CA2258131A1 - Process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives - Google Patents
Process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
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Abstract
The present invention relates to process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives of formula (I) useful as intermediate of agricultural chemicals and pharmaceutical products, wherein X is selected from the group consisting of hydrogen, halogen, hydroxy group, aldehyde group and C1-C6 alkyl group; and R is selected from the group consisting of C1-C6 alkyl group.
Description
CA 022~8131 1998-12-10 PROCESS FOR PREPARING 2,3-DIHYDRO-2-METHYL-2-ALKYLBENZOFURAN DERIVATIVES
BACKGROUND OF THE INVENTION
Technical Field The present invention relates to process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives of the formula(I) useful as intermediate of agricultural chemicals and pharmaceutical products.
~ K ( I ) X
wherein, X is selected from the group consisting of hydrogen, halogen, hydroxy group, aldehyde group and C~~C6 alkyl group; and R is selected from the group consisting of C,~C6 alkyl group.
Description of the Related Art 2,3-Dihydro-2-methyl-2-alkylbenzofuran derivatives of the formula(I) were already known as intermediates of agricultural chemicals such as insecticides and pharmaceutical products. Among the compounds of the formula(I), 2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuran, known as carbofuranphenol, was very useful intermediate of 2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuranyl methylcarbamate as an insecticide.
In addition, 2,3-dihydro-2,2-dimethylbenzofuranaldehyde derivatives were known as intermediate of pyrethroide derivatives which were known in the art as an insecticide[Japanese Patent No. 402,753 A1; European Patent unexamined publication No. 0473,041(1992); German Patent No.2108,932;
European Patent No. 0271,170].
.
CA 022~8131 1998-12-10 A few conventional process for preparing carbofuranphenol was known in the art. For example it was prepared by alkylation of catechol and methallyl halide to 2-methallyloxyphenol which then was cyclized in the presence of a strong acid or Lewis acid at high temperature [U.S. Patent No.
4,380,654; Japanese Patent Kokai Soh 60-100,569; European Patent unexamined publication No. 115,837(1984); Japanese Patent Kokai Soh 58-174,375; Japanese Patent Kokai Pyung 5-835,180; Japanese Patent Kokai Pyung 5-839,679;
Japanese Patent Kokai Soh 58-21,676]. Also carbofuranphenol was prepared by Claisen rearrangement of 2-methallyl oxyphenol which was cyclized in the o presence of a strong acid or Lewis acid at high temperature Uapanese PatentKokai Soh 62-178,580; Brazilian Patent Application No.8301,980; German Patent unexamined publication No.3,027,335(1981)~.
The present invention is accomplished the new and easy process to prepare 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives, which is characterized by the cyclization of 2-(~ - alkylallyl)phenols and 2-(2-alkylpropenyl)phenols, prepared by Claisen rearrangement of (,~
- alkylallyl)oxybenzene.
SUMMARY OF THE INVENTION
The object of the present invention is to provide a new process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives, which may be used for the intermediates of agricultural chemicals and pharmaceutical products such as 2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuranyl methylcarbamate or pyrethroide as an insecticide.
It is to be understood that both the forgoing general description and the following detailed description are examplary and are intended to provide further explanation of the invention as claimed.
CA 022~8131 1998-12-lO
DETAILED DESCRIPTION OF THE INVENTION
The present invention is a process for preparing the compounds of the formula(I), which is characterized by the Claisen rearrangement of (,~
-alkylallyl)oxybenzene derivatives of the formula(II) to give stereoisomers of the formula (III-1) and (III-2), and then cyclization of formula(III-1) and (III-2) in the presence of a catalytic amount of iodine and an inert organic solvent at room temperature, x~ aJ~ R
OH
X5~ ( m-l) X ( III-2) X CRH3 ( I ) wherein, X and R are respectively defined as described above.
In the process according to the present inventon, Claisen rearrangement of (,~ -alkylallyl)oxybenzene derivatives of the formula(II) may be carried out in high boiling solvent or in the absence of solvent at a temperature ranged from 180 ~ to 250 ~C, preferably at a temperature ranged from 210 ~C to 220 5 ~C . Suitably preferred solvents are N,N-dimethylaniline, or dodecane etc..
The reaction products prepared by Claisen rearrangement, which are 2-(~-alkylallyl)phenol derivatives having the formula(III-1) and . .
CA 022~8131 1998-12-lO
W O 97/47615 PCT~KR96/00090 2-(alkylpropenyl)phenol derivatives having the formula(III-2) can occur in any of the possible stereoisomeric configuration. The stereoisomers may be used as the mixtures of stereoisomers or may be used respectively as essentially pure stereoisomer to afford the compound of the formula(I). The stereoisomers of the formular (III-1) and (III-2) can be separated using generally known methods, and were identified by nuclear magnetic resonance spectra, infrared spectra, and mass spectra.
A pure stereoismer or the mixtures of them were cyclized in the presence of a catalytic amount of iodine in an inert organic solvent at room o temperature for ranging from 30 minutes to 4 hours to obtain the compounds of formula(I). In the cyclization, the amount of iodine as catalyst is preferably 0.1 ~ 1 equimolar quantity, more preferably 0.2 equimolar quantity to the compound of the formula(III-1) and/or (III-2). The preferred solvents are hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, toluene, xylene etc The main feature of process according to the present invention is not caused iodocyclization by reacting iodine with 2-methallyl phenol or 2-iosobutenyl phenol~Tetrahedron, Vol. 46, pp. 3321 ~ 3408(1990)]. And the compounds of the formula(I) are obtained quantitatively in mild condition.
The present invention may be illustrated as the following examples.
These examples are for illustrative purposes and are not intended to limit the scopes of the invention.
A. 2-Methallyloxyphenol To a mixture of catechol(22 g, 0.2 mol) in acetone(120 ml ) and N,N-dimethylformamide(30 ml ), were added anhydrous potassium carbonate(14 g, 0.1 mol) and methallyl chloride(20 ml, 0.2 mol) with stirring.
The reaction mixture was heated at reflux for 18 hours. The reaction mixture CA 022~8131 1998-12-lO
was cooled to room temperature and filtered, and the filtrate was concentrated. The residue was dissolved in 2N hydrochloric acid(100 ml), and extracted sequentially with hexane(50 ml x 3 ) and ethyl acetate(50 ml x 3).The organic layer was washed with 20% aqueous sodium hydroxide (50 ml x 5 3), acidified with conc. hydrochloric acid, and extracted with hexane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to provide a crude product, which was purified using silicagel column chromatography to provide 17.8 g of 2-methallyloxyphenol.
o b.p.: 78 ~ 80 ~ / 0.05 torr H NMR(CDCl3): ~ 1.8~s, 3H), 4.46(s, 2H), 4.95(s, lH), 5.05(s, lH), 5.68(br, lH), 6.76 ~ 6.95(m, 4H).
B. 2-Methallyl catachol and 2-isobutenyl catechol A mixture of 2-methallyloxyphenol(15.94 g) and N,N-dimethyl aniline( 15 30 g) was heated at 200 ~C for 1 hour and cooled to room temperature. The reaction mixture was added 2N hydrochloric acid(100 ml), and extracted sequentially with hexane and ethyl acetate(50 ml X 4). The resulting organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was distilled under 20 high vaccum to provide 11.6 g of a mixture of 2-methallyl catachol and 2-isobutenyl catechol(3: 1 molar ratio) as a yellow oil.
Yield(mixture): 73 %
b.p.(mixture): 104 ~C / 0.05 torr 2-methallyl catachol:
25 IH NMR(CDC13) : ~ 1.7(s, 3H), 3.35(s, 2H), 4.85(dd, 2H), 5.7(br, 2H), 6.76(m, 3H).
2-isobutenyl catechol:
'H NMR(CDCl3): ~ 1.68(s, 3H), 1.90(s, 3H), 4.72(dd, 2H), 5.7(br, 2H), 6.76(m, CA 022~8131 1998-12-10 3H).
C. 2,3-Dihydro-2,2-dimethyl-7-hydroxybenzofuran To a mixture of 2-methallyl catachol and 2-isobutenyl catechol(3: 1 molar ratio, 7.75 g) in carbon tetrachloride(50 ml), was added iodine(I2, 2.4 g,0.2 eq.) and stirred at room temperature for 30 minutes. The reaction mixture was diluted with 5% aqueous Na2S2O3 solution until the dark color turned to clear. The resulting organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified using silicagel column chromatography o to provide 6.5 g of 2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuran.
Yield: 84%
b.p.: 84 ~ 85 ~ / 0.002 torr IH NMR(CDCl3): ~ 1.45(s, 3H), 3.0(s, 2H), 5.42(s, lH), 5.7(br, 2H), 6.7(m, 3H).
A. 4-Methallyloxybenzaldehyde To a mixture of 4-hydroxybenzaldehyde(61 ml, 0.5 mol) in acetone( 150 ml) and N,N-dimethylformamide(25 ml), were added anhydrous potassium carbonate(51 g) and methallyl chloride(63 ml, 0.75 mol) with stirring. The reaction mixture was heated at reflux for 18 hours. The reaction mixture was cooled to room temperature and filtered, and the filtrate was concentrated. The residue was dissolved in ethyl ether(100 ml ), and washed sequentially with water, 20% aqueous sodium hydroxide and brine. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified using silicagel column chromatography to provide 76.5 g of a colorless 4-methallyl oxybenzaldehyde .
Yield: 86.8 %
b.p.: 95 ~C / 0.001 torr CA 022~8l3l l998-l2-lO
W O 97/47615 PCTnKR961'~A~9 H NMR(CDCl3): ~ 1.80(s, 3H), 4.45(s, 2H), 4.98(dd, lH), 5.15(dd, lH), 6.70(d, lH), 7.50(dd, 2H), 9.7(s, lH).
B. 2-Methallylphenol-4-aldehyde and 2-isobutenylphenol-4-aldehyde The mixture of 4-methallyloxybenzaldehyde(57 g, 0.33 mol) and N,N-dimethyl aniline(50 g) was heated at 210 ~C for 1 hour with stirring and cooled to room temperature. The reaction mixture was diluted with hexane(50 ml), extracted with Claisen alkali(50 ml x 2), and washed with hexane. The alkali layer was cooled to 0 ~C, neutralized with conc. hydrochloric acid, and extracted with diethyl ether(30 ml x 3). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified using silicagel column chromatography to provide 36 g of a mixture of 2-methallylphenol-4-aldehyde and 2-isobutenylphenol-4-aldehyde as yellow oil.
Yield(mixture): 63 %
H NMR(CDC13) : ~ 1.74(s, 3H), 3.38(s, 2H), 4.70(s, lH), 4.84(s, lH), 5.69(br, lH), 6.70(d, lH), 7.50(dd, 2H), 9.7(s, lH).
C. 2,3-Dihydro-2,2-dimethylbenzofuran-5-aldehyde To a solution of 27.5 g mixture of 2-methallylphenol-4-aldehyde and 2-isobutenylphenol-4-aldehyde in dichloromethane(160 ml), was added of iodine(6.0 g, 0.2 eq.) and stirred at room temperature for 2 hours. The reaction mixture was diluted with 10% aqueous Na2S2O3 solution. The resulting organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified using silicagel column chromatography to provide 20.3 g of 2,3-dihydro-2,2-dimethylbenzofuran-5-aldehyde.
Yield: 74 %
H NMR(CDC13): ~ 1.48(s, 3H), 3.00(s, 2H), 6.70(d, lH), 7.50(dd, 2H), 9.7(s, lH).
CA 022~8131 1998-12-10 A. 2-Methallyloxybenzaldehyde To a mixture of salicyl aldehyde(36.6 g, 0.3 mol) in acetone(150 ml ) and N,N-dimethylformamide(25 ml), were added anhydrous potassium carbonate(31 g, 0.2 mol) and methallyl chloride(44.4 ml, 0.45 mol) with stirring.
The reaction mixture was heated at reflux for 18 hours. The reaction mixture was cooled to room temperature and filtered, the filtrate was concentrated.
The residue was dissolved in ethyl ether(100 ml) and washed sequentially with 20% aqueous sodium hydroxide (50 ml X 3) and brine. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was distilled under high vaccum to provide 47 g of 2-methallyloxybenzaldehyde as a pale yellow oil.
Yield: 90 %
b.p.: 84 ~C / 0.05 torr H NMR(CDCl3) : ~ 1.8(s, 3H), 4.32(s, 2H), 4.97(d, lH), 6.7 ~ 7.2(m, 4H), 11.5(m, 4H).
B. 2-Methallylphenol-7-aldehyde A mixture of 2-methallyloxybenzaldehyde(36.6 g) and N,N-dimethyl aniline(40 g) was heated at 170 ~ 175 ~C for 1 hour with stirring and cooled to room temperature. The reaction mixture was diluted with hexane(50 ml), extracted with Claisen alkali(25 ml x 3), and washed with hexane. The alkali layer was cooled to 0 ~C, neutralized with conc. hydrochloric acid, and extracted with diethyl ether. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified using silicagel column chromatography to provide 23.53 g of 2-methallylphenol-7-aldehyde as a yellow oil.
'H NMR(CDCl3) : ~ 1.68(s, 3H), 3.31(s, 2H), 4.66(d, 2H), 5.6(br, lH), 6.5 ~
7.2(m, 3H), 9.62(s, lH).
CA 022~8131 1998-12-10 PCTnKR96/00090 C. 2,3-Dihydro-2,2-dimethylbenzofuran-7-aldehyde To a solution of 2-methallylphenol-7-aldehyde(7.04 g) in dichloromethane(60 ml), was added iodine(2.1 g, 0.2 eq.) and stirred at room temperature for 3 hours. The reaction mixture was diluted with 5% aqueous 5 Na2S2O3. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified using silicagel column chromatography to provide 4.43 g of 2,3-dihydro-2,2-dimethylbenzofuran-7-aldehyde .
Yield: 63 %
b.p.:81 ~ 82~C
lH NMR(CDCl3): ~ 1.49(s, 6H), 3.00(s, 2H), 6.60 ~ 7.55(m, 3H), 10.05(s, lH).
EXAMPLE 4 ~ 13 The compounds of formular (I) in Table 1 and Table 2 were prepared substantially in accordance with the procedure detailed from Example 1 to 15 Example 3, using essentially pure stereoisomers. These compounds are identified in Heterocycles, 1993, Vol.36, pp. 497 ~ 505 Table 1.
~CH3 (III-l) ( I ) (III-1), X condition of (I), X Yield(%) cyclization I2 (0.2eq ) Example4 3,5,6-Me3 room temperature4,6,7-Me3 98 30 min.
I2 (0.1eq ) o Example 5 3,5,6-Me3 room temperature 4,6,7-Me3 100 6 hours I2 (0.2eq ) Example6 6-CI-3,4-Me2 room temperature 7-Cl-4,5-Me2 97 30 min.
I2 (0.2eq ) Example 7 6-Cl room temperature 7-C1 96 30 min.
I2 (0.2eq ) Example8 6-CHO room temperature 7-CHO 63 30 min.
I2 (0.2eq ) Example9 4-CHO roomtemperature 5-CHO 74 30 min.
I2 (0.2eq ) Example 10 6-OH room temperature 7-OH 84 30 min.
CA 02258131 1998-12-lO
Table 2.
.
5X~ 5~CH3 X X
(III-2) ( I ) (III-1), X condition of (I), X Yield(%) cyclization I2 (0.2eq ) o Example 113,5,6-Me3room temperature 4,6,7-Me3 97 4 hours I2 (0.2eq ) Example 12 6-Me roomtemperature 7-Me 80 1 hour I2 (0 2eq ) Example 13 H room temperature H 80 1 hour
BACKGROUND OF THE INVENTION
Technical Field The present invention relates to process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives of the formula(I) useful as intermediate of agricultural chemicals and pharmaceutical products.
~ K ( I ) X
wherein, X is selected from the group consisting of hydrogen, halogen, hydroxy group, aldehyde group and C~~C6 alkyl group; and R is selected from the group consisting of C,~C6 alkyl group.
Description of the Related Art 2,3-Dihydro-2-methyl-2-alkylbenzofuran derivatives of the formula(I) were already known as intermediates of agricultural chemicals such as insecticides and pharmaceutical products. Among the compounds of the formula(I), 2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuran, known as carbofuranphenol, was very useful intermediate of 2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuranyl methylcarbamate as an insecticide.
In addition, 2,3-dihydro-2,2-dimethylbenzofuranaldehyde derivatives were known as intermediate of pyrethroide derivatives which were known in the art as an insecticide[Japanese Patent No. 402,753 A1; European Patent unexamined publication No. 0473,041(1992); German Patent No.2108,932;
European Patent No. 0271,170].
.
CA 022~8131 1998-12-10 A few conventional process for preparing carbofuranphenol was known in the art. For example it was prepared by alkylation of catechol and methallyl halide to 2-methallyloxyphenol which then was cyclized in the presence of a strong acid or Lewis acid at high temperature [U.S. Patent No.
4,380,654; Japanese Patent Kokai Soh 60-100,569; European Patent unexamined publication No. 115,837(1984); Japanese Patent Kokai Soh 58-174,375; Japanese Patent Kokai Pyung 5-835,180; Japanese Patent Kokai Pyung 5-839,679;
Japanese Patent Kokai Soh 58-21,676]. Also carbofuranphenol was prepared by Claisen rearrangement of 2-methallyl oxyphenol which was cyclized in the o presence of a strong acid or Lewis acid at high temperature Uapanese PatentKokai Soh 62-178,580; Brazilian Patent Application No.8301,980; German Patent unexamined publication No.3,027,335(1981)~.
The present invention is accomplished the new and easy process to prepare 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives, which is characterized by the cyclization of 2-(~ - alkylallyl)phenols and 2-(2-alkylpropenyl)phenols, prepared by Claisen rearrangement of (,~
- alkylallyl)oxybenzene.
SUMMARY OF THE INVENTION
The object of the present invention is to provide a new process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives, which may be used for the intermediates of agricultural chemicals and pharmaceutical products such as 2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuranyl methylcarbamate or pyrethroide as an insecticide.
It is to be understood that both the forgoing general description and the following detailed description are examplary and are intended to provide further explanation of the invention as claimed.
CA 022~8131 1998-12-lO
DETAILED DESCRIPTION OF THE INVENTION
The present invention is a process for preparing the compounds of the formula(I), which is characterized by the Claisen rearrangement of (,~
-alkylallyl)oxybenzene derivatives of the formula(II) to give stereoisomers of the formula (III-1) and (III-2), and then cyclization of formula(III-1) and (III-2) in the presence of a catalytic amount of iodine and an inert organic solvent at room temperature, x~ aJ~ R
OH
X5~ ( m-l) X ( III-2) X CRH3 ( I ) wherein, X and R are respectively defined as described above.
In the process according to the present inventon, Claisen rearrangement of (,~ -alkylallyl)oxybenzene derivatives of the formula(II) may be carried out in high boiling solvent or in the absence of solvent at a temperature ranged from 180 ~ to 250 ~C, preferably at a temperature ranged from 210 ~C to 220 5 ~C . Suitably preferred solvents are N,N-dimethylaniline, or dodecane etc..
The reaction products prepared by Claisen rearrangement, which are 2-(~-alkylallyl)phenol derivatives having the formula(III-1) and . .
CA 022~8131 1998-12-lO
W O 97/47615 PCT~KR96/00090 2-(alkylpropenyl)phenol derivatives having the formula(III-2) can occur in any of the possible stereoisomeric configuration. The stereoisomers may be used as the mixtures of stereoisomers or may be used respectively as essentially pure stereoisomer to afford the compound of the formula(I). The stereoisomers of the formular (III-1) and (III-2) can be separated using generally known methods, and were identified by nuclear magnetic resonance spectra, infrared spectra, and mass spectra.
A pure stereoismer or the mixtures of them were cyclized in the presence of a catalytic amount of iodine in an inert organic solvent at room o temperature for ranging from 30 minutes to 4 hours to obtain the compounds of formula(I). In the cyclization, the amount of iodine as catalyst is preferably 0.1 ~ 1 equimolar quantity, more preferably 0.2 equimolar quantity to the compound of the formula(III-1) and/or (III-2). The preferred solvents are hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, toluene, xylene etc The main feature of process according to the present invention is not caused iodocyclization by reacting iodine with 2-methallyl phenol or 2-iosobutenyl phenol~Tetrahedron, Vol. 46, pp. 3321 ~ 3408(1990)]. And the compounds of the formula(I) are obtained quantitatively in mild condition.
The present invention may be illustrated as the following examples.
These examples are for illustrative purposes and are not intended to limit the scopes of the invention.
A. 2-Methallyloxyphenol To a mixture of catechol(22 g, 0.2 mol) in acetone(120 ml ) and N,N-dimethylformamide(30 ml ), were added anhydrous potassium carbonate(14 g, 0.1 mol) and methallyl chloride(20 ml, 0.2 mol) with stirring.
The reaction mixture was heated at reflux for 18 hours. The reaction mixture CA 022~8131 1998-12-lO
was cooled to room temperature and filtered, and the filtrate was concentrated. The residue was dissolved in 2N hydrochloric acid(100 ml), and extracted sequentially with hexane(50 ml x 3 ) and ethyl acetate(50 ml x 3).The organic layer was washed with 20% aqueous sodium hydroxide (50 ml x 5 3), acidified with conc. hydrochloric acid, and extracted with hexane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure to provide a crude product, which was purified using silicagel column chromatography to provide 17.8 g of 2-methallyloxyphenol.
o b.p.: 78 ~ 80 ~ / 0.05 torr H NMR(CDCl3): ~ 1.8~s, 3H), 4.46(s, 2H), 4.95(s, lH), 5.05(s, lH), 5.68(br, lH), 6.76 ~ 6.95(m, 4H).
B. 2-Methallyl catachol and 2-isobutenyl catechol A mixture of 2-methallyloxyphenol(15.94 g) and N,N-dimethyl aniline( 15 30 g) was heated at 200 ~C for 1 hour and cooled to room temperature. The reaction mixture was added 2N hydrochloric acid(100 ml), and extracted sequentially with hexane and ethyl acetate(50 ml X 4). The resulting organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was distilled under 20 high vaccum to provide 11.6 g of a mixture of 2-methallyl catachol and 2-isobutenyl catechol(3: 1 molar ratio) as a yellow oil.
Yield(mixture): 73 %
b.p.(mixture): 104 ~C / 0.05 torr 2-methallyl catachol:
25 IH NMR(CDC13) : ~ 1.7(s, 3H), 3.35(s, 2H), 4.85(dd, 2H), 5.7(br, 2H), 6.76(m, 3H).
2-isobutenyl catechol:
'H NMR(CDCl3): ~ 1.68(s, 3H), 1.90(s, 3H), 4.72(dd, 2H), 5.7(br, 2H), 6.76(m, CA 022~8131 1998-12-10 3H).
C. 2,3-Dihydro-2,2-dimethyl-7-hydroxybenzofuran To a mixture of 2-methallyl catachol and 2-isobutenyl catechol(3: 1 molar ratio, 7.75 g) in carbon tetrachloride(50 ml), was added iodine(I2, 2.4 g,0.2 eq.) and stirred at room temperature for 30 minutes. The reaction mixture was diluted with 5% aqueous Na2S2O3 solution until the dark color turned to clear. The resulting organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified using silicagel column chromatography o to provide 6.5 g of 2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuran.
Yield: 84%
b.p.: 84 ~ 85 ~ / 0.002 torr IH NMR(CDCl3): ~ 1.45(s, 3H), 3.0(s, 2H), 5.42(s, lH), 5.7(br, 2H), 6.7(m, 3H).
A. 4-Methallyloxybenzaldehyde To a mixture of 4-hydroxybenzaldehyde(61 ml, 0.5 mol) in acetone( 150 ml) and N,N-dimethylformamide(25 ml), were added anhydrous potassium carbonate(51 g) and methallyl chloride(63 ml, 0.75 mol) with stirring. The reaction mixture was heated at reflux for 18 hours. The reaction mixture was cooled to room temperature and filtered, and the filtrate was concentrated. The residue was dissolved in ethyl ether(100 ml ), and washed sequentially with water, 20% aqueous sodium hydroxide and brine. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified using silicagel column chromatography to provide 76.5 g of a colorless 4-methallyl oxybenzaldehyde .
Yield: 86.8 %
b.p.: 95 ~C / 0.001 torr CA 022~8l3l l998-l2-lO
W O 97/47615 PCTnKR961'~A~9 H NMR(CDCl3): ~ 1.80(s, 3H), 4.45(s, 2H), 4.98(dd, lH), 5.15(dd, lH), 6.70(d, lH), 7.50(dd, 2H), 9.7(s, lH).
B. 2-Methallylphenol-4-aldehyde and 2-isobutenylphenol-4-aldehyde The mixture of 4-methallyloxybenzaldehyde(57 g, 0.33 mol) and N,N-dimethyl aniline(50 g) was heated at 210 ~C for 1 hour with stirring and cooled to room temperature. The reaction mixture was diluted with hexane(50 ml), extracted with Claisen alkali(50 ml x 2), and washed with hexane. The alkali layer was cooled to 0 ~C, neutralized with conc. hydrochloric acid, and extracted with diethyl ether(30 ml x 3). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified using silicagel column chromatography to provide 36 g of a mixture of 2-methallylphenol-4-aldehyde and 2-isobutenylphenol-4-aldehyde as yellow oil.
Yield(mixture): 63 %
H NMR(CDC13) : ~ 1.74(s, 3H), 3.38(s, 2H), 4.70(s, lH), 4.84(s, lH), 5.69(br, lH), 6.70(d, lH), 7.50(dd, 2H), 9.7(s, lH).
C. 2,3-Dihydro-2,2-dimethylbenzofuran-5-aldehyde To a solution of 27.5 g mixture of 2-methallylphenol-4-aldehyde and 2-isobutenylphenol-4-aldehyde in dichloromethane(160 ml), was added of iodine(6.0 g, 0.2 eq.) and stirred at room temperature for 2 hours. The reaction mixture was diluted with 10% aqueous Na2S2O3 solution. The resulting organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified using silicagel column chromatography to provide 20.3 g of 2,3-dihydro-2,2-dimethylbenzofuran-5-aldehyde.
Yield: 74 %
H NMR(CDC13): ~ 1.48(s, 3H), 3.00(s, 2H), 6.70(d, lH), 7.50(dd, 2H), 9.7(s, lH).
CA 022~8131 1998-12-10 A. 2-Methallyloxybenzaldehyde To a mixture of salicyl aldehyde(36.6 g, 0.3 mol) in acetone(150 ml ) and N,N-dimethylformamide(25 ml), were added anhydrous potassium carbonate(31 g, 0.2 mol) and methallyl chloride(44.4 ml, 0.45 mol) with stirring.
The reaction mixture was heated at reflux for 18 hours. The reaction mixture was cooled to room temperature and filtered, the filtrate was concentrated.
The residue was dissolved in ethyl ether(100 ml) and washed sequentially with 20% aqueous sodium hydroxide (50 ml X 3) and brine. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was distilled under high vaccum to provide 47 g of 2-methallyloxybenzaldehyde as a pale yellow oil.
Yield: 90 %
b.p.: 84 ~C / 0.05 torr H NMR(CDCl3) : ~ 1.8(s, 3H), 4.32(s, 2H), 4.97(d, lH), 6.7 ~ 7.2(m, 4H), 11.5(m, 4H).
B. 2-Methallylphenol-7-aldehyde A mixture of 2-methallyloxybenzaldehyde(36.6 g) and N,N-dimethyl aniline(40 g) was heated at 170 ~ 175 ~C for 1 hour with stirring and cooled to room temperature. The reaction mixture was diluted with hexane(50 ml), extracted with Claisen alkali(25 ml x 3), and washed with hexane. The alkali layer was cooled to 0 ~C, neutralized with conc. hydrochloric acid, and extracted with diethyl ether. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified using silicagel column chromatography to provide 23.53 g of 2-methallylphenol-7-aldehyde as a yellow oil.
'H NMR(CDCl3) : ~ 1.68(s, 3H), 3.31(s, 2H), 4.66(d, 2H), 5.6(br, lH), 6.5 ~
7.2(m, 3H), 9.62(s, lH).
CA 022~8131 1998-12-10 PCTnKR96/00090 C. 2,3-Dihydro-2,2-dimethylbenzofuran-7-aldehyde To a solution of 2-methallylphenol-7-aldehyde(7.04 g) in dichloromethane(60 ml), was added iodine(2.1 g, 0.2 eq.) and stirred at room temperature for 3 hours. The reaction mixture was diluted with 5% aqueous 5 Na2S2O3. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified using silicagel column chromatography to provide 4.43 g of 2,3-dihydro-2,2-dimethylbenzofuran-7-aldehyde .
Yield: 63 %
b.p.:81 ~ 82~C
lH NMR(CDCl3): ~ 1.49(s, 6H), 3.00(s, 2H), 6.60 ~ 7.55(m, 3H), 10.05(s, lH).
EXAMPLE 4 ~ 13 The compounds of formular (I) in Table 1 and Table 2 were prepared substantially in accordance with the procedure detailed from Example 1 to 15 Example 3, using essentially pure stereoisomers. These compounds are identified in Heterocycles, 1993, Vol.36, pp. 497 ~ 505 Table 1.
~CH3 (III-l) ( I ) (III-1), X condition of (I), X Yield(%) cyclization I2 (0.2eq ) Example4 3,5,6-Me3 room temperature4,6,7-Me3 98 30 min.
I2 (0.1eq ) o Example 5 3,5,6-Me3 room temperature 4,6,7-Me3 100 6 hours I2 (0.2eq ) Example6 6-CI-3,4-Me2 room temperature 7-Cl-4,5-Me2 97 30 min.
I2 (0.2eq ) Example 7 6-Cl room temperature 7-C1 96 30 min.
I2 (0.2eq ) Example8 6-CHO room temperature 7-CHO 63 30 min.
I2 (0.2eq ) Example9 4-CHO roomtemperature 5-CHO 74 30 min.
I2 (0.2eq ) Example 10 6-OH room temperature 7-OH 84 30 min.
CA 02258131 1998-12-lO
Table 2.
.
5X~ 5~CH3 X X
(III-2) ( I ) (III-1), X condition of (I), X Yield(%) cyclization I2 (0.2eq ) o Example 113,5,6-Me3room temperature 4,6,7-Me3 97 4 hours I2 (0.2eq ) Example 12 6-Me roomtemperature 7-Me 80 1 hour I2 (0 2eq ) Example 13 H room temperature H 80 1 hour
Claims (2)
1. A process for preparing the compounds of the formula (I), which is characterized by the Claisen rearrangement of (.beta.
-alkylallyl)oxybenzene derivatives of the formula(II) to stereoisomers of the formula(III-1) and (III-2); and then cyclization in the presence a catalytic amount of iodine in an inert organic solvent at room temperature, wherein, X is selected from the group consisting of hydrogen, halogen, hydroxy group, aldehyde group and C1-C6 alkyl group;
R is selected from the group consisting of C1-C6 alkyl group.
-alkylallyl)oxybenzene derivatives of the formula(II) to stereoisomers of the formula(III-1) and (III-2); and then cyclization in the presence a catalytic amount of iodine in an inert organic solvent at room temperature, wherein, X is selected from the group consisting of hydrogen, halogen, hydroxy group, aldehyde group and C1-C6 alkyl group;
R is selected from the group consisting of C1-C6 alkyl group.
2. The process according to claim 1, wherein said stereoisomers are used as mixed with 2-(.beta.-alkylallyl)phenol derivatives having the formula (III-1) and 2-(alkylpropenyl)phenol derivatives having the formula (III-2), or are used alone as essentially pure stereoisomers.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU61392/96A AU6139296A (en) | 1996-06-12 | 1996-06-12 | Process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives |
| CA002258131A CA2258131A1 (en) | 1996-06-12 | 1996-06-12 | Process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives |
| PCT/KR1996/000090 WO1997047615A1 (en) | 1996-06-12 | 1996-06-12 | Process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives |
| JP10501468A JP2000507600A (en) | 1996-06-12 | 1996-06-12 | Method for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivative |
| EP96918908A EP0912538A1 (en) | 1996-06-12 | 1996-06-12 | Process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives |
| BR9612639-6A BR9612639A (en) | 1996-06-12 | 1996-06-12 | "process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives" |
| CN96180326.6A CN1224423A (en) | 1996-06-12 | 1996-06-12 | Process for preparing 2,3-dihydro-2-methyl-2-alkyl-benzofuran derivs |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002258131A CA2258131A1 (en) | 1996-06-12 | 1996-06-12 | Process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives |
| PCT/KR1996/000090 WO1997047615A1 (en) | 1996-06-12 | 1996-06-12 | Process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives |
| CN96180326.6A CN1224423A (en) | 1996-06-12 | 1996-06-12 | Process for preparing 2,3-dihydro-2-methyl-2-alkyl-benzofuran derivs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2258131A1 true CA2258131A1 (en) | 1997-12-18 |
Family
ID=27170905
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002258131A Abandoned CA2258131A1 (en) | 1996-06-12 | 1996-06-12 | Process for preparing 2,3-dihydro-2-methyl-2-alkylbenzofuran derivatives |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0912538A1 (en) |
| JP (1) | JP2000507600A (en) |
| CN (1) | CN1224423A (en) |
| CA (1) | CA2258131A1 (en) |
| WO (1) | WO1997047615A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2964025A4 (en) | 2013-03-06 | 2016-10-26 | Syngenta Participations Ag | Dihydrobenzofuran derivatives as insecticidal compounds |
| CN114213371A (en) * | 2021-12-29 | 2022-03-22 | 江苏三吉利化工股份有限公司 | Method for synthesizing furan phenol by magnesium system Lewis acid catalysis |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2461708A1 (en) * | 1979-07-18 | 1981-02-06 | Rhone Poulenc Agrochimie | PREPARATION OF DIHYDRODIMETHYLHYDROXY-7 BENZOFURAN |
| DE2932458A1 (en) * | 1979-08-10 | 1981-02-26 | Bayer Ag | PRODUCTION OF MONOALKYL ETHERS FROM HYDROXYPHENOLS AND THEIR CONVERSION TO HYDROXYCUMARANES |
| JPS59184172A (en) * | 1983-04-05 | 1984-10-19 | Ube Ind Ltd | Production of 2,3-dyhydrobenzofuran derivative |
| JPS60100567A (en) * | 1983-11-08 | 1985-06-04 | Ube Ind Ltd | Production of 2,3-dihydro-2,2-dimethyl-7- hydroxybenzofuran |
| JPS60100566A (en) * | 1983-11-08 | 1985-06-04 | Ube Ind Ltd | Production of 2,3-dihydrobenzofuran derivative |
| JPH0699418B2 (en) * | 1986-01-30 | 1994-12-07 | 三菱化成株式会社 | Method for producing 2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuran |
| DE4027573A1 (en) * | 1990-08-31 | 1992-03-05 | Basf Ag | NEW 2,3-DIHYDROBENZOFURANE AND METHOD FOR THEIR PRODUCTION |
-
1996
- 1996-06-12 EP EP96918908A patent/EP0912538A1/en not_active Withdrawn
- 1996-06-12 CN CN96180326.6A patent/CN1224423A/en active Pending
- 1996-06-12 CA CA002258131A patent/CA2258131A1/en not_active Abandoned
- 1996-06-12 JP JP10501468A patent/JP2000507600A/en active Pending
- 1996-06-12 WO PCT/KR1996/000090 patent/WO1997047615A1/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO1997047615A1 (en) | 1997-12-18 |
| JP2000507600A (en) | 2000-06-20 |
| CN1224423A (en) | 1999-07-28 |
| EP0912538A1 (en) | 1999-05-06 |
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