CN103497163A - Synthesis method of dimethyl isobutyl pyrazine - Google Patents
Synthesis method of dimethyl isobutyl pyrazine Download PDFInfo
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Abstract
The invention provides a synthesis method of 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine. The synthesis method comprises the following steps: heating 5-methyl-2,3-hexanedione and 1,2-propane diamine in ethanol to react to generate an intermediate product; adding copper oxide into the reaction system obtained in step S1 to oxidize the intermediate product to 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine; and rectifying the reaction liquid obtained in the step S2 to obtain the 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine. Compared with the prior art, the technical scheme of the invention improves the synthetic reaction yield, reduces the cost and especially improves the product purity to a large extent so as to make the fragrance of the product purer.
Description
Technical field
The present invention relates to the chemical intermediate synthetic method, relate in particular to the synthetic method of 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine.
Background technology
3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine are intermediates good in medicine and synthetic perfume industry.Pyrazine compound is widely used in the food blending, odour characteristics is very outstanding, mostly there is coffee aroma, cocoa aroma and bake burnt sample fragrance, be widely used in the blending of coffee, cocoa, walnut, peanut, sesame, cream, chocolate, candy, beverage, biscuit, tobacco and wine, only need to add 1-2ppm, just can play obvious flavouring effect.At present, China has obtained some achievements in pyrazine class flavor compounds study on the synthesis, have more than 10 the synthetic of kind pyrazine class spices to realize commercialization, but this also can not meet the requirement of blending far away.External realized commercialization and reached kind more than 40 for the product of perfuming.Therefore for China's chemical enterprise, further strengthen the research of pyrazine class flavor compounds synthetic process is very important.
For 3,5-dimethyl-2-isobutyl pyrazine and 3, synthesizing of 6-dimethyl-these two kinds of compounds of 2-isobutyl pyrazine, it is 93113380.5 that application number is arranged, and the European patent that publication number is 0590296B1 has been reported a kind of method of utilizing pyruvic alcohol and corresponding aldehyde to become the described product of ring preparation in ammonium acetate, sodium acetate aqueous solution.Yet, in the method, the yield of 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine only has 23.2%.Although the raw material that method adopts is comparatively cheap and easy to get, yield is too low, can not meet well the needs of actual production.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of 3 of higher yields that has, the synthetic method of 5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine.
For solving the problems of the technologies described above, the technical solution used in the present invention is:
The method of a kind of synthetic 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine comprises the following steps:
S1,5-methyl-2,3-hexanedione and 1,2-propylene diamine reacting by heating in ethanol, generate 5-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine and 6-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine;
S2, add cupric oxide in S1 gained reaction system, 5-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine and 6-isobutyl--2,6-dimethyl-2, the oxidized generation 3 of 3-dihydro pyrazine, 5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine;
S3, rectification process S2 gained reaction solution, obtain 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine.
Preferably, in the method for described synthetic 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, step S1 specifically comprises the steps:
S11, add ethanol in reactor, the 5-methyl-2 that will to account for total reactant per-cent be 5 ± 2%, 3-hexanedione and 1,2-propylene diamine add reactor, while feeding intake, keep material evenly to mix;
S12, in 60-90 minute, residual reactant is added to reactor, feed intake at every turn and add 5-methyl-2 simultaneously, 3-hexanedione and 1,2-propylene diamine, and by controlling rate of feeding, temperature of reaction system is controlled to 45 ± 5 ℃;
S13, maintenance material evenly are mixed to reaction to be finished.
Preferably, described synthetic 3,5-dimethyl-2-isobutyl pyrazine and 3, in the method for 6-dimethyl-2-isobutyl pyrazine, start to add 5-methyl-2,3-hexanedione and 1,2-propylene diamine post-heating to 40 ± 2 ℃, and by controlling rate of feeding, temperature of reaction system is controlled to 45 ± 5 ℃ in the process of feeding intake.
Preferably, in the method for described synthetic 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, step S2 specifically comprises the steps:
S21, S1 gained reaction solution is cooled to 30 ± 2 ℃, adds potassium hydroxide, continue to stir 30 ± 5 minutes;
S22, slowly be heated to 50 ± 2 ℃, stop heating, add cupric oxide;
S23, slowly be heated to 80 ± 2 ℃, stop heating;
S24, waiting temperature rise to 90 ± 2 ℃, produce and reflux; Keep backflow 80-100 minute, the assurance oxidizing reaction is carried out continuously until react end;
S25, be cooled to 30 ± 2 ℃, filter to isolate cupric oxide, obtain reaction solution;
Slowly be heated to be the heating that rate of rise in temperature is not more than 0.5 ℃/minute described in step S22 and S23.
Preferably, in the method for described synthetic 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, step S3 is specially:
S31, rectification step S2 gained reaction solution, reclaim ethanol;
S32, S31 is removed to ethanol gained reaction solution separate organic phase and water;
S33, get S32 gained organic phase, rectifying obtains the first crude product;
S34, in the first crude product, add potassium hydroxide, mix, separate organic phase and water, get organic phase, obtain the second crude product;
S35, rectifying the second crude product, obtain product 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine.
Preferably, in the method for described synthetic 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, step S31 is specially:
Rectification step S2 gained reaction solution under normal pressure is to reclaim ethanol under 105 ± 2 ℃, the reflux ratio condition that is 1 in the tower reactor temperature.
Preferably, in the method for described synthetic 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, step S32 is specially:
Step S31 is removed to ethanol gained reaction solution and be cooled to 30 ℃, separate organic phase and water, obtain organic phase.
Preferably, in the method for described synthetic 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, step S33 is specially:
In vacuum tightness, be separating alcohol under 300 ± 50mbar and the reflux ratio condition that is 1, rectifying goes out described the first crude product.
Preferably, in the method for described synthetic 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, step S34 is specially:
Described the first crude product is put into to clean container, add potassium hydroxide;
Keep material evenly to mix 30 ± 10 minutes, separate organic phase and water, get organic phase, obtain the second crude product.
Preferably, in the method for described synthetic 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, step S35 is specially:
Vacuum tightness be 10-100mbar, reflux ratio be 0.1 and the tower top temperature condition that is 70-120 ℃ under collect product 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine.
After adopting above technical scheme, the beneficial effect that the present invention has is: compared with prior art, improved the building-up reactions yield, reduced cost; Particularly greatly promote product purity, made product fragrance more pure.
The accompanying drawing explanation
The main route schematic diagram that Fig. 1 is building-up reactions of the present invention.
Embodiment
By describing technology contents of the present invention, structural attitude in detail, being realized purpose and effect, below in conjunction with embodiment and coordinate accompanying drawing to be explained in detail.
Refer to Fig. 1, Fig. 1 is the main route schematic diagram of reaction of the present invention, comprises three steps:
S1,5-methyl-2,3-hexanedione and 1,2-propylene diamine reacting by heating in methyl alcohol or ethanol, generate 5-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine and 6-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine;
S2, add cupric oxide in S1 gained reaction system, 5-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine and 6-isobutyl--2,6-dimethyl-2, the oxidized generation 3 of 3-dihydro pyrazine, 5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine;
S3, rectification process S2 gained reaction solution, obtain 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine.
Corresponding reaction formula is as follows:
Below by specific embodiment, synthetic method provided by the invention is specifically introduced.
Embodiment 1
Refer to Fig. 1, Fig. 1 is a kind of schema that synthesizes the method for 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine that the present embodiment provides.The concrete technology method of the present embodiment is as follows:
S101, add ethanol in reactor, will account for the 5-methyl-2 of participating in reaction, the 5-methyl-2 of the total amount 3% of 3-hexanedione, 3-hexanedione and account for and participate in 1 of reaction, 1 of the total amount 3% of 2-propylene diamine, the 2-propylene diamine adds reactor, while feeding intake, stirs; And be heated to 38 ℃.
Consider the character such as solvability, polarity, security of reactant and product, ethanol is the reaction medium that is suitable for this reaction selected after optimization design.In ethanol, two kinds of reactants can access and spread preferably and mix, and are of value to fully carrying out of reaction, also are conducive to the conduction that reaction produces heat.
In step S101, add at first on a small quantity two kinds of reactants mildly heating, be in order to guide the generation of reaction; While feeding intake, keep stirring is in order to make two kinds of reactants fully spread evenly in ethanol and fully contact, to reach best reaction effect.
S102 added reactor by residual reactant in 60 minutes, and feed intake at every turn and add 5-methyl-2 simultaneously, 3-hexanedione and 1,2-propylene diamine, and by controlling rate of feeding, temperature of reaction system is controlled to 40 ℃.
Because this reaction can discharge certain heat in the process of carrying out, so can not disposable all reactants be dropped in reactor; By the charging time proper extension, drop into two kinds of reactants while feeding intake at every turn simultaneously, control each charging capacity, and keep stirring fully when feeding intake, to such an extent as to the heat that reaction produces like this is unlikely to accumulate the generation that too much causes side reaction.
S103, continue to be stirred to reaction and finish.
Proceed to process after half at response estimator, reaction system is carried out to sampling analysis, until determine that reaction is complete.
S104, S103 gained reaction solution is cooled to 28 ℃, adds potassium hydroxide, continue to stir 25 minutes.
The purpose that adds potassium hydroxide is the acidic substance that may generate in the neutralization reaction system, and provides alkaline environment for subsequent step.
S105, slowly be heated to 48 ℃, stop heating, add cupric oxide;
Cupric oxide be in this reaction to 5-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine and 6-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine carries out the oxygenant of dehydrogenation oxidation.
S106, slowly be heated to 78 ℃, stop heating;
In step S105 and S106, describedly slowly be heated to be the heating that rate of rise in temperature is not more than 0.5 ℃/minute.Because reaction system unstable, if rate of heating is too fast, will cause not wishing the generation of the side reaction seen, greatly reduce overall yield of reaction, and will have by product to produce, later separation and purification step are caused to obstacle.Control rate of heating lower than certain limit, can make reactant and product that abundant diffusion and the time contacted are arranged.Yet, in actual production process, in order to guarantee certain production efficiency, the lift velocity of Heating temperature should not be excessively slow, so be not that any rate of rise in temperature in 0-0.5 ℃ of/minute scope can be accepted, be limited to 0.1 ℃/minute under the general rate of temperature change of formulating, that is to say, in actual production process, adoptable rate of heating scope is generally between 0.1-0.5 ℃/minute.
S107, waiting temperature rise to 88 ℃, produce and reflux; Keep refluxing 80 minutes, the assurance oxidizing reaction is carried out continuously until react end.
This reaction is thermopositive reaction, so, after heating makes the reaction beginning, even stop heating, the temperature of reaction system also can rise gradually.In addition in this step, by reaction process, reaction system constantly being carried out to sampling analysis, guarantee that oxidizing reaction continues to carry out, until reaction finishes.
S108, be cooled to 28 ℃, filter to isolate cupric oxide, obtain reaction solution.
In order to guarantee fully carrying out of reaction, it is excessive that cupric oxide requires when feeding intake, but cupric oxide is again a kind of relatively costly raw material, so the recycling of the cupric oxide of complete reaction is not necessary and useful yet; Cupric oxide is pressed powder in addition, and it is also necessary by itself and other solid impurity, from liquid phase, separating for rectification step thereafter.
Rectification step S108 gained reaction solution under S109, normal pressure is to reclaim ethanol under 103 ℃, the reflux ratio condition that is 1 in the tower reactor temperature;
Ethanol is as reaction medium, and large usage quantity in this reaction is also no small input with regard to expense of raw materials, so utilize rectification method to reclaim ethanol, can utilize to large extent material, increases economic efficiency.
S110, step S109 reaction system is removed to the remaining reaction solution of institute after ethanol be cooled to 30 ℃, stratification, separate water layer;
Reaction product 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine is organism, be present in organic phase, by the abundant stirring under certain hour, stratification, separation organic layer and water layer, can remove much water-soluble impurity, and make to greatest extent products distribution in organic layer.
S111, in vacuum tightness, be separating alcohol under 250mbar and the reflux ratio condition that is 1, rectifying goes out the first crude product;
Ethanol is as reaction medium, and large usage quantity in this reaction is also no small input with regard to expense of raw materials, so further rectifying recovery ethanol can utilize material to a greater extent, increases economic efficiency; Rectifying can also the remove portion boiling point and the approximate impurity of ethanol in addition.
S112, the first crude product is put into to clean container, add potassium hydroxide; Stir 20 minutes, stratification, separate water layer, obtains the second crude product.
May generate some acidic substance in this reaction, yet described reaction system reaction product under acidic conditions may occur to decompose or other side reactions, so it is that we are reluctant to see that reaction system is acidity, adding appropriate potassium hydroxide in step S112 is exactly in order to guarantee the alkalescence of reaction system, by repeatedly groping, we find that this step is to add potassium hydroxide alkalization system the most effectively and the most necessary opportunity.In addition, reaction product 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine is organism, be present in organic phase, by the abundant stirring under certain hour, stratification, separation organic layer and water layer, can remove much water-soluble impurity, and make to greatest extent products distribution in organic layer.
S113, vacuum tightness be 10mbar, reflux ratio be 0.1 and the tower top temperature condition that is 70 ℃ under collect product.
What described product referred to is exactly product 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, these two kinds of material effects as spices the time be do not have differentiated, so need in reaction designing and building-up process, the two not treated with a certain discrimination.
The total reaction yield of the synthetic method that the present embodiment provides (relative 5-methyl-2, the 3-hexanedione calculates gained) and product purity are in Table 1.
Embodiment 2
The concrete technology method of the present embodiment is as follows:
S101, add methyl alcohol in reactor, will account for the 5-methyl-2 that total reactant per-cent is 3%, 3-hexanedione and 1,2-propylene diamine add reactor, while feeding intake, keep stirring; And be heated to 38 ℃.
Consider the character such as solvability, polarity of reactant and product, methyl alcohol and ethanol are all the reaction mediums that is suitable for this reaction selected after optimization design.Although compare ethanol, methyl alcohol is not enough to some extent in security, and (as considered the concrete condition of production of factory) methyl alcohol may be more convenient for obtaining than ethanol under given conditions.In methyl alcohol, two kinds of reactants can access and spread preferably and mix, and are of value to fully carrying out of reaction, also are conducive to the conduction that reaction produces heat.
In step S101, add at first on a small quantity two kinds of reactants mildly heating, be in order to guide the generation of reaction; While feeding intake, keep stirring is in order to make two kinds of reactants fully spread evenly in methyl alcohol and fully contact, to reach best reaction effect.
S102 added reactor by residual reactant in 60 minutes, and feed intake at every turn and add 5-methyl-2 simultaneously, 3-hexanedione and 1,2-propylene diamine, and by controlling rate of feeding, temperature of reaction system is controlled to 40 ℃.
Because this reaction can discharge certain heat in the process of carrying out, so can not disposable all reactants be dropped in reactor; By the charging time proper extension, drop into two kinds of reactants while feeding intake at every turn simultaneously, control each charging capacity, and keep stirring fully when feeding intake, to such an extent as to the heat that reaction produces like this is unlikely to accumulate the generation that too much causes side reaction.
S103, continue to be stirred to reaction and finish.
After response estimator proceeds to half, start reaction system is carried out to sampling analysis, until determine that reaction is complete.
S104, S103 gained reaction solution is cooled to 28 ℃, adds potassium hydroxide, continue to stir 25 minutes.
The purpose that adds potassium hydroxide is the acidic substance that may generate in the neutralization reaction system, and provides alkaline environment for subsequent step.
S105, slowly be heated to 48 ℃, stop heating, add cupric oxide;
Cupric oxide be in this reaction to 5-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine and 6-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine carries out the oxygenant of dehydrogenation oxidation.
S106, slowly be heated to 78 ℃, stop heating;
In step S105 and S106, describedly slowly be heated to be the heating that rate of rise in temperature is not more than 0.5 ℃/minute.Because reaction system unstable, if rate of heating is too fast, will cause not wishing the generation of the side reaction seen, greatly reduce overall yield of reaction, and will have by product to produce, later separation and purification step are caused to obstacle.Control rate of heating lower than certain limit, can make reactant and product that abundant diffusion and the time contacted are arranged.
S107, waiting temperature rise to 88 ℃, produce and reflux; Keep refluxing 80 minutes, the assurance oxidizing reaction is carried out continuously until react end.
In this step, by reaction process, reaction system constantly being carried out to sampling analysis, guarantee that oxidizing reaction continues to carry out, until reaction finishes.
S108, be cooled to 28 ℃, filter to isolate cupric oxide, obtain reaction solution.
In order to guarantee fully carrying out of reaction, it is excessive that cupric oxide requires when feeding intake, but cupric oxide is again a kind of relatively costly raw material, so the recycling of the cupric oxide of complete reaction is not necessary and useful yet; Cupric oxide is pressed powder in addition, and it is also necessary by itself and other solid impurity, from liquid phase, separating for rectification step thereafter.
Rectification step S108 gained reaction solution under S109, normal pressure is to reclaim methyl alcohol under 103 ℃, the reflux ratio condition that is 1 in the tower reactor temperature;
Methyl alcohol is as reaction medium, and large usage quantity in this reaction is also no small input with regard to expense of raw materials, so utilize rectification method to reclaim methyl alcohol, can utilize to large extent material, increases economic efficiency.
S110, step S109 reaction system is removed to the remaining reaction solution of institute after methyl alcohol be cooled to 30 ℃, stratification, separate water layer;
Reaction product 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine is organism, be present in organic phase, by the abundant stirring under certain hour, stratification, separation organic layer and water layer, can remove much water-soluble impurity, and make to greatest extent products distribution in organic layer.
S111, in vacuum tightness, be separation of methanol under 250mbar and the reflux ratio condition that is 1, rectifying goes out the first crude product;
Methyl alcohol is as reaction medium, and large usage quantity in this reaction is also no small input with regard to expense of raw materials, so further rectifying recovery methyl alcohol can utilize material to a greater extent, increases economic efficiency; Rectifying can also the remove portion boiling point and the approximate impurity of methyl alcohol in addition.
S112, the first crude product is put into to clean container, add potassium hydroxide; Stir 20 minutes, stratification, separate water layer, obtains the second crude product.
May generate some acidic substance in this reaction, yet described reaction system reaction product under acidic conditions may occur to decompose or other side reactions, so it is that we are reluctant to see that reaction system is acidity, adding appropriate potassium hydroxide in step S112 is exactly in order to guarantee the alkalescence of reaction system, by repeated multiple times, grope, we find that this step is to add potassium hydroxide alkalization system the most effectively and the most necessary opportunity.In addition, reaction product 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine is organism, be present in organic phase, by the abundant stirring under certain hour, stratification, separation organic layer and water layer, can remove much water-soluble impurity, and make to greatest extent products distribution in organic layer.
S113, vacuum tightness be 10mbar, reflux ratio be 0.1 and the tower top temperature condition that is 70 ℃ under collect product.
What described product referred to is exactly product 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, these two kinds of material effects as spices the time be do not have differentiated, so need in reaction designing and building-up process, the two not treated with a certain discrimination.
The total reaction yield of the synthetic method that the present embodiment provides (relative 5-methyl-2, the 3-hexanedione calculates gained) and product purity are in Table 1.
Embodiment 3
S101, add ethanol in reactor, will account for the 5-methyl-2 that total reactant per-cent is 7%, 3-hexanedione and 1,2-propylene diamine add reactor, while feeding intake, keep stirring; And be heated to 42 ℃;
S102 added reactor by residual reactant in 90 minutes, and feed intake at every turn and add 5-methyl-2 simultaneously, 3-hexanedione and 1,2-propylene diamine, and by controlling rate of feeding, temperature of reaction is controlled to 50 ℃;
S103, continue to be stirred to reaction and finish;
S104, S103 gained reaction solution is cooled to 32 ℃, adds potassium hydroxide, continue to stir 35 minutes;
S105, slowly be heated to 52 ℃, stop heating, add cupric oxide;
S106, slowly be heated to 82 ℃, stop heating;
Slowly be heated to be the heating that rate of rise in temperature is not more than 0.5 ℃/minute described in step S105 and S106;
S107, waiting temperature rise to 92 ℃, produce and reflux; Keep refluxing 100 minutes, the assurance oxidizing reaction is carried out continuously until react end;
S108, be cooled to 32 ℃, filter to isolate cupric oxide, obtain reaction solution;
Rectification step S108 gained reaction solution under S109, normal pressure is to reclaim ethanol under 107 ℃, the reflux ratio condition that is 1 in the tower reactor temperature.
S110, step S109 reaction system is removed to the remaining reaction solution of institute after ethanol be cooled to 30 ℃, stratification, separate water layer;
S111, in vacuum tightness, be separating alcohol under 350mbar and the reflux ratio condition that is 1, rectifying goes out described the first crude product.
S112, described the first crude product is put into to clean container, add potassium hydroxide; Stir 40 minutes, stratification, separate water layer, obtains the second crude product.
S113, vacuum tightness be 100mbar, reflux ratio be 0.1 and the tower top temperature condition that is 120 ℃ under collect product.
The total reaction yield of the synthetic method that the present embodiment provides (relative 5-methyl-2, the 3-hexanedione calculates gained) and product purity are in Table 1.
Embodiment 4
S101, add ethanol in reactor, will account for the 5-methyl-2 that total reactant per-cent is 5%, 3-hexanedione and 1,2-propylene diamine add reactor, while feeding intake, keep stirring; And be heated to 40 ℃;
S102 added reactor by residual reactant in 75 minutes, and feed intake at every turn and add 5-methyl-2 simultaneously, 3-hexanedione and 1,2-propylene diamine, and by controlling rate of feeding, temperature of reaction system is controlled to 45 ℃;
S103, continue to be stirred to reaction and finish;
S104, S103 gained reaction solution is cooled to 30 ℃, adds potassium hydroxide, continue to stir 30 minutes;
S105, slowly be heated to 50 ℃, stop heating, add cupric oxide;
S106, slowly be heated to 80 ℃, stop heating;
S107, waiting temperature rise to 90 ℃, produce and reflux; Keep refluxing 90 minutes, the assurance oxidizing reaction is carried out continuously until react end;
S108, be cooled to 30 ℃, filter to isolate cupric oxide, obtain reaction solution;
Wherein, slowly be heated to be the heating that rate of rise in temperature is not more than 0.5 ℃/minute described in step S105 and S106;
Rectification step S108 gained reaction solution under S109, normal pressure is to reclaim ethanol under 105 ℃, the reflux ratio condition that is 1 in the tower reactor temperature.
S110, step S109 reaction system is removed to the remaining reaction solution of institute after ethanol be cooled to 30 ℃, stratification, separate water layer;
S111, in vacuum tightness, be separating alcohol under 300mbar and the reflux ratio condition that is 1, rectifying goes out described the first crude product.
S112, described the first crude product is put into to clean container, add potassium hydroxide; Stir 30 minutes, stratification, separate water layer, obtains the second crude product.
S113, vacuum tightness be 55mbar, reflux ratio be 0.1 and the tower top temperature condition that is 95 ℃ under collect product.
The total reaction yield of the synthetic method that the present embodiment provides (relative 5-methyl-2, the 3-hexanedione calculates gained) and product purity are in Table 1.
Table 1
| Embodiment | Reaction yield (%) | Product purity (%) |
| 1 | 65.0 | 99.2 |
| 2 | 64.7 | 99.0 |
| 3 | 65.5 | 99.4 |
| 4 | 65.7 | 99.1 |
The foregoing is only embodiments of the invention; not thereby limit the scope of the claims of the present invention; every equivalent structure or conversion of equivalent flow process that utilizes specification sheets of the present invention and accompanying drawing content to do; or directly or indirectly be used in other relevant technical fields, all in like manner be included in scope of patent protection of the present invention.
Claims (10)
1. a method of synthesizing 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, is characterized in that, comprises the following steps:
S1,5-methyl-2,3-hexanedione and 1,2-propylene diamine reacting by heating in methyl alcohol or ethanol, generate 5-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine and 6-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine;
S2, add cupric oxide in S1 gained reaction system, 5-isobutyl--2,6-dimethyl-2,3-dihydro pyrazine and 6-isobutyl--2,6-dimethyl-2, the oxidized generation 3 of 3-dihydro pyrazine, 5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine;
S3, rectification process S2 gained reaction solution, obtain 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine.
2. the method for synthetic 3,5-dimethyl as claimed in claim 1-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, is characterized in that, step S1 specifically comprises the steps:
S11, add ethanol in reactor, the 5-methyl-2 that will to account for total reactant per-cent be 5 ± 2%, 3-hexanedione and 1,2-propylene diamine add reactor, while feeding intake, keep material evenly to mix;
S12, in 60-90 minute, residual reactant is added to reactor, feed intake at every turn and add 5-methyl-2 simultaneously, 3-hexanedione and 1,2-propylene diamine, and by controlling rate of feeding, temperature of reaction system is controlled to 45 ± 5 ℃;
S13, maintenance material evenly are mixed to reaction to be finished.
3. the method for synthetic 3,5-dimethyl as claimed in claim 2-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine is characterized in that:
In step S11, the post-heating to 40 that feeds intake ± 2 ℃;
In step S12, in the process of feeding intake, by controlling rate of feeding, temperature of reaction system is controlled to 45 ± 5 ℃, while feeding intake, keeps material evenly to mix.
4. the method for synthetic 3,5-dimethyl as claimed in claim 1-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, is characterized in that, step S2 specifically comprises the steps:
S21, S1 gained reaction solution is cooled to 30 ± 2 ℃, adds potassium hydroxide, keep material evenly to mix 30 ± 5 minutes;
S22, slowly be heated to 50 ± 2 ℃, stop heating, add cupric oxide;
S23, slowly be heated to 80 ± 2 ℃, stop heating;
S24, waiting temperature rise to 90 ± 2 ℃, produce and reflux; Keep backflow 80-100 minute, the assurance oxidizing reaction is carried out continuously until react end;
S25, be cooled to 30 ± 2 ℃, filter to isolate cupric oxide, obtain reaction solution;
Slowly be heated to be the heating that rate of rise in temperature is not more than 0.5 ℃/minute described in step S22 and S23.
5. the method for synthetic 3,5-dimethyl as claimed in claim 1-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, is characterized in that, step S3 is specially:
S31, rectification step S2 gained reaction solution, reclaim ethanol;
S32, step S31 is removed to the reaction solution after ethanol, separate organic phase and water;
S33, to step S32 gained organic phase, rectifying obtains the first crude product;
S34, in the first crude product, add potassium hydroxide, mix, separate organic phase and water, get organic phase, obtain the second crude product;
S35, rectifying the second crude product, obtain product 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine.
6. the method for synthetic 3,5-dimethyl as claimed in claim 5-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, is characterized in that, step S31 is specially:
Rectification step S2 gained reaction solution under normal pressure is to reclaim ethanol under 105 ± 2 ℃, the reflux ratio condition that is 1 in the tower reactor temperature.
7. the method for synthetic 3,5-dimethyl as claimed in claim 5-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, is characterized in that, step S32 is specially:
After step S31 is removed to ethanol, the gained reaction solution is cooled to 30 ℃, separates organic phase and water, obtains organic phase.
8. the method for synthetic 3,5-dimethyl as claimed in claim 5-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, is characterized in that, step S33 is specially:
In vacuum tightness, be separating alcohol under 300 ± 50mbar and the reflux ratio condition that is 1, rectifying goes out described the first crude product.
9. the method for synthetic 3,5-dimethyl as claimed in claim 5-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, is characterized in that, step S34 is specially:
Described the first crude product is put into to clean container, add potassium hydroxide;
Keep material evenly to mix 30 ± 10 minutes, separate organic phase and water, get organic phase, obtain the second crude product.
10. the method for synthetic 3,5-dimethyl as claimed in claim 5-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine, is characterized in that, step S35 is specially:
Vacuum tightness be 10-100mbar, reflux ratio be 0.1 and the tower top temperature condition that is 70-120 ℃ under collect product 3,5-dimethyl-2-isobutyl pyrazine and 3,6-dimethyl-2-isobutyl pyrazine.
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| EP0590296B1 (en) * | 1992-09-29 | 1995-11-02 | Societe Des Produits Nestle S.A. | Process for the preparation of 2,3,5(6) trialkyl pyrazines |
| CN1191220A (en) * | 1997-06-13 | 1998-08-26 | 李加荣 | Improved process for preparing pyrazines compounds |
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| EP0590296B1 (en) * | 1992-09-29 | 1995-11-02 | Societe Des Produits Nestle S.A. | Process for the preparation of 2,3,5(6) trialkyl pyrazines |
| CN1191220A (en) * | 1997-06-13 | 1998-08-26 | 李加荣 | Improved process for preparing pyrazines compounds |
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