Benzoic acid 4106 224676196 2008-07-09T22:40:34Z 207.233.32.18 /* Carboxyl group */ {{chembox new | ImageFile = Benzoic acid.svg | ImageSize = | ImageFile1 = Benzoic-acid-3D-vdW.png | IUPACName = Benzoic acid,<br />benzene carboxylic acid | OtherNames = Carboxybenzene,<br/>[[E210]], dracylic acid | Section1 = {{Chembox Identifiers | Abbreviations = | CASNo = 65-85-0 | EINECS = | PubChem = 243 | SMILES = c1ccccc1C(=O)O | InChI = 1/C7H6O2/c8-7(9)6-4-2-1-3-5-6/h1-5H,(H,8,9)/f/h8H | RTECS = DG0875000 | MeSHName = benzoic Acid | ChEBI = 30746 | KEGG = C00180 | 3DMet = B00053 | Beilstein = 636131 | Gmelin = 2946 | ATCCode_prefix = | ATCCode_suffix = | ATC_Supplemental =}} | Section2 = {{Chembox Properties | Formula = C<sub>6</sub>H<sub>5</sub>COOH | MolarMass = 122.12 g/mol | Appearance = Colourless crystalline solid | Density = 1.32 g/cm<sup>3</sup>, solid | MeltingPt = 122.4 °C (395 K) | Melting_notes = | BoilingPt = 249 &nbsp;°C (522 K) | Boiling_notes = | Solubility = Soluble (hot water)<br/>3.4 g/l (25&nbsp;°C) | SolubleOther = Soluble | Solvent = methanol, diethylether | pKa = 4.21 | pKb = | IsoelectricPt = | LambdaMax = | Absorbance = | SpecRotation = | RefractIndex = | Viscosity = | Dipole = }} | Section3 = {{Chembox Structure | CrystalStruct = [[Monoclinic]] | Coordination = | MolShape = [[planar]] | Dipole = 1.72 [[Debye|D]] in [[Dioxane]]}} | Section4 = {{Chembox Thermochemistry | DeltaHf = | DeltaHc = | Entropy = | HeatCapacity = }} | Section5 = {{Chembox Pharmacology | AdminRoutes = | Bioavail = | Metabolism = | HalfLife = | ProteinBound = | Excretion = | Legal_status = | Legal_US = | Legal_UK = | Legal_AU = | Legal_CA = | PregCat = | PregCat_AU = | PregCat_US = }} | Section6 = {{Chembox Explosive | ShockSens = | FrictionSens = | ExplosiveV = | REFactor = }} | Section7 = {{Chembox Hazards | ExternalMSDS = [http://sciencelab.com/msds.php?msdsId=9927096 ScienceLab.com] | EUClass = | EUIndex = | MainHazards = Irritating | NFPA-H = 2 | NFPA-F = 1 | NFPA-R = 0 | NFPA-O = &nbsp; | RPhrases = {{R22}}, {{R36}} | SPhrases = {{S24}} | RSPhrases = | FlashPt = 121 °C (394 K) | Autoignition = | ExploLimits = | PEL = }} | Section8 = {{Chembox Related | OtherAnions = | OtherCations = | OtherFunctn = [[phenylacetic acid]],<br/>[[hippuric acid]],<br/>[[salicylic acid]] | Function = carboxylic acid | OtherCpds = [[benzene]],<br/>[[benzaldehyde]],<br/>[[benzyl alcohol]],<br/>[[benzylamine]],<br/>[[benzyl benzoate]],<br/>[[benzoyl chloride]]}} }} '''Benzoic acid''', C<sub>7</sub>H<sub>6</sub>O<sub>2</sub> (or C<sub>6</sub>H<sub>5</sub>COOH), 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]]).<ref>{{cite book | author= Neumüller O-A | year = 1988| title = Römpps Chemie-Lexikon| edition = 6| publisher = Frankh'sche Verlagshandlung | location = Stuttgart| id = ISBN 3-440-04516-1 }}</ref> [[Justus von Liebig]] and [[Friedrich Wöhler]] determined the structure of benzoic acid in [[1832]].<ref>{{cite journal | author= [[Justus von Liebig|Liebig J]], [[Friedrich Wöhler|Wöhler F]] | title=Untersuchungen über das Radikal der Benzoesäure | journal = [[Liebigs Annalen|Annalen der Chemie]] | year = 1832 | volume = 3 | pages = 249–282 | doi = 10.1002/jlac.18320030302}}</ref> 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 [[Cloudberry|fruits]].<ref>{{cite journal | author= Salkowski E| title= | journal=Berl Klin Wochenschr| year=1875 | volume=12 | pages=297–298}}</ref> == Production == === Industrial preparations === Benzoic acid is produced commercially by partial oxidation of [[toluene]] with [[oxygen]]. The process is catalyzed by [[cobalt]] or [[manganese]] [[naphthenate]]s. The process uses cheap raw materials, proceeds in high yield, and is considered environmentally green. [[Image:Benzoic acid-chemical-synthesis-1.png|220px|toluene oxidation]] U.S. production capacity is estimated to be 126,000 [[tonne]]s 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. 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.<ref>{{cite book | title = Purification of Laboratory Chemicals | edition = 3rd Edition | author = D. D. Perrin; W. L. F. Armarego | publisher = Pergamon Press | pages = 94 | year = 1988 | isbn = 0-08-034715-0}}</ref> ==== 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|400px]] ==== From bromobenzene ==== [[Bromobenzene]] in diethyl ether is stirred with magnesium [[swarf|turnings]] to produce [[phenylmagnesium bromide]] (C<sub>6</sub>H<sub>5</sub>MgBr). This [[Grignard reagent]] is slowly added to [[dry ice]] to give benzoate. Dilute acid is added to form benzoic acid.<ref>{{cite book | title = Introduction to Organic Laboratory Techniques: A Small Scale Approach | author = Donald L. Pavia | year = 2004 | publisher = Thomson Brooks/Cole | isbn = 0534408338 | pages = 312-314}}</ref> [[Image:Benzoic acid synthesis.png|400px]] ==== 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(III) chloride|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.<ref>{{cite web |url=http://www.columbian.com/lifeHome/whatsinmy/10102006news66192.cfm |title=What's in my... |accessdate=2007-09-08 |last=Killinger-Mann |first=Karen |coauthors= |date=2007-09-07 |work= |publisher=The Columbian}}</ref> [[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]], [[sodium benzoate|E211]], [[potassium benzoate|E212]], and [[calcium benzoate|E213]]. Benzoic acid inhibits the growth of [[mold]], [[yeast]]<ref>{{cite journal | author=A D Warth | title= Mechanism of action of benzoic acid on Zygosaccharomyces bailii: effects on glycolytic metabolite levels, energy production, and intracellular pH. | journal=Appl Environ Microbiol. 1991 December | year=1991 | url=http://aem.asm.org/cgi/content/abstract/57/12/3410 | volume=1|pages=1 | pmid= 1785916 }}</ref> and some [[bacterium|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 [[Fermentation (biochemistry)|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.<ref>{{cite journal | author=Pastrorova I, de Koster CG, Boom JJ | title= Analytic Study of Free and Ester Bound Benzoic and Cinnamic Acids of Gum Benzoin Resins by GC-MS HPLC-frit FAB-MS | journal=Phytochem Anal | year=1997 | volume=8|pages=63–73 |doi= 10.1002/(SICI)1099-1565(199703)8:2<63::AID-PCA337>3.0.CO;2-Y }}</ref> Acidic food and beverage like [[fruit juice]] ([[citric acid]]), sparkling drinks ([[carbon dioxide]]), [[soft drinks]] ([[phosphoric acid]]), [[Pickling|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.<ref>[http://www.codexalimentarius.net/gsfaonline/groups/details.html?id=162 GSFA Online Food Additive Group Details: Benzoates (2006)]</ref><ref>[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)]</ref> 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]].<ref>{{cite news|last= Goldstein| first=David|url=http://www.ewg.org/news/story.php?id=5134| date=[[2006-03-03]]| title=FDA finds benzene in soft drinks| publisher=[[Knight Ridder]]}}</ref><ref>http://www.bfr.bund.de/cm/245/indications_of_the_possible_formation_of_benzene_from_benzoic_acid_in_foods.pdf BfR article</ref> {{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]], C<sub>6</sub>H<sub>5</sub>C(O)Cl, is obtained by treatment of benzoic with [[thionyl chloride]], [[phosgene]] or one of the [[phosphorus chlorides|chlorides of phosphorus]]. C<sub>6</sub>H<sub>5</sub>C(O)Cl is an important starting material for several benzoic acid derivates like [[benzyl benzoate]], which is used as [[Flavouring|artificial flavours]] and [[insect repellent]]s. * Benzoate [[plasticizer]]s, 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]], C<sub>6</sub>H<sub>5</sub>OH, 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|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's Ointment]] which is used for the treatment of fungal skin diseases such as tinea, [[ringworm]], and [[athlete's foot]]. <ref>[http://www.medipharmalimited.com/whitfield_ointment.asp Whitfield Ointment<!-- Bot generated title -->]</ref> <ref>{{cite book | title = Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical | author = Charles Owens Wilson; Ole Gisvold; John H. Block | year = 2004 | publisher = Lippincott Williams & Wilkins | isbn = 0781734819 | pages = 234}}</ref> == 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]]'').<ref name="concise">[http://www.inchem.org/documents/cicads/cicads/cicad26.htm Concise International Chemical Assessment Document 26: BENZOIC ACID AND SODIUM BENZOATE]</ref> [[Gum benzoin]] contains up to 20% of benzoic acid and 40% benzoic acid esters.<ref>{{cite journal| author= Tomokuni K, Ogata M| title=Direct Colorimetric Determination of Hippuric Acid in Urine| journal=Clin Chem | year=1972 | pages=349–351| volume=18}}</ref> 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.<ref>{{cite journal | author=Krebs HA, Wiggins D, Stubbs M | title= Studies on the mechanism of the antifungal action of benzoate | journal= Biochem J | year=1983 | volume=214 | pages=657–663| url = http://www.biochemj.org/bj/214/0657/2140657.pdf }}</ref> 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.<ref name="concise">[http://www.inchem.org/documents/cicads/cicads/cicad26.htm Concise International Chemical Assessment Document 26: BENZOIC ACID AND SODIUM BENZOATE]</ref> [[Cats]] have a significantly lower tolerance against benzoic acid and its [[salts]] than [[rats]] and [[mouse|mice]]. Lethal dose for cats can be as low as 300 mg/kg body weight.<ref>{{cite journal| author= Bedford PG, Clarke EG |title=Experimental benzoic acid poisoning in the cat|journal=Vet Rec |year=1972|pages=53–58|volume=90 |pmid = 4672555}}</ref> The oral [[LD50|LD<font size="-1"><sub>50</sub></font>]] for rats is 3040 mg/kg, for mice it is 1940-2263 mg/kg.<ref name="concise" /> == Chemistry == Reactions of benzoic acid can occur at either the [[aromaticity|aromatic ring]] or the [[carboxyl group]]: === Aromatic ring === [[Image:Benzoic acid-chemical-reaction-1.png|440px|benzoic acid aromatic ring reactions]] [[Electrophilic aromatic substitution]] reaction will take place mainly in 3-position to the [[deactivating group|electron-withdrawing]] [[carboxylic group]], i.e. benzoic acid is [[Electrophilic aromatic substitution#Meta directors|''meta'' directing]]. The second substitution reaction (on the right) is slower because the first nitro group is deactivating.<ref>{{OrgSynth | author=Brewster, R. Q.; Williams, B.; Phillips, R. |title=3,5-Dinitrobenzoic Acid| | collvol = 3 | collvolpages = 337 | year= 1955 | prep = cv3p0337}}</ref> 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. === Carboxyl group === All the reactions mentioned for [[carboxylic acid]]s 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 [[Dicyclohexylcarbodiimide|DCC]] and [[DMAP]]. * The more active benzoic [[acid anhydride|anhydride]] is formed by dehydration using [[acetic anhydride]] or [[phosphorus pentoxide]]. * Highly reactive acid derivatives such as [[Acyl halide|acid halides]] are easily obtained by mixing with [[halogenation]] agents like [[phosphorus chlorides]] or [[thionyl chloride]]. * [[Orthoester]]s 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]], [[lithium aluminium hydride|LiAlH<sub>4</sub>]] or [[sodium borohydride]]. * The copper catalysed [[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. [[Image:Benzoic acid-chemical-reaction-2.png|490px|benzoic acid group reactions]] == References == {{Reflist}} == Further reading == * {{cite journal | author= Cosmetic Ingredient Review Expert Panel Bindu Nair | title= Final Report on the Safety Assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate| journal=Int J Tox | year=2001 | volume= 20 | issue=Suppl. 3 | pages=23–50 | doi= 10.1080/10915810152630729}} == External links == * [http://www.ilo.org/public/english/protection/safework/cis/products/icsc/dtasht/_icsc01/icsc0103.htm International Chemical Safety Card 0103] * [http://www.chemicalland21.com/arokorhi/industrialchem/organic/BENZOIC%20ACID.htm ChemicalLand] [[Category:Organic acids]] [[Category:Benzoic acids|Benzoic acids]] [[Category:Aromatic compounds]] [[ar:حمض بنزويك]] [[bg:Бензоена киселина]] [[cs:Kyselina benzoová]] [[da:Benzoesyre]] [[de:Benzoesäure]] [[et:Bensoehape]] [[es:Ácido benzoico]] [[fr:Acide benzoïque]] [[ga:Aigéad beansóch]] [[ko:벤조산]] [[id:Asam benzoat]] [[it:Acido benzoico]] [[lv:Benzoskābe]] [[hu:Benzoesav]] [[nl:Benzoëzuur]] [[ja:安息香酸]] [[no:Benzosyre]] [[pl:Kwas benzoesowy]] [[pt:Ácido benzóico]] [[ro:Acid benzoic]] [[ru:Бензойная кислота]] [[sk:Kyselina benzoová]] [[fi:Bentsoehappo]] [[sv:Bensoesyra]] [[vi:Axít benzoic]] [[zh:苯甲酸]]