Benzene is a natural constituent ofpetroleum and is one of the elementarypetrochemicals. Due to the cyclic continuouspi bonds between the carbon atoms and satisfyingHückel's rule, benzene is classed as anaromatic hydrocarbon. Benzene is a colorless and highlyflammable liquid with a sweet smell, and is partially responsible for the aroma ofgasoline. It is used primarily as aprecursor to the manufacture of chemicals with more complex structures, such asethylbenzene andcumene, of which billions of kilograms are produced annually. Although benzene is a majorindustrial chemical, it finds limited use in consumer items because of its toxicity. Benzene is avolatile organic compound.[14]
Benzene is classified as acarcinogen. Its particular effects onhuman health, such as the long-term results of accidental exposure, have been reported on by news organizations such asThe New York Times. For instance, a 2022 article stated that benzene contamination in theBoston metropolitan area caused hazardous conditions in multiple places, with the publication noting that the compound may eventually causeleukemia in some individuals.[15]
The word "benzene" derives from "gum benzoin" (benzoin resin), an aromatic resin known since ancient times in Southeast Asia, and later to European pharmacists and perfumers in the 16th century via trade routes.[16] Anacidic material was derived from benzoin bysublimation, and named "flowers of benzoin", or benzoic acid. The hydrocarbon derived from benzoic acid thus acquired the name benzin, benzol, or benzene.[17]Michael Faraday first isolated and identified benzene in 1825 from the oily residue derived from the production of illuminating gas, giving it the namebicarburet of hydrogen.[18][19] In 1833,Eilhard Mitscherlich produced it bydistillingbenzoic acid (fromgum benzoin) andlime. He gave the compound the namebenzin.[20] In 1836, the French chemistAuguste Laurent named the substance "phène";[21] this word has become the root of the English word "phenol", which ishydroxylated benzene, and "phenyl", the radical formed by abstraction of a hydrogen atom from benzene.
In 1845,Charles Blachford Mansfield, working underAugust Wilhelm von Hofmann, isolated benzene fromcoal tar.[22] Four years later, Mansfield began the first industrial-scale production of benzene, based on the coal-tar method.[23][24] Gradually, the sense developed among chemists that a number of substances were chemically related to benzene, comprising a diverse chemical family. In 1855, Hofmann was the first to apply the word "aromatic" to designate this family relationship, after a characteristic property of many of its members.[25] In 1997, benzene wasdetected in deep space.[26]
Theempirical formula for benzene was long known, but its highlypolyunsaturated structure, with just onehydrogen atom for eachcarbon atom, was challenging to determine.Archibald Scott Couper in 1858 andJohann Josef Loschmidt in 1861[36] suggested possible structures that contained multiple double bonds or multiple rings, but in these years very little was known about aromatic chemistry, and so chemists were unable to adduce appropriate evidence to favor any particular formula.
But many chemists had begun to work on aromatic substances, especially in Germany, and relevant data was coming fast. In 1865, the German chemistFriedrich August Kekulé published a paper in French (for he was then teaching in Francophone Belgium) suggesting that the structure contained a ring of six carbon atoms with alternating single and double bonds. The next year he published a much longer paper in German on the same subject.[30][37] Kekulé used evidence that had accumulated in the intervening years—namely, that there always appeared to be only oneisomer of anymonoderivative of benzene, and that there always appeared to be exactly three isomers of every disubstituted derivative—now understood to correspond to the ortho, meta, and para patterns ofarene substitution—to argue in support of his proposed structure.[38] Kekulé's symmetrical ring could explain these curious facts, as well as benzene's 1:1 carbon-hydrogen ratio.
Kekulé's 1872 modification of his 1865 theory, illustrating rapid alternation of double bonds[note 2]
The new understanding of benzene, and hence of all aromatic compounds, proved to be so important for both pure and applied chemistry that in 1890 theGerman Chemical Society organized an elaborate appreciation in Kekulé's honor, celebrating the twenty-fifth anniversary of his first benzene paper. Here Kekulé spoke of the creation of the theory. He said that he had discovered the ring shape of the benzene molecule after having a reverie or day-dream of a snake biting its own tail (a symbol in ancient cultures known as theouroboros).[39] This vision, he said, came to him after years of studying the nature of carbon-carbon bonds. This was seven years after he had solved the problem of how carbon atoms could bond to up to four other atoms at the same time. Curiously, a similar, humorous depiction of benzene had appeared in 1886 in a pamphlet entitledBerichte 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.[40] Some historians have suggested that the parody was a lampoon of the snake anecdote, possibly already well known through oral transmission even if it had not yet appeared in print.[17] Kekulé's 1890 speech[41] in which this anecdote appeared has been translated into English.[42] If the anecdote is the memory of a real event, circumstances mentioned in the story suggest that it must have happened early in 1862.[43]
In 1929, the cyclic nature of benzene was finally confirmed by thecrystallographerKathleen Lonsdale usingX-ray diffraction methods.[44][45] Using large crystals ofhexamethylbenzene, a benzene derivative with the same core of six carbon atoms, Lonsdale obtained diffraction patterns. Through calculating more than thirty parameters, Lonsdale demonstrated that the benzene ring could not be anything but a flat hexagon, and provided accurate distances for all carbon-carbon bonds in the molecule.[46]
The German chemistWilhelm Körner suggested the prefixes ortho-, meta-, para- to distinguish di-substituted benzene derivatives in 1867; however, he did not use the prefixes to distinguish the relative positions of the substituents on a benzene ring.[47][48] It was the German chemistCarl Gräbe who, in 1869, first used the prefixes ortho-, meta-, para- to denote specific relative locations of the substituents on a di-substituted aromatic ring (viz, naphthalene).[49] In 1870, the German chemistViktor Meyer first applied Gräbe's nomenclature to benzene.[50]
In 1903,Ludwig Roselius popularized the use of benzene todecaffeinatecoffee. This discovery led to the production ofSanka. This process was later discontinued. Benzene was historically used as a significant component in many consumer products such asliquid wrench, severalpaint strippers,rubber cements, spot removers, and other products. Manufacture of some of these benzene-containing formulations ceased in about 1950, although Liquid Wrench continued to contain significant amounts of benzene until the late 1970s.[51]
Trace amounts of benzene are found in petroleum and coal. It is a byproduct of the incomplete combustion of many materials. For commercial use, untilWorld War II, much of benzene was obtained as a by-product ofcoke production (or "coke-oven light oil") for thesteel industry. However, in the 1950s, increased demand for benzene, especially from the growingpolymers industry, necessitated the production of benzene from petroleum. Today, most benzene comes from thepetrochemical industry, with only a small fraction being produced from coal.[52] Benzene has been detected onMars.[53][54][55]
X-ray diffraction shows that all six carbon-carbon bonds in benzene are of the same length, at 140picometres (pm).[56] The C–Cbond lengths are greater than a double bond (135 pm) but shorter than a single bond (147 pm). This intermediate distance is caused by electrondelocalization: the electrons for C=C bonding are distributed equally between each of the six carbon atoms. Benzene has 6 hydrogen atoms, fewer than the corresponding parentalkane,hexane, which has 14. Benzene andcyclohexane have a similar structure; only the ring of delocalized electrons and the loss of one hydrogen per carbon distinguishes it from cyclohexane. The molecule is planar.[57] The molecular orbital description involves the formation of three delocalizedπ orbitals spanning all six carbon atoms, while the valence bond description involves a superposition ofresonance structures.[58][59][60][61] It is likely that this stability contributes to the peculiar molecular and chemical properties known asaromaticity. To reflect the delocalized nature of the bonding, benzene is often depicted with a circle inside a hexagonal arrangement of carbon atoms.
Derivatives of benzene occur sufficiently often as a component of organic molecules, so much so that theUnicode Consortium has allocated a symbol in theMiscellaneous Technical block with the code U+232C (⌬) to represent it with three double bonds,[62] and U+23E3 (⏣) for a delocalized version.[63]
Many important chemical compounds are derived from benzene by replacing one or more of its hydrogen atoms with anotherfunctional group. Examples of simple benzene derivatives arephenol,toluene, andaniline, abbreviated PhOH, PhMe, and PhNH2, respectively. Linking benzene rings givesbiphenyl, C6H5–C6H5. Further loss of hydrogen gives "fused" aromatic hydrocarbons, such asnaphthalene,anthracene,phenanthrene, andpyrene. The limit of the fusion process is the hydrogen-free allotrope of carbon,graphite.
Inheterocycles, carbon atoms in the benzene ring are replaced with other elements. The most important variations containnitrogen. Replacing one CH with N gives the compoundpyridine, C5H5N. Although benzene and pyridine arestructurally 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, orpyrazine.[64]
Four chemical processes contribute to industrial benzene production:catalytic reforming,toluene hydrodealkylation, toluene disproportionation, andsteam cracking etc. According to theATSDR Toxicological Profile for benzene, between 1978 and 1981, catalytic reformates accounted for approximately 44–50% of the total U.S. benzene production.[52]
In catalytic reforming, a mixture ofhydrocarbons with boiling points between 60 and 200 °C is blended withhydrogen gas and then exposed to abifunctionalplatinum chloride orrhenium chloridecatalyst at 500–525 °C and pressures ranging from 8–50 atm. Under these conditions,aliphatic hydrocarbons form rings and lose hydrogen to become aromatic hydrocarbons. The aromatic products of the reaction are then separated from the reaction mixture (or reformate) byextraction with any one of a number ofsolvents, includingdiethylene glycol orsulfolane, and benzene is then separated from the other aromatics by distillation. The extraction step of aromatics from the reformate is designed to produce aromatics with lowest non-aromatic components. Recovery of the aromatics, commonly referred to asBTX (benzene, toluene and xylene isomers), involves such extraction and distillation steps.
In similar fashion to this catalytic reforming,UOP andBP commercialized a method from LPG (mainly propane and butane) to aromatics.
Toluenehydrodealkylation convertstoluene to benzene. In this hydrogen-intensive process, toluene is mixed with hydrogen, then passed over achromium,molybdenum, orplatinumoxide catalyst at 500–650 °C and 20–60 atm pressure. Sometimes, higher temperatures are used instead of a catalyst (at the similar reaction condition). Under these conditions, toluene undergoes dealkylation to benzene andmethane:
C6H5CH3 + H2 → C6H6 + CH4
This irreversible reaction is accompanied by an equilibrium side reaction that producesbiphenyl (diphenyl) at higher temperature:
2C 6H 6 ⇌H 2 +C 6H 5–C 6H 5
If the raw material stream contains much non-aromatic components (paraffins or naphthenes), those are likely decomposed 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.
Given that demand forpara-xylene (p-xylene) substantially exceeds demand for other xylene isomers, a refinement of the TDP process calledSelective TDP (STDP) may be used. In this process, the xylene stream exiting the TDP unit is approximately 90%p-xylene. In some systems, even the benzene-to-xylenes ratio is modified to favor xylenes.
Steam cracking is the process for producingethylene and otheralkenes fromaliphatic hydrocarbons. Depending on the feedstock used to produce the olefins, steam cracking can produce a benzene-rich liquid by-product calledpyrolysis gasoline. Pyrolysis gasoline can be blended with other hydrocarbons as a gasoline additive, or routed through an extraction process to recoverBTX aromatics (benzene, toluene and xylenes).
Benzene is used mainly as an intermediate to make other chemicals, above allethylbenzene (and otheralkylbenzenes),cumene,cyclohexane, andnitrobenzene. In 1988, it was reported that two-thirds of all chemicals on theAmerican Chemical Society's lists contained at least one benzene ring.[66] More than half of the entire benzene production is processed into ethylbenzene, a precursor tostyrene, which is used to make polymers and plastics likepolystyrene. Some 20% of the benzene production is used to manufacture cumene, which is needed to producephenol and acetone for resins and adhesives.Cyclohexane consumes around 10% of the world's benzene production; it is primarily used in the manufacture of nylon fibers, which are processed into textiles and engineering plastics. Smaller amounts of benzene are used to make some types ofrubbers,lubricants,dyes,detergents,drugs,explosives, andpesticides. In 2013, the biggest consumer country of benzene was China, followed by the USA. Benzene production is currently expanding in the Middle East and in Africa, whereas production capacities in Western Europe and North America are stagnating.[67]
Toluene is now often used as a substitute for benzene, for instance as a fuel additive. The solvent-properties of the two are similar, but toluene is less toxic and has a wider liquid range. Toluene is also processed into benzene.[68]
Major commodity chemicals and polymers derived from benzene. Clicking on the image loads the appropriate article
As agasoline (petrol) additive, benzene increases theoctane rating and reducesknocking. As a consequence, gasoline often contained several percent benzene before the 1950s, whentetraethyl lead replaced it as the most widely used antiknock additive. With the global phaseout of leaded gasoline in the 1970s–1990s, benzene reappeared as a gasoline additive, although strictly limited in most nations. For example, in theUnited States, concern over its negative health effects and the possibility of benzene entering thegroundwater has led to stringent regulation of gasoline's benzene content, with limits typically around 1%.[69] European petrol specifications now contain the same 1% limit on benzene content. TheUnited States Environmental Protection Agency introduced new regulations in 2011 that lowered the benzene content in gasoline to 0.62%.[70]
In some European languages, the word for petroleum or gasoline is an exact cognate of "benzene". For instance allGermanic languages andScandinavian languages refer to gasoline as 'bensin' or 'benzin'. InTurkish and manyTurkic languages the word of 'benzin' is used to refer the gasoline. InCatalan andItalian the word 'benzina' can be used for gasoline. InPolish the word 'benzyna' is also used to mean gasoline or petrol.
The most common reactions of benzene involve substitution of a proton by other groups.[71]Electrophilic aromatic substitution is a general method of derivatizing benzene. Benzene is sufficientlynucleophilic that it undergoes substitution byacylium ions and alkylcarbocations to give substituted derivatives.
Electrophilic aromatic substitution of benzene
The most widely practiced example of this reaction is theethylation of benzene.
Using electrophilic aromatic substitution, many functional groups are introduced onto the benzene framework.Sulfonation of benzene involves the use ofoleum, a mixture of sulfuric acid withsulfur trioxide. Sulfonated benzene derivatives are usefuldetergents. Innitration, benzene reacts with nitronium ions (NO2+), which is a strong electrophile produced by combining sulfuric and nitric acids.Nitrobenzene is the precursor toaniline. Chlorination is achieved with chlorine to producechlorobenzene in the presence of a Lewis acid catalyst such as aluminium chloride.
Hydrogenation is achieved by introducinghydrogen to the unsaturated compounds under high pressure in the presence ofheterogeneous catalysts, such as finely dividednickel. This reaction converts benzene intocyclohexane. Benzene derivatives are also converted into their respective saturated equivalents. Whereas alkenes can be hydrogenated near room temperatures, benzene and its derivatives are more reluctant substrates, requiring temperatures exceeding 100 °C for hydrogenation to occur. This reaction is practiced on an industrial scale.[73] Typically, benzene is fully saturated into cyclohexane during hydrogenation. However, with the right conditions, benzene can be partially-hydrogenated to give cyclohexene or cyclohexadienes.[74] A similar reaction is theBirch reduction, which is a non-catalytic process that converts benzene into cyclohexadiene.
A bottle of benzene. The warnings show benzene is a toxic and flammable liquid.
Benzene is classified as acarcinogen, which increases the risk ofcancer and other illnesses, and is also a notorious cause ofbone marrow failure. Substantial quantities of epidemiologic, clinical, and laboratory data link benzene to aplastic anemia, acuteleukemia, bone marrow abnormalities and cardiovascular disease.[75][76][77] The specific hematologic malignancies that benzene is associated with include: acute myeloid leukemia (AML), aplastic anemia, myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML).[78]
Carcinogenic activity of benzene was discovered by Swedish pharmacologistC. G. Santesson [sv] in 1897 on female workers of a tire-making factory.[79][80] TheAmerican Petroleum Institute (API) stated in 1948 that "it is generally considered that the only absolutely safe concentration for benzene is zero".[81] There is no safe exposure level; even tiny amounts can cause harm.[82] TheUS Department of Health and Human Services (DHHS) classifies benzene as a human carcinogen. Long-term exposure to excessive levels of benzene in the air causes leukemia, a potentially fatal cancer of the blood-forming organs. In particular,acute myeloid leukemia oracute nonlymphocytic leukemia (AML & ANLL) is caused by benzene.[83] IARC rated benzene as "known to be carcinogenic to humans" (Group 1).
As benzene is ubiquitous in gasoline and hydrocarbon fuels that are in use everywhere, human exposure to benzene is a global health problem. Benzene targets the liver, kidney, lung, heart and brain and can causeDNA strand breaks andchromosomal damage, hence isteratogenic andmutagenic. Benzene causes cancer in animals including humans. Benzene has been shown to cause cancer in both sexes of multiple species of laboratory animals exposed via various routes.[84][85]
According to theAgency for Toxic Substances and Disease Registry (ATSDR) (2007), benzene is both a synthetically made and naturally occurring chemical from processes that include: volcanic eruptions, wild fires, synthesis of chemicals such asphenol, production ofsynthetic fibers, and fabrication ofrubbers,lubricants,pesticides, medications, anddyes. The major sources of benzene exposure aretobacco smoke, automobile service stations, exhaust from motor vehicles, and industrial emissions; however, ingestion and dermal absorption of benzene can also occur through contact with contaminated water. Benzene is hepatically metabolized and excreted in theurine. Measurement of air and water levels of benzene is accomplished through collection viaactivated charcoal tubes, which are then analyzed with agas chromatograph. The measurement of benzene in humans can be accomplished viaurine,blood, andbreath tests; however, all of these have their limitations because benzene is rapidly metabolized in the human body.[86]
OSHA regulates levels of benzene in the workplace.[88] The maximum allowable amount of benzene in workroom air during an 8-hour workday, 40-hour workweek is 1 ppm. As benzene can causecancer,NIOSH recommends that all workers wear specialbreathing equipment when they are likely to be exposed to benzene at levels exceeding the recommended (8-hour) exposure limit of 0.1 ppm.[89]
TheUnited States Environmental Protection Agency has set amaximum contaminant level for benzene indrinking water at 0.005 mg/L (5 ppb), as promulgated via the U.S. National Primary Drinking Water Regulations.[90] This regulation is based on preventing benzeneleukemogenesis. The maximum contaminant level goal (MCLG), a nonenforceable health goal that would allow an adequate margin of safety for the prevention of adverse effects, is zero benzene concentration in drinking water. The EPA requires that spills or accidental 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 part of 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.[91] These legal limits were based on studies demonstrating compelling evidence of health risk to workers exposed to benzene. The risk from exposure to 1 ppm for a working lifetime has been estimated as 5 excess leukemia deaths per 1,000 employees exposed. (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.[92]
The U.S.National Institute for Occupational Safety and Health (NIOSH) revised theImmediately Dangerous to Life and Health (IDLH) concentration for benzene to 500 ppm. The current NIOSH definition for an IDLH condition, as given in the NIOSH Respirator Selection Logic, is one that poses a threat of exposure to airborne contaminants when that exposure is likely to cause death or immediate or delayed permanent adverse health effects or prevent escape from such an environment.[93] The purpose of establishing an IDLH value is (1) to ensure that the worker can escape from a given contaminated environment in the event of failure of the respiratory protection equipment and (2) is considered a maximum level above which only a highly reliablebreathing apparatus providing maximum worker protection is permitted.[93][94] In September 1995, NIOSH issued a new policy for developingrecommended exposure limits (RELs) for substances, including carcinogens. As 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.[95] The NIOSH short-term exposure limit (STEL – 15 min) is 1 ppm.
American Conference of Governmental Industrial Hygienists (ACGIH) adopted Threshold Limit Values (TLVs) for benzene at 0.02 ppm TWA in 2024.[91][96]
Several tests can determine exposure to benzene. Benzene itself can be measured in breath, blood or urine, but such testing is usually limited to the first 24 hours post-exposure due to the relatively rapid removal of the chemical by exhalation or biotransformation. Most people in developed countries have measureable baseline levels of benzene and other aromatic petroleum hydrocarbons in their blood. In the body, benzene is enzymatically converted to a series of oxidation products includingmuconic acid,phenylmercapturic acid,phenol,catechol,hydroquinone and1,2,4-trihydroxybenzene. Most of these metabolites have some value as biomarkers of human exposure, since they accumulate in the urine in proportion to the extent and duration of exposure, and they may still be present for some days after exposure has ceased. The current ACGIH biological exposure 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.[97][98][99][100]
Even if it is not a common substrate for metabolism, benzene can be oxidized by bothbacteria andeukaryotes. In bacteria,dioxygenase enzyme can add anoxygen to the ring, and the unstable product is immediately reduced (byNADH) to a cyclicdiol with two double bonds, breaking the aromaticity. Next, the diol is newly reduced by NADH tocatechol. The catechol is then metabolized toacetyl CoA andsuccinyl CoA, used by organisms mainly in thecitric acid cycle for energy production.
Human metabolism of benzene is complex and begins in the liver. Several enzymes are involved. These includecytochrome P450 2E1 (CYP2E1), quinine oxidoreductase (NQ01 or DT-diaphorase orNAD(P)H dehydrogenase (quinone 1)), GSH, and myeloperoxidase (MPO). CYP2E1 is involved at multiple steps: converting benzene tooxepin (benzene oxide),phenol tohydroquinone, and hydroquinone to both benzenetriol andcatechol. Hydroquinone, benzenetriol and catechol 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 ofmicrotubules (which maintains cellular structure and organization), generation of oxygen free radicals (unstable species) that may lead to point mutations, increasing oxidative stress, inducingDNA strand breaks, and altering DNAmethylation (which can affect gene expression). NQ01 and GSH shift metabolism away from toxicity. NQ01 metabolizesbenzoquinone towardpolyphenols (counteracting the effect of MPO). GSH is involved with the formation ofphenylmercapturic acid.[78][101]
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 mutations result in loss of function and may result in decreased detoxification. Myeloperoxidase mutations result in loss of function and may result in decreased generation of toxic metabolites. GSH mutations or deletions result in loss of function and result in decreased detoxification. These genes may be targets for genetic screening for susceptibility to benzene toxicity.[102]
The paradigm of toxicological assessment of benzene is shifting towards the domain of molecular toxicology as it allows understanding of fundamental biological mechanisms in a better way.Glutathione seems to play an important role by protecting against benzene-induced DNA breaks and it is being identified as a new biomarker for exposure and effect.[103] Benzene causes chromosomal aberrations in the peripheral blood leukocytes and bone marrow explaining the higher incidence of leukemia and multiple myeloma caused by chronic exposure. These aberrations can be monitored usingfluorescent in situ hybridization (FISH) with DNA probes to assess the effects of benzene along with the hematological tests as markers of hematotoxicity.[104] Benzene metabolism involves enzymes coded for by polymorphic genes. Studies have shown that genotype at these loci may influence susceptibility to the toxic effects of benzene exposure. Individuals carrying variant of NAD(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.[105]
One way of understanding the carcinogenic effects of benzene is by examining the products of biological oxidation. Pure benzene, for example, oxidizes in the body to produce an epoxide,benzene oxide, which is not excreted readily and can interact with DNA to produce harmful mutations.
Outdoor air may contain low levels of benzene from automobile service stations, wood smoke, tobacco smoke, the transfer of gasoline, exhaust from motor vehicles, and industrial emissions.[106] About 50% of the entire nationwide (United States) exposure to benzene results from smoking tobacco or from exposure to tobacco smoke.[107] After smoking 32 cigarettes per day, the smoker would take in about 1.8 milligrams (mg) of benzene. This amount is about 10 times the average daily intake of benzene by nonsmokers.[108]
Inhaled benzene is primarily expelled unchanged through exhalation. In a human study 16.4 to 41.6% of retained benzene was eliminated through the lungs within five to seven hours after a two- to three-hour exposure to 47 to 110 ppm and only 0.07 to 0.2% of the remaining benzene was excreted unchanged in the urine. After exposure to 63 to 405 mg/m3 of benzene for 1 to 5 hours, 51 to 87% was excreted in the urine as phenol 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.[109]
Under specific conditions and in the presence of other chemicalsbenzoic acid (a preservative) andascorbic acid (Vitamin C) may interact to produce benzene. In March 2006, the officialFood Standards Agency inUnited Kingdom conducted a survey of 150 brands of soft drinks. It found that four contained benzene levels aboveWorld Health Organization limits. The affected batches were removed from sale. Similar problems were reported by the FDA in the United States.[110]
^ Dewar included this isomer in a list of possible C6H6 structures in 1869. However, he did not propose it for benzene, and in fact he supported the correct structure proposed by Kekulé. SeeDewar benzene
^Critics pointed out a problem with Kekulé's original (1865) structure for benzene: Whenever benzene underwent substitution at the ortho position, two distinguishable isomers should have resulted, depending on whether a double bond or a single bond existed between the carbon atoms to which the substituents were attached; however, no such isomers were observed. In 1872, Kekulé suggested that benzene had two complementary structures and that these forms rapidly interconverted, so that if there were a double bond between any pair of carbon atoms at one instant, that double bond would become a single bond at the next instant (and vice versa). To provide a mechanism for the conversion process, Kekulé proposed that the valency of an atom is determined by the frequency with which it collided with its neighbors in a molecule. As the carbon atoms in the benzene ring collided with each other, each carbon atom would collide twice with one neighbor during a given interval and then twice with its other neighbor during the next interval. Thus, a double bond would exist with one neighbor during the first interval and with the other neighbor during the next interval. Therefore, between the carbon atoms of benzene there were no fixed (i.e., constant) and distinct single or double bonds; instead, the bonds between the carbon atoms were identical. Seepages 86–89Archived 2020-03-20 at theWayback Machine of Auguste Kekulé (1872) "Ueber einige Condensationsprodukte des Aldehyds" (On some condensation products of aldehydes),Liebig's Annalen der Chemie und Pharmacie,162(1): 77–124, 309–320. From p. 89:"Das einfachste Mittel aller Stöße eines Kohlenstoffatoms ergiebt sich aus der Summe der Stöße der beiden ersten Zeiteinheiten, die sich dann periodisch wiederholen. ... man sieht daher, daß jedes Kohlenstoffatom mit den beiden anderen, ... daß diese Verschiedenheit nur eine scheinbare, aber keine wirkliche ist." (The simplest average of all the collisions of a carbon atom [in benzene] comes from the sum of the collisions during the first two units of time, which then periodically repeat. ... thus one sees that each carbon atom collides equally often with the two others against which it bumps, [and] thus stands in exactly the same relation with its two neighbors. The usual structural formula for benzene expresses, of course, only the collisions that occur duringone unit of time, thus during one phase, and so one is led to the view [that] doubly substituted derivatives [of benzene] must be different at positions 1,2 and 1,6 [of the benzene ring]. If the idea [that was] just presented—or a similar one—can be regarded as correct, then [it] follows therefrom that this difference [between the bonds at positions 1,2 and 1,6] is only an apparent [one], not a real [one].)
^abcBenzene in Linstrom, Peter J.; Mallard, William G. (eds.);NIST Chemistry WebBook, NIST Standard Reference Database Number 69, National Institute of Standards and Technology, Gaithersburg (MD) (retrieved 2014-05-29)
^The word "benzoin" is derived from the Arabic expression "luban jawi", or "frankincense ofJava".Morris, Edwin T. (1984).Fragrance: The Story of Perfume from Cleopatra to Chanel. Charles Scribner's Sons. p. 101.ISBN978-0-684-18195-0.
^Kaiser, R. (1968). "Bicarburet of Hydrogen. Reappraisal of the Discovery of Benzene in 1825 with the Analytical Methods of 1968".Angewandte Chemie International Edition in English.7 (5):345–350.doi:10.1002/anie.196803451.
^Mitscherlich, E. (1834)."Über das Benzol und die Säuren der Oel- und Talgarten" [On benzol and oily and fatty types of acids].Annalen der Pharmacie.9 (1):39–48.doi:10.1002/jlac.18340090103.Archived from the original on 2015-11-23. Retrieved2015-06-27. In a footnote on page 43, Liebig, the journal's editor, suggested changing Mitscherlich's original name for benzene (namely, "benzin") to "benzol", because the suffix "-in" suggested that it was 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 Namen Benzol, da der Name Benzoïn schon für die mit dem Bittermandelöl isomerische Verbindung von Liebig und Wöhler gewählt worden ist." (Since this liquid [benzene] is obtained from benzoic acid and probably is related to benzoyl compounds, the best name for it is "benzol", since the name "benzoïn" has already been chosen, by Liebig and Wöhler, for the compound that's isomeric with the oil of bitter almonds [benzaldehyde].)
^Laurent, (1836) "Sur la chlorophénise et les acides chlorophénisique et chlorophénèsique,"Annales de Chemie et de Physique, vol. 63, pp. 27–45, seep. 44Archived 2015-03-20 at theWayback Machine:"Je donne le nom de phène au radical fondamental des acides précédens (φαινω, j'éclaire), puisque la benzine se trouve dans le gaz de l'éclairage." (I give the name of "phène" (φαινω, I illuminate) to the fundamental radical of the preceding acids, because benzene is found in illuminating gas.)
^Charles Mansfield filed for (November 11, 1847) and received (May 1848) a patent (no. 11,960) for the fractional distillation of coal tar.
^Hoffman, Augustus W. (1856). "On insolinic acid".Proceedings of the Royal Society.8:1–3.doi:10.1098/rspl.1856.0002.S2CID97105342.The existence and mode of formation of insolinic acid prove that to the series of monobasic aromatic acids, Cn2Hn2-8O4, the lowest known term of which is benzoic acid, ... . [Note: The empirical formulas of organic compounds that appear in Hofmann's article (p. 3) are based upon an atomic mass of carbon of 6 (instead of 12) and an atomic mass of oxygen of 8 (instead of 16).]
^Cernicharo, José; et al. (2001), "Infrared Space Observatory's Discovery of C4H2, C6H2, and Benzene in CRL 618",Astrophysical Journal Letters,546 (2):L123 –L126,Bibcode:2001ApJ...546L.123C,doi:10.1086/318871
^Claus, Adolph K.L. (1867) "Theoretische Betrachtungen und deren Anwendungen zur Systematik der organischen Chemie" (Theoretical considerations and their applications to the classification scheme of organic chemistry),Berichte über die Verhandlungen der Naturforschenden Gesellschaft zu Freiburg im Breisgau (Reports of the Proceedings of the Scientific Society of Freiburg in Breisgau),4 : 116–381. In the sectionAromatischen Verbindungen (aromatic compounds), pp. 315–347, Claus presents Kekulé's hypothetical structure for benzene (p. 317), presents objections to it, presents an alternative geometry (p. 320), and concludes that his alternative is correct (p. 326). See also figures onp. 354 orp. 379.
^abKekulé, F. A. (1865)."Sur la constitution des substances aromatiques".Bulletin de la Société Chimique de Paris.3:98–110.Archived from the original on 2015-11-14. Retrieved2015-06-27. On p. 100, Kekulé suggests that the carbon atoms of benzene could form a "chaîne fermée" (closed chain).
^In his 1890 paper, Armstrong represented benzene nuclei within polycyclic benzenoids by placing inside the benzene nuclei a letter "C", an abbreviation of the word "centric". Centric affinities (i.e., bonds) acted within a designated cycle of carbon atoms. From p. 102: " ... benzene, according to this view, may be represented by a double ring, in fact." See:
^Loschmidt, J. (1861).Chemische Studien (in German). Vienna, Austria-Hungary: Carl Gerold's Sohn. pp. 30, 65.Archived from the original on 2016-05-07. Retrieved2015-06-27.
^English translationWilcox, David H.; Greenbaum, Frederick R. (1965). "Kekule's benzene ring theory: A subject for lighthearted banter".Journal of Chemical Education.42 (5):266–67.Bibcode:1965JChEd..42..266W.doi:10.1021/ed042p266.
^Benfey O. T. (1958). "August Kekulé and the Birth of the Structural Theory of Organic Chemistry in 1858".Journal of Chemical Education.35 (1):21–23.Bibcode:1958JChEd..35...21B.doi:10.1021/ed035p21.
^Gillis Jean (1966). "Auguste Kekulé et son oeuvre, réalisée à Gand de 1858 à 1867".Mémoires de la Classe des Sciences - Académie Royale des Sciences, des Lettres et des Beaux-arts de Belgique.37 (1):1–40.
^Wilhelm Körner (1867)"Faits pour servir à la détermination du lieu chimique dans la série aromatique"Archived 2017-07-07 at theWayback Machine (Facts to be used in determining chemical location in the aromatic series),Bulletins de l'Académie royale des sciences, des lettres et des beaux-arts de Belgique, 2nd series,24 : 166–185; see especially p. 169. From p. 169:"On distingue facilement ces trois séries, dans lesquelles les dérivés bihydroxyliques ont leurs terms correspondants, par les préfixes ortho-, para- et mêta-." (One easily distinguishes these three series – in which the dihydroxy derivatives have their corresponding terms – by the prefixes ortho-, para- and meta-.)
^Hermann von Fehling, ed.,Neues Handwörterbuch der Chemie [New concise dictionary of chemistry] (Braunschweig, Germany: Friedrich Vieweg und Sohn, 1874), vol. 1,p. 1142.
^Williams, P.R.D.; Knutsen, J.S.; Atkinson, C.; Madl, A.K.; Paustenbach, D.J. (2007). "Airborne Concentrations of Benzene Associated with the Historical Use of Some Formulations of Liquid Wrench".Journal of Occupational and Environmental Hygiene.4 (8):547–561.Bibcode:2007JOEH....4..547W.doi:10.1080/15459620701446642.PMID17558801.S2CID32311057.
^Chang, Kenneth (June 7, 2018)."Life on Mars? Rover's Latest Discovery Puts It 'On the Table'".The New York Times.Archived from the original on May 28, 2019. RetrievedJune 8, 2018.The identification of organic molecules in rocks on the red planet does not necessarily point to life there, past or present, but does indicate that some of the building blocks were present.
^Moran D, Simmonett AC, Leach FE, Allen WD, Schleyer PV, Schaefer HF (2006). "Popular Theoretical Methods Predict Benzene and Arenes To Be Nonplanar".Journal of the American Chemical Society.128 (29):9342–3.Bibcode:2006JAChS.128.9342M.doi:10.1021/ja0630285.PMID16848464.
^Stranks, D. R.; M. L. Heffernan; K. C. Lee Dow; P. T. McTigue; G. R. A. Withers (1970).Chemistry: A structural view.Carlton, Victoria: Melbourne University Press. p. 347.ISBN978-0-522-83988-3.
^US patent 5589600A, inventor list; Dostalek, Roman & Marosi Laszlo, "Preparation of cyclohexene by partial hydrogenation of benzene", issued 1996-12-31, assigned to BASF SE
^Kasper, Dennis L.et al. (2004)Harrison's Principles of Internal Medicine, 16th ed., McGraw-Hill Professional, p. 618,ISBN0071402357.
^"Public Health Statement for Benzene".Agency for Toxic Substances and Disease Registry. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health. August 2007.Archived from the original on 2012-01-20. Retrieved2011-11-23 – via Atsdr.cdc.gov.
^Fustinoni S, Buratti M, Campo L, Colombi A, Consonni D, Pesatori AC, Bonzini M, Farmer P, Garte S, Valerio F, Merlo DF, Bertazzi PA (2005). "Urinary t,t-muconic acid, S-phenylmercapturic acid and benzene as biomarkers of low benzene exposure".Chemico-Biological Interactions.153–154:253–6.Bibcode:2005CBI...153..253F.doi:10.1016/j.cbi.2005.03.031.PMID15935823.
^ACGIH (2009).2009 TLVs and BEIs. American Conference of Governmental Industrial Hygienists, Cincinnati, Ohio.
^Baselt, R. (2008)Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, pp. 144–148,ISBN0962652377.
^Dougherty, D; Garte, S; Barchowsky, A; Zmuda, J; Taioli, E (2008). "NQO1, MPO, CYP2E1, GSTT1 and STM1 polymorphisms and biological effects of benzene exposure—a literature review".Toxicology Letters.182 (1–3):7–17.doi:10.1016/j.toxlet.2008.09.008.PMID18848868.
^Fracasso ME, Doria D, Bartolucci GB, Carrieri M, Lovreglio P, Ballini A, Soleo L, Tranfo G, Manno M (2010). "Low air levels of benzene: Correlation between biomarkers of exposure and genotoxic effects".Toxicol Lett.192 (1):22–8.doi:10.1016/j.toxlet.2009.04.028.PMID19427373.
^Eastmond, D.A.; Rupa, DS; Hasegawa, LS (2000). "Detection of hyperdiploidy and chromosome breakage in interphase human lymphocytes following exposure to the benzene metabolite hydroquinone using multicolor fluorescence in situ hybridization with DNA probes".Mutat Res.322 (1):9–20.doi:10.1016/0165-1218(94)90028-0.PMID7517507.
^Garte, S; Taioli, E; Popov, T; Bolognesi, C; Farmer, P; Merlo, F (2000). "Genetic susceptibility to benzene toxicity in humans".J Toxicol Environ Health A.71 (22):1482–1489.doi:10.1080/15287390802349974.PMID18836923.S2CID36885673.
^ToxFAQs for Benzene, Agency for Toxic Substances and Disease Registry, Department of Health and Human Services
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