2218-68-0

Usage

Originator

Beta-Chlor,Mead Johnson,US,1963

Uses

Sedative-hypnotic.

Manufacturing Process

An intimate mixture of betaine hydrate (67.5 g) and chloral hydrate (100 g) was warmed to ca. 60°C when an exothermic reaction occurred and the mixture became pasty. It was then stirred at 60°C for 30 minutes. The residue solidified on cooling and was crystallized from a small amount of water. The product separated in hard, colorless prisms of MP 122.5 to 124.5°C (corr).

Therapeutic Function

Sedative

InChI:InChI=1/C5H11NO2.C2H3Cl3O2/c1-6(2,3)4-5(7)8;3-2(4,5)1(6)7/h4H2,1-3H3;1,6-7H

Upstream product

• 302-17-0 chloral hydrate 
• 107-43-7 betaine 

Relevant academic research and scientific papers

Chloral Hydrate Polymorphs and Cocrystal Revisited: Solving Two Pharmaceutical Cold Cases

Chloral hydrate has the distinction of perhaps being the first reported example of a pharmaceutical compound to exhibit polymorphism (1877) and the first use of a pharmaceutical cocrystal in a drug product (Beta-Chlor, 1960s). Nevertheless, chloral hydrate represents a microcosm of contemporary issues in solid-state chemistry and its importance to pharmaceutical science. Ironically, the single crystal structures of the β-form of chloral hydrate and its pharmaceutical cocrystal with betaine have not yet been reported. In this contribution, the single crystal structures and physical properties of these crystal forms are reported for the first time. The previously termed "high temperature" β-form of chloral hydrate was obtained by melting the α-form of chloral hydrate and crystallizing from the melt. The α-form of chloral hydrate is comprised of diol-diol homodimers that further assemble into a sheet of six-membered rings. The β-form is sustained by head-to-tail OH?O hydrogen bonds that form a sheet built from two types of three- and five-membered rings. The diol-diol interactions that sustain these polymorphs are placed in context through a Cambridge Structural Database analysis. The chloral hydrate-betaine cocrystal (CHOBTN) was obtained by slow cooling from water, exhibits higher thermal stability than the chloral hydrate polymorphs, and is sustained by a previously known 2-point diol-carboxylate supramolecular heterosynthon that could be of general utility.

Oral and rectal absorption of chloral hydrate and its betaine complex

Chloral hydrate and its betaine complex were administered orally and rectally to nine healthy male subjects. The urinary excretion, which was a reflection of absorption, of a metabolite, trichloroacetic acid, was determined. No statistically significant difference was found between the oral absorption of chloral hydrate and its betaine complex and between the rectal absorption of chloral hydrate and its betaine complex. A statistical difference was found between the oral and rectal absorption of chloral hydrate and between the oral and rectal absorption of chloral betaine.