CN106810458B - A method of it splitting DL-2- aminopropanol and prepares L-2- aminopropanol - Google Patents
A method of it splitting DL-2- aminopropanol and prepares L-2- aminopropanol Download PDFInfo
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- CN106810458B CN106810458B CN201611268213.8A CN201611268213A CN106810458B CN 106810458 B CN106810458 B CN 106810458B CN 201611268213 A CN201611268213 A CN 201611268213A CN 106810458 B CN106810458 B CN 106810458B
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- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
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Abstract
The present invention relates to a kind of methods that fractionation DL-2- aminopropanol prepares L-2- aminopropanol comprising following steps: 1) being dissolved in water for L-TARTARIC ACID, obtains L-TARTARIC ACID aqueous solution；2) DL-2- aminopropanol at room temperature, is dissolved in alcoholic solvent, then in the cooling condition, L-TARTARIC ACID aqueous solution is added dropwise while stirring, 0-5 DEG C of heat preservation is cooled to after being added dropwise, obtains cooling solution；3) a small amount of crystal seed is added into cooling solution, 16-24 hours are stood still for crystals in -15 DEG C -+25 DEG C, L-TARTARIC ACID-L-2- aminopropanol acid salt crystal is precipitated；4) L-TARTARIC ACID-L-2- aminopropanol acid salt crystal is dissolved with alcoholic solvent, inorganic base is added portionwise, stirring to the complete separate out of amino alcohol filters, and filtrate decompression distills to obtain L-2- aminopropanol.Technological operation of the invention is simple, and raw material availability is high, is suitble to large-scale production.
Description
Technical field
The invention belongs to technical field of fine, are related to a kind of fractionation DL-2- aminopropanol preparation L-2- aminopropanol
Method.
Background technique
L-2- aminopropanol is a kind of important organic chemical industry's intermediate, is that fluoroquinolone drug is left-handed
One of the intermediate of Ofloxacin and pesticide essence dimethenamid, and a kind of important organic synthesis chiral building block.Chiral
L-2- aminopropanol is made generally by 2- alanine or derivatives thereof of also prochirality, and chiral raw material therein and also
The price of former agent is costly.The 2- aminopropanol that general synthetic method obtains is mostly racemic modification, there is no a kind of economy at present
The method that feasible resolution of racemic 2- aminopropanol prepares L-2- aminopropanol.
Summary of the invention
The technical problem to be solved by the present invention is to aiming at the above shortcomings existing in the prior art, provide a kind of fractionation
The method that DL-2- aminopropanol prepares L-2- aminopropanol, technological operation is simple, and raw material availability is high, and the yield of fractionation reaches
74.7-92.2%, resolving agent winestone acid recovering rate are suitble to large-scale production up to 95% or more.
In order to solve the above technical problems, present invention provide the technical scheme that
There is provided a kind of method that fractionation DL-2- aminopropanol prepares L-2- aminopropanol comprising following steps:
1) L-TARTARIC ACID is dissolved in water, obtains L-TARTARIC ACID aqueous solution；
2) DL-2- aminopropanol at room temperature, is dissolved in alcoholic solvent, obtains the DL-2- aminopropan that mass concentration is 5~20%
Alcoholic solution, then in the cooling condition, a dropping step 1 while stirring) gained L-TARTARIC ACID aqueous solution, wherein molar ratio L- winestone
Acid: DL-2- aminopropanol=1:1, control system temperature is not higher than 50 DEG C during dropwise addition, is cooled to 0-5 DEG C after being added dropwise
Heat preservation, obtains cooling solution；
3) a small amount of crystal seed (L-TARTARIC ACID-L-2- aminopropanol crystal seed) is added into solution cooling obtained by step 2), in-
15 DEG C -+25 DEG C stand still for crystals 16-24 hours, and L-TARTARIC ACID-L-2- aminopropanol acid salt crystal is precipitated, and filter, and on a small quantity
The crystal that is precipitated of alcoholic solvent washing, filtrate is then used to recycle D-2- aminopropanol；
4) L-TARTARIC ACID-L-2- aminopropanol acid salt crystal obtained by step 3) is dissolved with alcoholic solvent, divides 2~6 batches to add
Enter inorganic base, inorganic base and L-TARTARIC ACID-L-2- aminopropanol acid salt crystal molar ratio are 2:1, are stirred complete to amino alcohol
Separate out filters, and for filter cake for recycling L-TARTARIC ACID salt, filtrate decompression distills to obtain L-2- aminopropanol.
According to the above scheme, step 1) the L-TARTARIC ACID aqueous solution mass concentration is 20~60%.
According to the above scheme, the step 2) alcoholic solvent is one or more of methanol, ethyl alcohol, normal propyl alcohol, isopropanol.
According to the above scheme, the step 3) temperature that stands still for crystals is 0-5 DEG C.
According to the above scheme, the method for step 3) the recycling D-2- aminopropanol is as follows: at 180-200 DEG C, using Raney Ni
Catalytic racemization D-2- aminopropanol obtains racemic DL-2- aminopropanol, then using gained racemic DL-2- aminopropanol as
Raw material splits preparation L-2- aminopropanol using step 1) to 4) the method.
According to the above scheme, the step 4) inorganic base is sodium hydroxide, in potassium hydroxide, calcium hydroxide, magnesium hydroxide
It is one or more of.
According to the above scheme, the method for step 4) the recycling L-TARTARIC ACID salt is as follows: L-TARTARIC ACID salt is dissolved with methanol,
Inorganic acid is added dropwise, L-TARTARIC ACID salt and inorganic acid molar ratio are 1:2, and stirring is precipitated completely to inorganic salts, filters, and filtrate is evaporated
To L-TARTARIC ACID.
According to the above scheme, the inorganic acid is one or more of concentrated hydrochloric acid, the concentrated sulfuric acid, phosphoric acid.
The beneficial effects of the present invention are: the present invention carries out fractionation system to DL-2- aminopropanol using better simply technique
Standby L-2- aminopropanol, resolution yield is high (reaching 74.7-92.2%), and resolving agent winestone acid recovering rate is up to 95% or more,
D-2- aminopropanol after fractionation also may be recovered and be converted into racemic DL-2- aminopropanol, then as raw material, use
Claim 1 the method splits preparation L-2- aminopropanol, to improve the utilization rate of raw material, is suitble to scale metaplasia
It produces.
Specific embodiment
Technical solution in order to enable those skilled in the art to better understand the present invention makees the present invention below with reference to embodiment
It is described in further detail.
Embodiment 1
In 1 liter of flask, 450 grams of ethyl alcohol and 37.5 grams of (0.5 mole) racemic DL-2- aminopropanols are added, room temperature is stirred
Dissolution clarification is mixed, the clear solution of 75 grams of (0.5 mole) L-TARTARIC ACIDs and 150 grams of distilled water, control is added dropwise in the stirring of the side Bian Jiangwen
Rate of addition makes interior temperature be no more than 50 DEG C, is cooled to 0-5 DEG C after adding.It is added into 3 grams of crystal seeds (L-TARTARIC ACID-L-2- aminopropan
Alcohol crystal seed), it is slowly stirred crystallization 20 hours, a large amount of crystal is precipitated.Filtering, a small amount of ethanol washing of solid, 25 DEG C of vacuum are dry
It is dry, 49.4 grams of acid salt of L-TARTARIC ACID-L-2 aminopropanol are obtained, filtrate decompression is spin-dried for, and obtains 63 grams of acid salt.
It will obtain the anhydrous second that 49.4 grams of (0.22 mole) L-TARTARIC ACID-L-2 aminopropanol acid salt are scattered in 200 milliliters
In alcohol, room temperature point 3 batches of 17.6 grams of addition sodium hydroxides (0.44 mole), after be stirred at room temperature, it is complete that TLC tracks to 2- aminopropanol
Free, filtering, the suitable ethanol washing of filter cake obtains L-TARTARIC ACID disodium salt, is evaporated under reduced pressure after filtrate concentration, obtains 16.3 grams of L-
2- aminopropanol, resolution yield 86.9%.After tested, L-2- aminopropanol specific rotation [α] obtained by the present embodiment20=+21.9 ° of (C
=2, ethyl alcohol), illustrate its purity is high.
Embodiment 2
In 1000 milliliters of flasks, 270 grams of methanol and 37.5 grams of (0.5 mole) racemic DL-2- aminopropanols, room is added
The clear solution of 75 grams of (0.5 mole) L-TARTARIC ACIDs and 70 grams of distilled water is added dropwise in warm stirring and dissolving clarification, the stirring of the side Bian Jiangwen,
The speed being added dropwise is controlled, so that interior temperature is no more than 40 DEG C, is cooled to 0-5 DEG C after adding, adds 3 grams of crystal seeds, be slowly stirred crystallization 16
Hour, a large amount of crystal is precipitated.Filtering, filter cake are washed with a small amount of methanol, and 25 DEG C of vacuum drying obtain L-TARTARIC ACID-L-2 aminopropan
51.8 grams of alcohol acid salt, filtrate decompression is spin-dried for, and obtains 60 grams of acid salt.
51.8 grams of (0.23 mole) L-TARTARIC ACID-L-2- aminopropanol acid salt will be obtained to be scattered in 150 ml methanols,
Room temperature point 3 batches of 25.8 grams of additions potassium hydroxide (0.46 mole), after be stirred at room temperature, TLC tracks to 2- aminopropanol and dissociates completely,
Filtering, solid are washed with suitable methanol, are obtained L-TARTARIC ACID di-potassium, are evaporated under reduced pressure after filtrate concentration, obtain 17.3 grams of L-2- ammonia
Base propyl alcohol, resolution yield 92.2%.
Embodiment 3
In 1000 milliliters of flasks, 270 grams of isopropanols and 37.5 grams of (0.5 mole) racemic DL-2- aminopropanols are added,
Dissolution clarification is stirred at room temperature, the side Bian Jiangwen is stirred, and the clarification that 75 grams of (0.5 mole) L-TARTARIC ACIDs and 180 grams of distilled water are added dropwise is molten
Liquid controls the speed of dropwise addition, and interior temperature is made to be no more than 50 DEG C, and 0-5 degrees Celsius is cooled to after adding, and adds about 5 grams of crystal seeds, slowly stirs
Crystallization 24 hours is mixed, a large amount of crystal is precipitated, is filtered, filter cake is washed with a small amount of isopropanol, and 25 DEG C of vacuum drying obtain L- winestone
42.2 grams of acid salt of acid-L-2 aminopropanol, filtrate decompression is spin-dried for, and obtains 70 grams of acid salt.
150 milliliters of isopropyls are dispersed by obtain 42.2 grams of (0.188 mole) L-TARTARIC ACID-L-2- aminopropanol acid salt
In alcohol, room temperature point 3 batches of 13.1 grams of addition magnesium hydroxides (0.226 mole), after be stirred at room temperature, it is complete that TLC tracks to 2- aminopropanol
Complete free, filtering, solid is washed with suitable isopropanol, is obtained L-TARTARIC ACID magnesium salts, is evaporated under reduced pressure after filtrate concentration, obtains 14.0 grams
L-2- aminopropanol, resolution yield 74.7%.
Embodiment 4
In 1 liter of flask, 400 grams of normal propyl alcohols and 37.5 grams of (0.5 mole) racemic DL-2- aminopropanols, room temperature is added
The clear solution of 75 grams of (0.5 mole) L-TARTARIC ACIDs and 200 grams of distilled water, control is added dropwise in stirring and dissolving clarification, the stirring of the side Bian Jiangwen
The speed being added dropwise is made, interior temperature is made to be no more than 50 DEG C, 0-5 degrees Celsius is cooled to after adding, about 2 grams of crystal seeds is added, is slowly stirred knot
It is 24 hours brilliant, a large amount of crystal is precipitated, filters, filter cake is washed with a small amount of normal propyl alcohol, and 25 DEG C of vacuum drying obtain L-TARTARIC ACID-L-2
49.2 grams of aminopropanol acid salt, filtrate decompression is spin-dried for, and obtains 63 grams of acid salt.
200 milliliters positive third are dispersed by obtain 49.2 grams of (0.22 mole) L-TARTARIC ACID-L-2- aminopropanol acid salt
In alcohol, room temperature point 4 batches of 19.5 grams of addition calcium hydroxides (0.264 mole), after be stirred at room temperature, it is complete that TLC tracks to 2- aminopropanol
Complete free, filtering, solid is washed with suitable normal propyl alcohol, obtains L-TARTARIC ACID calcium salt, and filtrate concentration is rear to be evaporated under reduced pressure, and obtains 16.0
Gram L-2- aminopropanol, resolution yield 85.3%.
Embodiment 5
1 19.4 grams of gained L-TARTARIC ACID disodium salt (0.1 mole) of embodiment is accurately weighed in conical flask, is added 50 milliliters
36% 20.3 grams of concentrated hydrochloric acid (0.2 mole) is added dropwise while stirring, is stirred at room temperature to solid and is not redissolved for methanol, mistake after freezing
Filter, filter cake are washed with a small amount of methanol, and merging filtrate is concentrated to dryness, and obtains 14.3 grams of crude product L-TARTARIC ACID, the rate of recovery
95.3%, the L-TARTARIC ACID of recycling is directly used in fractionation, without purifying.Specific rotation [α]20=+14.0 ° (C=3.6, water).
Embodiment 6
4 18.8 grams of gained L-TARTARIC ACID calcium salt (0.1 mole) of embodiment is accurately weighed in conical flask, 50 milliliters of first are added
Alcohol is added dropwise 2.7 grams of phosphatase 11 (0.13 mole) while stirring, is stirred at room temperature to solid and is not redissolved, filter after freezing, and filter cake is used
A small amount of methanol washing, merging filtrate are concentrated to dryness, and obtain 14.8 grams of crude product L-TARTARIC ACID, the rate of recovery 98.7%.
Embodiment 7
3 17.2 grams of gained L-TARTARIC ACID magnesium salts (0.1 mole) of embodiment is accurately weighed in conical flask, 60 milliliters of first are added
Alcohol is added dropwise 9.8 grams of the concentrated sulfuric acid (0.1 mole) while stirring, is stirred at room temperature to solid and is not redissolved, filter after freezing, and filter cake is used
A small amount of methanol washing, merging filtrate are concentrated to dryness, and obtain 13.2 grams of crude product L-TARTARIC ACID, the rate of recovery 88%.
Embodiment 8
It is 20% suspension that 1 gained acid salt of embodiment, which is made into mass concentration with methanol, is adjusted with solid sodium hydroxide
PH value is to 11-12, and filtering, filtrate concentration, vacuum distillation recycling 2- aminopropanol, wherein most is D configuration, is urged through Raney Ni
Change racemization, racemic can be made and obtain 2- aminopropanol, apply the detachable preparation L-2- aminopropanol of method of embodiment 1 again.
Claims (8)
1. a kind of method for splitting DL-2- aminopropanol and preparing L-2- aminopropanol, it is characterised in that the following steps are included:
1) L-TARTARIC ACID is dissolved in water, obtains L-TARTARIC ACID aqueous solution；
2) DL-2- aminopropanol at room temperature, is dissolved in alcoholic solvent, it is molten to obtain the DL-2- aminopropanol that mass concentration is 5~20%
Liquid, then in the cooling condition, a dropping step 1 while stirring) gained L-TARTARIC ACID aqueous solution, wherein molar ratio L-TARTARIC ACID:
DL-2- aminopropanol=1:1, control system temperature is not higher than 50 DEG C during dropwise addition, and 0-5 DEG C of guarantor is cooled to after being added dropwise
Temperature obtains cooling solution；
3) a small amount of crystal seed is added into solution cooling obtained by step 2), 16-24 hours is stood still for crystals in -15 DEG C -+25 DEG C, analyse
L-TARTARIC ACID-L-2- aminopropanol acid salt crystal out, filtering, and the crystal being precipitated is washed with a small amount of alcoholic solvent, filtrate is then
For recycling D-2- aminopropanol；
4) L-TARTARIC ACID-L-2- aminopropanol acid salt crystal obtained by step 3) is dissolved with alcoholic solvent, point 2~6 batches of addition nothings
Machine alkali, inorganic base and L-TARTARIC ACID-L-2- aminopropanol acid salt crystal molar ratio are 2:1, and stirring to amino alcohol is completely free
Out, it filters, for filter cake for recycling L-TARTARIC ACID salt, filtrate decompression distills to obtain L-2- aminopropanol.
2. the method according to claim 1 for splitting DL-2- aminopropanol and preparing L-2- aminopropanol, it is characterised in that step
Rapid 1) the described L-TARTARIC ACID aqueous solution mass concentration is 20~60%.
3. the method according to claim 1 for splitting DL-2- aminopropanol and preparing L-2- aminopropanol, it is characterised in that step
Rapid 2) the described alcoholic solvent is one or more of methanol, ethyl alcohol, normal propyl alcohol, isopropanol.
4. the method according to claim 1 for splitting DL-2- aminopropanol and preparing L-2- aminopropanol, it is characterised in that step
Rapid 3) the described temperature that stands still for crystals is 0-5 DEG C.
5. the method according to claim 1 for splitting DL-2- aminopropanol and preparing L-2- aminopropanol, it is characterised in that step
The method of rapid 3) the described recycling D-2- aminopropanol is as follows: at 180-200 DEG C, with Raney Ni catalytic racemization D-2- aminopropanol,
Racemic DL-2- aminopropanol is obtained, then using gained racemic DL-2- aminopropanol as raw material, using step 1) to 4) institute
It states method and splits preparation L-2- aminopropanol.
6. the method according to claim 1 for splitting DL-2- aminopropanol and preparing L-2- aminopropanol, it is characterised in that step
Rapid 4) the described inorganic base is one or more of sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide.
7. the method according to claim 1 for splitting DL-2- aminopropanol and preparing L-2- aminopropanol, it is characterised in that step
The method of rapid 4) the described recycling L-TARTARIC ACID salt is as follows: L-TARTARIC ACID salt being dissolved with methanol, inorganic acid, L-TARTARIC ACID salt is added dropwise
It is 1:2 with inorganic acid molar ratio, stirring is precipitated completely to inorganic salts, filters, and filtrate is evaporated to obtain L-TARTARIC ACID.
8. the method according to claim 7 for splitting DL-2- aminopropanol and preparing L-2- aminopropanol, it is characterised in that institute
Stating inorganic acid is one or more of concentrated hydrochloric acid, the concentrated sulfuric acid, phosphoric acid.
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