CN101508628B - Method of preparing 1-phenyl-1-(bicycle [2.2.1]-5-heptylene-2)-ethyl alcohol - Google Patents
Method of preparing 1-phenyl-1-(bicycle [2.2.1]-5-heptylene-2)-ethyl alcohol Download PDFInfo
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- CN101508628B CN101508628B CN2009101151192A CN200910115119A CN101508628B CN 101508628 B CN101508628 B CN 101508628B CN 2009101151192 A CN2009101151192 A CN 2009101151192A CN 200910115119 A CN200910115119 A CN 200910115119A CN 101508628 B CN101508628 B CN 101508628B
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Abstract
The invention discloses a method for preparing 1-phenyl-1-(dicyclo [2, 2, 1]-5-heptylene-2)-ethanol. The method is characterized by firstly heating dicyclopentadiene to 170 DEG C to crack into monocyclopentadiene which then reacts with methylketene by Diels-Alder at room temperature to obtain bridged cyclic ketone, and lastly adding the bridged cyclic ketone into Grignard reagent synthesized from iodine-induced bromobenzene and magnesium by taking absolute ethyl ether as solvent to carry out Grignard reaction so as to prepare the target product. As organic compounds containing the structure of the 1-phenyl-1-(dicyclo [2, 2, 1]-5-heptylene-2)-ethanol and a series of medicaments synthesized by taking the 1-phenyl-1-(dicyclo [2, 2, 1]-5-heptylene-2)-ethanol as intermediate product have function of treating symptoms of neurology and psychiatry, so the 1-phenyl-1-(dicyclo [2, 2, 1]-5-heptylene-2)-ethanol is a medicinal intermediate product having potential researching value. The method has advantages of simple reaction conditions, mild and stable reaction, and is easily operated in workshops.
Description
Technical field
The present invention relates to a kind of 1-phenyl-1-(two ring [2.2.1]-5-heptene-2)-alcoholic acid preparation method.
Background technology
1-phenyl-1-(two ring [2.2.1]-5-heptene-2)-ethanol, because of the organism that contains this structure reaches the purposes that has treatment neurological and psychiatric disorders with its a series of medicines that are intermediate synthesizes, thereby become a kind of important medicine intermediate with potential researching value.Abroad to this compound research be not a lot, and do not have complete synthetic this organic preparation method; Not domestic the appearance as yet to its synthetic report.At this fact, the present invention has at length set forth whole preparation technology: be raw material with the dicyclopentadiene, finally made target product by cracking, Diels-Alder reaction, grignard reaction successively.
Summary of the invention
The object of the present invention is to provide a kind of 1-phenyl-1-(two ring [2.2.1]-5-heptene-2)-alcoholic acid preparation method, this preparation method has made target product 1-phenyl-1-(two ring [2.2.1]-5-heptene-2)-ethanol by cracking, Diels-Alder reaction, grignard reaction successively.
The present invention is achieved like this, and it is characterized in that the preparation method is:
1, in 250 milliliters of four-hole bottles that whipping appts, Ke Shi still head, thermometer are housed, adds dicyclopentadiene 200 grams, be heated to 170 ℃ and carry out air distillation, collect 41.5 ℃～42 ℃ cut, quick weighing products obtained therefrom, calculate next step the used ethylene methacrylic ketone and the amount of anhydrous diethyl ether, after having claimed, be equipped with on the receiving bottle of product and plug drying tube, continue to cool off with icy salt solution;
2, reflux condensing tube is being housed, thermometer, whipping appts, add 150 milliliters of anhydrous diethyl ethers in the four-hole bottle of constant pressure funnel earlier and add 125 gram ethylene methacrylic ketone again, cool off four-hole bottle with icy salt solution before feeding in raw material, add 150 milliliters of ether in the constant pressure funnel earlier, take out the new 1 that steams of 132 grams again and join wherein, icy salt solution is chilled to 0 ℃, start stirring, drip the 1 diethyl ether solution, temperature control is below 10 ℃, it rises to room temperature naturally to drip off relief, stirs 12 hours;
3, in 5 liters exsiccant four-hole bottle, add 144 and restrain magnesium silk and the 1000 milliliters of anhydrous diethyl ethers that are cut into plurality of sections, 2 gram iodine, stir, 28 ℃～30 ℃ of water-bath temperature controls, drip 942 gram bromobenzene and 632 milliliters of solution that anhydrous diethyl ether is made into, water temperature refluxed 3 hours for 50 ℃, ice-water bath drips 408 gram bridged ring ketone, 40 ℃ of reactions of water-bath temperature control 4 hours, ice-water bath cooling below 15 ℃, below 0 ℃, drip the solution that 450 gram ammonium chlorides and 1680 ml waters are made into, have at last that a large amount of solids are molten not to be fallen, add a large amount of water, use extracted with diethyl ether, tell ether layer, wash with water, steam ether to neutrality, in water-bath below 80 ℃, concentrating under reduced pressure promptly gets 1-phenyl-1-(two ring [2.2.1]-5-heptene-2)-ethanol again.
Reflux condensing tube of the present invention top has the drying tube of Calcium Chloride Powder Anhydrous.
Advantage of the present invention is: reaction conditions is simple, reaction temperature and and stable, be easy to amplify produce and enter plant operations.
Embodiment
1. dicyclopentadiene is cracked into the monocycle pentadiene
Whipping appts is housed, (its mouth connects shape prolong always to the Ke Shi still head, the prolong end opening connects a vacuum tail and takes over, the vacuum tail is taken over end opening and is connect a single port bottle, the single port bottle cools off with icy salt solution, the arm that the vacuum tail is taken over connects a drying tube that Calcium Chloride Powder Anhydrous is housed), add dicyclopentadiene 200 grams in 250 milliliters of four-hole bottles of thermometer, be heated to 170 ℃ and carry out air distillation.Collect 41.5 ℃ cut.The weighing products obtained therefrom calculates next step the used ethylene methacrylic ketone and the amount of anhydrous diethyl ether fast.After having claimed, be equipped with on the receiving bottle of product and plug drying tube, continue to cool off with icy salt solution. after treating that next step device is put up, be used for next step reaction immediately.
2.Diels-Alder prepared in reaction bridged ring ketone
Reflux condensing tube (the top band is equipped with the drying tube of Calcium Chloride Powder Anhydrous) is being housed, thermometer, whipping appts adds 150 milliliters of anhydrous diethyl ethers earlier and adds 125 gram ethylene methacrylic ketone again in the four-hole bottle of constant pressure funnel (cooling off with icy salt solution before reinforced).Add 150 milliliters of ether in the constant pressure funnel earlier, take out the new 1 that steams of 132 grams again and join wherein.Icy salt solution is chilled to 0 ℃, starts stirring, drips the 1 diethyl ether solution.Temperature control is below 10 ℃.It rises to room temperature naturally to drip off relief, stirs 12 hours, boils off ether, and residuum steams low-boiling-point substance fall with the water pump decompression.
3. target product 1-phenyl-1-(two ring [2.2.1]-5-heptene-2)-alcoholic acid preparation
Add 144 gram magnesium silks (being cut into a lot of segments), 1000 milliliters of anhydrous diethyl ethers and 2 gram iodine in 5 liters exsiccant four-hole bottle, stir, 28 ℃ of water-bath temperature controls drip 942 gram bromobenzene and 632 milliliters of solution that anhydrous diethyl ether is made into.To note cooling when in the dropping process, vigorous reflux occurring, otherwise be easy to dash material, produce dangerous.Water temperature refluxed 3 hours for 50 ℃, and ice-water bath drips 408 gram bridged ring ketone, 40 ℃ of reactions of water-bath temperature control 4 hours below 15 ℃.The ice-water bath cooling below 0 ℃, drips the solution that 450 gram ammonium chlorides and 1680 ml waters are made into, and the beginning temperature rises very fast, notes the control rate of addition.Have at last that a large amount of solids are molten not to be fallen, add a large amount of water, use extracted with diethyl ether, tell ether layer, wash with water, steam ether to neutrality.Promptly get target product at water-bath concentrating under reduced pressure below 80 ℃ again.
Claims (2)
1. a 1-phenyl-1-(two ring [2.2.1]-5-heptene-2)-alcoholic acid preparation method is characterized in that the preparation method is:
(1) in 250 milliliters of four-hole bottles that whipping appts, Ke Shi still head, thermometer are housed, adds dicyclopentadiene 200 grams, be heated to 170 ℃ and carry out air distillation, collect 41.5 ℃～42 ℃ cut, quick weighing products obtained therefrom, calculate next step the used ethylene methacrylic ketone and the amount of anhydrous diethyl ether, after having claimed, be equipped with on the receiving bottle of product and plug drying tube, continue to cool off with icy salt solution;
(2) in the four-hole bottle that reflux condensing tube, thermometer, whipping appts, constant pressure funnel are housed, add 150 milliliters of anhydrous diethyl ethers earlier and add 125 gram ethylene methacrylic ketone again, cool off four-hole bottle with icy salt solution before reinforced, add 150 milliliters of ether in the constant pressure funnel earlier, take out again 132 grams new steam 1, the 3-cyclopentadiene joins wherein, icy salt solution is chilled to 0 ℃, starts stirring, drips 1,3-cyclopentadiene diethyl ether solution, temperature control is below 10 ℃, and it rises to room temperature naturally to drip off relief, stirs 12 hours;
(3) in 5 liters exsiccant four-hole bottle, add the magnesium silk that 144 grams are cut into plurality of sections, 1000 milliliters of anhydrous diethyl ethers and 2 gram iodine, stir, 28 ℃～30 ℃ of water-bath temperature controls, drip 942 gram bromobenzene and 632 milliliters of solution that anhydrous diethyl ether is made into, water temperature refluxed 3 hours for 50 ℃, ice-water bath drips 408 gram bridged ring ketone below 15 ℃, 40 ℃ of reactions of water-bath temperature control 4 hours, the ice-water bath cooling, drip the solution that 450 gram ammonium chlorides and 1680 ml waters are made into below 0 ℃, have at last that a large amount of solids are molten not to be fallen, add a large amount of water, use extracted with diethyl ether, tell ether layer, wash with water, steam ether to neutrality, in water-bath below 80 ℃, concentrating under reduced pressure promptly gets 1-phenyl-1-(two ring [2.2.1]-5-heptene-2)-ethanol again.
2. a kind of 1-phenyl-1-according to claim 1 (two ring [2.2.1]-5-heptene-2)-alcoholic acid preparation method is characterized in that the reflux condensing tube top has the drying tube of Calcium Chloride Powder Anhydrous.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101151192A CN101508628B (en) | 2009-03-30 | 2009-03-30 | Method of preparing 1-phenyl-1-(bicycle [2.2.1]-5-heptylene-2)-ethyl alcohol |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101151192A CN101508628B (en) | 2009-03-30 | 2009-03-30 | Method of preparing 1-phenyl-1-(bicycle [2.2.1]-5-heptylene-2)-ethyl alcohol |
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| Publication Number | Publication Date |
|---|---|
| CN101508628A CN101508628A (en) | 2009-08-19 |
| CN101508628B true CN101508628B (en) | 2011-12-28 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2009101151192A Expired - Fee Related CN101508628B (en) | 2009-03-30 | 2009-03-30 | Method of preparing 1-phenyl-1-(bicycle [2.2.1]-5-heptylene-2)-ethyl alcohol |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2789110A (en) * | 1953-03-14 | 1957-04-16 | Knoll Ag | Amino alcohols substituted by bicycloalkyl residues and a process of making same |
| CN1525964A (en) * | 2001-05-18 | 2004-09-01 | Method for the production of biperidin |
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2009
- 2009-03-30 CN CN2009101151192A patent/CN101508628B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2789110A (en) * | 1953-03-14 | 1957-04-16 | Knoll Ag | Amino alcohols substituted by bicycloalkyl residues and a process of making same |
| CN1525964A (en) * | 2001-05-18 | 2004-09-01 | Method for the production of biperidin |
Non-Patent Citations (1)
| Title |
|---|
| Manfred Meyer zur Heyde.Neuere Anwendungen von Trichloracetylisocyanat in der 1H-NMR-Spektroskopie.《Fresenius Z. Anal. Chem.》.1979,第295卷125-142. * |
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| CN101508628A (en) | 2009-08-19 |
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