CN101774934A - Method for synthesizing lauroyl L-carnitine hydrochloride - Google Patents
Method for synthesizing lauroyl L-carnitine hydrochloride Download PDFInfo
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- CN101774934A CN101774934A CN 200910273506 CN200910273506A CN101774934A CN 101774934 A CN101774934 A CN 101774934A CN 200910273506 CN200910273506 CN 200910273506 CN 200910273506 A CN200910273506 A CN 200910273506A CN 101774934 A CN101774934 A CN 101774934A
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- Prior art keywords
- lauroyl
- carnitine
- carnitine hydrochloride
- synthesizing
- crude product
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- PDBBUDRTWRVCFN-UNTBIKODSA-N [(2R)-3-carboxy-2-dodecanoyloxypropyl]-trimethylazanium chloride Chemical compound [Cl-].CCCCCCCCCCCC(=O)O[C@H](CC(O)=O)C[N+](C)(C)C PDBBUDRTWRVCFN-UNTBIKODSA-N 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 19
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 30
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 claims abstract description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000012043 crude product Substances 0.000 claims abstract description 16
- 238000003756 stirring Methods 0.000 claims abstract description 14
- 238000002425 crystallisation Methods 0.000 claims abstract description 13
- 230000008025 crystallization Effects 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims abstract description 8
- 238000000967 suction filtration Methods 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 239000000706 filtrate Substances 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 13
- 238000004821 distillation Methods 0.000 claims description 7
- 239000012141 concentrate Substances 0.000 claims description 6
- 238000009413 insulation Methods 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- 238000010025 steaming Methods 0.000 claims description 3
- FUJLYHJROOYKRA-QGZVFWFLSA-N O-lauroyl-L-carnitine Chemical compound CCCCCCCCCCCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C FUJLYHJROOYKRA-QGZVFWFLSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 abstract description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 abstract description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract 6
- 238000001816 cooling Methods 0.000 abstract 3
- 238000001704 evaporation Methods 0.000 abstract 2
- 238000001914 filtration Methods 0.000 abstract 2
- 239000002778 food additive Substances 0.000 abstract 1
- 235000013373 food additive Nutrition 0.000 abstract 1
- 238000013341 scale-up Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 7
- 229960004756 ethanol Drugs 0.000 description 4
- 239000007791 liquid phase Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 235000013350 formula milk Nutrition 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000007654 ischemic lesion Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010016 myocardial function Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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Abstract
The invention relates to a method for synthesizing aminocarboxylic acid compounds, in particular to a method for synthesizing lauroyl L-carnitine hydrochloride, belonging to the technical field of preparation of medical intermediates and food additives. A method for synthesizing lauroyl L-carnitine hydrochloride is characterized by comprising the following steps: 1) taking L-carnitine as a raw material, taking acetic acid as a solvent, adding lauroyl chloride, heating to react, then evaporating the acetic acid under reduced pressure, adding acetone, stirring to disperse, cooling to crystallize, then carrying out suction filtration, and drying to obtain a crude product; 2) dissolving the crude product in ethanol or methanol under heating, filtering to obtain filtrate, vacuum distilling and concentrating, evaporating to remove part of ethanol or methanol, cooling, adding acetone, stirring, cooling for crystallization, filtering, and drying to obtain pure lauroyl L-carnitine hydrochloride. The method has the characteristics of simplicity, practicability, small pollution, short reaction period, low cost, yield at least up to 92 percent and suitability for industrial scale-up production.
Description
Technical field
The present invention relates to a kind of synthetic method of aminocarboxylic acid compounds, particularly relate to a kind of method of synthesizing lauroyl L-carnitine hydrochloride, belong to medicine intermediate and foodstuff additive preparing technical field.
Background technology
L-carnitine (L-carnitine, the L-vitamin BT) the existing a lot of reports of effect, L-carnitine is a kind of important food enrichment, be widely used in foodstuffs industry, as infant formula, diet food, in nutrition of athlete's product and the person in middle and old age's nutritional supplement and in the feed processing industry, the curative effect that also has medical aspect in addition, cardiovascular disorder, hepatic diseases, kidney disease, hyperlipidaemia, diabetes, neuromuscular disease etc. all can improve illness by taking the L-carnitine flanker, report that L-carnitine can also improve reproductive performance.
Aspect cardiovascular research, L-carnitine can alleviate the palpitaition ischemic lesions, reduce the area of myocardial infarction, improve myocardial function and vascular disease, blood fat reducing etc.The L-carnitine derivative that alkoxyl group replaces is better than L-carnitine, and is difficult for the moisture absorption, is easy to preserve the preparation of transportation and solid preparation.
The synthetic report that does not all have lauroyl L-carnitine hydrochloride at present both at home and abroad.
Summary of the invention
The object of the present invention is to provide a kind of method of synthesizing lauroyl L-carnitine hydrochloride, this method is simple, cost is low.
To achieve these goals, technical scheme that the present invention adopts is: a kind of method of synthesizing lauroyl L-carnitine hydrochloride is characterized in that it comprises the steps:
1). with the L-carnitine is raw material, is solvent with the acetate that adds 0.8～3 times of L-carnitine quality, is 1: 1～1.5 by the mol ratio of L-carnitine and lauroyl chloride, and { chemical formula is the adding lauroyl chloride: CH
3(CH
2)
10COCl}, in 50～80 ℃ of reactions, reacted 5～8 hours then, reaction finishes back pressure reducing and steaming acetate [at vacuum-0.09Mpa, temperature boils off acetate below 80 ℃], the acetone that adds 2～5 times of L-carnitine quality, abundant dispersed with stirring is cooled to the crystallization that (contains 5 ℃) below 5 ℃, and 0～5 ℃ of insulation at least 2 hours, suction filtration then, drying, the lauroyl L-carnitine hydrochloride crude product;
The building-up reactions formula of described lauroyl L-carnitine hydrochloride is as follows:
C
7H
15O
3N+C
12H
23ClO→C
19H
38ClNO
4；
2). gained lauroyl L-carnitine hydrochloride crude product is (darker as color with ethanol or methyl alcohol heating for dissolving, can add a little activated carbon decolorizing), being warming up to 65 ℃ also kept 0.5 hour at least, suction filtration while hot, the distillation of gained filtrate concentrates [60 ℃ of temperature, vacuum is-condition of 0.08Mpa under distillation concentrate], boil off part ethanol or methyl alcohol, after being cooled to 40 ℃ then, the acetone that adds 1～2 times of lauroyl L-carnitine hydrochloride crude product quality stirs, be cooled to the crystallization that (contains 10 ℃) below 10 ℃, and, filter then 0～10 ℃ of insulation at least 1 hour, drying gets the pure product of lauroyl L-carnitine hydrochloride.
Purpose to better implement the present invention, described step 2) in, ethanol or methyl alcohol: acetone: the mass ratio of lauroyl L-carnitine crude product is 0.4～3: 1.4～2.0: 1.
Utilize the yield of the pure product of the prepared lauroyl L-carnitine hydrochloride of the present invention to be at least 92%.
The invention has the beneficial effects as follows:
1, when reaction, do not use catalyzer, be convenient to purifying;
2, reaction time spent weak point has improved production efficiency;
3, add the acetone crystallization again after after reaction finishes acetate decompression being steamed, the used acetone of acetate and crystallization is all recyclable in this method, has reduced the waste of solvent greatly, has saved cost;
4, recrystallization is selected ethanol or methyl alcohol system recrystallization for use, has solved purifying products problem in the industrial production;
5, products obtained therefrom is up-to-standard, and yield is higher, is fit to industry's enlarging production.
6, this method is simple.
Description of drawings
Fig. 1 is a process flow sheet of the present invention.
Embodiment
In order to understand the present invention better, further illustrate content of the present invention below in conjunction with embodiment, but content of the present invention not only is confined to the following examples.
Embodiment 1:
As shown in Figure 1, a kind of method of synthesizing lauroyl L-carnitine hydrochloride, it comprises the steps:
1). load weighted acetate 161.2g is added four-hole boiling flask (capacity of four-hole boiling flask is 1L), and stirring adds L-carnitine 161.2g dissolving down, after treating thoroughly to dissolve, adds lauroyl chloride 221g; Be warming up to 75 ℃ of constant temperature then 5 hours; Reaction finishes the back at vacuum-0.09Mpa, and temperature boils off acetate below 80 ℃, is cooled to 40 ℃ and adds acetone 600g, and fully dispersed with stirring is 0.5 hour, is cooled to the crystallization that (contains 5 ℃) below 5 ℃, and 0～5 ℃ of insulation 2 hours; Filter, use the washing with acetone material, suction filtration gets crude product, in vacuum-0.09Mpa, 80～105 ℃ of following dryings, gets lauroyl L-carnitine hydrochloride crude product 372.7g, yield 98.1%.
2). get lauroyl L-carnitine hydrochloride crude product 200g, add stirring and dissolving in the reactor that dehydrated alcohol 600g has been housed; Be warming up to 65 ℃ and also keep at least 0.5 hour to guarantee that dissolving fully; Filtered while hot, in 60 ℃ of temperature, vacuum be-condition of 0.08Mpa under distillation concentrate crystallization, reduce to 40 ℃ then, add acetone 400g dispersed with stirring, be cooled to 0～10 ℃ of crystallization 1 hour; Filter dry lauroyl L-carnitine hydrochloride (finished product) 190.6g, the yield 95.3% of getting then.Amount to total recovery 93.5%.Adopt following high performance liquid phase condition alkali content and impurity to detect, recording mass content is 99.5%, specific rotation :-25.4 ° (c=10, H2O), pH value: 2.5, white crystalline powder.
The HPLC condition:
Chromatographic column (APS-2HYPERSIL, 4.6mmID * 250mm, 5 μ m)
Temperature: 30 ℃,
Detect wavelength: 205mm,
Flow velocity: 0.8 ml/min,
PH：4.7?NaOH。
Embodiment 2:
A kind of method of synthesizing lauroyl L-carnitine hydrochloride, it comprises the steps:
1). load weighted acetate 200g is added in the four-hole boiling flask, and stirring adds L-carnitine 161.2g dissolving down, after treating thoroughly to dissolve, drips lauroyl chloride 263g; Be warming up to 70 ℃ of constant temperature then 8 hours; Boil off acetate below 80 ℃ to separating out a large amount of crystal in vacuum-0.09Mpa, temperature after reaction finishes, be cooled to 40 ℃ and add acetone 600g, fully dispersed with stirring is 0.5 hour, is cooled to crystallization below 5 ℃, and 0～5 ℃ of insulation 2 hours; Filter, suction filtration gets crude product, 80 ℃ of dryings, gets lauroyl L-carnitine hydrochloride crude product 374g, yield 98.4% with vacuum-0.09Mpa.
2). get lauroyl L-carnitine hydrochloride crude product 200g, add stirring and dissolving in the reactor that anhydrous methanol 420g has been housed; Be warming up to 65 ℃ and also keep at least 0.5 hour to guarantee that dissolving fully; Filtered while hot, in 60 ℃ of temperature, vacuum be-condition of 0.08Mpa under distillation concentrate crystallization, reduce to 40 ℃ then, add acetone 400g dispersed with stirring, be cooled to 0～10 ℃ of crystallization 1 hour; Filter the dry pure product 191.6g of lauroyl L-carnitine hydrochloride, the yield 95.8% of getting then.Amount to total recovery 94.2%.To record mass content with embodiment 1 identical high performance liquid phase condition is 99.7%, specific rotation :-25.5 ° (c=10, H2O), pH value: 2.5, white crystalline powder.
Embodiment 3:
Lauroyl chloride feeds intake and is 218.76g, and other implementation step is with example 2, and total recovery 92.5% is 99.23% to record mass content with embodiment 1 identical high performance liquid phase condition.Specific rotation :-25.3 ° (c=10, H2O), pH value: 2.5, white crystalline powder.
Embodiment 4:
Lauroyl chloride feeds intake and is 328.14g, and other implementation step is with example 2, and total recovery 95.5% is 99.10% to record mass content with embodiment 1 identical high performance liquid phase condition, specific rotation :-25.3 ° (c=10, H2O), pH value: 2.5, white crystalline powder.
Each raw material that the present invention is cited, and the bound of each raw material of the present invention, interval value can both be realized the present invention; The bound of each processing parameter of the present invention (as temperature, time etc.), interval value can both realize the present invention; Those skilled in the art can realize the present invention fully according to prompting of the present invention, do not enumerate embodiment one by one at this.
Claims (4)
1. the method for a synthesizing lauroyl L-carnitine hydrochloride is characterized in that it comprises the steps:
1). with the L-carnitine is raw material, is solvent with the acetate that adds 0.8～3 times of L-carnitine quality, is 1: 1～1.5 by the mol ratio of L-carnitine and lauroyl chloride, add lauroyl chloride,, reacted 5～8 hours then in 50～80 ℃ of reactions, pressure reducing and steaming acetate after reaction finishes, add the acetone of 2～5 times of L-carnitine quality, dispersed with stirring is cooled to crystallization below 5 ℃, and 0～5 ℃ of insulation at least 2 hours, suction filtration then, drying, the lauroyl L-carnitine hydrochloride crude product;
2). gained lauroyl L-carnitine hydrochloride crude product is with ethanol or methyl alcohol heating for dissolving, be warming up to 65 ℃ and kept at least 0.5 hour, suction filtration while hot, the distillation of gained filtrate concentrates, boil off part ethanol or methyl alcohol, after being cooled to 40 ℃ then, the acetone that adds 1～2 times of lauroyl L-carnitine hydrochloride crude product quality stirs, and is cooled to crystallization below 10 ℃, and 0～10 ℃ of insulation at least 1 hour, filter then, drying gets lauroyl L-carnitine hydrochloride.
2. the method for a kind of synthesizing lauroyl L-carnitine hydrochloride according to claim 1, it is characterized in that: pressure reducing and steaming acetate is in the described step 1): at vacuum-0.09Mpa, temperature boils off acetate below 80 ℃.
3. the method for a kind of synthesizing lauroyl L-carnitine hydrochloride according to claim 1, it is characterized in that: described step 2), ethanol or methyl alcohol: acetone: the mass ratio of lauroyl L-carnitine crude product is 0.4～3: 1.4～2.0: 1.
4. the method for a kind of synthesizing lauroyl L-carnitine hydrochloride according to claim 1 is characterized in that: gained filtrate distillation simmer down to described step 2): 60 ℃ of temperature, vacuum for the condition of-0.08Mpa under distillation concentrate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910273506 CN101774934B (en) | 2009-12-31 | 2009-12-31 | Method for synthesizing lauroyl L-carnitine hydrochloride |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910273506 CN101774934B (en) | 2009-12-31 | 2009-12-31 | Method for synthesizing lauroyl L-carnitine hydrochloride |
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| Publication Number | Publication Date |
|---|---|
| CN101774934A true CN101774934A (en) | 2010-07-14 |
| CN101774934B CN101774934B (en) | 2012-12-12 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112079738A (en) * | 2020-09-18 | 2020-12-15 | 内蒙古精晶生物科技有限公司 | Preparation method of L-carnitine catecholate |
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|---|---|---|---|---|
| CN1995010B (en) * | 2006-12-29 | 2012-12-12 | 辽宁科硕营养科技有限公司 | Method for synthesizing propionyl levo-carnitine hydrochlorate |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112079738A (en) * | 2020-09-18 | 2020-12-15 | 内蒙古精晶生物科技有限公司 | Preparation method of L-carnitine catecholate |
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