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

Chemical Properties

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Uses

3,5-Dichloroanisole, is a chlorinated anisole derivative, possessing possible antibacterial activity. It is also an organic building block that can be used for the synthesis of chlorinated chemical compounds, such as polychlorinated dibenzofurans (PCDD/F).

General Description

3,5-Dichloroanisole on nitration under mild conditions yields 3,5-dichloro-2,4,6-trinitroanisole. The 35Cl Nuclear Quadrupole Resonance (NQR) frequency and spin lattice relaxation time in 3,5-dichloroanisole has been measured.

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

Downstream Products

• 82477-66-5 1-chloro-3-methoxy-5-methylbenzene 
• 60964-09-2 2,6-dichloro-4-hydroxybenzaldehyde 
• 82772-93-8 2,6-dichloro-4-methoxy-benzaldehyde 
• 164650-68-4 3-methoxy-5-chlorobenzaldehyde 
• 174913-20-3 4-bromo-3,5-dichloroanisole 
• 73931-43-8 C₇H₅BrCl₂O 
• 65262-96-6 3-chloro-5-methoxyphenol 
• 100-96-9 1-methoxy-3,5-diamino-benzene 
• 10272-06-7 3-chloro-5-methoxyaniline 
• 94294-10-7 methyl 2,4-dichloro-6-methoxybenzoate 
• 94294-09-4 2,4-dichloro-6-methoxybenzoic acid 
• 1445972-33-7 3,3'-diamino-5,5'-dimethoxy-diphenylamine 
• 1439936-11-4 N-(4-(2,6-dichloro-4-methoxyphenyl)thiazol-2-yl)isonicotinamide 
• 1439936-13-6 4-(2,6-dichloro-4-methoxyphenyl)thiazol-2-ylamine 

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.