CN106542982A - A kind of preparation method of the deuterium-labeled acetone of stable isotope - Google Patents
A kind of preparation method of the deuterium-labeled acetone of stable isotope Download PDFInfo
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- CN106542982A CN106542982A CN201610928559.XA CN201610928559A CN106542982A CN 106542982 A CN106542982 A CN 106542982A CN 201610928559 A CN201610928559 A CN 201610928559A CN 106542982 A CN106542982 A CN 106542982A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/001—Acyclic or carbocyclic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
- C07C45/82—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
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Abstract
The present invention relates to a kind of preparation method of the deuterium-labeled acetone of stable isotope, it is radioisotope starting material using cold labeling heavy water, certain hour is reacted under base catalyst effect, carry out hydrogen deuterium exchange with natural abundance acetone, obtain stable isotope D labelling acetone after purification.Compared with the synthetic technology of existing deuterium-labeled acetone, the method has the advantages that reaction condition is gentle, exchange times are few, isotope utilization rate is high, stable isotope D labelling acetone prepared by the present invention is separated after purification, and up to more than 99%, isotope abundance reaches more than 99.5atom%D to chemical purity.
Description
Technical field
The invention belongs to stable isotope labelled compound synthesis field, deuterium-labeled more particularly, to a kind of stable isotope
The preparation method of acetone.
Background technology
Stable isotope and its labelled compound as a kind of unique brand-new material, compared with radiosiotope, its
Have the advantages that it is stable in properties, easy to operate, do not need special protection, there is high technology content and high added value as a class
Commodity, have been widely used in agricultural, food safety, life sciences, environment, clinical medicine, pharmacy etc. since the seventies in last century
Field.During common agents of the deuterated acetone as nuclear-magnetism detection technique, and the deuterium-labeled tube- nursery of stable isotope
Basic material, has been widely used in scientific research field.
The main preparation methods of deuterated acetone are exchanged with the multiple H/D of heavy water for acetone.Deuterated acetone system traditional at present
Standby technology is, with dry potassium carbonate as catalyst, separated to intercept 95 DEG C of fraction, add fresh heavy water after reaction
Repeatedly exchanged, after having carried out 21 hydrogen deuterium exchange, in acetone, the isotope abundance of D-atom reaches 99.3atom%D.The mistake
Journey is cumbersome, except loss caused during separating for several times, it is easier to midway failure, causes a large amount of wastes of raw material, to people
The technology and operation level requirement of member is also very high, so as to be difficult to promote.In the reality to acetone and heavy water hydrogen-deuterium exchange catalyst
Test in research and find, during the mineral acid such as the phosphoric acid of the natural abundance used in the reaction system, hydrochloric acid, acetic acid, nothing can be caused
The D-atom on H atom substitution product in machine acid, causes the reduction of isotope utilization rate.And for the H/D of acetone in document
The basic conditions such as the reaction temperature in exchange procedure also have no report.The country also not yet retrieves relevant stable isotope D
The patent report of the synthetic method of labelling acetone.
The content of the invention
The purpose of the present invention be exactly in order to overcome defect that above-mentioned prior art is present and provide a kind of course of reaction it is simple,
The synthetic method of the high stable isotope D labelling acetone of isotope utilization rate.
The purpose of the present invention can be achieved through the following technical solutions：
A kind of preparation method of the deuterium-labeled acetone of stable isotope, is that isotope is former using cold labeling heavy water
Material, under base catalyst effect reacts certain hour, carries out hydrogen-deuterium exchange with natural abundance acetone, stablized after purification
Isotope D labelling acetone, specifically using following steps：
In the there-necked flask equipped with magnetic agitation, thermometer and reflux condenser, base catalyst and heavy water are added, is made
Base catalyst is maintained at certain molar concentration scope, then heats to certain reaction temperature, under stirring, adds third
Ketone, insulation reaction 3～12 hours, then Jing rectification is isolated and purified, and above-mentioned steps are carried out 3-15 time altogether, prepares stably same position
The deuterium-labeled acetone of element.
Described heavy water is the heavy water that deuterium isotope abundance is 99.5atom%D～99.9atom%D.
Described base catalyst is sodium paranitrophenol, sodium bicarbonate, potassium bicarbonate, potassium carbonate, deuterium potassium oxide, deuterium oxygen
Change one kind of sodium, sodium sulfite, sodium acetate or sodium carbonate.
Used as preferred embodiment, the base catalyst for adopting is deuterium sodium oxide, sodium sulfite, sodium acetate or sodium carbonate
In one kind.
The concentration of described base catalyst is 0.05mol/L～0.1mol/L.
Described heavy water is 3: 1～25: 1 with the mol ratio of acetone.
Described reaction temperature is 20 DEG C～60 DEG C, and reaction temperature is less than 20 DEG C, the hydrogen deuterium exchange reaction of acetone and heavy water
Speed is slow, less efficient；When reaction temperature is more than 60 DEG C, acetone can occur enolization, and assemble symphysis into wadding dress precipitation,
Make the dilution of product abundance, yield reduction.
For traditional catalyst potassium carbonate, the catalyst such as sodium carbonate has in catalytic effect and cheap and easily-available aspect
Significantly advantage, while being also easy to drying, will not introduce the active hydrogen for causing isotope abundance to dilute in course of reaction, and existing
Technology is compared, and the present invention has advantages below：
(1) deuterium sodium oxide used in the present invention, sodium sulfite, sodium acetate, sodium carbonate are relative to traditional catalyst carbon
There is obvious catalysis advantage for sour potassium, as sodium ion radius is less, effective nuclear charge is slightly higher, therefore sodium salt more holds than potassium salt
Easily combined with heavy water so as in deuterium element participate in reaction；
(2) operating process of the present invention is simple, and reaction condition is gentle, it is adaptable to the synthesis of cold labeling reagent；
(3) present invention has significant loss few, the characteristics of high income, yield up to more than 85%, material saving cost；
(3) the deuterium-labeled product acetone chemical purity more than 99% of stable isotope of present invention gained, deuterium isotope abundance
More than 99.5atom%D；
(4) present invention it is easier than 21 times traditional exchange process, traditional handicraft using distillation method by acetone with
Heavy water is separated, and new technology is separated using the method for rectification, can improve the purity of acetone when exchanging every time, front once exchanged
Low abundance heavy water afterwards will not cause abundance to dilute in the heavy water of new addition, thus using new H-D exchange process only need to into
3～15 exchanges of row, with good economy and actual application value.
Specific embodiment
With reference to specific embodiment, the present invention is described in detail.
Embodiment 1
In the there-necked flask equipped with magnetic agitation, thermometer and reflux condenser, 600mL heavy water is added
(99.9atom%D's), 90mL acetone (mol ratio 25: 1 of heavy water and ketone), prepares the sodium acetate solution of 0.05mol/L, heats up
To 20 DEG C, under stirring, insulation reaction 3 hours；After reaction terminates, deuterium-labeled acetone and water are separated using the method for rectification,
And 3 exchanges are carried out with this condition, obtain the deuterated acetone 77mL that D-atom isotope abundance is 99.5atom%D, yield
85.5%, single yield is up to 96.2%.
Embodiment 2
In the there-necked flask equipped with magnetic agitation, thermometer and reflux condenser, 480mL heavy water is added
(99.9atom%D's), 90mL acetone (mol ratio 20: 1 of heavy water and ketone), prepares the sodium sulfite solution of 0.065mol/L,
50 DEG C, under stirring are warming up to, insulation reaction 10 hours；After reaction terminates, deuterium-labeled acetone is separated using the method for rectification
And water, and 5 exchanges are carried out with this condition, the deuterated acetone 78.5mL that D-atom isotope abundance is 99.6atom%D is obtained,
Yield 87.2%, single yield is up to 96.6%.
Embodiment 3
In the there-necked flask equipped with magnetic agitation, thermometer and reflux condenser, 180mL heavy water is added
(99.9atom%D's), 90mL acetone (mol ratio 7.5: 1 of heavy water and ketone), prepares the sodium carbonate liquor of 0.075mol/L, rises
Temperature to 30 DEG C, under stirring, insulation reaction 7.5 hours；After reaction terminates, using the method for rectification separate deuterium-labeled acetone and
Water, and 8 exchanges are carried out with this condition, the deuterated acetone 77.4mL that D-atom isotope abundance is 99.5atom%D is obtained, is received
Rate 86%, single yield is up to 96.3%.
Embodiment 4
In the there-necked flask equipped with magnetic agitation, thermometer and reflux condenser, 192mL heavy water is added
(99.8atom%D's), 90mL acetone (mol ratio 8: 1 of heavy water and ketone), prepares the deuterium sodium hydroxide solution of 0.09mol/L, rises
Temperature to 60 DEG C, under stirring, insulation reaction 5 hours；After reaction terminates, using the method for rectification separate deuterium-labeled acetone and
Water, and 6 exchanges are carried out with this condition, the deuterated acetone 78.8mL that D-atom isotope abundance is 99.5atom%D is obtained, is received
Rate 87.5%, single yield is up to 96.7%.
Embodiment 5
In the there-necked flask equipped with magnetic agitation, thermometer and reflux condenser, 72mL heavy water (99.9atom% are added
D's), 90mL acetone (mol ratio 5: 1 of heavy water and ketone) is prepared the deuterium sodium hydroxide solution of 0.1mol/L, is warming up to 40 DEG C, stirs
Under state, insulation reaction 3 hours；After reaction terminates, deuterium-labeled acetone and water are separated using the method for rectification, and is entered with this condition
15 exchanges of row, obtain the deuterated acetone 80mL that D-atom isotope abundance is 99.5atom%D, and yield 88.8%, single are received
Rate is up to 97.1%.
Embodiment 6
The preparation method of the deuterium-labeled acetone of a kind of stable isotope, equipped with magnetic agitation, thermometer and reflux condenser
There-necked flask in, add base catalyst deuterium sodium oxide and deuterium isotope abundance for the heavy water of 99.5atom%D, control alkalescence
The concentration of catalyst is 0.05mol/L, then heats to 20 DEG C, under stirring, adds the mol ratio of acetone, heavy water and acetone
For 3: 1, insulation reaction 12 hours, then Jing rectification is isolated and purified, and above-mentioned steps are carried out 3 times altogether, prepare stable isotope
Deuterium-labeled acetone.
Embodiment 7
The preparation method of the deuterium-labeled acetone of a kind of stable isotope, equipped with magnetic agitation, thermometer and reflux condenser
There-necked flask in, add base catalyst sodium sulfite and deuterium isotope abundance for the heavy water of 99.6atom%D, control alkalescence
The concentration of catalyst is 0.08mol/L, then heats to 30 DEG C, under stirring, adds the mol ratio of acetone, heavy water and acetone
For 5: 1, insulation reaction 10 hours, then Jing rectification is isolated and purified, and above-mentioned steps are carried out 5 times altogether, prepare stable isotope
Deuterium-labeled acetone.
Embodiment 8
The preparation method of the deuterium-labeled acetone of a kind of stable isotope, equipped with magnetic agitation, thermometer and reflux condenser
There-necked flask in, add base catalyst sodium acetate and deuterium isotope abundance for the heavy water of 99.7atom%D, control alkalescence is urged
The concentration of agent is 0.06mol/L, then heats to 40 DEG C, under stirring, addition acetone, and heavy water with the mol ratio of acetone is
10: 1, insulation reaction 8 hours, then Jing rectification is isolated and purified, and above-mentioned steps are carried out 8 times altogether, prepare stable isotope deuterium
Labelling acetone.
Embodiment 9
The preparation method of the deuterium-labeled acetone of a kind of stable isotope, equipped with magnetic agitation, thermometer and reflux condenser
There-necked flask in, add base catalyst sodium carbonate and deuterium isotope abundance for the heavy water of 99.8atom%D, control alkalescence is urged
The concentration of agent is 0.09mol/L, then heats to 50 DEG C, under stirring, addition acetone, and heavy water with the mol ratio of acetone is
20: 1, insulation reaction 5 hours, then Jing rectification is isolated and purified, and above-mentioned steps are carried out 12 times altogether, prepare stable isotope deuterium
Labelling acetone.
Embodiment 10
The preparation method of the deuterium-labeled acetone of a kind of stable isotope, equipped with magnetic agitation, thermometer and reflux condenser
There-necked flask in, add base catalyst sodium paranitrophenol and deuterium isotope abundance for the heavy water of 99.9atom%D, control
The concentration of base catalyst is 0.1mol/L, then heats to 60 DEG C, under stirring, adds acetone, heavy water to rub with acetone
, than being 25: 1, insulation reaction 3 hours, then Jing rectification are isolated and purified, and above-mentioned steps are carried out 15 times altogether, are prepared stably same for you
The plain deuterium-labeled acetone in position.
Claims (9)
1. the preparation method of the deuterium-labeled acetone of a kind of stable isotope, it is characterised in that the method utilizes cold labeling
Heavy water is radioisotope starting material, reacts certain hour, carry out hydrogen-deuterium exchange with natural abundance acetone under base catalyst effect,
Stable isotope D labelling acetone is obtained after purification.
2. a kind of preparation method of the deuterium-labeled acetone of stable isotope according to claim 1, it is characterised in that the method
Following steps are adopted specifically：
In the there-necked flask equipped with magnetic agitation, thermometer and reflux condenser, base catalyst and heavy water are added, alkalescence is made
Catalyst is maintained at certain molar concentration scope, then heats to certain reaction temperature, under stirring, adds acetone, protects
Temperature reaction 3～12 hours, then Jing rectification separate deuterium-labeled acetone and water, then using fresh heavy water with separate after acetone
Carry out repeating to exchange, prepare the deuterium-labeled acetone of stable isotope.
3. a kind of preparation method of the deuterium-labeled acetone of stable isotope according to claim 1 and 2, it is characterised in that institute
The heavy water stated is the heavy water that deuterium isotope abundance is 99.5atom%D～99.9atom%D.
4. a kind of preparation method of the deuterium-labeled acetone of stable isotope according to claim 1 and 2, it is characterised in that institute
The one kind of the base catalyst stated for sodium paranitrophenol, sodium bicarbonate, deuterium sodium oxide, sodium sulfite, sodium acetate or sodium carbonate.
5. a kind of preparation method of the deuterium-labeled acetone of stable isotope according to claim 1 and 2, it is characterised in that institute
One kind in the preferred deuterium sodium oxide of base catalyst, sodium sulfite, sodium acetate or the sodium carbonate stated.
6. the preparation method of the deuterium-labeled acetone of a kind of stable isotope according to claim 2, it is characterised in that described
The concentration of base catalyst is 0.05mol/L～0.1mol/L.
7. the preparation method of the deuterium-labeled acetone of a kind of stable isotope according to claim 2, it is characterised in that described
Heavy water is 3: 1～25: 1 with the mol ratio of acetone.
8. the preparation method of the deuterium-labeled acetone of a kind of stable isotope according to claim 2, it is characterised in that described
Reaction temperature is 20 DEG C～60 DEG C.
9. a kind of preparation method of the deuterium-labeled acetone of stable isotope according to claim 2, it is characterised in that hydrogen-deuterium
Exchange step repeats 3-15 time, prepares stable isotope D labelling acetone.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114105768A (en) * | 2021-12-11 | 2022-03-01 | 上海化工研究院有限公司 | Preparation by exchange method18Method for marking ethyl formate by using O |
| CN114773174A (en) * | 2022-04-29 | 2022-07-22 | 常州大学 | Synthetic method of alpha-deuterated carbonyl compound |
| CN114890878A (en) * | 2022-05-27 | 2022-08-12 | 安徽贵朋功能材料科技有限公司 | Method for preparing deuterated acetone by photocatalysis |
| CN115010566A (en) * | 2022-07-05 | 2022-09-06 | 宁波萃英化学技术有限公司 | Method for producing deuterated compound by using tower equipment |
| CN115353443A (en) * | 2022-09-19 | 2022-11-18 | 上海安谱实验科技股份有限公司 | Synthesis method of deuterium-labeled diethylstilbestrol |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1661880A1 (en) * | 2003-09-04 | 2006-05-31 | Taiyo Nippon Sanso Corporation | Method for producing deuterated methyl methacrylate |
-
2016
- 2016-10-31 CN CN201610928559.XA patent/CN106542982A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1661880A1 (en) * | 2003-09-04 | 2006-05-31 | Taiyo Nippon Sanso Corporation | Method for producing deuterated methyl methacrylate |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114105768A (en) * | 2021-12-11 | 2022-03-01 | 上海化工研究院有限公司 | Preparation by exchange method18Method for marking ethyl formate by using O |
| CN114773174A (en) * | 2022-04-29 | 2022-07-22 | 常州大学 | Synthetic method of alpha-deuterated carbonyl compound |
| CN114773174B (en) * | 2022-04-29 | 2024-05-28 | 常州大学 | Synthesis method of alpha-deuterated carbonyl compound |
| CN114890878A (en) * | 2022-05-27 | 2022-08-12 | 安徽贵朋功能材料科技有限公司 | Method for preparing deuterated acetone by photocatalysis |
| CN114890878B (en) * | 2022-05-27 | 2023-01-13 | 诺泰生物科技(合肥)有限公司 | Method for preparing deuterated acetone by photocatalysis |
| CN115010566A (en) * | 2022-07-05 | 2022-09-06 | 宁波萃英化学技术有限公司 | Method for producing deuterated compound by using tower equipment |
| WO2024007464A1 (en) * | 2022-07-05 | 2024-01-11 | 宁波萃英化学技术有限公司 | Method for producing deuterated compound with tower device |
| CN115353443A (en) * | 2022-09-19 | 2022-11-18 | 上海安谱实验科技股份有限公司 | Synthesis method of deuterium-labeled diethylstilbestrol |
| CN115353443B (en) * | 2022-09-19 | 2023-09-15 | 上海安谱实验科技股份有限公司 | Synthetic method of deuterium-labeled diethylstilbestrol |
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Address after: 200062 Shanghai city Putuo District Yunling Road No. 345 Applicant after: Shanghai Chemical Research Institute Co., Ltd. Address before: 200062 Shanghai city Putuo District Yunling Road No. 345 Applicant before: Shanghai Research Institute of Chemical Industry |
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Application publication date: 20170329 |