CN102115463B - Method for synthesizing 4,6-dihydroxy pyrimidine - Google Patents
Method for synthesizing 4,6-dihydroxy pyrimidine Download PDFInfo
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Abstract
The invention discloses a method for preparing 4,6-dihydroxy pyrimidine. Raw materials comprise malonate, formamide and alkali metal alcoholate. The method comprises the following steps of: a, mixing an effective amount of malonate and formamide with an effective amount of alkali metal alcoholate/solvent suspension for reacting for 1-2 hours in a heat preservation way under the conditions of keeping a normal pressure condition and controlling the temperature between 50 DEG C and 90 DEG C; b, controlling the kettle temperature to be lower than or equal to 65 DEG C under a negative pressure condition, distilling a solvent till the content of the solvent in a reaction system is less than or equal to 45 percent by mass, wherein in the solvent distilling process, water is gradually added to dissolve 4,6-dihydroxy pyrimidine sodium salt obtained by the reaction; and c, acidifying to finally obtain the 4,6-dihydroxy pyrimidine. The method has the advantages of easy, convenient and feasible preparation technology, easiness for industrialization and capability of obtaining the high-yield and high-quality 4,6-dihydroxy pyrimidine product with the yield up to over 86 percent, and the main content of 4,6-dihydroxy pyrimidine can be up to over 99 percent.
Description
Technical field
The present invention relates to a kind ofly prepare 4, the method for-dihydroxy-pyrimidine relates in particular to a kind of method for preparing 4,6-dihydroxy-pyrimidine take malonic ester, methane amide and alkali metal alcoholate as raw material.
Background technology
4,6-dihydroxy-pyrimidine (DHP) is a kind of important intermediate, and in particular for agrochemicals industry, its tautomer is called 1-H-pyrimidine-4, the 6-diketone.
The method of early stage preparation 4,6-dihydroxy-pyrimidine mainly is (to see for example R.Hull, J.Chem.Soc., 2214,1951 take Malonamide as basic material; C.Hennart and E.Merlin, Bull.Soc.Chem., 741,1959; D.J.Brown, J.Chem.Soc., 2312-2314,1956 and A.Sommer, DE-OS1200308 or V.A.Zasonov, Khim.-Farm.Zh., 8 (12), 28-31), make with ethyl formate or methane amide and alkali metal alcoholate reaction.The shortcoming of these methods is except the raw material Malonamide can not obtain with business-like quantity, and key issue is that also yield is low, supplies consumption is large.
Now preparation 4, the method of 6-dihydroxy-pyrimidine mainly be directly take dimethyl malonate as basic material and the reaction of methane amide and alkali metal alcoholate make (referring to for example CN1214044A, CN1406934A, CN1175576A), mainly contain non-pressure process (CN1214044A) and pressurization (CN1406934A, CN1175576A).These methods and Malonamide method comparison raw material are easy to get, yield is relatively high, but the non-pressure process actual recovery is low, and pressurization industrialization difficulty is large.
Summary of the invention
The purpose of this invention is to provide a kind of take malonic ester, methane amide and alkali metal alcoholate as raw material, the method for preparation 4,6-dihydroxy-pyrimidine.Adopt the inventive method to be easy to industrialization, can produce high yield, high-quality 4, the 6-dihydroxy-pyrimidine.
The present invention seeks to realize like this:
A kind of 4, the preparation method of 6-dihydroxy-pyrimidine, its raw material comprises malonic ester, methane amide and alkali metal alcoholate, comprises the steps: that a. mixes the alkali metal alcoholate of the malonic ester of significant quantity, methane amide and significant quantity/solvent suspension liquid, react under the condition of normal pressure; B. the described solvent of Distillation recovery is dissolved in water in described still-process and reacts 4 of gained, 6-dihydroxy-pyrimidine sodium salt; C. carry out acidifying, finally make product; It is characterized in that: the distillating recovering solvent process of described b step is to carry out under condition of negative pressure.
Temperature of reaction under the above-mentioned condition of normal pressure is 50～70 ℃, and the reaction times is 1～2 hour; Described distillating recovering solvent is the quality percentage composition that is distilled to the still internal solvent≤45%; In the process of above-mentioned condition of negative pressure distillating recovering solvent, its pressure is-0.03Mpa～-0.1Mpa, preferred pressure is-0.04Mpa～-vacuum condition of 0.06Mpa under Distillation recovery.
Above-mentioned malonic ester is preferably dimethyl malonate, and alkali metal alcoholate/solvent is preferably and is sodium methylate/methyl alcohol.
The alkali metal alcoholate of above-mentioned malonic ester, methane amide and significant quantity/solvent suspension liquid mix specifically will malonic ester and methane amide add again alkali metal alcoholate/solvent suspension liquid after mixing and mix, or add again the malonic ester mixing after first methane amide being added to alkali metal alcoholate/solvent suspension liquid mixing, or add again the methane amide mixing after first malonic ester being added alkali metal alcoholate/solvent suspension liquid mixing; In order further to improve yield, preferably first methane amide is added to and adds again malonic ester after alkali metal alcoholate/solvent suspension liquid mixes and mix.
Particular methanol sodium of the present invention is catalyzer, and its solvent methanol is that the by product in 4, the 6-dihydroxy-pyrimidine building-up process is again solvent and the dispersion agent in the building-up process, and what of quantity of methyl alcohol are huge on reaction effect impact.The system quantity of methyl alcohol causes too greatly sodium methylate concentration low, makes the sodium methylate catalytic effect poor; The pasty state intermediate dissolving that system methyl alcohol makes sodium methylate and methane amide form very little not exclusively can cause the phenomenon of 4,6-dihydroxy-pyrimidine sodium salt parcel intermediate to occur, and makes reaction not exclusively, and yield reduces.For alkali metal alcoholate such as sodium methylate catalytic effect are further improved, make reaction more complete, further improve yield, above-mentioned alkali metal alcoholate/solvent such as sodium methylate/methanol quality ratio is 1: 0.7～1.3, be preferably 1: 0.8～and 1.2, most preferably be 1: 1.
In order to bring into play better the katalysis of alkali metal alcoholate, the pasty state intermediate dissolving that alkali metal alcoholate and methane amide are formed is more complete in to avoid 4, the intermediate phenomenon of 6-dihydroxy-pyrimidine sodium salt parcel occurs, and the mol ratio of above-mentioned reaction raw materials is malonic ester: methane amide: alkali metal alcoholate=1: 2～4: 3～5.
In order to make reaction carry out more thoroughly, temperature is reduced to 30～40 ℃ first after the above-mentioned a step, insulation reaction 0.5～3 hour, preferred 1～2 hour, and then carry out the b step.
More high-quality 4 in order to obtain, 6-dihydroxy-pyrimidine product, the acid that above-mentioned acidifying is used is hydrochloric acid.
Also comprise drying step after the above-mentioned acid adding, in order to prevent the variable color in air of 4,6-dihydroxy-pyrimidine, drying treatment adopts the vacuum drying treatment mode, and its vacuum tightness is 0～-0.1Mpa.
Further in order to make reaction thoroughly, the amount of the used malonic ester of a step charging reaction and methane amide is preferably 2/3 of malonic ester and the total consumption of methane amide, in reaction system, again add again malonic ester and methane amide behind a step charging reaction, wherein the malonic ester of second batch adding and the amount of methane amide are preferably 1/3 of total consumption, keep condition of normal pressure, the control temperature is at 50～70 ℃, and insulation reaction 1～2 hour is carried out the b step again; Described methane amide and malonic ester are to adopt minute two batches of feed way, certainly, adopt three batches and three batches of above feed way feasible equally, are that this mode is uneconomical.
In order to maximize the decomposition that reduces methane amide, above-mentioned each charge temperature preferably is controlled at 60～70 ℃; Temperature of reaction is controlled at 60～70 ℃.
In order to make reaction carry out more thoroughly, before above-mentioned second batch feeds in raw material after above-mentioned a step, temperature is reduced to 30～40 ℃, insulation reaction 0.5～3 hour, preferred 1～2 hour; Or-0.03～-condition of negative pressure of 0.1Mpa under control still temperature at≤65 ℃, distilling off solvent, the mass ratio that makes remaining alkali metal alcoholate and solvent is 1: 0.7～1.3, be preferably 1: 0.8～1.2, most preferably be approximately 1: 1, this moment, alkali metal alcoholate was present in the reaction solution with aerosol form.Also can be before above-mentioned second batch feeds in raw material after above-mentioned a step, temperature to be reduced to 30～40 ℃, insulation reaction 0.5～3 hour, preferred 1～2 hour; Then-0.03～-condition of negative pressure of 0.1Mpa under control still temperature at≤65 ℃, distilling off solvent, the mass ratio that makes remaining alkali metal alcoholate and solvent is 1: 0.7～1.3, be preferably 1: 0.8～1.2, most preferably be 1: 1, this moment, alkali metal alcoholate was present in the reaction solution with aerosol form.
In order more thoroughly to react completely, temperature is reduced to 30～40 ℃ again after the above-mentioned second time is reinforced, be incubated 0.5～3 hour, preferred 1～2 hour, carry out again above-mentioned b step reaction.
More particularly, a kind of method for preparing 4,6-dihydroxy-pyrimidine take dimethyl malonate, methane amide and sodium methylate as raw material reaction is characterized in that:
Dimethyl malonate, the methane amide that a. will react total consumption 2/3 mix with the sodium methylate/methanol suspension of significant quantity, keep condition of normal pressure, control temperature of reaction at 50～70 ℃, and preferred 60～70 ℃, insulation reaction 1～2 hour; Wherein sodium methylate is 1: 0.7～1.3 with the methanol quality ratio, be preferably 1: 0.8～and 1.2, most preferably be 1: 1; Dimethyl malonate: methane amide: sodium methylate=1: 2～4: 3～5, with molar ratio computing;
Temperature is reduced to 30～40 ℃, insulation reaction 0.5～3 hour, preferred 1～2 hour; Or/and-0.03～-condition of negative pressure of 0.1Mpa under control still temperature at≤65 ℃, distill out methyl alcohol, make the mass ratio 1: 0.7～1.3 of remaining sodium methylate and methyl alcohol, be preferably 1: 0.8～1.2, most preferably be 1: 1, this moment, sodium methylate was present in the reaction solution with aerosol form;
Second batch is reinforced: add dimethyl malonate and the methane amide of the total consumption 1/3 of reaction in reaction system, keep condition of normal pressure, control temperature at 50～70 ℃, insulation reaction 1～2 hour;
Low temperature insulation after the reaction: temperature is reduced to 30～40 ℃, is incubated 0.5～3 hour, preferred 1～2 hour;
B.-0.03～-condition of negative pressure of 0.1Mpa under control still temperature at≤65 ℃ of Distillation recovery methyl alcohol, material methanol quality percentage composition≤45% to the still; In this distillating carbinol process, progressively be dissolved in water and react 4 of gained, 6-dihydroxy-pyrimidine sodium salt;
C. carry out acidifying with hydrochloric acid again, cooling reactor temperature, suction filtration, washing, centrifugal, vacuum tightness is 0～-dry under the 0.1Mpa condition, finally make 4,6-dihydroxy-pyrimidine.
In addition, above-mentioned sodium methylate/methanol solution can adopt other alkali metal alcoholate/solvent to substitute, and such as sodium ethylate/ethanolic soln, but considers particular methanol sodium/methanol solution from reclaiming the pure and mild cost of material of by-product.Dimethyl malonate can adopt other malonic esters to substitute, such as diethyl malonate, but preferred dimethyl malonate.
The present invention has following advantage:
1, the present invention 4, the preparation of 6-dihydroxy-pyrimidine is to adopt to hocket at synthesis under normal pressure and vacuum distillation, vacuum distillation can effectively prevent the decomposition of methane amide in the reaction system, finally obtain high yield, high-quality 4,6-dihydroxy-pyrimidine product, simultaneously so that preparation technology of the present invention simple and easy to do, be easy to industrialization.
2, the present invention is by controlling the specific proportion relation of sodium methylate/methyl alcohol in reaction system, so that in the reaction system not only as byproduct of reaction but also suitable as the methanol content of solvent in the reaction process and dispersion agent, thereby make the sodium methylate excellent catalytic effect as catalyzer, the pasty state intermediate dissolving that sodium methylate and methane amide are formed has avoided 4 more fully, the intermediate phenomenon of 6-dihydroxy-pyrimidine sodium salt parcel occurs, so that reaction is carried out more fully, the raising yield.
3, the present invention adopts the rear low temperature incubation step of reaction, has further reduced the generation of byproduct of reaction, makes simultaneously reaction carry out more thoroughly.
4, the present invention is by the specific proportion relation of dimethyl malonate, methane amide and sodium methylate, further so that sodium methylate produces better catalytic effect, the pasty state intermediate dissolving that sodium methylate and methane amide are formed has avoided 4 more fully, the intermediate phenomenon of 6-dihydroxy-pyrimidine sodium salt parcel occurs, and makes reaction more fully, further improve yield.
5, the present invention cooperates and adopts suitable reinforced hybrid reaction temperature so that in the present invention's reaction methane amide without obvious decomposition.
6, the present invention has adopted the batch charging mode, make reaction more complete, reach higher yield.
7, adopt production method yield of the present invention high, its yield can reach more than 86%; The superior product quality of producing, its 4,6-dihydroxy-pyrimidine master content can be up to more than 99%.
Embodiment
Below by embodiment the present invention is carried out concrete description; be necessary to be pointed out that at this following examples only are used for the present invention is further specified; can not be interpreted as limiting the scope of the invention, the person skilled in art can make some nonessential improvement and adjustment to the present invention according to the invention described above content.
Embodiment 1 is 1520kg sodium methylate (〉=27.5% commercially available specification, following same) the adding reactor, steam 650～700L and reclaim methyl alcohol, make that the mass ratio of sodium methylate and methyl alcohol is 1: 0.8～1.1 in the reaction system, after be cooled to 75 ℃, disposable adding 200kg methane amide (〉=99% commercially available specification, following same), half an hour with interior 190kg dimethyl malonate (〉=99% the commercially available specification that adds, following with), add that still temperature kept 65～70 ℃ of insulation reaction 1.5 hours behind the dimethyl malonate, then lower the temperature, make the still temperature 30～40 ℃ of insulation reaction 1 hour again, be warming up to afterwards 60～65 ℃ of still temperature.Control still temperature≤65 ℃ of Distillation recovery methyl alcohol 250～300L under-0.05 ± 0.01Mpa vacuum condition, make that sodium methylate is 1: 0.7～1.2 with the methanol quality ratio in the reaction system, once add methane amide 100kg (〉=99%) 60～70 ℃ of elder generations afterwards, add 90kg dimethyl malonate (〉=99%) in 10 minutes.Add that the still temperature keeps 65～70 ℃ of insulations 1 hour behind the dimethyl malonate, then cooling makes the still temperature 30～40 ℃ of insulation reaction 1 hour again, is warming up to afterwards 60～65 ℃ of still temperature.Control still temperature under-0.05 ± 0.01Mpa vacuum condition≤65 ℃ again steams 300～350L and reclaims methyl alcohol, after this process progressively adds water 1000L dissolving 4,6-dihydroxy-pyrimidine sodium salt, steamed methyl alcohol, cools off.Keep the still temperature to be no more than 40 ℃, add hydrochloric acid 920kg (〉=30% commercially available specification, following same), make the still temperature be chilled to suction filtration below 10 ℃, washing, centrifugal after adding hydrochloric acid, dry under-0.09 ± 0.01MPa vacuum condition, get 4,6-dihydroxy-pyrimidine 204.6kg, content 99.1%, yield 86.2%, outward appearance pale yellow powder.
Embodiment 2
1520kg sodium methylate (〉=27.5%) is added reactor, steam 650～700L and reclaim methyl alcohol, make that the mass ratio of sodium methylate and methyl alcohol is 1: 0.8～1.1 in the reaction system, after be cooled to 75 ℃, disposable adding 200kg methane amide (〉=99%), half an hour with the interior 190kg dimethyl malonate (〉=99%) that adds, the still temperature kept 65～70 ℃ of insulation reaction 1.5 hours after adding dimethyl malonate, then cooling, make the still temperature 30～40 ℃ of insulation reaction 1 hour again, heat up afterwards.When the still temperature reaches 60 ℃, once add methane amide 100kg (〉=99%), add 90kg dimethyl malonate (〉=99%) in 10 minutes.Add behind the dimethyl malonate still temperature and keep 65～70 ℃ of insulation half an hour, then cooling makes the still temperature 30～40 ℃ of insulation reaction 1 hour again, is warming up to afterwards 60～65 ℃ of still temperature.Control still temperature under-0.05 ± 0.01MPa vacuum condition≤65 ℃ again steams 900～1000L and reclaims methyl alcohol, after this process progressively adds water 1000L dissolving 4,6-dihydroxy-pyrimidine sodium salt, steamed methyl alcohol, cools off.Keep the still temperature to be no more than 40 ℃, add hydrochloric acid 920kg (〉=30%), make the still temperature be chilled to suction filtration below 10 ℃, washing, centrifugal after adding hydrochloric acid, dry under-0.09 ± 0.01MPa vacuum condition, get 4,6-dihydroxy-pyrimidine 195.4kg, content 99.2%, yield 82.4%, the outward appearance pale yellow powder.
Embodiment 3
1520kg sodium methylate (〉=27.5%) is added reactor, steam 650～700L and reclaim methyl alcohol, make that the mass ratio of sodium methylate and methyl alcohol is 1: 0.8～1.1 in the reaction system, after be cooled to 75 ℃, disposable adding 200kg methane amide (〉=99%), half an hour with the interior 190kg dimethyl malonate (〉=99%) that adds, add that the still temperature kept 65～70 ℃ of insulation reaction 1.5 hours behind the dimethyl malonate.Methyl alcohol 250～300L is reclaimed in control still temperature≤65 ℃ of steamings under-0.05 ± 0.01MPa vacuum condition, make that sodium methylate is 1: 0.7～1.2 with the methanol quality ratio in the reaction system, once add methane amide 100kg (〉=99%) 60～70 ℃ of elder generations afterwards, add 90kg dimethyl malonate (〉=99%) in 10 minutes.The still temperature keeps 65～70 ℃ of insulations 2 hours after adding dimethyl malonate.Control still temperature under-0.05 ± 0.01MPa vacuum condition≤65 ℃ again steams 300～350L and reclaims methyl alcohol, after this process progressively adds water 1000L dissolving 4,6-dihydroxy-pyrimidine sodium salt, steamed methyl alcohol, cools off.Keep the still temperature to be no more than 40 ℃, add hydrochloric acid 920kg (〉=30%), make the still temperature be chilled to suction filtration below 10 ℃, washing, centrifugal after adding hydrochloric acid, dry under-0.09 ± 0.01MPa vacuum condition, get 4,6-dihydroxy-pyrimidine 198.9kg, content 98.9%, yield 83.6%, the outward appearance pale yellow powder.
Embodiment 4
1520kg sodium methylate (〉=27.5%) is added reactor, steam 650～700L and reclaim methyl alcohol, make that the mass ratio of sodium methylate and methyl alcohol is 1: 0.8～1.1 in the reaction system, after be cooled to 75 ℃, disposable adding 200kg methane amide (〉=99%), half an hour with the interior 200kg dimethyl malonate (〉=99%) that adds, add the dimethyl malonate process temperature and be controlled at 60～70 ℃.The still temperature keeps 65～70 ℃ of insulations 1.5 hours after adding dimethyl malonate.Once add methane amide 100kg (〉=99%) 60～70 ℃ of elder generations, add 100kg dimethyl malonate (〉=99%) in 10 minutes, add that the still temperature keeps 65～70 ℃ of insulations 2 hours behind the dimethyl malonate.Control still temperature under-0.05MPa vacuum condition≤65 ℃ steams 900～1000L and reclaims methyl alcohol, after this process progressively adds water 1000L dissolving 4,6-dihydroxy-pyrimidine sodium salt, steamed methyl alcohol, cools off.Keep the still temperature to be no more than 40 ℃, add hydrochloric acid 920kg (〉=30%), make the still temperature be chilled to suction filtration below 10 ℃, washing, centrifugal after adding hydrochloric acid, dry under-0.09 ± 0.01MPa vacuum condition, get 4,6-dihydroxy-pyrimidine 199kg, content 98.3%, yield 77.6%, the outward appearance pale yellow powder.
Embodiment 5～9: in the steps below, parameter carries out, all the other and embodiment 1 with.
| Embodiment | For the first time the charging reaction temperature (℃), the time (h) | For the first time low temperature holding temperature behind the charging reaction (℃), the time (h) | The front distillating carbinol of the charging reaction second time | For the second time the charging reaction temperature (℃), the time (h) | For the second time low temperature insulation degree behind the charging reaction (℃), the time (h) | The volume (L) of last Distillation recovery methyl alcohol | Final product 4, the content of 6-dihydroxy-pyrimidine (%), yield (%) |
| 5 | 63±3℃ 1h | Nothing | Carry out | 60±10℃ 1.8h | 32±2℃、 1.5h | 300～ 350 | 98.8％ 84.1％ |
| 6 | 67±3℃ 2h | 30～40℃ 1h | Nothing | 65±3℃ 1h | Nothing | 900～ 1000L | 98.5％ 81.2％ |
| 7 | 61±4℃ 1.3h | 30～40℃ 2.2h | Carry out | 71±4℃ 1.5h | Nothing | 300～ 350 | 97.6％ 80.9％ |
| 8 | 65±5℃ 1.5h | Nothing | Nothing | 64±4℃ 2h | 36±3℃、 2.2h | 900～ 1000L | 96.3％ 76.6％ |
| 9 | 64±4℃ 1.8h | 30～40℃ 2h | Carry out | 66±3℃ 1.4h | 34±4℃、 2.5h | 300～ 350 | 99.0％ 85.8％ |
The comparative example 1
1520kg sodium methylate (〉=27.5% commercially available specification, following same) the adding reactor, disposable adding 200kg methane amide (〉=99% commercially available specification, following same), half an hour with interior 190kg dimethyl malonate (〉=99% the commercially available specification that adds, following with), added behind the dimethyl malonate 67 ± 3 ℃ of insulation reaction of still temperature maintenance 1.5 hours.Methyl alcohol 250～300L is reclaimed in control still temperature≤65 ℃ of steamings under the normal pressure, once adds methane amide 100kg (〉=99%) 60～70 ℃ of elder generations afterwards, adds 90kg dimethyl malonate (〉=99%) in 10 minutes.The still temperature keeps 65～70 ℃ of insulations 0.5 hour after adding dimethyl malonate.Control still temperature under the condition of normal pressure≤65 ℃ steams 300～350L and reclaims methyl alcohol, after this process progressively adds water 1000L dissolving 4,6-dihydroxy-pyrimidine sodium salt, steamed methyl alcohol, cools off.Keep the still temperature to be no more than 40 ℃, add hydrochloric acid 920kg (〉=30% commercially available specification, following same), make the still temperature be chilled to suction filtration below 10 ℃, washing, centrifugal after adding hydrochloric acid, dry under-0.09 ± 0.01MPa vacuum condition, get 4,6-dihydroxy-pyrimidine 204.6kg, content 94.5%, yield 72.3%, outward appearance pale yellow powder.
By above embodiment as seen, the inventive method obviously is better than the synthetic method of the simple batch charging among the comparative example.
Claims (9)
1. one kind 4, the preparation method of 6-dihydroxy-pyrimidine, its raw material comprises malonic ester, methane amide and alkali metal alcoholate, comprises the steps: that a. mixes the alkali metal alcoholate of the malonic ester of significant quantity, methane amide and significant quantity/solvent suspension liquid, react under the condition of normal pressure; B. the described solvent of Distillation recovery is dissolved in water in described still-process and reacts 4 of gained, 6-dihydroxy-pyrimidine sodium salt; C. carry out acidifying, finally make product; It is characterized in that: the distillating recovering solvent process of described b step is to carry out under condition of negative pressure; Described charge temperature is 60～70 ℃; Temperature of reaction under the described condition of normal pressure is 60～70 ℃, and the reaction times is 1～2 hour; Behind the described a step charging reaction again batch charging react, wherein before the malonic ester that in reaction system, adds more than next batch of the amount of the malonic ester of a collection of adding and methane amide and the amount of methane amide, carry out again the b step after the batch charging reaction is finished; All carry out the low temperature insulation reaction before the b step before the batch charging and after the described batch charging reaction after the described a step, described low temperature insulation reaction temperature is 30～40 ℃, insulation reaction 0.5-3 hour.
2. as claimed in claim 14, the preparation method of 6-dihydroxy-pyrimidine is characterized in that: described negative pressure is-0.04～-0.06Mpa.
3. as claimed in claim 14, the preparation method of 6-dihydroxy-pyrimidine is characterized in that: described distillating recovering solvent is to be distilled to still internal solvent quality percentage composition≤45%.
4. as claimed in claim 14, the preparation method of 6-dihydroxy-pyrimidine is characterized in that: described alkali metal alcoholate and solvent quality are than being 1:0.7～1.3.
5. as claimed in claim 44, the preparation method of 6-dihydroxy-pyrimidine is characterized in that: described alkali metal alcoholate and solvent quality are than being 1:0.8～1.2.
6. as claimed in claim 14, the preparation method of 6-dihydroxy-pyrimidine is characterized in that: described alkali metal alcoholate and solvent quality are than being 1:1; Described malonic ester: methane amide: the alkali metal alcoholate mol ratio is 1:2～4:3～5.
7. as claimed in claim 14, the preparation method of 6-dihydroxy-pyrimidine is characterized in that: the acid that described acidifying is used is hydrochloric acid.
8. as claimed in claim 74, the preparation method of 6-dihydroxy-pyrimidine is characterized in that: also comprise drying step after the described acid adding, drying treatment adopts the vacuum drying treatment mode, and its vacuum tightness is 0～-0.1Mpa.
9. as claimed in claim 14, the preparation method of 6-dihydroxy-pyrimidine is characterized in that:
A. dimethyl malonate, the methane amide with the total consumption 2/3 of whole reaction mixes with the sodium methylate/methanol suspension of significant quantity, and charge temperature is 60～70 ℃, keeps condition of normal pressure, 60～70 ℃ of control temperature of reaction, insulation reaction 1～2 hour; Wherein, sodium methylate is 1:0.7～1.3 with the methanol quality ratio; Dimethyl malonate: methane amide: sodium methylate=1:2～4:3～5 are with molar ratio computing;
Temperature is reduced to 30～40 ℃, insulation reaction 0.5～3 hour;-0.03～-condition of negative pressure of 0.1Mpa under control still temperature at≤65 ℃, distill out methyl alcohol, the mass ratio that makes remaining sodium methylate and methyl alcohol is 1:0.7～1.3;
Second batch is reinforced: again add dimethyl malonate and the methane amide of the total consumption 1/3 of reaction in reaction system, keep condition of normal pressure, the control temperature was reacted 1～2 hour at 60～70 ℃;
Low temperature insulation after the reaction: temperature is reduced to 30～40 ℃, is incubated 0.5～3 hour;
B.-0.03～-condition of negative pressure of 0.1Mpa under control still temperature at≤65 ℃ of Distillation recovery methyl alcohol, material methanol quality percentage composition≤45% to the still; In this distillating carbinol process, progressively be dissolved in water and react 4 of gained, 6-dihydroxy-pyrimidine sodium salt;
C. carry out acidifying with hydrochloric acid, comprise cooling, centrifugal, drying step, finally make 4,6-dihydroxy-pyrimidine; Wherein drying is vacuum-drying, vacuum tightness is 0～-0.1Mpa.
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| CN105585192B (en) * | 2015-12-25 | 2018-03-09 | 石家庄杰克化工有限公司 | A kind of method of wastewater treatment of 4,6 dihydroxy-pyrimidine production |
| CN106366042B (en) * | 2016-08-29 | 2019-03-19 | 石家庄杰克化工有限公司 | A kind of 4,6- dihydroxy-pyrimidine continuously acidizing technique |
| CN110903252B (en) * | 2019-12-18 | 2021-08-10 | 潍坊滨海石油化工有限公司 | Preparation method of 4, 6-dihydroxypyrimidine |
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|---|---|---|---|---|
| CN1214044A (en) * | 1996-05-17 | 1999-04-14 | 曾尼卡有限公司 | Process for making 4,6-dihydroxypyrimidine |
| CN1406934A (en) * | 2001-08-16 | 2003-04-02 | 德古萨公司 | Preparation of 4,6-dihydric pyrimidine |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1214044A (en) * | 1996-05-17 | 1999-04-14 | 曾尼卡有限公司 | Process for making 4,6-dihydroxypyrimidine |
| CN1406934A (en) * | 2001-08-16 | 2003-04-02 | 德古萨公司 | Preparation of 4,6-dihydric pyrimidine |
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