Paraldehyde

Absorption

93% of orally administered paraldehyde is absorbed from the gastrointestinal tract.

Toxicity

Paraldehyde overdosage can produce headache, nausea, drowsiness, unconsciousness, coma, severe hypotension, respiratory depression, pulmonary edema and hemorrhages, and right-side heart failure . Inhalation of paraldehyde can produce sore throat, headache, dizziness, nausea, drowsiness and unconsciousness but exposure via this route is rare. Chronic use is dependence forming and withdrawal proceeds similarly to ethanol withdrawal producing hallucinations and convulsions. Toxic hepatitis and nephritis have been observed during chronic use.
The acute LD50 values determined for various species are as follows :
Rabbit - 3.3-5 g/kg (oral) Rat - 1.5-1.65 g/kg (oral), 1.3-1.45 g/kg (i.p.) Dog - 3-4 g/kg (oral) Mouse - 2.75 (oral) Cat - 3.3 (oral)

Description

Paraldehyde was first synthesized in 1829 by Wildenbusch and introduced into clinical practice in the United Kingdom by the Italian physician Vincenzo Cervello in 1882. Paraldehyde, a polymer of acetaldehyde, is a clear colorless or slightly yellow transparent liquid with a strong aromatic as well as a disagreeable taste that at low temperatures, it solidifies into a crystalline mass. This agent decomposes with strong into toxic products that may be released into water, soil, or atmosphere.

Chemical properties

Paraldehyde is a colourless to yellowish clear liquid. Pleasant, sweet odor. Less dense than water. Vapors are heavier than air.

Chemical properties

Paraldehyde has a characteristic aromatic odor and warm, but disagreeable burning taste.

The Uses of Paraldehyde

Paraldehyde is used as solvent for fats, oils, waxes, rubber and resins; as substitute for acetaldehyde; as intermediate for organic chemicals, dyestuffs, accelerators for vulcanizations, rubber oxidants, etc. Product Data Sheet

The Uses of Paraldehyde

Reactant involved in:• ;Modified Sanford reaction1• ;Synthesis of N-arylbenzoquinaldinium derivatives with antimicrobial activity2• ;Hydroformylation of alkenylamines3• ;Studies of molecules with inhibitory activity against HIV-1 integrase4• ;Irregular Wittig reactions for the formation of α-hydroxyketones5

The Uses of Paraldehyde

manufacture of organic compounds.

The Uses of Paraldehyde

Paraldehyde is used in ethanol hangover prevention. It is also used in the treatment of rectal diseases in patients with delirium tremens.

Background

Paraldehyde was initially introduced into medical practice in the United Kingdom in 1882 by the Italian physician Vincenzo Cervello. It is classified as a central nervous system (CNS) depressant and has also been found to be an effective anticonvulsant, hypnotic and sedative agent due to its CNS depressant properties. Paraldehyde is used as an ingredient in some cough medicines as an expectorant, but its efficacy for this indication has not been confirmed and its use as an expectorant may possibly be due to a placebo effect.

Indications

Paraldehyde was used historically as a sedative and hypnotic . It has been used in the treatment of seizures as an anticonvulsant .

Definition

ChEBI: Paraldehyde is a trioxane that is 1,3,5-trioxane substituted by methyl groups at positions 2, 4 and 6. It has a role as a sedative.

Preparation

Prepared by the polymerization of acetaldehyde catalyzed by hydrochloric acid and sulfuric acid at medium to high temperatures.

brand name

Paral (Forest).

Aroma threshold values

Recognition at 0.02 to 0.025 mg/m3 (air).

General Description

Paraldehyde is recognizable as the cyclictrimer of acetaldehyde. It is a liquid with a strong characteristicodor detectable in the expired air and an unpleasanttaste. These properties limit its use almost exclusively toan institutional setting (e.g., in the treatment of deliriumtremens). In the past, when containers were opened and airadmitted and then reclosed and allowed to stand, fatalitiesoccurred because of oxidation of paraldehyde to glacialacetic acid.

Air & Water Reactions

Highly flammable. Slightly soluble in water. Decomposed by light and air, on prolonged storage, to acetaldehyde and acetic acid.

Reactivity Profile

Paraldehyde is an aldehyde. Paraldehyde is decomposed by light and air, on prolonged storage, to acetaldehyde and acetic acid. Incompatible with alkalis, hydrocyanic acid iodides and oxidizers.

Health Hazard

INHALATION AND INGESTION: Irritation, headache, bronchitis, pulmonary edema. Irritating to digestive tract. Hypnotic and analgesic properties. Incoordination and drowsiness, followed by sleep. Larger doses-coma-weak pulse and shallow respiration, cyanosis-death from respiratory paralysis. EYES: irritation-can cause serious injury. SKIN: Dermatitis (skin inflammation).

Pharmacokinetics

Paraldehyde blocks neuromuscular transmission .

Safety Profile

A human poison by rectal route. Moderately toxic to humans by intramuscular route. Moderately toxic experimentally by inhalation, ingestion, intraperitoneal, and subcutaneous routes. Human systemic effects by rectal route: necrotic changes. A skin and severe eye irritant. Low doses produce hypnotic and analgesic effects. Larger doses depress the nervous system with loss of reflexes, coma, and respiratory depression leadmg to respiratory paralysis and death. Chronic effects include weight loss, muscular weakness, and mental fatigue. However, poisoning is rare. A hypnotic agent. Dangerous fire hazard when exposed to heat, flame, or oxidzers. Slight explosion hazard when exposed to heat or flame. Dangerous; keep away from heat and open flame. To fight fire, use alcohol foam, CO2, dry chemical. Potentially violent reaction with nitric acid. Incompatible with alkahes, hydrocyanic acid, iodides, oxidzers. When heated to decomposition it emits acrid smoke and irritating fumes. See also ALDEHYDES

Synthesis

Paraldehyde, 2,4,6-trimethyl-1,3,5-trioxane (4.3.2), is a trimeric acetaldehyde which is synthesized by the acid-catalyzed polymerization of acetaldehyde and at moderate and high temperatures [32,33].

Potential Exposure

Paraldehyde is used primarily in medicine. It is used as a hypnotic agent, in delirium tremens; and in treatment of psychiatric states characterized by excitement when drugs must be given over a long period of time. It also is administered for intractable pain which does not respond to opiates and for basal and obstetrical anesthesia. It is effective against experimentally induced convulsions and has been used in emergency therapy of tetanus, eclampsia, status epilepticus; and poisoning by convulsant drugs. Since it is used primarily in medicine, the chance of accidental human exposure or environmental contamination is low. However, paraldehyde decomposes to acetaldehyde and acetic acid; these compounds have been found to be toxic. In this case, occupational exposure or environmental contamination is possible. Since paraldehyde is prepared from acetaldehyde by polymerization in the presence of an acid catalyst, there exists a potential for adverse effects, although none have been reported in the available literature. It is also used in the manufacture of organic compounds.

Environmental Fate

Paraldehyde is used in resin manufacture, as a preservative, and in other processes as a solvent. Paraldehyde may enter to the environment via industrial effluents or hospital wastes. Acetaldehyde and acetic acid are two products of degradation of paraldehyde. This compound and its degradation products may be released into water, soil, or atmosphere and then they may be removed from the atmosphere by precipitation.

Metabolism

Paraldehyde is believed to undergo depolymerization to acetaldehyde followed by oxidation by aldehyde dehydrogenase . It is thought to ultimately be metabolized to carbon dioxide and water.

Shipping

UN1264 Paraldehyde, Hazard Class: 3; Labels: 3-Flammable liquid.

Purification Methods

Wash paraldehyde with water and fractionally distil it. Alternatively, it is purified by drying with anhydrous Na2SO4, then cooled to 5o, and the frozen material is separated by decantation. The solid is distilled (b 121-124o/atm), the distillate is collected, stored over anhydrous Na2SO4 for several days and re-distilled at atmospheric pressure before use [Le Fevre et al. J Chem Soc 290 1950]. The 2r,4c,6t-trimethyl-1,3,5-trioxane has m 14.5o, b 125o/760mm. [Beilstein 19 II 394, 19 III/IV 4715. 19/9 V 112.]

Incompatibilities

Vapor or liquid may form explosive mixture with air. Incompatible with strong oxidants, strong acids; alkalis, ammonia, amines, iodides, hydrocyanic acid. Violent reaction with liquid oxygen. Contact with acids form acetaldehyde. Attacks rubber and plastics.

Waste Disposal

Incineration in added solvent. Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposal.