CN101417929B - Synthetic method of hydroxybenzaldehyde - Google Patents
Synthetic method of hydroxybenzaldehyde Download PDFInfo
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- CN101417929B CN101417929B CN2008102447048A CN200810244704A CN101417929B CN 101417929 B CN101417929 B CN 101417929B CN 2008102447048 A CN2008102447048 A CN 2008102447048A CN 200810244704 A CN200810244704 A CN 200810244704A CN 101417929 B CN101417929 B CN 101417929B
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- synthetic method
- triphosgene
- sylvan
- ester
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Oc1ccccc1 Chemical compound Oc1ccccc1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N COc1ccccc1 Chemical compound COc1ccccc1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to a synthetic method of hydroxybenzaldehyde, taking methyl phenol as raw material, and comprises the following steps: first, methyl phenolic sodium and triphosgene carry out esterification reaction to generate dialkyl carbonate; then, under the condition of melting and sun illumination, ontology chlorination generates dialkyl carbonate; finally, hydroxybenzaldehyde is generated under the condition of acidic condition. The methyl is taken as raw material to generate hydroxybenzaldehyde, based on which the rest can be proposed. The synthetic method of hydroxybenzaldehyde has the advantages of simple technique, steady reaction, easy controlling, easy to obtain raw material, convenient for industrialization, rare corrosion to equipment, safe to environment, high product yield; when methyl is taken as raw material, the yield rate is equal to or more than 87 percent.
Description
One, technical field
The present invention relates to a kind of preparation method of known compound, exactly is a kind of synthetic method to (adjacent) hydroxy benzaldehyde.
Two, background technology
Hydroxy benzaldehyde is a kind of important organic intermediate, is widely used in industries such as medicine, spices and chemical industry, and annual requirement is huge, and supply falls short of demand in market, the nearly kiloton of the annual breach of China.
The hydroxy benzaldehyde of, quality better cheap in order to obtain, in recent years the candidate go out many new synthetic methods and Technology.The main method that now will produce hydroxy benzaldehyde is summed up as following a few class: the first is raw material with phenol, by with chloroform [Mark H F.Kirk-Othmer, EncylChemTech[M] .3rded.NewYork:JohnWiley﹠amp; Sons, 1981:1370-1378.] or formaldehyde [Kamimura, Hiroshi.JP, 62153240[P] (1987)]. wait the synthetic p-Hydroxybenzaldehyde of reaction, these method technologies are simple, but process recovery ratio is low, raw material consumption is big, and to the requirement height of equipment, phenolic wastewater is difficult for handling; It two is being raw material to (adjacent) cresols, have: 1. directly by and oxygen reaction synthetic to (adjacent) hydroxy benzaldehyde [Akada M, YoshikuniT.JP, 6124535[P] (1986)], this raw materials technology is cheap, but the technology generation contains phenol strong basicity waste water 20-30 ton/ton product [Wang F, et al.[J] .Chem Commun, 2003 (11): 1172-1173], technology is polluted more serious, and the difficult selection of catalyzer; 2. to (adjacent) cresols, through the aceticanhydride esterification, chlorination and hydrolysis make p-Hydroxybenzaldehyde [five Tian Bo etc. the open JP62155236A (1987) of Japan's special permission; Gold Ao profit is grand etc. the open JP63208550A (1988) of Japan's special permission]; 3. to utilizing the p.putkside-0160 bacterial classification to obtain hydroxy benzaldehyde [Edward S by biotransformation to (adjacent) cresols, Miller Jr, andSteven W, Peretti[J] .Green Chemisry, June 1999:143-152], though this technology green is pollution-free, the productive rate height, simple to operate, reaction conditions is also relatively gentleer, but the production cycle is oversize, and still is imitated the end.It three is to be raw material with other material, as aminobenzaldehyde method [Takeshita A, Tokumwu T.JP, 02172940[P] (1990)] etc., but all owing to exist at the bottom of complex process, the product purity and shortcoming such as production cost height.
Three, summary of the invention
The present invention aims to provide a kind of new synthetic method for preparing hydroxy benzaldehyde, and technical problem to be solved is to select new operational path.
The alleged hydroxy benzaldehyde of the present invention comprises p-Hydroxybenzaldehyde, m-hydroxybenzaldehyde and salicylaldhyde.Used raw material is p-cresol, meta-cresol and ortho-cresol successively.For sake of convenience, following general designation sylvan.
This operational path is starting raw material with the sylvan, at first carry out esterification and generate carbonic acid two (aminomethyl phenyl) ester with the esterifying agent triphosgene, the side chain chlorination generates carbonic acid two (dichloromethyl phenyl) ester (calling the dichloro-ester in the following text) then, and last hydrolysis generates the target product hydroxy benzaldehyde.This process flow is as follows:
The applicant once crossed patent of invention, ZL00119052.0 with regard to preparation method's application of triphosgene.
This synthetic method is raw material with the sylvan, physical process such as comprise esterification, chlorination and hydrolysis chemical process and separate accordingly, and its feature is being:
1, described esterification is that the sodium-salt aqueous solution of sylvan is stirring and having under antioxidant and the catalyzer existence condition in 25～35 ℃ of reactions 3～4 hours with triphosgene organic solution, reaction finishes with ammoniacal liquor, formic acid and water washing, standing demix is got the organic phase precipitation and is obtained carbonic acid two (aminomethyl phenyl) ester.
The mol ratio of sylvan and triphosgene is 1: 0.15～0.22, preferred 1: 0.17～0.19.
Described triphosgene organic solution promptly is that triphosgene is dissolved in the solution that forms in methylene dichloride or benzene or toluene or the tetrahydrofuran solvent, the preferred saturated organic solution of triphosgene.
Described antioxidant is selected from S-WAT or sodium bisulfite or Sulfothiorine etc., and addition is 2～3% of a raw material sylvan quality.
Described catalyzer is selected from N-methylmorpholine or triethylamine or triethylene diamine or pyridine or pyridine derivate etc., and addition is 2～3% of a raw material sylvan quality.
Experiment shows, uses sylvan sodium powder and triphosgene organic solution to carry out solid-liquid reaction under same processing condition and can obtain carbonic acid two (aminomethyl phenyl) ester too.
2, described chlorination is that carbonic acid two (aminomethyl phenyl) ester directly feeds chlorine under fusion and illumination and agitation condition, when passing to theoretical amount (mol ratio of ester and chlorine is 1: the 2) left and right sides, be cooled to 60～70 ℃, add hexamethylenetetramine and 80% (volume percent) aqueous ethanolic solution, back flow reaction 1～2 hour transfers reacting liquid pH value to 4～6 to continue back flow reaction 1～2 hour with alkali.
Described illumination is selected from high voltage mercury lamp or fluorescent ultraviolet lamp.
3, described hydrolysis is directly to carry out in not separated chlorination reaction liquid.Concrete grammar is to add water and phase-transfer catalyst in reaction solution, and transfers reacting liquid pH value to 1～2, heating reflux reaction 1～2 hour with mineral acid.Reaction finishes postcooling, separation, obtains the solid hydroxy benzaldehyde.
Described phase-transfer catalyst is selected from polyoxyethylene glycol (PEG) or quaternary ammonium salt, as 4 bromide or Tetrabutyl amonium bromide or triethyl benzyl ammonia chloride etc.Its consumption is 0.5～2% of a dichloro-ester quality.
Described mineral acid is selected from hydrochloric acid or sulfuric acid.
Present method has following having a few:
(1) compare with the acetic anhydride acidylate, triphosgene method toxicity is little, reaction process is simple, reacting balance is easy to control and safe.Because present method adopts into ester method protection hydroxyl, improved the yield of final product greatly, reduced production cost.
(2) chlorination stage adopts solvent-free substance law, has avoided use solvent C Cl
4, CCl
4Not only poisonous and atmospheric layer had strong destruction.
(3) chlorizate does not separate, and directly it is carried out the Shamir dealkylation reaction, improves the output of target product hydroxy benzaldehyde, has avoided because the material that separation brought of product is wasted and additional process, and cost is lower.In raw material sylvan target product yield 〉=87%.
(4) compare with hydrolysis final products such as acetic anhydride, the present invention has generated carbonic acid gas and water, and is little to the corrodibility of equipment.
(5) raw materials used being used always and cheap raw material, and synthesis condition is gentle, is convenient to suitability for industrialized production.
Four, embodiment
Embodiment 1
In 250 milliliters of four-hole boiling flasks that agitator, prolong, dropping funnel, thermometer are housed, add 21.612g p-cresol, 2% sodium bisulfite, 8g sodium hydroxide and 50ml water successively, stir fast, dissolve fully to p-cresol, at room temperature, dropping contains the methylene dichloride saturated solution of 10.8g triphosgene, after dropwising, add 2% catalyst n-methylmorpholine, reacted 2 hours, wash repeatedly repeatedly with ammoniacal liquor, formic acid, distilled water, get dichloromethane layer, solvent evaporated gets carbonic acid two (aminomethyl phenyl) ester.Yield is calculated as 98.4% with p-cresol.
With the methylene dichloride above-mentioned product ester of purifying, oven dry is put into and is equipped with in agitator, prolong, 250 milliliters of four-hole boiling flasks of thermometer, stir, heating is under the ester molten state, feed chlorine, pass to theoretical amount (about 6 hours) by the flow of 20～30 liters of/kilogram esters hour.Be cooled to 60～70 ℃.
Add 4.4g hexamethylenetetramine, 20ml ethanol, 5mL water successively in flask, stir, reflux 2 hours, cooling and stirring slowly add 6ml (50～70% sodium hydroxide liquid), keep pH 4～6, and heating in water bath refluxed 2 hours.
Steam ethanol, add 5～6 in 100ml water, 0.5% phase-transfer catalyst 4 bromide, concentrated hydrochloric acid in bottle, be heated to 90～110 ℃ of backflows, cooling is filtered, the p-Hydroxybenzaldehyde crude product, yield is calculated as 88.1% with p-cresol.
Embodiment 2
In 250 milliliters of four-hole boiling flasks that agitator, prolong, dropping funnel, thermometer are housed, add 25.8g meta-cresol sodium salt, 3% sodium bisulfite, 2% triethylamine and 50ml methylene dichloride successively, stir fast, at room temperature, begin to drip the toluene saturated solution that contains the 10.8g triphosgene, after dropwising, reacted 2 hours, wash repeatedly repeatedly with ammoniacal liquor, formic acid, distilled water, get toluene layer, solvent evaporated gets carbonic acid two (aminomethyl phenyl) ester.Yield is calculated as 97.6% with meta-cresol.
With the toluene above-mentioned product ester of purifying, oven dry is put into and is equipped with in agitator, prolong, 250 milliliters of four-hole boiling flasks of thermometer, stirs, and heating under the ester molten state, feeds chlorine, reacts 6 hours.Be cooled to 60～70 ℃.
In flask, add 4.4g hexamethylenetetramine, 20ml ethanol, 5mL water successively, stir, reflux 2 hours, cooling and stirring slowly adds a certain amount of sodium hydroxide solution, keeps pH 4～6, and heating in water bath refluxed 2 hours.
Steam ethanol, add 5～6 in 100ml water, PEG200g, concentrated hydrochloric acid in bottle, be heated to 90～110 ℃ of backflows, cooling is filtered, the m-hydroxybenzaldehyde crude product, yield is calculated as 87.2% with meta-cresol.
Embodiment 3
In 250 milliliters of four-hole boiling flasks that agitator, prolong, dropping funnel, thermometer are housed, add 21.612g ortho-cresol, 2% sodium bisulfite, 8g sodium hydroxide and 50ml water successively, stir fast, dissolve fully to ortho-cresol, at room temperature, dropping contains the methylene dichloride saturated solution of 10.8g triphosgene, after dropwising, add 2% catalyst n-methylmorpholine, reacted 2 hours, wash repeatedly repeatedly with ammoniacal liquor, formic acid, distilled water, get dichloromethane layer, solvent evaporated gets carbonic acid two (aminomethyl phenyl) ester.Yield is calculated as 98.4% with ortho-cresol.
With the methylene dichloride above-mentioned product ester of purifying, oven dry is put into and is equipped with in agitator, prolong, 250 milliliters of four-hole boiling flasks of thermometer, stirs, and heating under the ester molten state, feeds chlorine, reacts 6 hours.Be cooled to 60～70 ℃.
Add 4.4g hexamethylenetetramine, 20mL ethanol, 5mL water successively in flask, stir, reflux 2 hours, cooling and stirring slowly add 6ml (50～70% sodium hydroxide liquid), keep pH 4～6, and heating in water bath refluxed 2 hours.
Steam ethanol, add 5～6 in 100ml water, 0.5% phase-transfer catalyst, four J base brometo de amonio, concentrated hydrochloric acid in bottle, be heated to 90～110 ℃ of backflows, cooling is filtered, the salicylaldhyde crude product, yield is calculated as 88.1% with ortho-cresol.
Claims (8)
1. the synthetic method of a hydroxy benzaldehyde, with the sylvan is raw material, comprise esterification, chlorination and hydrolysis, it is characterized in that: to be sylvan sodium solid or sylvan sodium water solution and triphosgene organic solution generated carbonic acid two (aminomethyl phenyl) ester in 3～4 hours in 25～35 ℃ of reactions to described esterification under the condition that antioxidant and catalyzer exist, and the mol ratio of sylvan and triphosgene is 1: 0.15～0.22; Described triphosgene organic solution is that triphosgene is dissolved in the solution that forms in methylene dichloride or benzene or toluene or the tetrahydrofuran solvent; Described chlorination is that carbonic acid two (aminomethyl phenyl) ester carries out side chain chlorination generation carbonic acid two (dichloromethyl phenyl) ester under fusion and illumination condition, and described hydrolysis is that the hydrolysis under acidic conditions of carbonic acid (dichloromethyl phenyl) ester generates hydroxy benzaldehyde.
2. synthetic method according to claim 1 is characterized in that: the mol ratio of sylvan and triphosgene is 1: 0.17～0.19.
3. synthetic method according to claim 1 is characterized in that: described triphosgene organic solution is the saturated organic solution of triphosgene.
4. synthetic method according to claim 1 is characterized in that: described antioxidant is selected from S-WAT or sodium bisulfite or Sulfothiorine, and addition is 2～3% of a raw material sylvan quality.
5. synthetic method according to claim 1 is characterized in that: described catalyzer is selected from N-methylmorpholine or triethylamine or triethylene diamine or pyridine or pyridine derivate, and addition is 2～3% of a sylvan quality.
6. synthetic method according to claim 1, it is characterized in that: described chlorination is that carbonic acid two (aminomethyl phenyl) ester directly feeds chlorine under fusion and illumination and agitation condition, stop logical chlorine when passing to theoretical amount and be cooled to 60～70 ℃, add hexamethylenetetramine and 80% aqueous ethanolic solution, back flow reaction 1～2 hour, transfer reacting liquid pH value to 4～6 with alkali, continued back flow reaction 1～2 hour; Described illumination is selected from high voltage mercury lamp or fluorescent ultraviolet lamp.
7. synthetic method according to claim 1 is characterized in that: described hydrolysis is to add water and phase-transfer catalyst in chlorination reaction liquid, and transfers reaction solution pH to 1～2, heating reflux reaction 1～2 hour with mineral acid.
8. synthetic method according to claim 7 is characterized in that: described phase-transfer catalyst is selected from polyoxyethylene glycol or quaternary ammonium salt, and addition is 0.5～2% of a dichloro-ester quality.
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| CN2008102447048A CN101417929B (en) | 2008-11-26 | 2008-11-26 | Synthetic method of hydroxybenzaldehyde |
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| CN2008102447048A CN101417929B (en) | 2008-11-26 | 2008-11-26 | Synthetic method of hydroxybenzaldehyde |
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| CN101417929B true CN101417929B (en) | 2011-06-08 |
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| CN103204768A (en) * | 2013-03-12 | 2013-07-17 | 西北大学 | Synthetic method for hydroxybenzaldehyde |
| CN116253627A (en) * | 2022-12-27 | 2023-06-13 | 大连双硼医药化工有限公司 | Method for synthesizing 2-bromo-6-hydroxybenzaldehyde |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87102469A (en) * | 1987-03-30 | 1987-11-11 | 武汉市化学工业研究所 | The novel method of industrial production salicylaldhyde |
| CN1319581A (en) * | 2000-09-06 | 2001-10-31 | 吉林省石油化工设计研究院 | Process for preparation of p-hydroxy-benzaldehyde |
| CN1502406A (en) * | 2002-11-22 | 2004-06-09 | 中国科学院大连化学物理研究所 | Catalyst for synthesizing para-hydroxybenzenemethylal by using paracresol, preparation and use |
-
2008
- 2008-11-26 CN CN2008102447048A patent/CN101417929B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87102469A (en) * | 1987-03-30 | 1987-11-11 | 武汉市化学工业研究所 | The novel method of industrial production salicylaldhyde |
| CN1319581A (en) * | 2000-09-06 | 2001-10-31 | 吉林省石油化工设计研究院 | Process for preparation of p-hydroxy-benzaldehyde |
| CN1502406A (en) * | 2002-11-22 | 2004-06-09 | 中国科学院大连化学物理研究所 | Catalyst for synthesizing para-hydroxybenzenemethylal by using paracresol, preparation and use |
Non-Patent Citations (1)
| Title |
|---|
| 李超等.对羟基苯甲醛的应用及其合成技术.《安徽化工》.2008,第34卷(第3期),17-19. * |
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Assignee: Anhui JuKai Agricultural Co., Ltd. Assignor: Hefei University of Technology Contract record no.: 2011340000454 Denomination of invention: Synthetic method of hydroxybenzaldehyde Granted publication date: 20110608 License type: Exclusive License Open date: 20090429 Record date: 20111208 |
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