PRODUCTS

VANILLIC ACID

Vanillic Acid can be used in the synthesis of the analeptic drug etamivan, modecainide, brovanexine, vanitiolide, and vanyldisulfamide.
Vanillic acid is used as a flavoring agent in food.
Vanillic Acid acts as an intermediate in the production of vanillin from ferulic acid.

CAS Number： 121-34-6
EC Number： 204-466-8
MDL Number： MFCD00002551
IUPAC Name: 4-hydroxy-3-methoxybenzoic acid
Molecular Formula: C8H8O4
Molecular Weight (g/mol): 168.15

SYNONYMS:
vanillic acid, acide vanillique, p hydroxy m methoxy benzoic acid, p-vanillic acid, 4 hydroxy 3 methoxybenzoic acid, acid, vanillic, p-vanillate, 4-Hydroxy-3-methoxybenzoic acid, 4-Hydroxy-3-methoxybenzoate, Vanillate, 3-Methoxy-4-hydroxybenzoate, 3-Methoxy-4-hydroxybenzoic acid, 4-Hydroxy-3-methoxy-benzoate, 4-Hydroxy-3-methoxy-benzoic acid, 4-Hydroxy-m-anisate, 4-Hydroxy-m-anisic acid, Acide vanillique, p-Vanillate, p-Vanillic acid, Protocatechuic acid 3-methyl ester, Acid, 4-hydroxy-3-methoxybenzoic, p Hydroxy m methoxy benzoic acid, 4 Hydroxy 3 methoxybenzoic acid, Acid, vanillic, Acid, p-hydroxy-m-methoxy-benzoic, p-Hydroxy-m-methoxy-benzoic acid, 2-Methoxy-4-carboxyphenol, Methylprotocatechuic acid, VA, m-Methoxy-p-hydroxy-benzoic acid, Vanillic acid, Vanillic acid, 4-HYDROXY-3-METHOXYBENZOIC ACID, 121-34-6, Acide vanillique, Benzoic acid, 4-hydroxy-3-methoxy-, 3-Methoxy-4-hydroxybenzoic acid, GM8Q3JM2Y8, DTXSID6059522, NSC-3987, NSC-674322, FEMA NO. 3988, CHEBI:30816, Acid, Vanillic, 4 Hydroxy 3 methoxybenzoic Acid, p Hydroxy m methoxy benzoic Acid, p-Hydroxy-m-methoxy-benzoic Acid, Acid, 4-Hydroxy-3-methoxybenzoic, Acid, p-Hydroxy-m-methoxy-benzoic, RefChem:6346, DTXCID1033668, 204-466-8, p-Vanillic acid, VanillicAcid, m-Anisic acid, 4-hydroxy-, MFCD00002551, 4-hydroxy-3-methoxy-Benzoic acid, Protocatechuic acid, 3-methyl ester, NSC 3987, NSC 674322, 4-hydroxy-3-methoxy benzoic acid, VA, CHEMBL120568, NSC674322, VA (VAN), VNL, 4-hydroxy-m-Anisic acid, EINECS 204-466-8, UNII-GM8Q3JM2Y8, BRN 2208364, Vanillinsaure, vanillinic acid, p-Vanillate, Vanilic acid, 4-Hydroxy-3-methoxybenzoicacid, AI3-19542, 4-hydroxy-m-Anisate, Vanillic acid (M2), Vanillic acid, 97%, Vanillic acid (Standard), bmse000486, bmse000614, bmse010205, WLN: QVR DQ CO1, VANILLIC ACID [MI], 3-Methoxy-4-hydroxybenzoate, SCHEMBL26179, MLS000574833, 4-hydroxy-3-methoxy-Benzoate, SCHEMBL409710, orb1298357, Vanillic acid, >=97%, FG, 4-hydroxy-3methoxy benzoic acid, SCHEMBL29378740, HY-N0708R, 4-hydroxyl-3-methoxybenzoic acid, DROXIDOPA METABOLITE (VA), NSC3987, 2-METHOXY-4-CARBOXYPHENOL, 3-methoxy-4-hydroxy-benzoic acid, 4- hydroxy-3-methoxybenzoic acid, HMS2197E16, HMS5084K10, Protocatechuic acid 3-methyl ester, BB_NC-02254, HY-N0708, MSK40128, STR02334, BBL011982, BDBM50337364, CK2172, EBC-44422, s5343, SBB008280, STL163472, AKOS000113195, CCG-266343, FH00443, M-METHOXY-P-HYDROXY-BENZOIC ACID, NCGC00247610-01, NCGC00247610-02, AC-11841, BP-13246, SMR000156289, ST086485, SY001450, DB-003804, Vanillic acid, purum, >=97.0% (HPLC), CS-0009728, NS00014581, V0017, 4-HYDROXY-3-METHOXYBENZOIC ACID [FHFI], C06672, EN300-105765, Vanillic acid, Vetec(TM) reagent grade, 97%, AM-331/20714013, F075247, Q419672, Z381356666, Vanillic acid, certified reference material, TraceCERT(R), 3E9555E5-85F5-4FCE-A429-5182E959C6A3, InChI=1/C8H8O4/c1-12-7-4-5(8(10)11)2-3-6(7)9/h2-4,9H,1H3,(H,10,11, 4-Hydroxy-3-methoxybenzoic acid, 4-Hydroxy-m-anisic acid, Vanillate, Benzoic acid, 4-hydroxy-3-methoxy-, VA, 3-Methoxy-4-Hydroxybenzoic acid, 4-Hydroxy-3-methoxybenzoic acid, m-Anisic acid, 4-hydroxy-, Acide vanillique, Protocatechuic acid, 3-methyl ester, p-Vanillic acid, NSC 3987, NSC 674322, 4-Hydroxy-3-methoxybenzoic acid (vanillic acid), 3-Methoxy-4-Hydroxybenzoic acid, 4-Hydroxy-3-methoxybenzoic acid, 4-Hydroxy-3-methoxybenzoic acid (vanillic acid), Acide vanillique, Benzoic acid, 4-hydroxy-3-methoxy-, NSC 3987, NSC 674322, Protocatechuic acid, 3-methyl ester, VA, m-Anisic acid, 4-hydroxy-, p-Vanillic acid, VA, 4-HYDROXY-3-METHOXYBENZOIC ACID, vanillic, 3-Methoxy-4-Hydroxybenzoic acid, Benzoic acid, 4-hydroxy-3-methoxy-, Vanillate, Magnolioside, Vanilic acid, Vanilloid, Vallinic acid, 3-Methoxy-4-hydroxybenzoic acid, 4-Hydroxy-3-methoxybenzoic acid, p-Vanillic acid, 4-hydroxy-3-methoxybenzoic acid, 4-HYDROXY-3-METHOXYBENZOIC ACID, Acide Vanillique, Benzoic Acid, 4-Hydroxy-3-Methoxy-, P-Vanillic Acid, 3-Methoxy-4-Hydroxybenzoic Acid, Vanillate, Asam, FEMA 3988, Vanilic acid, Vanillic acid, VANILLIC ACID, VENILLIC ACID, AKOS BBS-00003785, TIMTEC-BB SBB008280, RARECHEM AL BO 0061, 4-hydroxy-3-methoxybenzoate, 4-HYDROXY-3-METHOXYBENZOIC ACID, 4-Hydroxy-3-methoxybenzoic acid, PROTOCATECHUIC ACID 3-METHYL ETHER

Vanillic acid is a naturally occurring compound recognized for its aromatic properties and is widely utilized in the food, fragrance, and pharmaceutical industries.
This white crystalline powder, Vanillic Acid, with a pleasant vanilla-like scent, serves as a flavoring agent in various food products, enhancing taste and aroma.

Vanillic Acid has a vanilla-like odor and taste.
Vanillic Acid is a white odourless crystals or powder.
Vanillic Acid is a monohydroxybenzoic acid that is 4-hydroxybenzoic acid substituted by a methoxy group at position 3.

Vanillic acid is one of the key aromatic volatile compounds of vanilla beans.
Vanillic Acid is a white odourless crystals or powder.
Vanillic Acid has a vanilla-like odor and taste.

Vanillic acid is a dihydroxybenzoic acid that can be used as a flavoring agent.
As an oxidized form of vanillin, Vanillic Acid is the intermediate product during the two-step bioconversion process from ferulic acid to vanillin.

Vanillic Acid is a white to beige powder or needle; vanilla like odour.
Vanillic acid is a monohydroxybenzoic acid that is 4-hydroxybenzoic acid substituted by a methoxy group at position 3.
Vanillic Acid has a role as a plant metabolite.

Vanillic Acid is a monohydroxybenzoic acid and a methoxybenzoic acid.
Vanillic Acid is a conjugate acid of a vanillate.
Vanillic Acid is a colorless liquid with a spoilage odor, B. p.186.2 ℃, n20D 1.4100, relative density 0.939, dissolved in 20 ℃ water 13%, soluble in ethanol and ether and other organic solvents.

Vanillic acid is a flavoring agent found in edible plants and fruits, also found in Angelica sinensis.
Vanillic acid inhibits NF-κB activation.
Vanillic Acid has anti-inflammatory, antibacterial, and chemopreventive effects.

Vanillic Acid exists in high amount in the root of Angelica sinenisis, which is a plant used in traditional Chinese medicine.
Vanillic Acid also exists in acal oil, argan oil as well as wine and vinegar.
Vanillic acid is a phenolic acid found in some forms of vanilla and many other plant extracts.

Vanillic Acid is a flavouring and scent agent that produces a pleasant, creamy odour.
Vanillic Acid is the intermediate product in the two-step bioconversion of ferulic acid to vanillin.
Vanillic acid, which is a chlorogenic acid, is an oxidized form of vanillin.

Vanillic Acid is also an intermediate in the production of vanillin from ferulic acid.
Vanillic acid is a metabolic byproduct of caffeic acid and is often found in the urine of humans who have consumed coffee, chocolate, tea, and vanilla-flavoured confectionary.

Vanillic acid selectively and specifically inhibits 5'nucleotidase activity.
Vanillic acid is a microbial metabolite found in Amycolatopsis, Delftia, and Pseudomonas.
Vanillic acid is a monohydroxybenzoic acid that is 4-hydroxybenzoic acid substituted by a methoxy group at position 3.

Vanillic Acid has a role as a plant metabolite.
Vanillic Acid is a monohydroxybenzoic acid and a methoxybenzoic acid.
Vanillic Acid is a conjugate acid of a vanillate.

Vanillic Acid is a flavoring agent.
Vanillic Acid is the intermediate product in the two-step bioconversion of ferulic acid to vanillin.
Vanillic acid has been reported in Camellia sinensis, Paeonia obovata, and other organisms with data available.

Vanillic acid is a metabolite found in or produced by Saccharomyces cerevisiae.
Vanillic Acid belongs to the class of organic compounds known as m-methoxybenzoic acids and derivatives.
These are benzoic acids in which the hydrogen atom at position 3 of the benzene ring is replaced by a methoxy group.

Vanillic acid (4-hydroxy-3-methoxybenzoic acid) is a dihydroxybenzoic acid derivative used as a flavoring agent.
Vanillic Acid is an oxidized form of vanillin.
Vanillic Acid is also an intermediate in the production of vanillin from ferulic acid.

Vanillic Acid is soluble in water, alcohol and ether.
Vanillic Acid is incompatible with strong oxidizing agents.
Vanillic acid, a naturally occurring organic compound, is present in various plants like vanilla beans and cloves.

The scientific research applications of vanillic acid encompass both in vivo and in vitro studies.
In vivo investigations have focused on its anti-inflammatory and antioxidant.
In vitro, vanillic acid has been employed as a model compound to examine the impact of various oxidizing agents on the oxidation of aromatic compounds.

Vanillic acid, also known as 4-hydroxy-3-methoxybenzoic acid, is a naturally occurring phenolic acid with the molecular formula C₈H₈O₄ and a molecular weight of 168.15 g/mol.
Vanillic Acid features a benzoic acid core substituted with a hydroxyl group at the 4-position and a methoxy group at the 3-position, giving it a white to beige crystalline powder appearance and a characteristic vanilla-like odor and taste.

Vanillic Acid melts at approximately 211–213 °C and exhibits moderate solubility in water (about 1.5 g/L at 14 °C), with better solubility in ethanol, ether, and other organic solvents.
Vanillic acid is widely distributed in nature as a plant metabolite, particularly in vanilla beans (Vanilla planifolia), where it arises from the oxidation of vanillin, as well as in green tea, grapes, guava, wine, vinegar, and various fermented products like brandy, rum, whiskey, and sherry.

Biosynthetically, Vanillic Acid is produced via the phenylpropanoid pathway from precursors like L-phenylalanine or L-tyrosine in plants, and it can also be generated microbially from ferulic acid using bacteria such as Pseudomonas fluorescens.
In human metabolism, Vanillic Acid appears as a byproduct of caffeic acid breakdown and is detectable in urine following consumption of coffee, tea, chocolate, or vanilla-flavored foods, often conjugated with glucuronic acid, glycine, or sulfate.

Commercially, vanillic acid serves as a flavoring agent in the food industry, recognized as generally recognized as safe (GRAS) by the FDA, and acts as a key intermediate in the biotechnological production of vanillin from ferulic acid.
Beyond flavors, Vanillic Acid finds applications in pharmaceuticals as a precursor for synthesizing drugs like etamivan and in formulating nanoparticles or hydrogels to enhance bioavailability for therapeutic uses.

Research highlights its pharmacological potential, including antioxidant, anti-inflammatory, antidiabetic, neuroprotective, and anticancer activities, mediated through pathways such as NF-κB, PI3K/Akt, and AMPK, though Vanillic Acid remains an experimental compound without approved medical indications.

USES and APPLICATIONS of VANILLIC ACID:
Vanillic acid is used as a flavoring agent in food.
Vanillic Acid acts as an intermediate in the production of vanillin from ferulic acid.
Further, Vanillic Acid is used in wine and vinegar.

Vanillic Acid (Acide vanillique) is used as a condiment in food, which is used in wine and vinegar.
Vanillic Acid is an intermediate in the production of vanillin from ferulic acid.
Its antioxidant properties make Vanillic Acid valuable in cosmetic formulations, where it helps protect skin from oxidative stress.

Additionally, vanillic acid is employed in the synthesis of other chemical compounds, including pharmaceuticals and agrochemicals, showcasing its versatility in diverse applications.
Researchers and industry professionals appreciate vanillic acid for its role in developing functional foods and nutraceuticals, where it contributes to health benefits beyond basic nutrition.

Its unique ability to act as a natural preservative also positions Vanillic Acid as a safer alternative to synthetic additives.
With its multifaceted applications and benefits, vanillic acid stands out as a compound of interest for those seeking to enhance product quality and efficacy in various sectors.

Vanillic Acid can be used in the synthesis of the analeptic drug etamivan, modecainide, brovanexine, vanitiolide, and vanyldisulfamide.
Vanillic Acid can be manufactured through the oxidation of vanillin to the carboxylic acid.
Vanillic acid is used as a flavoring agent in food.

Vanillic Acid acts as an intermediate in the production of vanillin from ferulic acid.
Further, Vanillic Acid is used in wine and vinegar.
Vanillic Acid, a compound widely used in foods, beverages, cosmetics and drugs, has been reported to exhibit multifunctional effects such as antimutagenic, antiangiogenetic, anti-colitis, anti-sickling, and antianalgesic effects.

APPLICATIONS AND BIOLOGICAL ACTIVITY of VANILLIC ACID:
INDUSTRIAL AND FLAVORING USES OF VANILLIC ACID:
Vanillic acid serves as a flavoring agent in the food and beverage industries, imparting a mild vanilla-like taste and creamy aroma to products such as baked goods, confectionery, dairy items, and soft drinks.

Vanillic Acid is considered generally regarded as safe (GRAS) in scientific literature as a flavoring agent.
In perfumery and fragrances, Vanillic Acid contributes to sweet, balsamic notes in essential oils, candles, and aromatic compositions, often at concentrations of 0.1% to 1%.

As a chemical intermediate, vanillic acid is employed in the industrial production of vanillin, particularly through biotransformation pathways starting from ferulic acid derived from lignocellulosic biomass or agricultural waste.

Vanillic Acid also finds application in the synthesis of pharmaceutical intermediates, such as for taste-masking agents in oral medications and components in topical formulations.
Patents have been granted for methods extracting vanillic acid from rice bran oil waste residues via microbial fermentation using Aspergillus niger, enabling cost-effective recovery from industrial byproducts.

In the cosmetics sector, vanillic acid acts as an antioxidant in skincare products, including creams and lotions, where it helps stabilize formulations and provide mild preservative effects.
The global market for vanillic acid plays a niche but growing role within the broader flavor and fragrance industry, which exceeds USD 30 billion annually, driven by demand for natural-derived ingredients.

IN BEVERAGES AND OTHER SOURCES of VANILLIC ACID:
Vanillic acid occurs in various beverages, either directly or as a metabolite derived from precursors such as caffeic acid and catechins.
In wine, particularly red varieties, Vanillic Acid is present as a phenolic acid, with higher concentrations noted in certain regional wines like those from Brazil, where it contributes to the overall polyphenol profile.

Vinegar, especially fruit-based types such as raspberry and guelder-rose, contains vanillic acid as a dominant phenolic compound, often alongside gallic and ferulic acids, at levels up to 0.06 mg/L in some formulations.
Coffee beverages feature vanillic acid as a metabolite of chlorogenic acids, detectable in the drink itself and as a key urinary excretion product following consumption.

Similarly, in tea, especially green tea, vanillic acid arises as a metabolite of catechins, and it is found in the beverage at trace levels.
Chocolate, including dark varieties, leads to increased vanillic acid presence through metabolism of its polyphenols, with hydroxybenzoic acids like vanillic acid comprising part of the phenolic fraction in cocoa products.

Vanillic Acid is also present in fermented alcoholic beverages such as brandy, rum, whiskey, and sherry.
Consumption of these beverages elevates vanillic acid concentrations in human urine, serving as a biomarker of intake.
After green tea ingestion, vanillic acid emerges as one of the primary catechin metabolites, with urinary levels reflecting the breakdown of epigallocatechin gallate and other flavonoids, with total catechin metabolites, including vanillic acid, averaging about 60 mg over 24–48 hours.

Coffee and chocolate intake similarly boosts urinary vanillic acid, identified among the main metabolites of chlorogenic and flavan-3-ol compounds, with rapid excretion peaking within 3 hours post-consumption.
These elevations highlight vanillic acid's role as a downstream product in the metabolism of beverage-derived phenolics.

Beyond beverages, vanillic acid appears in other sources such as argan oil, where it constitutes part of the phenolic acids, alongside ferulic and syringic acids, contributing to the oil's antioxidant properties.
In traditional medicines, Vanillic Acid is extracted from sources like the roots of Angelica sinensis, used in formulations for its bioactive potential, though concentrations vary by preparation method.

In metabolic studies, vanillic acid is commonly detected and quantified using high-performance liquid chromatography, often coupled with diode array detection or mass spectrometry, enabling precise measurement in biological fluids and food matrices at low concentrations.
This method facilitates tracking Vanillic Acid's levels post-consumption, supporting research on dietary impacts.

OCCURRENCES IN FOOD, VANILLIC ACID:
Açaí oil, obtained from the fruit of the açaí palm (Euterpe oleracea), is rich in vanillic acid (1616±94 mg/kg).
Vanillic Acid is one of the main natural phenols in argan oil.
Vanillic Acid is also found in wine and vinegar.

METABOLISM of VANILLIC ACID:
Vanillic acid is one of the main catechins metabolites found in humans after consumption of green tea infusions.

SYNTHESIS of VANILLIC ACID:
Vanillic acid can be obtained from the oxidation of vanillin by various oxidizing agents.

OCCURRENCE IN NATURE, VANILLIC ACID:
The highest amount of vanillic acid in plants known so far is found in the root of Angelica sinensis, an herb indigenous to China, which is used in traditional Chinese medicine.

ALTERNATIVE PARENTS of VANILLIC ACID:
*Methoxyphenols
*Hydroxybenzoic acid derivatives
*Benzoic acids
*Phenoxy compounds
*Methoxybenzenes
*Benzoyl derivatives
*Anisoles
*Alkyl aryl ethers
*1-hydroxy-2-unsubstituted benzenoids
*Monocarboxylic acids and derivatives
*Carboxylic acids
*Organic oxides
*Hydrocarbon derivatives

SUBSTITUENTS of VANILLIC ACID:
*M-methoxybenzoic acid or derivatives
*Hydroxybenzoic acid
*Methoxyphenol
*Benzoic acid
*Anisole
*Phenoxy compound
*Benzoyl
*Phenol ether
*Methoxybenzene
*1-hydroxy-2-unsubstituted benzenoid
*Alkyl aryl ether
*Phenol
*Monocarboxylic acid or derivatives
*Ether
*Carboxylic acid
*Carboxylic acid derivative
*Organic oxide
*Organic oxygen compound
*Organooxygen compound
*Hydrocarbon derivative
*Aromatic homomonocyclic compound

PHYSICAL AND CHEMICAL PROPERTIES of VANILLIC ACID:
Vanillic acid appears as a white to light yellow crystalline powder that may darken upon prolonged storage.
Vanillic Acid's melting point is reported as 211.5 °C, indicating thermal stability up to near this temperature before decomposition begins.

Vanillic Acid is slightly soluble in water (approximately 1.5 mg/mL at 14 °C) but exhibits good solubility in ethanol (≥9.14 mg/mL) and ether, as well as in alkaline solutions due to its acidic nature.
An estimated density of 1.3037 g/cm³ has been calculated, though experimental values are limited.

Chemically, vanillic acid is a weak diprotic acid with pKa values of 4.53 for the carboxylic acid group and 9.39 for the phenolic hydroxyl group at 25 °C.
The phenolic hydroxyl group imparts antioxidant reactivity by facilitating hydrogen atom donation to free radicals, enabling radical scavenging and reduction of oxidative stress.

This behavior is linked to its moderate oxidation potential, typical of phenolic compounds, allowing Vanillic Acid to quench reactive oxygen species.
Vanillic acid demonstrates good stability under ambient conditions and is combustible, but it undergoes photo-oxidation under UV-C light, with approximately 40% degradation after 3 hours of exposure.

Vanillic Acid remains stable to moderate heat but may decompose at elevated temperatures beyond its melting point.
Spectroscopically, vanillic acid shows characteristic UV-Vis absorption in aqueous solutions, with peaks around 260-280 nm attributed to the aromatic ring and conjugated carbonyl system.

In the infrared (IR) spectrum, key features include a broad O-H stretching band at 3350-3500 cm⁻¹ from the phenolic and carboxylic groups, a C=O stretching vibration at approximately 1700 cm⁻¹ for the carboxylic acid, and aromatic C-H stretches around 3000 cm⁻¹, as observed in KBr pellet measurements.

CHEMICAL CHARACTERISTICS of VANILLIC ACID:
Molecular Structure and Nomenclature
Vanillic acid is an organic compound classified as a phenolic acid, possessing the molecular formula C8H8O4 and a molar mass of 168.148 g/mol.
Vanillic Acid's systematic IUPAC name is 4-hydroxy-3-methoxybenzoic acid, with common synonyms including 4-hydroxy-m-anisic acid and vanillate (referring to its deprotonated form).

As a derivative of benzoic acid, vanillic acid features a benzene ring substituted with a carboxylic acid group at position 1, a methoxy group (−OCH3) at position 3, and a hydroxy group (−OH) at position 4, making it a monohydroxybenzoic acid.
This arrangement positions the phenolic hydroxy and methoxy groups ortho to each other and para to the carboxylic acid, contributing to its characteristic structure as an oxidized form of vanillin.

The molecular structure can be represented in SMILES notation as COC1=C(C=CC(=C1)C(=O)O)O, which encodes the benzene ring with the specified substituents in a canonical linear form.
This schematic depicts the core benzene ring (positions 1-6) with the carboxylic acid attached to carbon 1, the methoxy to carbon 3, and the hydroxy to carbon 4, highlighting the key functional groups responsible for its chemical identity.

NATURAL OCCURRENCE of VANILLIC ACID:
In Plants and Foods
Vanillic acid occurs naturally as a phenolic compound in various plants and food sources, serving primarily as a secondary metabolite.
The roots of Angelica sinensis, a plant used in traditional Chinese medicine, represent a major commercial natural source.

In edible oils derived from fruits, vanillic acid is notably abundant in açaí oil at concentrations of 1,616 ± 94 mg/kg, contributing to its antioxidant profile.
Vanillic Acid is also present in argan oil, albeit at trace levels around 0.067 mg/kg, alongside other phenols like caffeic and ferulic acids.

Vanilla beans contain vanillic acid at 0.1–0.2% dry weight, equivalent to 1,000–2,000 mg/kg, often as an oxidation product of vanillin.
Vanillic Acid is also found in fruits such as grapes and guava.
Among fruits and vegetables, vanillic acid appears in berries such as blueberries and cranberries (up to 4.13 mg/100 g fresh weight in the latter), as well as in grains like rice and wheat, where levels increase during grain filling.

Specific food matrices include rice husk, with contents in optimized enzymatic extracts reaching 10.9 ± 0.9 mg/g extract, olives (0.6 mg/100 g fresh weight in mature-green varieties), and spices like thyme.

These concentrations, typically in the mg/kg range, vary by plant variety, maturity, and processing.
As a secondary metabolite, vanillic acid plays roles in lignin degradation pathways and plant defense mechanisms against oxidative stress and pathogens, often derived briefly from ferulic acid or other phenolics during these processes.

BIOSYNTHESIS AND METABOLISM of VANILLIC ACID:
Biosynthetic Pathways
Vanillic acid is primarily biosynthesized in plants through the phenylpropanoid pathway, which originates from the aromatic amino acids L-phenylalanine and L-tyrosine.

This pathway begins with the deamination of phenylalanine by phenylalanine ammonia-lyase (PAL) to form cinnamic acid, followed by successive hydroxylations and methylations to yield ferulic acid, a key precursor structurally related to vanillic acid.
Ferulic acid then serves as an intermediate in lignin formation or degradation, where it can be further metabolized to vanillic acid via oxidation steps.

Key enzymes in this route include cinnamate 4-hydroxylase (C4H) for hydroxylation and caffeic acid/5-hydroxyferulic acid O-methyltransferase (COMT) for methoxylation, integrating vanillic acid into plant secondary metabolism for structural roles in lignins and suberins.
In fungi and plants, vanillic acid is also generated through the oxidation of vanillin, an aldehyde intermediate derived from lignin degradation.

Lignin, a complex polymer rich in ferulic acid units, is broken down by oxidative enzymes such as laccases and peroxidases, releasing ferulic acid, which is then converted to vanillin.
The primary enzymatic step to vanillic acid involves vanillin dehydrogenase (Vdh), a NAD+-dependent enzyme that catalyzes the irreversible oxidation of vanillin to vanillic acid.

This process is prominent in lignin-degrading fungi like Aspergillus niger, where feruloyl-CoA synthetase (Fcs) activates ferulic acid to feruloyl-CoA, followed by enoyl-CoA hydratase/lyase (Ech) to produce vanillin.
Microorganisms, particularly bacteria, produce vanillic acid as a key intermediate during the catabolic breakdown of lignin-derived aromatics.

Soil bacteria such as Pseudomonas fluorescens utilize ferulic acid from lignocellulosic biomass via the CoA-dependent pathway involving feruloyl-CoA synthetase (Fcs) and enoyl-CoA hydratase/lyase (Ech) to produce vanillin, while other bacteria like Bacillus subtilis may use ferulic acid decarboxylase (Fdc) to form 4-vinylguaiacol, which is then oxidized to vanillin; in both cases, vanillin is subsequently converted to vanillic acid by vanillin dehydrogenase.

This bacterial pathway integrates into broader aromatic compound catabolism, funneling vanillic acid into the protocatechuate branch of the β-ketoadipate pathway for energy generation.

A simplified representation of the core route is:
Ferulic acid→Ferulic acid decarboxylase / Fcs-Ech
Vanillin→Vanillin dehydrogenase
Vanillic acid
Ferulic acid
Ferulic acid decarboxylase / Fcs-Ech
Vanillin
Vanillin dehydrogenase
Vanillic acid
These enzymatic conversions highlight vanillic acid's role as a central metabolite in microbial lignin valorization.

Metabolism in Humans and Animals
Vanillic acid, a phenolic acid derived from dietary sources such as tea and coffee, is rapidly absorbed in the small intestine following oral ingestion.

In humans, Vanillic Acid reaches peak plasma concentrations rapidly, often within 30 minutes to 2 hours post-administration, with bioavailability influenced by the food matrix and individual gut microbiota composition.
Upon absorption, vanillic acid undergoes extensive biotransformation primarily through phase II conjugation in the liver and intestinal mucosa, forming vanillate glucuronide and sulfate conjugates.

Minimal phase I metabolism occurs, though gut microbiota can further modify it via reduction or decarboxylation to simpler phenolic compounds.
These conjugates predominate in plasma and represent the main circulating forms.
Excretion occurs predominantly via urine, where conjugated metabolites account for the majority of elimination, often exceeding 50% of the ingested dose within 24 hours.

For instance, after consumption of green tea rich in catechins, vanillic acid appears as a key urinary metabolite, reflecting colonic degradation of flavan-3-ols, with detectable levels persisting up to 48 hours.
The plasma half-life is short, typically around 1 hour.
Minor fecal and biliary excretion may occur, potentially involving enterohepatic recirculation.

PREPARATION of VANILLIC ACID:
Prepared by bioconversion of ferulic acid by means of a vanillate-negative mutant of Pseudomonas fluorescens strain BS13.
Also prepared by whole-cell bioconversion of vanillin to vanillic acid by Streptomyces viridosporus.

OCCURRENCE of VANILLIC ACID:
Reported found in guava, grape, brandy, rum, whiskey, sherry, red and white wines, Scotch and Canadian whiskey, pork (fried), cocoa, peanuts (raw), mushrooms, guava fruit, mangos (fresh), wort, vanilla and black chokeberries.

SYNTHESIS of VANILLIC ACID:
Laboratory Methods
One common laboratory method for preparing vanillic acid involves the oxidation of vanillin, where the aldehyde group is converted to a carboxylic acid.

A standard procedure uses silver oxide as the oxidant in an alkaline aqueous medium.
Silver oxide is first prepared by adding a solution of sodium hydroxide to silver nitrate, filtering, and washing the precipitate.
The oxide is then suspended in water with excess sodium hydroxide and heated to 55–60°C, followed by the addition of vanillin.

The mixture is stirred for 10 minutes, after which the silver is filtered off, and the filtrate is treated with sulfur dioxide gas to decolorize and remove excess oxidant.
Acidification with hydrochloric acid precipitates the vanillic acid, which is collected by filtration and washed with cold water.

This method, a modification of an earlier procedure, affords vanillic acid in 83–95% yield as white needles with a melting point of 209–210°C.
An alternative oxidation employs potassium permanganate in neutral or alkaline conditions, where vanillin forms a 1:1 intermediate complex with the permanganate ion prior to oxidation to vanillic acid.

This approach is suitable for small-scale research and has been characterized kinetically, typically proceeding at moderate temperatures.
Purification of vanillic acid from these oxidations is generally accomplished by recrystallization.
The crude product is dissolved in hot water containing a small amount of sulfur dioxide to prevent discoloration, or alternatively in a water-ethanol mixture (1:1), and cooled to yield pure crystals with a melting point of 210–211°C.

Historical laboratory methods for vanillic acid synthesis date to the early 20th century and include oxidation of vanillin with chromic acid or exposure to sunlight in the presence of nitrobenzene, though these afforded low yields suitable only for small quantities.
More efficient techniques, such as the silver oxide oxidation, were developed mid-century, as reported in 1946, building on prior caustic fusion and metal oxide approaches.

A multi-step laboratory route from guaiacol proceeds via nitration to introduce a nitro group at the 4-position, yielding 2-methoxy-4-nitroguaiacol, followed by reduction of the nitro group to an amine using tin or iron in acid, and finally carboxylation through diazotization of the amine, Sandmeyer reaction to the nitrile, and acid hydrolysis to the benzoic acid derivative, providing vanillic acid in overall yields of 40–60% across the sequence.

PHARMACOLOGICAL AND ANTIOXIDANT PROPERTIES of VANILLIC ACID:
Vanillic acid, a phenolic compound, exhibits potent antioxidant activity primarily through its hydroxyl and methoxy groups, which enable it to scavenge free radicals and chelate metal ions, thereby mitigating oxidative stress.
In vitro assays, such as the DPPH radical scavenging test, have demonstrated an IC50 value of approximately 48.2 µg/mL for vanillic acid, comparable to ascorbic acid (IC50 44.2 µg/mL), indicating effective neutralization of stable free radicals.

Similarly, in ABTS and hydroxyl radical assays, IC50 values range from 37.3 to 47.4 µg/mL, highlighting its broad-spectrum antioxidant capacity via hydrogen atom transfer and single electron transfer mechanisms.
Vanillic Acid also displays significant anti-inflammatory effects by modulating key signaling pathways.

In a collagen-induced arthritis model in DBA/1 mice, oral administration of vanillic acid at doses of 5–20 mg/kg/day reduced clinical symptoms, synovial inflammation, and bone erosion by inhibiting the NF-κB pathway, as evidenced by decreased phosphorylation of p65 and IκBα, along with suppression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β.

This inhibition extends to the MAPK pathway (ERK, JNK, p38), further attenuating macrophage polarization toward the pro-inflammatory M1 phenotype in affected tissues.
Beyond these, vanillic acid shows neuroprotective effects by crossing the blood-brain barrier and reducing oxidative damage in neuronal models, potentially alleviating vascular dementia through enhanced antioxidant enzyme activity (SOD, CAT, GPx).

Antimicrobial activity has been observed against fungal strains, attributed to disruption of microbial membranes.
Additionally, in ovariectomized rat models of osteoporosis, 100 mg/kg vanillic acid preserved bone mineral density and biomechanical strength by promoting osteoblast activity and inhibiting osteoclastogenesis.
These findings suggest therapeutic promise for metabolic diseases and bone loss, though human clinical trials remain limited, with animal dosages typically ranging from 50–200 mg/kg demonstrating efficacy without notable toxicity.

INDUSTRIAL PRODUCTION of VANILLIC ACID:
Vanillic acid is primarily produced on an industrial scale through biotechnological processes involving the microbial conversion of ferulic acid, a phenolic compound derived from lignocellulosic biomass such as agricultural waste.

Engineered strains of bacteria, including Pseudomonas putida and Escherichia coli, are utilized to catalyze this transformation via the ferulic acid degradation pathway, where ferulic acid is first converted to vanillin through a series of enzymatic steps involving feruloyl-CoA synthetase and enoyl-CoA hydratase/aldolase, followed by oxidation to vanillic acid by vanillin dehydrogenase.

This method leverages genetic modifications to enhance flux toward vanillic acid accumulation, minimizing further degradation to protocatechuic acid, and is favored for its use of renewable feedstocks, reducing reliance on petrochemicals.
Recent engineering efforts, such as in P. putida strains, have achieved up to 2.75 g/L vanillic acid in fed-batch fermentations using mixed sugars like glucose and xylose as of 2025.

An alternative chemical route involves the oxidation of vanillin, which itself is industrially synthesized from lignin or guaiacol.
In lignin-based processes, alkaline aerobic oxidation of lignosulfonates—byproducts from the paper and pulp industry—yields vanillin as the main product, with vanillic acid formed concurrently through further oxidation of the aldehyde group under high-temperature (around 170°C) and pressurized oxygen conditions, typically at low yields below 2 wt%.

For guaiacol-derived routes, vanillin is first produced via the Reimer-Tiemann reaction or similar formylation, then selectively oxidized to vanillic acid using agents like potassium permanganate or air in alkaline media, with molar conversions from vanillin exceeding 80% under optimized conditions.

These chemical methods dominate current commercial output due to established infrastructure in the flavor and fragrance sectors.
Yield optimization in biotechnological production focuses on fermentation parameters such as substrate concentration, pH, and aeration.
Chemical processes typically yield vanillic acid at low percentages from lignin oxidation.

Commercially, vanillic acid serves as a key intermediate in vanillin synthesis, particularly through biocatalytic reduction, and is supplied by firms specializing in fine chemicals for pharmaceuticals and food additives.
Global production was estimated at approximately 19 metric tons annually as of 2016, primarily from chemical lignin oxidation in Europe and Asia, with biotechnological routes gaining traction for eco-friendly variants amid rising demand for bio-based aromatics.

PHYSICAL and CHEMICAL PROPERTIES of VANILLIC ACID:
CAS: 121-34-6
IUPAC Name: 4-hydroxy-3-methoxybenzoic acid
Molecular Formula: C8H8O4
InChI Key: WKOLLVMJNQIZCI-UHFFFAOYSA-N
SMILES: COC1=CC(=CC=C1O)C(O)=O
Molecular Weight: 168.15 g/mol
Average Molecular Weight: 168.148
Monoisotopic Molecular Weight: 168.042258738
Traditional Name: vanillic acid
CAS Registry Number: 121-34-6

Physical State: powder
Color: light yellow
Odor: odorless
Melting Point: 208-210 °C
Water Solubility: slightly soluble
Partition Coefficient: No data available
Vapor Pressure: No data available
Density: No data available
Relative Density: No data available

Relative Vapor Density: No data available
Particle Characteristics: No data available
Explosive Properties: No data available
Oxidizing Properties: none
Other Safety Information: No data available
Compound Is Canonicalized: Yes
CAS: 121-34-6
Purity: 96.5 - 103.5 % (Assay by titration)

Molecular Formula: C8H8O4
Molecular Weight: 168.15
MDL Number: MFCD00002551
PubChem ID: 8468
Melting Point: 208-210 °C
Appearance: White to pale yellow to beige powder
Conditions: Store at RT
XLogP3: 1.4

Hydrogen Bond Donor Count: 2
Hydrogen Bond Acceptor Count: 4
Rotatable Bond Count: 2
Exact Mass: 168.04225873 Da
Monoisotopic Mass: 168.04225873 Da
Topological Polar Surface Area: 66.8 Å²
Heavy Atom Count: 12

Formal Charge: 0
Complexity: 168
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1

Compound Is Canonicalized: Yes
Appearance: White to light yellow powder or crystals
Melting Point: 210-213 °C
Assay (Silylated GC): ≥97.5%
Appearance (Color): White to cream to yellow to pale brown
Form: Powder
Assay (Aqueous acid-base Titration): ≥97.5 to ≤102.5%
Identification (FTIR): Conforms

Assay from Supplier's CofA: ≥97.5%
Melting Point (clear melt): 208-218 °C
CBNumber: CB2449434
Molecular Formula: C8H8O4
Molecular Weight: 168.15
MDL Number: MFCD00002551
MOL File: 121-34-6.mol
Melting Point: 208-210 °C
Boiling Point: 257.07 °C

Density: 1.3037
Refractive Index: 1.5090
FEMA: 3988 | 4-HYDROXY-3-METHOXYBENZOIC ACID
Storage Temp: Store below +30°C
Solubility: Acetonitrile (Slightly), Aqueous Base (Slightly), DMSO (Slightly), Methanol (Slightly)
pKa: 4.53
Form: Liquid
Color: Clear colorless to brown, may darken during storage

Odor: at 100.00 %. dairy milky custard creamy powdery vanilla bean
Odor Type: creamy
Biological Source: synthetic
Water Solubility: Soluble in water, alcohol and ether
JECFA Number: 959
Merck: 14,9931
BRN: 2208364
Stability: Stable. Combustible. Incompatible with strong oxidizing agents

Cosmetics Ingredients Functions: NOT REPORTED
InChI: 1S/C8H8O4/c1-12-7-4-5(8(10)11)2-3-6(7)9/h2-4,9H,1H3,(H,10,11)
InChIKey: WKOLLVMJNQIZCI-UHFFFAOYSA-N
SMILES: COc1cc(ccc1O)C(O)=O
LogP: 1.30
CAS DataBase Reference: 121-34-6
Substances Added to Food (formerly EAFUS): VANILLIC ACID
EWG's Food Scores: 1
FDA UNII: GM8Q3JM2Y8

NIST Chemistry Reference: Benzoic acid, 4-hydroxy-3-methoxy-(121-34-6)
EPA Substance Registry System: Vanillic acid (121-34-6)
UNSPSC Code: 41116107
NACRES: NA.24
Molecular Weight: 168.148
Exact Mass: 168.15
EC Number: 204-466-8
UNII: GM8Q3JM2Y8
NSC Number: 674322|3987

DSSTox ID: DTXSID6059522
HScode: 29189090
PSA: 66.8
XLogP3: 1.4
Appearance: Solid
Density: 1.3037
Melting Point: 211.5 °C
Boiling Point: 257.07 °C
Flash Point: 149.4 °C

Refractive Index: 1.5090
Water Solubility: 1.5 mg/mL at 14 °C
Storage Conditions: Keep container closed when not in use.
Store in a tightly closed container.
Store in a cool, dry, well-ventilated area away from incompatible substances
Vapor Pressure: 1.32E-05 mmHg at 25°C
Collision Cross Section: 136.2 Å² [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]
Molecular Weight: 168.15
XLogP3: 1.4
Hydrogen Bond Donor Count: 2

Hydrogen Bond Acceptor Count: 4
Rotatable Bond Count: 2
Exact Mass: 168.04225873
Monoisotopic Mass: 168.04225873
Topological Polar Surface Area: 66.8
Heavy Atom Count: 12
Complexity: 168
Covalently-Bonded Unit Count: 1

Compound Is Canonicalized: Yes
CAS Number: 121-34-6
Average Mass: 168.148
Monoisotopic Mass: 168.042258738
Chemical Formula: C8H8O4
IUPAC Name: 4-hydroxy-3-methoxybenzoic acid
InChI Key: WKOLLVMJNQIZCI-UHFFFAOYSA-N
Solubility (ALOGPS): 5.70 g/l
LogS (ALOGPS): -1.47
LogP (ALOGPS): 1.70

Hydrogen Acceptors: 4
Hydrogen Donors: 2
Rotatable Bond Count: 2
Polar Surface Area: 66.76
Refractivity: 41.7583
Polarizability: 15.868081533318291
Formal Charge: 0
Physiological Charge: -1
pKa (strongest basic): -4.901377890748089
pKa (strongest acidic): 4.155416072405769
Number of Rings: 1

Rule of Five: Yes
Bioavailability: Yes
Ghose Filter: Yes
Veber's Rule: No
MDDR-like Rule: No
CAS: 121-34-6
EINECS: 204-466-8
InChI: InChI=1/C8H8O4/c1-12-7-4-5(8(10)11)2-3-6(7)9/h2-4,9H,1H3,(H,10,11)/p-1
InChIKey: WKOLLVMJNQIZCI-UHFFFAOYSA-N
Molecular Formula: C8H8O4

Molar Mass: 168.15
Density: 1.3037 (rough estimate)
Melting Point: 208-210°C(lit.)
Boiling Point: 257.07°C (rough estimate)
Flash Point: 149.4°C
JECFA Number: 959
Water Solubility: Soluble in water, alcohol and ether.
Solubility: Soluble in ethanol, soluble in ether, slightly soluble in water.
Vapor Pressure: 1.32E-05 mmHg at 25°C

Appearance: Crystalline powder
Color: Clear colorless to brown, may darken during storage
Merck: 14,9931
BRN: 2208364
pKa: pKa 4.53(H2O t = 25 c = 0.016–0.001) (Uncertain)
Storage Condition: Store below +30°C.
Stability: Stable. Combustible. Incompatible with strong oxidizing agents.
Refractive Index: 1.5090 (estimate)
MDL: MFCD00002551

FIRST AID MEASURES of VANILLIC ACID:
-Description of first-aid measures
*General advice:
Show this material safety data sheet to the doctor in attendance.
*If inhaled:
After inhalation:
Fresh air.
*In case of skin contact:
Take off immediately all contaminated clothing.
Rinse skin with
water/ shower.
*In case of eye contact:
After eye contact:
Rinse out with plenty of water.
Call in ophthalmologist.
Remove contact lenses.
*If swallowed:
After swallowing:
Immediately make victim drink water (two glasses at most).
Consult a physician.
-Indication of any immediate medical attention and special treatment needed.
No data available

ACCIDENTAL RELEASE MEASURES of VANILLIC ACID:
-Environmental precautions:
Do not let product enter drains.
-Methods and materials for containment and cleaning up:
Cover drains.
Collect, bind, and pump off spills.
Observe possible material restrictions.
Take up dry.
Dispose of properly.
Clean up affected area.

FIRE FIGHTING MEASURES of VANILLIC ACID:
-Extinguishing media:
*Suitable extinguishing media:
Carbon dioxide (CO2)
Foam
Dry powder
*Unsuitable extinguishing media:
For this substance/mixture no limitations of extinguishing agents are given.
-Further information:
Prevent fire extinguishing water from contaminating surface water or the ground water system.

EXPOSURE CONTROLS/PERSONAL PROTECTION of VANILLIC ACID:
-Control parameters:
--Ingredients with workplace control parameters:
-Exposure controls:
--Personal protective equipment:
*Eye/face protection:
Use equipment for eye protection.
Safety glasses
*Body Protection:
protective clothing
*Respiratory protection:
Recommended Filter type: Filter A
-Control of environmental exposure:
Do not let product enter drains.

HANDLING and STORAGE of VANILLIC ACID:
-Conditions for safe storage, including any incompatibilities:
*Storage conditions:
Tightly closed.
Dry.

STABILITY and REACTIVITY of VANILLIC ACID:
-Chemical stability:
The product is chemically stable under standard ambient conditions (room temperature).
-Possibility of hazardous reactions:
No data available