阅读说明：本技术 一种醇的合成方法 (Alcohol synthesis method ) 是由 邵银林 施茵茵 周绒绒 王越 巫彩燕 谢瑶瑶 于 2021-11-02 设计创作，主要内容包括：本发明属于有机合成技术领域,具体为一种醇的合成方法；本发明在叔丁醇锂催化作用下,以酯类化合物和频哪醇硼烷为原料,四氢呋喃为溶剂,在100℃反应24h,随后加入2mol/LNaOH/MeOH溶液,室温搅拌过夜制得醇类化合物；本发明原料来源广泛或易于制备,反应条件较为温和且不需要大量/繁琐的添加剂,另外叔丁醇锂催化剂简单,且制备的醇类化合物品质高,分离收率高。(The invention belongs to the technical field of organic synthesis, in particular to a method for synthesizing alcohol; under the catalysis of lithium tert-butoxide, ester compounds and pinacolborane are used as raw materials, tetrahydrofuran is used as a solvent, the reaction is carried out for 24 hours at 100 ℃, then 2mol/LNaOH/MeOH solution is added, and the mixture is stirred at room temperature overnight to prepare alcohol compounds; the invention has the advantages of wide raw material source or easy preparation, mild reaction conditions, no need of a large amount of complex additives, simple tert-butyl alcohol lithium catalyst, high quality of the prepared alcohol compound and high separation yield.)

1. A method for synthesizing alcohol is characterized in that under the protection of nitrogen and the action of taking lithium tert-butoxide as a catalyst, a compound shown in a formula I and a compound shown in a formula II are taken as raw materials, and a compound shown in a formula III is prepared through hydroboration reaction;

the chemical reaction equation is as follows:

in the above chemical equation, formula I is various ester compounds; formula II is pinacolborane; the formula III is an alcohol compound.

2. The method of claim 1, wherein R is represented by the chemical reaction equation₁Is any one of phenyl, phenethyl, naphthyl and substituted phenyl; r₂Is an alkyl group.

3. The method of claim 2, wherein R is represented by the chemical reaction equation₁Is any one of phenyl, phenethyl, naphthyl and substituted phenyl; r₂Is methyl.

4. The method of claim 1, wherein the compound of formula I is present in a molar ratio of: a compound of formula II: catalyst 1.0: 2.5: 0.05.

5. the method for synthesizing alcohol according to claim 1, wherein the reaction temperature is 100 ℃ and the reaction time is 24 hours.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing alcohol.

Background

The reduction reaction for converting ester into alcohol compound is one of the most important functional group converting step and the most practical reaction in the field of organic synthesis (including fine chemical industry, medicine, pesticide, etc.), and has wide application prospect in the field of organic synthesis. In the existing method for preparing alcohol compounds, LiAlH is often used₄、NaBH₄The hydroboration of esters is catalyzed by alkali metals which are cheap and easy to obtain as catalysts such as metal double hydrides or transition metals such as Ir, Rh, Mn, Co and the like. The literature (J.org.chem.2009,74, 2598-2600) reports that Na-SG promotes borohydriding, but alkali metals are directly used and subjected to post-treatment to have potential safety hazards, and the reaction conditions are severe and have certain limitations. The literature (J.org.chem.2018,83,1431-1440) reports that NaOMe is used as a catalyst to catalyze the reduction of ester compounds to alcohol, but the yield is low, and the functional group tolerance is poor, so that the method has certain limitations.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a method for synthesizing alcohol, which can synthesize alcohol compounds with high selectivity and high yield by taking various ester compounds as raw materials under the catalysis of lithium tert-butoxide (LiOtBu).

The purpose of the invention is realized by the following technical scheme:

a method for synthesizing alcohol, which comprises the following steps,

under the protection of nitrogen and the action of taking lithium tert-butoxide as a catalyst, taking a compound shown in a formula I and a compound shown in a formula II as raw materials, and carrying out a hydroboration reaction to prepare a compound shown in a formula III;

the chemical reaction equation is as follows:

in the above chemical equation, formula I is various ester compounds; formula II is pinacolborane; the formula III is an alcohol compound.

Preferably, in the chemical reaction equation, R₁Is any one of phenyl, phenethyl, naphthyl and substituted phenyl; r₂Is an alkyl group.

Preferably, in the chemical reaction equation, R₂Is methyl.

Preferably, the compound of formula I: a compound of formula II: catalyst 1.0: 2.5: 0.05.

preferably, the reaction temperature is 100 ℃ and the reaction time is 24 h.

The reaction mechanism diagram of the invention is shown in figure 1,

firstly, reacting lithium tert-butoxide with pinacolborane to generate a lithium hydride intermediate A, reacting the intermediate A with an ester to generate an intermediate B, reacting the intermediate B with pinacolborane to generate an intermediate C, releasing the lithium hydride intermediate A, reacting the intermediate A with the intermediate C to generate a boron oxide compound D and an intermediate E, reacting the intermediate E with pinacolborane to obtain a boron oxide compound F, and finally hydrolyzing to obtain a product alcohol.

The invention has the beneficial effects that:

(1) the reaction universality is good, the yield is high, most of the reaction yield is over 90 percent, the atom economy is high, and the post-treatment is convenient;

(2) the method is an important supplement to the hydroboration of ester compounds, realizes the purpose of constructing alcohol compounds by using the base to catalyze the ester hydroboration, and provides an important idea for constructing the alcohol compounds;

(3) the reaction conditions are mild and no large amount of/fussy additives are needed;

(4) the tert-butyl alcohol lithium catalyst is simple, low in price and commercially available;

(5) the alcohol prepared by the method has high quality and high separation yield;

the invention provides a method for synthesizing alcohols with diversified structures by catalyzing ester hydroboration reaction under a tert-butyl alcohol lithium catalysis system, which has the advantages of high atom economy, high bonding efficiency and mild reaction conditions; compared with the prior method, the method has the advantages that the reaction conditions and the substrate universality are obviously improved, which is difficult to realize by other methods.

Drawings

FIG. 1: the reaction mechanism diagram of the invention.

Detailed Description

The present invention is further illustrated by the following examples, which are not intended to limit the scope of the present invention.

Example 1

The preparation of benzyl alcohol has the following structural formula:

under the protection of nitrogen, raw material methyl benzoate (1mmol) and pinacolborane (2.5mmol), a catalyst LiOtBu (0.05mol) and a solvent tetrahydrofuran (1.0mL) are added, reaction is carried out at 100 ℃ for 24h, then a 2mol/LNaOH/MeOH solution (namely, 2mol of sodium hydroxide in each liter of methanol) is added, and stirring is carried out at room temperature overnight, so that the product is isolated and obtained in a yield of 95%.

Performing nuclear magnetic resonance detection on the separated and purified product, wherein the result is as follows:

¹H NMR(500MHz,CDCl₃):δ7.36(d,J＝4.4Hz,4H),7.33-7.26(m,1H),4.68(s,2H),1.79(s,1H).¹³C NMR(125MHz,CDCl₃)δ141.0,128.7,127.8,127.1,65.4.

example 2

The preparation of 4-methyl benzyl alcohol has the following structural formula:

under the protection of nitrogen, raw material methyl 4-methylbenzoate (1mmol) and pinacolborane (2.5mmol), catalyst LiOtBu (0.05mol) and solvent tetrahydrofuran (1.0mL) are added to react at 100 ℃ for 24h, and then 2mol/L NaOH/MeOH solution (namely 2mol of sodium hydroxide in each liter of methanol) is added, and the mixture is stirred at room temperature overnight, so that the isolation yield of the product is 90%.

Performing nuclear magnetic resonance detection on the separated and purified product, wherein the result is as follows:

¹H NMR(500MHz,CDCl₃)δ7.27(d,J＝7.7Hz,2H),7.19(d,J＝7.7Hz,2H),4.65(s,2H),2.37(s,3H),1.85(bs,1H).¹³C NMR(125MHz,CDCl₃)δ138.1,137.5,129.4,127.2,65.4,21.2.

example 3

Preparation of 4- (trifluoromethyl) benzyl alcohol, structural formula:

under the protection of nitrogen, raw material 4- (trifluoromethyl) methyl benzoate (1mmol) and pinacolborane (2.5mmol), catalyst LiOtBu (0.05mol) and solvent tetrahydrofuran (1.0mL) are added, and the mixture is reacted at 100 ℃ for 24h, then 2mol/L NaOH/MeOH solution (namely 2mol of sodium hydroxide in each liter of methanol) is added, and the mixture is stirred at room temperature overnight, and the isolation yield of the product is 89%.

Performing nuclear magnetic resonance detection on the separated and purified product, wherein the result is as follows:

¹H NMR(500MHz,CDCl₃)δ7.60(d,J＝7.9Hz,2H),7.45(d,J＝7.9Hz,2H),4.73(s,2H),2.30(bs,1H).¹³C NMR(125MHz,CDCl₃)δ144.7,129.8(q,J＝32.4Hz),126.8,125.5(q,J＝3.7Hz),124.2(q,J＝71.7Hz),64.4.

example 4

Preparation of 4- (tert-butyl) benzyl alcohol, structural formula is as follows:

under the protection of nitrogen, raw material 4-tert-butyl methyl benzoate (1mmol) and pinacolborane (2.5mmol), catalyst LiOtBu (0.05mol) and solvent tetrahydrofuran (1.0mL) are added to react at 100 ℃ for 24h, and then 2mol/L NaOH/MeOH solution (namely 2mol of sodium hydroxide in each liter of methanol) is added to stir at room temperature overnight, and the product is isolated in 92% yield.

Performing nuclear magnetic resonance detection on the separated and purified product, wherein the result is as follows:

¹H NMR(400MHz,CDCl₃)δ7.40(d,J＝8.4Hz,2H),7.31(d,J＝8.5Hz,2H),4.64(s,2H),2.00(bs,1H),1.34(s,9H).¹³C NMR(125MHz,CDCl₃)δ150.8,138.1,127.0,125.6,65.2,34.7,31.5.

example 5

The preparation of 2-naphthalene methanol has the following structural formula:

under the protection of nitrogen, raw material methyl 2-naphthoate (1mmol) (1mmol) and pinacolborane (2.5mmol), a catalyst LiOtBu (0.05mol) and a solvent tetrahydrofuran (1.0mL) are added, reaction is carried out at 100 ℃ for 24h, then a 2mol/L NaOH/MeOH solution (namely 2mol of sodium hydroxide in each liter of methanol) is added, stirring is carried out at room temperature overnight, and the product is isolated and obtained in 98 percent.

Performing nuclear magnetic resonance detection on the separated and purified product, wherein the result is as follows:

¹H NMR(500MHz,CDCl₃)δ7.82-7.85(m,3H),7.80(s,1H),7.47-7.49(m,3H),4.85(s,2H),1.98(s,1H).¹³C NMR(125MHz,CDCl₃)δ138.5,133.5,133.1,128.5,128.0,127.8,126.3,126.0,125.6,125.3,65.6.

example 6

Preparation of 4-fluorobenzyl alcohol, the structural formula is as follows:

under the protection of nitrogen, raw material methyl 4-fluorobenzoate (1mmol) and pinacolborane (2.5mmol), a catalyst LiOtBu (0.05mol) and a solvent tetrahydrofuran (1.0mL) are added to react at 100 ℃ for 24h, then a 2mol/L NaOH/MeOH solution (namely, 2mol of sodium hydroxide in each liter of methanol) is added, and the mixture is stirred at room temperature overnight, so that the isolation yield of the product is 97%.

Performing nuclear magnetic resonance detection on the separated and purified product, wherein the result is as follows:

¹H NMR(500MHz,CDCl₃):δ7.33-7.30(m,2H),7.01-7.05(m,2H),4.64(s,2H),1.94(s,1H).¹³C NMR(125MHz,CDCl₃):δ163.5,161.5,136.8(d,J＝3.1Hz),128.9(d,J＝8.1Hz),115.5(d,J＝21.4Hz),64.7.

example 7

Preparation of 3-phenyl-1-propanol, the structural formula is as follows:

under the protection of nitrogen, raw material methyl 3-phenylpropionate (1mmol) and pinacolborane (2.5mmol), a catalyst LiOtBu (0.05mol) and a solvent tetrahydrofuran (1.0mL) are added to react at 100 ℃ for 24h, and then a 2mol/L NaOH/MeOH solution (namely 2mol of sodium hydroxide in each liter of methanol) is added to stir at room temperature overnight, so that the product is isolated in a yield of 92%.

Performing nuclear magnetic resonance detection on the separated and purified product, wherein the result is as follows:

¹H NMR(400MHz,CDCl₃)δ7.25(t,J＝7.5Hz,2H),7.15-7.17(m,3H),3.60(t,J＝6.5Hz,2H),2.80(bs,1H),2.65(t,J＝7.7Hz,2H),1.81-1.87(m,2H).¹³C NMR(125MHz,CDCl₃)δ141.9,128.4,128.4,125.8,62.0,34.2,32.1.

example 8

The preparation of 4-chlorobenzyl alcohol has the following structural formula:

under the protection of nitrogen, raw material methyl 4-chlorobenzoate (1mmol) and pinacolborane (2.5mmol), catalyst LiOtBu (0.05mol) and solvent tetrahydrofuran (1.0mL) are added to react at 100 ℃ for 24h, then 2mol/L NaOH/MeOH solution (2 mol of NaOH in each liter of methanol) is added, and the mixture is stirred at room temperature overnight, so that the isolation yield of the product is 96%.

Performing nuclear magnetic resonance detection on the separated and purified product, wherein the result is as follows:

¹H NMR(500MHz,CDCl₃)δ7.31(d,J＝8.4Hz,2H),7.27(d,J＝8.4Hz,2H),4.63(s,2H),2.11(bs,1H).¹³C NMR(125MHz,CDCl₃)δ139.4,133.5,128.8,128.4,64.6.

example 9

Preparation of 2-bromobenzyl alcohol, structural formula is as follows:

under the protection of nitrogen, raw material methyl 2-bromobenzoate (1mmol) and pinacolborane (2.5mmol), catalyst LiOtBu (0.05mol) and solvent tetrahydrofuran (1.0mL) are added to react at 100 ℃ for 24h, and then 2mol/L NaOH/MeOH solution (i.e. 2mol of sodium hydroxide per liter of methanol) is added, and the mixture is stirred at room temperature overnight, and the isolation yield of the product is 88%.

Performing nuclear magnetic resonance detection on the separated and purified product, wherein the result is as follows:

¹H NMR(500MHz,CDCl₃)δ7.54(d,J＝8.0Hz,1H),7.47(d,J＝7.6Hz,1H),7.31-7.34(m,1H),7.14-7.17(m,1H),4.73(s,2H),2.33(s,1H).¹³C NMR(125Mz,CDCl₃)δ139.9,132.7,129.2,129.0,127.8,122.7,65.1.

example 10

Preparation of (4-vinylphenyl) methanol, structural formula:

under the protection of nitrogen, raw material methyl 4-vinylbenzoate (1mmol) and pinacolborane (2.5mmol), a catalyst LiOtBu (0.05mol) and a solvent tetrahydrofuran (1.0mL) are added, reaction is carried out at 100 ℃ for 24h, then a 2mol/L NaOH/MeOH solution (namely 2mol of sodium hydroxide in each liter of methanol) is added, stirring is carried out at room temperature overnight, and the product is isolated with the yield of 82%.

Performing nuclear magnetic resonance detection on the separated and purified product, wherein the result is as follows:

¹H NMR(500MHz,CDCl3)δ7.40(d,J＝8.0Hz,2H),7.30(d,J＝7.9Hz,2H),6.7-6.8(m,1H),5.8(d,J＝17.6Hz,1H),5.30(d,J＝10.8Hz,1H),4.63(s,2H),2.35(bs,1H).¹³C NMR(125MHz,CDCl3)δ140.5,137.0,136.6,127.3,126.4,113.9,64.9.

comparative example 1

The reaction temperature was changed to 50 ℃ and the remaining steps were the same as in example 1, with an isolated yield of 24%.

Comparative example 2

The catalyst was changed to lithium carbonate, and the procedure was the same as in example 1 except that the isolation yield of the product was 30%.

Comparative example 3

The catalyst was not added, and the product was isolated in 0% yield in the same manner as in example 1.

And (4) conclusion:

(1) according to examples 1-10, ester compounds and pinacolborane are used as raw materials and tetrahydrofuran is used as a solvent to react for 24 hours at 100 ℃ under the catalysis of tert-butoxide, and then 2mol/L NaOH/MeOH solution is added to stir at room temperature overnight; the product separation yield of the alcohol compound prepared by the method is higher than 80%, even can reach 98%, and the method embodies that the lithium tert-butoxide plays an extremely remarkable role in the reaction of preparing the alcohol compound from the ester compound;

(2) comparing comparative example 1 and example 1, it can be seen that: the method is not carried out according to the reaction temperature in the invention, the separation yield of the prepared alcohol compound is extremely low, and the method for synthesizing the alcohol in the invention is further proved to be a complete system, and the steps, raw materials, catalysts, temperature, time and other parameters involved in the system are matched with each other, so that the alcohol compound with high separation yield can be finally obtained;

(3) comparing comparative examples 2 and 3 with example 1, it can be seen that the other conditions are the same, and the purpose of preparing alcohol compounds is difficult to realize without adding catalysts; and under the same other conditions, the product of the alcohol compound prepared by replacing the catalyst with lithium carbonate is extremely low, thereby showing that the catalyst in the invention has remarkable progress.

It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.