CN100519542C - Method for synthesizing 4,6-disubstituted amido-1,3,5-triazine derivative - Google Patents
Method for synthesizing 4,6-disubstituted amido-1,3,5-triazine derivative Download PDFInfo
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- CN100519542C CN100519542C CNB2007100683817A CN200710068381A CN100519542C CN 100519542 C CN100519542 C CN 100519542C CN B2007100683817 A CNB2007100683817 A CN B2007100683817A CN 200710068381 A CN200710068381 A CN 200710068381A CN 100519542 C CN100519542 C CN 100519542C
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- 238000000034 method Methods 0.000 title description 13
- 230000002194 synthesizing effect Effects 0.000 title description 6
- 150000001412 amines Chemical class 0.000 claims abstract description 28
- -1 4, 6-disubstituted-amino-1, 3, 5-triazine Chemical class 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 150000002460 imidazoles Chemical class 0.000 claims abstract description 3
- 150000003222 pyridines Chemical class 0.000 claims abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 78
- 239000000243 solution Substances 0.000 claims description 53
- 239000002608 ionic liquid Substances 0.000 claims description 52
- 238000003756 stirring Methods 0.000 claims description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 claims description 37
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 26
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 239000007788 liquid Substances 0.000 claims description 17
- 239000000047 product Substances 0.000 claims description 17
- 238000010189 synthetic method Methods 0.000 claims description 17
- 238000005406 washing Methods 0.000 claims description 16
- 239000012065 filter cake Substances 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 13
- 238000000605 extraction Methods 0.000 claims description 13
- 239000000706 filtrate Substances 0.000 claims description 12
- 239000011541 reaction mixture Substances 0.000 claims description 12
- 238000001291 vacuum drying Methods 0.000 claims description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 11
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 10
- 238000006467 substitution reaction Methods 0.000 claims description 9
- 239000003513 alkali Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- FIDRAVVQGKNYQK-UHFFFAOYSA-N 1,2,3,4-tetrahydrotriazine Chemical class C1NNNC=C1 FIDRAVVQGKNYQK-UHFFFAOYSA-N 0.000 claims description 6
- 239000012670 alkaline solution Substances 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 150000002500 ions Chemical class 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 239000012141 concentrate Substances 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 241001597008 Nomeidae Species 0.000 abstract 1
- ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 abstract 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 15
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 10
- 230000003292 diminished effect Effects 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 230000006837 decompression Effects 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 235000017550 sodium carbonate Nutrition 0.000 description 9
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 6
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 5
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000012752 auxiliary agent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical class C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
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- Plural Heterocyclic Compounds (AREA)
- Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
Abstract
The invention discloses a clean manufacturing method of 4, 6-disubstituted-amino-1, 3, 5-triazine derivant, which comprises the following steps: adopting cyanuric acid and substituted amine as raw material; adopting imidazole salt, pyridine salt or quaternaries as ionic solution; simplifying the operation; reducing environmental pollution; improving receiving rate; fitting for large scale of industrial manufacturing.
Description
(1) technical field
The present invention relates to a kind of weedicide 4, the synthetic method of 6-disubstituted amido-1,3,5-triazines analog derivative, especially a kind of synthetic a series of 4 in ionic liquid by amine and cyanuric chloride, the method for 6-two replacement-1,3,5-triazines analog derivatives.
(2) background technology
The method of synthetic herbicide s-triazine derivative is a raw material with the amine of cyanuric chloride, different substituents normally, makes through two step substitution reactions, according to the difference of solvent for use, is divided into water method, solvent method and homogeneous phase hybrid system.
The water method is as medium with water.Because cyanuric chloride is slightly soluble in water, bad dispersibility in water adopts auxiliary agent that cyanuric chloride is dispersed in the water, drips amine then, makes acid binding agent with sodium hydroxide.The cyanuric chloride chemical property is active, and hydrolysis reaction takes place easily.Envrionment temperature raises, and hydrolysis reaction is accelerated.Adopt the lesser temps reaction can reduce the hydrolysis of cyanuric chloride, but induce reaction not exclusively.The yield of general product is about 91.5%.
Solvent method is a production method the earliest, is solvent with chlorobenzene etc.Because cyanuric chloride dissolves fully, do not exist and disperse and resolution problem, reaction effect is good, and yield also increases, about 93%.But owing to adopt a large amount of solvents, correspondingly increased solvent consumption, facility investment increases when producing.Recovered solvent needs through CaCl
2Ability reuse after dewatering, production cost is close with the water method.
The homogeneous phase hybrid system is the technology in generation nineteen ninety, promptly adopts water solubilizing agent blending agent, under the effect and relative low temperature of multiple auxiliary agent, makes the cyanuric chloride uniformly emulsify in mixed solution.Both avoid the inhomogeneous scattering problem of water method, significantly reduced the usage quantity of solvent again, had reaction effect preferably.Yield is greater than 94%.But because water is almost insoluble with organic solvent (as chlorobenzene), and exists the difference of density, must select suitable composite assistant for use, reach water oil emulsification homogeneous phase and mix, and reduce density variation, in the hope of blend.
Therefore, synthetic herbicide 4 in the exploitation ionic liquid, the novel method of 6-disubstituted amido-1,3,5-triazines analog derivative avoids that the pollution to environment has higher using value in the suitability for industrialized production.
(3) summary of the invention
The purpose of this invention is to provide a kind ofly 4, the clean production method of 6-disubstituted amido-1,3,5-triazines analog derivative makes the three wastes few, the yield height, and synthesis technique is simple to operate, is easy to control.
For realizing the object of the invention, the technical solution used in the present invention is as follows:
4,6-disubstituted amido-1,3, the synthetic method of 5-triazine derivative generally is to be raw material with cyanuric chloride, replacement amine, is substituted reaction and makes, synthetic method of the present invention comprises two step substitution reactions, described substitution reaction all is to carry out in ionic liquid under alkaline condition, and described ionic liquid is imidazole salt, pyridine salt or ion liquid of quaternaries, respectively suc as formula shown in (I), (II), (III):
R in the formula
1, R
6, R
11Be hydrogen atom or phenyl ring; R
2～R
5, R
7～R
10, R
12～R
14Independent separately is the alkyl of hydrogen atom or C1～C18, and L is BF
4, PF
6, OA
C, CF
3SO
3Or N (SO
2CF
3)
2
Particularly, synthetic method of the present invention comprises the steps:
(1) in ionic liquid, be cooled to-20～10 ℃, add cyanuric chloride, drip replacement amine A (R in 0～30 ℃
1-NH
2) solution, under this temperature, drip 10%～30% alkaline solution again, reaction 10～60min;
(2) temperature is raised to 15～75 ℃ gradually, drips replacement amine B (R
2-NH
2) solution; Under this temperature, drip 10%～30% alkaline solution again, dropwise the back in 15～75 ℃ of reaction 10～60min;
(3) after reaction finished, separation and purification obtained product (IV);
Wherein, R
1, R
2Be the alkyl of carbonatoms≤12, the cycloalkyl of carbonatoms≤8 or the aryl of carbonatoms≤10, replacing amine A can be identical with replacing amine B, also can be inequality.
The amount of substance that feeds intake of above-mentioned reaction is than cyanuric chloride: replace amine A: replace amine B: alkali is 1:1～1.5:1～1.5:2～2.5.Described ion liquid consumption is every mole of cyanuric chloride with 2～5kg.
Described alkaline solution is one of following: sodium hydroxide solution, potassium hydroxide solution, sodium carbonate solution.
Described separation and purification is cooled to normal temperature with reaction solution after reacting, add water washing, filters, and filter cake water, washed with dichloromethane, drying obtain target product (IV).Merging filtrate, filtrate is used dichloromethane extraction, and the extraction liquid anhydrous magnesium sulfate drying concentrates, and can reclaim methylene dichloride and ionic liquid respectively.
Further, described ionic liquid is preferably 1-alkyl-3-methyl imidazolium tetrafluoroborate or 1-alkyl-3-Methylimidazole hexafluorophosphate.One of more preferably following: 1-butyl-3-methyl imidazolium tetrafluoroborate, 1-ethyl-3-methyl imidazolium tetrafluoroborate, 1-butyl-3-Methylimidazole hexafluorophosphate, 1-ethyl-3-Methylimidazole hexafluorophosphate.
The amount of substance that feeds intake of described reaction is than cyanuric chloride: replace amine A: replace amine B: alkali is 1:1～1.5:1～1.5:2～2.5, be preferably 1: 1～1.1: 1～1.1: 2～2.2, more preferably 1: 1: 1: 2, ion liquid consumption is preferably every mole of cyanuric chloride 3kg.
Recommend the alkali sodium hydroxide in the building-up reactions of the present invention, solion [C
4Mim] BF
4, described reactant feeds intake amount of substance than cyanuric chloride: replace amine A: replace amine B: alkali is 1:1:1:2, ionic liquid [C
4Mim] BF
4Consumption be every mole of cyanuric chloride 3kg, carry out according to following steps:
(1) one substitution reaction: with ionic liquid [C
4Mim] BF
4Join in the reaction vessel, be cooled to-5 ℃, add cyanuric chloride rapidly, stir, drip replacement amine A solution in 5 ℃; After dripping end, under this temperature, drip 30% sodium hydroxide solution; Dropwise, continue to stir 10min;
(2) two substitution reactions: temperature is raised to 15 ℃ gradually, drips replacement amine B solution; After dripping end, under this temperature, drip 30% sodium hydroxide solution; Dropwise, continue to stir 30min;
(3) in reaction mixture, add entry, stir, filter, filter cake water, washed with dichloromethane, vacuum-drying obtains product (IV).
The present invention compared with prior art has following advantage:
(1) synthetic method is simple, mild condition.
(2) reaction times weak point, speed of response is fast.
(3) the cyanuric chloride hydrolysis is few, the yield height.
(4) ionic liquid recovery set usefulness, solvent treatment is simple, does not have waste, pollutes and lacks, and meets the requirement of Green Chemistry.
(5) synthetic is various 4, and 6-two replacement-1,3,5-triazines analog derivatives have weeding activity.
Method of the present invention is simple to operation, and environmental pollution is less, the yield height, and ionic liquid is recyclable to be applied mechanically, and is fit to carry out large-scale industrial production.
(4) embodiment:
Below with specific embodiment technical scheme of the present invention is described, but protection scope of the present invention is not limited thereto.
Synthesizing of embodiment 1:2-chloro-4-ethylamino--6-isopropylamine base-1,3,5-triazines
In the 250mL there-necked flask, add 100g ionic liquid [C
4Mim] BF
4, temperature is cooled to-20 ℃ with the cryosel bath, add cyanuric chloride 6.05g (0.0328mol) rapidly, after stirring, (contain Isopropylamine 1.92g, 0.0325mol) in the Isopropylamine solution 2.74g of 0 ℃ of dropping 70%.After dripping end, under this temperature, the sodium hydroxide solution 4.3g of dropping 30% (contains sodium hydroxide 1.3g, 0.0325mol).Dropwise, continue to stir 10min.
Temperature is raised to 15 ℃ gradually, (contain ethamine 1.5g, 0.0333mol), after dropping finished, under this temperature, the sodium hydroxide solution 4.48g of dropping 30% (contained sodium hydroxide 1.344g, 0.0336mol) to the ethylamine solution 2.3g of dropping 65%.Dropwise, continue to stir 30min.
Add 100mL water in reaction mixture, stir, filtration under diminished pressure, filter cake be water 20mL * 2, methylene dichloride 20mL * 3 washings respectively, drains.110 ℃ of following vacuum-dryings, obtain product 6.7g then, yield 95.7%, 172～174 ℃ of fusing points, MS m/z:215 (M
+, 58.9), 172 (20.9), 158 (11.9), 58 (99.9).
Filtrate extracts with methylene dichloride 30mL * 3.The extraction liquid anhydrous magnesium sulfate drying after reclaiming methylene dichloride under the Rotary Evaporators normal pressure, is warmed up to 85 ℃, and decompression 30min reclaims ionic liquid 92g.Ionic liquid is applied mechanically.
Synthesizing of embodiment 2:2-chloro-4-ethylamino--6-isopropylamine base-1,3,5-triazines
In the 250mL there-necked flask, add 67g ionic liquid [C
4Mim] PF
6, with the cryosel bath temperature is cooled to 0 ℃, add cyanuric chloride 6.05g (0.0328mol) rapidly.After stirring, begin to drip 65% ethylamine solution 2.50g and (contain ethamine 1.63g, 0.0361mol), maintain the temperature at 0 ℃ in the dropping process, after dropping finishes, under this temperature, the potassium hydroxide solution 6.13g of dropping 30% (contains potassium hydroxide 1.84g, 0.0328mol).Dropwise, continue to stir 30min.
Temperature is raised to 20 ℃ gradually, the Isopropylamine solution 2.81g of dropping 70% (contains Isopropylamine 1.96g, 0.0333mol).After dripping end, under this temperature, the potassium hydroxide solution 6.27g of dropping 30% (contains potassium hydroxide 1.88g, 0.0336mol).Dropwise, continue to stir 30min.
Add 100mL water in reaction mixture, stir, filtration under diminished pressure, filter cake be water 20mL * 2, methylene dichloride 20mL * 3 washings respectively, drains.110 ℃ of following vacuum-dryings, obtain target product 6.5g then, yield 932%.
Embodiment 3:2-chloro-4,6-diisopropylamino-1,3,5-triazines synthetic
In the 250mL there-necked flask, add 100g ionic liquid [C
4Mim] BF
4, with the cryosel bath temperature is cooled to 10 ℃, add cyanuric chloride 6.05g (0.0328mol) rapidly.After stirring, begin to drip 70% Isopropylamine solution 2.88g (contain Isopropylamine 2.02g, 0.0341mol), drip finish after, under this temperature, drip 10% sodium carbonate solution 36.1g and (contain yellow soda ash 3.61g, 0.0340mol).Dropwise, continue to stir 20min.
Temperature is raised to 50 ℃ gradually, (contain Isopropylamine 2.06g, 0.0350mol), after dropping finished, under this temperature, the sodium carbonate solution 37.1g of dropping 10% (contained yellow soda ash 3.71g, 0.0350mol) to the Isopropylamine solution 2.94g of dropping 70%.Dropwise, continue to stir 30min.
Add 100mL water in reaction mixture, stir, filtration under diminished pressure, filter cake be water 20mL * 2, methylene dichloride 20mL * 2 washings respectively, drains.110 ℃ of following vacuum-dryings, obtain product 7.2g then, yield 96.1%, 215～216 ℃ of fusing points, MS m/z:229 (M
+, 45.1), 214 (57.0), 172 (39.0), 58 (99.9).
After filtrate is placed, layering (upper strata is a water layer, and lower floor is an ionic liquid layer).After isolating ionic liquid layer, water layer extracts with methylene dichloride 30mL * 2.Merge above-mentioned washings, ionic liquid layer, extraction liquid, use anhydrous magnesium sulfate drying, after reclaiming methylene dichloride under the Rotary Evaporators normal pressure, be warmed up to 85 ℃, decompression 60min reclaims ionic liquid and applies mechanically.
Embodiment 4:2-chloro-4,6-diethylin-1,3,5-triazines synthetic
In the 250mL there-necked flask, add 80g ionic liquid [C
4Mim] PF
6, with water-bath temperature is cooled to 5 ℃, add cyanuric chloride 6.05g (0.0328mol) rapidly.After stirring, at 30 ℃, the ethylamine solution 2.27g of dropping 65% (contains ethamine 1.48g, 0.0328mol).After dripping end, under this temperature, the sodium hydroxide solution 6.55g of dropping 20% (contains sodium hydroxide 1.31g, 0.0328mol).Dropwise, continue to stir 30min.
Temperature is raised to 60 ℃ gradually, the ethylamine solution 2.3g of dropping 65% (contains ethamine 1.5g, 0.0333mol).After dripping end, under this temperature, the sodium hydroxide solution 6.72g of dropping 20% (contains sodium hydroxide 1.344g, 0.0336mol).Dropwise, continue to stir 10min.
Add 100mL water in reaction mixture, stir, filtration under diminished pressure, filter cake be water 20mL * 2, methylene dichloride 20mL washing respectively, drains.110 ℃ of following vacuum-dryings, obtain product 6.3g then, yield 95.5%, 223～225 ℃ of fusing points, MS m/z:201 (M
+, 99.9), 186 (58.5), 158 (27.5), 68 (91.8).
After filtrate is placed, layering (upper strata is a water layer, and lower floor is an ionic liquid layer).After isolating ionic liquid layer, water layer extracts with methylene dichloride 30mL * 2.Merge above-mentioned washings, ionic liquid layer, extraction liquid, use anhydrous magnesium sulfate drying, after reclaiming methylene dichloride under the Rotary Evaporators normal pressure, be warmed up to 85 ℃, decompression 60min reclaims ionic liquid and applies mechanically.
Embodiment 5:2-chloro-4,6-two normal hexyl Amine base-1,3,5-triazines synthetic
In the 250mL there-necked flask, add 90g ionic liquid [C
4Mim] OAc, with the cryosel bath temperature is cooled to 10 ℃, add cyanuric chloride 6.05g (0.0328mol) rapidly.After stirring, at 10 ℃, (contain normal hexyl Amine 3.96g, 0.0390mol), after dropping finished, under this temperature, the sodium hydroxide solution 13.2g of dropping 10% (contained sodium hydroxide 1.32g, 0.0330mol) to the normal hexyl Amine solution 5.66g of dropping 70%.Dropwise, continue to stir 60min.
Temperature is raised to 75 ℃ gradually, the normal hexyl Amine solution 5.66g of dropping 70% (contains normal hexyl Amine 3.96g, 0.0390mol).After dripping end, under this temperature, the sodium hydroxide solution 15.6g of dropping 10% (contains sodium hydroxide 1.56g, 0.0390mol).Dropwise, continue to stir 10min.
Add 100mL water in reaction mixture, stir, filtration under diminished pressure, filter cake be water 20mL * 2, methylene dichloride 20mL washing respectively, drains.110 ℃ of following vacuum-dryings, obtain product 9.56g then, yield 88.3%, fusing point 192～194.
After filtrate is placed, layering (upper strata is a water layer, and lower floor is an ionic liquid layer).After isolating ionic liquid layer, water layer extracts with methylene dichloride 30mL * 2.Merge above-mentioned washings, ionic liquid layer, extraction liquid, use anhydrous magnesium sulfate drying, after reclaiming methylene dichloride under the Rotary Evaporators normal pressure, be warmed up to 85 ℃, decompression 60min reclaims ionic liquid and applies mechanically.
Embodiment 6:2-chloro-4,6-dicyclohexyl amine base-1,3,5-triazines synthetic
In the 250mL there-necked flask, add 110g ionic liquid [C
2Mim] BF
4, temperature is cooled to-20 ℃ with the cryosel bath, add cyanuric chloride 6.05g (0.0328mol) rapidly.After stirring, begin to drip 70% hexahydroaniline solution 5.94g in 0 ℃ and (contain hexahydroaniline 4.16g, 0.0422mol).After dripping end, under this temperature, the sodium hydroxide solution 19.4g of dropping 10% (contains sodium hydroxide 1.94g, 0.0484mol).Dropwise, continue to stir 30min.
Temperature is raised to 15 ℃ gradually, the hexahydroaniline solution 6.13g of dropping 70% (contains hexahydroaniline 4.29g, 0.0433mol).After dripping end, under this temperature, the sodium hydroxide solution 4.48g of dropping 30% (contains sodium hydroxide 1.344g, 0.0336mol).Dropwise, continue to stir 60min.
Add 100mL water in reaction mixture, stir, filtration under diminished pressure, filter cake be water 20mL * 2, methylene dichloride 20mL * 3 washings respectively, drains.110 ℃ of following vacuum-dryings, obtain product 8.2g then, yield 81.2%, 238～240 ℃ of fusing points.
Filtrate extracts with methylene dichloride 30mL * 3.The extraction liquid anhydrous magnesium sulfate drying after reclaiming methylene dichloride under the Rotary Evaporators normal pressure, is warmed up to 85 ℃, and decompression 30min reclaims ionic liquid 94.0g.Ionic liquid is applied mechanically.
Embodiment 7:2-chloro-4,6-two cyclopropyl aminos-1,3,5-triazines synthetic
In the 250mL there-necked flask, add 100g ionic liquid [mPy] OAc, bathe with cryosel and temperature is cooled to-5 ℃, add cyanuric chloride 6.05g (0.0328mol) rapidly.After stirring, begin to drip 70% cyclopropylamine solution 3.80g in 5 ℃ and (contain cyclopropylamine 2.66g, 0.0455mol).After dripping end, under this temperature, the potassium hydroxide solution 19.6g of dropping 10% (contains potassium hydroxide 1.96g, 0.0350mol).Dropwise, continue to stir 40min.
Temperature is raised to 15 ℃ gradually, the cyclopropylamine solution 3.80g of dropping 70% (contains cyclopropylamine 2.66g, 0.0455mol).After dripping end, under this temperature, the potassium hydroxide solution 25.2g of dropping 10% (contains potassium hydroxide 2.52g, 0.0450mol).Dropwise, continue to stir 50min.
Add 100mL water in reaction mixture, stir, filtration under diminished pressure, filter cake be water 20mL * 2, methylene dichloride 20mL * 2 washings respectively, drains.110 ℃ of following vacuum-dryings, obtain product 4.9g then, yield 67.5%, 209～210 ℃ of fusing points.
After filtrate is placed, layering (upper strata is a water layer, and lower floor is an ionic liquid layer).After isolating ionic liquid layer, water layer extracts with methylene dichloride 30mL * 2.Merge above-mentioned washings, ionic liquid layer, extraction liquid, use anhydrous magnesium sulfate drying, after reclaiming methylene dichloride under the Rotary Evaporators normal pressure, be warmed up to 85 ℃, decompression 60min reclaims ionic liquid 87.0g and applies mechanically.
Synthesizing of embodiment 8:2-chloro-4-ethylamino--6-cyclopropyl amino-1,3,5-triazines
In the 250mL there-necked flask, add 130g ionic liquid [C
4Mim] BF
4, temperature is cooled to-5 ℃ with the cryosel bath, add cyanuric chloride 6.05g (0.0328mol) rapidly.After stirring, begin to drip 70% cyclopropylamine solution 4.11g in 5 ℃ and (contain cyclopropylamine 2.88g, 0.0492mol).After dripping end, under this temperature, the sodium hydroxide solution 4.4g of dropping 30% (contains sodium hydroxide 1.32g, 0.0330mol).Dropwise, continue to stir 10min.
Temperature is raised to 15 ℃ gradually, the ethylamine solution 2.73g of dropping 65% (contains ethamine 1.77g, 0.0492mol).After dripping end, under this temperature, the sodium hydroxide solution 6.53g of dropping 30% (contains sodium hydroxide 1.96g, 0.0490mol).Dropwise, continue to stir 40min.
Add 100mL water in reaction mixture, stir, filtration under diminished pressure, filter cake be water 20mL * 2, methylene dichloride 20mL * 3 washings respectively, drains.110 ℃ of following vacuum-dryings, obtain target product 4.2g then, yield 60.6%, 198～200 ℃ of fusing points.
Filtrate extracts with methylene dichloride 30mL * 3.The extraction liquid anhydrous magnesium sulfate drying after reclaiming methylene dichloride under the Rotary Evaporators normal pressure, is warmed up to 85 ℃, and decompression 30min reclaims ionic liquid and applies mechanically.
Synthesizing of embodiment 9:2-chloro-4-isopropylamine base-6-cyclopropyl amino-1,3,5-triazines
In the 250mL there-necked flask, add 165g ionic liquid [C
4Mim] BF
4, temperature is cooled to-5 ℃ with the cryosel bath, add cyanuric chloride 6.05g (0.0328mol) rapidly.After stirring, begin to drip 70% cyclopropylamine solution 2.76g in 20 ℃ and (contain cyclopropylamine 1.93g, 0.0330mol).After dripping end, under this temperature, the potassium hydroxide solution 9.2g of dropping 20% (contains potassium hydroxide 1.84g, 0.0329mol).Dropwise, continue to stir 10min.
Temperature is raised to 25 ℃ gradually, the Isopropylamine solution 2.8g of dropping 70% (contains Isopropylamine 1.96g, 0.0333mol).After dripping end, under this temperature, the potassium hydroxide solution 11.9g of dropping 20% (contains potassium hydroxide 2.38g, 0.0425mol).Dropwise, continue to stir 30min.
Add 100mL water in reaction mixture, stir, filtration under diminished pressure, filter cake be water 20mL * 2, methylene dichloride 20mL * 3 washings respectively, drains.110 ℃ of following vacuum-dryings, obtain target product 7.0g then, yield 94.4%, 165～166 ℃ of fusing points.
Filtrate extracts with methylene dichloride 30mL * 3.The extraction liquid anhydrous magnesium sulfate drying after reclaiming methylene dichloride under the Rotary Evaporators normal pressure, is warmed up to 85 ℃, and decompression 30min reclaims ionic liquid and applies mechanically.
Synthesizing of embodiment 10:2-chloro-4-cyclopropyl amino-6-cyclohexylamino-1,3,5-triazines
In the 250mL there-necked flask, add 100g ionic liquid [C
2Mim] PF
6, temperature is cooled to-5 ℃ with the cryosel bath, add cyanuric chloride 6.05g (0.0328mol) rapidly.After stirring, begin to drip 70% hexahydroaniline solution 4.7g in 10 ℃ and (contain hexahydroaniline 3.3g, 0.0335mol).After dripping end, under this temperature, the sodium carbonate solution 17.4g of dropping 20% (contains yellow soda ash 3.48g, 0.0328mol).Dropwise, continue to stir 10min.
Temperature is raised to 15 ℃ gradually, the cyclopropylamine solution 2.89g of dropping 70% (contains cyclopropylamine 2.02g, 0.0345mol).After dripping end, under this temperature, the sodium carbonate solution 20.9g of dropping 20% (contains yellow soda ash 4.18g, 0.0394mol).Dropwise, continue to stir 30min.
Add 100mL water in reaction mixture, stir, filtration under diminished pressure, filter cake be water 20mL * 2, methylene dichloride 20mL * 2 washings respectively, drains.110 ℃ of following vacuum-dryings, obtain product 8.1g then, yield 93.4%, 153～155 ℃ of fusing points.
Filtrate extracts with methylene dichloride 30mL * 3.The extraction liquid anhydrous magnesium sulfate drying after reclaiming methylene dichloride under the Rotary Evaporators normal pressure, is warmed up to 85 ℃, and decompression 30min reclaims ionic liquid and applies mechanically.
Claims (9)
1. one kind 4,6-disubstituted amido-1,3, the synthetic method of 5-triazine derivative is to be raw material with cyanuric chloride, replacement amine, is substituted reaction and makes, it is characterized in that described synthetic method comprises two step substitution reactions, described substitution reaction all is to carry out in ionic liquid under alkaline condition, and described ionic liquid is imidazole salt, pyridine salt or ion liquid of quaternaries, respectively suc as formula shown in (I), (II), (III):
R in the formula
1, R
6, R
11Be hydrogen atom or phenyl ring; R
2～R
5, R
7～R
10, R
12～R
14Independent separately is the alkyl of hydrogen atom or C1～C18, and L is BF
4, PF
6Or OAc;
Described synthetic method comprises the steps:
(1) in ionic liquid, be cooled to-20～10 ℃, add cyanuric chloride, drip replacement amine A (R in 0～30 ℃
1-NH
2) solution; Under this temperature, drip 10%～30% alkaline solution again, reaction 10～60min;
(2) temperature is raised to 15～75 ℃ gradually, drips replacement amine B (R
2-NH
2) solution; Under this temperature, drip 10%～30% alkaline solution again, dropwise the back in 15～75 ℃ of reaction 10～60min;
(3) after reaction finished, separation and purification obtained product (IV);
Wherein, R
1, R
2Be the alkyl of carbonatoms≤12, the cycloalkyl of carbonatoms≤8 or the aryl of carbonatoms≤10.
2. as claimed in claim 14,6-disubstituted amido-1,3, the synthetic method of 5-triazine derivative, it is characterized in that feeding intake amount of substance than cyanuric chloride: replace amine A: replace amine B: alkali is 1:1～1.5:1～1.5:2～2.5, and described ion liquid consumption is every mole of cyanuric chloride with 2～5kg.
3. as claimed in claim 1 or 24, the synthetic method of 6-disubstituted amido-1,3,5-triazines analog derivative is characterized in that described alkaline solution is one of following: sodium hydroxide solution, potassium hydroxide solution, sodium carbonate solution.
4. as claimed in claim 14,6-disubstituted amido-1,3, the synthetic method of 5-triazine derivative is characterized in that after described separation and purification is for reaction reaction solution being cooled to normal temperature, adds water washing, filter, filter cake water, washed with dichloromethane, drying obtain target product (IV).
5. as claimed in claim 44, the synthetic method of 6-disubstituted amido-1,3,5-triazines analog derivative is characterized in that filtrate uses dichloromethane extraction, and the extraction liquid anhydrous magnesium sulfate drying concentrates, and reclaims methylene dichloride and ionic liquid respectively.
6. as claimed in claim 14, the synthetic method of 6-disubstituted amido-1,3,5-triazines analog derivative is characterized in that described ionic liquid is 1-alkyl-3-methyl imidazolium tetrafluoroborate or 1-alkyl-3-Methylimidazole hexafluorophosphate.
7. as claimed in claim 64,6-disubstituted amido-1,3, the synthetic method of 5-triazine derivative is characterized in that described ionic liquid is one of following: 1-butyl-3-methyl imidazolium tetrafluoroborate, 1-ethyl-3-methyl imidazolium tetrafluoroborate, 1-butyl-3-Methylimidazole hexafluorophosphate, 1-ethyl-3-Methylimidazole hexafluorophosphate.
8. as claimed in claim 24,6-disubstituted amido-1,3, the synthetic method of 5-triazine derivative, it is characterized in that feeding intake amount of substance than cyanuric chloride: replace amine A: replace amine B: alkali is 1:1～1.1:1～1.1:2～2.2, and described ion liquid consumption is every mole of cyanuric chloride 3kg.
9. as claimed in claim 14, the synthetic method of 6-disubstituted amido-1,3,5-triazines analog derivative, it is characterized in that described reactant feeds intake amount of substance than cyanuric chloride: replace amine A: replace amine B: alkali is 1:1:1:2, ionic liquid [C
4Mim] BF
4Consumption be every mole of cyanuric chloride 3kg, carry out according to following steps:
(1) one substitution reaction: with ionic liquid [C
4Mim] BF
4Join in the reaction vessel, be cooled to-5 ℃, add cyanuric chloride rapidly, stir, drip replacement amine A solution in 5 ℃; After dripping end, under this temperature, drip 30% sodium hydroxide solution; Dropwise, continue to stir 10min;
(2) two substitution reactions: temperature is raised to 15 ℃ gradually, drips replacement amine B solution; After dripping end, under this temperature, drip 30% sodium hydroxide solution; Dropwise, continue to stir 30min;
(3) in reaction mixture, add entry, stir, filter, filter cake water, washed with dichloromethane, vacuum-drying obtains product (IV).
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| CN101502265B (en) * | 2009-03-06 | 2011-11-23 | 山东潍坊润丰化工有限公司 | Method for catalytic synthesis of triazine herbicide |
| CN102295614B (en) * | 2011-07-01 | 2013-12-25 | 安徽中天化工有限公司 | Synthetic method of 2-methyl-4-dimethylamino-6-methoxy-1,3,5-triazine |
| CN102344422B (en) * | 2011-11-01 | 2014-03-26 | 山东胜邦绿野化学有限公司 | Novel synthesis process of atrazine |
| CN103571566B (en) * | 2012-07-30 | 2015-05-20 | 中国科学院兰州化学物理研究所 | S-triazine ionic liquid used as lubricant and preparation method thereof |
| CN107903384B (en) * | 2017-11-23 | 2019-07-23 | 武汉理工大学 | Flame retardant type Imidazole Type Latent Curing Agent and preparation method thereof |
| CN114230535A (en) * | 2021-12-31 | 2022-03-25 | 浙江工业大学 | Method for synthesizing triazine compound intermediate under catalysis of ionic liquid |
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