CN110724033A - Method for preparing alcohol by Suzuki reaction without exogenous base - Google Patents
Method for preparing alcohol by Suzuki reaction without exogenous base Download PDFInfo
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- CN110724033A CN110724033A CN201911010848.1A CN201911010848A CN110724033A CN 110724033 A CN110724033 A CN 110724033A CN 201911010848 A CN201911010848 A CN 201911010848A CN 110724033 A CN110724033 A CN 110724033A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/48—Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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Abstract
The invention belongs to the technical field of organic synthesis. In particular to a preparation method of alcohol compounds. The invention provides a high-efficiency, convenient and fast synthetic method for preparing alcohol compounds through Suzuki reaction, which does not need to use exogenous alkali and has excellent functional group compatibility, aiming at the problems that the preparation of alcohol compounds through the Suzuki type ring-opening coupling reaction of ternary epoxy has some defects, such as limited substrate types, excessive lithium tert-butoxide with strong alkalinity needed in the reaction and the like. Epoxy compounds and aryl boric acid are used as raw materials and react with a solvent under the conditions of a nickel catalyst and a ligand to obtain the alcohol compounds. The method for synthesizing the alcohol compound has mild reaction conditions, avoids using exogenous alkali, and has the advantages of high yield, less side reactions, convenient operation and wide substrate types. Meanwhile, the reaction system is convenient to feed, raw materials are easy to prepare, functional groups are good in compatibility, and a high-efficiency, practical and economical synthesis method is provided for synthesis of alcohol compounds.
Description
Technical Field
The invention belongs to the technical field of organic synthesis. In particular to a preparation method of alcohol compounds.
Background
The Suzuki reaction catalyzed by the transition metal plays an important role in organic and pharmaceutical synthesis, and provides a synthetic method for a large number of active and pharmaceutical molecules, so that the Suzuki reaction obtains the Nobel prize in 2010. Almost all Suzuki reactions require the addition of a stoichiometric amount of exogenous base, which causes the problems of waste in synthesis and functional group compatibility check.
Alcohol compounds are important organic structures and widely exist in various active molecules. Therefore, the synthesis of alcohol compounds has been the focus of research. The ternary epoxy compound can perform nucleophilic and ring-opening reactions with a nucleophilic reagent to obtain the alcohol compound. Thus, the ternary epoxy compound is an important synthon for alcohol compounds. The method is combined with the value of the Suzuki reaction in organic synthesis, researches the Suzuki type ring-opening coupling reaction of transition metal catalytic ternary epoxy, and the synthesized alcohol compound has important synthesis and application values.
Currently, only one example of a transition metal catalyzed Suzuki-type ring-opening coupling reaction of a ternary epoxy is reported, and professor Fu reports a method for preparing an alcohol by copper catalyzed ring-opening coupling of aryl boron and a ternary epoxy in 2010 (chem. This reaction has a great limitation on the type of substrate; epoxy substrates are only suitable for terminal epoxies, organoboron ester substrates are only suitable for arylboron. On the other hand, the reaction requires the addition of an excess of lithium tert-butoxide as exogenous base. The tert-butoxide lithium is expensive and strong in alkalinity, which causes the problems of high synthesis cost, poor functional group compatibility and the like.
In view of the limited types of substrates present in the transition copper catalyzed ternary epoxy and arylboron compounds, the reaction requires the addition of an excess of very basic lithium tert-butoxide. This brings problems of high synthesis cost, reagent waste, functional group compatibility check, etc. The novel transition metal catalysis is developed, and the alcohol compound is synthesized by the ternary epoxy Suzuki type ring-opening coupling reaction without adding exogenous alkali, so that the method has great application value.
In view of some disadvantages of the current Suzuki type ring-opening coupling reaction of ternary epoxy for preparing alcohol compounds. The patent reports a method for preparing alcohol compounds by nickel-catalyzed ternary epoxy Suzuki-type ring-opening coupling reaction without adding exogenous alkali. The method has the advantages of wide substrate types, good functional group compatibility and no need of using exogenous alkali.
Disclosure of Invention
The invention provides a high-efficiency, convenient and fast synthetic method for preparing alcohol compounds through Suzuki reaction, which does not need to use exogenous alkali and has excellent functional group compatibility, aiming at the problems that the preparation of alcohol compounds through the Suzuki type ring-opening coupling reaction of ternary epoxy has some defects, such as limited substrate types, excessive lithium tert-butoxide with strong alkalinity needed in the reaction and the like.
In order to solve the technical problems, the invention adopts the following technical scheme: a method for preparing alcohol by Suzuki reaction without exogenous base is characterized in that: epoxy compounds and aryl boric acid are used as raw materials, and react with a solvent under the conditions of a nickel catalyst and a ligand according to the following reaction formula to obtain alcohol compounds:
wherein R is1、R2Are various types of substituents; ar is aryl; r is aryl or alkenyl;
the nickel catalyst nickel (II) bromide glycol dimethyl ether;
the ligand is 4, 4 '-di-tert-butyl-2, 2' -bipyridine;
the solvent is ethanol;
preferably, the amount of the substance of boric acid is 2 times the amount of the substance of epoxy compound.
Preferably, the amount of material of the catalyst is 10% of the amount of material of the epoxy compound.
Preferably, the amount of substance of the ligand is 12% of the amount of substance of the epoxy compound.
Preferably, the amount of the substance of sodium iodide is 50% of the amount of the substance of the epoxy compound.
Preferably, the reaction temperature is 70 ℃ and the reaction time is 12 h.
Compared with the existing method for preparing the alcohol compound by the ternary epoxy Suzuki reaction, the method for synthesizing the alcohol compound has the advantages of mild reaction conditions, no use of exogenous alkali, high yield, less side reactions, convenience in operation and wide substrate types. Meanwhile, the reaction system is convenient to feed, raw materials are easy to prepare, functional groups are good in compatibility, and a high-efficiency, practical and economical synthesis method is provided for synthesis of alcohol compounds.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments:
example 1
The reaction of this example is as follows:
(1) nickel (II) bromide (10 mol%), 4, 4 '-di-tert-butyl-2, 2' -bipyridine (12 mol%), and sodium iodide (50 mol%) were added to a sealed reaction tube with a branch tube containing magnetons under air, and the reaction tube was purged with argon three times. Adding 0.8mL of ethanol into the reaction tube under the protection of argon, then adding phenylboronic acid (0.5mmol) and cyclohexene oxide (0.25mmol) into the reaction solution in sequence under the protection of argon, plugging a piston, and placing the reaction solution in a 70 ℃ oil bath kettle to stir for reaction for 12 hours.
(2) Adding ethyl acetate into the material obtained in the step (1), fully mixing, filtering solid residues by using a short silica gel column, and keeping an organic phase. The solvent in the organic phase was spin-dried to give the crude product, which was then purified by a silica gel column. The separation yield is 85 percent, and the product purity is 100 percent
Example 2
The reaction formula for this example is shown below:
(1) nickel (II) bromide (10 mol%), 4, 4 '-di-tert-butyl-2, 2' -bipyridine (12 mol%), and sodium iodide (50 mol%) were added to a sealed reaction tube with a branch tube containing magnetons under air, and the reaction tube was purged with argon three times. Adding 0.8mL of ethanol into the reaction tube under the protection of argon, then adding 3-acetylphenylboronic acid (0.5mmol) and cyclohexene oxide (0.25mmol) into the reaction solution in sequence under the protection of argon, plugging a piston, and placing the reaction solution in a 70 ℃ oil bath kettle to stir for reaction for 12 hours.
(2) Adding ethyl acetate into the material obtained in the step (1), fully mixing, filtering solid residues by using a short silica gel column, and keeping an organic phase. The solvent in the organic phase was spin-dried to give the crude product, which was then purified by a silica gel column. The separation yield is 81 percent, and the product purity is 100 percent
Example 3
The reaction formula for this example is shown below:
(1) nickel (II) bromide (10 mol%), 4, 4 '-di-tert-butyl-2, 2' -bipyridine (12 mol%), and sodium iodide (50 mol%) were added to a sealed reaction tube with a branch tube containing magnetons under air, and the reaction tube was purged with argon three times. Adding 0.8mL of ethanol into the reaction tube under the protection of argon, sequentially adding 3-methoxycarbonylphenylboronic acid (0.5mmol) and cyclohexene oxide (0.25mmol) into the reaction solution under the protection of argon, plugging a piston, and placing the reaction solution in an oil bath kettle at 70 ℃ for stirring reaction for 12 hours.
(2) Adding ethyl acetate into the material obtained in the step (1), fully mixing, filtering solid residues by using a short silica gel column, and keeping an organic phase. The solvent in the organic phase was spin-dried to give the crude product, which was then purified by a silica gel column. The separation yield is 80 percent, and the product purity is 100 percent
Example 4
The reaction formula for this example is shown below:
(1) nickel (II) bromide (10 mol%), 4, 4 '-di-tert-butyl-2, 2' -bipyridine (12 mol%), and sodium iodide (50 mol%) were added to a sealed reaction tube with a branch tube containing magnetons under air, and the reaction tube was purged with argon three times. Adding 0.8mL of ethanol into the reaction tube under the protection of argon, then adding styryl boric acid (0.5mmol) and epoxy cyclohexane (0.25mmol) into the reaction liquid in sequence under the protection of argon, plugging a piston, and placing the mixture into a 70 ℃ oil bath kettle to stir for reaction for 12 hours.
(2) Adding ethyl acetate into the material obtained in the step (1), fully mixing, filtering solid residues by using a short silica gel column, and keeping an organic phase. The solvent in the organic phase was spin-dried to give the crude product, which was then purified by a silica gel column. The separation yield is 80 percent, and the product purity is 100 percent
The various types of unnatural amino acids prepared in this way are shown in the following table:
the present invention has been described in detail, and it should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.
Drawings
FIGS. 1 and 2 show the NMR spectra of the synthesized alcohol (1).
Claims (5)
1. A method for preparing alcohol by Suzuki reaction without exogenous base is characterized in that: reacting organic boric acid and ternary epoxy serving as raw materials with a solvent under the action of a nickel catalyst and a ligand according to the following reaction formula to obtain various alcohol compounds:
R、R1、R2are various types of substituents;
the nickel catalyst nickel (II) bromide glycol dimethyl ether compound;
the ligand is 4, 4 '-di-tert-butyl-2, 2' -bipyridine;
the solvent is ethanol.
2. The method for preparing alcohol by Suzuki reaction without exogenous base according to claim 1, wherein: the amount of the organic boric acid is 2 times the amount of the alkyl halide.
3. The method for preparing alcohol by Suzuki reaction without exogenous base according to claim 1, wherein: the amount of the catalyst material is 10% of the amount of the alkyl halide material.
4. The method for preparing alcohol by Suzuki reaction without exogenous base according to claim 1, wherein: the amount of the substance of the ligand is 12% of the amount of the substance of the alkyl halide.
5. The method for preparing alcohol by Suzuki reaction without exogenous base according to claim 1, wherein: the reaction temperature is 70 ℃, and the reaction time is 12 h.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4311645A (en) * | 1980-03-24 | 1982-01-19 | Hoffmann-La Roche Inc. | Synthesis of SRS-active compounds |
| CN1137264A (en) * | 1994-10-19 | 1996-12-04 | 弗门尼舍有限公司 | Method for preparing alcohols |
| EP1179520A1 (en) * | 2000-08-11 | 2002-02-13 | Aventis Animal Nutrition S.A. | Process for the preparation of phytone and novel intermediates thereof |
| CN101456790A (en) * | 2008-11-04 | 2009-06-17 | 大连理工大学 | Method for preparing diaryl alcohol by catalyzing addition reaction of aryl boric acid and aldehyde by nickel |
| KR20190033745A (en) * | 2017-09-22 | 2019-04-01 | 주식회사 포스코 | Method for preparing electroformed fe-ni alloy foil and plating solution for preparing the electroformed fe-ni alloy foil |
| CN109678673A (en) * | 2018-11-07 | 2019-04-26 | 滁州学院 | A kind of synthetic method for the homoallylic alcohol that aryl replaces |
-
2019
- 2019-10-19 CN CN201911010848.1A patent/CN110724033B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4311645A (en) * | 1980-03-24 | 1982-01-19 | Hoffmann-La Roche Inc. | Synthesis of SRS-active compounds |
| CN1137264A (en) * | 1994-10-19 | 1996-12-04 | 弗门尼舍有限公司 | Method for preparing alcohols |
| EP1179520A1 (en) * | 2000-08-11 | 2002-02-13 | Aventis Animal Nutrition S.A. | Process for the preparation of phytone and novel intermediates thereof |
| CN101456790A (en) * | 2008-11-04 | 2009-06-17 | 大连理工大学 | Method for preparing diaryl alcohol by catalyzing addition reaction of aryl boric acid and aldehyde by nickel |
| KR20190033745A (en) * | 2017-09-22 | 2019-04-01 | 주식회사 포스코 | Method for preparing electroformed fe-ni alloy foil and plating solution for preparing the electroformed fe-ni alloy foil |
| CN109678673A (en) * | 2018-11-07 | 2019-04-26 | 滁州学院 | A kind of synthetic method for the homoallylic alcohol that aryl replaces |
Non-Patent Citations (3)
| Title |
|---|
| DANIEL K. NIELSEN ET AL.: "Nickel-Catalyzed Cross-Coupling of Styrenyl Epoxides with Boronic Acids", 《ANGEW.CHEM.INT.ED.》 * |
| XIAO-YU LU ET AL.: "Base-free Ni-catalyzed Suzuki-type cross-coupling reactions of epoxides with boronic acids", 《CHEM.COMMUN.》 * |
| 陆晓雨: "镍或铜催化C（sp2）-C（sp3）键构建研究", 《中国博士学位论文全文数据库工程科技Ⅰ辑》 * |
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