Paraldehyde is the cyclic
trimer of
acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...
molecules. Formally, it is a derivative of
1,3,5-trioxane, with a
methyl group
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...
substituted for a
hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic, an ...
atom at each carbon. The corresponding tetramer is
metaldehyde
Metaldehyde is an organic compound with the formula (C8H16O4). It is used as a pesticide against slugs, snails, and other gastropods. It is the cyclic tetramer of acetaldehyde.
Production and properties
Metaldehyde is flammable, toxic if ing ...
. A colourless liquid, it is sparingly soluble in
water
Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as a ...
and highly soluble in
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...
. Paraldehyde slowly oxidizes in air, turning brown and producing an odour of
acetic acid
Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...
. It quickly reacts with most plastics and rubber.
Paraldehyde was first observed in 1835 by the German chemist
Justus Liebig
Justus Freiherr von Liebig (12 May 1803 – 20 April 1873) was a German scientist who made major contributions to agricultural and biological chemistry, and is considered one of the principal founders of organic chemistry. As a professor at th ...
; its empirical formula was determined in 1838 by Liebig's student
Hermann Fehling Hermann or Herrmann may refer to:
* Hermann (name), list of people with this name
* Arminius, chieftain of the Germanic Cherusci tribe in the 1st century, known as Hermann in the German language
* Éditions Hermann, French publisher
* Hermann, Mis ...
. 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 was ''heated'' with a trace of the same acid, the reaction went the other way, recreating acetaldehyde.
Paraldehyde has uses in industry and medicine.
Preparation
Paraldehyde can be produced by the trimerization of three acetaldehyde molecules in the presence of
sulfuric acid
Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...
. The product of the reaction is dependent on the temperature. At room temperature, the formation of trimer is preferred, but at lower temperatures, around −10 °C, the
tetramer
A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti ...
metaldehyde
Metaldehyde is an organic compound with the formula (C8H16O4). It is used as a pesticide against slugs, snails, and other gastropods. It is the cyclic tetramer of acetaldehyde.
Production and properties
Metaldehyde is flammable, toxic if ing ...
is more likely to be produced.
:
![Paraldehyde metaldehyde synthesis](https://upload.wikimedia.org/wikipedia/commons/1/16/Paraldehyde_metaldehyde_synthesis.svg)
The trimerization reaction is exothermic, with the heat of reaction −113 kJ·mol
−1.
Stereochemistry
Paraldehyde is produced and used as a mixture of two diastereomers, known as ''cis''- and ''trans-''paraldehyde. For each diastereomer, two chair conformers are possible. The structures (1), (4) and (2), (3) are conformers of ''cis''- and ''trans''-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.
Reactions
Heated with catalytic amounts of acid, it depolymerizes back to
acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...
:
:C
6H
12O
3 → 3CH
3CHO
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 of
bromal (tribromoacetaldehyde):
: C
6H
12O
3 + 9 Br
2 → 3 CBr
3CHO + 9 HBr
Medical applications
Paraldehyde was introduced into clinical practice in the UK by the Italian physician
Vincenzo Cervello (1854–1918) in 1882.
It is a
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
depressant
A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the ...
and was soon found to be an effective
anticonvulsant
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
,
hypnotic
Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...
and
sedative
A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...
. It was included in some
cough medicine
Cold medicines are a group of medications taken individually or in combination as a treatment for the symptoms of the common cold and similar conditions of the upper respiratory tract. The term encompasses a broad array of drugs, including a ...
s as an expectorant (though there is no known mechanism for this function beyond the
placebo effect
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
).
Paraldehyde was the last injection given to
Edith Alice Morrell
Edith Alice Morrell (20 June 1869 – 13 November 1950) was a resident of Eastbourne, East Sussex, England, and patient of Dr John Bodkin Adams. Although Adams was acquitted in 1957 of her murder, the question of Adams' role in Morrell's death ...
in 1950 by the suspected serial killer
John Bodkin Adams. He was tried for her murder but acquitted.
As a hypnotic/sedative
It was commonly used to induce sleep in sufferers from
delirium tremens
Delirium tremens (DTs) is a rapid onset of confusion usually caused by withdrawal from alcohol. When it occurs, it is often three days into the withdrawal symptoms and lasts for two to three days. Physical effects may include shaking, shiver ...
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 in
psychiatric hospital
Psychiatric hospitals, also known as mental health hospitals, behavioral health hospitals, are hospitals or wards specializing in the treatment of severe mental disorders, such as schizophrenia, bipolar disorder, eating disorders, dissociative ...
s and
geriatric
Geriatrics, or geriatric medicine, is a medical specialty focused on providing care for the unique health needs of older adults. The term ''geriatrics'' originates from the Greek language, Greek γέρων ''geron'' meaning "old man", and ιατ ...
wards up until the 1970s
itation needed however 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.
As anti-seizure
It has been used in the treatment of
convulsion
A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
s.
Today, paraldehyde is sometimes used to treat
status epilepticus
Status epilepticus (SE), or status seizure, is a single seizure lasting more than 5 minutes or 2 or more seizures within a 5-minute period without the person returning to normal between them. Previous definitions used a 30-minute time limit. The s ...
. Unlike
diazepam
Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, a ...
and other
benzodiazepines, 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.
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.
Administration
Generic paraldehyde is available in 5 mL sealed glass ampoules. Production in the US has been discontinued, but it was previously marketed as Paral.
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.
* Injection. Intramuscular injection can be very painful and lead to sterile abscesses, nerve damage, and tissue necrosis. Intravenous administration can lead to
pulmonary edema
Pulmonary edema, also known as pulmonary congestion, is excessive edema, liquid accumulation in the parenchyma, tissue and pulmonary alveolus, air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia an ...
,
circulatory collapse
Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thi ...
and other complications.
* Oral. Paraldehyde has a hot burning taste and can upset the stomach. It is often mixed with milk or fruit juice in a glass cup and stirred with a metal spoon.
* Rectal. It may be mixed 1 part paraldehyde with 9 parts saline or, alternatively, with an equal mixture of
peanut
The peanut (''Arachis hypogaea''), also known as the groundnut, goober (US), pindar (US) or monkey nut (UK), is a legume crop grown mainly for its edible Seed, seeds. It is widely grown in the tropics and subtropics, important to both small ...
or
olive oil
Olive oil is a liquid fat obtained from olives (the fruit of ''Olea europaea''; family Oleaceae), a traditional tree crop of the Mediterranean Basin, produced by pressing whole olives and extracting the oil. It is commonly used in cooking: f ...
.
Industrial applications
Paraldehyde is used in
resin
In polymer chemistry and materials science, resin is a solid or highly viscous substance of plant or synthetic origin that is typically convertible into polymers. Resins are usually mixtures of organic compounds. This article focuses on natu ...
manufacture as an alternative to
formaldehyde
Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...
when making
phenol formaldehyde resin
Phenol formaldehyde resins (PF) or phenolic resins (also infrequently called phenoplasts) are synthetic polymers obtained by the reaction of phenol or substituted phenol with formaldehyde. Used as the basis for Bakelite, PFs were the first commerc ...
s. It has also found use as antimicrobial
preservative
A preservative is a substance or a chemical that is added to products such as food products, beverages, pharmaceutical drugs, paints, biological samples, cosmetics, wood, and many other products to prevent decomposition by microbial growth or by ...
, and rarely as a
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
. It has been used in the generation of
aldehyde fuchsin
:
The Schiff test is an early organic chemistry named reaction developed by Hugo Schiff, and is a relatively general chemical test for detection of many organic aldehydes that has also found use in the staining of biological tissues. The Schiff ...
.
References
External links
Paraldehyde Injection B.P Data Sheet
{{GABAAR PAMs
Acetals
Anticonvulsants
Hypnotics
Solvents
GABAA receptor positive allosteric modulators
Trioxanes