invention is the removal of the reaction product of catechol and 2, 3-bihydro-2, 3-dimethyl-7-benzofuranol from the reactants continuously in the vapor phase to produce. Therefore, the reaction should be carried out under fitting so as to eliminate it as completely as possible. The pressure range according to the above temperature range is useful in the range from 10 mmHg to 50 mmHg.

The reaction product thus obtained is condensed and then treated by conventional separation and purification methods.

The experimental examples below are for illustrative purposes and do not limit the invention.

Example 1-6: (4tert. Butyl-Catechol)

Example 1 (First Step)

71.4 g (0.43 mole) 4-tert in a 250 ml flask equipped with a magnetic stirrer and Marcusson's reflux device. Fill with butyl-catechol, 86 ml (68.3 g, 0.95 mole) of isobutyraldehyde, 6.4 g (0.118 mole) sodium methylate, and 160 ml toluene.

The mixture is boiled at about 120 ° C. under atmospheric pressure to remove it as an azeotrope as water is produced as a reaction byproduct. The reaction is stopped after about 9 hours, at which time about 6 ml of water is removed. In doing so, toluene and unreacted isobutyraldehyde are distilled from the reaction mixture. The remaining reaction mixture thus obtained has the following composition:

4-tert. Butyl catechol: 0.003 mol. 4-tert. Butyl-6-isobutenylcatechol: 0.024 mol and 1, 1-bis (2, 3-bihydroxy-5-tert. Butylbenzene) -dimethylethane: 0.08 mol.

The melting point of the last compound is 177 ° C.

The products listed above are identified by group-chromatography, mass spectrometry, infrared spectroscopy, NMR, and the like.

Example 2 (First Step)

249 g (1.5 moles) of 4-tert in 500 ml flask equipped with magnetic stirrer and Marcusson reflux device. Fill with butyl catechol, 170 ml (135 g, 1.87 moles) of isobutyraldehyde, 2 g (0.035 moles) of calcium oxide and 200 ml of toluene. When the mixture is boiled at about 120 ° C. under atmospheric pressure, water is produced as a reaction byproduct and removed as an azeotrope.

Toluene and unreacted isobutyraldehyde are removed by distillation from the reaction mixture. The raw reaction mixture thus obtained has the following composition:

4-tert. Butyl catechol: 0.217 mol

4-tert. Butyl-6 isobutenyl catechol: 0.516 mol and 1, 1-bis (2, 3-bihydroxy-5-tert. Butylbenzene) -dimethylethane: 0.38 mol

The melting point of the last compound is 177 ° C. These compounds are identified as in the above examples.

Example 3 (Second Step)

After adding 13.5 g of concentrated phosphoric acid (100%) to the reaction product obtained in Example 1, the temperature outside the reactor was gradually raised to 200 ° C. and distilled to produce a reaction product while maintaining the pressure at 5 mmHg.

4-tert for 2 hours. Butyl catechol: 0.067 mol and 2, 3-bihydro-2, 3-dimethyl-5-tert. 0.309 mole of butyl-7-benzofuranol is distilled off.

The final product has a melting point of 76 ° C. and a boiling point of 130 ° C. (5 mmHg). These products are confirmed by macro liquid chromatography, NMR and mass spectrometry.

Example 4 (Second Step)

10 g of concentrated phosphoric acid (100%) was added to the reaction product obtained in Example 2, and then the temperature outside the reaction tank was gradually raised to 210 ° C. and kept at an absolute pressure of 5 mmHg.

4-tert for 2 hours. Butyl catechol: 0.395 mol and 2, 3-bihydro-2, 3-dimethyl-5-tert. 0.6 mol of butyl-7-benzofuranol is distilled off and the final product has a melting point of 76 ° C. and a boiling point of 130 ° C. (5 mmHg).

This product is identified in the same manner as in the previous example.

Example 5 (third step)

In a 50 ml flask equipped with a magnetic stirrer, 40 g of 2, 3-bihydro-2, 2-dimethyl-5-tert. Fill with butyl-7-benzofuranol (obtained in the previous example) and 4 g of acidic alumina (HA-100-59, commercially known from Akzo Chemie), and raise the temperature outside the reactor to 200 ° C and 35 mmHg. Distillation with rectification under the pressure of This distillate contains 72 wt.% Of 2, 3-bihydro-2, 3-dimethyl-7-benzofuranol with a boiling point of 120 ° C. (20 mmHg) and unreacted 2, 3-bihydro-2, 3-dimethyl. -5-tert. And 27 wt.% Butyl-7-benzofuranol. The selectivity of the dealkylation reaction is 96% for the converted compound.

Example 6 (Third Step)

In a 50 ml flask equipped with a magnetic stirrer, 40 g of 2, 3-bihydro-2, 3-dimethyl-5-tert. Fill with butyl-7-benzofutanol and 1.2 g of 100% phosphoric acid (H ₃ PO ₄ ).

The distillate (37 g) obtained by heating and distilling the mixture in an easy-to-heat manner and in the same manner as in the previous example was obtained at a boiling point of 2, 3-bihydro-2, 3-dimethyl-7-benzobutanol (120 ° C. at 20 mmHg). With 16 wt.% And 2, 3-bihydro-2, 2-dimethyl-5-tert. It contains 83 wt.% Of butyl-7-benzofuranol (unreacted product).

The selectivity of the dealkylation reaction is 95% for the converted compound.

Example 7-9 (Catechol)

Example 7

In a 250 ml steel autoclave equipped with a magnetic stirrer, 165 g (1.5 moles) of catechol, 57.6 g (0.8 moles) of isobutidealdehyde and 0,6 g (0.01 moles) of calcium oxide (CaO) fine powder are placed.

The mixture was heated to 175 ° C. for 7 hours with vigorous stirring, and then cooled to 130 ° C., and the reaction byproduct water was distilled off together with unreacted isobutyraldehyde to distill the unreacted catechol under reduced pressure to about 10 mmHg. do. 85% phosphoric acid (H ₃ PO ₄ ) is added to the remaining mixture and the temperature is gradually raised to 240 ° C-250 ° C while maintaining the pressure at 10mmHg.

Evaporate with 43.5 g (0.27 moles) of 2, 3-bihydro-2, 2-dimethyl-7-benzobutanol catechol for about 4 hours. The total amount of catechol recovered was 118 g (1.07 moles) with a conversion rate of 28.5% based on catechol and selectivity of the useful reaction products 2, 3-bihydro-2, 3-dimethyl-7-benzobutanol. Is 62%.

Example 8

110 g (1 mol) of catechol and 50 ml (39.6 g = 0.55 mol) of isobutidealdehyde, 2.74 g (0.015 mol) in a 250 ml flask equipped with an azeotropic distillation system (Marcusone) and a stirrer Put zinc acetate, 30 ml toluene. The mixture is boiled at 120 ° C. for 7 hours to remove about 10 ml of water.

Toluene and unreacted isobutyraldehyde are distilled off from the reaction mixture under a pressure of 30 mmHg. 7.4g of 85% phosphoric acid (H ₃ PO ₄ ) was added to the remaining distillation, and the temperature was raised to 245 ° C. At this time, the pressure was maintained at 20mmHg.

In about 4 hours, 72.5 g (0.66 mole) of catechol and 21 g (0.13 mole) of 2, 3-bihydro-2, 2-dimethyl-7-benzobutanol were evaporated. Thus, the quench rate for catechol is 34% and the selectivity of useful reaction products 2, 3-bihydro-2, 2-dimethyl-7-benzofutanol is 37.5%.

Example 9

165 g (1.5 moles) of catechol, 85 ml (67.32 = 0.93 moles) of isobutidealdehyde, 1 g (0.018 moles) of calcium oxide (CaO) in a 250 ml flask equipped with a stirrer and a reflux system to remove water by azeotropic distillation Add 40 ml of toluene.

The mixture is boiled to 120 ° C. for 8 hours, and about 14 ml of water is lost in the process.

Toluene and isobutyraldehyde of this reaction are distilled off from the reaction mixture while maintaining an absolute pressure of 30 mmHg. After distillation, 9.4 g of 85% phosphoric acid (H ₃ PO ₄ ) was added to the residue, and the temperature was raised to 245 ° C. and the pressure was maintained at 20 mmHg.

In about 4 hours, 92 g (0.84 mole) of catechol and 50 g (0.31 mole) of 2, 3-bihydro-2, 2-dimethyl-7-benzofuranol are evaporated.

The conversion for catechol is therefore 55.7% and the selectivity of the required reaction product (2, 3-bihydro-2, 2-dimethyl-7-benzofuranol) is 46%.

Claims (11)

4-tert. In the presence of at least one compound selected from carboxylates, alcoholates, hydroxides and oxides of metals belonging to groups IA, IIA, IIB, VIIB of the Periodic Table of the Elements. After butyl catechol or catechol and isobutyraldehyde is pre-reacted, the low amorphous component is removed, and the resulting product is brought into contact with at least one acidic compound and subjected to a potential reaction, thereby recovering the potential reaction product. 2, 3-bihydro-2, 2-dimethyl-7-benzofuranol. The method of claim 1, wherein 4-tert. In using butylcatechol, 4-tert. Metal belonging to Periodic Tables IA, IIA, IIB and VIIB in the presence of a liquid organic solvent which is not reactive to the reaction medium at a molar ratio of butyl catechol and isobutyraldehyde at 0.3: 1, at a temperature of 80 ° -100 ° C. 4-tert in the presence of a catalytic amount of at least one compound selected from carboxylates, alcoholates, hydroxides and oxides. 1, 1-bis (2, 3-bihydroxy-5-tert. Butylbenzene) dimethylethane and 4-tert, which are intermediates of the reaction of butylcatechol and isobutyraldehyde. A mixture of butyl-6-isobutenylcatechol is obtained, and in the second reaction step, an inert solvent and unreacted isobutyraldehyde are removed from the mixture of intermediates produced in the first step, followed by at least one acidic organic compound or inorganic compound. The reaction was carried out under reduced pressure at a reaction temperature of 180 ° C.-250 ° C. to give the products 2, 3-nonhydro-2, 3, -dimethyl-5-tert. Butyl-7-benzofuranol and 4-tert. The butylcatechol is vaporized and 2,3-nonhydro-2, 2-dimethyl-5-tert. Butyl-7-benzofuranol was recovered, and in the third reaction step, 2, 3-bihydro-2, 2-dimethyl-5-tert. Dehydroalkylation of butyl-7-benzofuranol with catalyst yields nonhydro-2, 2-dimethyl-7-benzofuranol; 2, 3-bihydro-2, 2-dimethyl-7-benzo Method for preparing furanol. The method of claim 2, wherein the amount of catalyst used in the first step is 4-tert. A manufacturing method characterized by using 0.3-10% by weight based on butyl catechol. 3. A process according to claim 2, wherein the second step is carried out in the presence of a catalyst selected from sulfuric acid, phosphoric acid, forsyrium bisulfate, acid alumina, acid zeolite and p-toluenesulfonic acid. The process according to claim 2, wherein the amount of catalyst used in the second step is 1-10% by weight based on the intermediates obtained in the first step. The process according to claim 2, wherein the third step is carried out in the presence of a catalyst selected from acidic alumina and phosphoric acid. The process according to claim 2, wherein the amount of catalyst used in the third reaction step is 3-10% by weight. The method according to claim 1, wherein in the use of catechol as a starting material, the catechol and isobutyraldehyde are 1: 1 in a molar ratio in the first reaction step, and are reactive with other components of the reaction medium at a temperature of 80 ° -180 ° C. The reaction intermediate is reacted with catechol and isobutyraldehyde in the presence of a catalytic amount of at least one compound selected from carboxylates, alcoholates, hydroxides and oxides of metals belonging to the Periodic Tables IA, IIA, IIB, and VIIB in the presence of an organic solvent. Obtain 1,1-bis (nonhydroxybenzene) methyl ethane,-separate one or more low boiling compounds from the reaction mixture in the first reaction step,-in the second reaction step, one or more low boiling compounds At a temperature of 180 ° C.-250 ° C. with the catalytic amount of the inorganic compound, the reaction mixture was subjected to a potential reaction of the intermediate obtained in the first reaction step, 2, 3-nonhydro- characterized in that the reaction product is vaporized to produce a reaction product, and separated and recovered 2, 3-bihydro-2, 2, -dimethyl-7-benzofuranol as a vaporized potential reaction product. 2, 2-dimethyl-7-benzofuranol. The method according to claim 8, wherein the amount of catalyst used in the first step is 0.2-5% by weight based on catechol. The method according to claim 8, wherein the catalyst used in the second step is selected from sulfuric acid, phosphoric acid, potassium bisulfate, acid alumina, acid zeolite and P-toluenesulfonic acid. The method according to claim 8, wherein the amount of catalyst used in the second step is 1-10% by weight based on the intermediate compound obtained in the first step.