5086-74-8

Basic information

• Product Name: Tetramisole hydrochloride
• Synonyms: (+-)-2,3,5,6-tetrahydro-6-phenylimidazo(2,1-b)thiazolemonohydrochloride;(+-)-anthelvet;1-b)thiazole,2,3,5,6-tetrahydro-6-phenyl-,monohydrochloride,(+-)-imidazo(;anthelvet;bayer9051;citarin;dl-6-phenyl-2,3,5,6-tetrahydroimidazole(2,1-b)thiazole-hydrochloride;dl-tetramisolehydrochloride
• CAS NO: 5086-74-8
• Molecular Formula: C₁₁H₁₃N₂S*Cl
• Molecular Weight: 240.75
• EINECS: 225-799-5
• Product Categories: API;Veterinaries;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;METRIPHONATE
• Mol File: 5086-74-8.mol

Chemical Properties

• Melting Point: 266-267 °C(lit.)
• Boiling Point: 344.4 °C at 760 mmHg
• Flash Point: 162.1 °C
• Appearance: white to pale cream crystalline powder
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: Methanol (Slightly), Water (Slightly, Heated)
• Water Solubility: 200 g/L (20 ºC)
• Stability: Hygroscopic
• Merck: 13,5480
• BRN: 4358989
• CAS DataBase Reference: Tetramisole hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Tetramisole hydrochloride(5086-74-8)
• EPA Substance Registry System: Tetramisole hydrochloride(5086-74-8)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38-20/21/22
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: NJ5950000
• Hazardous Substances Data: 5086-74-8(Hazardous Substances Data)

Usage

Chemical Properties

Tetraimidazole hydrochloride is a white to pale cream crystalline powder, bitter and astringent, easily soluble in water , Methanol, slightly soluble in ethanol, insoluble in acetone. acid solutions are stable; however, hydrolysis occurs under alkaline conditions. The rate of hydrolysis increases with pH and temperature. It is used as levamisole intermediate, anthelmintic drug.

Uses

Tetramisole hydrochloride is an inhibitor of alkaline phosphatases, is a high purity antiparasitic. It is suitable for inhibition of various alkaline phosphatase (i.e., liver, kidney, placenta, bone and tumor)(Intestinal alkaline phosphatases are only slightly inhibited.). Tetramisole has biological response modifier with anthelmintic activity. Anthelmintic (nematodes); immunomodulator.

Definition

ChEBI: Tetramisole hydrochloride is an organic molecular entity. It is a broad-spectrum veterinary anthelmintic with high efficiency and low toxicity.

Application

Tetramisole is an alkaline phosphatase inhibitor. It is a racemic mixture of (+) and (-) isomers. The (-) isomer (levamisole) accounts for most of the biological activity of tetramisole.Tetramisole has been used to inhibit alkaline phosphatase in the effective range of 0.4 – 2 mM. Inhibition of intestinal alkaline phosphate requires higher concentrations. In addition to its use in enzyme and protein phosphorylation studies, tetramisole has been used to study membrane, tissue and animal systems.Tetramisole is an anthelminthic agent used in veterinary applications to treat helminth or worm infections.

in vitro

Tetramisole hydrochloride at 67.5 mg/kg is 88.8% effective against immature and 99.7% effective against adult Libyostrongylus douglassi of the ostrich. A dose of up to 408 mg/kg tetramisole hydrochloride had no adverse effects on young birds but at 529 mg/kg was lethal to both chicks and adult ostriches. The efficacy of pyrantel tartrate was erratic. At 50 - 60 mg/kg it was 72.3% effective against immatures and 50.2% effective against adult worms. At 100 mg/kg it fell to 43.6% against immature, but rose to 77.3% against adult worms. Pyrantel tartrate at 100 mg/kg caused the death .of three out of four chicks. The macroscopic lesions of the disease ""vrotmaag"" caused by L. douglassi are descriptionbed as well as some of the other pathological lesions observed at autopsy.

Mode of action

Tetramisole HCl inhibits parasitic worm growth by acting as an agonist to nicotinic acetylcholine receptors leading to paralysis. The mechanism of action for anticancer activity is unknown.

InChI:InChI=1/C11H12N2S.ClH/c1-2-4-9(5-3-1)10-8-13-6-7-14-11(13)12-10;/h1-5,10H,6-8H2;1H

Synthetic route

phosphorous pentasulfide + pyrographite (7440-44-0) + 1-(2-acetoxy-ethyl)-4-phenyl-imidazolidin-2-one (65329-73-9) → tetramisole hydrochloride (5086-74-8)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In ethanol; chloroform; toluene
With hydrogenchloride; sodium hydroxide In ethanol; chloroform; toluene

phosphorous pentasulfide + 1-(2-methoxy-ethyl)-4-phenyl-imidazolidin-2-one (65329-69-3) → tetramisole hydrochloride (5086-74-8)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In ethanol; chloroform; toluene

phosphorous pentasulfide + 1-(2-hydroxy-ethyl)-4-phenyl-imidazolidin-2-one (65329-72-8) → tetramisole hydrochloride (5086-74-8)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In ethanol; chloroform; toluene
With hydrogenchloride; sodium hydroxide In ethanol; chloroform; toluene

1-(2-methoxy-ethyl)-4-phenyl-imidazolidine-2-thione (65329-70-6) → tetramisole hydrochloride (5086-74-8)

Conditions	Yield
With hydrogenchloride In ethanol; acetone
With hydrogenchloride In ethanol; acetone

1-(2-methoxy-ethyl)-4-phenyl-imidazolidin-2-one (65329-69-3) → tetramisole hydrochloride (5086-74-8)

Conditions	Yield
With hydrogenchloride; diphosphorus pentasulfide; sodium hydroxide In ethanol; chloroform; toluene
Multi-step reaction with 2 steps 1: hydrogenchloride; sodium hydroxide / chloroform; acetone; toluene 2: hydrogenchloride / ethanol; acetone View Scheme

1-(2-hydroxy-ethyl)-4-phenyl-imidazolidine-2-thione (69510-65-2) → tetramisole hydrochloride (5086-74-8)

Conditions	Yield
In hydrogenchloride; isopropyl alcohol

α-bromoacetophenone (70-11-1) → tetramisole hydrochloride (5086-74-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid / methanol; dichloromethane; chloroform; water 2: palladium / ethanol; hydrogen 3: hydrogenchloride; diphosphorus pentasulfide; sodium hydroxide / ethanol; chloroform; toluene View Scheme
Multi-step reaction with 4 steps 1: acetic acid / methanol; dichloromethane; chloroform; water 2: palladium / ethanol; hydrogen 3: hydrogenchloride; sodium hydroxide / chloroform; acetone; toluene 4: hydrogenchloride / ethanol; acetone View Scheme

1-(2-methoxy-ethyl)-4-phenyl-1,3-dihydro-imidazol-2-one (65346-98-7) → tetramisole hydrochloride (5086-74-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium / ethanol; hydrogen 2: hydrogenchloride; diphosphorus pentasulfide; sodium hydroxide / ethanol; chloroform; toluene View Scheme
Multi-step reaction with 3 steps 1: palladium / ethanol; hydrogen 2: hydrogenchloride; sodium hydroxide / chloroform; acetone; toluene 3: hydrogenchloride / ethanol; acetone View Scheme

tetramisole hydrochloride (5086-74-8) → Tetramisole (5036-02-2)

Conditions	Yield
With sodium hydroxide In diethyl ether; water at 20℃; for 0.5h; Inert atmosphere;	95%

dodecacarbonyl-triangulo-triruthenium (15243-33-1) + tetramisole hydrochloride (5086-74-8) → [Ru3(μ-Cl)(μ-.eta(2)-levamisole-C,S)(CO)9]

Conditions	Yield
In tetrahydrofuran all manipulations under N2; mixt. of Ru and org. compds. in THF stirred and refluxed for 40 min; cooled to room temp., filtered, filtrate concd., pptd. with hexane, elem. anal.;	93%

tetramisole hydrochloride (5086-74-8) → 3-styryl-thiazolidin-2-ylideneamine (20406-02-4, 37430-07-2)

Conditions	Yield
In methanol

tetramisole hydrochloride (5086-74-8) → (+)-tetramisole*CSA

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water; diethyl ether / 0.5 h / 20 °C / Inert atmosphere 2: sodium hydroxide / chloroform / 12 h / -20 °C / Sealed tube View Scheme

tetramisole hydrochloride (5086-74-8) → R-(+)-6-phenyl-2,3,5,6-tetrahydro-imidazo<2,1b>thiazole (14769-74-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / water; diethyl ether / 0.5 h / 20 °C / Inert atmosphere 2: sodium hydroxide / chloroform / 12 h / -20 °C / Sealed tube 3: sodium hydroxide / diethyl ether; water / 0.5 h / 20 °C / Inert atmosphere View Scheme

Upstream product

• 7440-44-0 pyrographite 
• 65329-73-9 1-(2-acetoxy-ethyl)-4-phenyl-imidazolidin-2-one 
• 65329-69-3 1-(2-methoxy-ethyl)-4-phenyl-imidazolidin-2-one 
• 65329-72-8 1-(2-hydroxy-ethyl)-4-phenyl-imidazolidin-2-one 
• 65329-70-6 1-(2-methoxy-ethyl)-4-phenyl-imidazolidine-2-thione 
• 69510-65-2 1-(2-hydroxy-ethyl)-4-phenyl-imidazolidine-2-thione 
• 70-11-1 α-bromoacetophenone 
• 65346-98-7 1-(2-methoxy-ethyl)-4-phenyl-1,3-dihydro-imidazol-2-one 

Downstream Products

• 20406-02-4 2-Imino-3-styryl-thiazolidin 
• 14769-74-5 R-(+)-6-phenyl-2,3,5,6-tetrahydro-imidazo<2,1b>thiazole 
• 5036-02-2 Tetramisole 
• 32190-33-3 1-(2-Mercapto-ethyl)-4-phenyl-imidazolidin-2-one 
• 108291-53-8 (E)-1-nitroso-2-oxo-3-(2-nitrosothioethyl)-5-phenylimidazolidine 
• 108291-54-9 C₂₂H₂₄N₆O₄S₂ 

Relevant articles and documents

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Novel method for applying agrochemicals to plants, which method consists in attaching to the surface of the plants tablets comprising at least one agrochemically active compound and at least one adjuvant, which is solid, liquid of pasty at room temperature, and optionally, one or more excipients optionally in admixture with one or more other additives and/or water.

Method for racemissing d (or l) tetramisole, and the relative product

D-tetramisole, or its l-tetramisole enantiomer, is racemized in solution in dimethylsulphoxide in the presence of a catalytically effective amount of potassium hydroxide.

Derivatives of R,S-[X2-(2-hydroxyethylamino)-1-phenyl]-ethylamine, and process

An R,S-[2-(2-hydroxyethylamino)-1-phenyl]-ethylamine of the formula III STR1 wherein R represents hydrogen, allyl, propargyl or benzyl. These compounds provide valuable intermediates for the synthesis of Tetramisole.

Manufacture of tetramisole

Process for the manufacture of 2-imino-3-(2-chloro-2-phenylethyl)thiazolidine (known intermediate in manufacture of the anthelmintic agent tetramisole) by reacting 2-imino-3-(2-hydroxy-2-phenylethyl)thiazolidine with chlorosulphonic acid and either aqueous hydrochloric acid or water. Preferred procedure involves use of chlorosulphonic acid and concentrated hydrochloric acid.

Intermediates for synthesis of tetramisole, levamisole and their derivatives

A process for the manufacture of 1-(2-alkoxyethyl)-4-phenyl-4-imidazolin-2-ones, 1-(2-alkoxyethyl)-4-phenyl-2-imidazolidones, 1-(2-alkoxyethyl)-4-phenyl-imidazolidine-2-thiones, certain of the corresponding 1-(2-hydroxyethyl) derivatives and their 3-acylated derivatives, and certain related compounds which are all useful as intermediates in a new process for the manufacture of tetramisole, dl-2,3,5,6-tetrahydro-6-phenylimidazo-[2,1-b]thiazole, and its derivatives. The compound tetramisole is useful as an anthelmintic.

Optically active 1-oxyethyl-4-phenyl-2-imidazolidones

A process for the manufacture of 1-(2-alkoxyethyl)-4-phenyl-4-imidazolin-2-ones, 1-(2-alkoxyethyl)-4-phenyl-2-imidazolidones, 1-(2-alkoxyethyl)-4-phenyl-imidazolidine-2-thiones, certain of the corresponding 1-(2-hydroxyethyl) derivatives, and their 3-acylated derivatives, and certain related compounds which are all useful as intermediates in a new process for the manufacture of the anthelmintic levamisole, (-)-2,3,5,6-tetrahydro-6-phenylimidazo-[2,1-b]thiazole, and its derivatives through conventional resolution procedures. The new process also permits the direct manufacture of optically active 1-(2-alkoxyethyl)-4-phenyl-2-imidazolidone and their 3-acylated derivatives, optically active 1-(2-alkoxyethyl)-4-phenylimidazolidine-2-thiones, and levamisole, the levorotatory isomer of tetramisole, using catalytic amounts of a chiral reducing agent, with the elimination of conventional resolution procedures.

Process for preparing 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole

This disclosure relates to a process for the manufacture of compounds of the formula STR1 which comprises ring-closing a compound of the formula STR2 wherein the variables are as defined infra.