569-65-3

Basic information

• Product Name: Meclozine
• Synonyms: 1-(p-chloro-alpha-phenylbenzyl)-4-(m-methylbenzyl)-piperazin 1-(p-chloro-alpha-phenylbenzyl)-4-(m-methylbenzyl)piperazine 1-(p-chlorobenzhydryl)-4-(m-methylbenzyl)diethylenediamine 1-(p-chlorobenzhydryl)-4-(m-methylbenzyl)piperazine 1-[(4-chlorophenyl)phenylmethyl]-4-[(3-methylphenyl)methyl]piperazine 1-p-chlorobenzhydryl-4-m-methylbenzylpiperazine ancolan antivert;1-(P-CHLORO-ALPHA-PHENYLBENZYL)-4-(M-METHYLBENZYL)-PIPERAZIN;1-(p-Chlorobenzhydryl)-4-(m-methylbenzyl)diethylenediami;2-Methyl Meclizine IsoMer;1-(p-Chloro-alpha-phenylbenzyl)-4-(m-methylbenzyl)piperazine;1-(p-Chlorobenzhydryl)-4-(m-methylbenzyl)diethylenediamine;1-(p-Chlorobenzhydryl)-4-(m-methylbenzyl)piperazine;1-[(4-Chlorophenyl)(phenyl)methyl]-4-(3-methylbenzyl)piperazine
• CAS NO: 569-65-3
• Molecular Formula: C₂₅H₂₇ClN₂
• Molecular Weight: 390.95
• EINECS: 209-323-3
• Mol File: 569-65-3.mol
• Article Data: 5

Chemical Properties

• Melting Point: 153-157°C
• Boiling Point: bp2 230°
• Flash Point: 253.3 °C
• Appearance: /
• Density: 1.0318 (rough estimate)
• Refractive Index: 1.5940 (estimate)
• Storage Temp.: 2-8°C
• PKA: pKa 2.05(H2O,t =25,I=0.0051(NaCl)) (Uncertain)
• CAS DataBase Reference: Meclozine(CAS DataBase Reference)
• NIST Chemistry Reference: Meclozine(569-65-3)
• EPA Substance Registry System: Meclozine(569-65-3)

Safety Data

• Hazard Codes: Xn:
• Statements: R22;R36/37/38:
• Safety Statements: S26;S37/39:
• Hazardous Substances Data: 569-65-3(Hazardous Substances Data)

Usage

Description

Meclozine, also known by its synonyms such as antivert, bonine, lamin, roclizin, and vertol, is a pharmaceutical compound that belongs to the class of antihistamines. It is characterized by its ability to actively affect the vomiting center in the body, making it a potent anti-emetic agent. Meclozine is commonly used to treat symptoms of motion sickness, including vomiting and diarrhea, and is available under various brand names such as Antivert (Pfizer), Ancoloxine, Bonamina, Calmonal, and many others.

Uses

Used in Pharmaceutical Industry:
Meclozine is used as an anti-emetic agent for the treatment of vomiting and diarrhea caused by motion sickness. Its effectiveness in managing these symptoms is attributed to its ability to influence the vomiting center in the body, providing relief and comfort to individuals experiencing motion sickness.
Used in Travel and Tourism:
Meclozine is used as a preventive measure for individuals who are prone to motion sickness during travel, particularly those who engage in activities involving motion, such as boating, car rides, or air travel. By taking Meclozine before the journey, individuals can reduce the likelihood of experiencing nausea, vomiting, and diarrhea, allowing for a more enjoyable and comfortable travel experience.
Used in Medical Treatments:
Meclozine is also used in the medical field to manage symptoms of nausea and vomiting associated with various conditions, such as pregnancy, postoperative recovery, and chemotherapy treatments. Its anti-emetic properties make it a valuable asset in providing relief to patients undergoing these challenging situations.

Therapeutic Function

Antinauseant

World Health Organization (WHO)

Meclozine, an antihistamine with antiemetic activity, was introduced in 1953 for the treatment of nausea. The action taken in Indonesia in 1963 resulted from concern regarding its possible teratogenic potential. Subsequent epidemiological studies have been widely accepted, however, as dispelling this suspicion. Meclozine remains widely available in both prescription only and over-the-counter preparations and in some countries the licensed indications include management of nausea of pregnancy.

Synthesis

Meclizine, 1-[(4-chlorphenyl)methyl]-4-[(3-methylphenyl)phenyl]piperazine (16.1.16), is synthesized by reductive amination of a mixture of 3-methylbenzaldehyde with 1-(4-chlorbenzhydryl)piperazine using hydrogen over Raney nickel.

InChI:InChI=1/C25H27ClN2/c1-20-6-5-7-21(18-20)19-27-14-16-28(17-15-27)25(22-8-3-2-4-9-22)23-10-12-24(26)13-11-23/h2-13,18,25H,14-17,19H2,1H3

Synthetic route

1-(3-methylbenzyl)piperazine (5321-48-2) + 4-chlorobenzaldehyde (104-88-1) → meclizine (569-65-3)

Conditions	Yield
With hydrogenchloride; potassium cyanide; toluene anschl. Erh. der nach Abtrennung der wss. Phase erhaltenen Loesung mit Phenylmagnesiumbromid in Toluol;
With calcium sulfate; mercury dichloride; butan-1-ol anschl. mit methanol. Natriummethylat, Erw. des Rktprod. mit Phenylmagnesiumbromid in Aether;

(+-)-1-<4-chloro-benzhydryl>-piperazine + 3-methyl-benzyl halide → meclizine (569-65-3)

TentaGel-NEtC(O)CH2C2F4OC2F4SO3-{4-(1-[(α-4-chlorophenyl)benzyl]piperazin-4-yl)methyl-2-methylphenyl} resin → meclizine (569-65-3)

Conditions	Yield
With formic acid; 1,3-bis-(diphenylphosphino)propane; triethylamine; palladium diacetate In N,N-dimethyl-formamide at 85℃; for 2h;

N-(4-chlorobenzhydryl)piperazine (303-26-4) + m-tolyl aldehyde (620-23-5) → meclizine (569-65-3)

Conditions	Yield
With formic acid; C18H24Cl2IrN3 In water at 20℃; for 12h; Schlenk technique; Green chemistry;	1.56 g

meclizine (569-65-3) → 4-chlorophenyl(phenyl)methane (831-81-2)

Conditions	Yield
With tris(pentafluorophenyl)borate; phenylsilane at 120℃; for 24h; Inert atmosphere; Sealed tube; Glovebox;	97%

2-(2-methylphenyl)pyridine (10273-89-9) + meclizine (569-65-3) → C37H37N3

Conditions	Yield
With C17H24N5Ru(1+)*F6P(1-); potassium acetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 50℃; for 24h; Inert atmosphere;	90%

tetrahydroxydiboron (13675-18-8) + meclizine (569-65-3) + 2,2-Dimethyl-1,3-propanediol (126-30-7) → 1-((4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)(phenyl)methyl)-4-(3-methylbenzyl)piperazine

Conditions	Yield
Stage #1: tetrahydroxydiboron; meclizine With XPhos-Pd-G; potassium acetate; XPhos at 80℃; for 12h; Schlenk technique; Inert atmosphere; Stage #2: 2,2-Dimethyl-1,3-propanediol In dichloromethane at 20℃; for 12h; Schlenk technique; Inert atmosphere;	85%

2,3-dimethyl-2,3-butane diol (76-09-5) + tetrahydroxydiboron (13675-18-8) + meclizine (569-65-3) → 1-(3-methylbenzyl)-4-(phenyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl)piperazine

Conditions	Yield
Stage #1: tetrahydroxydiboron; meclizine With methanesulfonic acid(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II); potassium acetate; XPhos In ethanol at 80℃; for 4h; Inert atmosphere; Schlenk technique; Stage #2: 2,3-dimethyl-2,3-butane diol In dichloromethane at 20℃; for 8h; Inert atmosphere; Schlenk technique;	75%

meclizine (569-65-3) → (4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)(m-tolyl)methanone

Conditions	Yield
With DBN; oxygen; rose bengal In N,N-dimethyl-formamide at 20℃; for 48h; Irradiation;	61%

Grushin’s reagent + meclizine (569-65-3) → 1-((4-chlorophenyl)(phenyl)methyl)-4-(3-(2,2,2-trifluoroethyl)benzyl)piperazine

Conditions	Yield
With ammonium peroxydisulfate; chlorotriisopropylsilane; trifluoroacetic acid In water; acetone at 20℃; for 18h; Inert atmosphere; Sealed tube; Irradiation; Green chemistry;	26%

2,3-Dichloro-1,4-naphthoquinone (117-80-6) + meclizine (569-65-3) → 2-Chlor-3-{4-[(4-chlorphenyl)phenylmethyl]piperazin-1-yl}-1,4-naphthochinon

Conditions	Yield
In dichloromethane for 96h; Heating;	3.1%

meclizine (569-65-3) → 1-(3-methylbenzyl)-4-(phenyl(4-(trifluoromethylthio)phenyl)methyl)piperazine

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium acetate; XPhos-Pd-G; XPhos / 12 h / 80 °C / Schlenk technique; Inert atmosphere 1.2: 12 h / 20 °C / Schlenk technique; Inert atmosphere 2.1: tetrahydrofuran; pentane / 2 h / -40 - 0 °C / Schlenk technique 3.1: N,N-dimethyl acetamide; acetonitrile / 24 h / 60 °C View Scheme

Upstream product

• 5321-48-2 1-(3-methylbenzyl)piperazine 
• 104-88-1 4-chlorobenzaldehyde 
• 303-26-4 N-(4-chlorobenzhydryl)piperazine 
• 620-23-5 m-tolyl aldehyde 

Downstream Products

• 831-81-2 4-chlorophenyl(phenyl)methane 

Relevant articles and documents

Bisulfite Addition Compounds as Substrates for Reductive Aminations in Water

Highly valued products resulting from reductive aminations utilizing shelf-stable bisulfite addition compounds of aldehydes can be made under aqueous micellar catalysis conditions. Readily available α-picolineborane serves as the stoichiometric hydride source. Recycling of the aqueous reaction medium is easily accomplished, and several applications to targets in the pharmaceutical industry are documented.

BF3·Et2O as a metal-free catalyst for direct reductive amination of aldehydes with amines using formic acid as a reductant

A versatile metal- and base-free direct reductive amination of aldehydes with amines using formic acid as a reductant under the catalysis of inexpensive BF3·Et2O has been developed. A wide range of primary and secondary amines and diversely substituted aldehydes are compatible with this transformation, allowing facile access to various secondary and tertiary amines in high yields with wide functional group tolerance. Moreover, the method is convenient for the late-stage functionalization of bioactive compounds and preparation of commercialized drug molecules and biologically relevant N-heterocycles. The procedure has the advantages of simple operation and workup and easy scale-up, and does not require dry conditions, an inert atmosphere or a water scavenger. Mechanistic studies reveal the involvement of imine activation by BF3and hydride transfer from formic acid.

A traceless perfluoroalkylsulfonyl (PFS) linker for the deoxygenation of phenols

(Equation presented) The synthesis of a novel perfluoroalkylsulfonyl (PFS) fluoride is described for use as a traceless linker in solid-phase organic synthesis. Attachment to the resin and subsequent coupling of a phenol affords a stable arylsulfonate that behaves as a support-bound aryl triflate. Palladium-mediated reductive cleavage of a wide variety of phenols generated the parent arenes. The resin-bound aryl triflate was shown to be stable to reductive amination conditions, and the traceless synthesis of Meclizine is reported.