Benzoic acid

Benzoic acid
Image:Benzoic acid.svg
IUPAC name	Benzoic acid, benzene carboxylic acid
Other names	Carboxybenzene, E210, dracylic acid
Identifiers
CAS number	[65-85-0]
PubChem	243
KEGG	C00180
MeSH	Acid benzoic Acid
ChEBI	30746
RTECS number	DG0875000
SMILES	c1ccccc1C(=O)O
InChI	1/C7H6O2/c8-7(9)6-4-2-1-3-5-6/ h1-5H,(H,8,9)/f/h8H
Beilstein Reference	636131
Gmelin Reference	2946
3DMet	B00053
Properties
Molecular formula	C6H5COOH
Molar mass	122.12 g/mol
Appearance	Colourless crystalline solid
Density	1.32 g/cm3, solid
Melting point	122.4 °C (395 K)
Boiling point	249  °C (522 K)
Solubility in water	Soluble (hot water) 3.4 g/l (25 °C)
Solubility in methanol, diethylether	Soluble
Acidity (pKa)	4.21
Structure
Crystal structure	Monoclinic
Molecular shape	planar
Dipole moment	1.72 D in Dioxane
Hazards
MSDS	ScienceLab.com
Main hazards	Irritating
NFPA 704	1 2 0
R-phrases	R22, R36
S-phrases	S24
Flash point	121 °C (394 K)
Related compounds
Related carboxylic acid	phenylacetic acid, hippuric acid, salicylic acid
Related compounds	benzene, benzaldehyde, benzyl alcohol, benzylamine, benzyl benzoate, benzoyl chloride
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Benzoic acid, C₇H₆O₂ (or C₆H₅COOH), is a colorless crystalline solid and the simplest aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the only source for benzoic acid. This weak acid and its salts are used as a food preservative. Benzoic acid is an important precursor for the synthesis of many other organic substances.

History

Benzoic acid was discovered in the 16th century. The dry distillation of gum benzoin was first described by Nostradamus (1556), and subsequently by Alexius Pedemontanus (1560) and Blaise de Vigenère (1596).^[1]

Justus von Liebig and Friedrich Wöhler determined the structure of benzoic acid in 1832.^[2] They also investigated how hippuric acid is related to benzoic acid.

In 1875 Salkowski discovered the antifungal abilities of benzoic acid, which were used for a long time in the preservation of benzoate containing fruits.^[3]

Production

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.

Image:Benzoic acid-chemical-synthesis-1.png

U.S. production capacity is estimated to be 126,000 tonnes per year (139,000 tons), much of which is consumed domestically to prepare other industrial chemicals.

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 and a convenient property of the compound is that its melting point equals its molecular weight (122).

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, petroleum ether, and a mixture of ethanol and water.^[4]

By hydrolysis

Like any other nitrile or amide, benzonitrile and benzamide can be hydrolyzed to benzoic acid or its conjugate base in acid or basic conditions.

From benzaldehyde

The base-induced disproportionation of benzaldehyde, the Cannizzaro reaction, affords equal amounts of benzoate and benzyl alcohol; the latter can be removed by distillation.

Image:Benzaldehyde Cannizzaro reaction.png

From bromobenzene

Bromobenzene in diethyl ether is stirred with magnesium turnings to produce phenylmagnesium bromide (C₆H₅MgBr). This Grignard reagent is slowly added to dry ice to give benzoate. Dilute acid is added to form benzoic acid.^[5]

Image:Benzoic acid synthesis.png

From benzyl alcohol

Benzyl alcohol is refluxed with potassium permanganate or other oxidizing reagents in water. The mixture hot filtered to remove manganese oxide and then allowed to cool to afford benzoic acid.

Historical preparations

The first industrial process involved the reaction of benzotrichloride (trichloromethyl benzene) with calcium hydroxide in water, using iron or iron salts as catalyst. The resulting calcium benzoate is converted to benzoic acid with hydrochloric acid. The product contains significant amounts of chlorinated benzoic acid derivatives. For this reason, benzoic acid for human consumption was obtained by dry distillation of gum benzoin. Food-grade benzoic acid is now produced synthetically.^[6]

Alkyl substituted benzene derivatives give benzoic acid with the stoichiometric oxidants potassium permanganate, chromium trioxide, nitric acid.

Uses

Food preservative

Benzoic acid and its salts are used as a food preservative, represented by the E-numbers E210, E211, E212, and E213. Benzoic acid inhibits the growth of mold, yeast^[7] 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. If the intracellular pH changes to 5 or lower, the anaerobic fermentation of glucose through phosphofructokinase is decreased by 95%. The efficacy of benzoic acid and benzoate is thus dependent on the pH of the food.^[8] Acidic food and beverage like fruit juice (citric acid), sparkling drinks (carbon dioxide), soft drinks (phosphoric acid), pickles (vinegar) or other acidified food are preserved with benzoic acid and benzoates.

Typical levels of use for benzoic acid as a preservative in food are between 0.05 – 0.1%. Foods in which benzoic acid may be used and maximum levels for its application are laid down in international food law.^[9][10]

Concern has been expressed that benzoic acid and its salts may react with ascorbic acid (vitamin C) in some soft drinks, forming small quantities of benzene.^[11][12]

See also: Benzene in soft drinks

Feedstock

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 as artificial flavours and insect repellents.
• Benzoyl peroxide, [C₆H₅C(O)O]₂, is obtained by treatment with peroxide.^[13] The peroxide is a radical initiator in polymerization reactions and also a component in cosmetic products.
  • Benzoate plasticizers, such as the glycol-, diethylengylcol-, and triethyleneglycol esters are obtained by transesterification of methyl benzoate with the corresponding diol. Alternatively these species arise by treatment of benzoylchloride with the diol. These plasticizers are used similarly to those derived from terephthalic acid ester.
  • Phenol, C₆H₅OH, is obtained by oxidative decarboxylation at 300-400°C. The temperature required can be lowered to 200°C by the addition of catalytic amounts of copper(II) salts. The phenol can be converted to cyclohexanol, which is a starting material for nylon synthesis.

  Medicinal

  Benzoic acid is a constituent of Whitfield Ointment which is used for the treatment of fungal skin diseases such as tinea, ringworm, and athlete's foot. ^{[14] [15]}

  Biology and health 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 300-1300 mg free benzoic acid per kg fruit. 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 ptarmigan (Lagopus mutus) as well as in gland secretions of male muskoxen (Ovibos moschatus) or Asian bull elephants (Elephas maximus).^[16]

  Gum benzoin contains up to 20% of benzoic acid and 40% benzoic acid esters.^[17]

  Benzoic acid is present as part of hippuric acid (N-Benzoylglycine) in urine of mammals, especially herbivores (Gr. hippos = horse; ouron = urine). Humans produce about 0.44 g/L hippuric acid per day in their urine, and if the person is exposed to toluene or benzoic acid it can rise above that level.^[18]

  For humans ,the WHO's International Programme on Chemical Safety (IPCS) suggests a provisional tolerable intake would be 5 mg/kg body weight per day.^[16] Cats have a significantly lower tolerance against benzoic acid and its salts than rats and mice. Lethal dose for cats can be as low as 300 mg/kg body weight.^[19] The oral LD₅₀ for rats is 3040 mg/kg, for mice it is 1940-2263 mg/kg.^[16]

  Chemistry

  Reactions of benzoic acid can occur at either the aromatic ring or the carboxylic group:

  Aromatic ring

  Image:Benzoic acid-chemical-reaction-1.png

  Electrophilic aromatic substitution reaction will take place mainly in 3-position to the electron-withdrawing carboxylic group.

  The second substitution reaction (on the right) is slower because the first nitro group is deactivating.^[20] 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 not accumulate to a significant extent.

  Carboxylic 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.
  • Orthoesters 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, LiAlH₄ or sodium borohydride.
  • The copper catalysed decarboxylation of benzoate to benzene may be effected by heating in quinoline. Also, Hunsdiecker decoarboxylation can be achieved by forming the silver salt and heating.

  Image:Benzoic acid-chemical-reaction-2.png

  References

  1. ^ Neumüller O-A (1988). Römpps Chemie-Lexikon, 6, Stuttgart: Frankh'sche Verlagshandlung. ISBN 3-440-04516-1. 
  2. ^ Liebig J, Wöhler F (1832). "Untersuchungen über das Radikal der Benzoesäure". Annalen der Chemie 3: 249-282. doi:10.1002/jlac.18320030302. 
  3. ^ Salkowski E (1875). "". Berl Klin Wochenschr 12: 297-298. 
  4. ^ D. D. Perrin; W. L. F. Armarego (1988). Purification of Laboratory Chemicals, 3rd Edition, Pergamon Press, 94. ISBN 0-08-034715-0. 
  5. ^ Donald L. Pavia (2004). Introduction to Organic Laboratory Techniques: A Small Scale Approach. Thomson Brooks/Cole, 312-314. ISBN 0534408338. 
  6. ^ Killinger-Mann, Karen (September 7, 2007). What's in my.... The Columbian. Retrieved on 2007-09-08.
  7. ^ A D Warth (1991). "Mechanism of action of benzoic acid on Zygosaccharomyces bailii: effects on glycolytic metabolite levels, energy production, and intracellular pH.". Appl Environ Microbiol. 1991 December 1: 1. 
  8. ^ Pastrorova I, de Koster CG, Boom JJ (1997). "Analytic Study of Free and Ester Bound Benzoic and Cinnamic Acids of Gum Benzoin Resins by GC-MS HPLC-frit FAB-MS". Phytochem Anal 8: 63-73. doi:10.1002/(SICI)1099-1565(199703)8:2%3C63::AID-PCA337%3E3.0.CO;2-Y. 
  9. ^ GSFA Online Food Additive Group Details: Benzoates (2006)
  10. ^ EUROPEAN PARLIAMENT AND COUNCIL DIRECTIVE No 95/2/EC of 20 February 1995 on food additives other than colours and sweeteners (Consleg-versions do not contain the latest changes in a law)
  11. ^ Goldstein, David. "FDA finds benzene in soft drinks", Knight Ridder, 2006-03-03. 
  12. ^ http://www.bfr.bund.de/cm/245/indications_of_the_possible_formation_of_benzene_from_benzoic_acid_in_foods.pdf BfR article
  13. ^ Silbert, L. S.; Siegel, E.; Swern, D. (1973). "Peroxybenzoic Acid". Org. Synth.; Coll. Vol. 5: 904. 
  14. ^ Whitfield Ointment
  15. ^ Charles Owens Wilson; Ole Gisvold; John H. Block (2004). Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical. Lippincott Williams & Wilkins, 234. ISBN 0781734819. 
  16. ^ ^{a b c} Concise International Chemical Assessment Document 26: BENZOIC ACID AND SODIUM BENZOATE
  17. ^ Tomokuni K, Ogata M (1972). "Direct Colorimetric Determination of Hippuric Acid in Urine". Clin Chem 18: 349-351. 
  18. ^ Krebs HA, Wiggins D, Stubbs M (1983). "Studies on the mechanism of the antifungal action of benzoate". Biochem J 214: 657-663. 
  19. ^ Bedford PG, Clarke EG (1972). "Experimental benzoic acid poisoning in the cat". Vet Rec 90: 53-58. PMID 4672555. 
  20. ^ Brewster, R. Q.; Williams, B.; Phillips, R. (1955). "3,5-Dinitrobenzoic Acid". Org. Synth.; Coll. Vol. 3: 337. 

  
  

  Further reading

  • Cosmetic Ingredient Review Expert Panel Bindu Nair (2001). "Final Report on the Safety Assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate". Int J Tox 20 (Suppl. 3): 23-50. 

  External links

  • International Chemical Safety Card 0103
  • ChemicalLandbg:Бензоена киселина

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