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| p-Hydroxybenzaldehyde Chemical Properties |
| Hazard Codes |
Xi |
| Risk Statements |
36/37/38-R36/37/38 |
| Safety Statements |
26-36-24/25-37/39-S24/25 |
| WGK Germany |
2 |
| RTECS |
CU6475000 |
| Autoignition Temperature |
450 °C |
| Hazard Note |
Irritant/Air Sensitive |
| TSCA |
Yes |
| HS Code |
29124900 |
| Toxicity |
LD50 orally in Rabbit: 2250 mg/kg |
| Provider |
Language |
| 4-Hydroxybenzaldehyde |
English |
| ACROS |
English |
| SigmaAldrich |
English |
| ALFA |
English |
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| p-Hydroxybenzaldehyde Usage And Synthesis |
| description |
There are three kinds of isomers of hydroxybenzaldehyde, namely, o-hydroxybenzaldehyde, m-hydroxybenzaldehyde and p-hydroxybenzaldehyde. p-hydroxybenzaldehyde is also known as phenol formaldehyde. When precipitated from water, it is white to pale yellow needles. It has aromatic odor. At atmospheric pressure, it can be sublimated without decomposition. The molecular weight is 122.12. Melting point: 115~116 °C. The relative density is 1.129 (130/4 °C). The refractive index is 1.5705 (130 °C). It is slightly soluble in water and benzene, easily soluble in alcohol, ether, acetone, and ethyl acetate with water solubility at 30.5 °C being 1.38 and benzene solubility in 65 °C being 3.68. Intraperitoneal injection of mice: LD50: 500mg/kg.
p-Hydroxybenzaldehyde is an important intermediate of pharmaceutical, perfume, liquid crystal. It can generate anisaldehyde when having reaction with dimethyl sulfate, and can generate hydroxy cinnamic aldehyde upon its reaction with acetaldehyde which can further undergo oxidation to obtain cinnamic acid. The direct oxidation of this product can prepare hydroxybenzoic acid; Its reduction can generate p-hydroxyphenyl rmethanol; both of them can be used as spices; pharmaceutical intermediates; raw material of liquid crystal; other kinds of organic synthesis intermediates with a wide range of applications.
In addition to be used as a spice, m-hydroxybenzaldehyde can also be used as the intermediate of producing other kind of species; it can also be used as a kind of pharmaceutical raw materials for production of phenylephrine hydrochloride, epinephrine, and quinine; nickel plating; chemical analysis reagent (sugar quantitative analysis) ; photographic emulsion and fungicides.
O-hydroxybenzaldehyde, also known as salicylaldehyde, is a kind of colorless oily liquid with special odor and bitter almond flavor. It is chemically active and can have various kinds of reactions such as substitution condensation, oxidation, and Wei Tixi (Wittig) reaction. Its reaction with sulfuric acid generates orange color; its reaction with metal ions is to form a colored chelate. Its reaction with ferric chloride solution yields purple color and it can be reduced to salicyl alcohol. It is mainly used as the raw material for the production of perfume "coumarin" and "Dihydrocoumarins"; it can also be used as the raw material for preparation of violet fragrance; it can be also used as fungicides.
p-Hydroxybenzaldehyde Preparation method: take phenol as the raw material, have chloroform reacted with a phenol sodium salt at 60 °C; or have condensation reaction between phenol and chloral in the presence of potassium carbonate as the catalyst, and then they further undergo decomposition by sodium methylate; it can also be produced by pouring dry hydrogen chloride into the mixture between phenol and hydrogen cyanide in the presence of aluminum chloride as the catalyst and the decomposition reaction in ice water to obtain the finished p-hydroxybenzaldehyde product.
The above information is edited by the Chemicalbook of Dai Xiongfeng. |
| Chemical Properties |
It is colorless crystalline powder. Melting point: 115-116 ℃, the relative density is 1.129 (30/4 ℃). In the air, it is easily to be sublimated. It is easily soluble in alcohol, ether, acetone, and ethyl acetate, slightly soluble in water (at 30.5 ℃, its water solubility is 1.38g/100ml); it can also be dissolved in benzene (at 65 ℃, its solubility in benzene is 3.68g/ml). It has aromatic odor. |
| synthesis |
1. use chloroform and phenol as raw materials, have them heated in an alkaline solution for Reimer-Tiemann reaction while generating p-hydroxybenzaldehyde [1] and a small amount of salicylaldehyde (o-hydroxybenzaldehyde).
2. use phenol and hydrogen cyanide as the raw materials, in presence of aluminum chloride as the catalyst, have them reacted with anhydrous hydrogen chloride to generate the imine hydrochloric acid of p-hydroxybenzaldehyde, followed by hydrolysis to obtain p-hydroxybenzaldehyde [1]. For the reaction solvent, we can use benzene, chlorobenzene, and paraffins chloro; zinc cyanide can also be used as substitute of hydrogen cyanide.
3. phenol and trichloracetic aldehyde have condensation reaction in the presence of potassium carbonate as the catalyst, and then further undergo decomposition by sodium methylate in dimethyl formamide to obtain the final product.
4. take p-cresol as the starting material, have it reacted with acetic acid to produce para-toluene acetate ester, and then further perform chlorination reaction, hydrolysis reaction to obtain the p-hydroxybenzaldehyde.
5. take nitrotoluene as the raw material, have it reacted with sodium polysulfide with the catalyst to have reduction reaction to produce p-amino benzaldehyde; it further has diazotization reaction with sodium nitrite in sulfuric acid to generate diazonium salt which is then hydrolyzed at 100~110 ℃ to obtain hydroxybenzaldehyde [1].
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| Uses |
1. It can be used for the synthesis of organic compounds and medicine.
2. The good is also the intermediate of the pharmaceutical, perfume, and liquid crystal. p-Hydroxybenzaldehyde can be used for the production of TMP (trimethoprim), amoxicillin, cefadroxil cephalosporins, artificial gastrodin, farrerol, bezafibrate, and esmolol; it can also be used for the production of perfume anisaldehyde, vanillin, ethyl vanillin, and raspberry ketone.
3. It is the key raw material for the production of p-hydroxy phenylglycine (p-hydroxy phenylglycine is the key intermediate of the new generation of semi-synthetic penicillin amoxicillin). It is also the key intermediate raw material of the production of pesticides-bromoxynil.
4. p-Hydroxybenzaldehyde is an important intermediate of the pharmaceutical industry and the perfume industry.
5. It is an important intermediate of medicine, perfume, and pesticides for the synthesis of drugs like hydroxyl ampicillin, trimethoprim, and 3-methoxy benzaldehyde. It can also used for synthesizing polymers and producing pharmaceutical raw materials. |
| Production method |
There are multiple routes for p-hydroxybenzaldehyde production. Currently ways for industrial production includes various raw materials routes including phenol, cresol, and p-nitrotoluene. 1. Phenol method: phenol method also includes Reimer-Tiemann reaction, Gattermann reaction, phenol-chloral route, phenol-glyoxylate route, and phenol-formaldehyde synthesis routes. The technological features of phenol method include: raw material is easily available; the manufacturing process is relatively simple; but the yield is low and the cost is high. (1) Reimer-Tiemann reaction: put phenol and chloroform in alkaline aqueous solution for heating reaction at 60-100 °C for about 2-4h, while generating p-hydroxybenzaldehyde and salicylaldehyde (commonly known salicylaldehyde) with total yield of being around 50% among which p-hydroxybenzaldehyde has the highest yield being only 17%. This process is mainly used for synthesis of salicylaldehyde with p-hydroxybenzaldehyde as the byproduct, but it is one of the major existing production methods. This process has a low feed conversion rate as well as low product yield with a lot of tar being produced at the same time. It requires excess amount of chloroform with unreacted phenol being difficult for recovery and separation and purification of the product being difficult. Therefore, we must vigorously develop new efficient catalysts to improve the selectivity of the reaction, and also develop simple and efficient ways for product separation and purification in order to reduce costs and improve product yield. (2) Gattermann reaction: pour dry HCl into the mixture of phenol and HCN in the presence of AlCl3 for catalytic reaction and further perform decomposition in ice water to obtain p-hydroxybenzaldehyde with a relative high product yield. If you apply zinc cyanide instead of HCN, the yield would almost reach theoretical value. This technology product has a relative high selectivity but with one drawback being the high cyanide toxicity, technically demanding operation, and high difficulty; the second is the demanding of reaction equipment and high cost due to the use of dry operation; the third is a small amount of salicylaldehyde byproduct which makes the product separation and purification being difficult, thus limiting large-scale production. 2. p-Nitrotoluene: the nitrotoluene production process for producing p-hydroxybenzaldehyde includes three steps: oxidation reduction, diazotization and hydrolysis. (1) p-nitrotoluene oxidation reduction: p-nitrotoluene was subject to sodium polysulfide synchronized oxidation reduction to give amino benzaldehyde. Specific process is: mix p-nitrotoluene, ethanol solvent with a surfactant (such as OP Tween) uniformly in mass ratio of 1: 5: 0.02-0.04, add aqueous solution of sodium polysulfide at 80-85 °C for reaction for about 2-3 h. The product is subject to steam distillation to remove toluene and p-amino-nitro toluene. Further apply ether extraction to obtain p-amino benzaldehyde with both the conversion rate and yield rate being over 90%. Sodium polysulfide can be obtained with sodium hydrosulfide, caustic soda and sulfur as the raw materials. (2) Diazotization and hydrolysis: p-amino benzaldehyde is subject to the treatment of 40% sulfuric acid, add 30% sodium nitrite solution at 0-3 °C for reaction for about 30min, further apply a small amount of urea to decompose excess amount of sodium nitrite to give p-amino benzaldehyde diazonium salt solution. The solution is hydrolyzed in the presence of sulfuric acid at 80-85 °C for about 30min. The product is further subject to extraction, purification and drying to obtain p-hydroxybenzaldehyde products with yield being over 90%. The advantage of this process is its cheaper raw material prices, but the drawback is a long process route with large equipment and also intermediate p-amino benzaldehyde being toxic as well as the demanding of high freezing conditions due to the low temperature for diazotization. Currently the fine chemical plant in Qixian (Shanxi province) applies this process for producing p-hydroxybenzaldehyde. 3. p-cresol catalytic oxidation method: this process is that, in the presence of the catalyst, apply direct oxidation with air or oxygen to cresol for synthesis of p-hydroxybenzaldehyde. In 1980s, Japan, the United States, Germany had conducted in-depth research about this approach. In late 1980s and early 1990s, several institutes and production units in Jiangsu, Shanghai, and Dalian of china had also carried out research and development of this process, and further applied it in industrial production. The specific process is: put p-cresol, sodium hydroxide, methanol into a stainless steel autoclave, stir until they are completely dissolved, add cobalt acetate and seal the reactor, warm to 55 °C and start to pass through oxygen gas while maintaining the inner pressure at 1.5MPa for reaction for about 8-10 h; during the reaction process, strictly control the rate of passing through oxygen; there is coil cooling system in the tank, when the reaction temperature increases, cooling water can be passed through autoclave jacket when the inner coil begins to be pass through cooling water for strictly control of the amount of passed oxygen as well as keeping the autoclave at a temperature of about 60 °C. At the ending of the reaction, add the material into the distilled vessel for distilling off the methanol for recycling, then add water for dissolving and further add hydrochloric acid for salting. The solid-liquid material was filtered using a centrifuge with the resulting solid being placed in a vacuum oven at about 60 °C to be dried for 3-5h, then you can get p-hydroxybenzaldehyde with content being greater than 98%. |
| Chemical Properties |
yellow to light brown crystalline powder |
| Chemical Properties |
4-Hydroxybenzaldehyde has a very faint, sweet-woody-balsamic odor and a sweet taste with little or no other flavor impression. The odor is also reported as vanillic/nutty. |
| Occurrence |
It is found as a volatile in several food products, including cherries, grapes, papayas, tomatoes, cheese, beer, rum, brandy, wine, tea and peanuts. Occurs in the form of esters in several plants, notably in wintergreen leaves and the bark of sweet birch. |
| Uses |
Widely used starting material for polymers and pharmaceuticals. |
| Uses |
4-Hydroxybenzaldehyde maintains bactericidal activity when tested against certain bacteria strains. It also displays antioxidant potential when analyzed through assay. |
| Uses |
It's the important intermediates of pharmaceutical industry and spices. In foreign , it's also used for synthesis of bromoxynil and chloroxynil which are kind of herbicides, and also used in the manufacture of bactericide, photographic emulsifier, nickel plating luster agent, liquid crystal, etc; In the pharmaceutical field, it can be used for synthesis of amoxicillin, antibacterial synergistic agent named TMP, 3,4,5-Trimethoxybenzaldehyde，Artificial gastrodia elata, farrerol, esmololhydrochloride; In the spicery field, it can be used for synthesis of spicery,for example: vanillin, ethyl vanillin, piperonal, springaldehyde, p-anisaldehyde, raspberry ketone natural,etc. |
| Definition |
ChEBI: A hydroxybenzaldehyde that is benzaldehyde substituted with a hydroxy group at position C-4. |
| Preparation |
Prepared by heating sodium phenolate with carbon dioxide under pressure. |
| Synthesis Reference(s) |
Synthetic Communications, 9, p. 407, 1979 DOI: 10.1080/00397917908064169 |
| General Description |
4-hydroxybenzaldehyde occurs naturally in vanilla beans and is one of the keys contributors to the vanilla flavor.
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| Purification Methods |
Crystallise it from water (containing some H2SO4). Dry it over P2O5 under vacuum. [Beilstein 8 H 64, 8 IV 251.] |
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| p-Hydroxybenzaldehyde Preparation Products And Raw materials |
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| Tag:p-Hydroxybenzaldehyde(123-08-0) Related Product Information |
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