CN1158845A - New N-alkyl-cyano pyridone synthesizing method - Google Patents
New N-alkyl-cyano pyridone synthesizing method Download PDFInfo
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- CN1158845A CN1158845A CN 96102456 CN96102456A CN1158845A CN 1158845 A CN1158845 A CN 1158845A CN 96102456 CN96102456 CN 96102456 CN 96102456 A CN96102456 A CN 96102456A CN 1158845 A CN1158845 A CN 1158845A
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Abstract
In the new method, cyano-acetamide, acetoacetate and ammonia water reflux-react to obtain N-alkyl-cyano pyridone under the normal pressure or pressurized condition and at 50-150 deg.C. The reaction yield is higher than 90%.
Description
The present invention proposes a kind of synthetic method of new N-alkyl-cyano pyridone, and wherein the structural formula of N-alkyl-cyano pyridone is shown in (I):
R is the aliphatic chain of H or 1～6 carbon atom.This method is by Malonamide nitrile (I), wherein R with
(I) same meaning in the formula, or have the mixture of capacity Malonamide nitrile (I), under 50～150 ℃ of conditions, with solution state or suspended state, under the catalysis of minimum 1mol ammoniacal liquor (III), with acetylacetic ester (IV),
R
1Can be 1～8 fat of carbon atom chain, be preferably 3～6 fat of carbon atom chain back flow reaction and get.
Reaction equation is:
The N-alkyl-cyano pyridone is a kind of crucial N heterogeneous ring compound, in dyestuff, agricultural chemicals, medicine and other fields crucial purposes is arranged all.N-alkyl-cyano pyridone find first in the reaction of beta-keto acid esters and Malonamide nitrile by Guarsehi and note down (Mem.Accad.[2] volume 46, page 11Chemicals 1896 I, 601).Germany publication No 2,531, introduce Malonamide nitrile and methyl aceto acetate in 035 and in piperidines or sodium alkoxide, reacted acquisition N-alkyl-cyano pyridone, this is a synthetic method of introducing the N-alkyl-cyano pyridone as patented technology first, but this method exists the solvent complexity, the shortcoming that yield is lower.In other document (Journal of Organic Chemistry, Volume 25 (1960) pages 560～564), made research report about this respect technological improvement.At German publication No1, propose in 956,142 to utilize Fatty Alcohol(C12-C14 and C12-C18) to react as solvent, after reaction process finishes, separate the solvent alcohols with distillation method, separate out again and product.With the example that synthesizes of N-methyl-Cyanopyridone, need to use ethyl cyanoacetate 1mol, methyl aceto acetate 1mol, amine 2mol, butanols are as solvent, and reaction times 16hr, yield are 80%.This method shortcoming is long reaction time, and yield is relatively low, reclaims solvent and consumes energy bigger.United States Patent (USP) U.S.P 4,284,782 proposes in entire reaction on the basis of this method
System in add water and react, can improve the yield of reaction, N-butyl-Cyanopyridone can reach 85% to 95% respectively to the yield of N-H-Cyanopyridone.The principal feature of this method is to add a certain amount of water in reaction system, is generally 10%～1000%, is preferably 50～500%, and its advantage is that yield improves, and the purity requirement of raw material is reduced, the aqueous solution of available amine, or its mixture reacts.But this method still exists following shortcoming: the recovery of the raw material amine of excessive part still needs power consumption bigger; Reclaim halfway amine and can cause big pollution; Yield descends with the growth of R carbochain in general; R is long more in the process that cooling is separated out, and product may exist with tar attitude form more, separates out difficulty, seldom arrives product, is reflected under the pressurized conditions and carries out, and to the equipment requirements height, above problem directly influences the synthetic of N-alkyl-cyano pyridone (I) and produces.
The present invention is through discovering, by patent U.S.P4,284,782 in N-alkyl-cyano pyridone building-up process, and excessive 1mol amine role in reaction mainly is a catalyst for reaction, and the weakly alkaline effect of reaction environment is provided.But the existence of excess fats amine, its organic solvent effect that has reduces the finished product yield on the one hand, as the existence of organic solvent, product is separated out with the tar attitude simultaneously.
The present invention is when announcement excess fat amine exists the reaction system pros and cons, also point out with aqueous ammonia to replace excess fats amine, the catalytic effect and the weakly alkaline effect that both can keep original excess amine, eliminated simultaneously the organic solvent reaction of aliphatic amide again, and the situation of having avoided product to separate out with the tar attitude.
The present invention also points out simultaneously, U.S.P4, and the essence of pressure process is to improve the boiling point of reaction product by pressurization in 284,782, shortens the reaction times.
The present invention has proposed the new synthetic method of N-alkyl-cyano pyridone (I) on this basis.
Malonamide nitrile (II) or have the mixture of capacity Malonamide nitrile (II) is under 50～150 ℃ of conditions, with solution or suspended state, under the catalysis of minimum 1mol ammonia, get with acetylacetic ester (IV) back flow reaction, yield is more than 90%, and N-H-Cyanopyridone yield reaches 98%.
This synthetic method proposed by the invention, it is low to have a cost, with 1molNH
3Replace excess fats amine, reduced reaction cost, improved reaction yield simultaneously, bring up to 90% by 85% of the past, product appearance is good, becomes present white by original grey; Reaction conditions is more simple, not only can react under pressurized conditions, and can carry out under normal temperature condition.
The present invention has also introduced basic raw material, the building-up reactions of Malonamide nitrile simultaneously in the new synthetic method that proposes the N-alkyl-cyano pyridone.
Malonamide nitrile (II) can pass through ethyl cyanoacetate (VI) (R
2Can be 1～6 carbon alkyl, be preferably 2～3 alkyl chain length) and amine (VII), R is consistent with (I) meaning, the reaction and get, ethyl cyanoacetate then can by Mono Chloro Acetic Acid and sodium cyanide react cyanoacetic acid, the cyanoacetic acid resterification and ethyl cyanoacetate, in the process program that the present invention proposes, promptly adopt the reaction of ethyl cyanoacetate and amine obtain Malonamide nitrile again with methyl aceto acetate in the presence of ammoniacal liquor, condensation ring-closure reaction and must the N-alkyl-cyano pyridone.
The present invention proposes two kinds of concrete process programs
Pressurization step feeding scheme
Molar ratio: (amine: ethyl cyanoacetate: methyl aceto acetate: ammonia) be not less than 1.0: 1.0: 1.0: 1.0, be (1.0～4.0: 1: 1.0～4.0: 1.0～4.0) generally speaking.Operating process: earlier ethyl cyanoacetate is joined in the amine, stirring at normal temperature 0.5～8hr, add methyl aceto acetate and ammoniacal liquor, be warmed up to more than 100 ℃, pressure is the pressure that reactant self produces, and the reaction times is no less than 5hr, after the reactant cooling, through dilute, neutralize, filter, wash product, product yield is 90.0%.
Normal pressure step feeding scheme: (amine: ethyl cyanoacetate: methyl aceto acetate: ammonia) be not less than 1.0～1.0: generally speaking be (1.0～4.0: 1: 1.0～4.0: 1.0～4.0) to molar ratio at 1.0: 1.0.Operating process: earlier ethyl cyanoacetate is joined in the amine, normal temperature stirs 0.5～8hr down, add methyl aceto acetate and ammoniacal liquor, be warmed up to backflow, return time is no less than 12hr, is generally 14～20hr, after the reactant cooling, through dilution neutralization, filter, washing reflux product, product yield is 90.0%.
Pressurization step feeding scheme, two kinds of methods of normal pressure step feeding scheme and existing document, the synthetic method of mentioning in the patent is compared, and it is few to have the reaction times, the advantage that equipment requirements is low.
In sum, the present invention proposes a kind of synthetic method of new N-alkyl-cyano pyridone (I).
The present invention is by following example, and the synthetic method of the N-alkyl-cyano pyridone that proposes is described further.
Embodiment
Synthetic (the pressurization step feeding scheme) of example 1:N-ethyl-Cyanopyridone
The ethyl cyanoacetate of 11.3g is mixed stirring 3 hours at normal temperatures with the ethamine of 5.2g, then, add methyl aceto acetate 14.3g, ammoniacal liquor 10ml, sealed reaction, be warmed up to 140 ℃, reacted 6 hours, then reaction mixture is cooled off, again with the dilution of 200ml water, with 10% hydrochloric acid adjust pH is 5～6, and filtration drying gets product, and fusing point is that 184～185 ℃ of yields are 90.0%.
Synthetic (the normal pressure step feeding scheme) of example 2:N-ethyl-Cyanopyridone
The ethyl cyanoacetate of 11.3g is mixed stirring 3 hours at normal temperatures with the ethamine of 5.2g, then, add methyl aceto acetate 14.3g ammoniacal liquor 10ml, back flow reaction 18 hours is after the reaction mixture cooling, with the dilution of 200ml water, hydrochloric acid adjust pH with 10% is 5～6, and filtration drying gets product.Fusing point is that 184～185 ℃ of yields are 90.0%.
Synthetic (the pressurization step feeding scheme) of example 3:N-(γ-methoxy-propyl)-Cyanopyridone
The ethyl cyanoacetate of 11.3g is mixed at normal temperatures with γ-methoxy propanamine of 10.3g, stirred 3 hours, then, add methyl aceto acetate 14.3g, ammoniacal liquor 10ml, sealed reaction 14 hours is after the reaction mixture cooling, dilute with 200ml water, with 10% hydrochloric acid adjust pH is 5～6, filters, the dry product that gets, fusing point is 200～201 ℃, and yield is 90.0%.
Synthetic (the normal pressure step feeding) of example 4:N-(γ-methoxy-propyl)-Cyanopyridone
The ethyl cyanoacetate of 11.3g is mixed stirring 3 hours at normal temperatures with γ-methoxy propanamine of 10.3g, then, add methyl aceto acetate 14.3g, ammoniacal liquor 10ml, back flow reaction 14 hours, after the reaction mixture cooling,, be 5～6 with 10% hydrochloric acid adjust pH with the dilution of 200ml water, filter, the dry product that gets, fusing point is 200～201 ℃, yield is 90%.
Synthetic (the pressurization step feeding) of example 5:N-butyl-Cyanopyridone
The ethyl cyanoacetate of 11.3g is mixed stirring 3 hours at normal temperatures with the 9.0g n-Butyl Amine 99, then, add methyl aceto acetate 14.3g, ammoniacal liquor 10ml, sealed reaction is warmed up to 140 ℃, reacted 6 hours, after the reaction mixture cooling, with the dilution of 200ml water, with 10% hydrochloric acid adjust pH is 5～6, filtration drying gets product, and fusing point is 220 ℃～221 ℃, and yield is 90%.
Synthetic (the normal pressure step feeding) of example 6:N-butyl-Cyanopyridone
The ethyl cyanoacetate of 11.3g is mixed stirring 3 hours at normal temperatures with the n-Butyl Amine 99 of 9.0g, add methyl aceto acetate 14.3g then, ammoniacal liquor 10ml, back flow reaction 14 hours is after the reaction mixture cooling, with the dilution of 200ml water, with 10% hydrochloric acid adjust pH is 5～6, filter, the dry product that gets, fusing point is that 220 ℃～221 ℃ yields are: 90.0%.
Claims (4)
1.N-the new synthetic method of alkyl-cyano pyridone (I).This method obtains with the reaction of etheric acid (IV) ethyl ester in the presence of ammoniacal liquor (III) by Malonamide nitrile (II).R is H, the alkyl of 1～6 carbon atom, R
2OR
3(R
2, R
3Be 1～6 carbon atom alkyl), R
1It is the alkyl of 1～8 carbon atom.
2. according on the basis in 1, the pressurization step feeding method that is proposed: molar ratio (amine: ethyl cyanoacetate: methyl aceto acetate: be 1.0～1.0 ammonia): more than 1.0: 1.0, be generally 1.0～4.0: 1: 1.0～4.0: 1.0～4.0, amine and ethyl cyanoacetate reaction 0.5～8hr, after adding methyl aceto acetate and ammoniacal liquor, when compressive reaction is no less than 5hr, through dilute, neutralize, filter, wash product, yield is 90.0%.
3. according on the basis in 1, the normal pressure step feeding method that is proposed: molar ratio (amine: ethyl cyanoacetate: methyl aceto acetate: amine) be no less than 1.0: 1.0: 1.0: more than 1.0, be generally 1.0～4.0: 1: 1.0～4.0: 1.0～4.0, amine and ethyl cyanoacetate reaction 0.5～8hr, add methyl aceto acetate and ammoniacal liquor, normal temperature refluxes and to be no less than 10hr, through rare, release neutralization, filtration, wash and get, yield is 90.0%.
4. according on the basis in 1, N-ethyl-Cyanopyridone of being lifted, N-γ-methoxy-propyl-cyano group yl pyridines ketone, N-butyl-Cyanopyridone normal pressure, compressive reaction example.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96102456 CN1158845A (en) | 1996-03-04 | 1996-03-04 | New N-alkyl-cyano pyridone synthesizing method |
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| CN 96102456 CN1158845A (en) | 1996-03-04 | 1996-03-04 | New N-alkyl-cyano pyridone synthesizing method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558749A (en) * | 2018-05-12 | 2018-09-21 | 长乐智高生物科技有限公司 | It is a kind of synthesis 2,6- dihydroxy -3- cyano -4- trifluoromethyl pyridines catalyst and its application |
| CN108587229A (en) * | 2018-06-05 | 2018-09-28 | 杭州吉华江东化工有限公司 | A kind of preparation process containing pyridone structure disperse dyes and application |
-
1996
- 1996-03-04 CN CN 96102456 patent/CN1158845A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558749A (en) * | 2018-05-12 | 2018-09-21 | 长乐智高生物科技有限公司 | It is a kind of synthesis 2,6- dihydroxy -3- cyano -4- trifluoromethyl pyridines catalyst and its application |
| CN108587229A (en) * | 2018-06-05 | 2018-09-28 | 杭州吉华江东化工有限公司 | A kind of preparation process containing pyridone structure disperse dyes and application |
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