CN108250042B - Preparation method of (S) - (-) -1,1, 2-triphenyl-1, 2-glycol - Google Patents
Preparation method of (S) - (-) -1,1, 2-triphenyl-1, 2-glycol Download PDFInfo
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- CN108250042B CN108250042B CN201810211017.XA CN201810211017A CN108250042B CN 108250042 B CN108250042 B CN 108250042B CN 201810211017 A CN201810211017 A CN 201810211017A CN 108250042 B CN108250042 B CN 108250042B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 105
- 239000000243 solution Substances 0.000 claims abstract description 76
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 claims abstract description 46
- ITATYELQCJRCCK-UHFFFAOYSA-N Mandelic Acid, Methyl Ester Chemical compound COC(=O)C(O)C1=CC=CC=C1 ITATYELQCJRCCK-UHFFFAOYSA-N 0.000 claims abstract description 38
- 238000010791 quenching Methods 0.000 claims abstract description 35
- 230000000171 quenching effect Effects 0.000 claims abstract description 35
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000007864 aqueous solution Substances 0.000 claims abstract description 21
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 21
- 239000012074 organic phase Substances 0.000 claims abstract description 16
- 230000002378 acidificating effect Effects 0.000 claims abstract description 11
- GWVWUZJOQHWMFB-IBGZPJMESA-N (2s)-1,1,2-triphenylethane-1,2-diol Chemical compound C1([C@H](O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=CC=C1 GWVWUZJOQHWMFB-IBGZPJMESA-N 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 8
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- -1 Grignard reagent phenyl magnesium bromide Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- ISAOCJYIOMOJEB-ZDUSSCGKSA-N (S)-benzoin Chemical compound O=C([C@@H](O)C=1C=CC=CC=1)C1=CC=CC=C1 ISAOCJYIOMOJEB-ZDUSSCGKSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229910001092 metal group alloy Inorganic materials 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 description 1
- 229910010271 silicon carbide Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001256 stainless steel alloy Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a preparation method of (S) - (-) -1,1, 2-triphenyl-1, 2-glycol, which is characterized in that methyl mandelate and phenyl magnesium bromide are respectively dissolved in a solvent to prepare a methyl mandelate solution and a phenyl magnesium bromide solution; respectively inputting the prepared methyl mandelate solution and phenyl magnesium bromide solution into a first microchannel reactor through a metering pump to carry out main reaction, directly flowing the reaction solution obtained after the reaction into a second microchannel reactor, inputting the acidic aqueous solution into the second microchannel reactor through a metering pump to carry out quenching reaction while the reaction solution flows into the second microchannel reactor, obtaining reaction liquid after the quenching reaction is finished, layering the reaction liquid to obtain an organic phase, drying the organic phase, carrying out reduced pressure concentration, and recrystallizing with toluene to obtain the finished product (S) - (-) -1,1, 2-triphenyl-1, 2-ethylene glycol. The invention has the advantages of high yield and quick reaction.
Description
Technical Field
The invention relates to a preparation method of (S) - (-) -1,1, 2-triphenyl-1, 2-glycol, in particular to a method for preparing (S) - (-) -1,1, 2-triphenyl-1, 2-glycol by using a microchannel reaction device.
Background
(S) - (-) -1,1, 2-triphenyl-1, 2-glycol is an important intermediate for preparing optically active medicines, pesticides and functional materials, and has a structural formula shown in the specification (A)
）：
The main synthesis method comprises the following steps: slowly dripping a solution of methyl mandelate into a solution of Grignard reagent phenyl magnesium bromide at a certain temperature, carrying out heat preservation reaction, and carrying out aftertreatment to obtain a product, wherein the reaction formula is as follows:
the main references are 1, Advanced Synthesis and Catalysis, vol.352, nb. 14-15, (2010), p.2611-2620: reacting for 50h at 0-20 ℃ in tetrahydrofuran solvent under the protection of inert gas, and performing post-treatment to obtain a product; 2. tetrahedron, vol.42, nb. 9, (1986), p.2421-2428, ether as solvent, heating and reacting for 2 hours, the yield is 80%; 3. journal of the American Chemical Society, vol.112, nb. 10, (1990), p.3949-; 4. organic Letters, vol.9, nb. 4, (2007), p.635-.
Most of the methods reported in the above documents adopt conventional reaction devices, most of the reaction time is long, some reaction time even reaches 50 hours, the yield is not high generally, the reason for analyzing the reaction is probably 1), and incomplete reaction is easy to generate due to the limited mixing effect of a reactor, so that the product contains a high proportion of impurities (S) -2-hydroxy-1, 2-diphenylethanone, and the structural formula of the product is shown as the following formula (II); 2) when hydrochloric acid is added for quenching after the reaction is finished, the local acid concentration is too high, dehydration side reaction is generated to generate impurity 1,2, 2-triphenyl vinyl alcohol, and the structural formula of the impurity is shown as the following formula (A)
）。
Disclosure of Invention
In view of the above disadvantages, the present invention provides a method for preparing (S) - (-) -1,1, 2-triphenyl-1, 2-glycol with high yield and fast reaction speed.
The invention has the technical content that the preparation method of (S) - (-) -1,1, 2-triphenyl-1, 2-glycol is characterized in that methyl mandelate and phenyl magnesium bromide are respectively dissolved in a solvent to prepare a methyl mandelate solution and a phenyl magnesium bromide solution, the molar concentration of the methyl mandelate solution is 0.1-3 mol/L, the molar concentration of the phenyl magnesium bromide solution is 0.1-2 mol/L, and the solvent is diethyl ether, tetrahydrofuran or 2-methyltetrahydrofuran; respectively inputting the prepared methyl mandelate solution and phenyl magnesium bromide solution into a first microchannel reactor through a metering pump to carry out main reaction, directly flowing the reaction solution obtained after the reaction into a second microchannel reactor, inputting an acidic aqueous solution into the second microchannel reactor through a metering pump to carry out quenching reaction while the reaction solution flows into the second microchannel reactor, obtaining reaction liquid after the quenching reaction is finished, layering the reaction liquid to obtain an organic phase, drying the organic phase, carrying out reduced pressure concentration, and recrystallizing with toluene to obtain a finished product (S) - (-) -1,1, 2-triphenyl-1, 2-ethylene glycol; wherein the main reaction residence time in the first microchannel reactor is 0.5-5 min, the reaction temperature is 10-50 ℃, and the input molar weight ratio of the methyl mandelate solution to the phenyl magnesium bromide solution is 1: 1-1: 3; the residence time of the quenching reaction in the second microchannel reactor is 0.5-1.5 min, the temperature of the quenching reaction is-10-30 ℃, the molar concentration of the acidic aqueous solution is 0.05-4 mol/L, and the molar input amount of the acid in the acidic aqueous solution is 1-2 times of that of the phenylmagnesium bromide.
In the preparation method of the (S) - (-) -1,1, 2-triphenyl-1, 2-glycol, the molar concentration of a methyl mandelate solution is 0.5-1 mol/L, the molar concentration of a phenylmagnesium bromide solution is 0.5-1 mol/L, and the solvent is 2-methyltetrahydrofuran; the main reaction residence time in the first microchannel reactor is 1-3 min, the reaction temperature is 20-30 ℃, the residence time in the first microchannel reactor is 0.5-5 min, and the input molar weight ratio of the methyl mandelate solution to the phenyl magnesium bromide solution is 1: 1.05-1: 1.5; the residence time of the quenching reaction in the second microchannel reactor is 0.8-1.2 min, the temperature of the quenching reaction is 0-10 ℃, the molar concentration of the acidic aqueous solution is 1-2 mol/L, and the molar input amount of the acid in the acidic aqueous solution is 1.05-1.2 times of that of the phenylmagnesium bromide.
Drying, vacuum concentration and toluene recrystallization are conventional processes in the preparation method of the (S) - (-) -1,1, 2-triphenyl-1, 2-ethanediol.
The microchannel reactor used in the invention is assembled by a plurality of modules, and the modules can be assembled in parallel or in series. The thermocouple is used for measuring the actual temperature of the heat exchange medium in the heat exchange passage or the external heat-conducting medium. The module can be made of silicon carbide, glass, stainless steel or metal alloy. The specific number of modules is determined by the scale of the reaction and the residence time of the reaction.
Compared with the prior art, the invention has the advantages that:
(1) the invention adopts the continuous flow reactor of the continuous flow of the micro-channel, the reaction time is shortened from the traditional hours or even dozens of hours to dozens of seconds to several minutes, and the reaction efficiency is obviously improved.
(2) And because the raw materials are mixed in the micro-channel very well, the temperature is controlled accurately, and the conversion rate of the raw materials and the selectivity of products are obviously improved.
(3) According to the invention, the whole process of the feeding mixing and reaction process is a continuous flow reaction, so that the influence of air and water gas on the reaction in the conventional batch reaction is avoided.
Detailed Description
Example 1, separately dissolving methyl mandelate and phenylmagnesium bromide in 2-methyltetrahydrofuran to obtain a methyl mandelate solution with a molar concentration of 0.5mol/L and a phenylmagnesium bromide solution with a molar concentration of 0.5 mol/L; respectively inputting the prepared methyl mandelate solution and phenyl magnesium bromide solution into a first microchannel reactor through a metering pump to carry out main reaction, directly flowing the reaction solution obtained after reaction into a second microchannel reactor, inputting hydrochloric acid aqueous solution into the second microchannel reactor through a metering pump to carry out quenching reaction while the reaction solution flows into the second microchannel reactor, obtaining reaction liquid after the quenching reaction is finished, flowing the reaction liquid into a receiver in a high dispersion phase continuous flow state, layering the reaction liquid in the receiver to obtain an organic phase, drying the organic phase by using anhydrous magnesium sulfate, then carrying out reduced pressure concentration, and recrystallizing by using toluene to obtain a finished product (S) - (-) -1,1, 2-triphenyl-1, 2-ethylene glycol; wherein the main reaction residence time in the first microchannel reactor is 3min, the reaction temperature is 20 ℃, and the input molar weight ratio of the methyl mandelate solution to the phenyl magnesium bromide solution is 1: 1.1; the residence time of the quenching reaction in the second microchannel reactor is 1min, the temperature of the quenching reaction is 5 ℃, the molar concentration of the hydrochloric acid aqueous solution is 1mol/L, and the molar input amount of the hydrochloric acid is 1.09 times of that of the phenylmagnesium bromide; the total conversion rate is 99.8 percent, and the yield of the product (S) - (-) -1,1, 2-triphenyl-1, 2-glycol is 92 percent.
Example 2, separately dissolving methyl mandelate and phenylmagnesium bromide in 2-methyltetrahydrofuran to obtain a methyl mandelate solution with a molar concentration of 0.5mol/L and a phenylmagnesium bromide solution with a molar concentration of 0.5 mol/L; respectively inputting the prepared methyl mandelate solution and phenyl magnesium bromide solution into a first microchannel reactor through a metering pump to carry out main reaction, directly flowing the reaction solution obtained after reaction into a second microchannel reactor, inputting a sulfuric acid aqueous solution into the second microchannel reactor through a metering pump to carry out quenching reaction while the reaction solution flows into the second microchannel reactor, obtaining reaction liquid after the quenching reaction is finished, flowing the reaction liquid into a receiver in a high dispersion phase continuous flow state, layering the reaction liquid in the receiver to obtain an organic phase, drying the organic phase by using anhydrous magnesium sulfate, then carrying out reduced pressure concentration, and recrystallizing by using toluene to obtain a finished product (S) - (-) -1,1, 2-triphenyl-1, 2-ethylene glycol; wherein the main reaction residence time in the first microchannel reactor is 1.5min, the reaction temperature is 25 ℃, and the input molar weight ratio of the methyl mandelate solution to the phenyl magnesium bromide solution is 1: 1.2; the residence time of the quenching reaction in the second microchannel reactor is 1min, the temperature of the quenching reaction is 5 ℃, the molar concentration of the sulfuric acid aqueous solution is 1mol/L, and the molar input amount of the sulfuric acid is 1.16 times of that of the phenylmagnesium bromide; the total conversion rate is 99.5 percent, and the yield of the product (S) - (-) -1,1, 2-triphenyl-1, 2-glycol is 91 percent.
Example 3, separately dissolving methyl mandelate and phenylmagnesium bromide in 2-methyltetrahydrofuran to obtain a methyl mandelate solution with a molar concentration of 1mol/L and a phenylmagnesium bromide solution with a molar concentration of 1 mol/L; respectively inputting the prepared methyl mandelate solution and phenyl magnesium bromide solution into a first microchannel reactor through a metering pump to carry out main reaction, directly flowing the reaction solution obtained after reaction into a second microchannel reactor, inputting a nitric acid aqueous solution into the second microchannel reactor through a metering pump to carry out quenching reaction while the reaction solution flows into the second microchannel reactor, obtaining reaction liquid after the quenching reaction is finished, flowing the reaction liquid into a receiver in a high dispersion phase continuous flow state, layering the reaction liquid in the receiver to obtain an organic phase, drying the organic phase by using anhydrous magnesium sulfate, then carrying out reduced pressure concentration, and recrystallizing by using toluene to obtain a finished product (S) - (-) -1,1, 2-triphenyl-1, 2-ethylene glycol; wherein the main reaction residence time in the first microchannel reactor is 2.8min, the reaction temperature is 30 ℃, and the input molar weight ratio of the methyl mandelate solution to the phenyl magnesium bromide solution is 1: 1.2; the quenching reaction residence time in the second microchannel reactor is 1min, the quenching reaction temperature is 5 ℃, the molar concentration of the nitric acid aqueous solution is 1mol/L, and the molar input amount of the nitric acid is 1.16 times of that of the phenylmagnesium bromide; the total conversion rate is 100 percent, and the yield of the product (S) - (-) -1,1, 2-triphenyl-1, 2-glycol is 93 percent.
Example 4, separately dissolving methyl mandelate and phenylmagnesium bromide in 2-methyltetrahydrofuran to obtain a methyl mandelate solution with a molar concentration of 1mol/L and a phenylmagnesium bromide solution with a molar concentration of 0.5 mol/L; respectively inputting the prepared methyl mandelate solution and phenyl magnesium bromide solution into a first microchannel reactor through a metering pump to carry out main reaction, directly flowing the reaction solution obtained after reaction into a second microchannel reactor, inputting hydrochloric acid aqueous solution into the second microchannel reactor through a metering pump to carry out quenching reaction while the reaction solution flows into the second microchannel reactor, obtaining reaction liquid after the quenching reaction is finished, flowing the reaction liquid into a receiver in a high dispersion phase continuous flow state, layering the reaction liquid in the receiver to obtain an organic phase, drying the organic phase by using anhydrous magnesium sulfate, then carrying out reduced pressure concentration, and recrystallizing by using toluene to obtain a finished product (S) - (-) -1,1, 2-triphenyl-1, 2-ethylene glycol; wherein the main reaction residence time in the first microchannel reactor is 2.1min, the reaction temperature is 30 ℃, and the input molar weight ratio of the methyl mandelate solution to the phenyl magnesium bromide solution is 1: 1.1; the residence time of the quenching reaction in the second microchannel reactor is 1min, the temperature of the quenching reaction is 5 ℃, the molar concentration of the hydrochloric acid aqueous solution is 1mol/L, and the molar input amount of the hydrochloric acid is 1.18 times of that of the phenylmagnesium bromide; the total conversion rate is 99.6%, and the yield of the product (S) - (-) -1,1, 2-triphenyl-1, 2-glycol is 91.5%.
Example 5, separately dissolving methyl mandelate and phenylmagnesium bromide in 2-methyltetrahydrofuran to obtain a methyl mandelate solution with a molar concentration of 0.5mol/L and a phenylmagnesium bromide solution with a molar concentration of 1 mol/L; respectively inputting the prepared methyl mandelate solution and phenyl magnesium bromide solution into a first microchannel reactor through a metering pump to carry out main reaction, directly flowing the reaction solution obtained after reaction into a second microchannel reactor, inputting hydrochloric acid aqueous solution into the second microchannel reactor through a metering pump to carry out quenching reaction while the reaction solution flows into the second microchannel reactor, obtaining reaction liquid after the quenching reaction is finished, flowing the reaction liquid into a receiver in a high dispersion phase continuous flow state, layering the reaction liquid in the receiver to obtain an organic phase, drying the organic phase by using anhydrous magnesium sulfate, then carrying out reduced pressure concentration, and recrystallizing by using toluene to obtain a finished product (S) - (-) -1,1, 2-triphenyl-1, 2-ethylene glycol; wherein the main reaction residence time in the first microchannel reactor is 4min, the reaction temperature is 30 ℃, and the input molar weight ratio of the methyl mandelate solution to the phenyl magnesium bromide solution is 1: 1.3; the residence time of the quenching reaction in the second microchannel reactor is 1min, the temperature of the quenching reaction is 5 ℃, the molar concentration of the hydrochloric acid aqueous solution is 1mol/L, and the molar input amount of the hydrochloric acid is 1.2 times of that of the phenylmagnesium bromide; the total conversion rate is 100 percent, and the yield of the product (S) - (-) -1,1, 2-triphenyl-1, 2-glycol is 92 percent.
Claims (2)
1. A preparation method of (S) - (-) -1,1, 2-triphenyl-1, 2-glycol is characterized in that methyl mandelate and phenyl magnesium bromide are respectively dissolved in a solvent to prepare a methyl mandelate solution and a phenyl magnesium bromide solution, wherein the molar concentration of the methyl mandelate solution is 0.1-3 mol/L, the molar concentration of the phenyl magnesium bromide solution is 0.1-2 mol/L, and the solvent is diethyl ether, tetrahydrofuran or 2-methyltetrahydrofuran; respectively inputting the prepared methyl mandelate solution and phenyl magnesium bromide solution into a first microchannel reactor through a metering pump to carry out main reaction, directly flowing the reaction solution obtained after the reaction into a second microchannel reactor, inputting an acidic aqueous solution into the second microchannel reactor through a metering pump to carry out quenching reaction while the reaction solution flows into the second microchannel reactor, obtaining reaction liquid after the quenching reaction is finished, layering the reaction liquid to obtain an organic phase, drying the organic phase, carrying out reduced pressure concentration, and recrystallizing with toluene to obtain a finished product (S) - (-) -1,1, 2-triphenyl-1, 2-ethylene glycol; wherein the main reaction residence time in the first microchannel reactor is 0.5-5 min, the reaction temperature is 10-50 ℃, and the input molar weight ratio of the methyl mandelate solution to the phenyl magnesium bromide solution is 1: 1-1: 3; the residence time of the quenching reaction in the second microchannel reactor is 0.5-1.5 min, the temperature of the quenching reaction is-10-30 ℃, the molar concentration of the acidic aqueous solution is 0.05-4 mol/L, and the molar input amount of the acid in the acidic aqueous solution is 1-2 times of that of the phenylmagnesium bromide.
2. The process according to claim 1, wherein the molar concentration of the methyl mandelate solution is 0.5 to 1mol/L, the molar concentration of the phenylmagnesium bromide solution is 0.5 to 1mol/L, and the solvent is 2-methyltetrahydrofuran; the main reaction residence time in the first microchannel reactor is 1-3 min, the reaction temperature is 20-30 ℃, the residence time in the first microchannel reactor is 0.5-5 min, and the input molar weight ratio of the methyl mandelate solution to the phenyl magnesium bromide solution is 1: 1.05-1: 1.5; the residence time of the quenching reaction in the second microchannel reactor is 0.8-1.2 min, the temperature of the quenching reaction is 0-10 ℃, the molar concentration of the acidic aqueous solution is 1-2 mol/L, and the molar input amount of the acid in the acidic aqueous solution is 1.05-1.2 times of that of the phenylmagnesium bromide.
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| SYNTHETIC STUDIES OF THE DETOXIN COMPLEX. I. TOTAL SYNTHESIS OF (-) DETOXININE.;W. R. Ewing等;《Tcwahcdron》;19861231;第42卷(第9期);2421-2428 * |
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