CN102875525A - Preparation method of 4-(hydroxymethyl) benzo 15-crown-5 - Google Patents
Preparation method of 4-(hydroxymethyl) benzo 15-crown-5 Download PDFInfo
- Publication number
- CN102875525A CN102875525A CN2012104331733A CN201210433173A CN102875525A CN 102875525 A CN102875525 A CN 102875525A CN 2012104331733 A CN2012104331733 A CN 2012104331733A CN 201210433173 A CN201210433173 A CN 201210433173A CN 102875525 A CN102875525 A CN 102875525A
- Authority
- CN
- China
- Prior art keywords
- crown
- benzo
- methylol
- preparation
- formyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 0 ONC1C=C2O*COCCOCCOCCOC2CC1 Chemical compound ONC1C=C2O*COCCOCCOCCOC2CC1 0.000 description 2
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a synthesis and purifying method of 4-(hydroxymethyl) benzo 15-crown-5. According to the method provided by the invention, the final product has the yield of 54%, and the yield of an intermediate product 3 is over 80%; the production method is scientific and reasonable; and detailed theoretical and practical guidelines are provided for follow-up expanding production.
Description
Technical field
The invention belongs to the compound preparation field, the preparation method of especially a kind of 4-(methylol) benzo-15-crown-5.
Background technology
At present, because Bioexperiment makes new breakthroughs, make us in the process for the treatment of and the searching cause of disease, means are mistake more, the result is more accurate, so for treating various diseases the property pharmaceutical requirements is also increased gradually, therefore, various compounds with new function are in a large amount of being developed, and the whole world all has the new compound of the various difficult and complicated cases of opposing in searching, so in the process of these new compound exploitations, can produce the compound of numerous new textures and new configuration, and then searching is useful in these numerous new compounds, and the molecule for the treatment of use is arranged, and therefore developing new compound is one and important process.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, a kind of 4-(methylol) preparation method of benzo-15-crown-5 is provided, synthetic and this compound of purifying of the present invention makes its purity arrive certain requirement, can further test or application it.
The present invention realizes that the technical scheme of purpose is as follows:
The preparation method of a kind of 4-(methylol) benzo-15-crown-5, step is as follows:
⑴ synthesizing of 4'-formyl benzo-15-crown-5
Take by weighing TEG DAADBSA ester, be dissolved in DMF, stir the lower 0412 that adds, fully after the dissolving, slowly add potassium hydroxide, slowly heat up after the stirring at room reaction, react complete rear adding suitable quantity of water, extract with EA, the concentrated brown oil that to get of organic phase gets white solid through column chromatography, get white solid 2.6g and be 4 '-the formyl benzo-15-crown-5;
⑵ synthesizing of 4-(methylol) benzo-15-crown-5
Take by weighing 4'-formyl benzo-15-crown-5, be dissolved in MeOH, cryosel slowly adds sodium borohydride after bathing cooling.Stirring reaction 5h under the room temperature condition reacts an amount of saturated ammonium chloride solution cancellation of complete rear adding, and with the DCM extraction, organic phase is concentrated, and residue gets white solid 4-(methylol) benzo-15-crown-5 2 through column chromatography.
And described TEG DAADBSA ester: the mass ratio of 0412 is 4:1-5.
And described 4'-formyl benzo-15-crown-5: the mass ratio of sodium borohydride is 2.96:0.76.
Advantage of the present invention and beneficial effect are:
1, the invention provides the synthetic and purification process of a kind of 4-(methylol) benzo-15-crown-5, its final product productive rate is more than 80%, and production method science, reasonable instructs for follow-up expanding production provides detailed theory and practice.
2, the invention provides synthesis condition, the raw material of each step in 4-(methylol) the benzo-15-crown-5 building-up process, and the nuclear-magnetism figure of synthetic after product, for the analysis and identification of intermediate product in the building-up process provides detailed support.
Description of drawings
Fig. 1 is the nuclear-magnetism figure of the compounds of this invention 2,
1HNMR:1082019021 (300MHz, DMSO);
Fig. 2 is the nuclear-magnetism figure of 4-of the present invention (methylol) benzo-15-crown-5,
1H NMR:1132023021 (300MHz, DMSO).
Embodiment
Below in conjunction with embodiment, technical scheme of the present invention is further specified, following embodiment is illustrative, is not determinate, can not limit protection scope of the present invention with following embodiment.
The preparation method's of 4-of the present invention (methylol) benzo-15-crown-5 route map is as follows:
Raw material is as follows, is commercially available.
Sodium hydroxide
DMF
0412
Methylene dichloride
TEG DAADBSA ester
Sodium hydroxide
Sodium borohydride
Ammonium chloride
Methyl alcohol
1,7-pimeloyl chloride triethylamine
The preparation method of 4-(methylol) benzo-15-crown-5, step is as follows:
⑴ synthesizing compound 2(4'-formyl benzo-15-crown-5)
Take by weighing compound 1(4.3g), be dissolved in DMF, stir the lower 0412 (1.38g) that adds.After the dissolving, slowly be added dropwise to potassium hydroxide (1.68g) fully, slowly heat up after the stirring at room reaction.React complete rear adding suitable quantity of water, with the EA extraction, organic phase concentrates to get brown oil, gets white solid through column chromatography.Get white solid 2.6g and be compound 2, productive rate 45.7%.
⑵ synthesizing of 4-(methylol) benzo-15-crown-5
Take by weighing compound 2(2.96g), be dissolved in MeOH, cryosel slowly adds sodium borohydride (0.76g) after bathing cooling.Stirring reaction 5h under the room temperature condition.React an amount of saturated ammonium chloride solution cancellation of complete rear adding, with the DCM extraction, organic phase is concentrated, and residue gets white solid 2.4g through column chromatography, productive rate 81%.
Claims (3)
1. the preparation method of a 4-(methylol) benzo-15-crown-5, it is characterized in that: step is as follows:
⑴ synthesizing of 4'-formyl benzo-15-crown-5
Take by weighing TEG DAADBSA ester, be dissolved in DMF, stir the lower 0412 that adds, fully after the dissolving, slowly add potassium hydroxide, slowly heat up after the stirring at room reaction, react complete rear adding suitable quantity of water, extract with EA, the concentrated brown oil that to get of organic phase gets white solid through column chromatography, get white solid 2.6g and be 4 '-the formyl benzo-15-crown-5;
⑵ synthesizing of 4-(methylol) benzo-15-crown-5
Take by weighing 4'-formyl benzo-15-crown-5, be dissolved in MeOH, cryosel slowly adds sodium borohydride after bathing cooling.Stirring reaction 5h under the room temperature condition reacts an amount of saturated ammonium chloride solution cancellation of complete rear adding, and with the DCM extraction, organic phase is concentrated, and residue gets white solid 4-(methylol) benzo-15-crown-5 through column chromatography.
2. the preparation method of 4-according to claim 1 (methylol) benzo-15-crown-5, it is characterized in that: described TEG DAADBSA ester: the mass ratio of 0412 is 4:1-5.
3. the preparation method of 4-according to claim 1 (methylol) benzo-15-crown-5, it is characterized in that: described 4'-formyl benzo-15-crown-5: the mass ratio of sodium borohydride is 2.96:0.76.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104331733A CN102875525A (en) | 2012-11-02 | 2012-11-02 | Preparation method of 4-(hydroxymethyl) benzo 15-crown-5 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104331733A CN102875525A (en) | 2012-11-02 | 2012-11-02 | Preparation method of 4-(hydroxymethyl) benzo 15-crown-5 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102875525A true CN102875525A (en) | 2013-01-16 |
Family
ID=47477078
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012104331733A Pending CN102875525A (en) | 2012-11-02 | 2012-11-02 | Preparation method of 4-(hydroxymethyl) benzo 15-crown-5 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102875525A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007218823A (en) * | 2006-02-20 | 2007-08-30 | Saitama Univ | Chiral probe of self organization type, and absolute configuration determination method for chiral matter using the same |
| US20110054066A1 (en) * | 2009-08-25 | 2011-03-03 | Ivoclar Vivadent Ag | Use of polymerizable macrocyclic polyethers and macrocyclic heteroanalogous polyethers in dental materials |
-
2012
- 2012-11-02 CN CN2012104331733A patent/CN102875525A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007218823A (en) * | 2006-02-20 | 2007-08-30 | Saitama Univ | Chiral probe of self organization type, and absolute configuration determination method for chiral matter using the same |
| US20110054066A1 (en) * | 2009-08-25 | 2011-03-03 | Ivoclar Vivadent Ag | Use of polymerizable macrocyclic polyethers and macrocyclic heteroanalogous polyethers in dental materials |
Non-Patent Citations (2)
| Title |
|---|
| MANABU ISHIFUNE ET AL.: "Preparation of the Modified Platinum Electrodes Bearing the Alkali Metal Ion-Crown Ether Complexes as Mediatory Centers and Their Application to the Electroreduction of Methyl Decanoate", 《ELECTROCHEMISTRY》 * |
| XIAOXI LING ET AL.: "Cucurbituril Slippage: Cations as Supramolecular Lubricants", 《ORG. LETT.》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104262344B (en) | The preparation method of Chinese mugwort Dana Delany | |
| CN111925381B (en) | Synthesis method of baroxavir key intermediate | |
| CN103130719B (en) | A kind of polysubstituted imidazoles Calixarene Derivatives and preparation method | |
| CN103304467B (en) | Single stage method prepares the method for N-caffeoyl tryptamines | |
| CN102875525A (en) | Preparation method of 4-(hydroxymethyl) benzo 15-crown-5 | |
| CN102875524A (en) | Preparation method of 4'-formylbenzo 15-crown-5 | |
| CN102391254B (en) | Preparation method of Candesartan | |
| Yong et al. | Synthesis of rupestonic acid amide derivatives and their in vitro activity against type A 3 and B flu virus and herpes simplex I and II | |
| CN113045583B (en) | Preparation method of pinoxaden metabolite | |
| CN103626791B (en) | A kind of method of synthesizing 3-amino-4-fluorobenzoic boric acid | |
| CN104447776A (en) | Novel heterocyclic organic compound and preparation method thereof | |
| CN102887851B (en) | Compound 3,5-dimethyl-1H-pyrrole-2,4-diformaldehyde and preparation method thereof | |
| CN112745314B (en) | Preparation and synthesis method of aromatic amine compound with specific HIF-2 alpha inhibition effect | |
| CN102603560A (en) | Tetra-azido alkane and preparation method thereof | |
| Yang et al. | New synthesis of 2-benzimidazoleacetates and study of their Knoevenagel reaction | |
| CN105523908A (en) | Method for preparing 2,3-difluoro-6-methoxy-benzaldehyde | |
| CN102731498B (en) | Method for preparing 8-hydroxy julolidine and derivative thereof | |
| CN104892495B (en) | Novel method for synthesizing pyridine-containing compounds | |
| CN105601640A (en) | N-tert-butyloxycarbonyl-7-(aminomethyl)-6-oxo-2-spiro[4.5]decane synthesis method | |
| CN104418865A (en) | Compound biotin-coumarin and preparation method thereof | |
| CN104418791A (en) | Preparation method of compound 2-phenylindole-3-formaldehyde | |
| CN102875486A (en) | Preparation method of 2-benzoxazole acetonitrile | |
| CN104140401A (en) | Compound N-phenyl aza-15-crown-5 preparation method | |
| CN102875427B (en) | Synthetic method of 2-methoxy methylmesylate | |
| CN104447669A (en) | Organic compound and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20130116 |