Chloral hydrate
[CAS# 302-17-0]

Identification

• Classification: API >> Nervous system medication >> Sedative and hypnotics
• Name: Chloral hydrate
• Synonyms: 1,1,1-Trichloro-2,2-ethanediol; 2,2,2-Trichloro-1,1-ethanediol; Trichloroacetaldehyde monohydrate; TCA
• Molecular Formula: C₂H₃Cl₃O₂
• Molecular Weight: 165.40
• CAS Registry Number: 302-17-0
• EC Number: 206-117-5
• SMILES: C(C(Cl)(Cl)Cl)(O)O

Properties

• Water solubility: 660 g/100 mL
• Density: 1.8±0.1 g/cm³, Calc.^*, 1.908 g/mL (20 °C) (Expl.)
• Melting point: 57 °C (Expl.)
• Index of Refraction: 1.546, Calc.^*
• Boiling Point: 96.3±0.0 °C (760 mmHg), Calc.^*, 96.3 °C (760 mmHg) (Expl.)
• Flash Point: 57.3±25.9 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Risk Statements: H301-H315-H319
• Safety Statements: P264-P264+P265-P270-P280-P301+P316-P302+P352-P305+P351+P338-P321-P330-P332+P317-P337+P317-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332

• Transport Information: UN 2075
• Controlled Substance: DEA Drug Code Number: 2465

Discovery and Applications

Chloral hydrate, with the chemical formula C2H3Cl3O2, is a chemical compound that has been widely used in both medical and industrial applications. It is a colorless, crystalline solid that is known for its sedative and hypnotic properties. Chloral hydrate was first synthesized in 1832 by the German chemist Justus von Liebig, who created it by reacting chloral (trichloroacetaldehyde) with water. The substance quickly gained attention for its ability to induce sleep, and it was later used as a sedative in the medical field.

The discovery of chloral hydrate marked an important milestone in the development of hypnotic drugs. Initially, it was used in the treatment of insomnia and anxiety, especially before the advent of more modern sedatives and anesthetics. Chloral hydrate was particularly popular in the 19th and early 20th centuries, as it was considered a relatively safe and effective alternative to other sleep aids. The compound works by depressing the central nervous system, resulting in drowsiness and sedation.

However, over time, the use of chloral hydrate as a sedative declined due to the development of more potent and safer alternatives, such as barbiturates and benzodiazepines. Despite this, chloral hydrate continued to be utilized in certain medical procedures, such as in the treatment of agitation or as a pre-anesthetic. In the 21st century, its use is more limited, although it is still sometimes used in veterinary medicine and for certain pediatric applications under strict medical supervision.

In addition to its medicinal uses, chloral hydrate has been employed in industrial applications, particularly in the production of polyvinyl chloride (PVC) plastics. In this context, it is used as an intermediate in the production of chemicals that are important for the synthesis of various polymers. Chloral hydrate is also used in the manufacturing of certain resins and as a stabilizing agent in some chemical reactions.

Although its use has become more restricted, chloral hydrate remains an important compound in the history of pharmacology and chemistry. Its discovery as a sedative was one of the earliest examples of a synthetic drug designed to treat insomnia, and it played a significant role in the development of hypnotic and sedative pharmacology. Today, it is primarily used in specialized medical and industrial applications.

References

1990. Chloral hydrate anesthesia antagonizes the neurotoxicity of 3,4-methylenedioxymethamphetamine. European Journal of Pharmacology, 191(2).
DOI: 10.1016/0014-2999(90)94149-r

1979. Catecholamines in the yolk sac epithelium of the rat. Brain Structure and Function, 160(2).
DOI: 10.1007/bf00300013

1970. ANTAGONISM OF THE ANTIAVOIDANCE EFFECTS OF VARIOUS AGENTS BY ANTICHOLINERGIC DRUGS. The Journal of Pharmacology and Experimental Therapeutics, 173(1).
DOI: 10.1002/s0022-3565(25)28544-5