2709-56-0

Basic information

• Product Name: Flupentiol
• Synonyms: CIS(Z)-FLUPENTIXOL 2HCL;(alpha,beta)-flupenthixol;1-piperazineethanol,4-(3-(2-(trifluoromethyl)-9h-thioxanthen-9-ylidene)propy;2-trifluoromethyl-9-(3-(4-(beta-hydroxyethyl)-1-piperazinyl)propylidene)thio;4-(3-(2-(trifluoromethyl)-9h-thioxanthen-9-ylidene)propyl)-1-piperazineethan;4-(3-(2-(trifluoromethyl)thioxanthen-9-ylidene)propyl)-1-piperazineethano;4-(3-(2-(trifluoromethyl)thioxanthen-9-ylidene)propyl)-1-piperazineethanol;emergil
• CAS NO: 2709-56-0
• Molecular Formula: C₂₃H₂₅F₃N₂OS
• Molecular Weight: 434.52
• EINECS: 220-304-9
• Mol File: 2709-56-0.mol

Chemical Properties

• Boiling Point: 554.7±50.0 °C(Predicted)
• Appearance: white or off-white/solid
• Density: 1.2118 (estimate)
• Refractive Index: 1.607
• Solubility: H2O: soluble
• PKA: pKa 7.80 (Uncertain)
• CAS DataBase Reference: Flupentiol(CAS DataBase Reference)
• NIST Chemistry Reference: Flupentiol(2709-56-0)
• EPA Substance Registry System: Flupentiol(2709-56-0)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36/37/39
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: TL9900000
• Hazardous Substances Data: 2709-56-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Flupentiol is used as an antipsychotic agent for the treatment of various psychiatric disorders, such as schizophrenia and bipolar disorder. It helps in managing symptoms like hallucinations, delusions, and agitation by blocking the action of dopamine in the brain.
Used in Neurochemistry Research:
Flupentiol is utilized as a research tool in neurochemistry to study the effects of dopamine receptor antagonists. Its ability to block dopamine receptors makes it a valuable compound for understanding the role of dopamine in various brain functions and disorders.
Used in Animal Health:
In the veterinary field, Flupentiol is used as a tranquilizer and sedative for animals, particularly in the management of aggressive or anxious behavior in pets. It helps in calming the animals without causing significant sedation, making it a preferred choice for certain applications.

Therapeutic Function

Tranquilizer

InChI:InChI=1/C23H27F3N2OS/c24-23(25,26)17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)30-22)5-3-9-27-10-12-28(13-11-27)14-15-29/h1-2,4-8,16,20,22,29H,3,9-15H2

Synthetic route

(Z)-flupentixol p-chlorobenzoate dihydrochloride → cis-(Z)-flupenthixol (2709-56-0)

Conditions	Yield
Stage #1: (Z)-flupentixol p-chlorobenzoate dihydrochloride With potassium hydroxide In methanol; water at 55℃; for 1h; Stage #2: In water; toluene at 70℃; Stage #3: With cyclohexane at 60℃;	70%

1-(2-hydroxyethyl)piperazine (103-76-4) + 2-trifluoromethyl-9-(2-propenylidene)thioxanthene (28973-34-4) → cis-(Z)-flupenthixol (2709-56-0) + flupenthixol (53772-85-3)

Conditions	Yield
Stage #1: 1-(2-hydroxyethyl)piperazine; 2-trifluoromethyl-9-(2-propenylidene)thioxanthene at 100℃; under 0.2 - 1 Torr; for 7h; Stage #2: In water; toluene at 70℃; for 0.25h; Stage #3: With sulfuric acid; ammonia more than 3 stages;

n-decanoyl chloride (112-13-0) + cis-(Z)-flupenthixol (2709-56-0) → (Z)-flupentixol decanoate dihydrochloride

Conditions	Yield
Stage #1: n-decanoyl chloride; cis-(Z)-flupenthixol In acetone for 1.5h; Heating / reflux; Stage #2: With hydrogenchloride In ethyl acetate at 5 - 25℃;	85%

4-chloro-benzoyl chloride (122-01-0) + cis-(Z)-flupenthixol (2709-56-0) + flupenthixol (53772-85-3) → (Z)-flupentixol p-chlorobenzoate dihydrochloride + (E)-flupentixol p-chlorobenzoate hydrochloride

Conditions	Yield
Stage #1: 4-chloro-benzoyl chloride; cis-(Z)-flupenthixol; flupenthixol In ethyl acetate at 40 - 70℃; for 1h; Stage #2: With hydrogenchloride In water at 40℃; for 0.25h;	A 33% B n/a

Upstream product

• 53772-85-3 flupenthixol 
• 850808-70-7 2-trifluoromethyl-9-allyl-9-thioxanthenol 
• 103-76-4 1-(2-hydroxyethyl)piperazine 
• 28973-34-4 2-trifluoromethyl-9-(2-propenylidene)thioxanthene 
• 2340-57-0 (9RS)-9-[3-dimethylamino-propyl]-2-(trifluoromethyl)-9H-thioxanthene-9-ol 
• 95365-88-1 cis-10-(3-Dimethylamino-propyliden)-2-trifluormethyl-thiaxanthen 

Downstream Products

• 90331-36-5 Flupentixol-4-methyliodid 
• 90331-35-4 Flupentixol-1-methyliodid 
• 2413-38-9 flupentixol dihydrochloride 
• 2413-38-9 flupentixol hydrochloride 

Relevant articles and documents

A hydrochloric acid flupentixol preparation method

The invention provides a preparation method of flupentixol dihydrochloride, which comprises the following steps: reacting and dehydrating 10-hydroxy-10-(3-dimethylaminopropyl)-2-trifluoromethyl thioxanthene and sulfoxide chloride or acetic anhydride to prepare high-content Z-type 10-[3-(EZ)-dimethylaminopropyl]-2-trifluoromethyl thioxanthene, reacting with N-hydroxyethyl piperazidine to prepare flupentixol base, and finally, introducing sufficient hydrochloric acid gas into the flupentixol base to prepare the high-content Z-type flupentixol dihydrochloride. The method has the advantages of fewer steps, high yield and high product purity, is simple to operate, and does not use any extremely toxic substance to pollute the environment. The Z-type flupentixol dihydrochloride content in the flupentixol dihydrochloride prepared by the method is 42-52%, and conforms to the quality standard specification for flupentixol dihydrochloride in European Pharmacopoeia.

Preparation method of medicinal flupentixol dihydrochloride

The invention discloses a preparation method of medicinal flupentixol dihydrochloride. The preparation method comprises that 1), 2-trifluoromethyl-9-allylthioxanthenol, methyl tertiary-butyl ether and hydrochloric acid are uniformly mixed and undergo a reaction to produce 2-trifluoromethyl-9-(2-propenylidene)thiaxanthene, 2), 2-trifluoromethyl-9-(2-propenylidene)thiaxanthene and N-(2-hydroxyethyl)piperazine undergo an addition reaction in an organic solution at a reaction temperature of 100-150 DEG C for 5-20h to produce 9-[3-(4-ethoxy-1-piperazinyl)propylidene]-2-trifluoromethylthiaxanthene, 3), a flupentixol dihydrochloride crude product is prepared, and 4), the flupentixol dihydrochloride crude product is purified. The preparation method has simple processes and a short technical route, produces less by-products in the reaction, has a high yield, realizes high product purity and is suitable for industrial production.

PROCESS FOR THE PREPARATION OF Z-FLUPENTIXOL

The present invention relates to a process for the separation of flupentixol isomers, particularly, a process for the preparation of Z-flupentixol and the decanoate ester and novel synthetic intermediates thereof.