CN107513050A - The preparation method that a kind of olefin(e) acid bromine lactonizes - Google Patents
The preparation method that a kind of olefin(e) acid bromine lactonizes Download PDFInfo
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- CN107513050A CN107513050A CN201710732759.2A CN201710732759A CN107513050A CN 107513050 A CN107513050 A CN 107513050A CN 201710732759 A CN201710732759 A CN 201710732759A CN 107513050 A CN107513050 A CN 107513050A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/30—Oxygen atoms, e.g. delta-lactones
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to the preparation method that structural formula olefin(e) acid bromine as follows lactonizes：
Description
The present invention relates to the preparation method that a kind of olefin(e) acid bromine lactonizes.
Bromine lactonization reaction refers to alkene acid compounds in the presence of reagent containing bromine, and intramolecular cyclization occurs and obtains
Bromine lactone compound.In this course of reaction, the step of ethylene linkage one for being related to reaction produces two miscellaneous (O-C-C- of new carbon
Br) singly-bound.Olefin(e) acid substrate for producing two chiral centres simultaneously, bromine lactonization reaction show stereocpecificity.This is anti-
Answer since self-discovery just in Synthetic Organic Chemistry in occupation of consequence, be widely used in the fully synthetic research of natural products
In, it is a kind of very effective synthetic method.
In view of the importance of bromine lactonization reaction, its synthetic method receives more and more attention in recent years.Olefin(e) acid and bromine
The reaction of simple substance is to be most widely used at present, and the method that most common bromine lactonizes.But because bromine simple substance is that one kind has
Poison, it is corrosive, volatile liquid, not easy to operate, the application of the method is restricted.Then increasing research exists
It is improved in conventional method, finds the brominated reagent of alternative bromine.Synthetic method main at present has following two：(1)
Bromine of the olefin(e) acid under N- bromo-succinimides (NBS) and the like effect lactonizes；(2) olefin(e) acid is in oxidant and metal bromate
Bromine under compound effect lactonizes.These improved methods provide abundant safe optional approach for bromine lactonization reaction,
But the defects of different be present：Reagent price is expensive, and yield is not high, and regioselectivity is bad.
It is an object of the invention to provide the preparation method that a kind of new olefin(e) acid bromine lactonizes.It is characterized in that with olefin(e) acid (3- alkene
Acid, obtusilic acid, 5- olefin(e) acids) it is raw material, using dichloromethane as solvent, in the presence of dimethyl sulfoxide/oxalyl bromine composite reagent, obtain
Lactonized product to corresponding bromine.The present invention preparation method have reagent is cheap and easy to get, easy to operate, yield is high, selectivity
The advantages of good.Reaction equation is as follows：
The present invention relates to the preparation method that structural formula olefin(e) acid bromine as follows lactonizes：
Its main process is：The dichloromethane solution of dimethyl sulfoxide (1.5eq) is first added dropwise to oxalyl bromine at -78 DEG C
In the dichloromethane solution of (1.5eq), then raw material olefin(e) acid is added dropwise, is then back to 0 DEG C of reaction, obtain corresponding bromine and lactonize production
Thing, 3- olefin(e) acids and obtusilic acid obtain gamma lactone product, and 5- olefin(e) acids then obtain delta-lactone product, and yield is 45~85%.
The lactonize structure of product of the olefin(e) acid bromine prepared in the inventive method is all confirmed by nuclear magnetic resonance.Analysis
As a result after being attached to embodiment.
Embodiment
(1)(4R*, 5S*) the bromo- 5- phenyl of -4--dihydrofuran -2 (3H) -one preparation
Nitrogen is protected, in the 100mL three-necked flasks equipped with thermometer, addition oxalyl bromine (7.5mmol, 1.1mL,
1.5eq) and anhydrous methylene chloride (10mL).At liquid nitrogen--78 DEG C of ethanol bath, dimethyl sulfoxide is slowly added dropwise with constant pressure funnel
Anhydrous methylene chloride (10mL) solution of (7.5mmol, 0.53mL, 1.5eq).After being added dropwise, continue to stir at -78 DEG C
10min, then anhydrous methylene chloride (10mL) solution of (E) -4- phenyl -3-butenoic acid (5mmol, 810mg, 1.0eq) is added dropwise.Drop
After adding, continue to stir 10min at -78 DEG C, be then back to 0 DEG C of reaction 2h.At 0 DEG C of ice bath, 30mL sodium bicarbonate waters are added
Solution (5%), liquid separation, takes organic phase, is washed with saturated sodium-chloride water solution (50mL), anhydrous sodium sulfate drying.Filtering, revolving
Solvent afforded crude material is removed, is purified through column chromatography for separation and (petrol ether/ethyl acetate=15: 1), obtains (4R*, 5S*) the bromo- 5- benzene of -4-
Base-dihydrofuran -2 (3H) -one 915mg, yield 76%.1H NMR (300MHz, CDCl3) δ 7.46-7.36 (m, 5H), 5.66
(d, J=5.1Hz, 1H), 4.37 (ddd, J=7.2,6.3,5.1Hz, 1H), 3.24 (dd, J=18.3,7.5Hz, 1H), 2.97
(dd, J=18.3,6.6Hz, 1H).13C NMR (75MHz, CDCl3) δ 173.08,135.98,129.48,129.18,125.52,
87.99,45.70,38.94.
(2) preparation of 5- (bromomethyl) -3,3- dimethyl-dihydrofuran -2 (3H) -one
Nitrogen is protected, in the 100mL three-necked flasks equipped with thermometer, addition oxalyl bromine (7.5mmol, 1.1mL,
1.5eq) and anhydrous methylene chloride (10mL).At liquid nitrogen--78 DEG C of ethanol bath, dimethyl sulfoxide is slowly added dropwise with constant pressure funnel
Anhydrous methylene chloride (10mL) solution of (7.5mmol, 0.53mL, 1.5eq).After being added dropwise, continue to stir at -78 DEG C
10min, then 2 are added dropwise, anhydrous methylene chloride (10mL) solution of 2- dimethyl -4- penetenoic acids (5mmol, 640mg, 1.0eq).Drop
After adding, continue to stir 10min at -78 DEG C, be then back to 0 DEG C of reaction 2h.At 0 DEG C of ice bath, 30mL sodium bicarbonate waters are added
Solution (5%), liquid separation, takes organic phase, is washed with saturated sodium-chloride water solution (50mL), anhydrous sodium sulfate drying.Filtering, revolving
Solvent afforded crude material is removed, is purified through column chromatography for separation and (petrol ether/ethyl acetate=10: 1), obtains 5- (bromomethyl) -3,3- bis-
Methyl-dihydro furans -2 (3H) -one 880mg, yield 85%.1H NMR (300MHz, CDCl3) δ 4.66-4.57 (m, 1H),
3.54 (dd, J=10.8,5.1Hz, 1H), 3.47 (dd, J=10.8,6.0Hz, 1H), 2.25 (dd, J=12.9,6.3Hz,
1H), 1.91 (dd, J=12.9,9.3Hz, 1H), 1.28 (s, 3H), 1.26 (s, 3H).13C NMR (75MHz, CDCl3)δ
180.97,74.74,41.87,40.61,33.74,24.96,24.91.
(3) preparation of 6- (bromomethyl)-oxinane -2- ketone
Nitrogen is protected, in the 100mL three-necked flasks equipped with thermometer, addition oxalyl bromine (7.5mmol, 1.1mL,
1.5eq) and anhydrous methylene chloride (10mL).At liquid nitrogen--78 DEG C of ethanol bath, dimethyl sulfoxide is slowly added dropwise with constant pressure funnel
Anhydrous methylene chloride (10mL) solution of (7.5mmol, 1.52g, 1.5eq).After being added dropwise, continue to stir at -78 DEG C
10min, then 5- hexenoic acids (5mmol, 570mg, 1.0eq) anhydrous methylene chloride (10mL) solution is added dropwise.After being added dropwise ,-
Continue at 78 DEG C stir 10min, add potassium carbonate (25mmol, 3.45g, 5.0eq) and 18- crown ethers -6 (0.25mmol, 66mg,
0.05eq), room temperature reaction 5h is then returned.Filter, 30mL distilled water is added in filtrate, liquid separation, organic phase is taken, uses saturated sodium-chloride
The aqueous solution (50mL) washs, anhydrous sodium sulfate drying.Filtering, revolving remove solvent afforded crude material, (oil are purified through column chromatography for separation
Ether/ethyl acetate=10: 1), 6- (bromomethyl)-oxinane -2- ketone 435mg, yield 45% are obtained.1H NMR
(600MHz, CDCl3) δ 4.52-4.47 (m, 1H), 3.52 (dd, J=10.8,4.2Hz, 1H), 3.47 (dd, J=10.8,
6.0Hz, 1H), 2.60 (dddd, J=18.0,6.6,4.8,1.2Hz, 1H), 2.46 (ddd, J=17.4,9.6,7.2Hz, 1H),
2.14-2.08 (m, 1H), 1.97 (ddq, J=13.8,7.2,4.8Hz, 1H), 1.91-1.83 (m, 1H), 1.70 (dtd, J=
13.8,11.4,5.4Hz, 1H).13C NMR (150MHz, CDCl3) δ 170.45,78.70,33.89,29.50,26.42,
18.27。
Claims (1)
1. the preparation method that a kind of olefin(e) acid bromine lactonizes, it is characterized in that with olefin(e) acid (3- olefin(e) acids, obtusilic acid, 5- olefin(e) acids) for raw material,
Using dichloromethane as solvent, in the presence of dimethyl sulfoxide/oxalyl bromine composite reagent, obtain corresponding bromine and lactonize product, instead
Answer formula as follows：
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108383812A (en) * | 2018-04-25 | 2018-08-10 | 北京工商大学 | A kind of α, the preparation method of β-unsaturation-gamma lactone |
| CN108383708A (en) * | 2018-04-25 | 2018-08-10 | 北京工商大学 | A kind of preparation method of alpha-brominated ketone |
| CN113372310A (en) * | 2021-07-12 | 2021-09-10 | 江苏弘和药物研发有限公司 | Synthesis method of 4-n-octyl butenolide |
| CN113754616A (en) * | 2021-09-27 | 2021-12-07 | 北京工商大学 | Preparation method of trans-3-thiophenyl-gamma-lactone |
Citations (1)
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| WO2016183150A1 (en) * | 2015-05-12 | 2016-11-17 | Temple University-Of The Commonwealth System Of Higher Education | Novel sigma-2 receptor binders and their method of use |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016183150A1 (en) * | 2015-05-12 | 2016-11-17 | Temple University-Of The Commonwealth System Of Higher Education | Novel sigma-2 receptor binders and their method of use |
Non-Patent Citations (3)
| Title |
|---|
| ISABEL ALVARADO-BELTRAN 等: "Enantioselective synthesis of 4-alkenoic acids via Pd-catalyzed allylic alkylation: stereocontrolled construction of c and d-lactones", 《TETRAHEDRON: ASYMMETRY》 * |
| KENSUKE KIYOKAWA 等: "Hypervalent Iodine(III)-Mediated Decarboxylative Ritter-Type Amination Leading to the Production of α‑Tertiary Amine Derivatives", 《J. ORG. CHEM.》 * |
| 朱敏 等: "烯酸在碘化铵催化作用下的卤代内酯化反应", 《高等学校化学学报》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108383812A (en) * | 2018-04-25 | 2018-08-10 | 北京工商大学 | A kind of α, the preparation method of β-unsaturation-gamma lactone |
| CN108383708A (en) * | 2018-04-25 | 2018-08-10 | 北京工商大学 | A kind of preparation method of alpha-brominated ketone |
| CN113372310A (en) * | 2021-07-12 | 2021-09-10 | 江苏弘和药物研发有限公司 | Synthesis method of 4-n-octyl butenolide |
| CN113754616A (en) * | 2021-09-27 | 2021-12-07 | 北京工商大学 | Preparation method of trans-3-thiophenyl-gamma-lactone |
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