View source for Chloral hydrate

{{chembox
| verifiedrevid = 322110618
| ImageFile = Chloral-hydrate-montage.png
| ImageSize = 250px
| IUPACName = 2,2,2-trichloroethane-1,1-diol
| OtherNames = Trichloroacetaldehyde monohydrate<br/>'''Tradenames:''' Aquachloral, Novo-Chlorhydrate, Somnos, Noctec, Somnote
| Section1 = {{Chembox Identifiers
| InChIKey = RNFNDJAIBTYOQL-UHFFFAOYAY
| CASNo_Ref = {{cascite}}
| CASNo = 302-17-0
| ChemSpiderID  = 2606
| PubChem = 2707
| SMILES = ClC(Cl)(Cl)C(O)O
| InChI=1/C2H3Cl3O2/c3-2(4,5)1(6)7/h1,6-7H
 }}
| Section2 = {{Chembox Properties
| Formula = C<sub>2</sub>H<sub>3</sub>Cl<sub>3</sub>O<sub>2</sub>
| MolarMass = 165.40 g/mol
| Appearance = Colorless solid
| Density = 1.91 g/cm<sup>3</sup>
| MeltingPtC = 57
| BoilingPtC = 98
| Solubility = 
 }}
| Section5 = {{Chembox Pharmacology
| AdminRoutes = Oral codeine/syrup, rectal [[suppository]]
| Bioavail = well absorbed
| Metabolism = converted to trichloroethanol, hepatic and renal
| HalfLife = 8–10 hours in plasma
| ProteinBound =
| Excretion = bile, feces, urine (various metabolites not unchanged)
| Legal_status = 
| Legal_US = Schedule IV
| Legal_UK = 
| Legal_AU = 
| Legal_CA = 
| PregCat = 
| PregCat_AU = 
| PregCat_US = C}}
| Section7 = {{Chembox Hazards
| ExternalMSDS = [http://www.pcl.ox.ac.uk/MSDS/CH/chloral_hydrate.html External MSDS]
| EUClass = Harmful ('''Xn''')
| MainHazards = 
| FlashPt = 
| Autoignition = 
| RPhrases = {{R22}} {{R36}} {{R37}} {{R38}}
 }}
| Section8 = {{Chembox Other
| OtherCpds = [[Chloral]], [[chlorobutanol]]}}
}}

'''Chloral hydrate''' is a [[sedative]] and [[hypnotic]] [[approved drug|drug]] as well as a [[chemical reagent]] and precursor. The name chloral hydrate indicates that it is formed from [[chloral]] (trichloroacetaldehyde) by the addition of one molecule of water. Its [[chemical formula]] is [[Carbon|C]]<sub>2</sub>[[Hydrogen|H]]<sub>3</sub>[[Chlorine|Cl]]<sub>3</sub>[[Oxygen|O]]<sub>2</sub>.
 
It was discovered through the [[Halogenation|chlorination]] of [[ethanol]] in 1832 by [[Justus von Liebig]] in [[Gießen]].<ref>{{cite journal 
 | title = Ueber die Zersetzung des Alkohols durch Chlor 
 | author = Justus Liebig  
 | journal =  Annalen der Pharmacie
 | volume = 1 
 | issue = 1
 | pages = 31–32 
 | year = 1832 
 | url =  
 | doi = 10.1002/jlac.18320010109}}</ref><ref>{{cite journal 
 | title = Ueber die Verbindungen, welche durch die Einwirkung des Chlors auf Alkohol, Aether, ölbildendes Gas und Essiggeist entstehen 
 | author = Justus Liebig    
 | journal = Annalen der Pharmacie
 | volume = 1 
 | issue = 2
 | pages = 182–230 
 | year = 1832
 | url =  
 | doi = 10.1002/jlac.18320010203}}</ref> Its [[sedative]] properties were first published in 1869 and subsequently, because of its easy synthesis, its use was widespread.<ref>{{cite book
 | author = Liebreich, Oskar
 | title = Das Chloralhydrat : ein neues Hypnoticum und Anaestheticum und dessen Anwendung in der Medicin ; eine Arzneimittel-Untersuchung 
 | year = 1869
 | publisher = Müller
 |location= Berlin}}</ref> It was widely [[Recreational drug use|used recreationally]] and [[Medical prescription|misprescribed]] in the late 19th century.  Chloral hydrate is soluble in both water and [[Ethanol|alcohol]], readily forming concentrated solutions.  A solution of chloral hydrate in [[Ethanol|alcohol]] called "knockout drops" was used to prepare a [[Mickey Finn (drugs)|Mickey Finn]]. More reputable uses of chloral hydrate include its use as a clearing agent of [[chitin]] (and fibers) and as a key ingredient of Hoyer's mounting medium, which is used for slide-mounted observation of organisms under the [[microscope]].

It is, together with [[chloroform]], a minor [[side-product]] of the [[chlorination]] of [[water]] when organic residues are present in the water, though concentrations rarely exceed 5 [[microgram]]s per [[litre]] (µg/L).{{Citation needed|date=April 2010}}

==Production==
Chloral hydrate is produced from [[chlorine]] and [[ethanol]] in acidic solution. In basic conditions the [[haloform reaction]] takes place and [[chloroform]] is produced.

:4 Cl<sub>2</sub> + C<sub>2</sub>H<sub>5</sub>OH + H<sub>2</sub>O → Cl<sub>3</sub>CCH(OH)<sub>2</sub> + 5 HCl

==Uses==
===Building block===
Chloral hydrate is a starting point for the synthesis of more complex chemicals. It is the starting material for the production of [[chloral]], which is produced by the distillation of a mixture of chloral hydrate and [[sulfuric acid]], which serves as the [[desiccant]].

Notably, it is used to synthesize [[isatin]]. In this synthesis, chloral hydrate reacts with [[aniline]] and [[hydroxylamine]] to give a condensation product which cyclicizes in [[sulfuric acid]] to give the target compound:<ref>{{OrgSynth | title = Isatin | author = C. S. Marvel and G. S. Hiers | collvol = 1 | collvolpages = 327 | year = 1941 | prep = cv1p0327}}</ref>

[[Image:Synthesis of isatin.png|400px]]

===Hypnotic===
Chloral hydrate is used for the short-term treatment of [[insomnia]] and as a sedative before minor medical or dental treatment. It was largely displaced in the mid-20th century by [[barbiturate]]s<ref>Tariq, Syed H. and Shailaja Pulisetty; “Pharmacotherapy for Insomnia”, Clinics in Geriatric Medicine (24), 2008 p. 93-105 PMID: 18035234</ref> and subsequently by [[benzodiazepine]]s. It was also formerly used in veterinary medicine as a [[general anesthetic]].  Today, it is commonly used as an ingredient in the veterinary anesthetic [[Equithesin]]{{Citation needed|date=November 2008}}.  It is also still used as a sedative prior to [[Electroencephalography|EEG]] procedures, as it is one of the few available sedatives that does not suppress [[epilepsy|epileptiform]] discharges <ref>http://jcc.kau.edu.sa/Files/140/Researches/11822_Chloral.pdf</ref>.

In therapeutic doses for insomnia chloral hydrate is effective within sixty [[minute]]s, it is [[Metabolism|metabolized]] within 4 minutes into [[trichloroethanol]] by erythrocytes and plasma esterases and many hours later into [[trichloroacetic acid]]. Higher doses can depress [[Respiration (physiology)|respiration]] and [[blood pressure]].

==Adverse effects==
Long-term use of chloral hydrate is associated with a rapid development of [[Drug tolerance|tolerance]] to its effects as well as adverse effects including rashes, gastric discomfort and hepatic failure.<ref name="sleep_medicine_a04">{{Cite book | last1 = Lee-chiong | first1 = Teofilo | title = Sleep Medicine: Essentials and Review | date = 24 April 2008 | publisher = Oxford University Press, USA | url = http://books.google.com/?id=s1F_DEbRNMcC&pg=PT118 | isbn = 0-19-530659-7 | page = 118 }}</ref>

==Overdosage==
Acute overdosage is often characterized by [[nausea]], [[vomiting]], confusion, [[convulsion]]s, slow and irregular breathing, [[cardiac arrhythmia]] and coma. The plasma, serum or blood concentrations of chloral hydrate and/or trichloroethanol, its major active metabolite, may be measured to confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. Accidental overdosage of young children undergoing simple dental or surgical procedures has occurred. Hemodialysis has been used successfully to accelerate clearance of the drug in poisoning victims.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 259-261.</ref>

==Pharmacology==
Chloral hydrate exerts its pharmacological properties via enhancing the GABA receptor complex.<ref>{{cite journal |pmid=17557503 |year=2006 |last1=Lu |first1=J |last2=Greco |title=Sleep circuitry and the hypnotic mechanism of GABAA drugs. |volume=2 |issue=2 |pages=S19–26 |journal=Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine |first2=MA }}</ref> It is moderately [[Substance_use_disorder|addictive]], as [[chronic (medicine)|chronic]] use is known to cause [[Chemical dependency|dependency]] and [[withdrawal]] symptoms. The chemical can potentiate various [[anticoagulant]]s and is weakly [[mutagen]]ic [[in vitro]] and [[in vivo]].{{Citation needed|date=December 2007}}

==Legal status==
Chloral hydrate is now illegal in the United States without a prescription. Chloral hydrate is a [[Schedule IV (US)|schedule IV]] [[controlled substance]] in the [[United States]]. Its properties have sometimes led to its use as a [[date rape drug]].<ref>[http://www.nydailynews.com/news/ny_crime/2008/10/25/2008-10-25_attacked_by_the_gang.html?page=0 New York Daily News, 10/25/2008]</ref> Chloral hydrate is not a controlled substance in the United Kingdom.

==Hoyer's Mounting Medium==
Chloral hydrate is also an ingredient used for Hoyer's solution, a slide-mounting medium for microscopic observation of diverse organisms such as bryophytes, ferns, seeds, and small arthropods (especially mites). One recipe for making Hoyer's is dissolving gum arabic (30.0&nbsp;g) in water (50.0&nbsp;mL), then adding chloral hydrate (200.0&nbsp;g), and then finally adding glycerol (16.0&nbsp;mL). An advantage of this medium include an excellent refraction index and clearing (macerating) properties of the small specimens (especially advantageous if specimens require observation with [[differential interference contrast microscopy]]). The major disadvantage of Hoyer's is its susceptibility to the effects of dehydration, which causes the mountant to crystallize and threatening the slide to become unusable. It is therefore absolutely necessary, after drying a mounted specimen, to thoroughly ring (2 layers are best) cover slips with a protective coating (e.g., insulating [[Glyptol]]), which prevents rehydration and mountant deterioration. Chloral hydrate reportedly does not effectively clear larger specimens, or arthropods that are more heavily sclerotized (e.g., larger insects). These should first be cleared with another product (e.g., 10%&nbsp;[[potassium chloride|KCl]]), and then mounted in Hoyer's. Other disadvantages of Hoyer's (principally due to chloral hydrate) include toxicity (see above), and procurement problems due to chloral hydrate being a controlled substance.

==See also==
*Initiating the [[Jonestown]] Massacre, and metal vat with [[Flavor Aid]], poisoned with [[diazepam|Valium]], chloral hydrate, [[potassium cyanide|cyanide]] and [[Phenergan]], which was then consumed orally.
*[[Jennie Bosschieter]] (1882–1900) who was murdered with chloral hydrate in [[Paterson, New Jersey]] on 12 October 1900.
*[[John Tyndall]] (1820–1893) who died of an accidental overdose.
*[[Anna Nicole Smith]] (1967–2007) who died of an accidental<ref>[http://www.thesmokinggun.com/archive/years/2007/0326074report14.html Anna Nicole Smith Autopsy Report. XI. Manner of death. A. The Exclusion of Homicide] The Smoking Gun</ref> combination of chloral hydrate with three [[benzodiazepine]]s, as announced by forensic pathologist Dr. [[Joshua Perper]] on 26 March 2007. Chloral hydrate was the major factor, but none of these drugs would have been sufficient by itself to cause her death.<ref>[http://www.thesmokinggun.com/archive/years/2007/0326071anna1.html Anna Nicole Smith Autopsy Released. Coroner: Ex-Playmate died from accidental sedative overdose] The Smoking Gun</ref>
*[[Marilyn Monroe]] had chloral hydrate in her system at her death.
*[[Hank Williams]] came under the spell of a man calling himself "Doctor" Toby Marshall (actually a paroled forger), who often supplied him with prescriptions and injections of chloral hydrate, which Marshall claimed was a pain reliever.<ref>[http://www.bookrags.com/Hank_Williams Hank Williams summary] Book Rags</ref>
*[[William S. Burroughs]] was expelled from school for experimenting with chloral hydrate along with another pupil. The incident is detailed in the writer's foreword to [[Junkie (novel)|Junkie]].
*[[Mary Todd Lincoln]] was given chloral hydrate for sleep problems.  See ''Mary Todd Lincoln'' by Jean Baker and ''Mary: Mrs. A. Lincoln'', by Janis Cooke Newman.
*[[André Gide]] (1869–1951) was given chloral hydrate as a boy for sleep problems by a Doctor named Lizart. Gide states in his autobiography, ''If It Die...'' that "all my later weaknesses of will or memory I attribute to him."<ref>Gide, André and Dorothy Bussey (trans). ''If It Die…An Autobiography''. New York: Vintage International, 2001. p105</ref>
*''[[House of Mirth]]'' (published in 1905), a novel whose heroine, Lily Bart, dies of an overdose of chloral hydrate.
*[[Dante Gabriel Rossetti]] (1830–1882), the English painter, was a regular user of chloral hydrate, originally against insomnia.  He is quoted as saying to his friend [[Hall Caine]]: 'Everyone has skeletons in their cupboards, and this is mine.'
*[[James Bond]] says, "that's...chloral hydrate" in the movie "The Living Daylights" before collapsing from its effects.
*In the movie ''[[From Russia with Love]]'', Tatiana Romanava is knocked out by chloral hydrate, which SPECTRE agent Red Grant slips in her drink.

==Notes==
{{reflist}}

==External links==
{{Commons category-inline|Chloral hydrate}}

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{{Sedative|state=collapsed}}

[[Category:Aldehydes]]
[[Category:Hydrates]]
[[Category:Hypnotics]]
[[Category:Sedatives]]
[[Category:Organochlorides]]

[[de:Chloralhydrat]]
[[es:Hidrato de cloral]]
[[fr:Hydrate de chloral]]
[[hi:क्लोराल हाइड्रेट]]
[[nl:Chloraalhydraat]]
[[ja:抱水クロラール]]
[[no:Kloralhydrat]]
[[pl:Wodzian chloralu]]
[[pt:Hidrato de cloral]]
[[ru:Хлоралгидрат]]
[[sr:Хлорал хидрат]]
[[fi:Kloraalihydraatti]]
[[sv:Kloralhydrat]]
[[tr:Kloralhidrat]]
[[zh:水合氯醛]]
[[Category:2Fix]]