CN107304175A - A kind of synthetic method of dodine - Google Patents
A kind of synthetic method of dodine Download PDFInfo
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- CN107304175A CN107304175A CN201610252297.XA CN201610252297A CN107304175A CN 107304175 A CN107304175 A CN 107304175A CN 201610252297 A CN201610252297 A CN 201610252297A CN 107304175 A CN107304175 A CN 107304175A
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- synthetic method
- dodine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
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Abstract
The invention provides a kind of synthetic method of dodine, it is reacted and intermediate A is made by this method using guanidine hydrochloride as initiation material with chlorinated dodecane, then strong alkali aqueous solution is added into intermediate A to be reacted, then glacial acetic acid reaction is added, target product dodine is made in post processing.The synthetic method raw material is easy to get, reactions steps are few, reaction condition is gentle, simple to operate, yield is higher, and is a kind of environmentally friendly synthetic method, therefore, it is adaptable to large-scale industrial production, with good application prospect and market potential.
Description
Technical field
The invention belongs to organic synthesis field, more particularly to a kind of synthetic method of dodine.
Background technology
Dodine is a kind of agricultural chemicals, is also that one kind is efficient, quickly sterilizes paint scrubber, can be applied to food production
And manufacture field, the effect with excellent killing food pathogenic.The molecular formula of dodine is：
C15H33N3O2, title is：Dodine, English name：dodine；No. CAS is：2439-10-3；
Structural formula
In the prior art, describe and dodine acetic acid is prepared by cyanamide and lauryl amine and glacial acetic acid reaction
The method of salt, such as patent DE3248115, US3004065 etc..However, cyanamide property is active, it is difficult steady
Store calmly, and such method often needs to make raw material using high energy consumption lime nitrogen in production, can draw after skin contact
Strong allergy is played, therefore, such method is not suitable for large-scale industrial production.And for example patent CN1629138A
Deng disclosing following synthetic method：Dimethyl suflfate is first passed through to be reacted with urea, then with acetic acid and 12
Amine synthesis obtains dodine；However, the synthetic method has used the sulfuric acid as alkylating reagent
Dimethyl ester, it is well known that the toxicity of dimethyl suflfate is very big, so that production safety can be influenceed, and is advised to operation
Journey requires very high with operation equipment；It can be seen that, this method is also not suitable for large-scale industrial production.
Therefore, in order to synthesize dodine, seek and develop a kind of synthesis work suitable for large-scale industrial production
Skill is always one of research emphasis of art technology research staff.
The content of the invention
In order to overcome the defect of various synthesis dodine methods that prior art provided, the present invention is intended to provide one
Kind reactions steps are few, the synthetic method that reaction condition is gentle, simple to operate, yield is higher and environmentally friendly,
The industrialized production synthesized suitable for dodine.
Therefore, the invention provides a kind of synthetic method of dodine, the synthetic method has following synthesis road
Line：
Also, comprise the following steps：
(1) using guanidine hydrochloride as initiation material, it is reacted with chlorinated dodecane intermediate A is made；
(2) strong alkali aqueous solution is first added into the intermediate A, adds glacial acetic acid reaction, target product is made
Dodine.
Preferably, above-mentioned synthetic method comprises the following steps：
(1) it will be added as the guanidine hydrochloride of initiation material and solvent S1 in reaction vessel, stirring and dissolving then adds
Enter chlorinated dodecane, intermediate A is made in back flow reaction, post processing；
(2) intermediate A made from step (1) is added into another reaction vessel, and is added immiscible with water
Strong alkali aqueous solution is then added dropwise in solvent S2, stirring and dissolving, and stirring reaction is divided after 1~2 hour and goes aqueous phase,
Glacial acetic acid reaction is slowly added into again, and target product dodine is made in post processing.
It is further preferred that the time of back flow reaction described in the step of above-mentioned synthetic method (1) is 8~14
Hour.
It is further preferred that the time of back flow reaction described in the step of above-mentioned synthetic method (1) is 10~12
Hour.
It is further preferred that the solvent S1 described in the step of above-mentioned synthetic method (1) is selected from following any
Plant or a variety of combinations：Dichloromethane, dichloroethanes, chloroform, toluene, dimethylbenzene, hexahydrotoluene, second
Acetoacetic ester, sec-butyl alcohol, n-butanol, absolute methanol, absolute ethyl alcohol, isopropanol, n-hexane.
It is further preferred that the solvent S1 described in the step of above-mentioned synthetic method (1) is selected from following
It is a kind of：Dichloromethane, toluene, ethyl acetate, n-butanol, absolute ethyl alcohol.
It is further preferred that the post processing described in the step of above-mentioned synthetic method (1) includes：Cooling reaction
Liquid, wait after the crude product for separating out intermediate A, is recrystallized to room temperature.
It is further preferred that the recrystallization solvent used when being recrystallized is selected from following any one or more
Combination：Dimethylbenzene, toluene, benzene, methanol, ethanol, isopropanol, dichloromethane, chloroform, carbon tetrachloride,
Ethyl acetate, tetrahydrofuran.
It is further preferred that the strong alkali aqueous solution described in the step of above-mentioned synthetic method (2) is sodium hydroxide
The aqueous solution or potassium hydroxide aqueous solution.
It is further preferred that the step of above-mentioned synthetic method in (2), the sodium hydrate aqueous solution is
20% sodium hydrate aqueous solution.
It is further preferred that the post processing described in the step of above-mentioned synthetic method (2) includes：Filter while hot
Reaction solution removes insoluble solids salt, then filtrate is cooled into less than 0 DEG C, after a large amount of white solids are separated out, takes out
Filter, collects filter cake, drying.
It is further preferred that the solvent S2 described in the step of above-mentioned synthetic method (2) is selected from following any
Plant or a variety of combinations：Dimethylbenzene, toluene, benzene, ethyl acetate.
Compared with dodine synthetic method of the prior art, new synthetic method provided by the present invention have with
Lower beneficial effect：The reactions steps of the synthetic method are few, reaction condition is gentle, simple to operate, yield is higher,
And it is a kind of environmentally friendly synthetic method, therefore, it is adaptable to large-scale industrial production, with fine
Application prospect and market potential.
Embodiment
With reference to embodiment, the present invention is further elaborated, but the present invention is not limited to following implementation
Mode.
The invention provides a kind of synthetic method of dodine, the synthetic method has following synthetic route：
Also, comprise the following steps：
(1) using guanidine hydrochloride as initiation material, it is reacted with chlorinated dodecane intermediate A is made；
(2) strong alkali aqueous solution is first added into the intermediate A, adds glacial acetic acid reaction, target product is made
Dodine.
In a preferred embodiment, above-mentioned synthetic method comprises the following steps：
(1) it will be added as the guanidine hydrochloride of initiation material and solvent S1 in reaction vessel, stirring and dissolving then adds
Enter chlorinated dodecane, intermediate A is made in back flow reaction, post processing；
(2) intermediate A made from step (1) is added into another reaction vessel, and is added immiscible with water
Strong alkali aqueous solution is then added dropwise in solvent S2, stirring and dissolving, and stirring reaction is divided after 1~2 hour and goes aqueous phase,
Glacial acetic acid reaction is slowly added into again, and target product dodine is made in post processing.
In a further preferred embodiment, back flow reaction described in (1) the step of above-mentioned synthetic method
Time be 8~14 hours.
In an embodiment still more preferably, backflow is anti-described in (1) the step of above-mentioned synthetic method
The time answered is 10~12 hours.
In a further preferred embodiment, solvent S1 the step of above-mentioned synthetic method described in (1)
Selected from following any one or more combination：Dichloromethane, dichloroethanes, chloroform, toluene, dimethylbenzene, first
Butylcyclohexane, ethyl acetate, sec-butyl alcohol, n-butanol, absolute methanol, absolute ethyl alcohol, isopropanol, n-hexane.
In an embodiment still more preferably, solvent the step of above-mentioned synthetic method described in (1)
S1 is selected from following any：Dichloromethane, toluene, ethyl acetate, n-butanol, absolute ethyl alcohol.
In a further preferred embodiment, post processing the step of above-mentioned synthetic method described in (1)
Including：Reaction solution is cooled down to room temperature, wait after the crude product for separating out intermediate A, is recrystallized.
In an embodiment still more preferably, the recrystallization solvent used when being recrystallized be selected from
Under any one or more combination：Dimethylbenzene, toluene, benzene, methanol, ethanol, isopropanol, dichloromethane,
Chloroform, carbon tetrachloride, ethyl acetate, tetrahydrofuran.
In a further preferred embodiment, highly basic water the step of above-mentioned synthetic method described in (2)
Solution is sodium hydrate aqueous solution or potassium hydroxide aqueous solution.
In an embodiment still more preferably, the step of above-mentioned synthetic method in (2), the hydrogen
Aqueous solution of sodium oxide is 20% sodium hydrate aqueous solution.
In a further preferred embodiment, post processing the step of above-mentioned synthetic method described in (2)
Including：Filtering reacting liquid removes insoluble solids salt while hot, then filtrate is cooled into less than 0 DEG C, waits to separate out largely
After white solid, suction filtration collects filter cake, drying.
In a further preferred embodiment, solvent S2 the step of above-mentioned synthetic method described in (2)
Selected from following any one or more combination：Dimethylbenzene, toluene, benzene, ethyl acetate.
Embodiment 1
The synthesis of dodine, comprises the following steps：
(1) synthetic intermediate A
9.5g (0.10mol) guanidine hydrochlorides and 150ml absolute ethyl alcohols are added into 250ml round-bottomed flasks, is stirred
Dissolving is mixed, chlorinated dodecane 30.6g (0.15mol), back flow reaction 10h is added, is monitored using TLC,
It was found that reaction is complete, cooling reaction solution to room temperature, wait after the crude product for separating out intermediate A, with re crystallization from toluene,
Obtain intermediate A 19.7g, yield 75%, content 97%.
(2) target product dodine is synthesized
10.5g (0.04mol) intermediate A is added into 100ml round-bottomed flasks, toluene 60ml is added,
After stirring and dissolving, 20% sodium hydrate aqueous solution 16.0g (0.08mol) is then added dropwise, stirring is then proceeded to
1h is reacted, point sub-cloud aqueous phase, then glacial acetic acid 3.5g is slowly added into, and it is same using TLC monitorings, until anti-
Should be complete, filtering reacting liquid removes insoluble solids salt while hot, then filtrate is cooled into less than 0 DEG C, waits to separate out greatly
Measure after white solid, suction filtration, collect filter cake, drying obtains desired product as white solid 10.9g, yield 95%,
Content 98%.
The specific embodiment of the present invention is described in detail above, but it is intended only as example, and the present invention is simultaneously
It is not restricted to particular embodiments described above.To those skilled in the art, it is any to present invention progress
Equivalent modifications and substitute also all among scope of the invention.Therefore, the spirit and model of the present invention are not being departed from
Enclose lower made impartial conversion and change, all should be contained within the scope of the invention.
Claims (11)
1. a kind of synthetic method of dodine, it is characterised in that the synthetic method has following synthetic route：
Also, comprise the following steps：
(1) using guanidine hydrochloride as initiation material, it is reacted with chlorinated dodecane intermediate A is made；
(2) strong alkali aqueous solution is first added into the intermediate A, adds glacial acetic acid reaction, target product is made
Dodine.
2. the synthetic method of dodine according to claim 1, it is characterised in that the synthetic method includes
Following steps：
(1) it will be added as the guanidine hydrochloride of initiation material and solvent S1 in reaction vessel, stirring and dissolving then adds
Enter chlorinated dodecane, intermediate A is made in back flow reaction, post processing；
(2) intermediate A made from step (1) is added into another reaction vessel, and is added immiscible with water
Strong alkali aqueous solution is then added dropwise in solvent S2, stirring and dissolving, after then proceeding to stirring reaction 1~2 hour, point
Aqueous phase is gone, then is slowly added into glacial acetic acid reaction, target product dodine is made in post processing.
3. the synthetic method of dodine according to claim 2, it is characterised in that described in step (1)
The time of back flow reaction is 8~14 hours.
4. the synthetic method of dodine according to claim 3, it is characterised in that described in step (1)
The time of back flow reaction is 10~12 hours.
5. the synthetic method of dodine according to claim 2, it is characterised in that described in step (1)
Solvent S1 is selected from following any one or more combination：Dichloromethane, dichloroethanes, chloroform, toluene, two
Toluene, hexahydrotoluene, ethyl acetate, sec-butyl alcohol, n-butanol, absolute methanol, absolute ethyl alcohol, isopropanol,
N-hexane.
6. the synthetic method of dodine according to claim 2, it is characterised in that described in step (1)
Post processing include：Reaction solution is cooled down to room temperature, wait after the crude product for separating out intermediate A, is recrystallized.
7. the synthetic method of dodine according to claim 6, it is characterised in that adopted when being recrystallized
Recrystallization solvent is selected from following any one or more combination：Dimethylbenzene, toluene, benzene, methanol, ethanol,
Isopropanol, dichloromethane, chloroform, carbon tetrachloride, ethyl acetate, tetrahydrofuran.
8. the synthetic method of dodine according to claim 2, it is characterised in that described in step (2)
Strong alkali aqueous solution be sodium hydrate aqueous solution or potassium hydroxide aqueous solution.
9. the synthetic method of dodine according to claim 8, it is characterised in that the sodium hydroxide is water-soluble
Liquid is 20% sodium hydrate aqueous solution.
10. the synthetic method of dodine according to claim 2, it is characterised in that described in step (2)
Post processing include：Filtering reacting liquid removes insoluble solids salt while hot, then filtrate is cooled into less than 0 DEG C, treats
Separate out after a large amount of white solids, suction filtration, collect filter cake, drying.
11. the synthetic method of dodine according to claim 2, it is characterised in that described in step (2)
Solvent S2 be selected from following any one or more combination：Dimethylbenzene, toluene, benzene, ethyl acetate.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610252297.XA CN107304175A (en) | 2016-04-21 | 2016-04-21 | A kind of synthetic method of dodine |
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| CN201610252297.XA CN107304175A (en) | 2016-04-21 | 2016-04-21 | A kind of synthetic method of dodine |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3004065A (en) * | 1957-11-29 | 1961-10-10 | American Cyanamid Co | Preparation of alkylguanidine salts |
| US3312589A (en) * | 1965-11-26 | 1967-04-04 | Union Carbide Corp | Fungicidal liquid concentrate with propylene glycol |
| DE3248115A1 (en) * | 1982-12-24 | 1984-06-28 | A.P.A.- Antiparassitari per Agricoltura S.p.A., Rovigo | Process for the preparation of dodecylguanidine acetate |
| WO2005014528A1 (en) * | 2003-07-22 | 2005-02-17 | Zhenhua Yang | Straight-chain and branched-chain lipid compounds as selective inhibitors of cyclooxygenase-2, anti-inflammatory agents, and anti-cancer agents |
| CN1629138A (en) * | 2004-08-24 | 2005-06-22 | 巨化集团公司 | Process for preparing n-dodecylguanidineacetate |
| CN101933522A (en) * | 2010-08-19 | 2011-01-05 | 沈金龙 | Dodecyl Robenidine hydrochloride sterilized algicide |
-
2016
- 2016-04-21 CN CN201610252297.XA patent/CN107304175A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3004065A (en) * | 1957-11-29 | 1961-10-10 | American Cyanamid Co | Preparation of alkylguanidine salts |
| US3312589A (en) * | 1965-11-26 | 1967-04-04 | Union Carbide Corp | Fungicidal liquid concentrate with propylene glycol |
| DE3248115A1 (en) * | 1982-12-24 | 1984-06-28 | A.P.A.- Antiparassitari per Agricoltura S.p.A., Rovigo | Process for the preparation of dodecylguanidine acetate |
| WO2005014528A1 (en) * | 2003-07-22 | 2005-02-17 | Zhenhua Yang | Straight-chain and branched-chain lipid compounds as selective inhibitors of cyclooxygenase-2, anti-inflammatory agents, and anti-cancer agents |
| CN1629138A (en) * | 2004-08-24 | 2005-06-22 | 巨化集团公司 | Process for preparing n-dodecylguanidineacetate |
| CN101933522A (en) * | 2010-08-19 | 2011-01-05 | 沈金龙 | Dodecyl Robenidine hydrochloride sterilized algicide |
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