 | |
| Names | |
|---|---|
| IUPAC name 2,4,6-Trimethyl-1,3,5-trioxane | |
| Systematic IUPAC name 2,4,6-Trimethyl-1,3,5-trioxane | |
| Identifiers | |
| |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
|
| ECHA InfoCard | 100.004.219 |
| EC Number |
|
| KEGG |
|
| MeSH | Paraldehyde |
| UNII | |
| |
| |
| Properties | |
| C6H12O3 | |
| Molar mass | 132.159 g·mol−1 |
| Appearance | Colourless liquid |
| Odor | Sweet |
| Density | 0.996 g/cm3 |
| Melting point | 12 °C (54 °F; 285 K) |
| Boiling point | 124 °C (255 °F; 397 K)[1] |
| soluble 10% vv at 25 Deg. | |
| Vapor pressure | 13 hPa at 20 °C[1] |
| −86.2·10−6 cm3/mol | |
| Pharmacology | |
| N05CC05 (WHO) | |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards | Flammable |
| GHS labelling: | |
 | |
| Warning | |
| H226 | |
| P210,P233,P303+P361+P353,P370+P378,P403+P235,P501 | |
| Flash point | 24°C - closed cup |
| Explosive limits | Upper limit: 17 %(V) Lower limit: 1.3 %(V) |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose) | Oral - Rat - 1,530 mg/kg Dermal - Rabbit - 14,015 mg/kg |
| Safety data sheet (SDS) | [1] |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Paraldehyde is the cyclictrimer ofacetaldehyde molecules.[2] Formally, it is a derivative of1,3,5-trioxane, with amethyl group substituted for ahydrogen atom at each carbon. The corresponding tetramer ismetaldehyde. A colourless liquid, it is sparingly soluble inwater and highly soluble inethanol. Paraldehyde slowly oxidizes in air, turning brown and producing an odour ofacetic acid. It attacks most plastics and rubbers and should be kept in glass bottles.
Paraldehyde was first observed in 1835 by the German chemistJustus Liebig; its empirical formula was determined in 1838 by Liebig's studentHermann Fehling.[3][4] The German chemist Valentin Hermann Weidenbusch (1821–1893), another of Liebig's students, synthesized paraldehyde in 1848 by treating acetaldehyde with acid (either sulfuric or nitric acid) and cooling to 0°C. He found it quite remarkable that when paraldehyde washeated with a trace of the same acid, the reaction went the other way, recreating acetaldehyde.[5][6]
Paraldehyde has uses in industry and medicine.
Paraldehyde can be produced by the direct reaction ofacetaldehyde andsulfuric acid. The product of the reaction is dependent on the temperature. At room temperature and higher, the formation of trimer is preferred, but at lower temperatures, around −10 °C, thetetramermetaldehyde is more likely to be produced.[7]
The reaction of sulfuric acid and acetaldehyde is exothermic, with the heat of reaction being −113 kJ·mol−1.[8]
Paraldehyde is produced and used as a mixture of two diastereomers, known ascis- andtrans-paraldehyde. For each diastereomer, two chair conformers are possible. The structures (1), (4) and (2), (3) are conformers ofcis- andtrans-paraldehyde, respectively. The structures (3) (a conformer of (2)) and (4) (a conformer of (1)) are high energy conformers on steric grounds (1,3-diaxial interactions are present) and do not exist to any appreciable extent in a sample of paraldehyde.[9][10]
Heated with catalytic amounts of acid, it depolymerizes back toacetaldehyde:[11][12]
Since paraldehyde has better handling characteristics, it may be used indirectly or directly as a synthetic equivalent of anhydrous acetaldehyde (b.p. 20 °C). For example, it is used as-is in the synthesis ofbromal (tribromoacetaldehyde):[13]
Paraldehyde was introduced into clinical practice in the UK by the Italian physicianVincenzo Cervello (1854–1918) in 1882.[14][15][16]
It is acentral nervous systemdepressant and was soon found to be an effectiveanticonvulsant,hypnotic andsedative. It was included in somecough medicines as an expectorant (though there is no known mechanism for this function beyond theplacebo effect).
Paraldehyde was the last injection given toEdith Alice Morrell in 1950 by the suspected serial killerJohn Bodkin Adams. He was tried for her murder but acquitted.
It was commonly used to induce sleep in sufferers fromdelirium tremens but has been replaced by other drugs in this regard. It was considered to have been one of the safest hypnotics and was regularly given at bedtime inpsychiatric hospitals andgeriatric wards until the 1970s[citation needed], but after it was confirmed that acetaldehyde is a confirmed category-1 human carcinogen, it could no longer be considered appropriately safe to use. Up to 30% of the dose is excreted via the lungs (the rest via the liver). This contributes to a strong unpleasant odour on the breath.
Today, paraldehyde is sometimes used to treatstatus epilepticus. Unlikediazepam and otherbenzodiazepines, it does not suppress breathing at therapeutic doses and so is safer when no resuscitation facilities exist or when the patient's breathing is already compromised.[17] This makes it a useful emergency medication for parents and other caretakers of children with epilepsy. Since the dose margin between the anticonvulsant and hypnotic effect is small, paraldehyde treatment usually results in sleep.
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Generic paraldehyde is available in 5 mL sealed glass ampoules. Production in the US has been discontinued, but it was previously marketed asParal.
Paraldehyde has been given orally, rectally, intravenously and by intramuscular injection. It reacts with rubber and plastic which limits the time it may safely be kept in contact with some syringes or tubing before administration.
Paraldehyde is used inresin manufacture as an alternative toformaldehyde when makingphenol formaldehyde resins. It has also found use as antimicrobialpreservative, and rarely as asolvent. It has been used in the generation ofaldehyde fuchsin.[18]
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