Paraldehyde

Key takeaways

Paraldehyde belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Paraldehyde to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Paraldehyde from memory before moving on to harder problems.

Reference excerpt

Paraldehyde is the cyclic trimer of acetaldehyde molecules. Formally, it is a derivative of 1,3,5-trioxane, with a methyl group substituted for a hydrogen atom at each carbon. The corresponding tetramer is metaldehyde. A colourless liquid, it is sparingly soluble in water and highly soluble in ethanol. Paraldehyde slowly oxidizes in air, turning brown and producing an odour of acetic acid. It attacks most plastics and rubbers and should be kept in glass bottles. Paraldehyde was first observed in 1835 by the German chemist Justus Liebig; its empirical formula was determined in 1838 by Liebig's student Hermann Fehling. 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 direct reaction of acetaldehyde and sulfuric 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, the tetramer metaldehyde is more likely to be produced.

The reaction of sulfuric acid and acetaldehyde is exothermic, with the heat of reaction being −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:

C6H12O3 → 3CH3CHO 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):

C6H12O3 + 9 Br2 → 3 CBr3CHO + 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 depressant and was soon found to be an effective anticonvulsant, hypnotic and sedative. It was included in some cough medicines as an expectorant (though there is no known mechanism for this function beyond the placebo effect). Paraldehyde was the last injection given to Edith Alice Morrell in 1950 by the alleged 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 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 hospitals and geriatric wards until the 1970s , 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.

As anti-seizure drug Today, paraldehyde is sometimes used to treat status epilepticus. Unlike diazepam 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, circulatory collapse 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 or olive oil.

Industrial applications Paraldehyde is used in resin manufacture as an alternative to formaldehyde when making phenol formaldehyde resins. It has also found use as antimicrobial preservative, and rarely as a solvent. It has been used in the generation of aldehyde fuchsin.

References

External links

Paraldehyde Injection B.P Data Sheet Drugs.com: Paraldehyde

Illustrations

Paraldehyde: A 5 mL glass ampoule of paraldehyde. — A 5 mL glass ampoule of paraldehyde.

Worked examples

Example 1 — a first encounter with Paraldehyde

Start with the simplest possible case. Write down what Paraldehyde claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Paraldehyde before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Paraldehyde ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Paraldehyde

In research: Paraldehyde appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Paraldehyde in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Paraldehyde is common in secondary-school and first-year university syllabi. It links to neighbouring topics Acetals, Anticonvulsants, GABAA receptor positive allosteric modulators, so understanding it makes those chapters shorter.
In everyday life: Look for Paraldehyde outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Paraldehyde in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Paraldehyde means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Paraldehyde out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Paraldehyde in simple terms?

Paraldehyde is the cyclic trimer of acetaldehyde molecules. Formally, it is a derivative of 1,3,5-trioxane, with a methyl group substituted for a hydrogen atom at each carbon.

Why does Paraldehyde matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Paraldehyde?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Paraldehyde.