4-Hydroxyphenylacetic acid

Definition

4-Hydroxyphenylacetic acid (chemical formula: C8H8O3, CAS No. 156-38-7) is an organic compound that is a derivative of phenylacetic acid. It has a molecular weight of 152.15, a melting point of 148-151°C, a boiling point of about 234.6°C, and is soluble in dimethyl sulfoxide and methanol. This compound has a wide range of applications in the chemical industry, e.g. as a raw material for the synthesis of esters.

4-Hydroxyphenylacetic acid is a monocarboxylic acid, an acetic acid in which one of the methyl hydrogens is replaced by 4-hydroxyphenyl. It is a plant metabolite, a fungal metabolite, a human metabolite and a mouse metabolite. It is a monocarboxylic acid and belongs to the phenolic group. It is derived from acetic acid. It is the conjugate acid of 4-hydroxyphenylacetic acid.4-Hydroxyphenylacetic acid (4-HPAA) is a compound that occurs naturally in a wide variety of organisms, including plants, animals, and humans.Dopamine and norepinephrine are used in the manufacture of dopamine and norepinephrine. Dopamine and norepinephrine, two neurotransmitters, produce this essential metabolite during catabolism. It is functionally related to acetic acid. It is a conjugate of 4-hydroxyphenylacetic acid.

4-hydroxyphenylacetic acid is a natural product found in Epichloe typhina, Oenothera glazioviana, and other organisms for which data are available.4-hydroxyphenylacetic acid is a metabolite found in or produced by brewer’s yeast.

4-Hydroxyphenylacetic acid has a wide range of biological activities and is considered a compound of potential medical value. It also has applications in the food industry, for example as a precursor substance for food additives. In addition, it is used as an analytical standard in environmental sciences to detect and study the behaviour and effects of environmental pollutants.

4-Hydroxyphenylacetic acid also shows its importance in drug development. It is used as an intermediate in drug synthesis for the preparation of a number of anti-inflammatory and antioxidant drugs. The presence of hydroxyl group in its structure makes it highly active in chemical synthesis and can be converted into different compounds through various chemical reactions.

Synthesis

4-Hydroxyphenylacetic acid (4HPAA) is obtained by reduction of 4-hydroxymandelic acid (4-hydroxymandelic acid) with elemental phosphorus and iodine.

4HPAA can currently only be produced chemically, but this method is prone to environmental pollution and harsh reaction conditions.

The use of microbial cell factories would be a new way of thinking about the production of 4HPAA, as well as a more desirable and sustainable method. In the study “Combining Directed Evolution of Pathway Enzymes and Dynamic Pathway Regulation Using Quorum Sensing Circuits to Enhance 4-Hydroxyphenylacetic Acid Production in Escherichia coli”, the scientists established a microbial biosynthesis system for the production of 4HPAA using glucose in E. coli.

4- Hydroxymandelic acid can be obtained by reducing 4-hydroxymandelic acid with elemental phosphorus and iodine.

Chemical Properties

Appearance and properties White or slightly yellow crystalline powder.

Can sublimate. Soluble in ether, ethanol, ethyl acetate.

Melting point 148-151 °C (lit.)

Boiling point 234.6 °C (rough estimate)

Density 1.2143 (rough estimate)

Vapour pressure 0.007 Pa at 25 °C

Refractive index 1.4945 (estimate)

Storage conditionInert atmosphere,Room Temperature

Solubility 50g/litre

Acidity coefficient(pKa)4.50±0.10(Predicted)

FormCrystalline powder

Colour White to cream or light tan

PH value 2.0-2.4 (30g/l, H2O, 20℃)

Soluble in dimethyl sulfoxide and methanol. Slightly soluble in water.

Physicochemical properties

White needle-like crystals when precipitated from water. Relative molecular mass 152.15, melting point 149～151℃. Can sublimate. Difficult to dissolve in cold water, soluble in hot water, ether, ethanol and ethyl acetate. P-hydroxyphenylacetic acid is purple-green precipitate when met with ferric chloride. Used as pharmaceutical raw materials, used in the preparation of cephalosporin antibiotic drugs, antipyretic and analgesic, etc.; pesticide raw materials, used in the preparation of pyrethroid insecticides; used as a fluorescent reagent for the determination of oxidative enzymes; intermediates in organic synthesis. 4-hydroxybenzeneacetic acid is a white to creamy white or light brown crystalline powder. Insoluble in cold water, soluble in hot water, ether, ethanol and ethyl acetate. If ferric chloride, it is purple-green precipitate.

Appearance and Properties: 4-Hydroxyphenylacetic acid is a white or slightly yellowish crystalline powder, which can be sublimated. It is soluble in ether, ethanol and ethyl acetate.

Density and Vapour Pressure: The density is about 1.2143 and the vapour pressure is about 0.007 Pa at 25 °C.

STORAGE CONDITIONS AND SOLUBILITY: It is best stored at room temperature in an inert atmosphere. Its solubility is about 50 g/litre

Biological activity

4-Hydroxyphenylacetic acid (p-Hydroxyphenylacetic acid, parahydroxy phenylacetate) is a compound found in olive oil and beer, and is used as a chemical intermediate in the synthesis of atenolol and 3,4-hydroxyphenylacetic acid. dihydroxyphenylacetic acid.

4-Hydroxyphenylacetic acid has been found to have anti-inflammatory and anti-fatty liver activity and can be metabolised by gut microbes into aromatic amino acids and polyphenols. In addition, studies have shown that 4-hydroxyphenylacetic acid acts through modulation of the catecholamine neurotransmitter system, but its specific mechanism of action has not been fully elucidated.

Production method

It is obtained by diazotisation and hydrolysis of p-aminophenylacetic acid. Prepare p-aminophenylacetic acid with alkali solution to form sodium salt, then add sulfuric acid. Cold to 0 ℃, control the temperature at 0-5 ℃ dropwise addition of sodium nitrate solution, plus graduate reaction 0.5h. The resulting diazo solution was added dropwise to dilute sulfuric acid at 90-95 ℃, about 1h drop, and then continue to react for 1h. The reaction solution was decolourised and filtered, cooled and extracted with ethyl acetate, and the finished product was obtained after the extract was recovered from the ethyl acetate. The yield is about 85%.2.3-Fluoro-p-hydroxyphenylacetic acid.

Uses

In industry, 4-hydroxyphenylacetic acid is an intermediate in the synthesis of atenolol, 3,4-dihydroxyphenylacetic acid and cocaine.

Hydroxyphenylacetic acid (4HPAA) is an important raw material for the synthesis of drugs, pesticides and biochemical products. It can be used in the synthesis of hypertensive drugs (Atenolol), cardiovascular drugs (Metoprolol and Betaxolol) as well as antidepressants, anti-inflammatory and analgesic drugs, antibiotics, etc. It is an intermediate for the synthesis of the new drug 4,7-Dihydroxyisoflavones, and it can be used as a pesticide intermediate as well.

It also has relevant applications in polymers and liquid crystal materials. It is also the active ingredient of Rhodiola rosea glycosides, with anti-inflammatory, anti-tumour, anti-anxiety, anti-platelet and hepatoprotective activities. In addition, 4-hydroxyphenylacetic acid is a reagent used for phenol and amine acylation.

Although the exact mechanism of action of 4-hydroxyphenylacetic acid has not yet been fully elucidated, current research suggests that it acts by modulating the catecholamine neurotransmitter system.

Applications:

1. Used as a pharmaceutical raw material Used as a pharmaceutical raw material, e.g. for the preparation of “indomethacin” and “indolpiperidine”.

2. Used as pharmaceutical raw materials, such as the preparation of cephalosporin antibiotic drugs, antipyretic and analgesic drugs.

3. Pesticide raw materials, used in the preparation of pyrethroid insecticide.

4. Used for the determination of oxidase fluorescent reagent.

5. Organic synthesis intermediates, used in the synthesis of atenolol and 3,4-dihydroxyphenylacetic acid.

6. It has anti-inflammatory and anti-fatty liver activity and can be metabolised by intestinal microorganisms to form aromatic amino acids and polyphenolic compounds.

Areas of application:

It is the intermediate for synthesising new drug 4,7-dihydroxyisoflavone, and can also be used as pesticide intermediate.

Organic synthesis intermediates, used in the production of β-blocker atenolol and Pueraria Mirifica soybean glycoside yuan active ingredient -4,7-dihydroxyisoflavone synthesis; can also be used as pesticide intermediates.

Organic synthesis. Organic synthesis intermediates, used in the production of β-blocking drug atenolol and Pueraria lobata glycosides active ingredient-

A compound in olive oil. An important fine chemical intermediate with broad application development prospects.

Used as an acylation reagent for phenol and amines. It can also be used for fluorescence determination of oxidase.

Used as pharmaceutical raw material for synthesising cephalosporin antibiotics and antipyretic and analgesic drugs.

4-Hydroxyphenylacetic acid has also shown its importance in drug development. It can be used as an intermediate in drug synthesis for the preparation of a number of anti-inflammatory and antioxidant drugs. The presence of hydroxyl group in its structure makes it highly active in chemical synthesis and it can be converted into different compounds through various chemical reactions.

Applications: Used as a pharmaceutical raw material Used as a pharmaceutical raw material, e.g. for the preparation of “indomethacin” and “indolpiperidine”.

Used as pharmaceutical raw materials, such as the preparation of cephalosporin antibiotic drugs, antipyretic and analgesic drugs.

Pesticide raw materials, used in the preparation of pyrethroid insecticide.

Used for the determination of oxidase fluorescent reagent.

Organic synthesis intermediates, used in the synthesis of atenolol and 3,4-dihydroxyphenylacetic acid.

It has anti-inflammatory and anti-fatty liver activity, and can be metabolised by intestinal microorganisms to form aromatic amino acids and polyphenolic compounds.

In addition to its pharmaceutical applications, 4-hydroxyphenylacetic acid has relevant applications in polymers and liquid crystal materials. In addition, it is the active ingredient in Rhodiola rosea glycosides, which are widely used in China for the treatment of lung diseases, hepatitis B virus infections and cancer.4-Hydroxyphenylacetic acid is also used as a reagent for the acylation of phenols and amines, and as a reagent for the fluorescence determination of enzymes.

4-Hydroxyphenylacetic acid (4-Hydroxyphenylacetic acid) is an acetic acid derivative used in the acylation of phenols and amines. It is the active ingredient in the Chinese herb Aster tataricus, which is widely used in China for the treatment of lung diseases, HBV and cancer.

It is an active metabolite of amino acid metabolism. It has also been shown to reduce inflammation and oedema by inhibiting the induction of HIF-1α by hypertonicity and hypoxia in seawater aspiration-induced lung injury in rats.

Method of Preparation

4-Hydroxyphenylacetic acid was synthesised by diazotization and hydrolysis of 4-aminophenylacetic acid.

4-aminophenylacetic acid and a base solution were prepared to form the sodium salt, then sulphuric acid was added. The reaction was cooled to 0°C, controlled at 0-5°C and sodium nitrate solution was added dropwise and the reaction was completed in 0.5 hours.

At 90-95°C, the resulting diazo was added dropwise to dilute sulphuric acid and reacted for about 1 h. The reaction was continued for 1 h. The reaction solution was decoloured and filtered.

The reaction solution was decoloured and filtered, cooled and extracted with ethyl acetate, and the extract was recovered with ethyl acetate to obtain 4-hydroxyphenylacetic acid. The yield was about 85%.

In addition to chemical synthesis, existing research suggests that the use of microbial cell factories for the production of 4-hydroxyphenylacetic acid is a preferable and sustainable approach. In a study entitled “Enhancing 4-hydroxyphenylacetic acid production in Escherichia coli using directed evolution of pathway enzymes and dynamic pathway regulation using population-sensing circuits”, scientists have established a microbial biosynthetic system for the production of 4-hydroxyphenylacetic acid in Escherichia coli using glucose.

Safety Data.

May cause skin irritation, severe eye irritation, and single exposure specific target organ toxicity (respiratory) according to OSHA HCS classification.

Environmental Effects.

4-Hydroxyphenylacetic acid is a major microbial metabolite involved in antioxidant action.

According to the OSHA HCS classification, 4-hydroxyphenylacetic acid may cause skin irritation, severe eye irritation, and single-exposure specific target organ toxicity (respiratory). In addition, it plays an important role in microbial metabolism, participating in antioxidant responses and inducing Nrf2.c expression.