Chloral hydrate

Structural formula
General
Non-proprietary name	Chloral hydrate
other names	Trichloroaldehyde hydrate 2,2,2-trichloroacetaldehyde hydrate 2,2,2-trichloro-1,1-ethanediol
Molecular formula	C 2 H 3 Cl 3 O 2
Brief description	colorless transparent crystals with a pungent odor
External identifiers / databases
CAS number 302-17-0 EC number 206-117-5 ECHA InfoCard 100.005.562 PubChem 2707 DrugBank DB01563 Wikidata Q412340
Drug information
ATC code	N05 CC01
Drug class	Hypnotics
properties
Molar mass	165.40 g · mol -1
Physical state	firmly
density	1.91 g cm −3 (20 ° C)
Melting point	52 ° C
boiling point	97 ° C (decomposition)
Vapor pressure	9.9 mmHg (20 ° C)
solubility	very light in water (6600 g l −1 at 20 ° C) soluble in diethyl ether and ethanol
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary danger H and P phrases H: 301-315-319 P: 301 + 310-305 + 351 + 338
Toxicological data	479 mg kg −1 ( LD 50 ,  rat ,  oral ) 3030 mg kg −1 ( LD 50 ,  rat ,  transdermal )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Chloral hydrate was the first synthetically produced sleep aid . It is formed when chloral reacts with water and therefore belongs to the group of aldehyde hydrates .

discovery

Chloral hydrate crystals

Chloral hydrate was first produced by Justus von Liebig in 1832 . In 1869, Oskar Liebreich tested it for its suitability as a sleeping aid on the erroneous assumption that it would be converted into chloroform in the body , as it was known that chloral hydrate breaks down into chloroform and formate in the presence of alkalis (cf. haloform reaction ). Chloral hydrate was one of the first products of the chemical factory founded in Berlin in 1873 by the chemist Heinrich Byk . Chloral hydrate was as widespread as the later benzodiazepines . In the first 18 months after its introduction, 17 million single doses were used in England.

Manufacturing

Chloral hydrate can be produced directly from chlorine and ethanol in acidic solution both industrially and on a laboratory scale. The reaction takes place via the oxidation and subsequent chlorination of ethanol with elemental chlorine; the chloral formed then reacts with water to form chloral hydrate:

${\displaystyle \mathrm {C_{2}H_{5}OH+4\,Cl_{2}\rightarrow CCl_{3}CHO+5\,HCl} }$

${\displaystyle \mathrm {CCl_{3}CHO+H_{2}O\rightarrow CCl_{3}CH(OH)_{2}} }$

application

Chloral hydrate is converted in the body into 2,2,2-trichloroethanol as the main active ingredient. It is mainly used in older patients, as they sometimes react paradoxically to benzodiazepines. As with other organic halogen compounds, there is a risk of sensitization of the heart muscle to catecholamines . Due to the side effects and the danger of addiction it emanates ( chloralism ), chloral hydrate requires a prescription and is no longer of great importance today.

In the past, chloral hydrate was sometimes used to treat whooping cough , neuralgia , Huntington's disease (St. Vitus's dance) and seasickness . It was used externally to treat wounds and ulcers. In veterinary medicine it was used as a narcotic .

The mechanism of action is based on a GABAa receptor complex with enhancement of the GABA effect. Chloral hydrate does not affect the sleep profile and has a rapid onset of action.

Chloral hydrate is still used today as a plant brightener in microscopy for determining / interpreting parts of plants. When heated, it destroys the coloring plastids such as chloro- or amyloplasts. In addition, the air that interferes with microscopy is expelled so that plant-specific cells can be better identified. Because of its tissue-whitening effect, it is also an essential component of tissue preparations of the type of gum arabic-chloral hydrate mixtures used in entomology.

Of chloral hydrate and glucose is rodenticide chloralose [(2,2,2-trichloroethylidene) -α- D -glucofuranose] is produced.

Specialty

Chloral hydrate is one of the few compounds that contradict the Erlenmeyer rule. According to this rule, two hydroxyl groups on the same carbon atom ( geminal diol ) are not stable and usually lead to the splitting off of water. However, the strong −I effect of the three chlorine atoms on the neighboring carbon atom prevents this reaction and stabilizes the molecule.

Trade names

Monopreparations

Germany: Chloraldurate 500 and 250 mg: soft gelatine capsules for the short-term treatment of sleep disorders. Chloraldurate blue 250 mg: gastric juice-resistant soft gelatin capsules for the short-term treatment of sleep disorders without sleep disorders.

Switzerland: Chloraldurate red 500 and 250 mg: capsules for the short-term treatment of sleep disorders requiring therapy. Nervifene solution: For sleep and falling asleep disorders.

safety instructions

The IARC classified chloral hydrate as likely carcinogenic in 2014.

Others

John Tyndall , a well-known British physicist, died on December 4, 1893 at his Hind Head country estate near Haslemere as a result of an accidental overdose of chloral hydrate.

Also Antonin Artaud died on March 4, 1948 probably by overdose of chloral hydrate.

Individual evidence

1. ↑ ^{a b} Entry on chloral hydrate. In: Römpp Online . Georg Thieme Verlag, accessed on November 11, 2014.
2. ↑ ^{a b c d e f g h} Entry on chloral hydrate in the GESTIS substance database of the IFA , accessed on January 10, 2017(JavaScript required) .
3. ↑ Chemical Industry Association, VNCI, the Netherlands: Chemical Safety Sheets: Working Safely with Hazardous Chemicals . Springer Science & Business Media, 2012, ISBN 978-94-011-3256-5 ( books.google.com ).
4. ↑ Entry on 2,2,2-trichloroethane-1,1-diol in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
5. ↑ Entry on chloral hydrate in the ChemIDplus database of the United States National Library of Medicine (NLM) .
6. ↑ Harry Auterhoff : Textbook of pharmaceutical chemistry. Scientific publishing company, Stuttgart 1968.
7. ↑ Peter Oehme : Oscar Liebreich and his chloral hydrate. Milestones in pharmacology in Berlin. Deutsche Apotheker Zeitung, Volume 159, January 24, 2019, No. 4, pp. 56–60.
8. ^ Ernst Peter Fischer: Byk Gulden. Inquiry and entrepreneurship. 2nd edition, Piper, Munich 1998. ISBN 3-492-04073-X .
9. ↑ Hans Bangen: History of the drug therapy of schizophrenia. Berlin 1992, p. 22, ISBN 3-927408-82-4 .
10. ↑ Patent US2443183 : Process for chlorination of ethanol. Published June 15, 1948 , inventor: Oliver W Cass. ‌
11. ↑ Wolfram Braune, Alfred Leman, Hans Taubert: Plant anatomical internship I: For an introduction to the anatomy of ... Springer DE, 2009, ISBN 3-8274-2289-2 , p. 317 ( limited preview in Google Book search).
12. ^ Murray S. Upton: Aqueous gum-chloral slide mounting media: an historical review . Bulletin of Entomological Research 83, 267-274.
13. ↑ Red List 2009.
14. ↑ Medicinal Compendium d. Switzerland Online, as of October 2009.
15. ↑ IARC Monograph 106 - Chloral Hydrate, 2014

Web links

Commons : Chloral hydrate  - Collection of pictures, videos and audio files

• Chloral hydrate . In: Erowid . (English)
• Lueger: Lexicon of all technology

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !