阅读说明：本技术 一种二醇的合成方法 (Method for synthesizing diol ) 是由 邵银林 施茵茵 张建平 黄哲帆 王越 孙佳雯 姜含笑 吴瑶 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,具体为一种二醇的合成方法；本发明通过二(三甲基硅基)氨基锂催化内酯的硼氢化从而合成结构多样化的二醇化合物；具体是在二(三甲基硅基)氨基锂催化体系下,以各种内酯化合物和频哪醇硼烷为原料,制备二醇类化合物；本发明方法原料来源广泛或易于制备,操作简便、选择性可控,收率高,条件温和,普适性广。(The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing diol; the invention synthesizes diol compounds with diversified structures by hydroboration of lactone catalyzed by lithium bis (trimethylsilyl) amide; in particular to a method for preparing diol compounds by taking various lactone compounds and pinacol borane as raw materials under a lithium bis (trimethylsilyl) amide catalytic system; the method has the advantages of wide raw material source or easy preparation, simple and convenient operation, controllable selectivity, high yield, mild conditions and wide universality.)

1. A method for synthesizing diol is characterized in that lithium bis (trimethylsilyl) amide is used as a catalyst, a compound shown in a formula I and a compound shown in a formula II are used as raw materials, and a compound shown in a formula III is prepared through a hydroboration reaction, wherein the chemical reaction equation is as follows:

in the formula, the formula I is various lactone compounds; formula II is pinacolborane; formula III is a diol.

2. The process for the synthesis of diols according to claim 1, wherein R in formula I₁Is phenyl or alkyl.

3. 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: 2.0: 0.08.

4. the method for synthesizing diol according to claim 1, wherein the reaction temperature is 80 ℃ and the reaction time is 20 hours.

Technical Field

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

Background

The hydroboration reaction of the lactone is relatively difficult due to the factors of larger steric hindrance, electronic effect and the like of the lactone, so that few examples are reported at present. In 2014, Sadow et al reported in detail that tris (4, 4-dimethyl-2-oxazolinyl) phenylmagnesium borate methyl compound catalyzed the hydroboration reaction of lactone (Chem Sci,2014,5, 959-; 2017, Nembenna et al used guanidino ligands directly with Mg { N (SiMe)₃)₂}₂Two different methods of reaction or reaction of guanidino ligand potassium salt and magnesium chloride successfully synthesize corresponding magnesium amide (Dalton Trans,2017,46, 4152-4156) with stable guanidino, and realize hydroboration reaction of magnesium amide to internal ester. In 2020, Cao et al reported a complex magnesium complex catalyzed hydroboration reduction of lactones (Dalton trans.2020,49, 2776-2780). However, the metal catalysts used in these reported lactone hydroboration reactions are quite complex in structure and have certain limitations.

Disclosure of Invention

The invention aims to provide a method for synthesizing diol, which uses a simple catalyst, namely lithium bis (trimethylsilyl) amide, to realize the method for synthesizing the diol from lactone through hydroboration.

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

a method for synthesizing diol uses lithium bis (trimethylsilyl) amide (abbreviation: LiHMDS) as a catalyst, and compounds shown in formula I and formula II as raw materials to prepare a compound shown in formula III through hydroboration reaction, wherein the chemical reaction equation is as follows:

in the above formula, formula I is various lactone compounds (lactones with or without benzene ring); formula II is pinacolborane; formula III is a diol.

Preferably, R in formula I₁Is phenyl or alkyl.

Preferably, the molar ratio of: a compound of formula I: a compound of formula II: catalyst 1.0: 2.0: 0.08.

preferably, the reaction temperature is 80 ℃ and the reaction time is 20 h.

The reaction mechanism of the present invention is shown in FIG. 1:

firstly, reacting silicon amido lithium with pinacol borane to generate a lithium hydride intermediate A, reacting the intermediate A with lactone to generate an intermediate B, reacting the intermediate B with pinacol borane to generate an intermediate C, reacting the intermediate C with the lithium hydride intermediate A to obtain an intermediate D, reacting the intermediate D with pinacol borane to obtain a boron oxide compound E, and finally hydrolyzing to obtain a product diol.

The invention has the beneficial effects that:

(1) the invention catalyzes the lactone hydroboration reaction under a lithium bis (trimethylsilyl) amide catalytic system so as to realize the synthesis of diol with diversified structures.

(2) Compared with a complex metal catalyst, the nonmetal catalyst adopted by the invention has obvious advantages of the catalyst in the process of carrying out the hydroboration reduction reaction of the lactone, realizes the construction of the alcohol compound by carrying out the hydroboration of the lactone under the catalysis of the alkali, and provides an important reference for the construction of the diol compound.

(3) Compared with the prior method, the lithium bis (trimethylsilyl) amide catalyst is simple, does not need complex synthesis, has low price and can be purchased commercially.

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

Preparation of 1, 2-benzenedimethanol, structural formula:

the starting material phthalide (1mmol) and pinacolborane (2.0mmol), LiHMDS (0.08mmol) as catalyst, toluene (1.0mL) as solvent were added under nitrogen and reacted at 80 ℃ for 20h followed by 2mol/L NaOH/MeOH solution (i.e., 2mol sodium hydroxide per liter methanol) and stirred at room temperature overnight. The product isolation yield was 89%.

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

¹H NMR(500MHz,CDCl₃):δ7.24(s,4H),4.52(s,4H),4.46(s,2H).¹³C NMR(125MHz,CDCl₃):δ139.2,129.5,128.4,63.5.

example 2

Preparation of 2- (2- (hydroxymethyl) phenyl) ethanol, structural formula:

under nitrogen protection, add the starting material 3-isochromone (1mmol) and pinacolborane (2.0mmol), LiHMDS (0.08mol), solvent toluene (1.0mL), react at 80 ℃ for 20h, then add 2mol/L NaOH/MeOH solution (i.e., 2mol NaOH per liter of methanol), stir at room temperature overnight. The product isolation yield was 91%.

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

¹H NMR(500MHz,CDCl₃)δ7.24(d,J＝8.0Hz,2H),7.17(t,J＝6.2Hz,2H),4.51(s,2H),4.32(bs,1H),3.73(t,J＝6.0Hz,2H),2.83(t,J＝5.9Hz,2H),2.40(bs,1H).¹³C NMR(125MHz,CDCl₃)δ139.3,138.3,130.2,129.8,128.6,126.8,63.3,63.0,35.2.

example 3

Preparation of 1, 5-nonanediol, the structural formula is as follows:

under nitrogen protection, the starting material delta-nonalactone (1mmol) and pinacolborane (2.0mmol), LiHMDS (0.08mmol), solvent toluene (1.0mL) were added and reacted at 80 ℃ for 20h, followed by addition of 2mol/L NaOH/MeOH solution (i.e., 2mol sodium hydroxide per liter of methanol) and stirring at room temperature overnight. The product isolation yield was 88%.

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

¹H NMR(500MHz,CDCl₃)δ3.54-3.59(m,3H),3.28(bs,1H),2.93(bs,1H),1.27-1.56(m,12H),0.85-0.88(m,3H).¹³C NMR(125MHz,CDCl₃)δ71.7,62.4,37.3,36.9,32.5,28.0,22.8,21.9,14.1.

example 4

Preparation of 3-methyl-1, 4-octanediol, structural formula:

under nitrogen, the starting materials whiskey lactone (1mmol) and pinacolborane (2.0mmol), LiHMDS (0.08mmol), toluene (1.0mL) as a solvent were added and reacted at 80 ℃ for 20h, followed by addition of 2mol/L NaOH/MeOH solution (i.e., 2mol NaOH per liter of methanol) and stirring at room temperature overnight. The product isolation yield was 87%.

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

¹H NMR(500MHz,CDCl₃)δ3.72-3.82(m,1H),3.53-3.69(m,2H),2.54-2.88(s,2H),1.63-1.82(m,2H),1.22-1.58(m,7H),0.85-1.04(m,6H).¹³C NMR(125MHz,CDCl₃)δ75.1,60.6,36.1,35.4,34.3,28.2,22.9,16.7,14.0.

example 5

Preparation of 1, 4-butanediol, structural formula is as follows:

under nitrogen, delta-valerolactone (1mmol) and pinacolborane (2.0mmol) as starting materials, LiHMDS (0.08mmol) as a catalyst, toluene (1.0mL) as a solvent were added and reacted at 80 ℃ for 20h, followed by addition of a 2mol/L NaOH/MeOH solution (i.e., 2mol of NaOH per liter of methanol) and stirring at room temperature overnight. The product isolation yield was 86%.

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

¹H NMR(400MHz,CDCl₃)δ3.77-3.64(m,4H),1.97(s,2H),1.75-1.64(m,4H).¹³C NMR(125MHz,CDCl₃)δ62.8,29.8.

example 6

Preparation of 1, 4-pentanediol, the structural formula is as follows:

under the protection of nitrogen, raw materials of gamma-valerolactone (1mmol) and pinacolborane (2.0mmol) and a catalyst LiHMDS are added

(0.08mmol), solvent toluene (1.0mL), was reacted at 80 ℃ for 20h, followed by addition of 2mol/L NaOH/MeOH solution (i.e., 2mol sodium hydroxide per liter of methanol) and stirring at room temperature overnight. The product isolation yield was 91%.

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

¹H NMR(400MHz,CDCl₃):δ4.11(s,2H),3.88-3.73(m,1H),3.71-3.52(m,2H),1.77-1.41(m,4H),1.19(d,J＝6.3Hz,3H).¹³C NMR(125MHz,CDCl₃):δ67.6,62.4,36.1,28.9,23.3.

comparative example 1

The reaction temperature was changed to 60 ℃ and the other steps were the same as in example 1. The product isolation yield was 58%.

Comparative example 2

If the catalyst is changed to lithium tert-butoxide, the other steps are the same as in example 1. The product isolation yield was 72%.

Comparative example 3

The procedure is as in example 1 except that no catalyst is added. The product isolation yield was 0.

And (4) conclusion:

(1) from examples 1 to 6, the reaction was carried out at 80 ℃ for 20 hours under LiHMDS catalysis using the lactone compound and pinacolborane as raw materials and toluene as a solvent, and then 2mol/L NaOH/MeOH solution was added and stirred at room temperature overnight. The product separation yield of the diol prepared by the method is higher than 86%, and the method embodies that the LiHMDS is added in the catalysis in the reaction of preparing the diol compound from the lactone compound to play an extremely remarkable role;

(2) comparing comparative example 1 and example 1, it can be seen that: the reaction temperature plays a positive role in the reaction of preparing the diol compound from the lactone compound, and the reaction temperature is matched with parameters such as a catalyst, reaction steps, reaction raw materials and the like to form a reaction system in the invention; if the reaction is not carried out at the reaction temperature in the present invention, the isolation yield is directly lowered;

(3) comparing comparative examples 2 and 3 with example 1, it can be seen that the other conditions are the same, and it is difficult to achieve the object of preparing a diol compound from a lactone compound without adding a catalyst; and under the same other conditions, the separation yield of the alcohol compound prepared by replacing the catalyst with other catalysts such as lithium tert-butoxide and the like is lower than that of LiHMDS, thereby showing that the catalyst of 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.