CN102701912A - Synthetic method of 2,5-dimethyl-1,3-dihydro-1H-indene-2-base methanol essence - Google Patents
Synthetic method of 2,5-dimethyl-1,3-dihydro-1H-indene-2-base methanol essence Download PDFInfo
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- CN102701912A CN102701912A CN201210225775XA CN201210225775A CN102701912A CN 102701912 A CN102701912 A CN 102701912A CN 201210225775X A CN201210225775X A CN 201210225775XA CN 201210225775 A CN201210225775 A CN 201210225775A CN 102701912 A CN102701912 A CN 102701912A
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Abstract
The invention discloses a synthetic method of a 2,5-dimethyl-1,3-dihydro-1H-indene-2-base methanol essence. The target substance 2,5-dimethyl-1,3-dihydro-1H-indene-2-base methanol is prepared by a series of reaction with 4-methyl phthalic anhydride as an initial material. By the method, the synthetic route is short, the materials are cheap and can be easily obtained, the reaction condition is mild and the operation is simple, so that industrial production can be realized.
Description
Technical field
The invention belongs to spices synthetic novel process, particularly relate to a kind of 2,5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices.
Background technology
2,5-dimethyl--1,3-dihydro-1H-indenes-2-base methyl alcohol is a floral type spices midbody, can be used for allocating floral type spices.Do not see about 2 5-dimethyl--1, the synthetic report of 3-dihydro-1H-indenes-2-base methyl alcohol at present as yet.
Summary of the invention
The objective of the invention is to, provide a kind of 2,5-dimethyl--1, the 3-dihydro-1H-indenes-new synthetic line of 2-base methyl alcohol spices, this route is brief, raw material cheaply is easy to get, reaction conditions gentle, easy to operate.
For solving the problems of the technologies described above, the technical scheme that the present invention adopts is: a kind of 2, and 5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices is characterized in that this method comprises the steps:
(1) be starting raw material with 4-methylphthalic acid acid anhydride, Li-Al hydrogen, Peng Qinghuana or catalytic hydrogenating reduction obtain 1,2-dihydroxymethyl-4-methylbenzene through filtering, concentrating;
The reaction of (2) 1,2-dihydroxymethyl-4-methylbenzene and bromine, phosphorus tribromide, or with thionyl chloride, phosphorus pentachloride, phosphorus oxychloride reaction, obtain 1,2-dichloromethyl-4-methylbenzene through filtering, concentrating;
(3) 1; 2-two brooethyls-4-methylbenzene or 1, the cyclization in the presence of sodium alkoxide or sodium hydrogen of 2-dichloromethyl-4-methylbenzene and ethyl malonate or methyl-malonate, concentrating under reduced pressure; Resistates adds the Hydrogen chloride neutrality that neutralizes; Through extraction, washing, filtration, concentrated, distillation, obtain key intermediate 5-methyl-2,3-dihydro-1H-indenes-2-base dicarboxylate;
(4) 5-methyl-2; 3-dihydro-1H-indenes-2-base dicarboxylate takes off ester group under methyl-sulphoxide, sodium-chlor and water catalysis, or hydrolysis, decarboxylation, resterification, through extraction, washing, filter, concentrate, distillation; Obtain 5-methyl-2,3-dihydro-1H-indenes-2-base ethyl formate;
(5) with sodium hydrogen, lithium diisopropyl amido, just or tert-butyl lithium be alkali, 5-methyl-2,3-dihydro-1H-indenes-2-base ethyl formate reacts with methyl iodide or methyl-sulfate; After filtering, distilling, the pad filtered through silica gel is used sherwood oil: rinsed; Concentrate; Obtain 2,5-dimethyl--2,3-dihydro-1H-indenes-2-base ethyl formate;
(6) 2,5-dimethyl--2,3-dihydro-1H-indenes-2-base ethyl formate and Li-Al hydrogen, Peng Qinghuana or catalytic hydrogenating reduction is after the washing of filtering, filtrate, concentrating; The pad filtered through silica gel, use sherwood oil: rinsed concentrates; Obtain 2,5-dimethyl--1,3-dihydro-1H-indenes-2-base methyl alcohol.
In the above-mentioned steps (1), solvent is an ether, and the frozen water cooling rises to stirring at room 12h, filtrating washing, anhydrous sodium sulfate drying.
In the above-mentioned steps (2), solvent is an ether, and the frozen water cooling adds pyridine, and filtrating is respectively with sodium carbonate solution, water, saturated brine washing, anhydrous sodium sulfate drying.
In the above-mentioned steps (3), solvent is an absolute ethyl alcohol, reflux 8h, ethyl acetate extraction, saturated brine washing, anhydrous sodium sulfate drying, high vacuum rectification under vacuum.
In the above-mentioned steps (4), reflux 50h, cool to room temperature, anhydrous sodium sulfate drying, acetic acid ethyl dissolution, saturated brine washing, high vacuum rectification under vacuum.
In the above-mentioned steps (5), under nitrogen protection, in anhydrous tetrahydro furan, add diisopropylamine; Be cooled to-78 ℃, drip n-butyllithium solution, behind the stirring 45min; Add 5-methyl-2,3-dihydro-1H-indenes-2-base ethyl formate keeps-78 ℃ to continue to stir 1h; Add methyl iodide, be warmed up to room temperature, reaction 5h.
In the above-mentioned steps (5), sherwood oil: the ratio of ETHYLE ACETATE is 20:1.
In the above-mentioned steps (6), solvent is an ether, and the frozen water cooling rises to stirring at room 2h.
In the above-mentioned steps (6), sherwood oil: the ratio of ETHYLE ACETATE is 20:1.
Advantage of the present invention is: synthetic route is brief, and raw material cheaply is easy to get, and reaction conditions is gentle, and operation can realize suitability for industrialized production easily.
Description of drawings
Fig. 1 is a synthesis process flow diagram of the present invention.
Embodiment
For further disclosing technical scheme of the present invention, combine accompanying drawing Fig. 1 to specify embodiment of the present invention at present:
Embodiment 1:1,2-dihydroxymethyl-4-methylbenzene synthetic
65.0 gram (0.4 mol) compd As (4-methylphthalic acid acid anhydride) are dissolved in 1000 milliliters of ether, and the frozen water cooling adds 24.2 gram (0.6 mol) tetrahydrochysene lithium aluminium, is raised to room temperature, stirs 12 hours.The frozen water cooling adds 20 ml water termination reactions, filters, and filtrating washing, anhydrous sodium sulfate drying filter, concentrate, and obtains 44 gram white solid B (1,2-dihydroxymethyl-4-methylbenzene), and productive rate is 75%.
Embodiment 2:1,2-two brooethyls-4-methylbenzene synthetic
30 gram (0.2mol) compd Bs (1,2-dihydroxymethyl-4-methylbenzene) are dissolved in 300 milliliters of anhydrous diethyl ethers, the frozen water cooling; Add 16 gram (0.2mol) pyridines, stir, Dropwise 5 4.5 gram (0.2mol) phosphorus tribromides; Be raised to room temperature after dropwising, stirred 12 hours.With 300 milliliters of sodium carbonate solutions, 300 ml waters, 300 milliliters of saturated brine washings, anhydrous sodium sulfate drying filters, concentrates respectively for solids removed by filtration, filtrating, gets 46 gram white solid C (1,2-two brooethyls-4-methylbenzene), and productive rate is 80%.
Embodiment 3: key intermediate 5-methyl-2,3-dihydro-1H-indenes-2-base dicarboxylate synthetic
6.4 gram (0.28mol) sodium Metal 99.5s are added 500 milliliters of absolute ethyl alcohols, be stirred to dissolving fully, add 28.4 gram (0.22mol) ethyl malonates; Stirred 30 minutes; Add 40 gram (0.14mol) Compound C (1,2-two brooethyls-4-methylbenzene), reflux 8 hours.The reaction mixture cooling adds 20 ml waters, and concentrating under reduced pressure is closely dried; Resistates adds the Hydrogen chloride neutrality that neutralizes, ETHYLE ACETATE (3X200 milliliter) extraction, saturated brine washing; Anhydrous sodium sulfate drying filters, concentrates the high vacuum rectification under vacuum; Get little yellow oil D (5-methyl-2,3-dihydro-1H-indenes-2-base dicarboxylate) 20.6 grams, productive rate is 52%.
Embodiment 4:5-methyl-2,3-dihydro-1H-indenes-2-base ethyl formate synthetic
In 200 milliliters of methyl-sulphoxides, add 27.6 gram (0.1mol) D (5-methyl-2,3-dihydro-1H-indenes-2-base dicarboxylate), 10 gram sodium-chlor, 5 ml waters, reflux 50 hours.Cool to room temperature, anhydrous sodium sulfate drying filters; The most of solvent of reclaim under reduced pressure adds 200 milliliters of acetic acid ethyl dissolutions, the saturated brine washing; Anhydrous sodium sulfate drying filters, concentrates the high vacuum rectification under vacuum; Get colorless oil E (5-methyl-2,3-dihydro-1H-indenes-2-base ethyl formate) 15 grams, productive rate is 74%.
Embodiment 5:2,5-dimethyl--2,3-dihydro-1H-indenes-2-base ethyl formate synthetic
Under the nitrogen protection, in 400 milliliters of anhydrous tetrahydro furans, add 29.2 gram (0.3mol) diisopropylamines, be cooled to-78 ℃; Drip 116 milliliters of n-butyllithium solutions (closing 0.3mol), stir after 45 minutes, add 20.4 gram (0.1mol) compd E (5-methyl-2; 3-dihydro-1H-indenes-2-base ethyl formate), keeps-78 ℃ to continue to stir 1 hour, add 49 gram (0.33mol) methyl iodide; Naturally be warmed up to room temperature, reacted 5 hours.Filter, most of solvent is reclaimed in underpressure distillation, the pad filtered through silica gel, with 200 milliliters of sherwood oils: ETHYLE ACETATE (20:1) flushing, concentrate, light yellow oil F (2,5-dimethyl--2,3-dihydro-1H-indenes-2-base ethyl formate) 21.1 restrains, productive rate is 97%.
Embodiment 6:2,5-dimethyl--1,3-dihydro-1H-indenes-2-base methyl alcohol synthetic
In 200 milliliters of ether, add 22 gram (0.1mol) compound F 17-hydroxy-corticosterones (2,5-dimethyl--2,3-dihydro-1H-indenes-2-base ethyl formate), the frozen water cooling adds 4.6 gram (0.12mol) tetrahydrochysene lithium aluminium, is raised to room temperature, stirs 2 hours.The frozen water cooling adds 20 ml water termination reactions, filters filtrating washing, anhydrous sodium sulfate drying; Filter, concentrate, the pad filtered through silica gel, with 200 milliliters of sherwood oils: ETHYLE ACETATE (20:1) washes; Concentrate, obtain 15.8 gram target compounds 2,5-dimethyl--1; 3-dihydro-1H-indenes-2-base methyl alcohol is light yellow liquid, and productive rate is 90%.
More than, basic design of the present invention and ultimate principle have been set forth through introduction to listed embodiment.But the present invention never is limited to above-mentioned listed embodiment, and every equivalent variations, improvement and deliberately of inferior quality behavior of doing based on technical scheme of the present invention of change all should belong to protection scope of the present invention.
Claims (9)
1. one kind 2,5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices is characterized in that this method comprises the steps:
(1) be starting raw material with 4-methylphthalic acid acid anhydride, Li-Al hydrogen, Peng Qinghuana or catalytic hydrogenating reduction obtain 1,2-dihydroxymethyl-4-methylbenzene through filtering, concentrating;
The reaction of (2) 1,2-dihydroxymethyl-4-methylbenzene and bromine, phosphorus tribromide, or with thionyl chloride, phosphorus pentachloride, phosphorus oxychloride reaction, obtain 1,2-dichloromethyl-4-methylbenzene through filtering, concentrating;
(3) 1; 2-two brooethyls-4-methylbenzene or 1, the cyclization in the presence of sodium alkoxide or sodium hydrogen of 2-dichloromethyl-4-methylbenzene and ethyl malonate or methyl-malonate, concentrating under reduced pressure; Resistates adds the Hydrogen chloride neutrality that neutralizes; Through extraction, washing, filtration, concentrated, distillation, obtain key intermediate 5-methyl-2,3-dihydro-1H-indenes-2-base dicarboxylate;
(4) 5-methyl-2; 3-dihydro-1H-indenes-2-base dicarboxylate takes off ester group under methyl-sulphoxide, sodium-chlor and water catalysis, or hydrolysis, decarboxylation, resterification, through extraction, washing, filter, concentrate, distillation; Obtain 5-methyl-2,3-dihydro-1H-indenes-2-base ethyl formate;
(5) with sodium hydrogen, lithium diisopropyl amido, just or tert-butyl lithium be alkali, 5-methyl-2,3-dihydro-1H-indenes-2-base ethyl formate reacts with methyl iodide or methyl-sulfate; After filtering, distilling, the pad filtered through silica gel is used sherwood oil: rinsed; Concentrate; Obtain 2,5-dimethyl--2,3-dihydro-1H-indenes-2-base ethyl formate;
(6) 2,5-dimethyl--2,3-dihydro-1H-indenes-2-base ethyl formate and Li-Al hydrogen, Peng Qinghuana or catalytic hydrogenating reduction is after the washing of filtering, filtrate, concentrating; The pad filtered through silica gel, use sherwood oil: rinsed concentrates; Obtain 2,5-dimethyl--1,3-dihydro-1H-indenes-2-base methyl alcohol.
2. according to claim 1 a kind of 2,5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices; It is characterized in that: in the above-mentioned steps (1), solvent is an ether, the frozen water cooling; Rise to stirring at room 12h, filtrating washing, anhydrous sodium sulfate drying.
3. according to claim 1 a kind of 2,5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices; It is characterized in that: in the above-mentioned steps (2); Solvent is an ether, and the frozen water cooling adds pyridine; Filtrating is respectively with sodium carbonate solution, water, saturated brine washing, anhydrous sodium sulfate drying.
4. according to claim 1 a kind of 2,5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices; It is characterized in that: in the above-mentioned steps (3), solvent is an absolute ethyl alcohol, reflux 8h; Ethyl acetate extraction; The saturated brine washing, anhydrous sodium sulfate drying, high vacuum rectification under vacuum.
5. according to claim 1 a kind of 2,5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices; It is characterized in that: in the above-mentioned steps (4), reflux 50h, cool to room temperature; Anhydrous sodium sulfate drying; Acetic acid ethyl dissolution, saturated brine washing, high vacuum rectification under vacuum.
6. according to claim 1 a kind of 2,5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices is characterized in that: in the above-mentioned steps (5); Under nitrogen protection, in anhydrous tetrahydro furan, add diisopropylamine, be cooled to-78 ℃, drip n-butyllithium solution; After stirring 45min, add 5-methyl-2,3-dihydro-1H-indenes-2-base ethyl formate keeps-78 ℃ to continue to stir 1h; Add methyl iodide, be warmed up to room temperature, reaction 5h.
7. according to claim 1 a kind of 2,5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices, it is characterized in that: in the above-mentioned steps (5), sherwood oil: the ratio of ETHYLE ACETATE is 20:1.
8. according to claim 1 a kind of 2,5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices, it is characterized in that: in the above-mentioned steps (6), solvent is an ether, the frozen water cooling rises to stirring at room 2h.
9. according to claim 1 a kind of 2,5-dimethyl--1, the compound method of 3-dihydro-1H-indenes-2-base methyl alcohol spices, it is characterized in that: in the above-mentioned steps (6), sherwood oil: the ratio of ETHYLE ACETATE is 20:1.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1022265A1 (en) * | 1999-01-22 | 2000-07-26 | Firmenich Sa | 2-Indanemethanol derivatives and their use as perfuming ingredients |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1022265A1 (en) * | 1999-01-22 | 2000-07-26 | Firmenich Sa | 2-Indanemethanol derivatives and their use as perfuming ingredients |
Non-Patent Citations (6)
| Title |
|---|
| 《Can.J.Chem.》 19891231 P. Canonne, et al. "Etude de l'annelation a partir de derives dibromomes-1,4 et-1,5 en presence de carbanions" 555-564 1-9 第67卷, * |
| 《Helvetica Chimica Acta》 20041231 Serge Lamboley, et al. "Synthesis and Properties of Conformationally Constrained Analogues of Floral-Type Odorants" 1767-1793 1-9 第87卷, * |
| 《ORGANIC LETTERS》 20100120 Sergiy Levin, et al. "Rapid Assembly of the Salvileucalin B Norcaradiene Core" 780-783 1-9 第12卷, 第4期 * |
| P. CANONNE, ET AL.: ""Etude de l’annelation a partir de derives dibromomes-1,4 et-1,5 en presence de carbanions"", 《CAN.J.CHEM.》 * |
| SERGE LAMBOLEY, ET AL.: ""Synthesis and Properties of Conformationally Constrained Analogues of Floral-Type Odorants"", 《HELVETICA CHIMICA ACTA》 * |
| SERGIY LEVIN, ET AL.: ""Rapid Assembly of the Salvileucalin B Norcaradiene Core"", 《ORGANIC LETTERS》 * |
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Application publication date: 20121003 |