CN102174023B - Preparation method of hydroxyl pyridine compound - Google Patents
Preparation method of hydroxyl pyridine compound Download PDFInfo
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- CN102174023B CN102174023B CN 201110051827 CN201110051827A CN102174023B CN 102174023 B CN102174023 B CN 102174023B CN 201110051827 CN201110051827 CN 201110051827 CN 201110051827 A CN201110051827 A CN 201110051827A CN 102174023 B CN102174023 B CN 102174023B
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Abstract
The invention discloses a preparation method of a hydroxyl pyridine compound, which comprises the following steps of: taking hydrochloride or sulfate or nitrate of alkyl guanidine (shown in the formula II) as a reaction raw material; neutralizing with sodium hydroxide or potassium hydroxide; and then, taking toluene or xylene or chlorobenzene as a reaction solvent, and taking methanol or ethanol as a cosolvent for refluxing, dehydrating and dealcoholizing with alpha-alkyl acetoacetic ester (shown in the formula III) to react to obtain the hydroxyl pyridine compound (shown in the formula I). In the invention, by adding the methanol or ethanol as the cosolvent in the hydroxyl pyridine synthesis reaction, the solubility of the alkyl guanidine can be well increased, the decomposition of the reactants (alpha-alkyl acetoacetic ester and alkyl guanidine) is effectively controlled, the formation rate of the target product namely the hydroxyl pyridine compound shown in the general formula (I) is greatly increased, and the yield and content of the hydroxyl pyridine compound product shown in the general formula (I) are obviously improved, wherein the product yield is greater than 94%, and the product content is greater than 97%.
Description
Technical field:
The present invention relates to the preparation method of hydroxyl pyridine compound.
Background technology:
Hydroxyl pyridine compound is the intermediate of very important sterilant and agricultural chemicals, general structure (formula I) as follows:
Formula I: hydroxy pyrimidine general structure
For example: compound 2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine (is R
1CH
3, R
2H, R
3N-C
4H
9, compound) be key intermediate (GB1,182,584 of the phonetic phenol of sterilant second (ethirimol) or bupirimate (bupirimate), GB1,400,710, J.R.Finney et al Proc.Br.Insectic.Fungic.Conf.8th.1975,2,667); Compound 2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine (is R
1CH
3, R
2CH
3, R
3N-C
4H
9, compound) be the phonetic phenol of sterilant first (dimethirimol, GB1,182,584); Compound 2,2-dimethylamino-5-methyl-6-methyl-4-hydroxyl-pyrimidine (is R
1, R
2, R
3All be CH
3Compound) be the key intermediate (pirimicarb, GB1,181,657) of sterilant Aphox; Compound 2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine (is R
1, R
2CH
3, R
3Be H, compound) be the key intermediate (pirimiphos-methyl, GB1,019,227, GB1,204,552) of sterilant pririmiphos_methyl.
The general synthetic method of above-mentioned hydroxyl pyridine compound be by the hydrochloride of alkyl guanidine or vitriol or nitrate in alkali and after obtain alkyl guanidine (formula II), in organic solvent, prepare with a-alkyl Acetacetic acid alkyl ester (formula III) dehydration, dealcoholysis cyclization reaction again, used organic solvent generally is dimethylbenzene or toluene or chlorobenzene (DE2,308,858, GB1,341,844), reaction expression is as follows:
In the above-mentioned hydroxy pyrimidine synthetic method that all documents and industrialization provide at present, product yield is scarcely high, between 60-94%.(DE2,109,880; ZA7,101,152; DE2,308,858; Wu Jun, forestry garden, gold are built 2-dimethylamino-5, the study on the synthesis of 6-dimethyl-4-hydroxy pyrimidine, " agricultural chemicals ", Vol.36.No.1, P14-15 (1997); Tan Chengxia, Weng Jianquan, Sun Nabo etc., synthesizing of 2-diethylin-6-methyl-4-hydroxy pyrimidine, " agricultural chemicals ", Vol.44.No.6, P261-261 (2005): Lu Qingsong, the study on the synthesis of 2-diethylin-6-methyl-4-hydroxy pyrimidine, " printing during chemical industry ", Vol.15, No.8, P39-41 (2001)).
Cause the not high major cause of yield to be because the solubleness of alkyl guanidine (formula II) in organic solvent toluene, dimethylbenzene or chlorobenzene is little, cause itself and a-alkyl Acetacetic acid alkyl ester (formula III) speed of response very slow, and a-methyl-acetoacetic acid alkyl ester (formula III) easily decomposes under alkaline condition:
Alkyl guanidine (formula II) is at high temperature also unstable simultaneously, easily is decomposed into urea and amine, Ammonia material:
Summary of the invention:
The present invention provides the preparation method of the hydroxyl pyridine compound shown in the general formula (I),
R in the general formula (I)
1CH
3R
2H, CH
3R
3N-C
4H
9Or CH
3, H;
The reaction equation of general formula of the present invention (I) compound is as follows:
The present invention is as reaction raw materials take the hydrochloride of alkyl guanidine (formula II) or vitriol or nitrate, in sodium hydroxide or potassium hydroxide and after, take toluene or dimethylbenzene or chlorobenzene as reaction solvent, take methyl alcohol or ethanol as solubility promoter, make the hydroxyl pyridine compound shown in the general formula (I) with the reaction of a-alkyl Acetacetic acid alkyl ester.
The molar ratio of the hydrochloride of alkyl guanidine of the present invention or vitriol or nitrate and sodium hydroxide or potassium hydroxide and a-alkyl Acetacetic acid alkyl ester is hydrochloride or vitriol or the nitrate of alkyl guanidine: sodium hydroxide or potassium hydroxide: a-alkyl Acetacetic acid alkyl ester=1～0.5: 1.15: 1.2, the vitriol solubilizing agent toluene of the alkyl guanidine of the hydrochloride of 1 mole alkyl guanidine or nitrate or 0.5 mole or the consumption of dimethylbenzene or chlorobenzene were 2 liters; The consumption of solubility promoter is the 10%-25% of reaction solvent for use weight, temperature of reaction is the solvent boiling point temperature, and in 2～4 hours reaction times, reaction solution water and the vitriol oil are regulated pH value to 7, standing demix, the decompression precipitation obtains the hydroxyl pyridine compound shown in the product general formula of the present invention (I).Product yield＞94%, content＞97%
Concrete operation step of the present invention is:
Solvent, solubility promoter, guanidinesalt and sodium hydroxide (or potassium hydroxide) are added in the reactor, in 20-40 ℃ stir 2～4 hours after, begin to drip a-alkyl Acetacetic acid alkyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol (or ethanol), continuing temperature rising reflux reacts to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add entry and the vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, oil reservoir solvent that reduces pressure obtains the hydroxyl pyridine compound shown in white or the off-white color solid phase prod general formula (I).
The present invention is by adding methyl alcohol or ethanol as solubility promoter in the hydroxy pyrimidine building-up reactions, can increase well the solubleness of alkyl guanidine, effectively controlled the decomposition of reactant a-alkyl Acetacetic acid alkyl ester and alkyl guanidine, greatly accelerated the formation speed of the hydroxyl pyridine compound shown in the target product general formula (I), yield and the content of the hydroxyl pyridine compound product shown in the general formula (I) are significantly improved, product yield＞94%, content＞97%.
Further specify the present invention below in conjunction with specific embodiment
Embodiment: (following % all refers to weight percentage, and the yield of hydroxy pyrimidine is all in guanidinesalt)
Embodiment 1:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml toluene, 30ml methyl alcohol, start and stir, add 15.0g (0.05mol) sulfuric acid dimethylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 16.4g (0.12mol) a-methyl-acetoacetic acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature reaction to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 16.2g off-white color solid phase prod, content: 98.0%, and yield: 95.1%.
Embodiment 2:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml toluene, 20ml ethanol, start and stir, add 15.0g (0.05mol) sulfuric acid dimethylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 18.1g (0.12mol) a-methyl-acetoacetic acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature reaction to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.3g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 16.3g off-white color solid phase prod, content: 97.5%, and yield: 95.2%.
Embodiment 3:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml dimethylbenzene, 30ml methyl alcohol, start and stir, add 15.0g (0.05mol) sulfuric acid dimethylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 16.4g (0.12mol) a-methyl-acetoacetic acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature reaction to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 16.4g off-white color solid phase prod, content: 98.2%, and yield: 96.4%.
Embodiment 4:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml dimethylbenzene, 40ml ethanol, start and stir, add 15.0g (0.05mol) sulfuric acid dimethylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 18.1g (0.12mol) a-methyl-acetoacetic acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.4g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 16.2g off-white color solid phase prod, content: 97.5%, and yield: 94.6%.
Embodiment 5:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add the 200ml chlorobenzene, 30ml methyl alcohol, start and stir, add 15.0g (0.05mol) sulfuric acid dimethylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 4 hours, begin to drip 16.4g (0.12mol) a-methyl-acetoacetic acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 0.8g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 16.7g off-white color solid phase prod, content: 97.0%, and yield: 97%.
Embodiment 6:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add the 200ml chlorobenzene, 30ml ethanol, start and stir, add 15.0g (0.05mol) sulfuric acid dimethylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 18.1g (0.12mol) a-methyl-acetoacetic acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.5g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 16.2g off-white color solid phase prod, content: 98.0%, and yield: 95.1%.
Embodiment 7:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 1 gets product 16.1g, content: 98.5%, and yield: 95.6%.
Embodiment 8:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 2 gets product 16.0g, content: 98.4%, and yield: 94.3%.
Embodiment 9:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 3 gets product 16.4g, content: 97.7%, and yield: 96.0%.
Embodiment 10:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 4 gets product 16.2g, content: 98.3%, and yield: 95.3%.
Embodiment 11:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 5 gets product 16.1g, content: 99.2%, and yield: 95.6%.
Embodiment 12:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, other gets product 16.3g, content with embodiment 6: 97.7%, and yield: 95.4%.
Synthesizing of embodiment 13:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 150ml toluene, 50ml methyl alcohol, start and stir, add 15.0g (0.05mol) sulfuric acid one second guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 21.7g (0.12mol) a-butyl etheric acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 40ml water and the 1.2g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.5g white solid product, content: 98.5%, and yield: 96.6%.
Synthesizing of embodiment 14:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 150ml toluene, 50ml ethanol, start and stir, add 15.0g (0.05mol) sulfuric acid one second guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 4 hours, begin to drip 23.5g (0.12mol) a-butyl etheric acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 40ml water and the 1.2g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.1g white solid product, content: 98.5%, and yield: 94.7%.
Synthesizing of embodiment 15:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml dimethylbenzene, 30ml methyl alcohol, start and stir, add 15.0g (0.05mol) sulfuric acid one second guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 21.7g (0.12mol) a-butyl etheric acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.6g off-white color solid phase prod, content: 98.0%, and yield: 96.6%.
Synthesizing of embodiment 16:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 150ml dimethylbenzene, 20ml ethanol, start and stir, add 15.0g (0.05mol) sulfuric acid one second guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 23.5g (0.12mol) a-butyl etheric acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.4g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.5g off-white color solid phase prod, content: 98.3%, and yield: 96.4%.
Synthesizing of embodiment 17:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add the 150ml chlorobenzene, 20ml ethanol, start and stir, add 16.1g (0.05mol) sulfuric acid one second guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 4 hours, begin to drip 23.5g (0.12mol) a-butyl etheric acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.4g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.4g off-white color solid phase prod, content: 97.9%, and yield: 95.5%.
Synthesizing of embodiment 18:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add the 150ml chlorobenzene, 20ml methyl alcohol, start and stir, add 16.1g (0.05mol) sulfuric acid one second guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 21.7g (0.12mol) a-butyl etheric acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.4g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.4g off-white color solid phase prod, content: 98.0%, and yield: 95.6%.
Synthesizing of embodiment 19:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change solid caustic soda into potassium hydroxide, the other the same as in Example 13 gets product 20.5g, content: 97.8%, and yield: 95.9%.
Embodiment: 20:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 14 gets product 20.2g, content: 98.0%, and yield: 94.7%.
Synthesizing of embodiment 21:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change solid caustic soda into potassium hydroxide, the other the same as in Example 15 gets product 20.1g, content: 97.9%, and yield: 94.1%.
Synthesizing of embodiment 22:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change solid caustic soda into potassium hydroxide, the other the same as in Example 16 gets product 21.4g, content: 97.6%, and yield: 95.2%.
Synthesizing of embodiment 23:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change solid caustic soda into potassium hydroxide, the other the same as in Example 17 gets product 20.6g, content: 97.7%, and yield: 96.3%.
Synthesizing of embodiment 24:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change solid caustic soda into potassium hydroxide, the other the same as in Example 18 gets product 21.2g, content: 97.1%, and yield: 98.4%.
Embodiment 25:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml toluene, 20ml ethanol, start and stir, add 18.2g (0.05mol) sulfuric acid diethyl guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 16.0g (0.12mol) etheric acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.1g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 17.8g white solid product, content: 98.5%, and yield: 96.9%.
Embodiment 26:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml toluene, 20ml methyl alcohol, start and stir, add 18.2g (0.05mol) sulfuric acid diethyl guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 14g (0.12mol) etheric acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 0.9g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 18.1g white solid product, content: 97.5%, and yield: 97.5%.
Embodiment 27:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml dimethylbenzene, 20ml methyl alcohol, start and stir, add 18.2g (0.05mol) sulfuric acid diethyl guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 14g (0.12mol) etheric acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.2g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 18.3g white solid product, content: 97.5%, and yield: 98.6%.
Embodiment 28:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml dimethylbenzene, 20ml ethanol, start and stir, add 18.2g (0.05mol) sulfuric acid diethyl guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 16.0g (0.12mol) etheric acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.1g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 17.8g white solid product, content: 98.0%, and yield: 96.4%.
Embodiment 29:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add the 200ml chlorobenzene, 20ml methyl alcohol, start and stir, add 18.2g (0.05mol) sulfuric acid diethyl guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 14g (0.12mol) etheric acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.5g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 17.6g white solid product, content: 98.5%, and yield: 95.8%.
Embodiment 30:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add the 200ml chlorobenzene, 20ml ethanol, start and stir, add 18.2g (0.05mol) sulfuric acid diethyl guanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 16.0g (0.12mol) etheric acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.3g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 17.3g white solid product, content: 99.0%, and yield: 94.6%.
Embodiment 31:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 25 gets product 17.9g, content: 97.2%, and yield: 96.2%
Embodiment 32:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 26 gets product 17.8g, content: 97.8%, and yield: 96.2%.
Embodiment 33:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 27 gets product 18.0g, content: 97.7%, and yield: 97.2%.
Embodiment 34:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 28 gets product 18.2g, content: 97.5%, and yield: 97.9%.
Embodiment 35:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 29 gets product 18.2g, content: 97.0%, and yield: 97.5%.
Embodiment 36:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 30 gets product 17.9g, content 97.5%, yield: 96.5%.
Embodiment 37:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml toluene, 40ml methyl alcohol, start and stir, add 16g (0.05mol) sulfuric acid dimethylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 21.7g (0.12mol) a-butyl etheric acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 0.8g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.7g off-white color solid, content: 98.2%, and yield: 97.2%.
Embodiment 38:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml toluene, 40ml ethanol, start and stir, add 15g (0.05mol) sulfuric acid dimethylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 23.5g (0.12mol) a-butyl etheric acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.6g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.2g off-white color solid, content: 98.5%, and yield: 95.1%.
Embodiment 39:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml dimethylbenzene, 40ml methyl alcohol, start and stir, add 15g (0.05mol) sulfuric acid dimethylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 21.7g (0.12mol) a-butyl etheric acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.3g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.3g off-white color solid, content: 98.0%, and yield: 95.4%.
Embodiment 40:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add 200ml dimethylbenzene, 40ml ethanol, start and stir, add 15g (0.05mol) sulfuric acid dimethylguanidine and the oxidation of 4.8g (0.115mol) solid hydrogen, keep 20-40 ℃ to stir after 2 hours, begin to drip 23.5g (0.12mol) a-butyl etheric acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 35ml water and the 0.8g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.0g off-white color solid, content: 98.7%, and yield 94.4%.
Embodiment 41:2,2-dimethylamino-5-normal-butyl-6 methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add the 200ml chlorobenzene, 30ml methyl alcohol, start and stir, add 15g (0.05mol) sulfuric acid dimethylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 21.7g (0.12mol) a-butyl etheric acid methyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1.2g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.2g off-white color solid, content: 98.4%, and yield: 95.0%.
Embodiment 42:2,2-dimethylamino-5-normal-butyl-6 methyl-4-hydroxyl-pyrimidine synthetic
Stirring is being housed, thermometer, in three mouthfuls of reaction flasks of the 500ml of reflux exchanger, add the 200ml chlorobenzene, 30ml ethanol, start and stir, add 15g (0.05mol) sulfuric acid two: methylguanidine and 4.8g (0.115mol) solid sodium hydroxide, keep 20-40 ℃ to stir after 2 hours, begin to drip 23.5g (0.12mol) a-butyl etheric acid ethyl ester, drip to finish and be warming up to backflow, divide water outlet and ethanol, continue temperature rising reflux and react to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add 30ml water and the 1g vitriol oil, stirred conditioned reaction liquid pH=7 15 minutes, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains 20.4g off-white color solid, content: 98.0%, and yield: 95.6%.
Embodiment 43:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 37 gets product 20.5g, content: 98.2%, and yield: 96.3%.
Embodiment 44:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 38 gets product 20.3g, content: 98.5%, and yield: 95.6%.
Embodiment 45:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 39 gets product 21.0g, content: 96.3%, and yield: 96.7%.
Embodiment 46:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 40 gets product 20.6g, content: 97.0%, and yield: 95.6%.
Embodiment 47:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 41 gets product 20.2g, content: 98.4%, and yield: 95.0%.
Embodiment 48:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change solid caustic soda into potassium hydroxide, the other the same as in Example 42 gets product 20.0g, content: 98.6%, and yield: 94.3%.
Embodiment 49:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 1 gets product 16.1g, content: 98.5%, and yield: 95.6%.
Embodiment 50:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 2 gets product 16.0g, content: 98.4%, and yield: 94.3%.
Embodiment 51:2,2-dimethylamino-5,6-dimethyl-4-hydroxy pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 3 gets product 16.4g, content: 97.7%, and yield: 96.0%.
Embodiment 52:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 4 gets product 16.3g, content: 98.2%, and yield: 95.8%.
Embodiment 53:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 5 gets product 15.8g, content: 99.2%, and yield: 94.0%.
Embodiment 54:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, other gets product 16.2g, content with embodiment 6: 98.3%, and yield: 95.3%.
Embodiment 55:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 1 gets product 16.3g, content: 97.7%, and yield: 95.4%.
Embodiment 56:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 2 gets product 16.2g, content: 98.0%, and yield: 95.1%.
Embodiment 57:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 3 gets product 16.2g, content: 98.3%, and yield: 95.3%.
Embodiment 58:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 4 gets product 16.4g, content: 97.2%, and yield 95.4%.
Embodiment 59:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 5 gets product 16.3g, content: 97.6%, and yield: 95.3%.
Embodiment 60:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and other gets product 16.2g, content with embodiment 6: 98.3%, and yield: 95.3%.
Synthesizing of embodiment 61:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, the other the same as in Example 13 gets product 20.5g, content: 98.2%, and yield: 96.3%.
Synthesizing of embodiment 62:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, other gets product 20.4g, content with implementing 14: 98.0%, and yield: 95.6%.
Synthesizing of embodiment 63:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, other gets product 20.0g, content with implementing 15: 98.5%, and yield: 94.2%.
Synthesizing of embodiment 64:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, the other the same as in Example 16 gets product 20.5g, content: 97.6%, and yield: 95.7%.
Synthesizing of embodiment 65:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, other gets product 20.2g, content with implementing 17: 97.8%, and yield: 94.5%.
Synthesizing of embodiment 66:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, the other the same as in Example 18 gets product 20.2g, content: 98.4%, and yield: 95.1%.
Embodiment: 67:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 13 gets product 20.4g, content: 98.1%, and yield: 95.7%.
Synthesizing of embodiment 68:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 14 gets product 19.9g, content: 99.4%, and yield: 94.6%.
Synthesizing of embodiment 69:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 15 gets product 20.4g, content: 98.2%, and yield: 95.8%.
Synthesizing of embodiment 70:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 16 gets product 20.6g, content: 98.2%, and yield: 96.8%.
Synthesizing of embodiment 71:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 17 gets product 20.9g, content: 97.1%, and yield: 97.1%.
Synthesizing of embodiment 72:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 molar nitric acid one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 18 gets product 20.3g, content: 98.3%, and yield: 95.5%.
Embodiment 73:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, the other the same as in Example 25 gets product 17.8g, content: 98.2%, and yield: 96.6%.
Embodiment 74:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, the other the same as in Example 26 gets product 17.7g, content: 98.0%, and yield 95.8%.
Embodiment 75:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, the other the same as in Example 27 gets product 18.2g, content: 97.0%, and yield 97.0%.
Embodiment 76:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, the other the same as in Example 28 gets product 17.3g, content: 98.8%, and yield: 94.4%.
Embodiment 77:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, the other the same as in Example 29 gets product 17.6g, content: 98.6%, and yield 96.1%.
Embodiment 78:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, the other the same as in Example 30 gets product 17.4g, content: 98.7%, and yield: 94.9%.
Embodiment 79:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 25 gets product 17.3g, content: 98.8%, and yield: 94.5%.
Embodiment 80:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 26 gets product 17.8g, content: 98.5%, and yield: 96.9%.
Embodiment 81:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 27 gets product 17.9g, content: 97.0%, and yield 96.1%.
Embodiment 82:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 28 gets product 17.6g, content: 97.6%, and yield: 95.1%.
Embodiment 83:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 29 gets product 17.6g, content: 98.6%, and yield: 95.9%.
Embodiment 84:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 molar nitric acid diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 30 gets product 17.8g, content: 98.3%, and yield: 95.6%.
Embodiment 85:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 37 gets product and gets product 20.5g, content: 98.2%, and yield: 96.3%.
Embodiment 86:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 38 gets product 20.3g, content: 98.5%, and yield: 95.6%.
Embodiment 87:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 39 gets product 20.8g, content: 97.3%, and yield: 96.7%.
Embodiment 88:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 40 gets product 20.6g, content: 97.0%, and yield: 95.6%.
Embodiment 89:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 41 gets product 20.2g, content: 98.4%, and yield: 95.0%.
Embodiment 90:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, the other the same as in Example 42 gets product 20.0g, content: 98.5%, and yield: 94.5%.
Embodiment 91:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 37 gets product 20.2g, content: 98.6%, and yield: 95.3%.
Embodiment 92:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 38 gets product 20.6g, content: 97.6%, and yield: 96.2%.
Embodiment 93:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 39 gets product 20.6g, content: 97.1%, and yield: 95.7%.
Embodiment 94:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 40 gets product 20.3g, content: 99.0%, and yield: 96.1%.
Embodiment 95:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 41 gets product 20.4g, content: 98.0%, and yield: 95.6%.
Embodiment 96:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 molar nitric acid diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 42 gets product 20.3g, content: 98.1%, and yield: 95.2%.
Embodiment 97:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 1 gets product 16.1g, content: 98.5%, and yield: 95.6%.
Embodiment 98:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 2 gets product 16g, content: 98.4%, and yield: 94.3%.
Embodiment 99:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 3 gets product 16.4g, content: 97.7%, and yield: 96.0%.
Embodiment 100:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 4 gets product 16.2g, content: 98.3%, and yield: 95.3%.
Embodiment 101:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 5 gets product 16.1g, content: 99.2%, and yield: 95.9%.
Embodiment 102:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, other gets product 16.3g, content with embodiment 6: 97.7%, and yield: 95.4%.
Embodiment 103:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 1 gets product 16.4g, content: 97.3%, and yield: 95.6%
Embodiment 104:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 2 gets product 16.2, content: 98.2%, and yield: 95.1%.
Embodiment 105:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 3 gets product 16.2g, content: 97.3%, and yield: 94.4%.
Embodiment 106:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 4 gets product 16.1g, content: 98.5%, and yield: 95.0%.
Embodiment 107:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 5 gets product 16.2g, content: 98.4%, and yield: 95.5%.
Embodiment 108:2,2-dimethylamino-5,6-dimethyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and other gets product 16.5g, content with embodiment 6: 98.3%, and yield: 97.1%.
Synthesizing of embodiment 109:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, the other the same as in Example 13 gets product 20.4, content: 97.0%, and yield: 94.6%.
Synthesizing of embodiment 110:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, the other the same as in Example 14 gets product 20.2g, content: 98.7%, and yield: 95.4%.
Synthesizing of embodiment 111:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, the other the same as in Example 15 gets product 20.5g, content: 98.6%, and yield: 96.6%.
Synthesizing of embodiment 112:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, the other the same as in Example 16 gets product 10.1g, content: 98.3%, and yield: 94.5%.
Synthesizing of embodiment 113:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, the other the same as in Example 17 gets product 20.5g, content: 98.0%, and yield: 96.1%.
Synthesizing of embodiment 114:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, the other the same as in Example 18 gets product 20.0g, content: 99.0%, and yield: 94.5%.
Synthesizing of embodiment 115:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 13 gets product 20.4g, content: 97.7%, and yield: 95.3%.
Synthesizing of embodiment 116:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 14 gets product 20.2g, content: 97.8%, and yield: 94.5%.
Synthesizing of embodiment 117:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride guanidine one second salt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 15 gets product 20.7g, content: 97.5%, and yield: 96.6%.
Synthesizing of embodiment 118:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 16 gets product 20.5g, content: 97.3%, and yield: 95.4%.
Synthesizing of embodiment 119:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 17 gets product 20.4g, content: 98.0%, and yield: 95.6%.
Synthesizing of embodiment 120:2-ethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine
Change 0.05 mol sulfuric acid, one second guanidinesalt into 0.1 mole hydrochloride one second guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 18 gets product 20.6g, content: 98.0%, and yield: 96.7%.
Embodiment 121:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, the other the same as in Example 25 gets product 20.5g, content: 98.2%, and yield: 96.2%.
Embodiment 122:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, the other the same as in Example 26 gets product 17.8g, content: 97.8%, and yield: 96.2%.
Embodiment 123:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, the other the same as in Example 27 gets product 18g, content: 97.7%, and yield: 97.2%.
Embodiment 124:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, the other the same as in Example 28 gets product 18.3g, content: 96.8%, and yield: 97.9%
Embodiment 125:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, the other the same as in Example 29 gets product 18.2g, content: 97.0%, and yield: 97.5%.
Embodiment 126:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, the other the same as in Example 30 gets product 17.3g, content: 98.5%, and yield: 94.1%.
Embodiment 127:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 25 gets product 17.6g, content: 98.6%, and yield: 95.9%.
Embodiment 128:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 26 gets product 17.6g, content: 98.4%, and yield: 95.7%.
Embodiment 129:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 27 gets product 17.8g, content: 97.5%, and yield: 96.5%.
Embodiment 130:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 28 gets product 17.6g, content: 97.8%, and yield: 95.1%.
Embodiment 131:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 29 gets product 17.5g, content: 98.0%, and yield: 94.8%.
Embodiment 132:2,2-diethylin-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diethyl guanidinesalt into 0.1 mole hydrochloride diethyl guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 30 gets product 17.9g, content: 96.6%, and yield: 95.5%.
Embodiment 133:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 37 gets product 20.5g, content: 98.2%, and yield: 96.3%.
Embodiment 134:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 38 gets product 20.2g, content: 98.5%, and yield: 95.2%.
Embodiment 135:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 39 gets product 20.8g, content: 97.3%, and yield: 96.7%.
Embodiment 136:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 40 gets product 20.6g, content: 97.0%, and yield: 95.6%.
Embodiment 137:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 41 gets product 20.2g, content: 98.4%, and yield: 95.0%.
Embodiment 138:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid guanidine diformazan salt into 0.1 mole hydrochloride diformazan guanidinesalt, the other the same as in Example 42 gets product 20.0g, content: 98.6%, and yield: 94.3%.
Embodiment 139:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid guanidine diformazan salt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 37 gets product 20.4g, content: 98.0%, and yield: 95.6%.
Embodiment 140:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 38 gets product 20.2g, content: 98.4%, and yield: 95.3%.
Embodiment 141:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 39 gets product 20.5g, content: 97.6%, and yield: 95.6%.
Embodiment 142:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 40 gets product 20.4g, content: 98.1%, and yield: 95.7%.
Embodiment 143:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 41 gets product 19.6g, content: 98.8%, and yield: 94.5%.
Embodiment 144:2,2-dimethylamino-5-normal-butyl-6-methyl-4-hydroxyl-pyrimidine synthetic
Change 0.05 mol sulfuric acid diformazan guanidinesalt into 0.1 mole hydrochloride diformazan guanidinesalt, sodium hydroxide changes potassium hydroxide into, and the other the same as in Example 42 gets product 20.2g, content: 97.6%, and yield: 95.2%.
Claims (2)
1. the preparation method of hydroxyl pyridine compound is characterized in that: hydroxyl pyridine compound represents with logical formula I,
R in the logical formula I
1CH
3R
2H, CH
3R
3N-C
4H
9Or CH
3, H; Reaction equation is:
As reaction raw materials take the hydrochloride of the described alkyl guanidine of formula II or vitriol or nitrate, in sodium hydroxide or potassium hydroxide and after, take toluene or dimethylbenzene or chlorobenzene as reaction solvent, take methyl alcohol or ethanol as solubility promoter, make hydroxyl pyridine compound shown in the general formula (I) with alpha-alkyl Acetacetic acid alkyl ester or Acetacetic acid alkyl ester reaction;
The molar ratio of the hydrochloride of alkyl guanidine or vitriol or nitrate and sodium hydroxide or potassium hydroxide and alpha-alkyl Acetacetic acid alkyl ester or Acetacetic acid alkyl ester is hydrochloride or nitrate or the vitriol of alkyl guanidine: sodium hydroxide or potassium hydroxide: alpha-alkyl Acetacetic acid alkyl ester or Acetacetic acid alkyl ester=1～0.5:1.15:1.2, and the vitriol solubilizing agent toluene of the alkyl guanidine of the hydrochloride of 1 mole alkyl guanidine or nitrate or 0.5 mole or the consumption of dimethylbenzene or chlorobenzene are 2 liters; The consumption of solubility promoter is the 10%-25% of reaction solvent for use weight, temperature of reaction is the solvent boiling point temperature, 2～4 hours reaction times, reaction solution water and the vitriol oil are regulated pH value to 7, standing demix, the decompression precipitation obtains hydroxyl pyridine compound product shown in the general formula (I), product yield＞94%, content＞97%.
2. the preparation method of hydroxyl pyridine compound according to claim 1, it is characterized in that: concrete operation step is with solvent, solubility promoter, guanidinesalt and sodium hydroxide or potassium hydroxide add in the reactor, in 20-40 ℃ stir 2～4 hours after, begin to drip alpha-alkyl Acetacetic acid alkyl ester or Acetacetic acid alkyl ester, drip to finish and be warming up to backflow, divide water outlet and methyl alcohol or ethanol, continuing temperature rising reflux reacts to solvent boiling point, reaction finishes, be cooled to below 100 ℃, add entry and the vitriol oil, stirred 15 minutes, conditioned reaction liquid pH=7, static minute water-yielding stratum, the oil reservoir solvent that reduces pressure obtains the hydroxyl pyridine compound shown in white or the off-white color solid phase prod general formula (I).
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