CN108276296A - A kind of synthetic method of cyanide antidote - Google Patents
A kind of synthetic method of cyanide antidote Download PDFInfo
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- CN108276296A CN108276296A CN201711326503.8A CN201711326503A CN108276296A CN 108276296 A CN108276296 A CN 108276296A CN 201711326503 A CN201711326503 A CN 201711326503A CN 108276296 A CN108276296 A CN 108276296A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
Abstract
The present invention relates to a kind of synthetic methods of cyanide antidote, are included in ethanol solution, and formalin and paranitroanisole is added, and adjust pH=4 with hydrochloric acid, heating is slowly added to iron powder, is reacted after adding, obtains 4 dimethylamino methyl phenyl ethers anisoles；4 dimethylamino methyl phenyl ethers anisoles are added in toluene, alchlor is added, temperature rising reflux takes off methyl, cooling, and saturated sodium bicarbonate solution is added, filters out solid while hot, liquid separation is washed with water toluene phase, evaporated under reduced pressure toluene after liquid separation, then heats up and steam product.The product that the present invention cures, purity is 99% or more, 80% or more yield；The method raw material of the present invention is cheap and easy to get, and the waste water of no risky operation, production is less, and environmental pollution is small, and overall yield is high, is suitble to large-scale production.
Description
Technical field
The invention belongs to medical synthesis technical field more particularly to a kind of synthetic methods of cyanide antidote.
Background technology
4-DMAP is a kind of aromatic compound containing phenol and amido, and chemical formula is C8H11NO, 4- diformazan ammonia
Base phenol is the antidote of cyanide poisoning, it detoxifies through methamoglobin is generated, but this is only applicable to acute poisoning
The case where, sodium thiosulfate or cobalamin-therapeutic must be used thereafter, and in the experiment of animal, it is generated in intramuscular injection
Effect.
There are three ways to the prior art produces 4-DMAP：
Method one：Synthetic route is as follows
It is that formaldehyde and sodium borohydride is added, is using boron in alcoholic solvent that this method, which has lot of documents report, synthetic method,
Sodium hydride generate hydrogen, production get up it is risky, which also has a large amount of intermediate state 4- methylaminophenols, is not easy to remove.
Method two：Synthetic route is as follows
The operation of document report is added catalyst Kocide SD, adds highly basic sodium hydroxide mainly in ethylene glycol
Or potassium hydroxide, hydrolysis is heated at 120 DEG C, then alkali tune obtains product.The route starting material is expensive, is generated in production
A large amount of salt and waste water, are not easy to mass produce.
Method three：Synthetic route is as follows：
The raw material 4- dimethylamino methyl phenyl ethers anisoles of this method mainly by paraphenetidine under alkaline condition with sulfuric acid two
Methyl esters or iodomethane reaction are made, and the reaction yield is low, and only 50% or so, dimethyl suflfate and iodomethane have strong carcinogenic
Effect, brings greater risk, and synthesize 4-DMAP to production, there are mainly two types of method in document report, first
It is Boron tribromide, which greatly improves production cost；Second method is the hydrobromic acid solution with acetic acid,
Product is obtained in 110 degrees Celsius of reflux, which generates a large amount of waste acid waters, there is certain environmental protection pressure.
Invention content
In order to solve the above technical problem, the present invention provides a kind of synthetic method of cyanide antidote, present invention solidifications
Obtained product, purity is 99% or more, 80% or more yield；The method raw material of the present invention is cheap and easy to get, no risky operation, raw
The waste water of production is less, and environmental pollution is small, and overall yield is high, is suitble to large-scale production.
The present invention is achieved through the following technical solutions, and the present invention provides a kind of synthetic method of cyanide antidote,
The reaction equation of synthesis is as follows：
Formalin and paranitroanisole is added in ethanol solution in the first step, adjusts pH=4 with hydrochloric acid, heats up,
It is slowly added to iron powder, is reacted after adding, 4- dimethylamino methyl phenyl ethers anisoles are obtained；
Second step 4- dimethylamino methyl phenyl ethers anisoles is added in toluene, alchlor is added, temperature rising reflux takes off methyl, cold
But, saturated sodium bicarbonate solution is added, filters out solid while hot, liquid separation is washed with water toluene phase, evaporated under reduced pressure first after liquid separation
Benzene, then heat up and steam product.
Preferably, in the first step, reaction temperature is 50 DEG C, and the reaction time is 12 hours.
Preferably, in the first step, product is purified after reaction, the step of purification is：Reaction product is slowly added
Enter sodium carbonate solid, adjust pH=10, leach out iron powder, be spin-dried for ethanol solution, ethyl acetate dissolving is added, then use saturated brine
Ethyl acetate phase is washed, ethyl acetate phase is dried with anhydrous sodium sulfate after liquid separation, is spin-dried for obtaining yellow oil i.e. 4- dimethylaminos
Methyl phenyl ethers anisole.
Preferably, the temperature rising reflux time is 6 hours in second step.
Preferably, in second step, saturated sodium bicarbonate solution is added after being cooled to 80 DEG C.
Beneficial effects of the present invention are：
The product that the present invention cures, purity is 99% or more, 80% or more yield；The method raw material of the present invention is inexpensive
It is easy to get, the waste water of no risky operation, production is less, and environmental pollution is small, and overall yield is high, is suitble to large-scale production.
Description of the drawings
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technology description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
Some embodiments of invention for those of ordinary skill in the art without creative efforts, can be with
Obtain other attached drawings according to these attached drawings.
Fig. 1 is 4-DMAP H1NMR spectra；
Fig. 2 is the gas chromatogram of 4-DMAP；
Fig. 3 is 4- dimethylamino methyl phenyl ethers anisoles H1NMR spectra；
Fig. 4 is the gas chromatogram of 4- dimethylamino methyl phenyl ethers anisoles.
Specific implementation mode
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
Below in conjunction with the accompanying drawings and specific embodiment is further described the application principle of the present invention.Embodiment 1
200ml ethyl alcohol, 30.6g paranitroanisoles, the first of 60ml 37% is added in 500ml there-necked flasks in the first step
Aldehyde solution adds 5ml concentrated hydrochloric acids, is put into oil bath pan, and 50 DEG C are warming up under stirring, 33 grams of iron powders is slowly added to, after adding
It keeps temperature to continue stirring 12 hours, is slowly added to sodium carbonate solid, adjust pH=10, leach out iron powder, be spin-dried for ethanol solution,
The dissolving of 200ml ethyl acetate is added, then ethyl acetate phase, the anhydrous sulphur of ethyl acetate phase after liquid separation are washed with 100ml saturated salts
Sour sodium drying, is spin-dried for obtaining 28.2 grams of yellow oil, purity 98.8%；
Second step, 28.2 grams of grease, 200 milliliters of toluene, 500 milliliters of there-necked flask is added in 27 grams of aluminum trichloride (anhydrous)s
In, temperature rising reflux 6 hours in oil bath pan cool to 80 DEG C, and 100 milliliters of saturated sodium bicarbonate solution is slowly added dropwise, and generate solid
Body continues stirring 10 minutes, filters out insoluble matter while hot, liquid separation while hot after filtering, then 50 milliliters of water are added into toluene, together
80 DEG C are warming up to, is stirred 10 minutes, liquid separation, toluene is mutually spin-dried for, then is evaporated under reduced pressure with oil pump, and solidification obtains 20.8 grams of product, pure
Degree 99.8%, yield 81%.
Fig. 1 is 4-DMAP H1NMR spectra；It is the hydrogen of product Fig. 4-dimethyl p-aminophenol as seen from Figure 1
Nuclear magnetic spectrogram；Fig. 2 is the gas chromatogram of 4-DMAP, and Fig. 2 is used for the purity of analysis product；Table 1 is 4- diformazan ammonia
Peak area percent data in the gas-chromatography of base phenol, from table 2 and it can be seen from the figure that, the purity of 4-DMAP
Reach 99.8%.
Table 1
Fig. 3 is 4- dimethylamino methyl phenyl ethers anisoles H1NMR spectra；It is intermediate 4- dimethylamino methyl phenyl ethers anisoles as seen from Figure 1
Hydrogen nuclear magnetic spectrogram；Fig. 4 is the gas chromatogram of 4- dimethylamino methyl phenyl ethers anisoles；Table 2 is the gas phase color of 4- dimethylamino methyl phenyl ethers anisoles
Peak area percent data in spectrum, from table 2 and it can be seen from the figure that, the purity of intermediate 4- dimethylamino methyl phenyl ethers anisoles reaches
98.8%.
Table 2
Certainly, above description is also not limited to the example above, technical characteristic of the present invention without description can by or
It is realized using the prior art, details are not described herein；Above example and attached drawing are only used to illustrate the technical scheme of the present invention not
It is limitation of the present invention, is described the invention in detail with reference to preferred embodiment, the ordinary skill people of this field
Member is it should be appreciated that variation, remodeling, the addition that those skilled in the art are made in the essential scope of the present invention
Or replace the claims that should also belong to the present invention without departure from spirit of the invention.
Claims (5)
1. a kind of synthetic method of cyanide antidote, it is characterised in that：The reaction equation of synthesis is as follows：
Formalin and paranitroanisole is added in ethanol solution in the first step, adjusts pH=4 with hydrochloric acid, heats up, slowly
Iron powder is added, is reacted after adding, obtains 4- dimethylamino methyl phenyl ethers anisoles；
Second step 4- dimethylamino methyl phenyl ethers anisoles is added in toluene, and alchlor is added, and temperature rising reflux takes off methyl, cooling,
Saturated sodium bicarbonate solution is added, filters out solid while hot, liquid separation is washed with water toluene phase, evaporated under reduced pressure toluene after liquid separation, then
Heating steams product.
2. according to a kind of synthetic method for cyanide antidote that claim 1 is stated, it is characterised in that：In the first step, reaction temperature
Degree is 50 DEG C, and the reaction time is 12 hours.
3. according to a kind of synthetic method for cyanide antidote that claim 1 is stated, it is characterised in that：In the first step, after reaction
Product is purified, the step of purification is：Reaction product is slowly added to sodium carbonate solid, pH=10 is adjusted, leaches out iron
Powder is spin-dried for ethanol solution, ethyl acetate dissolving is added, then wash ethyl acetate phase with saturated salt, ethyl acetate phase is used after liquid separation
Anhydrous sodium sulfate is dried, and is spin-dried for obtaining yellow oil i.e. 4- dimethylaminos methyl phenyl ethers anisole.
4. according to a kind of synthetic method for cyanide antidote that claim 1 is stated, it is characterised in that：Temperature rising reflux in second step
Time is 6 hours.
5. according to a kind of synthetic method for cyanide antidote that claim 1 is stated, it is characterised in that：In second step, it is cooled to
Saturated sodium bicarbonate solution is added after 80 DEG C.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109134270A (en) * | 2018-10-11 | 2019-01-04 | 中国科学院青岛生物能源与过程研究所 | A kind of reaction method of nitro compound N- methylation |
| CN109896967A (en) * | 2019-04-04 | 2019-06-18 | 上海工程技术大学 | A kind of preparation method of m-diethylaminophenol |
| CN109896966A (en) * | 2019-04-04 | 2019-06-18 | 上海工程技术大学 | A kind of preparation method of N, N- dibutyl m-aminophenol |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2649229A1 (en) * | 1975-11-14 | 1977-11-24 | Eprova Ag | Cyanide antidote (4)-dimethylamino-phenol prodn. - by reacting (4)-amino-anisole with dimethyl sulphate, heating with sodium hydroxide and (O)-dimethylating |
| WO2013027694A1 (en) * | 2011-08-24 | 2013-02-28 | 国立大学法人京都大学 | Molecular imaging probes for diagnosing conformation disease |
-
2017
- 2017-12-13 CN CN201711326503.8A patent/CN108276296B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2649229A1 (en) * | 1975-11-14 | 1977-11-24 | Eprova Ag | Cyanide antidote (4)-dimethylamino-phenol prodn. - by reacting (4)-amino-anisole with dimethyl sulphate, heating with sodium hydroxide and (O)-dimethylating |
| WO2013027694A1 (en) * | 2011-08-24 | 2013-02-28 | 国立大学法人京都大学 | Molecular imaging probes for diagnosing conformation disease |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109134270A (en) * | 2018-10-11 | 2019-01-04 | 中国科学院青岛生物能源与过程研究所 | A kind of reaction method of nitro compound N- methylation |
| CN109134270B (en) * | 2018-10-11 | 2021-04-13 | 中国科学院青岛生物能源与过程研究所 | Reaction method for N-methylation of nitro compound |
| CN109896967A (en) * | 2019-04-04 | 2019-06-18 | 上海工程技术大学 | A kind of preparation method of m-diethylaminophenol |
| CN109896966A (en) * | 2019-04-04 | 2019-06-18 | 上海工程技术大学 | A kind of preparation method of N, N- dibutyl m-aminophenol |
| CN109896967B (en) * | 2019-04-04 | 2021-10-22 | 上海工程技术大学 | Preparation method of m-diethylaminophenol |
| CN109896966B (en) * | 2019-04-04 | 2021-10-22 | 上海工程技术大学 | Preparation method of N, N-dibutyl m-aminophenol |
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