CN1215715A - Process for synthesis of stereoselective 1,3-diol - Google Patents
Process for synthesis of stereoselective 1,3-diol Download PDFInfo
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- CN1215715A CN1215715A CN 97118857 CN97118857A CN1215715A CN 1215715 A CN1215715 A CN 1215715A CN 97118857 CN97118857 CN 97118857 CN 97118857 A CN97118857 A CN 97118857A CN 1215715 A CN1215715 A CN 1215715A
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- alcohol
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Abstract
A process for synthesizing 1,3-diol with stereo selectivity includes such steps as reaction of allyl epoxy alcohol with excess Lewis acid in alcohol or non-protonic solvent for 4-8 hr and chromatographic separation, and features high yield (30-100%) and completing opening of oxygen ring, group migration and reduction in one step.
Description
The present invention relates to a kind of compound stereoscopic selectivity 1, the synthetic method of 3-glycol.
The existing allylic epoxy alcohol that utilizes produces 1, and the 3-glycol mainly adopts hydroborating reagent (LiBH for example
4, i-Bu
2AlH etc.) method of reducing (reference: 1.Tetrahedron Lett., 1986,27, p4343; 2.Tetrahedron Lett., 1982,23, p2719; 3. " The Chemistryof the Hydroxyl Group, " Ed.S.Patai, Interscience, New York, 1971).The deficiency of this method is to realize that carbon skeleton is reset or the group migration, can not control a plurality of three-dimensional centers, and complicated operating process, the experiment condition harshness, and agents useful for same is expensive, and productive rate is not high, is difficult to realize industrialization.
The purpose of this invention is to provide a kind of prior art deficiency that overcomes, agents useful for same economy is easy to get, and toxicity, corrodibility, pungency are all very little, easy, the safety of operation, and yield higher, be easy to industrialized stereoselectivity 1, the synthetic method of 3-glycol.
The objective of the invention is such realization: with allylic epoxy alcohol is raw material, obtains product with the reaction of alkoxide Lewis acid in alcohol or aprotic solvent, as shown in the formula expression.
Reaction expression
The R of reaction raw materials A in the inventive method
1-R
4Be various substituting groups.Lewis acid used in the reaction can provide the sky atomic orbital for various, and the various alkoxide Lewis acids (as aluminum isopropylate) of hydrogen atom can be provided again.The inventive method is prepared 1, and the 3-glycol is that a reduction (be product many than raw material two hydrogen atoms) resets (is C
1On the group C that in product, has moved
2On the position).And as a rule, it (is C that this reaction can be controlled three carbon simultaneously
1, C
2And C
3) configuration.If suppose the priority ordering of group be: C
3＞C
1＞R
3＞R
2, then in most cases the relative configuration of products therefrom is 1R
*, 2R
*, 3S
*Split if carry out enantiomorph, then the absolute configuration of gained two isomer should be respectively 1R, 2R, 3S and 1S, 2S, 3R.
Advantage of the present invention is that step is simple and direct, and only single step reaction can obtain product, easy, the safety of operation, used starting material economy is easy to get, its toxicity, corrodibility, pungency are all less, and in most cases the yield of this method is higher than prior art all at 70-100%.
Embodiments of the invention below are provided
Example 1: by the synthetic (1S of 1-(phenylbenzene-methylol)-cyclohexene oxide (1a)
*, 2S
*, 1 ' S
*)-2-(phenyl-methylol)-2-phenylcyclohexanol (1b) and (1S
*, 2S
*, 1 ' R
*)-2-(phenyl-methylol)-2-phenylcyclohexanol (1c).Reaction formula is as follows.
Reaction formula (one)
Synthesis step: 2.8g (10mmol) allylic epoxy alcohol (1a) and 4.08g (20mmol) aluminum isopropylate are dissolved in the 30ml propyl alcohol, reflux 6 hours, boil off solvent, crude product silica gel column chromatography (drip washing condition: the mixture (2.56g, yield 91%) that gets (1b and 1c) 2/10 ethyl acetate/petroleum ether).Determine that through gas chromatographic analysis the ratio of 1b and 1c is 80: 20.Nucleus magnetic resonance (NMR, 400MHz, CDCl
3, two isomer mixtures) analyze: δ
H(1b+1c): 1.19-2.42 (8H, m), 4.71,4.74,4.75,4.94 (2H, 4 * s), 6.65-7.37 (10, Hm).δc(1b):18.9,19.9,20.7,29.4(4CH
2),49.3(C),74.0,82.9,(2CH),125.9-128.5(10CH),140.0,140.5(2C)。δc(1c):19.6,21.2,26.7,28.9(4CH
2),49.5(C),67.0,81.4(2CH),125.9-128.5(10CH),139.8,140.4(2C)。
Example 2: by the synthetic (1S of 1-(sec.-propyl-phenyl-methylol)-cyclohexene oxide (2a)
*, 2S
*, 1 ' S
*)-2-(phenyl-methylol)-2-isopropyl cyclohexanol (2b) and (1S
*, 2S
*, 1 ' R
*)-2-(phenyl-methylol)-2-isopropyl cyclohexanol (2c).Reaction formula is as follows.
Reaction formula (two)
Synthesis step: 0.4g (1.62mmol) allylic epoxy alcohol (2a) and 0.66g (3.25mmol) aluminum isopropylate are dissolved in the 10ml propyl alcohol, reflux 8 hours, boil off solvent, crude product silica gel column chromatography (drip washing condition: the mixture (0.38g, yield 95%) that gets (2b and 2c) 2/10 ethyl acetate/petroleum ether).Warp
1The ratio that HNMR analyzes 2b and 2c is 73: 27.Nucleus magnetic resonance (NMR, 400MHz, CDCl
3, two isomer mixtures) analyze: δ
H(2b): 0.72 (3H, d, J=6.5Hz), 0.73 (3H, d, J=6.5Hz), 1.24-2.26 (9H, m) .3.51 (2H, s), 3.84 (1H, d, J=1Hz), 4.63 (1H, s), 7.21-7.40 (5H, m).δc(2b):16.0(CH
3),18.8,21.1,21.2(3CH
2),23.2(CH
3),28.7(CH),29.5(CH
2),49.4(C),76.0,84.4(2CH),126.0-129.5(5CH),141.9(C)。δ
H(2c):0.38,0.82(2×3H,2×d,J=6.5Hz),1.24-2.26(9H,m),3.51(2H,s),3.56(1H,d,J=1Hz),4.87(1H,s),7.21-7.40(5H,m)。δc(2c):15.8(CH
3),19.8,21.4(2CH
2),23.8(CH
3),27.3(CH
2),27.8(CH),29.0(CH
2),49.2(C),70.0,82.9(2CH),126.0-129.5(5CH),141.2(C)。
Example 3: by the synthetic (1S of 1-(1 '-hydroxyl suberyl)-cyclopentene oxide (3a)
*, 5S
*, 6R
*)-1,3-dihydroxyl-volution [4,7] dodecane (3b).Reaction formula is as follows.
Reaction formula (three)
Synthesis step: 0.52g (2.65mmol) allylic epoxy alcohol (3a) and 1.08g (5.3mmol) aluminum isopropylate are dissolved in the 10ml propyl alcohol, reflux 6 hours, boil off solvent, crude product silica gel column chromatography (drip washing condition: get product (3b) (0.405g, yield 77%) 2/10 ethyl acetate/petroleum ether).Nucleus magnetic resonance (NMR, 400MHz, CDCl
3) analyze: δ
H(3b): 1.43-2.15 (18H, m), 3.92 (1H, d, J=8.3Hz), 4.00 (1H, dd, J=2,2.5Hz).δc(3b):21.2,22.3,25.5,25.7,28.4,31.2,33.0,34.6,34.8(9CH
2),52.6(C),74.2,82.1(2CH)。
Claims (1)
1. stereoselectivity 1, and the synthetic method of 3-glycol is characterized in that with allylic epoxy alcohol be raw material, in alcohol or aprotic solvent, prepare 1 through single step reaction with alkoxide Lewis acid reagent, the 3-diol compound, products therefrom also has the characteristics of rearrangement except that manying than raw material two hydrogen atoms.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 97118857 CN1215715A (en) | 1997-10-28 | 1997-10-28 | Process for synthesis of stereoselective 1,3-diol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 97118857 CN1215715A (en) | 1997-10-28 | 1997-10-28 | Process for synthesis of stereoselective 1,3-diol |
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|---|---|
| CN1215715A true CN1215715A (en) | 1999-05-05 |
Family
ID=5175017
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|---|---|---|---|
| CN 97118857 Pending CN1215715A (en) | 1997-10-28 | 1997-10-28 | Process for synthesis of stereoselective 1,3-diol |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013538800A (en) * | 2010-08-10 | 2013-10-17 | アッヴィ・インコーポレイテッド | New TRPV3 modulator |
| CN111138243A (en) * | 2019-12-27 | 2020-05-12 | 郑州手性药物研究院有限公司 | Preparation method of (1S,2R) -2-phenylcyclohexanol |
-
1997
- 1997-10-28 CN CN 97118857 patent/CN1215715A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013538800A (en) * | 2010-08-10 | 2013-10-17 | アッヴィ・インコーポレイテッド | New TRPV3 modulator |
| CN111138243A (en) * | 2019-12-27 | 2020-05-12 | 郑州手性药物研究院有限公司 | Preparation method of (1S,2R) -2-phenylcyclohexanol |
| CN111138243B (en) * | 2019-12-27 | 2022-06-24 | 郑州手性药物研究院有限公司 | Preparation method of (1S,2R) -2-phenylcyclohexanol |
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