CN101525310A - Method for compounding 1-benzoyl-3-(2-oxhydryl-1, 1-dimethylethyl) thiourea - Google Patents
Method for compounding 1-benzoyl-3-(2-oxhydryl-1, 1-dimethylethyl) thiourea Download PDFInfo
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- CN101525310A CN101525310A CN200910011256A CN200910011256A CN101525310A CN 101525310 A CN101525310 A CN 101525310A CN 200910011256 A CN200910011256 A CN 200910011256A CN 200910011256 A CN200910011256 A CN 200910011256A CN 101525310 A CN101525310 A CN 101525310A
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Abstract
The invention relates to a method for preparing an organic compound, in particular to a method for compounding 1-benzoyl-3-(2-oxhydryl-1,1-dimethylethyl) thiourea, which comprises the steps: an organic solvent and a raw material, namely 2-amido-2-methylpropanol are added into a reactor, the temperature is kept at 18 20 DEG C, a raw material, namely benzoyl isorhodanic ester is dissolved into the organic solvent to prepare mixed solution, the mixed solution is added into the reactor at the temperature of 18-20 DEG C, the mixture is stirred and reacts for 1 to 3 hours at the room temperature of 25 DEG C, and the organic solvent is rotationally evaporated to obtain a crude product, namely 1-benzoyl-3-(2-oxhydryl-1,1-dimethylethyl) thiourea. The method compounds the 1-benzoyl-3-(2-oxhydryl-1,1-dimethylethyl) thiourea in one step, uses simple raw materials, has reasonable proportion and proper and controllable reaction temperature.
Description
One, technical field:
The present invention relates to the synthetic method of compound, especially for the synthetic method of the compound of medicine intermediate.
Two, background technology:
1-benzoyl-3-(2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide mainly is to be applied to synthetic medicine intermediate, and this product is not seen bibliographical information by literature search, is a kind of new compound, and document does not provide the concrete synthesis technique of this compound yet.
Three, summary of the invention:
Main purpose of the present invention provides the synthetic method of a kind of 1-benzoyl-3-(2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide, and processing step is simple, and the synthesis condition gentleness is easy to operate, the product yield height.
The technical scheme that the present invention is adopted for achieving the above object is: 1-benzoyl-3-(2-hydroxyl-1; the 1-dimethyl ethyl) synthetic method of thiocarbamide; in reactor, add organic solvent and raw material 2-amino-2-methyl propyl alcohol; keep 18-20 ℃ of temperature; benzene feedstock formyl radical lsothiocyanates is dissolved in makes mixing solutions in the organic solvent; mixing solutions joins in the reactor; controlled temperature is at 18-20 ℃ during adding; add 25 ℃ of following stirring reaction 1～3h of back room temperature; rotation steams organic solvent and gets crude product 1-benzoyl-3-(2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide.
Add entry in the described crude product; 60 ℃ are stirred the 0.5h after-filtration, get product after the drying, use the mixed solution recrystallization crude product of ethyl acetate and sherwood oil (volume ratio 1: 1) at last; get purified product 1-benzoyl-3-(2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide after the drying.
The mol ratio of described benzene feedstock formyl radical isocyanic ester and 2-amino-2-methyl propyl alcohol is 1: 1～1.5, preferred 1: 1.2.
Described organic solvent can adopt methylene dichloride, chloroform, 1,2-ethylene dichloride, methyl tertiary butyl ether (MTBE), acetonitrile, methyl alcohol or ethanol equal solvent.
Reaction formula:
The present invention produces needs according to medicine, has designed a kind of synthetic route of new intermediate, adopts one-step synthesis 1-benzoyl-3-(2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide, and is raw materials used simple, and reasonable ratio, and temperature of reaction is suitable, better control.The product purity height that reaction makes, elaboration purity can reach more than 99%, is widely used in medicine production.
Four, embodiment:
Below in conjunction with embodiment the present invention is described in further detail, but the invention is not restricted to specific embodiment.
Embodiment 1
By synthetic 1-benzoyl-3-(2-hydroxyl-1, the 1-dimethyl ethyl) thiocarbamide of following reaction formula, reaction formula:
The raw material ingredient proportion:
| Name of material | Quality/g feeds intake | Mol ratio | Remarks |
| The benzoyl lsothiocyanates | 8.2 | 1 | Industrial goods, content 84.07% |
| 2-amino-2-methyl propyl alcohol | 4.7 | 1.2 | Industrial goods, content 95.7% |
| Methylene dichloride | 40 | Solvent |
Experimental procedure:
In the 100ml four-hole reactor that mechanical stirring, thermowell, reflux condensing tube are housed, add methylene dichloride 15g, 2-amino-2-methyl propyl alcohol 4.7g (0.05mol).Keep about 19 ℃ with water-bath.Benzoyl lsothiocyanates 8.2g (0.042mol) is dissolved in the methylene dichloride of 25g and is added drop-wise in the reaction system.Drip process control temp at 18-20 ℃.After dripping off, stir 1h down for 25 ℃ in room temperature.Rotation steams methylene dichloride and gets crude product 12.6g, purity 85.7%, crude product yield 95.3%.Add 100ml water in the 12.6g crude product, 60 ℃ are stirred the 0.5h after-filtration, get product 10.4g, purity 91.4% after the drying.Use the crude product of 40ml ethyl acetate and 40ml sherwood oil recrystallization 10.4g content 91.4% at last, get product 6.9g, purity 99.2% after the drying.Obtain content greater than 99% qualified product, yield is 63.5%.
Embodiment 2
The synthetic method of 1-benzoyl-3-(2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide adds ethanol 30g, 2-amino-2-methyl propyl alcohol 9.4g (0.1mol) in the 500ml four-hole reactor that mechanical stirring, thermowell, reflux condensing tube are housed.Keep about 19 ℃ with water-bath.Benzoyl lsothiocyanates 19.5g (0.1mol) is dissolved in the ethanol of 50g and is added drop-wise in the reaction system.Drip process control temp at 18-20 ℃.After dripping off, stir 1h down for 25 ℃ in room temperature.Rotation steams ethanol and gets crude product, purity 85.7%, crude product yield 95.3%.Add 200ml water in crude product, 60 ℃ are stirred the 0.5h after-filtration, get product purity 91% after the drying.Use 40ml ethyl acetate and 40ml sherwood oil recrystallization crude product at last, after the drying product, purity 99% is greater than 99% qualified product, yield is 65%.
Embodiment 3
1-benzoyl-3-(2-hydroxyl-1; the 1-dimethyl ethyl) synthetic method of thiocarbamide; in the 500ml four-hole reactor that mechanical stirring, thermowell, reflux condensing tube are housed, add methyl tertiary butyl ether 90g, 2-amino-2-methyl propyl alcohol 28.2g (0.3mol).Keep about 19 ℃ with water-bath.Benzoyl lsothiocyanates 19.5g (0.1mol) is dissolved in the methyl tertiary butyl ether of 50g and is added drop-wise in the reaction system.Drip process control temp at 18-20 ℃.After dripping off, stir 1h down for 25 ℃ in room temperature.Rotation steams methyl tertiary butyl ether and gets crude product, purity 85%, crude product yield 96%.Add 300ml water in crude product, 60 ℃ are stirred the 0.5h after-filtration, after the drying product, use 40ml ethyl acetate and 40ml sherwood oil recrystallization crude product at last, after the drying product purity greater than 99% qualified product, yield is 68%.
Embodiment 4
The synthetic method of 1-benzoyl-3-(2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide adds chloroform 100g, 2-amino-2-methyl propyl alcohol 37.6g (0.4mol) in the 500ml four-hole reactor that mechanical stirring, thermowell, reflux condensing tube are housed.Keep about 19 ℃ with water-bath.Benzoyl lsothiocyanates 19.5g (0.1mol) is dissolved in the chloroform of 50g and is added drop-wise in the reaction system.Drip process control temp at 18-20 ℃, after dripping off, stir 1h down for 25 ℃ in room temperature, rotation steams chloroform and gets crude product, adds 200ml water in crude product, and 60 ℃ are stirred the 0.5h after-filtration, after the drying product purity 90%.Use 40ml ethyl acetate and 40ml sherwood oil recrystallization crude product at last, after the drying product, purity 99% is greater than 99% qualified product, yield is 65%.
Claims (5)
1,1-benzoyl-3-(2-hydroxyl-1; the 1-dimethyl ethyl) synthetic method of thiocarbamide; it is characterized in that: in reactor, add organic solvent and raw material 2-amino-2-methyl propyl alcohol; keep 18-20 ℃ of temperature; benzene feedstock formyl radical lsothiocyanates is dissolved in makes mixing solutions in the organic solvent; mixing solutions joins in the reactor; controlled temperature is at 18-20 ℃ during adding; add 25 ℃ of following stirring reaction 1～3h of back room temperature; rotation steams organic solvent and gets crude product 1-benzoyl-3-(2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide.
2,1-benzoyl-3-(2-hydroxyl-1 according to claim 1; the 1-dimethyl ethyl) synthetic method of thiocarbamide; it is characterized in that: add entry in the crude product; 60 ℃ are stirred the 0.5h after-filtration; get product after the drying; use the mixed solution recrystallization crude product of ethyl acetate and sherwood oil (volume ratio 1: 1) at last, get purified product 1-benzoyl-3-(2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide after the drying.
3, the synthetic method of 1-benzoyl-3-according to claim 1 and 2 (2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide, it is characterized in that: the mol ratio of benzene feedstock formyl radical isocyanic ester and 2-amino-2-methyl propyl alcohol is 1: 1～1.5.
4, the synthetic method of 1-benzoyl-3-according to claim 1 and 2 (2-hydroxyl-1,1-dimethyl ethyl) thiocarbamide, it is characterized in that: the mol ratio of benzoyl isocyanic ester and 2-amino-2-methyl propyl alcohol is 1: 1.2.
5,1-benzoyl-3-(2-hydroxyl-1 according to claim 1 and 2; the 1-dimethyl ethyl) synthetic method of thiocarbamide; it is characterized in that: organic solvent can adopt methylene dichloride, chloroform, 1,2-ethylene dichloride, methyl tertiary butyl ether (MTBE), acetonitrile, methyl alcohol or ethanol equal solvent.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108642926A (en) * | 2018-04-26 | 2018-10-12 | 浙江汉邦化工有限公司 | A kind of thiourea derivative and preparation method thereof of dyeing terylene cleaning |
| CN115368282A (en) * | 2022-08-09 | 2022-11-22 | 吉安宏达秋科技有限公司 | Method for synthesizing 1, 3-disubstituted thiourea in aqueous phase |
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| CN1849301A (en) * | 2003-07-10 | 2006-10-18 | 艾其林医药公司 | Substituted arylthiourea derivatives useful as inhibitors of viral replication |
| WO2008021339A2 (en) * | 2006-08-15 | 2008-02-21 | Wyeth | Pyrrolidine and related derivatives useful as pr modulators |
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|---|---|---|---|---|
| CN1849301A (en) * | 2003-07-10 | 2006-10-18 | 艾其林医药公司 | Substituted arylthiourea derivatives useful as inhibitors of viral replication |
| WO2008021339A2 (en) * | 2006-08-15 | 2008-02-21 | Wyeth | Pyrrolidine and related derivatives useful as pr modulators |
| WO2008021331A2 (en) * | 2006-08-15 | 2008-02-21 | Wyeth | Oxazolidone derivatives as pr modulators |
| WO2008021309A1 (en) * | 2006-08-15 | 2008-02-21 | Wyeth | Imidazolidin-2-one derivatives useful as pr modulators |
| US20080045579A1 (en) * | 2006-08-15 | 2008-02-21 | Wyeth | Oxazolidine derivatives as PR modulators |
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| 张斌 等: "苯甲酰基硫脲衍生物及其配合物的合成及表征", 《西北民族大学学报( 自然科学版)》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108642926A (en) * | 2018-04-26 | 2018-10-12 | 浙江汉邦化工有限公司 | A kind of thiourea derivative and preparation method thereof of dyeing terylene cleaning |
| CN108642926B (en) * | 2018-04-26 | 2023-11-14 | 浙江汉邦新材料股份有限公司 | Thiourea derivative for dyeing and cleaning terylene and preparation method thereof |
| CN115368282A (en) * | 2022-08-09 | 2022-11-22 | 吉安宏达秋科技有限公司 | Method for synthesizing 1, 3-disubstituted thiourea in aqueous phase |
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