Benzene is an organic chemical compound with the Benzene · Benzene is an organic chemical compound...

Benzene

benzene

cyclohexa-1,3,5-triene

1,3,5-cyclohexatriene

benzol

phene

Identifiers

CAS number 71-43-2

PubChem 241

ChemSpider 236

UNII J64922108F

EC number 200-753-7

KEGG C01407

From Wikipedia, the free encyclopediaSee also: Benzole

Benzene is an organic chemical compound with themolecular formula C6H6. Its molecule is composed of 6carbon atoms joined in a ring, with 1 hydrogen atomattached to each carbon atom. Because its molecules containonly carbon and hydrogen atoms, benzene is classed as ahydrocarbon.

Benzene is a natural constituent of crude oil, and is one ofthe most elementary petrochemicals. Benzene is an aromatichydrocarbon and the second [n]-annulene ([6]-annulene), acyclic hydrocarbon with a continuous pi bond. It issometimes abbreviated Ph–H. Benzene is a colorless andhighly flammable liquid with a sweet smell. It is mainly usedas a precursor to heavy chemicals, such as ethylbenzene andcumene, which are produced on a billion kilogram scale.Because it has a high octane number, it is an importantcomponent of gasoline, composing a few percent of its mass.Most non-industrial applications have been limited bybenzene's carcinogenicity.

1 History1.1 Discovery1.2 Ring formula1.3 Early applications

2 Structure3 Benzene derivatives4 Production

4.1 Catalytic reforming4.2 Toluene hydrodealkylation4.3 Toluene disproportionation4.4 Steam cracking4.5 Other sources

5 Uses5.1 Component of gasoline

6 Reactions6.1 Sulfonation, chlorination, nitration6.2 Hydrogenation6.3 Metal complexes

7 Health effects8 Exposure to benzene

8.1 Inhalation8.2 Exposure through smoking

IUPAC name

Systematic name

Other names

Benzene - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Benzene#Production

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tighe

Text Box

captured 8/27/13

ChEBI CHEBI:16716

ChEMBL CHEMBL277500

RTECS number CY1400000

Jmol-3D images Image 1

(http://chemapps.stolaf.edu

/jmol/jmol.php?model=c1ccccc1)

Properties

Molecular formula C6H6

Molar mass 78.11 g mol−1

Appearance Colorless liquid

Odor aromatic, gasoline-like

Density 0.8765(20) g/cm3[1]

Melting point5.5 °C, 278.7 K, 41.9 °F

Boiling point80.1 °C, 353.3 K, 176.18 °F

Solubility in water 1.79 g/L (15 °C)[2][3][4]

Solubility soluble in alcohol, chloroform,

CCl4, diethyl ether, acetone

log P 2.13

Vapor pressure 10 kPa

λmax 255 nm

Magnetic

susceptibility

54.8 x 10−6 cm3/mol

Refractive index (nD) 1.50108

Viscosity 0.652 cP at 20 °C

Dipole moment 0 D

Thermochemistry

Std enthalpy of

formation ΔfHo

298

82.93 kJ/mol

Standard molar

entropy So298

173.26 J/K mol

Specific heat

capacity, C

136.0 J/K mol

Hazards

MSDS External MSDS

EU classification Flammable (F)

Carc. Cat. 1

8.3 Exposure from soft drinks8.4 Case examples8.5 Benzene exposure limits8.6 Exposure monitoring8.7 Biomarkers of exposure8.8 Biotransformations8.9 Molecular toxicology8.10 Biological oxidation and carcinogenicactivity8.11 Summary

9 See also10 References11 External links

Discovery

The word "benzene" derives historically from "gumbenzoin", sometimes called "benjamin" (i.e., benzoin resin),an aromatic resin known to European pharmacists andperfumers since the 15th century as a product of southeast

Asia.[5] An acidic material was derived from benzoin bysublimation, and named "flowers of benzoin", or benzoicacid. The hydrocarbon derived from benzoic acid thus

acquired the name benzin, benzol, or benzene.[6]

Michael Faraday first isolated and identified benzene in 1825from the oily residue derived from the production ofilluminating gas, giving it the name bicarburet of hydrogen.[7][8]

In 1833, Eilhard Mitscherlich produced it via the distillationof benzoic acid (from gum benzoin) and lime. He gave the

compound the name benzin.[9]

In 1836, the French chemist Auguste Laurent named the

substance "phène";[10] this is the root of the word phenol,which is hydroxylated benzene, and phenyl, which is theradical formed by abstraction of a hydrogen atom (freeradical H•) from benzene.

In 1845, Charles Mansfield, working under August Wilhelm

von Hofmann, isolated benzene from coal tar.[12] Four yearslater, Mansfield began the first industrial-scale production of

benzene, based on the coal-tar method.[13][14] Gradually thesense developed among chemists that substances related tobenzene represent a diverse chemical family. In 1855 August

SMILES

InChI


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Muta. Cat. 2

Toxic (T)

R-phrases R45, R46, R11, R16,

R36/38,R48/23/24/25, R65

S-phrases S53, S45

NFPA 704

Flash point −11.63 °C, 262 K

Autoignition

temperature

497.78 °C (770.93 K)

Explosive limits 1.2–7.8%

LD50 930 mg/kg (rat, oral)

Related compounds

Related compounds toluene

borazine

Supplementary data page

Structure and

properties

n, εr, etc.

Thermodynamic

data

Phase behaviour

Solid, liquid, gas

Spectral data UV, IR, NMR, MS

(verify) (what is: / ?)

Except where noted otherwise, data are given for

materials in their standard state (at 25 °C, 100 kPa)

Infobox references

Historic benzene formulae as proposed by

Kekulé.[11]

Historic benzene formulae (from left to right) by Claus (1867),[21] Dewar (1867),[22] Ladenburg

(1869),[23] Armstrong (1887),[24] Thiele (1899)[25] and Kekulé (1865). Dewar benzene and prismane are

different chemicals that have Dewar's and Ladenburg's structures. Thiele and Kekulé's structures are used

today.

WilhelmHofmannused theword

"aromatic" to designate this family relationship, after a

characteristic property of many of its members.[15]

Ring formula

The empirical formula for benzene was long known, but itshighly polyunsaturated structure, with just one hydrogenatom for each carbon atom, was challenging to determine.Archibald Scott Couper in 1858 and Joseph Loschmidt in

1861[16] suggested possible structures that containedmultiple double bonds or multiple rings, but too littleevidence was then available to help chemists decide on anyparticular structure.

In 1865, the German chemist Friedrich August Kekulépublished a paper in French (for he was then teaching inFrancophone Belgium) suggesting that the structurecontained a six-membered ring of carbon atoms withalternating single and double bonds. The next year hepublished a much longer paper in German on the same

subject.[17][18] Kekulé used evidence that had accumulatedin the intervening years—namely, that there always appearedto be only one isomer of any monoderivative of benzene,and that there always appeared to be exactly three isomers of every derivative—now understood to correspond

to the ortho, meta, and para patterns of arene substitution—to argue in support of his proposed structure.[19]

Kekulé's symmetrical ring could explain these curious facts, as well as benzene's 1:1 carbon-hydrogen ratio.[20]

The new

understanding of benzene, and hence of all aromatic compounds, proved to be so important for both pure andapplied chemistry that in 1890 the German Chemical Society organized an elaborate appreciation in Kekulé's


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Frozen benzene

honor, celebrating the twenty-fifth anniversary of his first benzene paper. Here Kekulé spoke of the creation ofthe theory. He said that he had discovered the ring shape of the benzene molecule after having a reverie orday-dream of a snake seizing its own tail (this is a common symbol in many ancient cultures known as the

Ouroboros or Endless knot).[26] This vision, he said, came to him after years of studying the nature of carbon-carbon bonds. This was 7 years after he had solved the problem of how carbon atoms could bond to up to fourother atoms at the same time. It is curious that a similar, humorous depiction of benzene had appeared in 1886 inthe Berichte der Durstigen Chemischen Gesellschaft (Journal of the Thirsty Chemical Society), a parody of theBerichte der Deutschen Chemischen Gesellschaft, only the parody had monkeys seizing each other in a circle,

rather than snakes as in Kekulé's anecdote.[27] Some historians have suggested that the parody was a lampoonof the snake anecdote, possibly already well known through oral transmission even if it had not yet appeared in

print.[6] (Some others have speculated that Kekulé's story in 1890 was a re-parody of the monkey spoof, and

was a mere invention rather than a recollection of an event in his life.[citation needed]) Kekulé's 1890 speech[28]

in which these anecdotes appeared has been translated into English.[29] If the anecdote is the memory of a real

event, circumstances mentioned in the story suggest that it must have happened early in 1862.[30]

The cyclic nature of benzene was finally confirmed by the crystallographer Kathleen Lonsdale in 1929.[31][32]

Early applications

In the 19th and early-20th centuries, benzene was used as an after-shave lotion because of its pleasant smell.Prior to the 1920s, benzene was frequently used as an industrial solvent, especially for degreasing metal. As itstoxicity became obvious, benzene was supplanted by other solvents, especially toluene (methyl benzene), whichhas similar physical properties but is not as carcinogenic.

In 1903, Ludwig Roselius popularized the use of benzene to decaffeinatecoffee. This discovery led to the production of Sanka. This process waslater discontinued. Benzene was historically used as a significantcomponent in many consumer products such as Liquid Wrench, severalpaint strippers, rubber cements, spot removers and other hydrocarbon-containing products. Some ceased manufacture of their benzene-containing formulations in about 1950, while others continued to usebenzene as a component or significant contaminant until the late 1970swhen leukemia deaths were found associated with Goodyear's Pliofilmproduction operations in Ohio. Until the late 1970s, many hardwarestores, paint stores, and other retail outlets sold benzene in small cans,such as quart size, for general-purpose use. Many students were exposedto benzene in school and university courses while performing laboratory experiments with little or no ventilationin many cases. This very dangerous practice has been almost totally eliminated.

Main article: Aromaticity

Benzene represents a special problem in that, to account for the bond lengths quantitatively, there must either be

electron delocalization (MO theory) or a spin coupling of the p-orbitals (VB theory):[33]

X-ray diffraction shows that all six carbon-carbon bonds in benzene are of the same length, at 140 picometres(pm). The C–C bond lengths are greater than a double bond, (135 pm), but shorter than a single bond, (147 pm).


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The various representations of benzene

This intermediate distance is consistent with electron delocalization: theelectrons for C–C bonding are distributed equally between each of thesix carbon atoms. Benzene has 8 hydrogen atoms fewer than the

corresponding parent alkane, hexane. The molecule is planar.[34] TheMO description involves the formation of three delocalized π orbitalsspanning all six carbon atoms, while in VB theory the aromaticproperties of benzene originate from spin coupling of all six π orbitals.[35][36][37][38] It is likely that this stability contributes to the peculiarmolecular and chemical properties known as aromaticity. To indicate the

delocalized nature of the bonding, benzene is often depicted with a circle inside a hexagonal arrangement ofcarbon atoms.

As is common in organic chemistry, the carbon atoms in the diagram above have been left unlabeled. Realizingeach carbon has 2p electrons, each carbon donates an electron into the delocalized ring above and below thebenzene ring. It is the side-on overlap of p-orbitals that produces the pi clouds.

Derivatives of benzene occur sufficiently often as a component of organic molecules that there is a Unicodesymbol in the Miscellaneous Technical block with the code U+232C (⌬) to represent it with three double

bonds,[39] and U+23E3 ( ) for a delocalized version.[40]

Main articles: Aromatic hydrocarbons and Alkylbenzenes

Many important chemical compounds are derived from benzene by replacing one or more of its hydrogen atomswith another functional group. Examples of simple benzene derivatives are phenol, toluene, and aniline,abbreviated PhOH, PhMe, and PhNH2, respectively. Linking benzene rings gives biphenyl, C6H5–C6H5. Furtherloss of hydrogen gives "fused" aromatic hydrocarbons, such as naphthalene and anthracene. The limit of thefusion process is the hydrogen-free allotrope of carbon, graphite.

In heterocycles, carbon atoms in the benzene ring are replaced with other elements. The most importantderivatives are the rings containing nitrogen. Replacing one CH with N gives the compound pyridine, C5H5N.Although benzene and pyridine are structurally related, benzene cannot be converted into pyridine.Replacement of a second CH bond with N gives, depending on the location of the second N, pyridazine,pyrimidine, and pyrazine.

Four chemical processes contribute to industrial benzene production: catalytic reforming, toluenehydrodealkylation, toluene disproportionation, and steam cracking. According to the ATSDR ToxicologicalProfile for benzene, between 1978 and 1981, catalytic reformats accounted for approximately 44–50% of thetotal U.S benzene production.

Until World War II, most benzene was produced as a by-product of coke production (or "coke-oven light oil") inthe steel industry. However, in the 1950s, increased demand for benzene, especially from the growing polymersindustry, necessitated the production of benzene from petroleum. Today, most benzene comes from thepetrochemical industry, with only a small fraction being produced from coal.

Catalytic reforming


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In catalytic reforming, a mixture of hydrocarbons with boiling points between 60–200 °C is blended withhydrogen gas and then exposed to a bifunctional platinum chloride or rhenium chloride catalyst at 500–525 °Cand pressures ranging from 8–50 atm. Under these conditions, aliphatic hydrocarbons form rings and losehydrogen to become aromatic hydrocarbons. The aromatic products of the reaction are then separated from thereaction mixture (or reformate) by extraction with any one of a number of solvents, including diethylene glycolor sulfolane, and benzene is then separated from the other aromatics by distillation. The extraction step ofaromatics from the reformate is designed to produce aromatics with lowest non-aromatic components. Recoveryof the aromatics, commonly referred to as BTX (benzene, toluene and xylene isomers), involves such extractionand distillation steps. There are a good many licensed processes available for extraction of the aromatics.

In similar fashion to this catalytic reforming, UOP and BP commercialized a method from LPG (mainly propaneand butane) to aromatics.

Toluene hydrodealkylation

Toluene hydrodealkylation converts toluene to benzene. In this hydrogen-intensive process, toluene is mixedwith hydrogen, then passed over a chromium, molybdenum, or platinum oxide catalyst at 500–600 °C and40–60 atm pressure. Sometimes, higher temperatures are used instead of a catalyst (at the similar reactioncondition). Under these conditions, toluene undergoes dealkylation to benzene and methane:

C6H5CH3 + H2 → C6H6 + CH4

This irreversible reaction is accompanied by an equilibrium side reaction that produces biphenyl (aka diphenyl)at higher temperature:

2 C6H6 H2 + C6H5–C6H5

If the raw material stream contains much non-aromatic components (paraffins or naphthenes), those are likelydecomposed to lower hydrocarbons such as methane, which increases the consumption of hydrogen.

A typical reaction yield exceeds 95%. Sometimes, xylenes and heavier aromatics are used in place of toluene,with similar efficiency.

This is often called "on-purpose" methodology to produce benzene, compared to conventional BTX (benzene-toluene-xylene) extraction processes.

Toluene disproportionation

Where a chemical complex has similar demands for both benzene and xylene, then toluene disproportionation(TDP) may be an attractive alternative to the toluene hydrodealkylation. In the broad sense, 2 toluenemolecules are reacted and the methyl groups rearranged from one toluene molecule to the other, yielding onebenzene molecule and one xylene molecule.

Given that demand for para-xylene (p-xylene) substantially exceeds demand for other xylene isomers, arefinement of the TDP process called Selective TDP (STDP) may be used. In this process, the xylene streamexiting the TDP unit is approximately 90% paraxylene. In some current catalytic systems, even the benzene-to-xylenes ratio is decreased (more xylenes) when the demand of xylenes is higher.

Steam cracking


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Steam cracking is the process for producing ethylene and other alkenes from aliphatic hydrocarbons. Dependingon the feedstock used to produce the olefins, steam cracking can produce a benzene-rich liquid by-productcalled pyrolysis gasoline. Pyrolysis gasoline can be blended with other hydrocarbons as a gasoline additive, orrouted through an extraction process to recover BTX aromatics (benzene, toluene and xylenes).

Other sources

Trace amounts of benzene may result whenever carbon-rich materials undergo incomplete combustion. It isproduced in volcanoes and forest fires, and is also a component of cigarette smoke. Benzene is a principalproduct from the combustion of PVC (polyvinyl chloride).

Benzene is used mainly as an intermediate to make other chemicals. About 80% of benzene is consumed in theproduction of three chemicals, ethylbenzene, cumene, and cyclohexane. Its most widely produced derivative isethylbenzene, precursor to styrene, which is used to make polymers and plastics. Cumene is converted phenolfor resins and adhesives. Cyclohexane is used in the manufacture of Nylon. Smaller amounts of benzene areused to make some types of rubbers, lubricants, dyes, detergents, drugs, explosives, and pesticides.

In both the US and Europe, 50% of benzene is used in the production of ethylbenzene/styrene, 20% is used inthe production of cumene, and about 15% of benzene is used in the production of cyclohexane (eventually to

nylon).[citation needed]

Currently, the production of and demand for benzene in the Middle East register the greatest increasesworldwide. It will probably see its share of the global supply and demand expand by 3.7 and 3.3 percentagepoints, respectively, until 2018. However, the Asia-Pacific region will continue to dominate the market and

account for almost half of the global demand.[41]

In laboratory research, toluene is now often used as a substitute for benzene. The solvent-properties of the twoare similar, but toluene is less toxic and has a wider liquid range.


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Major commodity chemicals and polymers derived from benzene. Clicking on the image loads the

appropriate article

Component of gasoline

As a gasoline (petrol) additive, benzene increases the octane rating and reduces knocking. As a consequence,gasoline often contained several percent benzene before the 1950s, when tetraethyl lead replaced it as the mostwidely used antiknock additive. With the global phaseout of leaded gasoline, benzene has made a comeback as agasoline additive in some nations. In the United States, concern over its negative health effects and thepossibility of benzene's entering the groundwater have led to stringent regulation of gasoline's benzene content,

with limits typically around 1%.[42] European petrol specifications now contain the same 1% limit on benzenecontent. The United States Environmental Protection Agency introduced new regulations in 2011 that lowered

the benzene content in gasoline to 0.62%.[43]

The most common reactions of benzene involve substitution of a proton by other groups.[44] Electrophilicaromatic substitution is a general method of derivatizing benzene. Benzene is sufficiently nucleophilic that itundergoes substitution by acylium ions and alkyl carbocations to give substituted derivatives.

Electrophilic aromatic substitution of benzene

The most widely practiced example of this reaction is the ethylation of benzene.


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Approximately 24,700,000 tons were produced in 1999.[45] Highly instructive but of far less industrialsignificance is the Friedel-Crafts alkylation of benzene (and many other aromatic rings) using an alkyl halide inthe presence of a strong Lewis acid catalyst. Similarly, the Friedel-Crafts acylation is a related example ofelectrophilic aromatic substitution. The reaction involves the acylation of benzene (or many other aromaticrings) with an acyl chloride using a strong Lewis acid catalyst such as aluminium chloride or Iron(III) chloride.

Friedel-Crafts acylation of benzene by acetyl chloride

Sulfonation, chlorination, nitration

Using electrophilic aromatic substitution, many functional groups are introduced onto the benzene framework.Sulfonation of benzene involves the use of oleum, a mixture of sulfuric acid with sulfur trioxide. Sulfonated

benzene derivatives are useful detergents. In nitration, benzene reacts with nitronium ions (NO2+), which is a

strong electrophile produced by combining sulfuric and nitric acids. Nitrobenzene is the precursor to aniline.Chlorination in achieved with chlorine to give chlorobenzene in the presence of a catalyst such as aluminiumtrichloride.

Hydrogenation

Via hydrogenation, benzene and its derivatives convert to cyclohexane and derivatives. This reaction is achievedby the use of high pressures of hydrogen at high temperatures in the presence of a finely divided nickel, whichserves as a catalyst. In the absence of the catalyst, benzene is impervious to hydrogen. This reaction is practicedon a very large scale industrially.

Metal complexes

Benzene is an excellent ligand in the organometallic chemistry of low-valent metals. Important examples includethe sandwich and half-sandwich complexes, respectively, Cr(C6H6)2 and [RuCl2(C6H6)]2.

Benzene increases the risk of cancer and other illnesses. Benzene is a notorious cause of bone marrow failure.Substantial quantities of epidemiologic, clinical, and laboratory data link benzene to aplastic anemia, acute

leukemia, and bone marrow abnormalities.[46][47] The specific hematologic malignancies that benzene isassociated with include: acute myeloid leukemia (AML), aplastic anemia, myleodysplastic syndrome (MDS),

acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML).[48]

The American Petroleum Institute (API) stated in 1948 that "it is generally considered that the only absolutely

safe concentration for benzene is zero."[49] The US Department of Health and Human Services (DHHS)


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A bottle of benzene. The warnings

show benzene is a toxic and flammable

liquid.

Light refraction of benzene (above)

and water (below)

classifies benzene as a human carcinogen. Long-term exposure toexcessive levels of benzene in the air causes leukemia, a potentially fatalcancer of the blood-forming organs, in susceptible individuals. Inparticular, Acute myeloid leukemia or acute nonlymphocytic leukemia

(AML & ANLL) is not disputed to be caused by benzene.[50] IARCrated benzene as "known to be carcinogenic to humans" (Group 1).

Human exposure to benzene is a global health problem. Benzene targetsliver, kidney, lung, heart and the brain and can cause DNA strand breaks,chromosomal damage, etc. Benzene causes cancer in animals includinghumans. Benzene has been shown to cause cancer in both sexes of

multiple species of laboratory animals exposed via various routes.[51][52]

Some women who inhaled high levels of benzene for many months hadirregular menstrual periods and a decrease in the size of their ovaries.Benzene exposure has been linked directly to the neural birth defects

spina bifida and anencephaly.[53] Men exposed to high levels of benzeneare more likely to have an abnormal amount of chromosomes in their

sperm, which impacts fertility and fetal development.[54]

See also : Benzene in soft drinks#Environmental exposure tobenzene

Vapors from products that contain benzene, such as glues, paints,furniture wax, and detergents, can also be a source of exposure, althoughmany of these have been modified or reformulated since the late 1970sto eliminate or reduce the benzene content. Air around hazardous wastesites or gas stations may contain higher levels of benzene. Becausepetroleum hydrocarbon products are complex mixtures of chemicals, riskassessments for these products, in general, focus on specific toxicconstituents. The petroleum constituents of primary interest to humanhealth have been the aromatic hydrocarbons (i.e., benzene,ethylbenzene, toluene, and xylenes). In the U.S., OSHA requires that amixture "shall be assumed to present a carcinogenic hazard if it containsa component in concentrations of 0.1% or greater, which is considered to

be a carcinogen.[55][56]

Outdoor air may contain low levels of benzene from automobile servicestations, wood smoke, tobacco smoke, the transfer of gasoline, exhaust

from motor vehicles, and industrial emissions.[57] About 50% of theentire nationwide (United States) exposure to benzene results from

smoking tobacco or from exposure to tobacco smoke.[58]

Inhalation

Inhaled benzene is primarily expelled unchanged through exhalation. In a human study 16.4 to 41.6% of


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retained benzene was eliminated through the lungs within five to seven hours after a two- to three-hourexposure to 47 to 110 ppm and only 0.07 to 0.2% of the remaining benzene was excreted unchanged in theurine. After exposure to 63 to 405 mg/m3 of benzene for 1 to 5 hours, 51 to 87% was excreted in the urine asphenol over a period of 23 to 50 hours. In another human study, 30% of absorbed dermally applied benzene,

which is primarily metabolized in the liver, was excreted as phenol in the urine.[59]

Exposure through smoking

Exposure of the general population to benzene occurs mainly through breathing, the major sources of benzenebeing tobacco smoke (about 50%) as well as automobile service stations, exhaust from motor vehicles andindustrial emissions (about 20% altogether). According to the CDC, "The mean number of cigarettes per day(cpd) among daily smokers in 1993 was 19.6 (21.3 cpd for men and 17.8 cpd for women) and in 2004 was 16.8

(18.1 cpd for men and 15.3 cpd for women)."[60] According to the August 2007 Public Health Statement, theaverage smoker smokes 32 cpd, which in turn the average smoker would take in about 1.8 milligrams (mg) of

benzene per day. This amount is about 10 times the average daily intake of benzene by nonsmokers.[61]

Exposure from soft drinks

In March 2006, the official Food Standards Agency in Britain conducted a survey of 150 brands of soft drinks.It found that four contained benzene levels above World Health Organization limits. The affected batches were

removed from sale.[62] (See also benzene in soft drinks).

Case examples

Water and soil contamination are important pathways of concern for transmission of benzene. In the US alone,

approximately 100,000 sites have soil or groundwater contaminated with benzene.[citation needed]

In 2005, the water supply to the city of Harbin in China with a population of almost nine million people, was cutoff because of a major benzene exposure. Benzene leaked into the Songhua River, which supplies drinking waterto the city, after an explosion at a China National Petroleum Corporation (CNPC) factory in the city of Jilin on

13 November.[citation needed]

Benzene exposure limits

The United States Environmental Protection Agency has set a maximum contaminant level (MCL) for benzenein drinking water at 0.005 mg/L (5 ppb), as promulgated via the U.S. National Primary Drinking Water

Regulations.[63] This regulation is based on preventing benzene leukemogenesis. The maximum contaminantlevel goal (MCLG), a nonenforceable health goal that would allow an adequate margin of safety for theprevention of adverse effects, is zero benzene concentration in drinking water. The EPA requires that spills oraccidental releases into the environment of 10 pounds (4.5 kg) or more of benzene be reported.

The U.S. Occupational Safety and Health Administration (OSHA) has set a permissible exposure limit of 1 partof benzene per million parts of air (1 ppm) in the workplace during an 8-hour workday, 40-hour workweek. The

short term exposure limit for airborne benzene is 5 ppm for 15 minutes.[64] These legal limits were based onstudies demonstrating compelling evidence of health risk to workers exposed to benzene. The risk fromexposure to 1 ppm for a working lifetime has been estimated as 5 excess leukemia deaths per 1,000 employeesexposed. (This estimate assumes no threshold for benzene's carcinogenic effects.) OSHA has also established an

action level of 0.5 ppm to encourage even lower exposures in the workplace.[65]


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The U.S. National Institute for Occupational Safety and Health (NIOSH) revised the Immediately Dangerous toLife and Health (IDLH) concentration for benzene to 500 ppm. The current NIOSH definition for an IDLHcondition, as given in the NIOSH Respirator Selection Logic, is one that poses a threat of exposure to airbornecontaminants when that exposure is likely to cause death or immediate or delayed permanent adverse healtheffects or prevent escape from such an environment [NIOSH 2004]. The purpose of establishing an IDLH valueis (1) to ensure that the worker can escape from a given contaminated environment in the event of failure of therespiratory protection equipment and (2) is considered a maximum level above which only a highly reliable

breathing apparatus providing maximum worker protection is permitted [NIOSH 2004[66]].[67] In September1995, NIOSH issued a new policy for developing recommended exposure limit (RELs) for substances, includingcarcinogens. Because benzene can cause cancer, NIOSH recommends that all workers wear special breathing

equipment when they are likely to be exposed to benzene at levels exceeding the REL (10-hour) of 0.1 ppm.[68]

The NIOSH STEL (15 min) is 1 ppm.

American Conference of Governmental Industrial Hygienists (ACGIH) adopted Threshold Limit Values (TLVs)for benzene at 0.5 ppm TWA and 2.5 ppm STEL.

Exposure monitoring

Airborne exposure monitoring for benzene must be conducted in order to properly assess personal exposuresand effectiveness of engineering controls. Initial exposure monitoring should be conducted by an industrialhygienist or person specifically trained and experienced in sampling techniques. Contact an AIHA Accredited

Laboratory for advice on sampling methods.[69]

Each employer with a place of employment where occupational exposures to benzene occur shall monitor eachof these workplaces and work operations to determine accurately the airborne concentrations of benzene to

which employees may be exposed.[70] Representative 8-hour TWA employee exposures need to be determinedon the basis of one sample or samples representing the full shift exposure for each job classification in eachwork area. Unless air samples are taken frequently, the employer does not know the concentration and would

not know how much of a protection factor is needed.[71]

In providing consultation on work safety during oil clean-up operations following the Deepwater Horizonaccident, OSHA has worked with a number of other government agencies to protect Gulf cleanup workers.OSHA partnered with the NIOSH to issue "Interim Guidance for Protecting Deepwater Horizon ResponseWorkers and Volunteers" and recommend measures that should be taken to protect workers from a variety of

different health hazards that these workers face.[72] OSHA conceded that it recognizes that most of its PELs areoutdated and inadequate measures of worker safety. In characterizing worker exposure, OSHA instead relies onmore up-to-date recommended protective limits set by organizations such as NIOSH, the ACGIH, and theAmerican Industrial Hygiene Association (AIHA), and not on the older, less protective PELS. Results of airmonitoring are compared to the lowest known Occupational Exposure Limit for the listed contaminant for

purposes of risk assessment and protective equipment recommendations.[73]

Biomarkers of exposure

Several tests can determine exposure to benzene. Benzene itself can be measured in breath, blood or urine, butsuch testing is usually limited to the first 24 hours post-exposure due to the relatively rapid removal of thechemical by exhalation or biotransformation. Most persons in developed countries have measureable baselinelevels of benzene and other aromatic petroleum hydrocarbons in their blood. In the body, benzene is


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enzymatically converted to a series of oxidation products including muconic acid, phenylmercapturic acid,phenol, catechol, hydroquinone and 1,2,4-trihydroxybenzene. Most of these metabolites have some value asbiomarkers of human exposure, since they accumulate in the urine in proportion to the extent and duration ofexposure, and they may still be present for some days after exposure has ceased. The current ACGIH biologicalexposure limits for occupational exposure are 500 μg/g creatinine for muconic acid and 25 μg/g creatinine for

phenylmercapturic acid in an end-of-shift urine specimen.[74][75][76][77]

Biotransformations

Even if it is not a common substrate for the metabolism of organisms, benzene can be oxidized by both bacteriaand eukaryotes. In bacteria, dioxygenase enzyme can add an oxygen molecule to the ring, and the unstableproduct is immediately reduced (by NADH) to a cyclic diol with two double bonds, breaking the aromaticity.Next, the diol is newly reduced by NADH to catechol. The catechol is then metabolized to acetyl CoA andsuccinyl CoA, used by organisms mainly in the Krebs Cycle for energy production.

The pathway for the metabolism of benzene is complex and begins in the liver. Several key enzymes areinvolved. These include cytochrome P450 2E1 (CYP2E1), quinine oxidoreductase (NQ01), GSH, andmyeloperoxidase (MPO). CYP2E1 is involved at multiple steps: converting benzene to oxepin (benzene oxide),phenol to hydroquinone, and hydroquinone to both benzenetriol and catechol. Hydroquinone, benzenetriol andcatechol are converted to polyphenols. In the bone marrow, MPO converts these polyphenols to benzoquinones.These intermediates and metabolites induce genotoxicity by multiple mechanisms including inhibition oftopoisomerase II (which maintains chromosome structure), disruption of microtubules (which maintains cellularstructure and organization), generation of oxygen free radicals (unstable species) that may lead to pointmutations, increasing oxidative stress, inducing DNA strand breaks, and altering DNA methylation (which canaffect gene expression). NQ01 and GSH shift metabolism away from toxicity. NQ01 metabolizes benzoquinonetoward polyphenols (counteracting the effect of MPO). GSH is involved with the formation of

phenylmercapturic acid.[48][78]

Genetic polymorphisms in these enzymes may induce loss of function or gain of function. For example,mutations in CYP2E1 increase activity and result in increased generation of toxic metabolites. NQ01 mutationsresult in loss of function and may result in decreased detoxification. Myeloperoxidase mutations result in loss offunction and may result in decreased generation of toxic metabolites. GSH mutations or deletions result in lossof function and result in decreased detoxification. These genes may be targets for genetic screening for

susceptibility to benzene toxicity.[79]

Molecular toxicology

The paradigm of toxicological assessment of benzene is shifting towards the domain of molecular toxicology asit allows understanding of fundamental biological mechanisms in a better way. Glutathione seems to play animportant role by protecting against benzene-induced DNA breaks and it is being identified as a new biomarker

for exposure and effect.[80] Benzene causes chromosomal aberrations in the peripheral blood leukocytes andbone marrow explaining the higher incidence of leukemia and multiple myeloma caused by chronic exposure.These aberrations can be monitored using fluorescent in situ hybridization (FISH) with DNA probes to assess the

effects of benzene along with the hematological tests as markers of hematotoxicity.[81] Benzene metabolisminvolves enzymes coded for by polymorphic genes. Studies have shown that genotype at these loci mayinfluence susceptibility to the toxic effects of benzene exposure. Individuals carrying variant ofNAD(P)H:quinone oxidoreductase 1 (NQO1), microsomal epoxide hydrolase (EPHX) and deletion of the

glutathione S-transferase T1 (GSTT1) showed a greater frequency of DNA single-stranded breaks.[82]


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Biological oxidation and carcinogenic activity

One way of understanding the carcinogenic effects of benzene is by examining the products of biologicaloxidation. Pure benzene, for example, oxidizes in the body to produce an epoxide, benzene oxide, which is notexcreted readily and can interact with DNA to produce harmful mutations.

Summary

According to the Agency for Toxic Substances and Disease Registry (ATSDR) (2007), benzene is both ananthropogenically produced and naturally occurring chemical from processes that include: volcanic eruptions,wild fires, synthesis of chemicals such as phenol, production of synthetic fibers, and fabrication of rubbers,lubricants, pesticides, medications, and dyes. The major sources of benzene exposure are tobacco smoke,automobile service stations, exhaust from motor vehicles, and industrial emissions; however, ingestion anddermal absorption of benzene can also occur through contact with contaminated water. Benzene is hepaticallymetabolized and excreted in the urine. Measurement of air and water levels of benzene is accomplished throughcollection via activated charcoal tubes, which are then analyzed with a gas chromatograph. The measurement ofbenzene in humans can be accomplished via urine, blood, and breath tests; however, all of these have their

limitations because benzene is rapidly metabolized in the human body into by-products called metabolites.[83]

OSHA regulates levels of benzene in the workplace.[84] The maximum allowable amount of benzene inworkroom air during an 8-hour workday, 40-hour workweek is 1 ppm. Because benzene can cause cancer,NIOSH recommends that all workers wear special breathing equipment when they are likely to be exposed to

benzene at levels exceeding the recommended (8-hour) exposure limit of 0.1 ppm.[85]

6-membered aromatic rings with one carbon replaced by another group: borabenzene, benzene,silabenzene, germabenzene, stannabenzene, pyridine, phosphorine, arsabenzene, pyrylium saltIndustrial Union Department v. American Petroleum InstituteBenzene in soft drinksBTEXBenzene in Kekulé's article

^ Lide, D. R., ed. (2005). CRC Handbook of Chemistry and Physics (86th ed.). Boca Raton (FL): CRC Press.ISBN 0-8493-0486-5.

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^ Arnold, D.; Plank, C.; Erickson, E.; Pike, F. (1958). "Solubility of Benzene in Water". Industrial & EngineeringChemistry Chemical & Engineering Data Series 3 (2): 253. doi:10.1021/i460004a016 (http://dx.doi.org/10.1021%2Fi460004a016).

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^ Breslow, R.; Guo, T. (1990). "Surface tension measurements show that chaotropic salting-in denaturants are notjust water-structure breakers" (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC53221). Proceedings of the NationalAcademy of Sciences of the United States of America 87 (1): 167–9. Bibcode:1990PNAS...87..167B(http://adsabs.harvard.edu/abs/1990PNAS...87..167B). doi:10.1073/pnas.87.1.167 (http://dx.doi.org/10.1073%2Fpnas.87.1.167). PMC 53221 (//www.ncbi.nlm.nih.gov/pmc/articles/PMC53221). PMID 2153285(//www.ncbi.nlm.nih.gov/pubmed/2153285).

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^ Coker, A. Kayode; Ludwig, Ernest E. (2007). Ludwig's Applied Process Design for Chemical And PetrochemicalPlants (http://books.google.com/books?id=N8RcH8juG_YC&pg=PA114) 1. Elsevier. p. 114. ISBN 0-7506-7766-X.Retrieved 2012-05-31.

4.


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^ The word "benzoin" is derived from the Arabic expression "luban jawi", or "frankincense of Java".[citation needed]5.^ a b Rocke, A. J. (1985). "Hypothesis and Experiment in the Early Development of Kekule's Benzene Theory".Annals of Science 42 (4): 355–81. doi:10.1080/00033798500200411 (http://dx.doi.org/10.1080%2F00033798500200411).

6.

^ Faraday, M. (1825). "On new compounds of carbon and hydrogen, and on certain other products obtained duringthe decomposition of oil by heat" (http://gallica.bnf.fr/ark:/12148/bpt6k559209/f473.image). PhilosophicalTransactions of the Royal Society of London 115: 440–466. doi:10.1098/rstl.1825.0022 (http://dx.doi.org/10.1098%2Frstl.1825.0022). JSTOR 107752 (http://www.jstor.org/stable/107752). On pages 443–450, Faradaydiscusses "bicarburet of hydrogen" (benzene). On pages 449–450, he shows that benzene's empirical formula isC6H6, although he doesn't realize it because he (like most chemists at that time) used the wrong atomic mass forcarbon (6 instead of 12).

7.

^ Kaiser, R. (1968). "Bicarburet of Hydrogen. Reappraisal of the Discovery of Benzene in 1825 with the AnalyticalMethods of 1968". Angewandte Chemie International Edition in English 7 (5): 345–350.doi:10.1002/anie.196803451 (http://dx.doi.org/10.1002%2Fanie.196803451).

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^ Mitscherlich, E. (1834). "Über das Benzol und die Säuren der Oel- und Talgarten (http://books.google.com/books?id=JEs9AAAAcAAJ&pg=PA39#v=onepage&q&f=false) (On benzol and oily and fatty types of acids)".Annalen der Pharmacie 9 (1): 39–48. doi:10.1002/jlac.18340090103 (http://dx.doi.org/10.1002%2Fjlac.18340090103). In a footnote on page 43, Liebig, the journal's editor, suggested changingMitscherlich's original name for benzene (namely, "benzin") to "benzol", because the suffix "-in" suggested that itwas an alkaloid (e.g., Chinin (quinine)), which benzene isn't, whereas the suffix "-ol" suggested that it was oily,which benzene is. Thus on page 44, Mitscherlich states: Da diese Flüssigkeit aus der Benzoësäure gewonnen wird,und wahrscheinlich mit den Benzoylverbindungen im Zusammenhang steht, so gibt man ihr am besten den NamenBenzol, da der Name Benzoïn schon für die mit dem Bittermandelöl isomerische Verbindung von Liebig und Wöhlergewählt worden ist. (Since this liquid [benzene] is obtained from benzoic acid and probably is related to benzoylcompounds, the best name for it is "benzol", since the name "benzoïn" has already been chosen, by Liebig andWöhler, for the compound that's isomeric with the oil of bitter almonds [benzaldehyde].)

9.

^ Laurent, Auguste (1836) "Sur la chlorophénise et les acides chlorophénisique et chlorophénèsique," Annales deChemie et de Physique, vol. 63, pp. 27–45, see p. 44 (http://books.google.com/books?id=Lx0AAAAAMAAJ&pg=PA44): Je donne le nom de phène au radical fondamental des acides précédens (φαινω, j'éclaire), puisque labenzine se trouve dans le gaz de l'éclairage. (I give the name of "phène" (φαινω, I illuminate) to the fundamentalradical of the preceding acid, because benzene is found in illuminating gas.)

10.

^ Kekulé, August (1872). "Ueber einige Condensationsproducte des Aldehyds". Liebigs Ann. Chem. 162 (1):77–124. doi:10.1002/jlac.18721620110 (http://dx.doi.org/10.1002%2Fjlac.18721620110).

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^ Hofmann, A. W. (1845) "Ueber eine sichere Reaction auf Benzol" (http://books.google.com/books?id=E-1AAAAAYAAJ&pg=PA200) (On a reliable test for benzene), Annalen der Chemie und Pharmacie, vol. 55, pp.200–205; on pp. 204–205, Hofmann found benzene in coal tar oil.

12.

^ Mansfield, Charles Blachford (1849) "Untersuchung des Steinkohlentheers" (http://books.google.com/books?id=kD4aAQAAMAAJ&pg=PA162) (Investigation of coal tar), Annalen der Chemie und Pharmacie, vol.69, pp. 162–180.

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^ Charles Mansfield filed for (November 11, 1847) and received (May 1848) a patent (no. 11,960) for the fractionaldistillation of coal tar.

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^ Hoffman, Augustus W. (1856). "On insolinic acid". Proceedings of the Royal Society of London 8: 1–3.doi:10.1098/rspl.1856.0002 (http://dx.doi.org/10.1098%2Frspl.1856.0002). "The existence and mode of formationof insolinic acid prove that to the series of monobasic aromatic acids, Cn2Hn2-8O4, the lowest known term of whichis benzoic acid, ...." [Note: The empirical formulas of organic compounds that appear in Hoffmann's article (p. 3)are wrong because he uses the incorrect atomic masses of carbon (6 instead of 12) and oxygen (8 instead of 16).]

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^ J. Loschmidt, Chemische Studien (Vienna, Austria-Hungary: Carl Gerold's Sohn, 1861), pp. 30, 65(http://books.google.com/books?id=ksw5AAAAcAAJ&pg=PA30).

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^ Kekulé, F. A. (1865). "Sur la constitution des substances aromatiques" (http://books.google.com/books?id=bFsSAAAAYAAJ&pg=PA98). Bulletin de la Societe Chimique de Paris 3: 98–110. On p. 100, Kekulésuggests that the carbon atoms of benzene could form a "chaîne fermée" (a closed chain, a loop).

17.

^ Kekulé, F. A. (1866). "Untersuchungen über aromatische Verbindungen] (Investigations of aromatic compounds)"(http://books.google.com/books?id=pNryAAAAMAAJ&lpg=PA129). Liebigs Annalen der Chemie und Pharmacie137 (2): 129–36. doi:10.1002/jlac.18661370202 (http://dx.doi.org/10.1002%2Fjlac.18661370202).

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^ Rocke, A. J. (2010) Image and Reality: Kekule, Kopp, and the Scientific Imagination, University of Chicago19.


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Press, pp. 186–227, ISBN 0226723356.^ Critics pointed out a problem with Kekulé's original (1865/1866) structure for benzene: Whenever benzeneunderwent substitution at the ortho position, two distinguishable isomers should have resulted, depending onwhether the double bond at the ortho position extended clockwise or counterclockwise; however, no such isomerswere observed. In 1872, Kekulé suggested that benzene had two complementary structures and that these formsrapidly interconverted, so that if there were a double bond between any pair of carbon atoms at one instant, thatdouble bond would become a single bond at the next instant (and vice-versa). To provide a mechanism for theconversion process, Kekulé proposed that the valency of an atom is determined by the frequency with which itcollided with its neighbors in a molecule. As the carbon atoms in the benzene ring collided with each other, eachcarbon atom would collide twice with one neighbor during a given interval and then twice with its other neighborduring the next interval. Thus, a double bond would exist with one neighbor during the first interval and the otherneighbor during the next interval. See pages 86–89 (http://de.wikipedia.org/w/index.php?title=Datei:Kekule_-_Ueber_einige_Condensationsproducte_des_Aldehyds.pdf&page=10) of Auguste Kekulé (1872) "Ueber einigeCondensationsprodukte des Aldehyds" (On some condensation products of aldehydes), Liebig's Annalen derChemie und Pharmacie, 162(1): 77–124, 309–320.

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^ Kekulé, F. A. (1890). "Benzolfest: Rede" (http://gallica.bnf.fr/ark:/12148/bpt6k90720c/f1304.chemindefer).Berichte der Deutschen Chemischen Gesellschaft 23: 1302–11. doi:10.1002/cber.189002301204 (http://dx.doi.org/10.1002%2Fcber.189002301204).

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Benzene (http://www.periodicvideos.com/videos/mv_benzene.htm) at The Periodic Table of Videos(University of Nottingham)Benzene (www.eco-usa.net) (http://www.eco-usa.net/toxics/chemicals/benzene.shtml)International Chemical Safety Card 0015 (http://www.inchem.org/documents/icsc/icsc/eics0015.htm)USEPA Summary of Benzene Toxicity (http://www.epa.gov/iris/subst/0276.htm)NIOSH Pocket Guide to Chemical Hazards (http://www.cdc.gov/niosh/npg/npgd0049.html)CID 241 (http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=241) from PubChemDept. of Health and Human Services: TR-289: Toxicology and Carcinogenesis Studies of Benzene(http://ntp.niehs.nih.gov/index.cfm?objectid=0707525C-0F07-05BF-A16CAC7B0ECC97B5)Video Podcast (http://www.ch.ic.ac.uk/video/faraday_l.m4v) of Sir John Cadogan giving a lecture onBenzene since Faraday, in 1991Substance profile (http://web.archive.org/web/20070224171424/http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s019benz.pdf)Benzene (http://chem.sis.nlm.nih.gov/chemidplus/direct.jsp?regno=71-43-2) in the ChemIDplus databaseNLM Hazardous Substances Databank – Benzene (http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+35)

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