carbon, graphite. in heterocycles, carbon atoms in the benzene ring are replaced with other elements. the most important variations contain 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, or pyrazine. production four chemical processes contribute to industrial benzene production: catalytic reforming, toluene hydrodealkylation, toluene disproportionation, and steam cracking etc. according to the atsdr toxicological profile for benzene, between 1978 and 1981, catalytic reformates accounted for approximately 44–50% of the total u.s benzene production. catalytic reforming in catalytic reforming, a mixture of hydrocarbons with boiling points between 60 and 200 °c is blended with hydrogen gas and then exposed to a bifunctional platinum chloride or rhenium chloride catalyst 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) by extraction with any one of a number of solvents, including diethylene glycol or sulfolane, 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 as btx (benzene, toluene and xylene isomers), involves such extraction and distillation steps. in similar fashion to this catalytic reforming, uop and bp commercialized a method from lpg (mainly propane and butane) to aromatics. toluene hydrodealkylation toluene hydrodealkylation converts toluene to benzene. in this hydrogen-intensive process, toluene is mixed with hydrogen, then passed over a chromium, molybdenum, or platinum oxide 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 and methane: c 6 h 5 ch 3 + h 2 ⟶ c 6 h 6 + ch 4 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 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. toluene disproportionation toluene disproportionation (tdp) is the conversion of toluene to benzene and xylene. given that demand for para-xylene (p-xylene) substantially exceeds demand for other xylene isomers, a refinement of the tdp process called selective 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 steam cracking is the process for producing ethylene and other alkenes from aliphatic hydrocarbons. depending on the feedstock used to produce the olefins, steam cracking can produce a benzene-rich liquid by-product called pyrolysis gasoline. pyrolysis gasoline can be blended with other hydrocarbons as a gasoline additive, or routed through an extraction process to recover btx aromatics (benzene, toluene and xylenes). other methods although of no commercial significance, many other routes to benzene exist. phenol and halobenzenes can be reduced with metals. benzoic acid and its salts undergo decarboxylation to benzene. the reaction of the diazonium compound derived from aniline with hypophosphorus acid gives benzene. alkyne trimerisation of acetylene gives benzene. complete decarboxylation of mellitic acid gives benzene. uses benzene is used mainly as an intermediate to make other chemicals, above all ethylbenzene (and other alkylbenzenes), cumene, cyclohexane, and nitrobenzene. in 1988 it was reported that two-thirds of all chemicals on the american chemical society's lists contained at least one benzene ring. more than half of the entire benzene production is processed into ethylbenzene, a precursor to styrene, which is used to make polymers and plastics like polystyrene. some 20% of the benzene production is used to manufacture cumene, which is needed to produce phenol 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 of rubbers, lubricants, dyes, detergents, drugs, explosives, and pesticides. 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. 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. 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 most widely used antiknock additive. with the global phaseout of leaded gasoline, benzene has made a comeback as a gasoline additive in some nations. in the united states, concern over its negative health effects and the possibility of benzene entering the groundwater has led to stringent regulation of gasoline's benzene content, with limits typically around 1%. european petrol specifications now contain the same 1% limit on benzene content. the united states environmental protection agency introduced new regulations in 2011 that lowered the benzene content in gasoline to 0.62%. in many european languages, the word for petroleum or gasoline is an exact cognate of "benzene". reactions the most common reactions of benzene involve substitution of a proton by other groups. electrophilic aromatic substitution is a general method of derivatizing benzene. benzene is sufficiently nucleophilic that it undergoes 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. approximately 24,700,000 tons were produced in 1999. highly instructive but of far less industrial significance is the friedel-crafts alkylation of benzene (and many other aromatic rings) using an alkyl halide in the presence of a strong lewis acid catalyst. similarly, the friedel-crafts acylation is a related example of electrophilic aromatic substitution. the reaction involves the acylation of benzene (or many other aromatic rings) 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 is achieved with chlorine to give chlorobenzene in the presence of a lewis acid catalyst such as aluminium tri-chloride. hydrogenation via hydrogenation, benzene and its derivatives convert to cyclohexane and derivatives. this reaction is achieved by the use of high pressures of hydrogen in the presence of heterogeneous catalysts, such as finely divided nickel. whereas alkenes can be hydrogenated near room temperatures, benzene and related compounds are more reluctant substrates, requiring temperatures >100 °c. this reaction is practiced on a large scale industrially. in the absence of the catalyst, benzene is impervious to hydrogen. hydrogenation cannot be stopped to give cyclohexene or cyclohexadienes as these are superior substrates. birch reduction, a non catalytic process, however selectively hydrogenates benzene to the diene. metal complexes benzene is an excellent ligand in the organometallic chemistry of low-valent metals. important examples include the sandwich and half-sandwich complexes, respectively, cr(c6h6)2 and 2. health effects a bottle of benzene. the warnings show benzene is a toxic and flammable liquid. benzene is classified as a carcinogen, which increases the risk of cancer and other illnesses, and is also a notorious cause of bone marrow failure. substantial quantities of epidemiologic, clinical, and laboratory data link benzene to aplastic anemia, acute leukemia, bone marrow abnormalities and cardiovascular disease. 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). the american petroleum institute (api) stated as early as 1948 that "it is generally considered that the only absolutely safe concentration for benzene is zero". there is no safe exposure level; even tiny amounts can cause harm. the us 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 or acute nonlymphocytic leukemia (aml & anll) is caused by benzene. 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 cause dna strand breaks and chromosomal damage. 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. exposure to benzene according to the agency 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 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 and dermal absorption of benzene can also occur through contact with contaminated water. benzene is hepatically metabolized and excreted in the urine. measurement of air and water levels of benzene is accomplished through collection via activated charcoal tubes, which are then analyzed with a gas chromatograph. the measurement of benzene 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. exposure to benzene may lead progressively to aplastic anemia, leukaemia, and multiple myeloma. osha regulates levels of benzene in the workplace. the maximum allowable amount of benzene in workroom air during an 8-hour workday, 40-hour workweek is 1 ppm. 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 recommended (8-hour) exposure limit of 0.1 ppm. benzene exposure limits the united states environmental protection agency has set a maximum contaminant level for benzene in drinking water at 0.0005 mg/l (5 ppb), as promulgated via the u.s. national primary drinking water regulations. this regulation is based on preventing benzene leukemogenesis. 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. 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. the u.s. national institute for occupational safety and health (niosh) revised the