View source for Organochlorine chemistry

{{Short description|Organic compound containing at least one covalent carbon-chlorine bond}}
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'''Organochlorine chemistry''' is concerned with the properties of '''organochlorine compounds''', or '''organochlorides''', [[organic compounds]] that contain one or more [[carbon]]–[[chlorine]] [[Chemical bond|bond]]s.<ref name=chebi>{{Cite web |title=organochlorine compound (CHEBI:36683) |work=[[ChEBI]] |access-date=10 January 2025 |url=https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:36683}}</ref> The '''chloroalkane''' class ([[alkane]]s with one or more hydrogens substituted by chlorine) includes common examples. The wide structural variety and divergent chemical properties of organochlorides lead to a broad range of names, applications, and properties. Organochlorine compounds have wide use in many applications, though some are of profound environmental concern, with [[2,3,7,8-Tetrachlorodibenzodioxin|TCDD]] being one of the most notorious.<ref name=Ullmann/>

Organochlorides such as [[trichloroethylene]], [[tetrachloroethylene]], [[dichloromethane]] and [[chloroform]] are commonly used as solvents and are referred to as "chlorinated solvents".{{cn|date=January 2025}}

==Physical and chemical properties==
[[Chlorination reaction|Chlorination]] modifies the physical properties of hydrocarbons in several ways. These compounds are typically denser than [[water]] due to the higher atomic weight of chlorine versus hydrogen. They have higher boiling and melting points compared to related hydrocarbons. Flammability reduces with increased chlorine substitution in hydrocarbons.{{cn|date=January 2025}}

Aliphatic organochlorides are often [[alkylating agent]]s as chlorine can act as a [[leaving group]], which can result in cellular damage.{{cn|date=January 2025}}

==Natural occurrence==
Many organochlorine compounds have been isolated from natural sources ranging from bacteria to humans.<ref name=Wagner>{{cite journal | title = Biohalogenation: Nature's Way to Synthesize Halogenated Metabolites | author = Claudia Wagner, Mustafa El Omari, Gabriele M. König | journal = J. Nat. Prod. | volume = 72| pages = 540–553 | year = 2009| issue = 3 | doi = 10.1021/np800651m| pmid = 19245259 }}</ref><ref name="Gribble99">{{cite journal | title = The diversity of naturally occurring organobromine compounds | author = Gordon W. Gribble | journal = [[Chemical Society Reviews]] | volume = 28 | issue = 5 | pages = 335–346| year = 1999 | doi = 10.1039/a900201d}}</ref> Chlorinated organic compounds are found in nearly every class of biomolecules and [[natural product]]s including [[alkaloid]]s, [[terpene]]s, [[amino acid]]s, [[flavonoid]]s, [[steroid]]s, and [[fatty acid]]s.<ref name=Wagner/><ref>{{cite journal | author = Kjeld C. Engvild | title = Chlorine-Containing Natural Compounds in Higher Plants | journal = [[Phytochemistry (journal)|Phytochemistry]] | volume = 25 | issue = 4 | pages = 7891–791 | year = 1986 | doi=10.1016/0031-9422(86)80002-4| bibcode = 1986PChem..25..781E }}</ref> [[Polychlorinated dibenzodioxins|Dioxins]], which are of particular concern to human and environmental health, are produced in the high temperature environment of forest fires and have been found in the preserved ashes of lightning-ignited fires that predate synthetic dioxins.<ref>{{cite journal|author=Gribble, G. W.|year=1994|title=The Natural production of chlorinated compounds|journal=Environmental Science and Technology|volume=28|pages=310A–319A|doi=10.1021/es00056a712|issue=7|pmid=22662801|bibcode=1994EnST...28..310G}}</ref> In addition, a variety of simple chlorinated hydrocarbons including [[dichloromethane]], [[chloroform]], and [[carbon tetrachloride]] have been isolated from marine algae.<ref>{{cite journal | doi = 10.1021/np50088a001 | author = Gribble, G. W. | title = Naturally occurring organohalogen compounds - A comprehensive survey | journal = Progress in the Chemistry of Organic Natural Products | year = 1996 | volume = 68 | pages = 1–423 | pmid = 8795309 | issue = 10}}</ref> A majority of the [[chloromethane]] in the environment is produced naturally by biological decomposition, forest fires, and volcanoes.<ref>[http://www.atsdr.cdc.gov/toxprofiles/tp106-c1-b.pdf Public Health Statement - Chloromethane], [[Centers for Disease Control]], Agency for Toxic Substances and Disease Registry</ref>

The natural organochloride [[epibatidine]], an alkaloid isolated from tree frogs, has potent [[analgesic]] effects and has stimulated research into new pain medication. However, because of its unacceptable [[therapeutic index]], it is no longer a subject of research for potential therapeutic uses.<ref name=Schwarcz>{{cite book|author=Schwarcz, Joe|year=2012|title=The Right Chemistry |publisher= Random House|isbn = 9780385671606}}</ref>  The frogs obtain epibatidine through their diet which is then sequestered into their skin. Likely dietary sources are beetles, ants, mites, and flies.<ref name="E.N. Lasley (1999)">{{Cite journal|title=Having Their Toxins and Eating Them Too Study of the natural sources of many animals' chemical defenses is providing new insights into nature's medicine chest |journal=BioScience |author=Elizabeth Norton Lasley |volume=45 |issue=12 |pages=945–950 |doi=10.1525/bisi.1999.49.12.945 |year=1999 |doi-access= }}</ref>

==Preparation==

===From chlorine===
[[Alkanes]] and [[aryl]] alkanes may be chlorinated under free radical conditions, with UV light. However, the extent of chlorination is difficult to control. Aryl chlorides may be prepared by the [[Friedel-Crafts halogenation]], using chlorine and a [[Lewis acid]] catalyst.<ref name=Ullmann/>

The [[haloform reaction]], using chlorine and [[sodium hydroxide]], is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.{{cn|date=January 2025}}

Chlorine adds to the multiple bonds on alkenes and alkynes as well, giving di- or tetra-chloro compounds.{{cn|date=January 2025}}

===Reaction with hydrogen chloride===
Alkenes react with [[hydrogen chloride]] (HCl) to give alkyl chlorides. For example, the industrial production of [[chloroethane]] proceeds by the reaction of [[ethylene]] with HCl:{{cn|date=January 2025}}
:H<sub>2</sub>C=CH<sub>2</sub> + HCl → CH<sub>3</sub>CH<sub>2</sub>Cl

In [[oxychlorination]], hydrogen chloride instead of the more expensive chlorine is used for the same purpose:
:CH<sub>2</sub>=CH<sub>2</sub> + 2 HCl + {{frac|2}} O<sub>2</sub> → ClCH<sub>2</sub>CH<sub>2</sub>Cl + [[water|H<sub>2</sub>O]].

Secondary and tertiary alcohols react with hydrogen chloride to give the corresponding chlorides.  In the laboratory, the related reaction involving [[zinc chloride]] in concentrated [[hydrochloric acid]]:
: <chem>{R-OH} + HCl ->[\ce{ZnCl2}] [\Delta] \overset{alkyl\ halide}{R-Cl} + H2O</chem>
Called the [[Lucas reagent]], this mixture was once used in [[qualitative organic analysis]] for classifying alcohols.

===Other chlorinating agents===
Alkyl chlorides are most easily prepared by treating alcohols with [[thionyl chloride]] (SOCl<sub>2</sub>) or [[phosphorus pentachloride]] (PCl<sub>5</sub>), but also commonly with sulfuryl chloride (SO<sub>2</sub>Cl<sub>2</sub>) and [[phosphorus trichloride]] (PCl<sub>3</sub>):
:ROH + SOCl<sub>2</sub> → RCl + SO<sub>2</sub> + HCl
:3 ROH + PCl<sub>3</sub> → 3 RCl + H<sub>3</sub>PO<sub>3</sub>
:ROH + PCl<sub>5</sub> → RCl + POCl<sub>3</sub> + HCl

In the laboratory, thionyl chloride is especially convenient, because the byproducts are gaseous.  Alternatively, the [[Appel reaction]] can be used:

:[[File:Appel reaction.svg|250px]]

==Reactions==
Alkyl chlorides are versatile building blocks in organic chemistry. While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available. Alkyl chlorides readily undergo attack by nucleophiles.{{cn|date=January 2025}}

Heating alkyl halides with [[sodium hydroxide]] or [[water]] gives alcohols. Reaction with [[alkoxide]]s or [[aryloxide]]s give [[ether]]s in the [[Williamson ether synthesis]]; reaction with [[thiol]]s give [[thioether]]s. Alkyl chlorides readily react with [[amine]]s to give substituted [[amine]]s. Alkyl chlorides are substituted by softer halides such as the [[iodide]] in the [[Finkelstein reaction]]. Reaction with other [[pseudohalide]]s such as [[azide]], [[cyanide]], and [[thiocyanate]] are possible as well. In the presence of a strong base, alkyl chlorides undergo dehydrohalogenation to give [[alkene]]s or [[alkyne]]s.{{cn|date=January 2025}}

Alkyl chlorides react with [[magnesium]] to give [[Grignard reagent]]s, transforming an [[electrophilic]] compound into a [[nucleophilic]] compound. The [[Wurtz reaction]] reductively couples two alkyl halides to couple with [[sodium]].{{cn|date=January 2025}}

Some organochlorides (such as [[ethyl chloride]]) may be used as [[alkylating agent]]s. [[Tetraethyllead]] was produced from [[ethyl chloride]] and a [[sodium]]–[[lead]] [[alloy]]:<ref name="Seyferth">{{cite journal |last= Seyferth |first=D. |title= The Rise and Fall of Tetraethyllead. 2 |journal= [[Organometallics]] |year= 2003 |volume= 22 |pages= 5154–5178 |doi= 10.1021/om030621b |issue= 25|doi-access=  }}</ref><ref name="Jewkes">{{cite book |last1=Jewkes |first1=John |last2=Sawers |first2=David |last3=Richard |first3=Richard |title=The sources of invention |date=1969 |publisher=W. W. Norton |location=New York |isbn=978-0-393-00502-8 |pages=[https://archive.org/details/sourcesofinventi0000jewk_x4v4/page/235 235]–237 |edition=2nd |url=https://archive.org/details/sourcesofinventi0000jewk_x4v4 |url-access=registration |access-date=11 July 2018}}</ref>
{{block indent|4 NaPb + 4 CH{{sub|3}}CH{{sub|2}}Cl → Pb(CH{{sub|3}}CH{{sub|2}}){{sub|4}} + 4 NaCl + 3 Pb}}

[[Reductive dechlorination]] is rarely useful in chemical synthesis, but is a key step in the [[biodegradation]] of several organochlorine [[persistent pollutant]]s.{{refneeded|date=September 2024}}

==Applications==

===Vinyl chloride===
The largest application of organochlorine chemistry is the production of [[vinyl chloride]]. The annual production in 1985 was around 13 million tons, almost all of which was converted into [[polyvinylchloride]] (PVC).{{cn|date=January 2025}}

===Chlorinated solvents===
Most low molecular weight and liquid chlorinated hydrocarbons such as [[dichloromethane]], [[chloroform]], [[carbon tetrachloride]], [[dichloroethylene]], [[trichloroethylene]], [[tetrachloroethylene]], [[1,2-Dichloroethane]] and [[hexachlorobutadiene]] are useful solvents. These solvents tend to be relatively [[chemical polarity|non-polar]]; they are therefore immiscible with water and effective in cleaning applications such as [[degreasing]] and [[dry cleaning]] for their ability to dissolve [[oil]]s and [[Grease (lubricant)|grease]]. They are mostly nonflammable or have very low flammability.{{cn|date=January 2025}}

Some, like carbon tetrachloride and [[1,1,1-Trichloroethane]]  have been phased out due to their toxicity or negative environmental impact (ozone depletion by 1,1,1-Trichloroethane).{{cn|date=January 2025}}

===Chloromethanes===
Several billion kilograms of chlorinated methanes are produced annually, mainly by chlorination of methane:
:CH<sub>4</sub> + x Cl<sub>2</sub> → CH<sub>4−x</sub>Cl<sub>x</sub> + x HCl

The most important is dichloromethane, which is mainly used as a solvent. Chloromethane is a precursor to [[chlorosilane]]s and [[silicone]]s. Historically significant (as an anaesthetic), but smaller in scale is chloroform, mainly a precursor to [[chlorodifluoromethane]] (CHClF<sub>2</sub>) and [[tetrafluoroethene]] which is used in the manufacture of Teflon.<ref name=Ullmann>{{Ullmann|title=Chlorinated Hydrocarbons|year=2006|doi=10.1002/14356007.a06_233.pub2||last1=Rossberg|first1=Manfred|last2=Lendle|first2=Wilhelm|last3=Pfleiderer|first3=Gerhard|last4=Tögel|first4=Adolf|last5=Dreher|first5=Eberhard-Ludwig|last6=Langer|first6=Ernst|last7=Rassaerts|first7=Heinz|last8=Kleinschmidt|first8=Peter|last9=Strack|first9=Heinz|last10=Cook|first10=Richard|last11=Beck|first11=Uwe|last12=Lipper|first12=Karl-August|last13=Torkelson|first13=Theodore R.|last14=Löser|first14=Eckhard|last15=Beutel|first15=Klaus K.|last16=Mann|first16=Trevor|isbn=3527306730}}</ref>

===Pesticides===
{{also|Insecticide#Organochlorides}}
The two main groups of organochlorine [[insecticide]]s are the [[DDT]]-type compounds and the chlorinated [[alicyclic]]s.
Their mechanism of action differs slightly.
* The DDT like compounds work on the [[peripheral nervous system]].  At the axon's [[sodium channel#Voltage-gated|sodium channel]], they prevent gate closure after activation and membrane [[depolarization]].  Sodium ions leak through the nerve membrane and create a destabilizing negative "afterpotential" with hyperexcitability of the nerve. This leakage causes repeated discharges in the neuron either spontaneously or after a single stimulus.<ref name=coats>{{cite journal|author1=J R Coats|title=Mechanisms of toxic action and structure-activity relationships for organochlorine and synthetic pyrethroid insecticides.|journal=Environmental Health Perspectives|date=July 1990|volume=87|pages=255–262|pmc=1567810|pmid=2176589|doi=10.1289/ehp.9087255|bibcode=1990EnvHP..87..255C }}</ref>{{rp|255}}
* Chlorinated cyclodienes include [[aldrin]], [[dieldrin]], [[endrin]], [[heptachlor]], [[chlordane]] and [[endosulfan]]. A 2- to 8-hour exposure leads to depressed [[central nervous system]] (CNS) activity, followed by hyperexcitability, tremors, and then seizures. The mechanism of action is the insecticide binding at the [[GABAA receptor|GABA<sub>A</sub>]] site in the [[GABAA receptor negative allosteric modulator|GABA-gated chloride channel]] [[Insecticide Resistance Action Committee#Table of modes of action and classes of insecticide|(IRAC]] group 2A), which inhibits chloride flow into the nerve.<ref name=coats/>{{rp|257}}
* Other examples include [[dicofol]], [[mirex]], [[kepone]], and [[pentachlorophenol]].  These can be either [[hydrophilic]] or [[hydrophobic]], depending on their molecular structure.<ref name=Ullmann2>Robert L. Metcalf "Insect Control" in ''Ullmann's Encyclopedia of Industrial Chemistry'' Wiley-VCH, Wienheim, 2002.  {{doi|10.1002/14356007.a14_263}}</ref>
[[file:Mirex.svg|thumb|Structure of mirex, a perchlorocarbon used as a pesticide]]

===Insulators===
[[Polychlorinated biphenyl]]s (PCBs) were once commonly used electrical insulators and heat transfer agents.  Their use has generally been phased out due to health concerns. PCBs were replaced by [[polybrominated diphenyl ethers]] (PBDEs), which bring similar toxicity and [[bioaccumulation]] concerns. {{Citation needed|date=May 2024}}

==Toxicity==
Some types of organochlorides have significant toxicity to plants or animals, including humans.  Dioxins, produced when organic matter is burned in the presence of chlorine, are [[persistent organic pollutant]]s which pose dangers when they are released into the environment, as are some insecticides (such as [[DDT]]).  For example, DDT, which was widely used to control insects in the mid-20th century, also accumulates in food chains, as do its metabolites [[Dichlorodiphenyldichloroethylene|DDE]] and [[Dichlorodiphenyldichloroethane|DDD]], and causes reproductive problems (e.g., eggshell thinning) in certain bird species.<ref>{{cite book | title=Introduction to Ecotoxicology | publisher=Blackwell Science | year=1999 | isbn=978-0-632-03852-7 | page=68 | author=Connell, D.|display-authors=etal}}</ref> DDT also posed further issues to the environment as it is extremely mobile, traces even being found in Antarctica despite the chemical never being used there. Some organochlorine compounds, such as [[sulfur mustard]]s, [[nitrogen mustard]]s, and [[Lewisite]], are even used as [[chemical weapon]]s due to their toxicity.{{cn|date=January 2025}}

However, the presence of chlorine in an organic compound does not ensure toxicity.  Some organochlorides are considered safe enough for consumption in foods and medicines. For example, peas and broad beans contain the natural chlorinated plant hormone [[4-chloroindole-3-acetic acid]] (4-Cl-IAA);<ref>{{cite journal |title=Occurrence of 4-Cl-indoleacetic acid in broad beans and correlation of its levels with seed development |journal=Plant Physiology |year=1984 |volume=74 |issue=2 |pages=320–3 | pmc = 1066676 |doi=10.1104/pp.74.2.320 |last1=Pless |first1=Tanja |last2=Boettger |first2=Michael |last3=Hedden |first3=Peter |last4=Graebe |first4=Jan |pmid=16663416}}</ref><ref>{{cite journal |title=4-chloroindole-3-acetic and indole-3-acetic acids in ''Pisum sativum'' |journal = [[Phytochemistry (journal)|Phytochemistry]] |year=1997 |volume=46 |issue=4 |pages=675–681 |doi=10.1016/S0031-9422(97)00229-X |last1=Magnus |first1=Volker |last2=Ozga |first2=Jocelyn A |last3=Reinecke |first3=Dennis M |last4=Pierson |first4=Gerald L |last5=Larue |first5=Thomas A |last6=Cohen |first6=Jerry D |last7=Brenner |first7=Mark L|doi-access=free |bibcode = 1997PChem..46..675M }}</ref> and the sweetener [[sucralose]] (Splenda) is widely used in diet products. {{As of|2004}}, at least 165 organochlorides had been approved worldwide for use as pharmaceutical drugs, including the natural antibiotic [[vancomycin]], the antihistamine [[loratadine]] (Claritin), the antidepressant [[sertraline]] (Zoloft), the anti-epileptic [[lamotrigine]] (Lamictal), and the inhalation anesthetic [[isoflurane]].<ref>MDL Drug Data Report (MDDR), Elsevier MDL, version 2004.2</ref>

== See also ==
* [[Organic halide]]

== References ==<!-- ZoolRes29:159. -->
{{reflist}}

==External links==
* [http://www-ssrl.slac.stanford.edu/research/highlights_archive/organo-Cl_compounds.html "Formation of Chlorinated Hydrocarbons in Weathering Plant Material" article at SLAC website]
* [https://web.archive.org/web/20060907135158/http://www.chem.cmu.edu/groups/collins/about/members/colin_horwitz/hydro.html "The oxidation of chlorinated hydrocarbons" article from The Institute for Green Oxidation Chemistry at the Carnegie Mellon University website]
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[[Category:Organochlorides| ]]