33719-74-3

Basic information

• Product Name: 3,5-Dichloroanisole
• Synonyms: 3,5-DICHLOROANISOLE;3,5-DICHLORANISOL;1,3-DICHLORO-5-METHOXYBENZENE;Benzene, 1,3-dichloro-5-methoxy-;TOLCLOFOS-METHYL PESTANAL, 250 MG;3,5-Dichloroanisole,98%;3,5-Dichloroanisole,1,3-Dichloro-5-methoxybenzene;1,3-Dichloro-5-methoxybenzene, 3,5-Dichlorophenyl methyl ether
• CAS NO: 33719-74-3
• Molecular Formula: C₇H₆Cl₂O
• Molecular Weight: 177.03
• EINECS: 251-655-6
• Product Categories: Aromatic Ethers;Anisole;Anisoles, Alkyloxy Compounds & Phenylacetates;Chlorine Compounds
• Mol File: 33719-74-3.mol
• Article Data: 9

Chemical Properties

• Melting Point: 39-41 °C (dec.)(lit.)
• Boiling Point: 97°C 7,6mm
• Flash Point: 223 °F
• Appearance: /
• Density: 1.289g/cm³
• Vapor Pressure: 0.142mmHg at 25°C
• Refractive Index: 1.534
• Storage Temp.: Refrigerator
• Solubility: Chloroform, Ethyl Acetate (Slightly), Methanol (Slightly)
• BRN: 1936395
• CAS DataBase Reference: 3,5-Dichloroanisole(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Dichloroanisole(33719-74-3)
• EPA Substance Registry System: 3,5-Dichloroanisole(33719-74-3)

Safety Data

• Hazard Codes: Xn
• Statements: 36/37/38-20/22
• Safety Statements: 22-24/25-37/39-26
• WGK Germany: 3
• Hazardous Substances Data: 33719-74-3(Hazardous Substances Data)

Usage

Description

3,5-Dichloroanisole is a chlorinated anisole derivative, which is a white to yellow crystalline powder. It is known for its possible antibacterial activity and serves as an organic building block for the synthesis of various chlorinated chemical compounds, such as polychlorinated dibenzofurans (PCDD/F). Additionally, it has been studied for its 35Cl Nuclear Quadrupole Resonance (NQR) frequency and spin lattice relaxation time.

Uses

Used in Chemical Synthesis:
3,5-Dichloroanisole is used as an organic building block for the synthesis of chlorinated chemical compounds. Its application is particularly relevant in the production of polychlorinated dibenzofurans (PCDD/F), which are important for various industrial processes.
Used in Pharmaceutical Industry:
3,5-Dichloroanisole is used as a potential antibacterial agent due to its chlorinated nature. This application is significant in the development of new drugs to combat bacterial infections, especially in the context of increasing antibiotic resistance.
Used in Research and Development:
The study of 3,5-dichloroanisole's 35Cl Nuclear Quadrupole Resonance (NQR) frequency and spin lattice relaxation time contributes to the understanding of its chemical properties. This knowledge can be applied in research and development for various applications, including the design of new materials and the improvement of existing chemical processes.

InChI:InChI=1/C7H6Cl2O/c1-10-7-3-5(8)2-6(9)4-7/h2-4H,1H3

Synthetic route

3,5-dichlorophenol (591-35-5) + dimethyl sulfate (77-78-1) → 3,5-dichloroanisole (33719-74-3)

Conditions	Yield
With potassium carbonate In acetone for 3h;	100%
With potassium carbonate In acetone for 3h; Ambient temperature;	100%
With sodium hydroxide

3,5-dichlorophenol (591-35-5) + carbonic acid dimethyl ester (616-38-6) → 3,5-dichloroanisole (33719-74-3)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene at 90℃; Inert atmosphere;	100%

1,3,5-trichlorobenzene (108-70-3) + sodium methylate (124-41-4) → 3,5-dichloroanisole (33719-74-3)

Conditions	Yield
In dimethyl sulfoxide at 80 - 90℃; Concentration; Reagent/catalyst; Solvent; Temperature; Time;	98%
In N,N,N,N,N,N-hexamethylphosphoric triamide at 120℃; for 1h;	78%
In methanol; dimethyl sulfoxide at 50.1℃; Rate constant;
With methanol at 180℃;

methanol (67-56-1) + 1,3,5-trichlorobenzene (108-70-3) + sodium methylate (124-41-4) → 3,5-dichlorophenol (591-35-5) + 3,5-dichloroanisole (33719-74-3)

Conditions	Yield
at 180℃; im Rohr;
at 175℃; Kinetics; im Rohr;

3,5-dichlorophenol (591-35-5) + methyl iodide (74-88-4) → 3,5-dichloroanisole (33719-74-3)

Conditions	Yield
With sodium hydroxide In N,N-dimethyl acetamide at 25℃; Rate constant;

3,5-dichlorophenolate (65800-69-3) + S-methyldibenzothiophenium tetrafluoroborate (29829-22-9) → 3,5-dichloroanisole (33719-74-3)

Conditions	Yield
In methanol at 30℃; for 3h;

3,5-Dichloroaniline (626-43-7) → 3,5-dichloroanisole (33719-74-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: Diazotization.Verkochen mit H2SO4 2: NaOH-solution View Scheme

2-(3-chloro-5-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (929626-16-4) → 3,5-dichloroanisole (33719-74-3)

Conditions	Yield
With copper dichloride In methanol at 90℃;	193 mg

3,5-dichloroanisole (33719-74-3) → 3,4,5-trichloroanisole (54135-82-9)

Conditions	Yield
With trichloroisocyanuric acid In N,N-dimethyl-formamide for 1h;	87%
With 1,3,5-trichloro-2,4,6-triazine In N,N-dimethyl-formamide for 1h; Ambient temperature;	87%
With chlorine

3,5-dichloroanisole (33719-74-3) + 2,4-dichlorobenzoyl chloride (89-75-8) → (2,6-dichloro-4-methoxyphenyl)(2,4-dichlorophenyl)methanone (934562-64-8)

Conditions	Yield
With aluminium trichloride In nitrobenzene at -78 - 20℃; for 25h; Friedel-Crafts reaction;	85%
With aluminum (III) chloride In nitrobenzene at -78 - 20℃; for 25h;	85%
Stage #1: 3,5-dichloroanisole; 2,4-dichlorobenzoyl chloride With aluminum (III) chloride In nitromethane at -78 - 20℃; for 25h; Friedel Crafts Acylation; Stage #2: With sodium hydroxide In diethyl ether; nitromethane at 0℃; Product distribution / selectivity; Friedel Crafts Acylation;	80%

3,5-dichloroanisole (33719-74-3) → 3-chloro-5-methoxyphenol (65262-96-6)

Conditions	Yield
With copper acetylacetonate; N1-(4-hydroxy-2,6-dimethylphenyl)-N2-(4-hydroxy-3,5-dimethylphenyl)oxalamide; water In water; dimethyl sulfoxide at 130℃; for 24h; Schlenk technique; Inert atmosphere;	82%

3,5-dichloroanisole (33719-74-3) → 1-methoxy-3,5-diamino-benzene (100-96-9) + 3-chloro-5-methoxyaniline (10272-06-7)

Conditions	Yield
With ammonium hydroxide; potassium phosphate; copper(l) iodide; N1,N2-bis(5-methyl-[1,1'-biphenyl]-2-yl)oxalamide In water; dimethyl sulfoxide at 110℃; for 24h; Concentration; Inert atmosphere; Sealed tube;	A 10% B 81%

3,5-dichloroanisole (33719-74-3) + 2,4,6-trichlorobenzoyl chloride (4136-95-2) → (2,6-dichloro-4-methoxyphenyl)(2,4,6-trichlorophenyl)methanone (1380572-64-4)

Conditions	Yield
With aluminum (III) chloride In nitrobenzene at 0 - 20℃; Friedel-Crafts reaction;	80%

3,5-dichloroanisole (33719-74-3) + Propionamid (79-05-0) → N-(3-chloro-5-methoxyphenyl)propionamide

Conditions	Yield
With copper(I) oxide; potassium phosphate; N1,N2-bis(thiophen-2-ylmethyl)oxalamide In tert-butyl alcohol at 130℃; for 24h; Schlenk technique;	78%

3,5-dichloroanisole (33719-74-3) → 1,3-dichloro-2-iodo-5-methoxybenzene (98273-17-7)

Conditions	Yield
With iodine; silver sulfate In acetonitrile at 20℃; for 72h; Inert atmosphere;	77%
Multi-step reaction with 3 steps 1: HNO3; H2SO4 / CH2Cl2 / 18 h / 20 °C 2: 7 percent / Na2S2O4 / aq. ethanol / 2 h / Heating View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid; nitric acid / dichloromethane / 18 h 1.2: 14 h / Heating 2.1: sulfuric acid; potassium iodide; sodium nitrite / water / 18 h / 0 °C / Heating View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid; nitric acid / dichloromethane / 18 h 2: sodium dithionite / ethanol; water / 14 h / Heating 3: sulfuric acid; potassium iodide; sodium nitrite / water / 18 h / 0 °C / Heating View Scheme
With iodine; silver sulfate In acetonitrile at 20℃; for 42h; regioselective reaction;	65 %Chromat.

3,5-dichloroanisole (33719-74-3) + 2,6-Dichlorobenzoyl chloride (4659-45-4) → (2,4-dichloro-6-hydroxyphenyl)(2,6-dichlorophenyl)methanone (34786-96-4)

Conditions	Yield
With aluminum (III) chloride at 0 - 110℃; for 15h; Inert atmosphere;	72%

3,5-dichloroanisole (33719-74-3) → 3,5-dichlorophenol (591-35-5)

Conditions	Yield
With boron triiodide-N,N-diethylaniline In benzene for 4h; Ambient temperature;	67%
With hydrogen bromide In water Reflux;

3,5-dichloroanisole (33719-74-3) + (2-(4-bromophenyl)ethynyl)triisopropylsilane (271242-20-7) → 2'-iodo-5'-methoxy-4,4''-bis[2-(triisopropylsilyl)ethynyl]-1,1':3',1''-terphenyl

Conditions	Yield
Stage #1: 3,5-dichloroanisole With [bis-(trifluoroacetoxy)iodo]benzene; iodine In dichloromethane at 20℃; for 2.5h; Stage #2: (2-(4-bromophenyl)ethynyl)triisopropylsilane With tert.-butyl lithium In diethyl ether; pentane at 10 - 20℃; for 15h; Stage #3: With iodine In diethyl ether; pentane at 0℃; for 1h;	66%

3,5-dichloroanisole (33719-74-3) → Potassium; 3,5-dichloro-phenolate

Conditions	Yield
With Triton X-114; potassium thioacyanate at 180℃; for 6h;	65%

3,5-dichloroanisole (33719-74-3) → 1,5-dichloro-2-iodo-3-methoxybenzene (1271523-34-2) + 1,3-dichloro-2-iodo-5-methoxybenzene (98273-17-7)

Conditions	Yield
With [bis-(trifluoroacetoxy)iodo]benzene; iodine In dichloromethane at 20℃; for 2.5h; Overall yield = 85 %; Overall yield = 3.20 g;	A 21% B 64%
With N-iodo-succinimide; toluene-4-sulfonic acid In acetonitrile for 18h; regioselective reaction;	A 14 %Chromat. B 68 %Chromat.

piperidine (110-89-4) + 3,5-dichloroanisole (33719-74-3) → 1,1′-(5-methoxy-1,3-phenylene)dipiperidine

Conditions	Yield
With potassium tert-butylate In toluene at 155℃; for 24h; Autoclave;	63%

furan (110-00-9) + 3,5-dichloroanisole (33719-74-3) → 7-chloro-5-methoxy-1,4-dihydro-1,4-epoxidonaphthalene

Conditions	Yield
With n-butyllithium; diisopropylamine In tetrahydrofuran at -78 - 0℃; for 3h;	60%

3,5-dichloroanisole (33719-74-3) + 2,4,6-trichlorobenzoyl chloride (4136-95-2) → (2,4-dichloro-6-hydroxyphenyl)(2,4,6-trichlorophenyl)methanone

Conditions	Yield
With aluminum (III) chloride at 0 - 110℃; for 15h; Inert atmosphere;	58.6%

3,5-dichloroanisole (33719-74-3) + ethylene dibromide (106-93-4) → 3-methoxy-5-chlorobenzaldehyde (164650-68-4)

Conditions	Yield
Stage #1: 3,5-dichloroanisole; ethylene dibromide With magnesium In tetrahydrofuran for 3h; Heating / reflux; Stage #2: With N,N-dimethyl-formamide In tetrahydrofuran at 0℃;	54%

3,5-dichloroanisole (33719-74-3) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 3-methoxy-5-chlorobenzaldehyde (164650-68-4)

Conditions	Yield
Stage #1: 3,5-dichloroanisole With magnesium; ethylene dibromide In tetrahydrofuran at 0 - 25℃; for 3h; Heating / reflux; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran Stage #3: With hydrogenchloride; water In tetrahydrofuran	54%
Stage #1: 3,5-dichloroanisole With magnesium; ethylene dibromide In tetrahydrofuran for 3h; Heating / reflux; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at 0℃;	54%
Stage #1: 3,5-dichloroanisole With magnesium; ethylene dibromide In tetrahydrofuran for 3h; Heating / reflux; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at 0℃;	54%
Stage #1: 3,5-dichloroanisole With magnesium; ethylene dibromide In tetrahydrofuran for 3h; Heating / reflux; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at 0℃;	54%

3,5-dichloroanisole (33719-74-3) + sodium methylate (124-41-4) → 3,5-dichlorophenol (591-35-5) + 3-chloro-5-methoxyphenol (65262-96-6) + 1-chloro-3,5-dimethoxybenzene (7051-16-3)

Conditions	Yield
In N,N,N,N,N,N-hexamethylphosphoric triamide at 120℃;	A 51% B 7% C 40%
In N,N,N,N,N,N-hexamethylphosphoric triamide at 120℃; for 1h;	A 51% B 7% C 40%

3,5-dichloroanisole (33719-74-3) → 3,5-dichlorophenol (591-35-5) + 3-chloro-5-methoxyphenol (65262-96-6) + 1-chloro-3,5-dimethoxybenzene (7051-16-3)

Conditions	Yield
With sodium methylate In N,N,N,N,N,N-hexamethylphosphoric triamide at 120℃; for 1h;	A 51% B 7% C 40%

carbon dioxide (124-38-9) + 3,5-dichloroanisole (33719-74-3) → 3-chloro-5-methoxy-benzoic acid (82477-67-6)

Conditions	Yield
Stage #1: 3,5-dichloroanisole With magnesium; ethylene dibromide In tetrahydrofuran for 2h; Heating / reflux; Stage #2: carbon dioxide In tetrahydrofuran	41%
With hydrogenchloride; magnesium Yield given. Multistep reaction;

3,5-dichloroanisole (33719-74-3) → 3-chloro-5-methoxy-benzoic acid (82477-67-6)

Conditions	Yield
Stage #1: 3,5-dichloroanisole With magnesium; ethylene dibromide In tetrahydrofuran for 2h; Heating / reflux; Stage #2: With hydrogenchloride In tetrahydrofuran; water	41%

3,5-dichloroanisole (33719-74-3) + acetyl chloride (75-36-5) → 1-(2,6-dichloro-4-methoxyphenyl)ethanone (157487-30-4)

Conditions	Yield
Stage #1: acetyl chloride With aluminum (III) chloride In dichloromethane at 0℃; for 0.5h; Stage #2: 3,5-dichloroanisole In dichloromethane at 20℃; for 2h;	40%

formaldehyd (50-00-0) + 3,5-dichloroanisole (33719-74-3) → (2,6-dichloro-4-methoxy-phenyl)-methanol (86111-47-9)

Conditions	Yield
Stage #1: formaldehyd; 3,5-dichloroanisole With hydrogenchloride; sulfuric acid In water at 60℃; Stage #2: With sodium hydroxide In 1,4-dioxane; water for 3h; Heating;	30%
With hydrogenchloride; sulfuric acid In water at 60℃;	30%
Stage #1: formaldehyd; 3,5-dichloroanisole With hydrogenchloride; sulfuric acid In water at 100℃; for 8h; Stage #2: With water; sodium hydroxide In 1,4-dioxane at 100℃; for 3h;	4.67 g

Dichloromethyl methyl ether (4885-02-3) + 3,5-dichloroanisole (33719-74-3) → 2,6-dichloro-4-methoxy-benzaldehyde (82772-93-8)

Conditions	Yield
With tin(IV) chloride In dichloromethane 1.) 0 deg C, 30 min, 2.) RT, 3 h;	28%

formaldehyd (50-00-0) + 3,5-dichloroanisole (33719-74-3) → 2,4-dichloro-6-methoxybenzyl alcohol (911718-18-8) + (2,6-dichloro-4-methoxy-phenyl)-methanol (86111-47-9)

Conditions	Yield
With hydrogenchloride; sulfuric acid In water at 60℃; for 7h; Inert atmosphere;	A 15% B 25%
Stage #1: formaldehyd; 3,5-dichloroanisole With hydrogenchloride; sulfuric acid In water at 70℃; for 7h; Inert atmosphere; Stage #2: With sodium hydroxide In 1,4-dioxane; water for 7h; Reflux; Inert atmosphere;	A 3.74 g B 7.9 g

3,5-dichloroanisole (33719-74-3) → 4-bromo-3,5-dichloroanisole + C7H5BrCl2O (73931-43-8)

Conditions	Yield
With hydrogenchloride; N-Bromosuccinimide In water; acetone at 20℃; for 0.5h;	A 25% B n/a
With hydrogenchloride; N-Bromosuccinimide; water In acetone at 20℃; for 0.0833333h; Inert atmosphere;

Upstream product

• 591-35-5 3,5-dichlorophenol 
• 74-88-4 methyl iodide 
• 929626-16-4 2-(3-chloro-5-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 
• 616-38-6 carbonic acid dimethyl ester 
• 626-43-7 3,5-Dichloroaniline 
• 65800-69-3 3,5-dichlorophenoxide 
• 29829-22-9 S-methyldibenzothiophenium tetrafluoroborate 
• 77-78-1 dimethyl sulfate 
• 108-70-3 1,3,5-trichlorobenzene 
• 124-41-4 sodium methylate 
• 67-56-1 methanol 

Downstream Products

• 94294-10-7 methyl 2,4-dichloro-6-methoxybenzoate 
• 94278-65-6 methyl 2,6-dichloro-4-methoxybenzoate 
• 82477-67-6 3-chloro-5-methoxy-benzoic acid 
• 100948-83-2 3,5-dichloro-4-nitroanisole 
• 74672-01-8 3,5-dichloro-2-nitroanisole 
• 2845-89-8 1-chloro-3-methoxy-benzene 
• 100-66-3 methoxybenzene 
• 934562-64-8 (2,6-dichloro-4-methoxyphenyl)(2,4-dichlorophenyl)methanone 
• 82772-93-8 2,6-dichloro-4-methoxy-benzaldehyde 
• 78444-52-7 2,4-dichloro-6-methoxybenzaldehyde 
• 934562-65-9 (2,6-dichloro-4-methoxyphenyl)(2,4-dichlorophenyl)methyl alcohol 
• 74390-79-7 (2,6-dichloro-4-hydroxyphenyl)(2,4-dichlorophenyl)methanone 
• 934562-66-0 methyl 2-(3,5-dichloro-4-(2,4-dichlorobenzoyl)phenoxy)acetate 
• 934562-67-1 methyl 2-(3,5-dichloro-4-((2,4-dichlorophenyl)(hydroxy)methyl)phenoxy)acetate 

Relevant articles and documents

METHOD FOR SYNTHESIZING 3,5-DICHLOROANISOLE FROM 1,3,5-TRICHLOROBENZENE

The invention relates to a method for synthesizing 3,5-dichloroanisole from 1,3,5-trichlorobenzene, which comprises: a) the reaction between 1,3,5-trichlorobenzene and a methanolate of an alkaline or alkaline-earth metal in a first solvent chosen from among dimethylsulfoxide and 1,1,3,3-tetramethylurea; b) the precipitation of the product resulting from step a) in a second solvent which is not included among substances considered carcinogenic, mutagenic and/or toxic for reproduction by Regulation (EC) n° 1272/2008 of the European Parliament and of the Council of 16 Dec. 2008; then c) the recovery of the precipitate thus obtained. Application: synthesis of 1,3,5-triamino-2,4,6-trinitrobenzene of which 3,5-dichloroanisole is an intermediate product.

Meta halogenation of 1,3-disubstituted arenes via iridium-catalyzed arene borylation

We report the meta halogenation of 1,3-disubstituted arenes to form 3,5-disubstituted aryl bromides and chlorides by using iridium-catalyzed arene borylation chemistry. Iridium-catalyzed borylation of arenes with B2pin2, followed by reaction of the boronic ester with copper(II) bromide or chloride converts arylboronic esters to the corresponding aryl halides. A variety of arenes containing alkoxy, alkyl, halogen, nitrile, ester, amide, and pivaloyl and TIPS-protected alcohols were converted to the corresponding 3,5-disubstituted aryl bromides and chlorides in yields ranging from 46% to 85%. In addition, 2,6-disubstituted and 3-substituted pyridines were converted to the 4-halo and 5-halopyridines, respectively. The utility of this methodology was demonstrated by the formal conversion of nicotine to Altinicline in three steps with an overall yield of 61% using meta bromination of nicotine as the first step. Copyright

Total synthesis of (+)- and (-)-neopyrrolomycins, chlorinated phenylpyrrole antibiotics

The first total synthesis of (+)- and (-)-neopyrrolomycins (11a and 11b) is detailed based on regioselective chlorinations of 3,5-dichloroanisole (2) and 1-(2,3,4-trichloro-6-methoxyphenyl)-1H-pyrrole-2-carboxylic acid (8) with isocyanuric trichloride, followed by optical resolution of racemic neopyrrolomycin (11) with N-(p-tolylsulfonyl)-L-phenylalanyl chloride. Several analogs (21-25) have been prepared from the intermediates, and the structure-activity relationships are also discussed.