Process for preparing polyalkyl-2-alkoxy-7-hydroxychroman derivatives

Abstract: Process for preparing polyalkyl-2-alkoxy-7-­ hydroxychroman derivative of the general formula (V) : wherein R¹ denotes C₁-C₄ primary alkyl, R² denotes hydrogen or C₁-C₄ primary alkyl and R³ denotes C₁-C₄ alkyl, by reacting resorcin with either an aliphatic ketone of the general formula(I) : wherein R¹ and R² are as defined above, and an alcohol of the formula(II) : R³OH (II) wherein R³ is as defined above, in the presence of an acid catalyst, or an aliphatic ketone acetal of the general formula(III) : wherein R¹ , R² and R³ are as defined above, in the presence of an acid catalyst.

Description: The present invention relates to a novel process for preparing polyalkyl-2-alkoxy-7-hydroxychroman derivatives of the general formula (V): wherein R¹ denotes C₁-C₄ primary alkyl, R² denotes hydrogen or C₁-C₄ primary alkyl and R³ denotes C₁-C₄ alkyl, The compounds of the formula (V) are useful as an intermediate for the preparation of agricultural chemicals. Both the processes for preparing polyalkyl-2-alkoxy-7-hydroxychroman derivatives by reacting resorcin with an α,β-unsaturated ketone and an ortho-ester in the presence of an acid catalyst, and by reacting resorcin with an α,β-unsaturated aldehyde acetal in the presence of an acid catalyst have already been filed by the present inventors and laid open to public with Japanese Patent LOP-Publn. No. 203677/1988. The processes disclosed in the aforementioned Japanese Patent LOP-Publn. No. 203677/1988 can produce the desired product in a single step and therefore industrially advantageous. However, those compounds having two alkyl substituents on the 4-carbon atom of the chroman ring could not be synthesized by the above described methods. The inventors tried to solve the above problem by replacing the reactants α,β-unsaturated ketone and ortho-ester or α,β-unsaturated aldehyde acetal with other reactant(s). Thus, the present invention relates to a process for preparing polyalkyl-2-alkoxy-7-hydroxychroman derivative of the general formula (V): wherein R¹ denotes C₁₋C₄ primary alkyl, R² denotes hydrogen or C₁₋C₄ primary alkyl and R³ denotes C₁₋C₄alkyl, which comprises reacting resorcin with either an aliphatic ketone of the general formula (I): wherein R¹ and R² are as defined above, and an alcohol of the formula (II): R³OH (II) wherein R³ is as defined above, in the presence of an acid catalyst The process will be described in detail hereinafter. The reaction of the process is diagramatically shown by the following reaction scheme: Suitable acid catalysts which may be mentioned include inorganic acids such as hydrochloric acid, and sulfuric acid, organic acids such as methanesulfonic acid, and trifluoroacetic acid, cation exchange resins such as Amberlist 15; solid acids such as phosphomolybdic acid, and phosphotungstic acid, Lewis acids such as cupric chloride, and cupric bromide, trityl hexafluorophosphate; and trityl pentachlorostannate. Among them, hydrochloric acid, sulfuric acid, methanesulfonic acid and cupric chloride are particularly preferred. The amount of the acid catalyst used in the present process is in the range of 0.01 to 2 mol, preferably 0.1 to 0.8 mol per mol of resorcin (IV). The amount of aliphatic ketone (I) is in the range of 0.5 to 10 mol, preferably 1 to 5 mol per mol of resorcin. The amount of the alcohol (II) is in the range of 1 to 100 mol, preferably 5 to 40 mol per mol of resorcin. The process may be carried out either in the presence of an inert solvent or without any solvent. Preferable inert solvents include aromatic hydrocarbons such as benzene, toluene, and xylene, halogenated hydrocarbons such as carbon tetrachloride, and 1,2-dichloroethane, ethers such as isopropyl ether, and n-butyl ether. These solvents may be used alone or in combinations thereof. The amount of the solvent used is in the range of 1 to 100 times, preferably 4 to 70 times the weight of resorcin. The reaction temperature ranges normally from 25 to 160°C and preferably 70 to 130°C. The reaction may be performed normally for 0.1 to 50 hours, preferably 0.5 to 20 hours. After the reaction has terminated, the reaction mixture is worked up in conventional manner such as extraction, distillation, chromatography, and the like to give the desired product (V). As mentioned above, there is provided an easy and single-step process for preparing polyalkyl-2-alkoxy-7-hydroxychroman derivatives having two alkyl substituents on the 4-carbon atom of the chroman ring. These compounds are useful as an intermediate for the preparation of agricultural chemicals. The invention is illustrated, by the following Examples. Example 1 30ml glass autoclave was charged with 2.2g (20mmol) of resorcin, 2.32g (40mmol) of acetone, 3.2g (100mmol) of methanol, 0.2g (2mmol) of conc. sulfuric acid and 10ml of toluene, then sealed, and allowed to react at 70°C for 4 hours. Then, the reaction mixture was cooled to room temperature, neutralized with saturated NaHCO₃, washed with water, and toluene was distilled off under reduced pressure. The residue was purified by column chromatography on silicagel using hexane-ethyl acetate as an eluent to give 0.75g (17.0%) of 7-hydroxy-2-methoxy-2,4,4-trimethylchroman as a colorless oil. Examples 2-9 The procedure of Example 1 was repeated except that respective acid catalysts as indicated in Table 1 were used instead of conc. sulfuric acid. The results are shown in Table 1. Example No. Acid Catalyst Yield(%) 2 HCl 17.3 3 CF₃COOH 4.1 4 CH₃SO₃H 15.2 5 Amberlist 15 4.1 6 Phosphotungstic Acid 17.6 7 CuCl₂ 19.0 8 CuBr₂ 13.2 9 Ph₃CSnCl₅ 12.0 Examples 10-12 The procedure of Example 1 was repeated except that respective solvents as indicated in Table 2 were used instead of toluene. The results are shown in Table 2. Example No. Solvent Yield(%) 10 1,2-Dichloroethane 16.0 11 Isopropyl Ether 4.0 12 None 8.8 Examples 13-18 The procedure of Example 1 was repeated except that varying amounts of sulfuric acid and varying periods of reaction time as indicated in Table 3 were employed. The results are shown in Table 3. Example No. conc.Sulfuric Acid (mmol) Reaction Time (hr.) Yield(%) 13 1.0 4 20.6 14 2.0 4 17.0 15 2.0 6 19.4 16 2.0 10 19.9 17 2.0 20 21.2 18 4.0 4 14.6 Examples 19-41 The procedure of Example 1 was repeated except that varying amounts each of sulfuric acid, acetone, methanol, and toluene and varying reaction temperatures as indicated in Table 4 were employed. The results are shown in Table 4. Example No. conc.Sulfuric Acid (mmol) Acetone (mmol) Methanol (mmol) Toluene (mℓ) Temp. (°C) Yield (%) 19 1.0 20 100 10 100 17.7 20 1.0 20 200 10 100 21.7 21 1.0 40 50 10 100 18.7 22 1.0 40 100 10 100 26.6 23 1.0 40 400 10 100 37.3 24 1.0 80 100 10 100 28.2 25 1.0 80 200 10 100 29.2 26 2.0 40 100 60 70 23.7 27 2.0 40 100 40 100 32.3 28 2.0 40 100 40 130 25.0 29 2.0 40 200 10 100 34.2 30 2.0 40 200 40 100 40.2 31 2.0 60 200 10 100 40.9 32 2.0 60 200 30 100 47.8 33 2.0 80 200 10 100 41.7 34 2.0 80 200 80 100 57.0 35 4.0 40 200 80 100 46.5 36 4.0 60 200 80 100 56.0 37 4.0 60 200 160 100 56.8 38 4.0 80 200 80 100 57.6 39 8.0 60 200 80 100 59.2 40 8.0 80 200 80 100 63.3 41 16 60 200 80 100 50.1 Example 42 50ml stainless steel autoclave was charged with 2.2g (20mmol) of resorcin, 2.32g (40mmol) of acetone, 9.2g (200mmol) of ethanol, 0.2g (2mmol) of conc. sulfuric acid and 10ml of toluene, then sealed and allowed to react at 100°C for 4 hours. Then, the reaction mixture was cooled to room temperature, neutralized with saturated NaHCO₃, washed with water, and toluene was distilled off under reduced pressure. The residue was purified by column chromatography on silicagel using hexane-ethyl acetate as an eluent to give 1.01g (21.4%) of 2-ethoxy-7-hydroxy-2,4,4-trimethylchroman as a colorless viscous liquid.

Claims: A process for preparing polyalkyl-2-alkoxy-7-hydroxychroman derivative of the general formula (V): wherein R' denotes C₁-C₄ primary alkyl, R² denotes hydrogen or C₁-C₄ primary alkyl and R³ denotes C₁-C₄ alkyl, which comprises reacting resorcin with an aliphatic ketone of the general formula (I): wherein R¹ and R² are as defined above, and an alcohol of the formula (II): R³OH (II) wherein R³ is as defined above, in the presence of an acid catalyst.

Inventors: FUKUOKA DAISUKE MITSUI PETROCH, IMUTA JUNICHI MITSUI PETROCHEM, ISHIGURO MASAHARU MITSUI PETRO, ISHITOKU TAKESHI MITSUI PETROC, KIHARA NORIAKI MITSUI PETROCHE, MUKAIYAMA TERUAKI - MINAMIOGIK, TAKAHASHI KATSUYA MITSUI PETRO, TAN HIROAKI MITSUI PETROCHEMIC, TASHIRO TAKASHI MITSUI PETROCH, FUKUOKA, DAISUKE, MITSUI PETROCHEMICAL IND., LTD., IMUTA, JUNICHI, MITSUI PETROCHEMICAL IND., LTD., ISHIGURO, MASAHARU, MITSUI PETROCHEMICAL IND., LTD, ISHITOKU, TAKESHI, MITSUI PETROCHEMICAL IND., LTD, KIHARA, NORIAKI, MITSUI PETROCHEMICAL IND., LTD, MUKAIYAMA, TERUAKI, 15-18 MINAMIOGIKUBO 1 CHOME, TAKAHASHI, KATSUYA, MITSUI PETROCHEMICAL IND., LTD, TAN, HIROAKI, MITSUI PETROCHEMICAL IND., LTD., TASHIRO, TAKASHI, MITSUI PETROCHEMICAL IND., LTD.
Applicants: MITSUI PETROCHEMICAL IND, MITSUI PETROCHEMICAL INDUSTRIES, LTD.
Application year: 1990
Main classification: C07D311
IPC codes: C07D311