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 quickly reacts with most plastics and rubber. 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 trimerization of three acetaldehyde molecules in the presence of sulfuric acid. 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 metaldehyde is more likely to be produced. 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: 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