Benzoic acid explained

Benzoic acid is a white (or colorless) solid organic compound with the formula, whose structure consists of a benzene ring with a carboxyl substituent. The benzoyl group is often abbreviated "Bz" (not to be confused with "Bn" which is used for benzyl), thus benzoic acid is also denoted as BzOH, since the benzoyl group has the formula –. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin, which was for a long time its only source.

Benzoic acid occurs naturally in many plants[1] and serves as an intermediate in the biosynthesis of many secondary metabolites. Salts of benzoic acid are used as food preservatives. Benzoic acid is an important precursor for the industrial synthesis of many other organic substances. The salts and esters of benzoic acid are known as benzoates .

History

Benzoic acid was discovered in the sixteenth century. The dry distillation of gum benzoin was first described by Nostradamus (1556), and then by Alexius Pedemontanus (1560) and Blaise de Vigenère (1596).[2]

Justus von Liebig and Friedrich Wöhler determined the composition of benzoic acid.[3] These latter also investigated how hippuric acid is related to benzoic acid.

In 1875 Salkowski discovered the antifungal properties of benzoic acid, which was used for a long time in the preservation of benzoate-containing cloudberry fruits.[4]

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 abundant materials, and proceeds in high yield.[5]

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.

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.

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. This process usually gives a yield of around 65%.[6]

By hydrolysis

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

From Grignard reagent

Bromobenzene can be converted to benzoic acid by "carboxylation" of the intermediate phenylmagnesium bromide.[7] This synthesis offers a convenient exercise for students to carry out a Grignard reaction, an important class of carbon–carbon bond forming reaction in organic chemistry.[8] [9] [10] [11] [12]

Oxidation of benzyl compounds

Benzyl alcohol[13] and benzyl chloride and virtually all benzyl derivatives are readily oxidized to benzoic acid.

Uses

Benzoic acid is mainly consumed in the production of phenol by oxidative decarboxylation at 300−400 °C:[14]

C6H5CO2H + 1/2 O2 -> C6H5OH + CO2The 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.

Precursor to plasticizers

Benzoate plasticizers, such as the glycol-, diethyleneglycol-, and triethyleneglycol esters, are obtained by transesterification of methyl benzoate with the corresponding diol.[14] These plasticizers, which are used similarly to those derived from terephthalic acid ester, represent alternatives to phthalates.[14]

Precursor to sodium benzoate and related preservatives

Benzoic acid and its salts are used as food preservatives, represented by the E numbers E210, E211, E212, and E213. Benzoic acid inhibits the growth of mold, yeast[15] 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 into 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.[16] Benzoic acid, benzoates and their derivatives are used as preservatives for acidic foods and beverages such as citrus fruit juices (citric acid), sparkling drinks (carbon dioxide), soft drinks (phosphoric acid), pickles (vinegar) and other acidified foods.

Typical concentrations of benzoic acid as a preservative in food are between 0.05 and 0.1%. Foods in which benzoic acid may be used and maximum levels for its application are controlled by local food laws.[17] [18]

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 carcinogenic benzene.[19]

See also: Benzene in soft drinks.

Medicinal

Benzoic acid is a constituent of Whitfield's ointment which is used for the treatment of fungal skin diseases such as ringworm and athlete's foot.[20] [21] As the principal component of gum benzoin, benzoic acid is also a major ingredient in both tincture of benzoin and Friar'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.[22]

Niche and laboratory uses

In teaching laboratories, benzoic acid is a common standard for calibrating a bomb calorimeter.[23]

Biology and health effects

Benzoic acid occurs naturally as do its esters in many plant and animal species. Appreciable amounts are found in most berries (around 0.05%). Ripe fruits of several Vaccinium species (e.g., cranberry, V. vitis macrocarpon; bilberry, V. myrtillus) 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.[24]

In terms of its biosynthesis, benzoate is produced in plants from cinnamic acid.[25] A pathway has been identified from phenol via 4-hydroxybenzoate.[26]

Reactions

Reactions of benzoic acid can occur at either the aromatic ring or at 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.

Carboxyl group

Reactions typical for carboxylic acids apply also to benzoic acid.[14]

Safety and mammalian metabolism

It is excreted as hippuric acid.[27] Benzoic acid is metabolized by butyrate-CoA ligase into an intermediate product, benzoyl-CoA,[28] which is then metabolized by glycine N-acyltransferase into hippuric acid.[29] Humans metabolize toluene which is also excreted as hippuric acid.[30]

For humans, the World Health Organization's International Programme on Chemical Safety (IPCS) suggests a provisional tolerable intake would be 5 mg/kg body weight per day.[31] 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.[32] The oral for rats is 3040 mg/kg, for mice it is 1940–2263 mg/kg.

In Taipei, Taiwan, a city health survey in 2010 found that 30% of dried and pickled food products had benzoic acid.[33]

External links

Notes and References

  1. Web site: Scientists uncover last steps for benzoic acid creation in plants . Purdue Agriculture News.
  2. Book: Neumüller O-A . 1988. Römpps Chemie-Lexikon. 6. Frankh'sche Verlagshandlung . Stuttgart. 978-3-440-04516-9 . 50969944 .
  3. Liebig J . Wöhler F. Untersuchungen über das Radikal der Benzoesäure. Annalen der Chemie. 1832. 3. 249–282. 10.1002/jlac.18320030302. 3. 2027/hvd.hxdg3f. Friedrich Wöhler. Justus von Liebig. free.
  4. Salkowski E. Berl Klin Wochenschr. 1875 . 12 . 297–298.
  5. Book: Wade. Leroy G.. Organic Chemistry. 2014. Pearson Education Limited. Harlow. 978-1-292-02165-2. 985. Pearson new international . OrgChem.
  6. Book: Purification of Laboratory Chemicals . registration . 3rd . D. D. Perrin . W. L. F. Armarego . Pergamon Press . 94 . 1988 . 978-0-08-034715-8.
  7. Book: Introduction to Organic Laboratory Techniques: A Small Scale Approach. Donald L. Pavia. 2004. Thomson Brooks/Cole. 978-0-534-40833-6. 312–314.
  8. Shirley. D. A.. 1954. The Synthesis of Ketones from Acid Halides and Organometallic Compounds of Magnesium, Zinc, and Cadmium. Org. React.. 8. 28–58.
  9. Book: Huryn, D. M.. 1991. Comprehensive Organic Synthesis, Volume 1: Additions to C - X π-Bonds, Part 1. 49–75. Carbanions of Alkali and Alkaline Earth Cations: (ii) Selectivity of Carbonyl Addition Reactions. Trost. B. M.. Fleming. I.. 978-0-08-052349-1. Barry Trost. Ian Fleming (chemist). Elsevier Science. 10.1016/B978-0-08-052349-1.00002-0.
  10. Web site: Portland Community College. The Grignard Reaction. Preparation of Benzoic Acid. 2015-03-12. dead. https://web.archive.org/web/20150226115836/http://spot.pcc.edu/~chandy/242/PreparationofBenzoicAcid.pdf. 26 February 2015. >
  11. Web site: University of Wisconsin-Madison. Experiment 9: Synthesis of Benzoic Acid via Carbonylation of a Grignard Reagent. 12 March 2015. https://web.archive.org/web/20150923202908/http://www.chem.wisc.edu/courses/342/Fall2004/Experiment_9.pdf. 23 September 2015. dead.
  12. Web site: Towson University. Experiment 3: Preparation of Benzoic Acid. 2015-03-12. dead. https://web.archive.org/web/20150413011353/http://pages.towson.edu/jdiscord/www/332_lab_info/332labsirpmr/expt3grignard.pdf . 13 April 2015 . dmy-all . >
  13. Santonastaso. Marco. Freakley. Simon J.. Miedziak. Peter J.. Brett. Gemma L.. Edwards. Jennifer K.. Hutchings. Graham J.. 2014-11-21. Oxidation of Benzyl Alcohol using in Situ Generated Hydrogen Peroxide. Organic Process Research & Development. 18. 11. 1455–1460. 10.1021/op500195e. 1083-6160.
  14. .
  15. A D Warth . Mechanism of action of benzoic acid on Zygosaccharomyces bailii: effects on glycolytic metabolite levels, energy production, and intracellular pH . Appl Environ Microbiol . 1 December 1991. 57. 3410–4 . 1785916 . 12 . 10.1128/AEM.57.12.3410-3414.1991 . 183988 . 1991ApEnM..57.3410W .
  16. Pastrorova I, de Koster CG, Boom JJ . Analytic Study of Free and Ester Bound Benzoic and Cinnamic Acids of Gum Benzoin Resins by GC-MS HPLC-frit FAB-MS . Phytochem Anal . 1997 . 8. 63–73 . 10.1002/(SICI)1099-1565(199703)8:2<63::AID-PCA337>3.0.CO;2-Y . 2 .
  17. http://www.codexalimentarius.net/gsfaonline/groups/details.html?id=162 GSFA Online Food Additive Group Details: Benzoates (2006)
  18. http://europa.eu.int/eur-lex/en/consleg/pdf/1995/en_1995L0002_do_001.pdf 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)
  19. Web site: Indications of the possible formation of benzene from benzoic acid in foods, BfR Expert Opinion No. 013/2006 . https://web.archive.org/web/20060426194742/http://www.bfr.bund.de/cm/245/indications_of_the_possible_formation_of_benzene_from_benzoic_acid_in_foods.pdf . 2006-04-26 . live . German Federal Institute for Risk Assessment . 1 December 2005 . 30 March 2022.
  20. Web site: Whitfield Ointment . 15 October 2007 . https://web.archive.org/web/20071009152212/http://www.medipharmalimited.com/whitfield_ointment.asp . 9 October 2007 . dead .
  21. Book: Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical . limited . Charles Owens Wilson . Ole Gisvold . John H. Block . 2004 . Lippincott Williams & Wilkins . 978-0-7817-3481-3 . 234.
  22. Troches of Benzoic Acid. Practical Druggist and Pharmaceutical Review of Reviews. Lillard. Benjamin. 1919.
  23. http://www.uwlax.edu/faculty/loh/pdf_files/chm313_pdf/Manual_current/chm313_Expt2_bomb.pdf Experiment 2: Using Bomb Calorimetry to Determine the Resonance Energy of Benzene
  24. Tomokuni K, Ogata M . Direct Colorimetric Determination of Hippuric Acid in Urine. Clin Chem . 1972 . 349–351. 18. 5012256. 4. 10.1093/clinchem/18.4.349. free.
  25. Molecular Plant. 3. 2010. 2–20. 10.1093/mp/ssp106. 20035037. Phenylpropanoid Biosynthesis. Vogt, T.. free.
  26. Pierre. Juteau. Valérie Côté. Marie-France Duckett. Réjean Beaudet. François Lépine. Richard Villemur. Jean-Guy Bisaillon. Cryptanaerobacter phenolicus gen. nov., sp. nov., an anaerobe that transforms phenol into benzoate via 4-hydroxybenzoate. International Journal of Systematic and Evolutionary Microbiology. 55. 1. 245–250. January 2005. 10.1099/ijs.0.02914-0. 15653882. free.
  27. Cosmetic Ingredient Review Expert Panel Bindu Nair . Final Report on the Safety Assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. Int J Tox . 2001 . 20 . Suppl. 3 . 23–50 . 10.1080/10915810152630729 . 11766131. 13639993.
  28. Web site: butyrate-CoA ligase. BRENDA. Technische Universität Braunschweig.. 7 May 2014. Substrate/Product
  29. Web site: glycine N-acyltransferase. BRENDA. Technische Universität Braunschweig.. 7 May 2014. Substrate/Product
  30. Krebs HA, Wiggins D, Stubbs M . Studies on the mechanism of the antifungal action of benzoate . Biochem J . 1983 . 214 . 657–663. 6226283 . 3 . 1152300 . 10.1042/bj2140657 .
  31. Web site: Concise International Chemical Assessment Document 26: BENZOIC ACID AND SODIUM BENZOATE.
  32. 10.1136/vr.90.3.53. Bedford PG, Clarke EG . Experimental benzoic acid poisoning in the cat. Vet Rec . 1972. 53–58. 90 . 4672555. 3. 2553612 .
  33. News: Jian. Chen. Y.L. Kao. Nearly 30% dried, pickled foods fail safety inspections. The China Post. 18 January 2010.