Chloral Hydrate

Base Information

• Chemical Name: Chloral Hydrate
• CAS No.: 302-17-0
• Deprecated CAS: 109128-19-0
• Molecular Formula: C2H3Cl3O2
• Molecular Weight: 165.404
• Hs Code.: HYSICAL AND CHEMICAL PROPERTIES PHYSICAL
• European Community (EC) Number: 206-117-5
• ICSC Number: 0234
• NSC Number: 3210
• UN Number: 2811
• UNII: 418M5916WG
• DSSTox Substance ID: DTXSID7020261
• Nikkaji Number: J1.517B
• Wikipedia: Chloral_hydrate
• Wikidata: Q412340
• NCI Thesaurus Code: C28922
• Metabolomics Workbench ID: 51596
• ChEMBL ID: CHEMBL455917
• Mol file: 302-17-0.mol

Synonyms:Chloral Hydrate;Hydrate, Chloral;Noctec

Chemical Property of Chloral Hydrate

Chemical Property:

• Appearance/Colour: colourless crystals with a pentrating odour
• Vapor Pressure: 0.297mmHg at 25°C
• Melting Point: 57 °C(lit.)
• Refractive Index: 1.4603 (estimate)
• Boiling Point: 96.3 °C at 760 mmHg
• PKA: 10(at 25℃)
• Flash Point: 57.3 °C
• PSA: 40.46000
• Density: 1.814 g/cm³
• LogP: 0.66730
• Storage Temp.: 0-6°C
• Solubility.: Very soluble in water, freely soluble in ethanol (96 per cent).
• Water Solubility.: 660 g/100 mL
• XLogP3: 1
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 163.919862
• Heavy Atom Count: 7
• Complexity: 56.4

Purity/Quality:

99% , ^*data from raw suppliers

Trichloro ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T, F
• Hazard Codes: T,F,Xn
• Statements: 25-36/38-39/23/24/25-23/24/25-11-36/37/38-36-20/21/22
• Safety Statements: 26-45-25-23-36/37-16-27

MSDS Files:

SDS file from LookChem

Useful:

• Chemical Classes: Other Classes -> Halogenated Alcohols
• Drug Classes: Sedatives and Hypnotics
• Canonical SMILES: C(C(Cl)(Cl)Cl)(O)O
• Recent ClinicalTrials: Sedation and Nursing Management in EEG Recording in Children
• Inhalation Risk: A harmful contamination of the air will be reached rather slowly on evaporation of this substance at 20 °C.
• Effects of Short Term Exposure: The substance is irritating to the eyes, skin and respiratory tract. The substance may cause effects on the central nervous system. This may result in disorientation, lowering of blood pressure and lowering of consciousness. Exposure at high levels could cause cardiac dysrhythmia and unconsciousness or death.
• Effects of Long Term Exposure: The substance may have effects on the liver. This may result in addiction, behavioural effects and liver impairment. This substance is probably carcinogenic to humans. May cause heritable genetic damage to human germ cells.
• Description: Chloral hydrate is one of the oldest sedatives used for dental sedation. It was first synthesized in 1832 by Justus von Liebig and was the first synthetic central nervous system (CNS) depressant. It was used to treat delirium tremens, insomnia, and anxiety, although it is considered an unapproved drug by the US Food and Drug Administration. Initially considered to be a safer alternative to opium, it was noted to produce rapid unconsciousness when combined with ethanol. Physical dependence can occur with chronic use.Chloral hydrate is classified as a sedative-hypnotic and is known to induce sleep in children. It has been very popular in pediatric dentistry since the mid-1950s. Chloral hydrate is rapidly absorbed following oral administration and is converted through its first pass in the liver to trichloroethanol，its active form. Trichloroethanol is conjugated in the liver and excreted in the urine. Like other agents that are metabolized in the liver, chloral hydrate may interact with other drugs, herbs, or foods resulting in clinically significant alterations of the agents (e.g.,warfarin).
• Uses: Trichloroacetaldehyde Hydrate is a useful chemical reagent used as a sedative/hypnotic agent for the short-term treatment of insomnia. First developed in 1832, chloral hydrate is the oldest sleep medication still in use today. This medication is also used to calm you just before surgery or other procedures. It works by affecting certain parts of the brain to cause calmness. Studies have shown that when used in pediatric sedation side effects such as hallucination, excessive sleep and seizures were observed. Drowsiness and trouble waking up in the morning, nausea, vomiting, stomach pain, diarrhea, and headache may occur. Stomach problems can be reduced by taking chloral hydrate with a full glass of water. It is sometimes administered to patients being treated with cyclophosphamide and it is known to inhibit some aldehyde dehydrogenases. Besides, Chloral hydrate is a starting point for the synthesis of other organic compounds. It is the starting material for the production of chloral, which is produced by the distillation of a mixture of chloral hydrate and sulfuric acid, which serves as the desiccant. Chloral hydrate is used as an intermediate in the production of insecticides, herbicides and hypnotic drugs. It has also been widely used as a sedative or hypnotic drug in humans at oral doses of up to about 750-1000 mg/day. Chloral hydrate is used as a sedative hypnotic, more commonly in pediatrics. With the advent of newer sedative hypnotics, its use has significantly decreased. It is also a drug of abuse, particularly in combination with ethanol to produce an amnestic effect in an individual who ingests it unknowingly.
• Biological Functions: Chloral hydrate (Noctec, Somnos) was developed in the late 1800s and is still used as a sedative–hypnotic agent. It is a hydrated aldehyde with a disagreeable smell and taste that is rapidly reduced in vivo to trichloroethanol, which is considered to be the active metabolite. It produces a high incidence of gastric irritation and allergic responses, occasionally causes cardiac arrhythmias, and is unreliable in patients with liver damage.
• Clinical Use: Although it is suggested that chloral hydrate per semay act as a hypnotic,chloral hydrate is very quickly convertedto trichloroethanol, which is generally assumed toaccount for almost all of the hypnotic effect. Thetrichloroethanol is metabolized by oxidation to chloral andthen to the inactive metabolite, trichloracetic acid, which is also extensively metabolized to acylglucuronidesvia conjugation with glucuronic acid. It appears tohave potent barbiturate-like binding to GABAAreceptors.Although an old drug, it still finds use as a sedative in nonoperatingroom procedures for the pediatric patient.
• Drug interactions: Potentially hazardous interactions with other drugs Anticoagulants: may transiently enhance effect of coumarins. Antipsychotics: enhanced sedative effects. Antivirals: concentration possibly increased by ritonavir.

Technology Process of Chloral Hydrate

There total 25 articles about Chloral Hydrate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 45.0%

chloral (75-87-6) → chloral hydrate (302-17-0)

Guidance literature:

In tetrachloromethane;

Reference yield: 2.7%

N,N-dichloro-p-toluenesulfonamide (473-34-7) + Trichloroethylene (79-01-6) → chloral hydrate (302-17-0) + N-(2,2,2-trichloro-1-hydroxyethyl)4-methylbenzenesulfonamide (83790-89-0) + N-(2,2,2-trichloro-1-p-toluenesulfonamidoethyl)-p-toluenesulfonamide (93018-67-8) + toluene-4-sulfonamide (70-55-3)

Guidance literature:

With water; tin(IV) chloride; at 20 - 22 ℃; for 1560h; Product distribution; other time, temperature, Lewis acid (AlCl₃);

Reference yield:

(2S)-2-(6-methoxy(2-naphthyl))propanoic acid (22204-53-1) → chloral hydrate (302-17-0) + chloroform (67-66-3,8013-54-5) + 1,1-Dichloroacetone (513-88-2) + 1,1,1-trichloroacetone (918-00-3,861255-82-5)

Guidance literature:

With chlorine; In aq. phosphate buffer; pH=7; pH-value; Kinetics; UV-irradiation;

DOI:10.1039/c7ra04540a

upstream raw materials:

ethanol

chloroacetylene

benzoic acid hydrazide

acetaldehyde

Downstream raw materials:

1,1,1-trichloro-2,2-di-[2]thienyl-ethane

n-propyl dichloroacetate

1,1,1-trichloro-2,2-bis-(4-isopropyl-phenyl)-ethane

1,1,1-trichloro-2,2-bis(2-methoxy-5-methylphenyl)ethane

Refernces

• 1、 Liebig. "-". . . Retrieved 1872.
• 2、 Rozentsveig,Levkovskaya,Mirskova,Kashik. "Hydrolysis of N-(2,2,2-trichloroethyl)arenesulfonamides". . p. 1760 - 1764. Retrieved 2007/10/03.