Benzoic acid

Description

Benzoic acid, the simplest benzene-based carboxylic acid, has been known since the 16th century. One of its discoverers was the legendary clairvoyant Nostradamus. Its most common natural source is gum benzoin, a resin found in the bark of trees of the genus Styrax.

Description

Benzoic acid is a colorless, crystalline solid also known as benzenecarboxylic acid. It is the simplest aromatic carboxylic acid, with a carboxyl group (-COOH) bonded directly to the benzene ring. It is found naturally in the benzoin resin of a number of plants.

Chemical properties

Benzoic acid,C6H5COOH, also known as benzene carboxylic acid and phenyl formic acid,is a colorless, monoclinic crystalline solid that has a melting point of 122.4"C and sublimes readily at 100·C. It is an aromatic carboxylic acid that is slightly soluble in water and moderately soluble in alcohol and ether. It is used as a preservative and its derivatives are valuable in medicine, commerce, and industry.

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.

History

Benzoic acid was first isolated from the dry distillation of benzoin by Blaise de Vigenère (1523–1596) in the 16th century. Friedrich W?hler (1800–1882) and Justus von Liebig (1803–1873) prepared benzoic acid from oxidizing bitter almond oil (benzaldehyde) in 1832 and determined the formula for each of these compounds. They proposed that bitter almond oil, C₇H₆O, and benzoic acid were derivatives from the benzoyl radical, C₇H₅O; the radical theory was a major early theory in the development of organic chemistry.

The Uses of Benzoic acid

Benzoic acid is a simple organic compound employed as a preservative. Benzoic acid and sodium benzoate (C6H5COONa) are used as food preservatives and added to foods, juices, and beverages that are acidic. It also is often found in topical antifungal preparations.

The Uses of Benzoic acid

Calorimetry
Benzoic acid is the most commonly used chemical standard to determine the heat of capacity of a bomb calorimeter.
Feed stock
Benzoic acid is used to make a large number of chemicals, important examples of which are :
Benzoyl chloride, C₆H₅C(O)Cl, is obtained by treatment of benzoic with thionyl chloride, phosgene or one of the chlorides of phosphorus. C₆H₅C(O) Cl is an important starting material for several benzoic acid derivates like benzyl benzoate, which is used in artificial flavours and insect repellents.
Food preservative
Benzoic acid and its salts are used as a food preservatives, represented by the E-numbers E210 , E211 , E212 , and E213 . Benzoic acid inhibits the growth of mold, yeast and some bacteria. It is either added directly or created from reactions with its sodium, potassium, or calcium salt. The mechanism starts with the absorption of benzoic acid in to the cell.
Medicinal
Benzoic acid is a constituent of Whitfiel's ointment which is used for the treatment of fungal skin diseases such as tinea, ringworm, and athlete's foot. As the principal component of benzoin resin, benzoic acid is also a major ingredient in both tincture of benzoin and Fria's balsam. Such products have a long history of use as topical antiseptics and inhalant decongestants.
Benzoic acid was used as an expectorant, analgesic, and antiseptic in the early 20th century.

Background

As a fungistatic compound Benzoic acid is widely used as a food preservative. It is conjugated to GLYCINE in the liver and excreted as hippuric acid. As the sodium salt form, sodium benzoate is used as a treatment for urea cycle disorders due to its ability to bind amino acids. This leads to excretion of these amino acids and a decrease in ammonia levels. Recent research shows that sodium benzoate may be beneficial as an add-on therapy (1 gram/day) in schizophrenia. Total Positive and Negative Syndrome Scale scores dropped by 21% compared to placebo.

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.

Preparation

By oxidation of toluene with nitric acid or sodium bichromate or from benzonitrile.

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.

Synthesis Reference(s)

Canadian Journal of Chemistry, 50, p. 3741, 1972 DOI: 10.1139/v72-592
Chemistry Letters, 5, p. 147, 1976
Tetrahedron Letters, 23, p. 2347, 1982 DOI: 10.1016/S0040-4039(00)87338-4

General Description

Boric acid,H3B03, also known as boracic acid, orthoboric acid, and sassolite, is a white solid composed of triclinic crystals.It is a derivative of barium oxide and is soluble in water. 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.

Air & Water Reactions

Vapor from molten Benzoic acid 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.

Reactivity Profile

At high temperature Benzoic acid can react with oxidizing reagents.

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.

Fire Hazard

Behavior in Fire: Vapor from molten Benzoic acid may form explosive mixture with air. Concentrated dust may form explosive mixture.

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®

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

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.

First aid

If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts theskin, remove contaminated clothing and wash immediatelywith 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 ifheart action has stopped. Transfer promptly to a medicalfacility. When this chemical has been swallowed, get medical attention. Give large quantities of water and inducevomiting. Do not make an unconscious person vomit.

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).

Production

Sodium benzoate is an important benzoic acid derivative produced industrially by neutralization of benzoic acid using sodium hydroxide or sodium bicarbonate solution. Calcium benzoate, potassium benzoate, and other benzoate salts are also produced. Its first industrial synthesis was the hydrolysis of benzotrichloride to calcium benzoate, followed by acidification. This method has been completely displaced by the air oxidation of toluene, which avoids the problem of product contamination with chlorinated byproducts.

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.

Shipping

UN3077 Environmentally hazardous substances, solid, n.o.s., Hazard class: 9; Labels: 9—Miscellaneous hazardous material, Technical Name Required.

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.]

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.

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.