CN101367763B - Synthesis process of 1-phenyl-3-methyl-5-pyrazolone - Google Patents
Synthesis process of 1-phenyl-3-methyl-5-pyrazolone Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 33
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 27
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 27
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 title claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 63
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- 239000013078 crystal Substances 0.000 claims abstract description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 14
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229940067157 phenylhydrazine Drugs 0.000 claims abstract description 10
- 238000010992 reflux Methods 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 238000001914 filtration Methods 0.000 claims abstract description 3
- 230000007935 neutral effect Effects 0.000 claims abstract 2
- 239000000243 solution Substances 0.000 claims description 21
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 claims description 19
- 238000001953 recrystallisation Methods 0.000 claims description 8
- 239000012046 mixed solvent Substances 0.000 claims description 7
- 238000002425 crystallisation Methods 0.000 claims description 6
- 230000008025 crystallization Effects 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 2
- 238000013019 agitation Methods 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 239000002932 luster Substances 0.000 abstract description 3
- 239000012043 crude product Substances 0.000 abstract 2
- 239000000047 product Substances 0.000 abstract 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 abstract 1
- 238000005516 engineering process Methods 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 238000001816 cooling Methods 0.000 description 5
- 239000012295 chemical reaction liquid Substances 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 150000004031 phenylhydrazines Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- ZRHUHDUEXWHZMA-UHFFFAOYSA-N 1,4-dihydropyrazol-5-one Chemical compound O=C1CC=NN1 ZRHUHDUEXWHZMA-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 229940038531 phenylhydrazine hydrochloride Drugs 0.000 description 2
- -1 pyrazole ketone Chemical class 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- HCQIUTXMZNVRAP-UHFFFAOYSA-N 5-methyl-2-phenyl-4H-pyrazol-3-one Chemical compound CC1=NN(C(C1)=O)C1=CC=CC=C1.CC1=NN(C(C1)=O)C1=CC=CC=C1 HCQIUTXMZNVRAP-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
- JOVOSQBPPZZESK-UHFFFAOYSA-N phenylhydrazine hydrochloride Chemical compound Cl.NNC1=CC=CC=C1 JOVOSQBPPZZESK-UHFFFAOYSA-N 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000002912 waste gas Substances 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
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- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention relates to a synthesis process of 1-benzyl-3-methyl-5-pyrazole alkone. The process comprises the following steps: firstly, the pH of methanol solution of phenylhydrazine is adjusted to be between 5.0 and 6.5 with hydrochloric acid, acetoacetic ester is added drop by drop when the solution is mixed, the temperature is controlled between 40 DEG C and 90 DEG C, and the reflux reaction lasts for 1 to 6 hours; secondly, the methanol in the reaction solution is distilled, the pH is adjusted to be neutral, the reaction solution is stirred, and the reflux reaction lasts for 1 to 3 hours at the temperature between 60 DEG C and 80 DEG C; thirdly, the reaction solution is cooled after the reaction is completed, the crystal is separated, and the crude product is acquired through filtration; fourthly, the crude product is dissolved in a solvent with methanol under the hot condition and recrystallized, and the finished product of white crystal 1-benzyl-3-methyl-5-pyrazole alkone can be prepared. The present invention has the advantages that the pollution is less, the process is simple, the cost is low, the yield rate of the product is high, the purity is high, and the luster is good.
Description
[technical field]
The present invention relates to a kind of preparation of organic fine chemical, be specifically related to the synthesis technique of 1-phenyl-3-methyl-5-pyrazolone.
[background technology]
1-phenyl-3-methyl-5-pyrazolone (1-phenyl-3-methyl-5-pyrazolone); Promptly 1,3, the 5-pyrazolone; It is a kind of important fine chemicals midbody; The staining agent of making color film commonly used also is the important source material of more synthetic medicine and agricultural chemicals, is widely used in synthesizing pyrazole ketone ntipyretic analgesic medicine, pyrazolone matching stain, agricultural chemicals and other fine chemistry midbody.The industrial preparative method of 1-phenyl-3-methyl-5-pyrazolone normally is raw material with the ketene dimer; Under the vitriolic katalysis, make with ethyl esterification; But can consume a large amount of acid in the production process and produce acid-bearing wastewater, waste gas; Environmental pollution is bigger, and production technique is longer, and productive rate is not high.
The phenylhydrazine of developing at present-methyl aceto acetate method is synthesized 1-phenyl-3-methyl-5-pyrazolone; Normally adopt the method that in the alcohol solvent of methyl aceto acetate, drips phenylhydrazine solution to synthesize; This art production process is short, pollution is little, and product yield is higher relatively.On the basis of this technology, Xiang Haiying (" 1,3; Study on Preparation of 5-pyrazolone "; " Tianjin chemical industry ", the 19th the 1st phase of volume, in January, 2005) explored with the technology of methyl alcohol replacement ethanol as solvent; And provided corresponding reaction conditions, make product yield obtain further raising.But need prepared beforehand phenylhydrazine hydrochloride diazonium salt for obtaining higher yields (about 99%) in this technology; (need reaction solution be bathed cooling with cryosel earlier in the process, the later stage needs the heated and boiled reaction soln again to one side reaction conditions complicacy, and operation easier is big in the preparation process of diazonium salt; Program is numerous and diverse; Cost is also high), auxiliary reagents such as employed Sodium Nitrite, sulfurous gas are easy to generate the high pollution wastewater in the technology on the other hand, and are unfriendly to environment; Moreover; Though the product purity that this technology makes has reached 99%, product is to be flaxen crystal, but not white crystal; Because these article are widely used in dyestuff, medicine intermediate, the bad purifying that will directly have influence on its finished product that in subsequent applications, makes of the color and luster of product.
[summary of the invention]
The present invention is directed to the above-mentioned deficiency that exists in the prior art, provide a kind of pollute little, technology is simple, the synthesis technique of lower-cost 1-phenyl-3-methyl-5-pyrazolone, prepared product yield is high, purity height and color and luster are good.
The present invention provides the synthesis technique of a kind of 1-phenyl-3-methyl-5-pyrazolone for the technical scheme that the realization above-mentioned purpose adopts is, its reaction principle is:
This technology comprises following steps:
S1. the methanol solution of phenylhydrazine is regulated pH to 5.0-6.5 with hydrochloric acid, under agitation dropwise add methyl aceto acetate then, controlled temperature is at 40-90 ℃, back flow reaction 1-6 hour;
S2. distill out the methyl alcohol in the above-mentioned reaction solution, and regulate pH to 7.0, stir, 60-80 ℃ of temperature refluxed reaction 1-3 hour;
S3. reaction finishes the postcooling reaction solution, separates out crystal, filters and obtains bullion;
S4. with bullion with containing the methanol solvent thermosol, carry out recrystallization again, white crystal shape 1-phenyl-3-methyl-5-pyrazolone finished product.
Preferably, the mol ratio of phenylhydrazine and methyl aceto acetate is 1:0.8～1:2 among the above-mentioned synthesis technique step S1, preferred 1:1～1:1.05.
Preferably, the dropping time of methyl aceto acetate is 0.5-4 hour among the above-mentioned synthesis technique step S1, preferred 1-2 hour.
Preferably, among the above-mentioned synthesis technique step S1 controlled temperature at 50-60 ℃.
Preferably, among the above-mentioned synthesis technique step S1 reflux time at 1.5-3 hour.
Preferably, among the above-mentioned synthesis technique step S2 controlled temperature at 70-75 ℃.
Preferably, among the above-mentioned synthesis technique step S2 reflux time at 1.5-2.5 hour.
Preferably, the recrystallization among the above-mentioned synthesis technique step S4 is to adopt the gac reflux type, back flow reaction 10-90 minute, and preferred 10-30 minute, heat filtering, crystallization then.
Preferably, the recrystallization among the above-mentioned synthesis technique step S4 is to adopt mixed solvent thermosol crystallization mode, and used mixed solvent is methyl alcohol-acetone or methyl alcohol-ETHYLE ACETATE mixed solution.
The beneficial effect that the 1-phenyl that embodiment of the present invention provided-3-methyl-5-pyrazolone synthesis technique is had is; Directly the methanol solution with phenylhydrazine is adjusted in the weak acid environment between the pH value 5.0-6.5; Make the reaction of phenylhydrazine and methyl aceto acetate be easier to carry out; Simplify the technology of prepared beforehand phenylhydrazine hydrochloride, and in the relatively short reaction times, reached higher reactivity; Optimize processing condition, slowly drip methyl aceto acetate, make reaction more abundant, obtain higher yield; This technology has added re-crystallization step in bullion refining; Adopt the means re-crystallization of gac thermal backflow crystallization or mixed solvent thermosol crystallization; Solve this defective of xln yellowing that exists in the prior art well, made purity height, coloury 1-phenyl-3-methyl-5-pyrazolone crystal.
[embodiment]
Embodiment 1
In the 500ml three-necked bottle, add 80ml methyl alcohol and 54.1 gram (0.5mol) phenylhydrazines, stir, add concentrated hydrochloric acid; Regulate the pH value to pH5.9; Heated soln to 45 ℃, and in 110 minutes, dropwise add 78.1 gram (0.6mol) methyl aceto acetates, control reaction temperature is at 45-50 ℃ simultaneously.After treating that methyl aceto acetate dropwises, reaction solution continued back flow reaction 2 hours.After reaction finished, methyl alcohol was reclaimed in the distillation that heats up, and again solution is adjusted to neutrality (pH value 7.0) with soda ash water, and stirred solution and be warming up to 70 ℃ is incubated back flow reaction 2 hours then.Follow cooling reaction liquid, separate out crystal, cross and filter bullion.
Above-mentioned bullion is used the anhydrous methanol thermosol, add gac then and refluxed filtered while hot 15 minutes; Leave standstill filtrating and separate out crystal, drying gets 1-phenyl-3-methyl-5-pyrazolone white crystal product 84.5 grams (yield is 96.3%); Recording its fusing point is 127-127.6 ℃, and purity is 99.3%.
Embodiment 2
In the 500ml three-necked bottle, add 80ml methyl alcohol and 54.1 gram (0.5mol) phenylhydrazines, stir, add concentrated hydrochloric acid; Regulate the pH value to pH5.8; Heated soln to 75 ℃, and in 60 minutes, dropwise add 65.1 gram (0.5mol) methyl aceto acetates, control reaction temperature is at 55-60 ℃ simultaneously.After treating that methyl aceto acetate dropwises, reaction solution continued back flow reaction 1.5 hours.After reaction finished, methyl alcohol was reclaimed in the distillation that heats up, and again solution is adjusted to neutrality (pH value 7.0) with soda ash water, and stirred solution and be warming up to 75 ℃ is incubated back flow reaction 2.5 hours then.Follow cooling reaction liquid, separate out crystal, cross and filter bullion.
Above-mentioned bullion is used the anhydrous methanol thermosol, add gac then and refluxed filtered while hot 30 minutes; Leave standstill filtrating and separate out crystal, drying gets 1-phenyl-3-methyl-5-pyrazolone white crystal product 82.8 grams (yield is 94.8%); Recording fusing point is 127-127.6 ℃, and purity is 99.7%.
Embodiment 3
In the 500ml three-necked bottle, add 80ml methyl alcohol and 54.1 gram (0.5mol) phenylhydrazines, stir, add concentrated hydrochloric acid; Regulate the pH value to pH6.0; Heated soln to 55 ℃, and in 90 minutes, dropwise add 68.3 gram (0.525mol) methyl aceto acetates, control reaction temperature is at 80-85 ℃ simultaneously.After treating that methyl aceto acetate dropwises, reaction solution continued back flow reaction 2 hours.After reaction finished, methyl alcohol was reclaimed in the distillation that heats up, and again solution is adjusted to neutrality (pH value 7.0) with soda ash water, and stirred solution and be warming up to 70 ℃ is incubated back flow reaction 2 hours then.Follow cooling reaction liquid, separate out crystal, cross and filter bullion.
Above-mentioned bullion is used the methanol-acetone mixed solvent thermosol, and filtered while hot leaves standstill filtrating and separates out crystal; Dry; Get 1-phenyl-3-methyl-5-pyrazolone white crystal product 85.4 grams (yield is 97.6%), recording fusing point is 127-127.6 ℃, and purity is 99.6%.
Embodiment 4
In the 500ml three-necked bottle, add 80ml methyl alcohol and 54.1 gram (0.5mol) phenylhydrazines, stir, add concentrated hydrochloric acid; Regulate the pH value to pH5.9; Heated soln to 50 ℃, and in 2 hours, dropwise add 65.1 gram (0.5mol) methyl aceto acetates, control reaction temperature is at 50-55 ℃ simultaneously.After treating that methyl aceto acetate dropwises, reaction solution continued back flow reaction 3 hours.After reaction finished, methyl alcohol was reclaimed in the distillation that heats up, and again solution is adjusted to neutrality (pH value 7.0) with soda ash water, and stirred solution and be warming up to 75 ℃ is incubated back flow reaction 2.5 hours then.Follow cooling reaction liquid, separate out crystal, cross and filter bullion.
With methyl alcohol-ETHYLE ACETATE mixed solvent thermosol, filtered while hot leaves standstill filtrating and separates out crystal with above-mentioned bullion; Dry; Get 1-phenyl-3-methyl-5-pyrazolone white crystal product 85.0 grams (yield is 97.1%), recording its fusing point is 127-127.6 ℃, and purity is 99.5%.
The above embodiment has only expressed several kinds of embodiments of the present invention, and it describes comparatively concrete and detailed, but can not therefore be interpreted as the restriction to claim of the present invention.Should be pointed out that for the person of ordinary skill of the art under the prerequisite that does not break away from the present invention's design, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with accompanying claims.
Claims (12)
1. the synthesis technique of 1-phenyl-3-methyl-5-pyrazolone is characterized in that, comprises following reactions step:
S1. the methanol solution of phenylhydrazine is regulated pH to 5.0-6.5 with hydrochloric acid, under agitation dropwise add methyl aceto acetate then, controlled temperature is at 40-90 ℃, back flow reaction 1-6 hour;
S2. distill out the methyl alcohol in the above-mentioned reaction solution, and to regulate pH be neutral, stir, reacted 1-3 hour 60-80 ℃ of temperature refluxed;
S3. reaction finishes the postcooling reaction solution, separates out crystal, filters and obtains bullion;
S4. with bullion with containing the methanol solvent thermosol, recrystallization, white crystal shape 1-phenyl-3-methyl-5-pyrazolone finished product.
2. synthesis technique according to claim 1 is characterized in that, the mol ratio of phenylhydrazine and methyl aceto acetate is 1: 0.8～1: 2 among the step S1.
3. synthesis technique according to claim 2 is characterized in that, the mol ratio of phenylhydrazine and methyl aceto acetate is 1: 1～1: 1.05 among the step S1.
4. synthesis technique according to claim 1 is characterized in that, the time that drips methyl aceto acetate among the step S1 is 0.5-4 hour.
5. synthesis technique according to claim 4 is characterized in that, the time of said dropping methyl aceto acetate is 1-2 hour.
6. synthesis technique according to claim 1 is characterized in that controlled temperature is at 50-60 ℃ among the step S1.
7. synthesis technique according to claim 1 is characterized in that, reflux time is 1.5-3 hour among the step S1.
8. synthesis technique according to claim 1 is characterized in that controlled temperature is at 70-75 ℃ among the step S2.
9. synthesis technique according to claim 1 is characterized in that reflux time was at 1.5-2.5 hour among the step S2.
10. synthesis technique according to claim 1 is characterized in that, recrystallization is to adopt the gac reflux type among the step S4, back flow reaction 10-90 minute, and heat filtering, crystallization then.
11. synthesis technique according to claim 10 is characterized in that, the reaction times that said gac refluxes is 10-30 minute.
12. synthesis technique according to claim 1 is characterized in that, recrystallization is to adopt mixed solvent thermosol crystallization mode among the step S4, and used mixed solvent is methyl alcohol-acetone or methyl alcohol-ETHYLE ACETATE mixed solution.
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| CN102060771A (en) * | 2009-11-18 | 2011-05-18 | 南京长澳医药科技有限公司 | Edaravone crystal form and preparation method thereof |
| CN101830852B (en) * | 2010-03-22 | 2012-05-09 | 海南美兰史克制药有限公司 | Edaravone compound of new route |
| CN102180834B (en) * | 2011-03-24 | 2012-09-26 | 江苏正大丰海制药有限公司 | Preparation method for edaravone |
| CN103833640B (en) * | 2012-11-16 | 2016-06-22 | 国药集团国瑞药业有限公司 | A kind of Edaravone crystal, its preparation method and application thereof |
| CN103319409B (en) * | 2013-07-12 | 2015-09-09 | 四川省惠达药业有限公司 | A kind of edaravone compound, its pharmaceutical composition and preparation method thereof |
| CN104262257A (en) * | 2014-10-12 | 2015-01-07 | 湖南华腾制药有限公司 | Preparation method of pyrazole derivative |
| CN105753850A (en) * | 2016-04-12 | 2016-07-13 | 叶芳 | Pyrazolone derivative and preparation method thereof |
| CN107501184A (en) * | 2017-08-01 | 2017-12-22 | 新华制药（寿光）有限公司 | A kind of SO for absorbing the pyrazolone production of 1 phenyl, 3 methyl 52The method of tail gas |
| CN107827821B (en) * | 2017-10-31 | 2021-01-26 | 南通醋酸化工股份有限公司 | Continuous flow clean production process of pyrazolone series products |
| CN107652237A (en) * | 2017-11-15 | 2018-02-02 | 天津瑞岭化工有限公司 | A kind of synthetic method of pyrazolone and its derivative |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4857542A (en) * | 1985-05-20 | 1989-08-15 | Mitsubishi Chemical Industries Limited | Prophylactic and therapeutic composition for circulatory disorders and method of treatment |
| CN1995021B (en) * | 2002-08-01 | 2010-09-08 | 庵原化学工业株式会社 | Production method of pyrazole derivatives |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4857542A (en) * | 1985-05-20 | 1989-08-15 | Mitsubishi Chemical Industries Limited | Prophylactic and therapeutic composition for circulatory disorders and method of treatment |
| CN1995021B (en) * | 2002-08-01 | 2010-09-08 | 庵原化学工业株式会社 | Production method of pyrazole derivatives |
Non-Patent Citations (1)
| Title |
|---|
| 陶琼华等.依达拉奉的合成.《中国医药工业杂志》.2005,第35卷(第11期),643. * |
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