CN109912475A - A kind of environment-friendly preparation method thereof of Z-3- thiocyanate groups acrylamide compound - Google Patents
A kind of environment-friendly preparation method thereof of Z-3- thiocyanate groups acrylamide compound Download PDFInfo
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- CN109912475A CN109912475A CN201910228054.6A CN201910228054A CN109912475A CN 109912475 A CN109912475 A CN 109912475A CN 201910228054 A CN201910228054 A CN 201910228054A CN 109912475 A CN109912475 A CN 109912475A
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Abstract
The invention discloses a kind of environment-friendly preparation method thereofs of Z-3- thiocyanate groups acrylamide compound.Under ultrasonic wave effect, lactic acid is catalyzed propine amide compound, rhodanate and water and carries out three component addition reactions, generates Z-3- thiocyanate groups acrylamide compound；After reaction, water dilution is added into system, high-purity Z-3- thiocyanate groups acrylamide product can be precipitated；This method good product selectivity, high income, separation process is simple, catalyst low cost, environmentally friendly, is conducive to industrialized production and application.
Description
Technical field
The present invention relates to a kind of environment-friendly preparation method thereofs of Z-3- thiocyanate groups acrylamide compound, in particular to a kind of
Z-3- thiocyanic acid is synthesized using ultrasonic wave auxiliary lactic acid catalysis propine amide compound, rhodanate and one step addition reaction of water
The method of ester group acrylamide compound belongs to Manufacturing Technologies of Organic Intermediates field.
Background technique
Z-3- thiocyanate groups acrylamide compound not only has very important physiological activity, the thiocyanic acid contained
Ester functional group, alkenyl, amide group, which are all important, can modify functional group, be in a kind of very important drug and organic synthesis
Intermediate compounds therefor.There are three components of presence of acidic ionic liquid catalyst propine amide, rhodanate and water to react to obtain in the prior art
Z-3- thiocyanate groups acrylamide compound, such as (Green Chem. 2018,20,3683), but the reaction there is also
Following deficiency limits its practical application:
1) acidic ion liquid is toxic, preparation process also not environmentally, and at high cost, commercial-free product.
2) yield of Z-3- thiocyanate groups acrylamide compound is 81~83%, in reaction there are E formula isomers with
And the decomposition product propiolic acid and unreacted propine amide raw material, purity of propine amide be not high.
3) separation of product needs to extract using volatile organic solvent, and the purification of product is needed through silica gel column chromatography point
From separation process is not only complicated, at high cost, can also generation environment pollution.
4) acidic ionic liquid body circulation 5 times, efficiency reduce by 13%, higher operating costs.
The three components reaction synthesis Z-3- sulphur cyanogen of existing presence of acidic ionic liquid catalyst propine amide, rhodanate and water
The method concrete condition of perester radical acrylamide compound is as follows:
Summary of the invention
For the synthesis and separation of Z-3- thiocyanate groups acrylamide compound in the prior art,
Nontoxic, cheap lactic acid catalysis propine amide compound, rhodanate and water are utilized the purpose of the invention is to provide a kind of
The method that one pot reaction synthesizes Z-3- thiocyanate groups acrylamide compound, this method good product selectivity, high income, separation
Process is simple, low cost, environmental-friendly, is conducive to industrialized production and application.
In order to achieve the above technical purposes, the present invention provides a kind of the green of Z-3- thiocyanate groups acrylamide compound
Color preparation method, this method are under ultrasonic wave effect, and lactic acid is catalyzed propine amide compound, rhodanate and water and carries out addition
Reaction, obtains Z-3- thiocyanate groups acrylamide compound.
Preferred scheme, propine amide compound have 1 structure of formula；
Z-3- thiocyanate groups acrylamide compound has 2 structure of formula:
Wherein,
R is selected from alkyl or aryl
Preferred scheme, R can be alkyl, such as C1~C10Alkyl, such as straight chained alkyl, or branched alkane
Base, or be C3~C7Naphthenic base, specific such as methyl, ethyl, isobutyl group, cyclohexyl.R can be aryl, specifically
Aryl is the substituted-phenyl containing common substituent group on phenyl or phenyl ring, and substituted-phenyl is on phenyl ring comprising common substituent group,
Such as C1~C5Short-chain alkyl, C1~C5Alkoxy, halogenic substituent (fluorine, chlorine, bromine etc.), trifluoromethyl, nitro, cyano, ammonia
Base, C2~C5Ester group, hydroxyl.The position of substituent group is unlimited, and substituent group quantity can be one or more, generally contains one
Substituent group.
Preferred scheme, the rhodanate can be the ease of solubilities salt such as common potassium rhodanide, sodium sulfocyanate.Most preferably
For potassium rhodanide.
Preferred scheme, propine amide compound, potassium rhodanide, water and lactic acid molar ratio be 1:1~2:1~2:2~
5.Most preferred molar ratio is 1:1.2:1:4.
Preferred scheme, the condition of the addition reaction are as follows: at room temperature, ultrasonic power is 25~45W, and supersonic frequency is
28KHz~60KHz, reaction time are 15~40min.Ultrasonic power still more preferably is 35W.Still more preferably
Supersonic frequency is 40KHz.Lactic acid catalysis propine amide compound, rhodanate and water are carried out under preferred ultrasound condition auxiliary
Addition reaction, not only can shorten the reaction time, moreover it is possible to promote conversion ratio.
Preferred scheme after the completion of addition reaction, water dilution is added into reaction system, Z-3- thiocyanate groups third is precipitated
Acrylamide product realizes the separation of product and lactic acid aqueous solution, obtains Z-3- thiocyanate groups third by liquid separation or filtering
Enamides product.The present invention uses water diluting reaction mix products, and high-purity Z-3- thiocyanate groups third can be precipitated
Enamides do not need to extract using traditional organic solvent, silica gel column chromatography separation method, avoid volatile having completely
The use of solvent.
Preferred scheme, water additional amount are 5 times or more of lactic acid quality.It is preferred that water more than 5 times of quality, can guarantee Z-3-
Thiocyanate groups acrylamide compound is smoothly precipitated.
The lactic acid that the present invention uses is in addition reaction while being used as catalyst and reaction medium.
The present invention carries out addition reaction by propine amide compound, rhodanate (by taking potassium rhodanide as an example) and water and synthesizes Z-
The route of 3- thiocyanate groups acrylamide compound is as follows:
Shown in specific reaction principle following reaction formula: lactic acid activates propine amide compound first and obtains connection alkene intermediate
IM2, thiocyanate radical nucleophilic attack join alkene intermediate compound I M2 beta carbon after with lactic acid formed intermolecular hydrogen bonding, obtain intermediate
IM3；The proton that intermediate compound I M3 is generated from the capture hydrone ionization of the opposite direction of hydrogen bond, obtains trans-addition product Z-3- sulphur cyanogen
Perester radical acrylamide compound.
Compared with the prior art, technical solution of the present invention bring advantageous effects:
1) present invention is easily recycled using lactic acid as reaction medium and catalyst, safe and non-toxic, environmentally friendly,
Source is easy to get, cheap.
2) present invention reacts at room temperature, mild condition.
3) present invention is wide to the selectivity of propine amide compound, and functional group compatibility is good, is easy to various base group modifications.
4) present invention promotes reaction using ultrasonic wave, and while shortening the reaction time, feed stock conversion is quantitative, product choosing
Selecting property 100% does not have the generation of E formula isomers in reaction.
5) present invention only needs the water that 5 times of lactic acid quality amounts are added in the reactive mixture, and product layering can be made to be precipitated, obtained
To pure product, it is complicated to avoid the Z-3- thiocyanate groups acrylamide compound separating-purifying process synthesized in the prior art
Problem.
6) lactic acid of the invention can be recycled and is recycled for multiple times, and be recycled 5 times, and efficiency reduces by 3%, kept higher and urged
Change activity, has a clear superiority compared to acidic ion liquid.
7) Z-3- thiocyanate groups acrylamide compound of the invention has the thiocyanic acid functional group of important physiological activity
And alkenyl group, amide groups can be modified etc., important organic intermediate is provided for drug and organic synthesis.
Specific embodiment
Following specific embodiments are intended to further illustrate the content of present invention, rather than limit the protection of the claims in the present invention
Range.
Comparative examples:
Following control experiment group 1~19 is reacted by following reaction equation:
Concrete operation step are as follows: in 20mL reaction tube, sequentially add N- phenyl propyne amide (1 equivalent, 10mmol),
Rhodanate, water and biomass acid, gained mixed liquor supersonic reaction device in react 30min.After reaction, add
The water for entering 18ml, can be obtained target product.
Experimental group 1~3 has investigated various thiocyanic acid sources to N- phenyl propyne amide, potassium rhodanide, three component of water in upper table
The influence of addition reaction, from experimental data as can be seen that cheap potassium rhodanide can be with respect to sodium sulfocyanate or ammonium thiocyanate etc.
Significantly improve the efficiency of three component addition reactions.
Experimental group 1 and 4~5 has investigated reaction raw materials KSCN dosage to N- phenyl propyne amide, potassium rhodanide, water in upper table
The influence of three component addition reactions is shown experimentally that the optimum molar dosage of KSCN is 1.2 equivalents；When KSCN dosage is too low,
The yield of target product reduces, and further increases KSCN, and the yield of target product is not further added by.
Experimental group 1 and 6~7 has investigated the dosage of reaction raw materials water to N- phenyl propyne amide, potassium rhodanide, water in upper table
The influence of three component addition reactions is shown experimentally that the optimum molar dosage of KSCN is 1 equivalent；When the dosage of water is too low, mesh
The yield for marking product reduces, and further increases the dosage of water, and the yield of target product is not further added by.
Experimental group 8~13 has investigated various reaction mediums to N- phenyl propyne amide, potassium rhodanide, three component of water in upper table
The influence of addition reaction can be mentioned obviously from experimental data as can be seen that reacting other opposite reaction mediums in lactic acid medium
The efficiency of high three components addition reaction, and reacting has single reaction addition selective.
Experimental group 1 and 14~15 has investigated lactic acid dosage to N- phenyl propyne amide, potassium rhodanide, three component of water in upper table
The influence of addition reaction is shown experimentally that the optimum molar dosage of lactic acid is 4 equivalents；When lactic acid dosage is higher than 4 equivalent, instead
Efficiency is answered not improve；When lactic acid dosage is lower than 4 equivalent, the yield of target product is reduced.
Experimental group 1 and 16~19 has investigated ultrasonic wave added and has been total to addition to N- phenyl propyne amide, potassium rhodanide, water in upper table
The influence of reaction, is shown experimentally that and is reacted by ultrasonic wave added, can greatly shorten the reaction time, improves reaction efficiency, special
It is not ultrasonic power when to be 35W/ frequency be 40KHz, addition reaction effect is best altogether, can obtain within a short period of time optimal
Target product yield.
Circulation experiment result
In 20mL reaction tube, sequentially add N- phenyl propyne amide (10mmol), potassium rhodanide (12 mmol,
1.16g), water (10mmol, 0.18g), lactic acid (40mmol, 3.60g), ultrasonic reaction of the gained mixed liquor in 35W/40KHz fill
Set middle reaction 30 minutes.After reaction, 18ml water is added and lactic acid forms lactic acid aqueous solution, Z-3- thiocyanate groups acryloyl
Amine does not dissolve in lactic acid aqueous solution, is precipitated, liquid separation, is dried in vacuo calculated weight.The water in lactic acid aqueous solution is removed under reduced pressure, directly uses
In next circulation experiment, gained yield data is as follows.
| 1 | 2 | 3 | 4 | 5 |
| 94% | 94% | 93% | 92% | 91% |
Examples 1 to 2
It is reacted by following reaction equation following example 1~2:
Concrete operation step are as follows: in 20mL reaction tube, sequentially add propine amide (10mmol), potassium rhodanide
(12mmol, 1.16g), water (10mmol, 0.18g), lactic acid (40mmol, 3.60g), gained mixed liquor is in the super of 35W/40KHz
It is reacted 30 minutes in phonoresponse device.After reaction, 18ml water is added and lactic acid forms lactic acid aqueous solution, Z-3- thiocyanates
Base acrylamide does not dissolve in lactic acid aqueous solution, is precipitated, liquid separation, is dried in vacuo calculated weight.
Embodiment 1
Raw material:Target product:
Z-N-octyl-3-thiocyanatoacrylamide:
Yield: 93%.
1H NMR(400MHz,CDCl3) δ 7.16 (d, J=10.0Hz, 1H), 6.33 (d, J=10.0Hz, 1H), 5.82
(brs, 1H), 3.34 (q, J=6.8Hz, 2H), 1.57-1.50 (m, 2H), 1.33-1.27 (m, 2H), 2.54 (t, J=
6.8Hz,3H).
13C NMR(100MHz,CDCl3)δ162.1,126.3,125.9,107.5,39.9,31.8,29.5,29.2,
29.0, 26.9,22.7,14.2.
Embodiment 2
Raw material:Target product:
Z-N-phenyl-3-thiocyanatoacrylamide:
Yield: 94%.
1H NMR(400MHz,CDCl3) δ 8.17 (d, J=6.4Hz, 1H), 7.58-7.55 (m, 2H), 7.46-7.42 (m,
2H), 7.35-7.30 (m, 1H), 6.33 (d, J=6.4Hz, 1H)
13C NMR(100MHz,CDCl3)δ167.7,139.6,136.5,129.4,128.8,127.6,124.8,114.8。
Claims (8)
1. a kind of environment-friendly preparation method thereof of Z-3- thiocyanate groups acrylamide compound, it is characterised in that: acted in ultrasonic wave
Under, lactic acid is catalyzed propine amide compound, rhodanate and water and carries out addition reaction, obtains Z-3- thiocyanate groups acrylamide
Compound.
2. a kind of environment-friendly preparation method thereof of Z-3- thiocyanate groups acrylamide compound according to claim 1, special
Sign is:
The propine amide compound has 1 structure of formula；
The Z-3- thiocyanate groups acrylamide compound has 2 structure of formula:
Wherein,
R is alkyl or aryl.
3. a kind of environment-friendly preparation method thereof of Z-3- thiocyanate groups acrylamide compound according to claim 2, special
Sign is:
The alkyl includes C1~C10Alkyl；
The aryl includes phenyl, or includes C1~C5Alkyl, halogen, nitro, cyano, amino, C2~C5Ester group, hydroxyl
Base, trifluoromethyl, C1~C5At least one of alkoxy substituent group phenyl.
4. a kind of environment-friendly preparation method thereof of Z-3- thiocyanate groups acrylamide compound according to claim 1, special
Sign is: the rhodanate is potassium rhodanide and/or sodium sulfocyanate.
5. a kind of environment-friendly preparation method thereof of Z-3- thiocyanate groups acrylamide compound according to claim 1, special
Sign is: propine amide compound, rhodanate, water and lactic acid molar ratio be 1:1~2:1~2:2~5.
6. the green preparation of described in any item a kind of Z-3- thiocyanate groups acrylamide compounds according to claim 1~5
Method, it is characterised in that: the condition of the addition reaction are as follows: at room temperature, ultrasonic power is 25~45W, and supersonic frequency is
28KHz~60KHz, reaction time are 15~40min.
7. the green preparation of described in any item a kind of Z-3- thiocyanate groups acrylamide compounds according to claim 1~5
Method, it is characterised in that: after the completion of addition reaction, water dilution is added into reaction system, Z-3- thiocyanate groups propylene is precipitated
Amide compound, filtering or liquid separation, obtain Z-3- thiocyanate groups acrylamide compound.
8. a kind of environment-friendly preparation method thereof of Z-3- thiocyanate groups acrylamide compound according to claim 7, special
Sign is: water additional amount is 5 times or more of lactic acid quality.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109020855A (en) * | 2018-07-20 | 2018-12-18 | 湖南科技学院 | A kind of method of the halogenated -1- thiocyanate groups vinyl compound of ultrasonic-assisted synthesis Z-2- |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109020855A (en) * | 2018-07-20 | 2018-12-18 | 湖南科技学院 | A kind of method of the halogenated -1- thiocyanate groups vinyl compound of ultrasonic-assisted synthesis Z-2- |
Non-Patent Citations (2)
| Title |
|---|
| CHAO WU等: "Natural Deep Eutectic Solvent-Catalyzed Selenocyanation of Activated Alkynes via an Intermolecular H‑Bonding Activation Process", 《ACS SUSTAINABLE CHEM.ENG.》 * |
| CHAO WU等: "Ultrasound-promoted Brønsted acid ionic liquid-catalyzed hydrothiocyanation of activated alkynes under minimal solvent conditions", 《GREEN CHEMISTRY》 * |
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Application publication date: 20190621 |