General Description
A white crystalline solid. Slightly soluble in water. The primary hazard is the potential for environmental damage if released. Immediate steps should be taken to limit spread to the environment. Used to make other chemicals, as a food preservative, and for other uses.
Reactivity Profile
At high temperature BENZOIC ACID can react with oxidizing reagents.
Air & Water Reactions
Vapor from molten BENZOIC ACID(65-85-0) may form explosive mixture with air. The finely powdered dry acid is a significant dust explosion hazard [Bretherick, 5th ed., 1995, p. 884]. In air very rapid combustion occurs [Wilson, L.Y. et al., J. Chem. Ed., 1985, 62(10), p. 902]. Slightly soluble in water.
Hazard
Moderately toxic by ingestion. Use
restricted to 0.1% in foods.
Health Hazard
Dust may be irritating to nose and eyes. At elevated temperatures, fumes may cause irritation of eyes, respiratory system, and skin.
Potential Exposure
Benzoic acid is used in production of
plasticizers, benzoyl chloride, sodium benzoate and alkyl
resins; in the manufacture of benzoates; in the manufacture
of food preservatives; as a dye binder in calico printing; in
curing of tobacco, flavors, perfumes, dentifrices; standard
in analytical chemistry; antifungal agent.
Fire Hazard
Behavior in Fire: Vapor from molten benzoic acid may form explosive mixture with air. Concentrated dust may form explosive mixture.
First aid
If this chemical gets into the eyes, remove any
contact lenses at once and irrigate immediately for at least
15 minutes, occasionally lifting upper and lower lids. Seek
medical attention immediately. If this chemical contacts the
skin, remove contaminated clothing and wash immediately
with soap and water. Seek medical attention immediately.
If this chemical has been inhaled, remove from exposure,
begin rescue breathing (using universal precautions, including
resuscitation mask) if breathing has stopped and CPR if
heart action has stopped. Transfer promptly to a medical
facility. When this chemical has been swallowed, get medical
attention. Give large quantities of water and induce
vomiting. Do not make an unconscious person vomit.
Shipping
UN3077 Environmentally hazardous substances,
solid, n.o.s., Hazard class: 9; Labels: 9—Miscellaneous
hazardous material, Technical Name Required.
Incompatibilities
Incompatible with oxidizers (chlorates,
nitrates, peroxides, permanganates, perchlorates, chlorine,
bromine, fluorine, etc.); contact may cause fires or explosions.
Keep away from alkaline materials, strong bases,
strong acids, oxoacids, epoxides, caustics, ammonia,
amines, isocyanates. Dust forms an explosive mixture with
air.
Waste Disposal
Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator
equipped with an afterburner and scrubber. All federal,
state, and local environmental regulations must be
observed.
Physical properties
Colorless to white needles, scales, or powder with a faint benzoin or benzaldehyde-like odor.
Shaw et al. (1970) reported a taste threshold in water of 85 ppm.
Occurrence
Reported found in fresh apple, apricot (Prunus armeniaca L.), strawberry fruit, cherry (Prunus cerasus L.),
butter, boiled and cooked beef, pork fat, white wine, black tea, green tea, fresh plum, mushroom, Bourbon vanilla (Vanilla planifolia
Andrews), and other natural sources. Reported as being a constituent of various oils, resins and flower absolutes; hyacinth, tuberose,
neroli bigarade, Chinese cinnamon, cinnamon leaves, anise, vertiver, ylang-ylang, Tolu balsam and clove; it is contained in fairly sizable
amounts in gum benzoin, from which benzoic acid is extracted by sublimation.
Definition
ChEBI: A compound comprising a benzene ring core carrying a carboxylic acid substituent.
Production Methods
Industrial preparations
Benzoic acid is produced commercially by partial oxidation of toluene with oxygen. The process is catalyzed by cobalt or manganese naphthenates. The process uses cheap raw materials, proceeds in high yield, and is considered environmentally green.
Laboratory synthesis
Benzoic acid is cheap and readily available, so the laboratory synthesis of benzoic acid is mainly practiced for its pedagogical value. It is a common undergraduate preparation.
For all syntheses, benzoic acid can be purified by recrystallization from water because of its high solubility in hot water and poor solubility in cold water. The avoidance of organic solvents for the recrystallization makes this experiment particularly safe. Other possible recrystallization solvents include acetic acid (anhydrous or aqueous), benzene, acetone, petroleum ether, and a mixture of ethanol and water. The solubility of benzoic acid in over 40 solvents with references to original sources can be found as part of the Open Notebook Science Challenge.
Production Methods
Although benzoic acid occurs naturally, it is produced commercially
by several synthetic methods. One process involves the continuous
liquid-phase oxidation of toluene in the presence of a cobalt catalyst
at 150–2008℃ and 0.5–5.0 MPa (5.0–50.0 atm) pressure to give a
yield of approximately 90% benzoic acid.
Benzoic acid can also be produced commercially from benzotrichloride
or phthalic anhydride. Benzotrichloride, produced by
chlorination of toluene, is reacted with 1 mole of benzoic acid to
yield 2 moles of benzoyl chloride. The benzoyl chloride is then
converted to 2 moles of benzoic acid by hydrolysis. Yield is
75–80%.
In another commercial process, phthalic anhydride is converted
to benzoic acid, in about an 85% yield, by hydrolysis in the presence
of heat and chromium and disodium phthalates.
Crude benzoic acid is purified by sublimation or recrystallization.
Production Methods
Benzoic acid can be synthesized using a number of processes. The industrial method is by the partial oxidation of toluene (C6H5CH3) in liquid phase using manganese, cobalt, vanadium-titanium, or other catalysts. The reaction is carried out at temperatures between 150°C and 200°C. It can also be prepared by the oxidation of benzaldehyde, benzyl alcohol (C6H5CH2OH), and cinnamic acid (C6H5CHCHO2) or by the oxidation of benzene with concentrated sulfuric acid. The hydrolysis of benzonitrile (C6H5CN) produces benzoic acid. It is also produced by the carboxylation of a Grignard reagent followed by acidification; typically carbonation occurs by pouring a Grignard ether over dry ice.
Reactions
Reactions of benzoic acid can occur at either the aromatic ring or the carboxyl group :
Aromatic ring
Electrophilic aromatic substitution reaction will take place mainly in 3- position due to the electron-withdrawing carboxylic group; i.e. benzoic acid is meta directing.
The second substitution reaction (on the right) is slower because the first nitro group is deactivating. Conversely, if an activating group (electron - donating) was introduced (e.g., alkyl), a second substitution reaction would occur more readily than the first and the disubstituted product might accumulate to a significant extent.
Carboxyl group
All the reactions mentioned for carboxylic acids are also possible for benzoic acid.
Benzoic acid esters are the product of the acid catalysed reaction with alcohols. Benzoic acid amides are more easily available by using activated acid derivatives (such as benzoyl chloride) or by coupling reagents used in peptide synthesis like DCC and DMAP.
The more active benzoic anhydride is formed by dehydration using acetic anhydride or phosphorus pentoxide.
Highly reactive acid derivatives such as acid halides are easily obtained by mixing with halogenation agents like phosphorus chlorides or thionyl chloride.
Ortho esters can be obtained by the reaction of alcohols under acidic water free conditions with benzonitrile.
Reduction to benzaldehyde and benzyl alcohol is possible using DIBAL- H , Li Al H4 or sodium boro hydride.
The copper catalyzed decarboxylation of benzoate to benzene may be effected by heating in quinoline. Also, Hunsdiecker decarboxylation can be achieved by forming the silver salt and heating. Benzoic acid can also be decarboxylated by heating with an alkali hydroxide or calcium hydroxide.
Biotechnological Production
Benzoic acid is exclusively chemically synthesized on an industrial scale. Toluene
from petrochemical routes is oxidized in the presence of the catalyst potassium
permanganate to benzoic acid . However, a recent study described for the first
time a benzoic acid production process by fermentation using Streptomyces
maritimus. The production of benzoic acid during cultivation on glucose,
starch, and cellobiose has been investigated. The best results have been achieved
with product concentrations of 460 mg.L-1 in 6 days using starch as substrate.
Additionally, a genetically modified S. maritimus optimized for endo-glucanasesecretion
has been tested on phosphoric acid swollen cellulose. A final product
concentration of 125 mg.L-1 was observed after 4 days of cultivation.
Aroma threshold values
85 ppm.
Chemical Reactivity
Transition-metal-catalyzed oxidative annulation reactions can be used to
synthesize various benzo-fused oxygen- and nitrogen-containing
heterocyclic compounds from benzoic acids
[1].
Agricultural Uses
Fungicide, Insecticide: Used in the manufacture of benzoates; plasticizers,
benzoyl chloride, alkyd resins, in the manufacture of food
preservatives, in use as a dye binder in calico printing; in
curing of tobacco, flavors, perfumes, dentifrices, standard
in analytical chemistry. Not currently registered for use in
the U.S. Benzoic acid is currently used in about a dozen
European countries.
Pharmaceutical Applications
Benzoic acid is widely used in cosmetics, foods, and pharmaceuticals, as an antimicrobial preservative. Greatest
activity is seen at pH values between 2.5–4.5.
Benzoic acid also has a long history of use as an antifungal
agent in topical therapeutic preparations such as Whitfield’s
ointment (benzoic acid 6% and salicylic acid 3%).
Trade name
RETARDER BA®; MICROL®
Preservative; TENN-PLAS®; RETARDEX®; SALVO
LIQUID®; SALVO POWDER®; TULSA®
Mechanism of action
Contact action, non-selective
Clinical Use
Benzoic acid is a metabolite of benzyl alcohol and sodium benzoate is the sodium salt of benzoic acid. These three related compounds are used as preservatives in a variety of products, such as cosmetics, toothpastes, hair products, medication preparations, and emollients, and in foods. They are well-recognized to cause nonimmunological CoU and reactions are concentration-dependent.Both oral intake and cutaneous contact of benzyl alcohol, benzoic acid, or sodium benzoate can cause immediate reactions; however, there is a lack of correlation between the two and skin tests should not be used to predict sensitivity to oral intake of these preservatives.
Immediate reactions to the oral ingestion of these preservatives are rare. Nettis et al. investigated 47 patients with a history of urticaria after the ingestion of meals or products containing sodium benzoate, and only one patient had a generalized urticarial reaction to an oral challenge test of 50 mg of sodium benzoate.
Side effects
Benzoic acid occurs naturally free and bound as benzoic acid esters in many plant and animal species. Appreciable amounts have been found in most berries (around 0.05 %). Ripe fruits of several Vaccinium species (e.g., cranberry, V. vitis idaea; bilberry, V. macrocarpon) contain as much as 0.03 – 0.13 % free benzoic acid. Benzoic acid is also formed in apples after infection with the fungus Nectria galligena. Among animals, benzoic acid has been identified primarily in omnivorous or phytophageous species, e.g., in viscera and muscles of the Rock Ptarmigan (Lagopus muta) as well as in gland secretions of male muskoxen (Ovibos moschatus) or Asian bull elephants (Elephas maximus).
Gum benzoin contains up to 20 % of benzoic acid and 40% benzoic acid esters.
Toxicology
Four-generation reproductive and developmental toxicities of benzoic acid were examined using diets containing 0, 0.5, and 1% of benzoic acid fed to male and female rats housed together for eight weeks. The second generation was observed through its entire life cycle and the third and fourth generations were examined by autopsy. No changes in normal patterns of growth, reproduction, or lactation during life were recorded and no morphological abnormalities were observed from the autopsies.
Degradation pathways for benzoic acid also have been studied in detail and the results have supported the harmlessness of this substance. The total dose of benzoic acid is excreted within 10 to 14 hours and 75 to 80% is excreted within 6 hours. After conjugation with glycine, 90% of benzoic acid appears in the urine as hippuric acid. The rest forms a glucuronide,1-benzoylglucuronic acid. The lower aliphatic esters of benzoic acid are first hydrolyzed by esterase, which abounds in the intestinal wall and liver. The resulting benzoic acid subsequently is degraded in the usual manner.
Safety
Ingested benzoic acid is conjugated with glycine in the liver to yield
hippuric acid, which is then excreted in the urine; care should be
taken when administering benzoic acid to patients with chronic liver
disease. Benzoic acid is a gastric irritant, and a mild irritant to the
skin. It is also a mild irritant to the eyes and mucous
membranes. Allergic reactions to benzoic acid have been
reported, although a controlled study indicated that the incidence
of urticaria in patients given benzoic acid is no greater than in those
given a lactose placebo. It has been reported that asthmatics may
become adversely affected by benzoic acid contained in some
antiasthma drugs.
The WHO acceptable daily intake of benzoic acid and other
benzoates, calculated as benzoic acid, has been set at up to 5 mg/kg
body-weight. The minimum lethal human oral dose of benzoic
acid is 500 mg/kg body-weight.
LD50 (cat, oral): 2 g/kg
LD50 (dog, oral): 2 g/kg
LD50 (mouse, IP): 1.46 g/kg
LD50 (mouse, oral): 1.94 g/kg
LD50 (rat, oral): 1.7 g/kg
Carcinogenicity
Benzoic acid was not genotoxic in bacterial
assays or in in vitro mammalian assays.
Source
Naturally occurs in cranberries, ligonberries (1,360 ppm), peppermint leaves (20–200
ppb), tea leaves, cassia bark, carob, blessed thistle, purple foxglove, jasmine, hyacinth, apples,
tobacco leaves, daffodils, autumn crocus, prunes, anise seeds, ripe cloves, and wild black cherry
tree bark (Duke, 1992; quoted, Verschueren, 1983).
Schauer et al. (1999) reported benzoic acid in diesel fuel at a concentration of 1,260 μg/g.
Identified as an oxidative degradation product in the headspace of a used engine oil (10–30W)
after 4,080 miles (Levermore et al., 2001).
The gas-phase tailpipe emission rate from California Phase II reformulated gasoline-powered
automobile equipped with a catalytic converter was 124 μg/km (Schauer et al., 2002).
Benzoic acid is a by-product of benzoyl peroxide used in the bleaching of freshly milled wheat
flour. A maximum benzoic acid concentration of 16 ppm was reported after 12 h of bleaching. The
concentration decreased to 6 ppm after 3 months (Saiz et al., 2001).
A liquid swine manure sample collected from a waste storage basin contained benzoic acid at a
concentration of 4.0 mg/L (Zahn et al., 1997).
Environmental Fate
Biological. Benzoic acid may degrade to catechol if it is the central metabolite whereas, if
protocatechuic acid (3,4-dihydroxybenzoic acid) is the central metabolite, the precursor is 3-
hydroxybenzoic acid (Chapman, 1972). Other compounds identified following degradation of
benzoic acid to catechol include cis,cis-muconic acid, (+)-muconolactone, 3-oxoadipate enol
lactone, and 3-oxoadipate (quoted, Verschueren, 1983). Pure microbial cultures hydroxylated
benzoic acid to 3,4-dihydroxybenzoic acid, 2- and 4-hydroxybenzoic acid (Smith and Rosazza,
1974). In activated sludge, 65.5% mineralized to carbon dioxide after 5 d (Freitag et al., 1985).
Photolytic. Titanium dioxide suspended in an aqueous solution and irradiated with UV light (λ
= 365 nm) converted benzoic acid to carbon dioxide at a significant rate (Matthews, 1986). An
aqueous solution containing chlorine and irradiated with UV light (λ = 350 nm) converted benzoic
acid to salicylaldehyde and unidentified chlorinated compounds (Oliver and Carey, 1977). A
carbon dioxide yield of 10.2% was achieved when benzoic acid adsorbed on silica gel was
irradiated with light (λ >290 nm) for 17 h (Freitag et al., 1985).
Brubaker and Hites (1998) measured the OH radical rate constant for benzoic acid between 333
and 363 K. The rate constants (x 1012 cm3/sec) were 0.42 and 0.66 at 333 K (two determinations),
0.84 at 343 K, and 0.72 at 363 K. In water, benzoic acid reacted with OH radicals at a rate of 1.2 x
1013/M·h at 25 °C (Armbrust, 2000).
Chemical/Physical. At an influent concentration of 1.0 g/L, treatment with GAC resulted in an
effluent concentration of 89 mg/L. The adsorbability of the carbon used was 183 mg/g carbon
(Guisti et al., 1974). Ward and Getzen (1970) investigated the adsorption of aromatic acids on
activated carbon under acidic, neutral, and alkaline conditions. The amount of benzoic acid (10-4
M) adsorbed by carbon at pH values of 3.0, 7.0, and 11.0 were 49.7, 11.2, and 2.5%, respectively.
Similarly, at influent concentrations of 1.0, 0.1, 0.01, and 0.001 mg/L, the respective GAC
adsorption capacities were 130, 51, 19, and 7.3 mg/g at pH 3.0 and 54, 0.76, 0.01, and 0.002 mg/g
at pH 7.0 At pH 9.0 and influent concentrations of 10 and 1.0 mg/L, the GAC adsorption
capacities were 21 and 0.008, respectively (Dobbs and Cohen, 1980).
storage
Aqueous solutions of benzoic acid may be sterilized by autoclaving
or by filtration.
A 0.1% w/v aqueous solution of benzoic acid has been reported
to be stable for at least 8 weeks when stored in polyvinyl chloride
bottles, at room temperature.
When added to a suspension, benzoic acid dissociates, with the
benzoate anion adsorbing onto the suspended drug particles. This
adsorption alters the charge at the surface of the particles, which
may in turn affect the physical stability of the suspension. The
addition of sodium azide has been shown to increase the stability of
benzoic acid in skin permeation experiments.
The bulk material should be stored in a well-closed container in a
cool, dry place.
Purification Methods
For use as a volumetric standard, analytical reagent grade benzoic acid should be carefully fused to ca 130o (to dry it) in a platinum crucible, and then powdered in an agate mortar. Benzoic acid has been crystallised from boiling water (charcoal), aqueous acetic acid, glacial acetic acid, *C6H6, aqueous EtOH, pet ether (b 60-80o), and from EtOH solution by adding water. It is readily purified by fractional crystallisation from its melt and by sublimation in a vacuum at 80o. The S-benzylisothiuronium salt has m 167o (from EtOH/H2O). [Beilstein 9 IV 273.]
Toxics Screening Level
The initial threshold screening level (ITSL) for benzoic acid is 5 μg/m3.
Regulatory Status
GRAS listed. Accepted as a food additive in Europe. Included in the
FDA Inactive Ingredients Database (IM and IV injections, irrigation
solutions, oral solutions, suspensions, syrups and tablets, rectal,
topical, and vaginal preparations). Included in nonparenteral
medicines licensed in the UK. Included in the Canadian List of
Acceptable Non-medicinal Ingredients.
References
[1] Yang, X., Sun, R. (2023). Progress in Transition‐Metal‐Catalyzed Synthesis of Benzo‐Fused Oxygen‐ and Nitrogen Heterocyclic Compounds from Benzoic Acids. Advanced Synthesis & Catalysis, 365 2, Pages 124-141.
https://doi.org/10.1002/adsc.202201172
Pesticide Type
Insecticide; Fungicide
