CN108358789A - A kind of preparation method of 5- halogen levulinate - Google Patents
A kind of preparation method of 5- halogen levulinate Download PDFInfo
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- CN108358789A CN108358789A CN201810396267.5A CN201810396267A CN108358789A CN 108358789 A CN108358789 A CN 108358789A CN 201810396267 A CN201810396267 A CN 201810396267A CN 108358789 A CN108358789 A CN 108358789A
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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
- C07C67/307—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
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Abstract
The invention discloses a kind of preparation methods of 5 halogen levulinate, and with levulic acid or levulinate and halogenated dose for raw material, this halogenated dose includes NBS, NCS, ferrous bromide, ferric bromide, alchlor, phosphorus tribromide, copper bromide and copper chloride.Using the levulic acid or levulinate that can be obtained from biomass by hydrolyzation as raw material halogenating reaction 5 halogen levulinates of synthesis occur under halogenated dose of existence condition for the present invention.The raw material sources that the present invention selects are extensive, cheap and easy to get；Reaction condition is mild, reaction yield and high selectivity；And selected halogenated dose as raw material relative to the bromine toxicity smaller applied in traditional mercury technique, it is more environmentally friendly, have good prospects for commercial application.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of preparation method of 5- halogen levulinate.
Background technology
5-ALA (5-ALA) is the substance being widely present in nature animal and plant body, is porphyrins
Synthesis precursor, agricultural and medically have important application.And 5- halogen levulinates are a kind of synthesis 5- glycyls third
Therefore the important intermediate of acid hydrochloride is sought a kind of with industrial levulic acid or levulinate cheap and easy to get to be original
Expect the method that efficient high yield prepares 5- halogen levulinates, the exploration to 5-ALA hydrochloride chemical synthesis process
There is particularly significant meaning.Currently, the correlation report both at home and abroad about the research of this intermediate synthesis is few, such as United States Patent (USP)
US4325877 describes a kind of method preparing 5-ALA as raw material using bromine, methyl ester levulinate.This method operation is multiple
It is miscellaneous, environment is polluted, by-product is more, and the selectivity of target product, yield are relatively low.In previous preparation process, it is with bromine
Bromating agent prepares 5- acetyl bromide propionic esters itself there are bromination efficiency the problems such as low, by-product is more, and by-product 3- bromoacetyls
Propionic ester and principal product 5- bromoacetyl propionic ester Nature comparisons are close, and bigger difficulty is caused to the separation of target product.
Invention content
It is an object of the invention to overcome prior art defect, a kind of preparation method of 5- halogen levulinate is provided.
Technical scheme is as follows：
A kind of preparation method of 5- halogen levulinate should with levulic acid or levulinate and halogenated dose for raw material
Halogenated dose includes NBS, NCS, ferrous bromide, ferric bromide, alchlor, phosphorus tribromide, copper bromide and copper chloride；
Specifically comprise the following steps：
(1) levulic acid or levulinate are dissolved in reaction dissolvent to a concentration of 0.08~0.16mol/L, in 8
Halogenated dose is added at~67 DEG C and is stirred to react 2~12h；
(2) reaction dissolvent in the material obtained by step (1) is removed, deionized water dissolving is then added, adds ether
It is extracted, is washed to neutrality with sodium bicarbonate solution after obtaining organic phase, after drying and removing ether, obtain 5- halogen levulic acids
Ester crude product；
(3) above-mentioned 5- halogen levulinate crude product is tied in ether-hexamethylene in the mixed solvent in -42~-18 DEG C again
Crystalline substance obtains the 5- halogen levulinate.
In a preferred embodiment of the invention, the reaction dissolvent is methanol, ethyl alcohol, propyl alcohol, octanol, dichloromethane
At least one of alkane, chloroform, carbon tetrachloride and ethyl acetate.
In a preferred embodiment of the invention, in the step (1), levulic acid or levulinate are dissolved
To a concentration of 0.082~0.15mol/L in reaction dissolvent, halogenated dose is added in 10~65 DEG C and is stirred to react 2~10h.
In a preferred embodiment of the invention, mole of the levulic acid or levulinate and halogenating agent
Than being 0.2~0.8: 1.
In a preferred embodiment of the invention, in the step (2) volume ratio of ether and deionized water be 4~
7∶1。
In a preferred embodiment of the invention, the ether-hexamethylene in the mixed solvent ether and hexamethylene
Volume ratio is 1: 1.
In a preferred embodiment of the invention, the temperature of the recrystallization is -40~-20 DEG C.
The beneficial effects of the invention are as follows：
1, the present invention is deposited using the levulic acid or levulinate that can be obtained from biomass by hydrolyzation as raw material in halogenating agent
Halogenating reaction occurs under conditions and synthesizes 5- halogen levulinates.
2, the raw material sources that the present invention selects are extensive, cheap and easy to get；Reaction condition is mild, reaction yield and high selectivity；
And halogenating agent as raw material relative to the bromine toxicity smaller applied in traditional mercury technique, it is more environmentally friendly, have very
Good prospects for commercial application.
Description of the drawings
Fig. 1 is the gas chromatogram of the 5- acetyl bromide methyl propionate sterlings of 1 to 6 gained of the embodiment of the present invention, residence time
10.99min is 5- acetyl bromide methyl propionates.
Fig. 2 is the mass spectrogram of the 5- acetyl bromide methyl propionate sterlings of 1 to 6 gained of the embodiment of the present invention.
Fig. 3 is to obtain the gas chromatogram of 5- chloracetyl methyl propionates in the embodiment of the present invention 7, and the residence time is
9.79min。
Fig. 4 is to have obtained the corresponding matter of 5- chloracetyl methyl propionates in 5- chloracetyl methyl propionates in the embodiment of the present invention 7
Spectrogram.
Specific implementation mode
Technical scheme of the present invention is further detailed and is described below by way of specific implementation mode combination attached drawing.
Embodiment 1
0.33g (0.0025mol) methyl ester levulinate, methanol 20mL, (levulic acid are added in the there-necked flask of 100mL
A concentration of 0.125mol/L of methyl esters).It connects condenser pipe to be placed in 60 DEG C of water-baths, total 1.67g copper bromides (levulic acid first is added
Ester is 0.33 with copper bromide molar ratio: 1) being reacted, react 2h, be after reaction evaporated under reduced pressure product.To remnants
20mL methanol is added in liquid to dissolve and filter, after filtrate dilutes 5 times, using gas chromatograph-mass spectrometer (GC-MS) (GC-MS) to mesh
Product carry out qualitative detection, and using quantified by external standard method calculate.The volumetric concentration for measuring product 5- acetyl bromide methyl propionates is
0.0079g/mL, yield 29.97%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains bromination mixture, be placed at -40~-20 DEG C repeatedly with ether and hexamethylene (volume ratio 1: 1) dissolving
Recrystallization, obtains 5- acetyl bromide methyl propionate sterlings.The gas chromatogram of sterling is as shown in Figure 1, mass spectrogram is as shown in Figure 2.
Embodiment 2
0.33g (0.0025mol) methyl ester levulinate, isometric methanol, chloroform mixing are added in the there-necked flask of 100mL
The total 20mL of liquid, (a concentration of 0.125mol/L of methyl ester levulinate).It connects condenser pipe to be placed in 55 DEG C of water-baths, be added altogether
1.67g copper bromides and potassium bromide (methyl ester levulinate is about 0.33: 1 with copper bromide, potassium bromide mixture molar ratio) carry out anti-
It answers, reacts 4h, be after reaction evaporated under reduced pressure product.20mL methanol is added into residual liquid and carries out dissolving and mistake
Filter after filtrate dilutes 5 times, carries out qualitative detection, and use using gas chromatograph-mass spectrometer (GC-MS) (GC-MS) to purpose product
Quantified by external standard method calculates.A concentration of 0.0081g/mL of product 5- acetyl bromide methyl propionates, yield 30.73%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains bromination mixture, be placed at -40~-20 DEG C repeatedly with ether and hexamethylene (volume ratio 1: 1) dissolving
Recrystallization, obtains 5- acetyl bromide methyl propionate sterlings.The gas chromatogram of sterling is as shown in Figure 1, mass spectrogram is as shown in Figure 2.
Embodiment 3
0.33g (0.0025mol) methyl ester levulinate, isometric methanol, chloroform mixing are added in the there-necked flask of 100mL
The total 20mL of liquid, (a concentration of 0.125mol/L of methyl ester levulinate).It connects condenser pipe to be placed in 40 DEG C of water-baths, be added altogether
1.67g copper bromides (methyl ester levulinate is 0.33: 1 with copper bromide molar ratio) are reacted, and are reacted 10h, after reaction will
Product is evaporated under reduced pressure.20mL methanol is added into residual liquid to dissolve and filter, after filtrate dilutes 5 times, using gas phase color
Spectrum-mass spectrometer (GC-MS) carries out qualitative detection to purpose product, and is calculated using quantified by external standard method.Measure product 5- bromines
The volumetric concentration of methyl ester levulinate is 0.0093g/mL, yield 35.28%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains bromination mixture, be placed at -40~-20 DEG C repeatedly with ether and hexamethylene (volume ratio 1: 1) dissolving
Recrystallization, obtains 5- acetyl bromide methyl propionate sterlings.The gas chromatogram of sterling is as shown in Figure 1, mass spectrogram is as shown in Figure 2.
Embodiment 4
0.65g (0.005mol) methyl ester levulinate, isometric methanol, carbon tetrachloride are added in the there-necked flask of 100mL
The total 40mL of mixed liquor, (a concentration of 0.125mol/L of methyl ester levulinate) are added initiator B PO 0.048g, connect condenser pipe and set
In 40 DEG C of water-baths, total NBS 0.98g (methyl ester levulinate is 0.33: 1 with NBS molar ratios) are added and are reacted, react
Product is evaporated under reduced pressure by 4h after reaction.20mL methanol is added into residual liquid to be dissolved and filtered, filtrate is dilute
After releasing 5 times, qualitative detection is carried out to purpose product using gas chromatograph-mass spectrometer (GC-MS) (GC-MS), and use quantified by external standard method
It calculates.A concentration of 0.0073g/mL of product 5- acetyl bromide methyl propionates, yield 27.69%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains bromination mixture, be placed at -40~-20 DEG C repeatedly with ether and hexamethylene (volume ratio 1: 1) dissolving
Recrystallization, obtains 5- acetyl bromide methyl propionate sterlings.The gas chromatogram of sterling is as shown in Figure 1, mass spectrogram is as shown in Figure 2.
Embodiment 5
0.65g (0.005mol) methyl ester levulinate, isometric methanol, carbon tetrachloride are added in the there-necked flask of 100mL
The total 40mL of mixed liquor, (a concentration of 0.125mol/L of methyl ester levulinate) are added initiator A IBN 0.088g, connect condenser pipe and set
In 65 DEG C of water-baths, total NBS 0.98g (methyl ester levulinate is 0.33: 1 with NBS molar ratios) are added and are reacted, react
Product is evaporated under reduced pressure by 4h after reaction.20mL methanol is added into residual liquid to be dissolved and filtered, filtrate is dilute
After releasing 5 times, qualitative detection is carried out to purpose product using gas chromatograph-mass spectrometer (GC-MS) (GC-MS), and use quantified by external standard method
It calculates.A concentration of 0.0083g/mL of product 5- acetyl bromide methyl propionates, yield 31.49%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains bromination mixture, be placed at -40~-20 DEG C repeatedly with ether and hexamethylene (volume ratio 1: 1) dissolving
Recrystallization, obtains 5- acetyl bromide methyl propionate sterlings.The gas chromatogram of sterling is as shown in Figure 1, mass spectrogram is as shown in Figure 2.
Embodiment 6
0.58g (0.005mol) levulic acid, isometric methanol, carbon tetrachloride mixing are added in the there-necked flask of 100mL
The total 40mL of liquid, (a concentration of 0.125mol/L of levulic acid) are added initiator B PO 0.048g, connect condenser pipe and be placed in 40 DEG C of water
In bath, total NBS 0.98g (levulic acid is 0.33: 1 with NBS molar ratios) are added and are reacted, react 4h, after reaction
Product is evaporated under reduced pressure.20mL methanol is added into residual liquid to be dissolved and filtered, after filtrate dilutes 5 times, uses
Gas chromatograph-mass spectrometer (GC-MS) (GC-MS) carries out qualitative detection to purpose product, and is calculated using quantified by external standard method.Product 5-
A concentration of 0.0043g/mL of acetyl bromide methyl propionate, yield 18.28%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains bromination mixture, be placed at -40~-20 DEG C repeatedly with ether and hexamethylene (volume ratio 1: 1) dissolving
Recrystallization, obtains 5- acetyl bromide methyl propionate sterlings.The gas chromatogram of sterling is as shown in Figure 1, mass spectrogram is as shown in Figure 2.
Embodiment 7
0.65g (0.005mol) methyl ester levulinate, isometric methanol, chloroform mixing are added in the there-necked flask of 100mL
The total 40mL of liquid, (a concentration of 0.125mol/L of methyl ester levulinate).It connects condenser pipe to be placed in 40 DEG C of water-baths, be added altogether
2.56g copper chlorides (methyl ester levulinate is 0.33: 1 with copper chloride molar ratio) are reacted, and 4h is reacted, after reaction will production
Object is evaporated under reduced pressure.20mL methanol is added into residual liquid to be dissolved and filtered, after filtrate dilutes 5 times, using gas phase
Chromatograph-mas spectrometer (GC-MS) carries out qualitative detection to purpose product, and is calculated using inner mark method ration.Product 5- chloroethenes
A concentration of 0.0041g/mL of acyl methyl propionate, yield 16.40%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains chlorinated mixture, recrystallized under stirring at normal temperature with methyl tertiary butyl ether(MTBE) and petroleum ether (volume ratio 1: 6),
Obtain 5- chloracetyl methyl propionate crude products.The gas chromatogram of 5- chloracetyl methyl propionates is as shown in figure 3, mass spectrogram is as shown in Figure 4.
Embodiment 8
0.37g (0.0026mol) ethyl levulinate, isometric methanol, chloroform mixing are added in the there-necked flask of 100mL
The total 20mL of liquid, (a concentration of 0.130mol/L of ethyl levulinate).It connects condenser pipe to be placed in 65 DEG C of water-baths, be added altogether
1.67g (0.0075mol) copper bromide (ethyl levulinate is 0.3: 1 with copper bromide molar ratio) is reacted, and 4h, reaction are reacted
After product is evaporated under reduced pressure.20mL methanol is added into residual liquid to be dissolved and filtered, filtrate dilutes 5 times
Afterwards, qualitative detection is carried out to purpose product using gas chromatograph-mass spectrometer (GC-MS) (GC-MS), and is calculated using inner mark method ration.
A concentration of 0.0071g/mL of product 5- acetyl bromide ethyl propionates, yield 27.17%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains bromination mixture, be placed at -40~-20 DEG C repeatedly with ether and hexamethylene (volume ratio 1: 1) dissolving
Recrystallization, obtains 5- acetyl bromide ethyl propionate crude products.
Embodiment 9
0.58g (0.005mol) levulic acid, 20ml the ethyl alcohol, (concentration of levulic acid are added in the there-necked flask of 100mL
For 0.25mol/L).Condenser pipe is connect to be placed in 40 DEG C of water-baths, be added total 3.33g (0.0150mol) copper bromide (levulic acid and
Copper bromide molar ratio is 0.33: 1) being reacted, react 4h, be after reaction evaporated under reduced pressure product.To residual liquid
Middle addition 20mL methanol is dissolved and is filtered, after filtrate dilutes 5 times, using gas chromatograph-mass spectrometer (GC-MS) (GC-MS) to mesh
Product carry out qualitative detection, and using inner mark method ration calculate.A concentration of 0.0083g/ of product 5- acetyl bromide ethyl propionates
ML, yield 31.32%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains bromination mixture, be placed at -40~-20 DEG C repeatedly with ether and hexamethylene (volume ratio 1: 1) dissolving
Recrystallization, obtains 5- acetyl bromide ethyl propionate crude products.
Embodiment 10
0.65g (0.005mol) methyl ester levulinate, chloroform 20mL, (levulic acid first are added in the there-necked flask of 100mL
A concentration of 0.25mol/L of ester).It connects condenser pipe to be placed in 40 DEG C of water-baths, total 3.33g copper bromides (methyl ester levulinate is added
It is 0.33 with copper bromide molar ratio: 1) is reacted, reacts 4h, be after reaction evaporated under reduced pressure product.To residual solution
20mL methanol is added in body to dissolve and filter, after filtrate dilutes 5 times, using gas chromatograph-mass spectrometer (GC-MS) (GC-MS) to purpose
Product carries out qualitative detection, and is calculated using quantified by external standard method.The volumetric concentration for measuring product 5- acetyl bromide methyl propionates is
0.0082g/mL, yield 31.03%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains bromination mixture, be placed at -40~-20 DEG C repeatedly with ether and hexamethylene (volume ratio 1: 1) dissolving
Recrystallization, obtains 5- acetyl bromide methyl propionate sterlings.The gas chromatogram of sterling is as shown in Figure 1, mass spectrogram is as shown in Figure 2.
Embodiment 11
0.65g (0.005mol) methyl ester levulinate, the methanol dichloromethane of isometric ratio are added in the there-necked flask of 100mL
The total 20mL of alkane, (a concentration of 0.25mol/L of methyl ester levulinate).It connects condenser pipe to be placed in 40 DEG C of water-baths, total 3.33g is added
Copper bromide is carried out with bromination iron mixture (molar ratio of methyl ester levulinate and copper bromide bromination iron mixture is about 0.33: 1)
Reaction reacts 4h, is after reaction evaporated under reduced pressure product.20mL methanol is added into residual liquid to dissolve and filter,
After filtrate dilutes 5 times, qualitative detection is carried out to purpose product using gas chromatograph-mass spectrometer (GC-MS) (GC-MS), and use external standard
Standard measure calculates.The volumetric concentration for measuring product 5- acetyl bromide methyl propionates is 0.0068g/mL, yield 25.76%.
The dissolved product of methanol is evaporated under reduced pressure again, a small amount of deionized water dissolving revolving object is added, adds
Appropriate ether standing separation water phase, is washed with a large amount of saturated sodium bicarbonate solutions, is then dried with anhydrous magnesium sulfate, is evaporated under reduced pressure
It removes ether and obtains bromination mixture, be placed at -40~-20 DEG C repeatedly with ether and hexamethylene (volume ratio 1: 1) dissolving
Recrystallization, obtains 5- acetyl bromide methyl propionate sterlings.The gas chromatogram of sterling is as shown in Figure 1, mass spectrogram is as shown in Figure 2.
Embodiment 12
0.65g (0.005mol) methyl ester levulinate, methanol 20mL, (levulic acid first are added in the there-necked flask of 100mL
A concentration of 0.25mol/L of ester).It connects condenser pipe to be placed in 40 DEG C of water-baths, total 3.98g aluminium bromides (methyl ester levulinate is added
It is 0.33 with bromination al mole ratio: 1) is reacted, reacts 4h, be after reaction evaporated under reduced pressure product.To residual solution
20mL methanol is added in body to dissolve and filter, after filtrate dilutes 5 times, using gas chromatograph-mass spectrometer (GC-MS) (GC-MS) to purpose
Product carries out qualitative detection, and is calculated using quantified by external standard method.The volumetric concentration for measuring product 5- acetyl bromide methyl propionates is
0.0001g/mL, yield 0.38%.
Those of ordinary skill in the art remain able to it is found that when technical scheme of the present invention changes in following ranges
To same as the previously described embodiments or similar technique effect, protection scope of the present invention is still fallen within：
A kind of preparation method of 5- halogen levulinate should with levulic acid or levulinate and halogenated dose for raw material
Halogenated dose includes NBS, NCS, ferrous bromide, ferric bromide, alchlor, phosphorus tribromide, copper bromide and copper chloride；
Specifically comprise the following steps：
(1) levulic acid or levulinate are dissolved in reaction dissolvent to a concentration of 0.08~0.16mol/L, in 8
Halogenated dose is added at~67 DEG C and is stirred to react 2~12h；Preferably, reaction dissolvent is methanol, ethyl alcohol, propyl alcohol, octanol, dichloro
At least one of methane, chloroform, carbon tetrachloride and ethyl acetate；
(2) reaction dissolvent in the material obtained by step (1) is removed, deionized water dissolving is then added, adds ether
It is extracted, is washed to neutrality with sodium bicarbonate solution after obtaining organic phase, after drying and removing ether, obtain 5- halogen levulic acids
Ester crude product；
(3) above-mentioned 5- halogen levulinate crude product is tied in ether-hexamethylene in the mixed solvent in -42~-18 DEG C again
Crystalline substance obtains the 5- halogen levulinate.
Preferably, in the step (1), levulic acid or levulinate are dissolved in reaction dissolvent to a concentration of
Halogenated dose is added in 10~65 DEG C and is stirred to react 2~10h by 0.1~0.15mol/L.The levulinate with halogenated dose
Molar ratio is 0.2~0.8: 1.The volume ratio of ether and deionized water is 4~7: 1 in the step (2).The ether hexamethylene
The volume ratio of in the mixed solvent ether and hexamethylene is 1: 1.The temperature of the recrystallization is -40~-20 DEG C.
The foregoing is only a preferred embodiment of the present invention, therefore cannot limit the scope of implementation of the present invention according to this, i.e.,
According to equivalent changes and modifications made by the scope of the claims of the present invention and description, all should still belong in the range of the present invention covers.
Claims (7)
1. a kind of preparation method of 5- halogen levulinate, it is characterised in that：With levulic acid or levulinate and halogenated dose
For raw material, this halogenated dose includes NBS, NCS, ferrous bromide, ferric bromide, alchlor, phosphorus tribromide, copper bromide and copper chloride；
Specifically comprise the following steps：
(1) levulic acid or levulinate are dissolved in reaction dissolvent to a concentration of 0.08~0.16mol/L, in 8~67
Halogenated dose is added at DEG C and is stirred to react 2~12h；
(2) reaction dissolvent in the material obtained by step (1) is removed, deionized water dissolving is then added, adds ether progress
Extraction is washed to neutrality with sodium bicarbonate solution after obtaining organic phase, after drying and removing ether, it is thick to obtain 5- halogen levulinates
Product；
(3) above-mentioned 5- halogen levulinate crude product is recrystallized in ether-hexamethylene in the mixed solvent in -42~-18 DEG C,
Obtain the 5- halogen levulinate.
2. preparation method as described in claim 1, it is characterised in that：The reaction dissolvent be methanol, ethyl alcohol, propyl alcohol, octanol,
At least one of dichloromethane, chloroform, carbon tetrachloride and ethyl acetate.
3. preparation method as claimed in claim 1 or 2, it is characterised in that：In the step (1), by levulic acid or acetyl
Propionic ester is dissolved in reaction dissolvent to a concentration of 0.082~0.15mol/L, and halogenated dose is added in 10~65 DEG C and is stirred to react
2~10h.
4. preparation method as claimed in claim 1 or 2, it is characterised in that：The levulic acid or levulinate with it is halogenated
The molar ratio of reagent is 0.2~0.8: 1.
5. preparation method as claimed in claim 1 or 2, it is characterised in that：The body of ether and deionized water in the step (2)
Product is than being 4~7: 1.
6. preparation method as claimed in claim 1 or 2, it is characterised in that：The ether-hexamethylene in the mixed solvent ether with
The volume ratio of hexamethylene is 1: 1.
7. preparation method as claimed in claim 1 or 2, it is characterised in that：The temperature of the recrystallization is -40~-20 DEG C.
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| CN113416142A (en) * | 2021-06-22 | 2021-09-21 | 邯郸市赵都精细化工有限公司 | Preparation method of 5-ALA intermediate 5-bromolevulinate |
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|---|---|---|---|---|
| CN113416142A (en) * | 2021-06-22 | 2021-09-21 | 邯郸市赵都精细化工有限公司 | Preparation method of 5-ALA intermediate 5-bromolevulinate |
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