569-57-3

Basic information

• Product Name: CHLOROTRIANISENE
• Synonyms: 1,1’,1’’-(1-chloro-1-ethenyl-2-ylidene)tris(4-methoxy)-benzen;1,1’,1’’-(1-chloro-1-ethenyl-2-ylidene)tris(4-methoxy-benzen;1,1’,1’’-(1-chloro-1-ethenyl-2-ylidene)-tris(4-methoxybenzene);1,1’,1’’-(1-chloro-1-ethenyl-2-ylidene)tris[4-methoxybenzene];1-[2-Chloro-1,2-bis(4-methoxyphenyl)vinyl]-4-methoxybenzene;Anisene;Benzene, 1,1',1''-(1-chloro-1-ethenyl-2-ylidene)tris*4-methoxy-;Benzene, 1,1',1''-(1-chloro-1-ethenyl-2-ylidene)tris[4-methoxy-
• CAS NO: 569-57-3
• Molecular Formula: C₂₃H₂₁ClO₃
• Molecular Weight: 380.86
• EINECS: 209-318-6
• Product Categories: API;Inhibitors
• Mol File: 569-57-3.mol
• Article Data: 3

Chemical Properties

• Melting Point: 114-116°
• Boiling Point: 496.07°C (rough estimate)
• Flash Point: 164.1°C
• Appearance: /
• Density: 1.1010 (rough estimate)
• Vapor Pressure: 3.57E-10mmHg at 25°C
• Refractive Index: 1.4585 (estimate)
• Storage Temp.: -70°C
• Solubility: insoluble in H2O; insoluble in EtOH; ≥16.1 mg/mL in DMSO
• CAS DataBase Reference: CHLOROTRIANISENE(CAS DataBase Reference)
• NIST Chemistry Reference: CHLOROTRIANISENE(569-57-3)
• EPA Substance Registry System: CHLOROTRIANISENE(569-57-3)

Safety Data

• WGK Germany: 3
• RTECS: KV0600000
• Hazardous Substances Data: 569-57-3(Hazardous Substances Data)

Usage

Originator

TACE,Merrell ,US ,1952

Uses

Different sources of media describe the Uses of 569-57-3 differently. You can refer to the following data:
1. Estrogen.
2. Chlorotrianisene USP (TACE) is used to treat Androgen dependent carcinoma of the prostate.

Manufacturing Process

The following method is described in US Patent 2,430,891. To a solution of 10 parts of tris-p-methoxyphenyl ethylene in 35 to 40 parts of carbon tetrachloride is added a solution of 2.0 parts of chlorine in 50 parts of carbon tetrachloride, with stirring, and over a period of ? hour. The carbon tetrachloride is then removed by distillation on a steam bath and the residual oil is recrystallized from 250 to 400 parts of methanol, decolorizing with charcoal or the like if necessary. Tris-p-methoxyphenyl chloroethylene is obtained in a yield of 65 to 75%. It melts at 113° to 114°C.

Brand name

Tace (Sanofi Aventis).

Therapeutic Function

Estrogen

General Description

Small white crystals or white powder. Softens at 226°F. Odorless.

Reactivity Profile

CHLOROTRIANISENE may react vigorously with strong oxidizing agents. Can react exothermically with reducing agents (such as alkali metals and hydrides) to release gaseous hydrogen. May react exothermically with both acids and bases. Various catalysts (such as acids) or initiators can cause very exothermic addition polymerization reactions.

Fire Hazard

Flash point data for CHLOROTRIANISENE are not available. CHLOROTRIANISENE is probably combustible.

Biological Activity

ed50: 2.0 μmglandular kallikrein, a trypsin-like serine protease, has been identified as a major estrogen-induced protein in the rat anterior pituitary. this induction appears to be mediated by increased gene expression since glandular kallikrein mrna is also estrogen-induced. chlorotrianisene is classified as an estrogen agonist.

in vitro

the ed50 of chlorotrianisene were lowered by 3.9-fold. chlorotrianisene inhibited the growth of both p388 and p388/adr cells in a concentration-dependent manner [1].

in vivo

chlorotrianisene markedly varied in its ability to elicit agonist responses on the three measures. on uterine weight and anterior pituitary prolactin, chlorotrianisene behaved as partial agonists. chlorotrianisene also exhibited strikingly less agonist activity on glandular kallikrein than on prl or the uterus. further, the small agonist activity of chlorotrianisene on glandular kallikrein induction differed from that on the uterus or prolactin [2].

references

[1] ramu a, glaubiger d, fuks z. reversal of acquired resistance to doxorubicin in p388 murine leukemia cells by tamoxifen and other triparanol analogues. cancer res. 1984 oct;44(10):4392-5.[2] powers ca, hatala ma, pagano pj. differential responses of pituitary kallikrein and prolactin to tamoxifen and chlorotrianisene. mol cell endocrinol. 1989 sep;66(1):93-100.[3] nulsen ro, carmon wb, hendrick ho. tace (chlorotrianisene), a new estrogen for inhibition of lactation. am j obstet gynecol. 1953 may;65(5):1048-51.

InChI:InChI=1/C23H21ClO3/c1-25-19-10-4-16(5-11-19)22(17-6-12-20(26-2)13-7-17)23(24)18-8-14-21(27-3)15-9-18/h4-15H,1-3H3

Synthetic route

1,1,2-tris(4-methoxyphenyl)ethene (7109-27-5) → chlorotrianisene (569-57-3)

Conditions	Yield
With tetrachloromethane; chlorine

4'-methoxy-2,2-bis(p-methoxyphenyl)acetophenone (61161-13-5) → chlorotrianisene (569-57-3)

Conditions	Yield
With phosphorus pentachloride; toluene

bis(p-methoxyphenyl)methanone (90-96-0) + Dimethyl 1-chloro-1-(4-methoxyphenyl)methanephosphonate (86457-76-3) → chlorotrianisene (569-57-3)

Conditions	Yield
With tert.-butyl lithium 1.) THF/pentane, -78 deg C, 30 min; 2.) THF, reflux; Yield given. Multistep reaction;

Methoxychlor (72-43-5) + methoxybenzene (100-66-3) → chlorotrianisene (569-57-3)

Conditions	Yield
With aluminium trichloride In carbon disulfide

1-bromo-1,2,2-tris(p-methoxyphenyl)ethene (25354-46-5) → bis(p-methoxyphenyl)methanone (90-96-0) + chlorotrianisene (569-57-3)

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride In dimethyl sulfoxide for 0.333333h; Ambient temperature; Irradiation; Yields of byproduct given;	A 21 % Chromat. B n/a

tetrachloromethane (56-23-5) + 1,1,2-tris(4-methoxyphenyl)ethene (7109-27-5) + chlorine (7782-50-5) → chlorotrianisene (569-57-3)

dimethyl 4-methoxybenzylphosphonate (17105-65-6) → chlorotrianisene (569-57-3)

Conditions	Yield
Multi-step reaction with 2 steps 2: 1.) tert-butyllithium / 1.) THF/pentane, -78 deg C, 30 min; 2.) THF, reflux View Scheme

p-methoxybenzyl chloride (824-94-2) → chlorotrianisene (569-57-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 59 percent / Heating 3: 1.) tert-butyllithium / 1.) THF/pentane, -78 deg C, 30 min; 2.) THF, reflux View Scheme

bis(p-methoxyphenyl)methanone (90-96-0) → chlorotrianisene (569-57-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: diethyl ether; benzene 2: 10 - 20 Torr View Scheme
Multi-step reaction with 3 steps 1: diethyl ether; benzene 2: aminosulfonic acid / 10 - 20 Torr View Scheme
Multi-step reaction with 3 steps 1: diethyl ether; benzene 2: 10 - 20 Torr 3: tetrachloromethane; chlorine View Scheme
Multi-step reaction with 3 steps 1: diethyl ether; benzene 2: aminosulfonic acid / 10 - 20 Torr 3: tetrachloromethane; chlorine View Scheme

ethyl p-methoxyphenylacetate (14062-18-1) → chlorotrianisene (569-57-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: diethyl ether 2: aminosulfonic acid / 10 - 20 Torr View Scheme
Multi-step reaction with 3 steps 1: diethyl ether 2: 10 - 20 Torr View Scheme
Multi-step reaction with 3 steps 1: diethyl ether 2: aminosulfonic acid / 10 - 20 Torr 3: tetrachloromethane; chlorine View Scheme
Multi-step reaction with 3 steps 1: diethyl ether 2: 10 - 20 Torr 3: tetrachloromethane; chlorine View Scheme

1,1,2-tris-(4-methoxy-phenyl)-ethanol (1817-87-4) → chlorotrianisene (569-57-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: aminosulfonic acid / 10 - 20 Torr View Scheme
Multi-step reaction with 2 steps 1: aminosulfonic acid / 10 - 20 Torr 2: tetrachloromethane; chlorine View Scheme
Multi-step reaction with 2 steps 1: 10 - 20 Torr View Scheme
Multi-step reaction with 2 steps 1: 10 - 20 Torr 2: tetrachloromethane; chlorine View Scheme

methoxybenzene (100-66-3) → chlorotrianisene (569-57-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; concentrated sulfuric acid 2: toluene; PCl5 View Scheme
Multi-step reaction with 2 steps 1: aqueous sulfuric acid / anschliessendes Behandeln mit konz.Schwefelsaeure 2: toluene; PCl5 View Scheme

p-methoxyphenylglyoxal (1076-95-5) → chlorotrianisene (569-57-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; concentrated sulfuric acid 2: toluene; PCl5 View Scheme

4-methoxyphenyl magnesium bromide (13139-86-1) → chlorotrianisene (569-57-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: diethyl ether 2: aminosulfonic acid / 10 - 20 Torr View Scheme
Multi-step reaction with 3 steps 1: diethyl ether 2: 10 - 20 Torr View Scheme
Multi-step reaction with 3 steps 1: diethyl ether 2: aminosulfonic acid / 10 - 20 Torr 3: tetrachloromethane; chlorine View Scheme
Multi-step reaction with 3 steps 1: diethyl ether 2: 10 - 20 Torr 3: tetrachloromethane; chlorine View Scheme

chlorotrianisene (569-57-3) → 1,1,2-tris(4-methoxyphenyl)ethene (7109-27-5)

Conditions	Yield
With lithium aluminium tetrahydride; nickel dichloride In tetrahydrofuran < 0 deg C;	95%

chlorotrianisene (569-57-3) + acetic acid (64-19-7) → 9-chloro-3,6-dimethoxy-10-(p-methoxyphenyl)phenanthrene (1040086-21-2) + bis(p-methoxyphenyl)methanone (90-96-0) + 1-Acetoxy-1,2,2-tris(4-methoxyphenyl)ethene (96784-47-3) + 9-acetoxy-3,6-dimethoxy-10-(p-methoxyphenyl)phenanthrene (133627-95-9)

Conditions	Yield
With air In acetonitrile at 23℃; Quantum yield; Further Variations:; Reagents; Irradiation;

Upstream product

• 13139-86-1 4-methoxyphenyl magnesium bromide 
• 1076-95-5 p-methoxyphenylglyoxal 
• 100-66-3 methoxybenzene 
• 1817-87-4 1,1,2-tris-(4-methoxy-phenyl)-ethanol 
• 14062-18-1 ethyl p-methoxyphenylacetate 
• 90-96-0 bis(p-methoxyphenyl)methanone 
• 824-94-2 p-methoxybenzyl chloride 
• 17105-65-6 dimethyl 4-methoxybenzylphosphonate 
• 56-23-5 tetrachloromethane 
• 7109-27-5 1,1,2-tris(4-methoxyphenyl)ethene 
• 7782-50-5 chlorine 
• 25354-46-5 1-bromo-1,2,2-tris(p-methoxyphenyl)ethene 
• 72-43-5 Methoxychlor 
• 86457-76-3 Dimethyl 1-chloro-1-(4-methoxyphenyl)methanephosphonate 

Downstream Products

• 7109-27-5 1,1,2-tris(4-methoxyphenyl)ethene 
• 1040086-21-2 9-chloro-3,6-dimethoxy-10-(p-methoxyphenyl)phenanthrene 
• 90-96-0 bis(p-methoxyphenyl)methanone 
• 96784-47-3 1-Acetoxy-1,2,2-tris(4-methoxyphenyl)ethene 
• 133627-95-9 9-acetoxy-3,6-dimethoxy-10-(p-methoxyphenyl)phenanthrene 

Relevant articles and documents

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