CN101417939B - Method for preparing caprylic-1-<13>C - Google Patents

Method for preparing caprylic-1-<13>C Download PDF

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CN101417939B
CN101417939B CN2008102038703A CN200810203870A CN101417939B CN 101417939 B CN101417939 B CN 101417939B CN 2008102038703 A CN2008102038703 A CN 2008102038703A CN 200810203870 A CN200810203870 A CN 200810203870A CN 101417939 B CN101417939 B CN 101417939B
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侯秀红
卢伟京
卢浩
李帅
杨维成
徐仲杰
李孝武
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Shanghai Research Institute of Chemical Industry SRICI
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Abstract

The invention relates to a preparation method of octanoic acid-1-<13>C, comprising the following steps: (1) metallic magnesium, bromoheptane and anhydrous solvent are mixed, stirred and heated, and a liquid one is obtained after reflux reaction; (2) concentrated sulfuric acid is dropped into Ba<13>CO3, and the produced gas is pumped into another vessel and frozen by liquid nitrogen; (3) the liquid one obtained in step (1) is dripped into the gas frozen by liquid nitrogen and produced in step (2) , and a liquid two is produced; (4) the anhydrous solvent is added to surplus liquid one; (5) the liquid two produced in step (3) is transferred to another vessel, and water or 5 percent sulfuric acid aqueous solution is added in to produce a liquid three; and (6) the liquid three generated in step (5) is extracted by ether for three times, and the extract liquid is neutralized to alkaline; the alkaline aqueous solution is neutralized to acid and extracted by ether for three times; the extractliquid is dried and filter by anhydrous sodium sulfate; after the ether is evaporated, the product is obtained. Compared with prior technology, the preparation method is suitable for continuous repeated preparation or amplified preparation.

Description

A kind of sad-1- 13The preparation method of C
Technical field
The present invention relates to a kind of sad-1- 13The preparation method of C particularly uses the grignard reaction method and prepares sad-1- 13The method of C.
Background technology
Since security and characteristics such as easy, no wound, sensitivity and specificity height that it is outstanding, in clinical medical medical diagnosis on disease, stable isotope 13The breathing reagent application prospect of C mark is long-range, replaces similar radioactive gradually in Europe 14C reagent.As one of two gold standard reagent of medical clinic applications, sad-1- 13C can be used for the test of stomach emptying, especially solid food emptying.Stomach is the most important digestion organs of human body, clinically, stomach emptying with comprise that nearly 20 kinds of diseases such as stomach ulcer, cancer of the stomach, diabetes, thyroprivia, Parkinson's disease are relevant, also with stomach operation (vagotomy and gastrectomy etc.), medicine (motilin receptor agonism medicine: cisapride, domperidone, metoclopramide etc.) etc. relevant.The test of stomach emptying is also relevant with doctor's delivery time, and is simple and the Validity Test stomach emptying has higher clinical meaning and applications well prospect.In addition, sad-1- 13C and octylate/ester-1- 13C also is used to test lipid acid (especially medium chain fatty acid) oxidation, the function of appraiser's hepatic mitochondria when pressure etc., and diagnosis heart disease or myocardial performance imbalance etc.Therefore, sad-1- 13C has great clinical value.
13C-mark carboxylic acid has multiple synthetic method: grignard reaction, mark prussiate hydrolysis reaction, with 13CO and alcohol are the catalyzed reaction method, organo-borane method of raw material etc.Wherein, use the grignard reaction method and synthesize sad-1- 13C is just finished by people such as Weinhouse as far back as 1944, is published in J.Biol.Chem., and 155,143, (1944), and its productive rate is 81%, people such as Wang Huiqiong openly use the grignard reaction method and synthesize sad-1-at Nuclear Technology 2000,23 (2) among the 136-141 13The productive rate of C is 93%, but be to feed in the good Grignard reagent of reaction in preparation process by the mark carbon dioxide, owing to reacted in the Grignard reagent well and also had unreacted magnesium, in follow-up reaction and treating processes, or adding excessive acid falls reactive magnesium, or adding acid less filters again, this has all caused the waste of magnesium, and excessive acid causes acid waste and pollutes, and filtering has increased operation steps, and the possibility of product loss is increased.If unreacted metal magnesium is carried out recycling, not only cost-saved, and because magnesium process first set reaction, the active increase helps promoting reaction next time.
Summary of the invention
Purpose of the present invention is exactly to provide a kind of for the defective that overcomes above-mentioned prior art existence to be suitable for the continuous several times preparation or to amplify the sad-1-of preparation 13The preparation method of C.
Purpose of the present invention can be achieved through the following technical solutions: a kind of sad-1- 13The preparation method of C is characterized in that, this method may further comprise the steps:
(1) with MAGNESIUM METAL, bromo heptane, the anhydrous solvent mixed in molar ratio by 1～2:1:5～20, stir, heating reflux reaction obtained liquid I in 30～90 minutes;
(2) vitriol oil is added drop-wise to Ba by the mol ratio of 1～20:1 13CO 3In, the gas of generation feeds another container liquid nitrogen freezing;
(3) the liquid I that step (1) is generated is added drop-wise in the liquid nitrogen freezing gas of step (2) generation, makes bromo heptane and Ba 13CO 3Mol ratio be 1～2:1, be warmed up to-20 ℃～-30 ℃, stir and obtained liquid II in 10～90 minutes;
(4) anhydrous solvent is joined among the remaining liquid I, under the condition of secluding air, proceed to react next time;
(5) the liquid II that step (3) is generated transfers in another container, to wherein dripping the water or the 5% vitriolic aqueous solution, makes itself and Ba 13CO 3Mol ratio be 5～20:1, obtain liquid III;
(6) the liquid III that step (5) is generated is with extracted with diethyl ether three times, in and extraction liquid to alkalescence, with this alkaline aqueous solution acidity that neutralizes, with extracted with diethyl ether three times, the extraction liquid anhydrous sodium sulfate drying filters, and ether is steamed remove, and gets product.
Described MAGNESIUM METAL, bromo heptane and Ba 13CO 3Mol ratio be 1.8～2.4:1.5～2:1.
MAGNESIUM METAL in the described step (1) is selected from one or more of magnesium powder, magnesium chips, magnesium rod, and described solvent is selected from one or both of ether, tetrahydrofuran (THF), benzene, triethylamine.
Described solvent is that mol ratio is the ether of 5～10:1 or the mixture of tetrahydrofuran (THF) and benzene.
Described solvent is that mol ratio is the ether of 5～10:1 or the mixture of tetrahydrofuran (THF) and triethylamine.
Liquid I can also be added drop-wise in the described step (3) in the liquid nitrogen freezing gas of step (2) generation, drip the back and continue to obtain in freezing 10～30 minutes liquid II.
Liquid I can also be added drop-wise in the described step (3) in the liquid nitrogen freezing gas of step (2) generation, be warmed up to-20～-30 ℃, stir 10～90 minutes, liquid nitrogen freezing 10～30 minutes is warmed up to-20～-30 ℃, stirs to obtain liquid II in 10～30 minutes.
Liquid I can also be added drop-wise in the described step (3) in the liquid nitrogen freezing gas of step (2) generation, be warmed up to-20～-30 ℃, stir 10～90 minutes, freezing 10～60 minutes of dry ice is warmed up to-20～-30 ℃, stirs to obtain liquid II in 10～30 minutes.
In the described step (5) liquid II being transferred in another container is to carry out under vacuum state.
Extraction liquid in the described step (6) adopts the aqueous solution of the 5% sodium hydroxide alkalescence that neutralizes, and described alkaline aqueous solution is with the 10% vitriolic aqueous solution acidity that neutralizes.
High pure nitrogen deoxygenation in the present invention and dewatering, under anhydrous and oxygen-free atmosphere, solvent dewaters with cuprous chloride deoxygenation, calcium chloride and sodium Metal 99.5, other reagent dewater with anhydrous sodium sulphate and anhydrous magnesium sulfate, 60 ℃ of dryings of barium carbonate vacuum, the online drying of MAGNESIUM METAL, used glassware all must be carried out drying treatment.
Compared with prior art, the present invention is raw material synthetic grignard reagent bromination n-heptylmagnesium and Ba with the bromo heptane 13CO 3Produce with vitriol oil effect 13CO 2Carry out carboxylation reaction,, purify, make sad-1-by hydrolysis 13C, unreacted in the method magnesium is recyclable to be utilized again, and present method also is suitable for the continuous several times preparation or amplifies preparation.
Embodiment
Now the present invention is further described in conjunction with specific embodiments.
Embodiment 1
On 500mL three neck round-bottomed flasks, reflux condensing tube is installed, balloon is installed in the exit, in logical nitrogen, in flask, add magnetic stir bar, 0.243g magnesium rod, 1.6mL bromo heptane, 10mL anhydrous diethyl ether rapidly, close nitrogen, open water of condensation and magnetic stirring apparatus, after stirring 3-5min, solution colour is a grey black, continues to stir 60min under reflux state, stopped reaction, solution is used for the next step.Grignard reagent transferred to be connected 13CO 2In the constant pressure funnel on the receptor two neck round-bottomed flasks, then will 13CO 2Producer and 13CO 2Receptor is evacuated to-700mmHg, opens 13CO 2The piston of constant pressure funnel in the producer slowly splashes into the vitriol oil 1.97g Ba is housed 13CO 3Round-bottomed flask in, control 13CO 2The speed that produces is simultaneously with the two neck round-bottomed flask liquid nitrogen freezings of 500mL.After the vitriol oil dripped off, heating impelled to react completely. 13CO 2All be transferred to closure piston behind the two neck round-bottomed flasks.Open the piston of the constant pressure funnel that grignard reagent is housed, grignard reagent splashes in the two neck round-bottomed flasks, drips off the back closure piston.Replace liquid nitrogen cold trap with the ethanol cryotrap, temperature of reaction is controlled at about-20 ℃, stir reaction 30min down.Reactant is changed in another round-bottomed flask, add 10% sulfuric acid 10mL then and carry out acidification hydrolization reaction 20min.With extracted with diethyl ether three times, in the aqueous solution of 5% sodium hydroxide and extraction liquid to alkalescence, with the 10% vitriolic aqueous solution acidity that neutralizes, with extracted with diethyl ether three times, extraction liquid anhydrous sodium sulfate drying, filtration removes the ether steaming, gets final product sadly-1-with alkaline aqueous solution 13The C product.
Embodiment 2
Process is with embodiment 1, but after grignard reagent moves away, in 500mL three neck round-bottomed flasks, adding the 10mL anhydrous diethyl ether under the condition of secluding air, after the reactant in the two neck round bottoms of 500mL burn changes another round-bottomed flask over to, under the condition of secluding air, washing with anhydrous diethyl ether.
Embodiment 3
Process is with embodiment 2, but in 500mL three neck round-bottomed flasks, add the 0.243g magnesium rod under the condition of secluding air, the 1.6mL bromo heptane reacts.
Embodiment 4
On 500mL three neck round-bottomed flasks, reflux condensing tube is installed, balloon is installed in the exit, in logical nitrogen, in flask, add magnetic stir bar, 2.296g magnesium rod, 14.3mL bromo heptane, 210mL anhydrous diethyl ether rapidly, close nitrogen, open water of condensation and magnetic stirring apparatus, after stirring 3-5min, solution colour is a grey black, continues to stir 30min under reflux state, stopped reaction, solution is used for the next step.Grignard reagent transferred to be connected 13CO 2In the constant pressure funnel on the receptor two neck round-bottomed flasks, then will 13CO 2Producer and 13CO 2Receptor is evacuated to-700mmHg, opens 13CO 2The piston of constant pressure funnel in the producer slowly splashes into the vitriol oil 13.830g Ba is housed 13CO 3Round-bottomed flask in, control 13CO 2The speed that produces is simultaneously with the two neck round-bottomed flask liquid nitrogen freezings of 1L.After the vitriol oil dripped off, heating impelled to react completely. 13CO 2All be transferred to closure piston behind the two neck round-bottomed flasks.Open the piston of the constant pressure funnel that grignard reagent is housed, grignard reagent splashes in the two neck round-bottomed flasks, drips off the back closure piston.Replace liquid nitrogen cold trap with the ethanol cryotrap, temperature of reaction is controlled at about-30 ℃, stir reaction 60min down.Change reactant over to another vacuum tightness in-700mmHg the round-bottomed flask, add entry 140mL then and carry out acidification hydrolization reaction 20min.With ether extraction acidification hydrolization thing, organic phase adds rare NaOH alkalization aqueous solution, extracts sad-1- 13The C sodium salt carries out acidification with 20% sulfuric acid then, use again ether extraction sad-1- 13C removes the ether steaming, gets final product sadly-1- 13The C product.
Embodiment 5
On 500mL three neck round-bottomed flasks, reflux condensing tube is installed, balloon is installed in the exit, in logical nitrogen, in flask, add magnetic stir bar, 0.6g magnesium rod, 3.2mL bromo heptane, 10mL anhydrous tetrahydro furan rapidly, close nitrogen, open water of condensation and magnetic stirring apparatus, after stirring 3-5min, solution colour is a grey black, continues to stir 60min under reflux state, stopped reaction, solution is used for the next step.Grignard reagent transferred to be connected 13CO 2In the constant pressure funnel on the receptor two neck round-bottomed flasks, then will 13CO 2Producer and 13CO 2Receptor is evacuated to-700mmHg, opens 13CO 2The piston of constant pressure funnel in the producer slowly splashes into the vitriol oil 1.97g Ba is housed 13CO 3Round-bottomed flask in, control 13CO 2The speed that produces is simultaneously with the two neck round-bottomed flask liquid nitrogen freezings of 500mL.After the vitriol oil dripped off, heating impelled to react completely. 13CO 2All be transferred to closure piston behind the two neck round-bottomed flasks.Open the piston of the constant pressure funnel that grignard reagent is housed, grignard reagent splashes in the two neck round-bottomed flasks, drips off the back closure piston.Replace liquid nitrogen cold trap with the ethanol cryotrap, temperature of reaction is controlled at about-25 ℃, stir reaction 90min down.Reactant is changed in another round-bottomed flask, add 10% sulfuric acid 10mL then and carry out acidification hydrolization reaction 20min.With extracted with diethyl ether three times, in the aqueous solution of 5% sodium hydroxide and extraction liquid to alkalescence, with the 10% vitriolic aqueous solution acidity that neutralizes, with extracted with diethyl ether three times, extraction liquid anhydrous sodium sulfate drying, filtration removes the ether steaming, gets final product sadly-1-with alkaline aqueous solution 13The C product.
Embodiment 6
On 500mL three neck round-bottomed flasks, reflux condensing tube is installed, balloon is installed in the exit, in logical nitrogen, in flask, add magnetic stir bar, 0.6g magnesium rod, 3.2mL bromo heptane, 30mL anhydrous diethyl ether, 1mL benzene rapidly, close nitrogen, open water of condensation and magnetic stirring apparatus, after stirring 3-5min, solution colour is a grey black, continues to stir 60min under reflux state, stopped reaction, solution is used for the next step.Grignard reagent transferred to be connected 13CO 2In the constant pressure funnel on the receptor two neck round-bottomed flasks, then will 13CO 2Producer and 13CO 2Receptor is evacuated to-700mmHg, opens 13CO 2The piston of constant pressure funnel in the producer slowly splashes into the vitriol oil 1.97g Ba is housed 13CO 3Round-bottomed flask in, control 13CO 2The speed that produces is simultaneously with the two neck round-bottomed flask liquid nitrogen freezings of 500mL.After the vitriol oil dripped off, heating impelled to react completely. 13CO 2All be transferred to closure piston behind the two neck round-bottomed flasks.Open the piston of the constant pressure funnel that grignard reagent is housed, grignard reagent splashes in the two neck round-bottomed flasks, drips off the back closure piston.Replace liquid nitrogen cold trap with the ethanol cryotrap, temperature of reaction is controlled at about-15 ℃, stir reaction 90min down.Reactant is changed in another round-bottomed flask, add 10% sulfuric acid 10mL then and carry out acidification hydrolization reaction 20min.With extracted with diethyl ether three times, in the aqueous solution of 5% sodium hydroxide and extraction liquid to alkalescence, with the 10% vitriolic aqueous solution acidity that neutralizes, with extracted with diethyl ether three times, extraction liquid anhydrous sodium sulfate drying, filtration removes the ether steaming, gets final product sadly-1-with alkaline aqueous solution 13The C product.
Embodiment 7
On 500mL three neck round-bottomed flasks, reflux condensing tube is installed, balloon is installed in the exit, in logical nitrogen, in flask, add magnetic stir bar, 0.34g magnesium rod, 2.2mL bromo heptane, 20mL anhydrous diethyl ether, 2mL triethylamine rapidly, close nitrogen, open water of condensation and magnetic stirring apparatus, after stirring 3-5min, solution colour is a grey black, continues to stir 60min under reflux state, stopped reaction, solution is used for the next step.Grignard reagent transferred to be connected 13CO 2In the constant pressure funnel on the receptor two neck round-bottomed flasks, then will 13CO 2Producer and 13CO 2Receptor is evacuated to-700mmHg, opens 13CO 2The piston of constant pressure funnel in the producer slowly splashes into the vitriol oil 1.97g Ba is housed 13CO 3Round-bottomed flask in, control 13CO 2The speed that produces is simultaneously with the two neck round-bottomed flask liquid nitrogen freezings of 500mL.After the vitriol oil dripped off, heating impelled to react completely. 13CO 2All be transferred to closure piston behind the two neck round-bottomed flasks.Open the piston of the constant pressure funnel that grignard reagent is housed, grignard reagent splashes in the two neck round-bottomed flasks, drips off the back closure piston.Replace liquid nitrogen cold trap with the ethanol cryotrap, temperature of reaction is controlled at about-18 ℃, stir reaction 30min down.Used liquid nitrogen freezing again 30 minutes, and replaced liquid nitrogen cold trap, temperature of reaction is controlled at about-20 ℃, stir reaction 20min down with the ethanol cryotrap.Reactant is changed in another round-bottomed flask then, add 10% sulfuric acid 10mL then and carry out acidification hydrolization reaction 20min.With extracted with diethyl ether three times, in the aqueous solution of 5% sodium hydroxide and extraction liquid to alkalescence, with the 10% vitriolic aqueous solution acidity that neutralizes, with extracted with diethyl ether three times, extraction liquid anhydrous sodium sulfate drying, filtration removes the ether steaming, gets final product sadly-1-with alkaline aqueous solution 13The C product.
Embodiment 8
On 500mL three neck round-bottomed flasks, reflux condensing tube is installed, balloon is installed in the exit, in logical nitrogen, in flask, add magnetic stir bar, 6.08g magnesium rod, 37.7mL bromo heptane, 300mL anhydrous diethyl ether rapidly, close nitrogen, open water of condensation and magnetic stirring apparatus, after stirring 3-5min, solution colour is a grey black, continues to stir 60min under reflux state, stopped reaction, solution is used for the next step.Grignard reagent transferred to be connected 13CO 2In the constant pressure funnel on the receptor two neck round-bottomed flasks, then will 13CO 2Producer and 13CO 2Receptor is evacuated to-700mmHg, opens 13CO 2The piston of constant pressure funnel in the producer slowly splashes into the vitriol oil 39.460g Ba is housed 13CO 3Round-bottomed flask in, control 13CO 2The speed that produces is simultaneously with the two neck round-bottomed flask liquid nitrogen freezings of 2L.After the vitriol oil dripped off, heating impelled to react completely. 13CO 2All be transferred to closure piston behind the two neck round-bottomed flasks.Open the piston of the constant pressure funnel that grignard reagent is housed, grignard reagent splashes in the two neck round-bottomed flasks, drips off the back closure piston.Dripping the back continued freezing 30 minutes.Replace liquid nitrogen cold trap with the ethanol cryotrap, temperature of reaction is controlled at about-20 ℃, stir reaction 90min down.Replace liquid nitrogen cold trap with the ethanol cryotrap, temperature of reaction is controlled at about-20 ℃, stir reaction 30min down.Used dry ice more freezing 60 minutes, and replaced liquid nitrogen cold trap, temperature of reaction is controlled at about-20 ℃, stir reaction 30min down with the ethanol cryotrap.Reactant is changed in another round-bottomed flask, add 10% sulfuric acid 200mL then and carry out acidification hydrolization reaction 20min.With ether extraction acidification hydrolization thing, organic phase adds rare NaOH alkalization aqueous solution, extracts sad-1- 13The C sodium salt carries out acidification with 20% sulfuric acid then, use again ether extraction sad-1- 13C removes the ether steaming, gets final product sadly-1- 13The C product.
Embodiment 9
A kind of sad-1- 13The preparation method of C may further comprise the steps:
(1) be that the ether of 5:1 and the mixture of benzene are solvent with the mol ratio, the mixed in molar ratio with magnesium chips, bromo heptane, anhydrous solvent are pressed 1:1:5 stirs, and heating reflux reaction obtained liquid I in 30 minutes;
(2) vitriol oil is added drop-wise to Ba by the mol ratio of 1:1 13CO 3In, the gas of generation feeds another container liquid nitrogen freezing;
(3) the liquid I that step (1) is generated is added drop-wise in the liquid nitrogen freezing gas of step (2) generation, makes bromo heptane and Ba 13CO 3Mol ratio be 1:1, be warmed up to-20 ℃, stir and obtained liquid II in 10 minutes;
(4) anhydrous solvent is joined among the remaining liquid I, under the condition of secluding air, proceed to react next time;
(5) the liquid II that step (3) is generated transfers in another container, to wherein dripping the water or the 5% vitriolic aqueous solution, makes itself and Ba 13CO 3Mol ratio be 5:1, obtain liquid III;
(6) liquid III extracted with diethyl ether three times that step (5) generated, adopt in the aqueous solution of 5% sodium hydroxide and extraction liquid to alkalescence, described alkaline aqueous solution is with the 10% vitriolic aqueous solution acidity that neutralizes, with this alkaline aqueous solution acidity that neutralizes, with extracted with diethyl ether three times, extraction liquid anhydrous sodium sulfate drying, filter, the ether steaming is removed, get product.
Embodiment 10
A kind of sad-1- 13The preparation method of C may further comprise the steps:
(1) be that the tetrahydrofuran (THF) of 10:1 and the mixture of triethylamine are solvent with the mol ratio, the mixed in molar ratio with magnesium powder, bromo heptane, anhydrous solvent are pressed 2:1:20 stirs, and heating reflux reaction obtained liquid I in 90 minutes;
(2) vitriol oil is added drop-wise to Ba by the mol ratio of 20:1 13CO 3In, the gas of generation feeds another container liquid nitrogen freezing;
(3) the liquid I that step (1) is generated is added drop-wise in the liquid nitrogen freezing gas of step (2) generation, makes bromo heptane and Ba 13CO 3Mol ratio be 2:1, be warmed up to-30 ℃, stirred 90 minutes, liquid nitrogen freezing 30 minutes is warmed up to-30 ℃, stirs to obtain liquid II in 30 minutes;
(4) anhydrous solvent is joined among the remaining liquid I, under the condition of secluding air, proceed to react next time;
(5) the liquid II that step (3) is generated transfers in another container, to wherein dripping the water or the 5% vitriolic aqueous solution, makes itself and Ba 13CO 3Mol ratio be 20:1, obtain liquid III;
(6) liquid III extracted with diethyl ether three times that step (5) generated, adopt in the aqueous solution of 5% sodium hydroxide and extraction liquid to alkalescence, described alkaline aqueous solution is with the 10% vitriolic aqueous solution acidity that neutralizes, with this alkaline aqueous solution acidity that neutralizes, with extracted with diethyl ether three times, extraction liquid anhydrous sodium sulfate drying, filter, the ether steaming is removed, get product.
Embodiment 11
Step is with embodiment 10, wherein MAGNESIUM METAL, bromo heptane and Ba 13CO 3Mol ratio be 1.8:1.5:1.
Liquid I is added drop-wise in the liquid nitrogen freezing gas of step (2) generation in the step (3), drips the back and continue to obtain in freezing 10～30 minutes liquid II.
Embodiment 12
Step is with embodiment 10, wherein MAGNESIUM METAL, bromo heptane and Ba 13CO 3Mol ratio be 2.4:2:1.
Liquid I is added drop-wise in the liquid nitrogen freezing gas of step (2) generation in the step (3), is warmed up to-20～-30 ℃, stirred 10～90 minutes, freezing 10～60 minutes of dry ice is warmed up to-20～-30 ℃, stirs to obtain liquid II in 10～30 minutes.

Claims (10)

1. sad-1- 13The preparation method of C is characterized in that, this method may further comprise the steps:
(1) with MAGNESIUM METAL, bromo heptane, anhydrous solvent by 1～2: 1: 5～20 mixed in molar ratio, stir, heating reflux reaction obtained liquid I in 30～90 minutes, described solvent is selected from one or both of ether, tetrahydrofuran (THF), benzene, triethylamine;
(2) with the vitriol oil by 1～20: 1 mol ratio is added drop-wise to Ba 13CO 3In, the gas of generation feeds another container liquid nitrogen freezing;
(3) the liquid I that step (1) is generated is added drop-wise in the liquid nitrogen freezing gas of step (2) generation, makes bromo heptane and Ba 13CO 3Mol ratio be 1～2: 1, be warmed up to-20 ℃～-30 ℃, stir and obtained liquid II in 10～90 minutes;
(4) anhydrous solvent is joined among the remaining liquid I, under the condition of secluding air, proceed to react next time;
(5) the liquid II that step (3) is generated transfers in another container, to wherein dripping the water or the 5% vitriolic aqueous solution, makes itself and Ba 13CO 3Mol ratio be 5～20: 1, obtain liquid III;
(6) the liquid III that step (5) is generated is with extracted with diethyl ether three times, in and extraction liquid to alkalescence, with this alkaline aqueous solution acidity that neutralizes, with extracted with diethyl ether three times, the extraction liquid anhydrous sodium sulfate drying filters, and ether is steamed remove, and gets product.
2. according to claim 1 a kind of sad-1- 13The preparation method of C is characterized in that, described bromo heptane and Ba 13CO 3Mol ratio be 1.5～2: 1.
3. according to claim 1 a kind of sad-1- 13The preparation method of C is characterized in that, the MAGNESIUM METAL in the described step (1) is selected from one or more of magnesium powder, magnesium chips, magnesium rod.
According to claim 1 or 3 described a kind of sad-1- 13The preparation method of C is characterized in that, described solvent is that mol ratio is 5～10: 1 the ether or the mixture of tetrahydrofuran (THF) and benzene.
According to claim 1 or 3 described a kind of sad-1- 13The preparation method of C is characterized in that, described solvent is that mol ratio is 5～10: 1 the ether or the mixture of tetrahydrofuran (THF) and triethylamine.
6. according to claim 1 a kind of sad-1- 13The preparation method of C is characterized in that, liquid I can also be added drop-wise in the described step (3) in the liquid nitrogen freezing gas of step (2) generation, drips the back and continues to obtain in freezing 10～30 minutes liquid II.
7. according to claim 1 a kind of sad-1- 13The preparation method of C, it is characterized in that, liquid I can also be added drop-wise in the described step (3) in the liquid nitrogen freezing gas of step (2) generation, be warmed up to-20～-30 ℃, stirred 10～90 minutes, liquid nitrogen freezing 10～30 minutes is warmed up to-20～-30 ℃, stirs to obtain liquid II in 10～30 minutes.
8. according to claim 1 a kind of sad-1- 13The preparation method of C, it is characterized in that, liquid I can also be added drop-wise in the described step (3) in the liquid nitrogen freezing gas of step (2) generation, be warmed up to-20～-30 ℃, stirred 10～90 minutes, freezing 10～60 minutes of dry ice is warmed up to-20～-30 ℃, stirs to obtain liquid II in 10～30 minutes.
9. according to claim 1 a kind of sad-1- 13The preparation method of C is characterized in that, in the described step (5) liquid II being transferred in another container is to carry out under vacuum state.
10. according to claim 1 a kind of sad-1- 13The preparation method of C is characterized in that, the extraction liquid in the described step (6) adopts the aqueous solution of the 5% sodium hydroxide alkalescence that neutralizes, and described alkaline aqueous solution is with the 10% vitriolic aqueous solution acidity that neutralizes.
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CN103319323A (en) * 2013-02-20 2013-09-25 上海晶纯实业有限公司 Odd-carbon saturated higher fatty acids, and preparation method for esters thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0384652A1 (en) * 1989-02-23 1990-08-29 The British Petroleum Company P.L.C. Process for preparing carboxylic acids

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0384652A1 (en) * 1989-02-23 1990-08-29 The British Petroleum Company P.L.C. Process for preparing carboxylic acids

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
王惠琼等.辛酸-1-13C的合成与分析.《核技术》.2000,第23卷(第2期),136-140. *

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