626-16-4

Basic information

• Product Name: 1,3-Bis(chloromethyl)benzene
• Synonyms: 1,3-Bis(chloroethyl)benzene;1,3-bis(chloromethyl)-benzen;alpha,alpha’-dichloro-m-xylen;benzene,1,3-bis(chloromethyl)-;m-Bis(chloromethyl)benzene;m-Dichloroxylene;m-Xylene, alpha,alpha'-dichloro-;α,α’-dichloro-m-xylene
• CAS NO: 626-16-4
• Molecular Formula: C₈H₈Cl₂
• Molecular Weight: 175.06
• EINECS: 210-932-1
• Product Categories: Intermediates of Dyes and Pigments;Aryl;Building Blocks;C8;Chemical Synthesis;Halogenated Hydrocarbons;Organic Building Blocks
• Mol File: 626-16-4.mol

Chemical Properties

• Melting Point: 33-35 °C(lit.)
• Boiling Point: 250-255 °C(lit.)
• Flash Point: >230 °F
• Appearance: Colorless to light yellow liquid
• Density: 1.202 g/mL at 25 °C(lit.)
• Refractive Index: 1.5544 (estimate)
• Storage Temp.: Store at
• Solubility: methanol: soluble1g/10 mL, clear, colorless
• Water Solubility: hydrolysis
• BRN: 2079898
• CAS DataBase Reference: 1,3-Bis(chloromethyl)benzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1,3-Bis(chloromethyl)benzene(626-16-4)
• EPA Substance Registry System: 1,3-Bis(chloromethyl)benzene(626-16-4)

Safety Data

• Hazard Codes: Xn,Xi,C
• Statements: 22-36/37/38-36-34
• Safety Statements: 26-24/25-45-36/37/39-27
• RIDADR: UN 2811 6.1/PG 2
• WGK Germany: 3
• RTECS: ZE4070000
• F: 19
• TSCA: Yes
• HazardClass: 6.1
• PackingGroup: II
• Hazardous Substances Data: 626-16-4(Hazardous Substances Data)

Usage

Uses

Used in Ionic Liquids:
1,3-Bis(chloromethyl)benzene is used as a precursor in the synthesis of ionic liquids to enhance their thermal stability. Ionic liquids are salts with low melting points, which have gained significant attention due to their unique properties, such as low vapor pressure, high thermal stability, and excellent solvation capabilities. By incorporating 1,3-bis(chloromethyl)benzene into the structure of ionic liquids, their thermal stability can be improved, making them suitable for applications in various industries, such as energy storage, catalysis, and separation processes.
Used in C2-Symmetric Small Molecule Inhibitors:
1,3-Bis(chloromethyl)benzene is also used as a reagent in the synthesis of C2-symmetric small molecule inhibitors. These inhibitors are designed to target specific enzymes or proteins involved in various biological processes, such as inflammation, cancer, and viral infections. The symmetrical structure of 1,3-bis(chloromethyl)benzene allows for the creation of C2-symmetric molecules with improved binding affinity and selectivity towards their target proteins, leading to more effective therapeutic agents.

Synthetic route

m-xylene (108-38-3) → 3-(chloromethyl)benzyl chloride (626-16-4)

Conditions	Yield
With chlorine; 1-butyl-3-methylimidazolium chloride at 58℃; for 3h; Reagent/catalyst; Temperature; Irradiation; Ionic liquid;	99.18%
With chlorine Sonnenlicht;
With phosphorus pentachloride at 190℃;

1,3-dimethanol benzene (626-18-6) → 3-(chloromethyl)benzyl chloride (626-16-4)

Conditions	Yield
With oxalyl dichloride; Tropone In dichloromethane at 20℃; for 0.416667h; Inert atmosphere;	76%
With hydrogenchloride

N-chloro-succinimide (128-09-6) + m-xylene (108-38-3) → 1-chloromethyl-3-methyl-benzene (620-19-9) + 3-(chloromethyl)benzyl chloride (626-16-4)

Conditions	Yield
Irradiation.UV-Licht;

N-chloro-succinimide (128-09-6) + m-xylene (108-38-3) → 3-(chloromethyl)benzyl chloride (626-16-4)

Conditions	Yield
Irradiation.UV-Licht;

dimethyl Isophthalate (1459-93-4) → 3-(chloromethyl)benzyl chloride (626-16-4)

Conditions	Yield
With lithium aluminium tetrahydride; diethyl ether anschliessend Behandeln des Reaktionsprodukts mit konz. wss. Salzsaeure;

formaldehyd (50-00-0) + benzyl chloride (100-44-7) → 3-(chloromethyl)benzyl chloride (626-16-4)

Conditions	Yield
With aluminium trichloride; 1,2-dichloro-ethane; zinc(II) chloride at 50℃; Einleiten von HCl;

m-xylene (108-38-3) → 1-chloromethyl-3-methyl-benzene (620-19-9) + 3-(chloromethyl)benzyl chloride (626-16-4) + m-chloromethylbenzylidene chloride (30220-25-8) + α,α-dichloro-m-xylene (2719-42-8) + α,α,α',α'-Tetrachloro-m-xylene (30430-40-1)

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); chlorine at 70℃; for 1.2h; Product distribution; various educt-reagent ratio, various time;

hydrogenchloride (7647-01-0) + formaldehyd (50-00-0) + aluminium trichloride (7446-70-0) + benzyl chloride (100-44-7) + ZnCl2 → 4,4'-bis(chloromethyl)diphenylmethane (14568-83-3) + o-Xylylene dichloride (612-12-4) + 3-(chloromethyl)benzyl chloride (626-16-4) + p-Xylylene dichloride (623-25-6)

Conditions	Yield
at 50℃; Verb. 5: 1.2-Dichlor-aethan;

...Expand

m-xylene (108-38-3) → 1-chloromethyl-3-methyl-benzene (620-19-9) + 3-(chloromethyl)benzyl chloride (626-16-4)

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); 1,3,4,6-tetrachloro-3α,6α-diphenyl glycoluril In tetrachloromethane at 81℃; for 2h; Inert atmosphere;	A 52 %Chromat. B 16 %Chromat.

3-(chloromethyl)benzyl chloride (626-16-4) + N1-(2,6-diisopropylphenyl)-N2-methylethane-1,2-diamine → C38H58N4

Conditions	Yield
With potassium carbonate In ethanol for 96h; Reflux;	99%

3-(chloromethyl)benzyl chloride (626-16-4) → 1,3-Bis-benzene (17604-82-9)

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride; potassium acetate In acetone; toluene	98.7%

1H-imidazole (288-32-4) + 3-(chloromethyl)benzyl chloride (626-16-4) → 1,3-bis(imidazol-1-ylmethyl)benzene (69506-92-9)

Conditions	Yield
With sodium hydride In 1,2-dimethoxyethane; mineral oil at 0 - 20℃; for 15h;	98%
Stage #1: 1H-imidazole With potassium hydroxide In acetonitrile at 20℃; for 1h; Stage #2: 3-(chloromethyl)benzyl chloride In acetonitrile at 20℃; for 6h;	73%
With potassium hydroxide In acetonitrile at 20℃;

N-Ethylimidazole (7098-07-9) + 3-(chloromethyl)benzyl chloride (626-16-4) → [(1,3-phenylene)bis(methylene)]bis(1-ethyl-imidazolium) dichloride

Conditions	Yield
Stage #1: N-Ethylimidazole; 3-(chloromethyl)benzyl chloride at 135℃; for 0.166667h; Stage #2: Inert atmosphere;	98%

para-xylene (106-42-3) + 3-(chloromethyl)benzyl chloride (626-16-4) → C24H26

Conditions	Yield
With silica gel; zinc(II) chloride at 30℃; for 0.5h;	97%

3-(chloromethyl)benzyl chloride (626-16-4) + phenylacetylene (536-74-3) → 1,1'-(m-phenylenedimethylene)bis<4-phenyl-1H-1,2,3-triazole> (137959-34-3)

Conditions	Yield
With copper(l) iodide; sodium azide In water at 100℃; for 10h;	97%
With sodium azide In water at 70℃; for 7h; Huisgen Cycloaddition; Green chemistry; regioselective reaction;	88%

3-(chloromethyl)benzyl chloride (626-16-4) + phenylboronic acid (98-80-6) → 1,3-dibenzylbenzene (15180-20-8)

Conditions	Yield
With potassium phosphate; SP-4-[1,3-bis[2,6-diisopropylphenyl]-1,3-dihydro-2H-imidazol-2-ylidene]chloro[2-(1-methyl-1H-imidazol-2-yl-κN3)phenyl-κC]palladium(II) In ethanol at 60℃; for 3h; Suzuki-Miyaura Coupling; Inert atmosphere;	97%

3-(chloromethyl)benzyl chloride (626-16-4) + 2-methylpropan-2-thiol (75-66-1) → 1,3-bis(t-butylthiomethyl)benzene (70606-45-0)

Conditions	Yield
Stage #1: 2-methylpropan-2-thiol With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Schlenk technique; Stage #2: 3-(chloromethyl)benzyl chloride In tetrahydrofuran for 5h; Inert atmosphere; Schlenk technique;	97%

1-methyl-1-propanethiol (513-53-1) + 3-(chloromethyl)benzyl chloride (626-16-4) → C16H26S2

Conditions	Yield
Stage #1: 1-methyl-1-propanethiol With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Schlenk technique; Stage #2: 3-(chloromethyl)benzyl chloride In tetrahydrofuran for 5h; Inert atmosphere; Schlenk technique;	97%

3-(chloromethyl)benzyl chloride (626-16-4) + mercaptoacetic acid (68-11-1) → 1,3-xylylenedimercaptoacetic acid (122591-10-0)

Conditions	Yield
With sodium hydroxide In methanol for 6h; Heating;	96%

3-(chloromethyl)benzyl chloride (626-16-4) + diphenylphosphane (829-85-6) → 1,3-bis(diphenylphosphinomethyl)benzene (89756-88-7)

Conditions	Yield
Stage #1: diphenylphosphane With n-butyllithium In tetrahydrofuran; hexane at -40 - 0℃; Metallation; Stage #2: 3-(chloromethyl)benzyl chloride In tetrahydrofuran; hexane at 20℃; Condensation; Heating; Further stages.;	96%
With n-butyllithium In tetrahydrofuran; hexane at -40℃; for 2h;

1-methyl-1H-imidazole (616-47-7) + 3-(chloromethyl)benzyl chloride (626-16-4) → 3,3'-dimethyl-1,1’-(1,3-phenylenedimethylene)-bis(1H-imidazolium) dichloride

Conditions	Yield
In N,N-dimethyl-formamide at 100℃; for 0.05h; Microwave irradiation;	96%
at 60℃; for 2h;	91.4%
at 135℃; for 10h;	91%
In toluene for 16h; Reflux;	70%

4,4'-Dihydroxybiphenyl (92-88-6) + 3-(chloromethyl)benzyl chloride (626-16-4) → 1,3-bis[4-(4-hydroxyphenyl)phenoxymethyl]benzene (815600-60-3)

Conditions	Yield
Stage #1: 4,4'-Dihydroxybiphenyl With sodium hydroxide In water; dimethyl sulfoxide at 80℃; Stage #2: 3-(chloromethyl)benzyl chloride In water; dimethyl sulfoxide at 80 - 120℃; for 2h;	96%

4-(2,6-dimethylphenyl)-1,2,4-4H-triazole (1245737-20-5) + 3-(chloromethyl)benzyl chloride (626-16-4) → 1-[1-(3-chloromethyl)phenyl(methyl)]-4-[2,6-dimethylphenyl]-1,2,4-4H-triazol-1-ium chloride (1429043-31-1)

Conditions	Yield
In neat (no solvent) at 120℃; for 2h;	96%

3-(chloromethyl)benzyl chloride (626-16-4) + bis(pinacol)diborane (73183-34-3) → 1,3-bis((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzene

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 20℃; for 18h;	96%

3-(chloromethyl)benzyl chloride (626-16-4) + ephedrine (299-42-3) → C28H36N2O2 (191990-87-1)

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃;	95%

3-(chloromethyl)benzyl chloride (626-16-4) + 2-Phenylphenol (90-43-7) → 1,3-bis(([1,1'-biphenyl]-2-yloxy)methyl)benzene (1409952-66-4)

Conditions	Yield
Stage #1: 2-Phenylphenol With potassium hydroxide In dimethyl sulfoxide at 35℃; for 0.75h; Inert atmosphere; Stage #2: 3-(chloromethyl)benzyl chloride In dimethyl sulfoxide at 35 - 50℃; for 3.41667h;	95%

N1-(2,6-dimethylphenyl)-N2-methylethane-1,2-diamine + 3-(chloromethyl)benzyl chloride (626-16-4) → C30H42N4

Conditions	Yield
With potassium carbonate In ethanol for 96h; Reflux;	95%

4-(2-benzylthiophenyl)-4H-1,2,4-triazole (1245737-22-7) + 3-(chloromethyl)benzyl chloride (626-16-4) → 1,1'-[1,3-phenylenedi(methylene)]bis[4-((2-benzylthio)phenyl)-4H-1,2,4-triazol-1-ium] dichloride

Conditions	Yield
at 130℃; for 2h; neat (no solvent);	94%

2-methylpropanethiol-1 (513-44-0) + 3-(chloromethyl)benzyl chloride (626-16-4) → C16H26S2

Conditions	Yield
Stage #1: 2-methylpropanethiol-1 With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Schlenk technique; Stage #2: 3-(chloromethyl)benzyl chloride In tetrahydrofuran for 5h; Inert atmosphere; Schlenk technique;	94%

3,4-dimethyl-7-hydroxycoumarin (2107-78-0) + 3-(chloromethyl)benzyl chloride (626-16-4) → 7-{[3-(chloromethyl)benzyl]oxy}-3,4-dimethyl-2H-chromen-2-one

Conditions	Yield
With potassium carbonate; potassium iodide In acetone at 130℃; for 0.5h; Microwave irradiation;	94%
With potassium carbonate In acetonitrile for 8h; Reflux;	65%

N,N,N',N'-tetramethyl-1,4-butanediamine (111-51-3) + 3-(chloromethyl)benzyl chloride (626-16-4) → C16H28N2(2+)*2Cl(1-)

Conditions	Yield
In acetonitrile for 24h; Alkylation; Cyclization; Heating;	93%

3-(chloromethyl)benzyl chloride (626-16-4) + diphenylthioselenophosphinic acid sodium salt (35351-90-7) → Se-prop-2-en-1-yl diphenylthioselenophosphinate (1427544-16-8)

Conditions	Yield
In ethanol at 40 - 43℃; for 0.166667h; Inert atmosphere;	93%

3-(chloromethyl)benzyl chloride (626-16-4) + 4,5-dihydro-1-[3-(triethoxysilyl)propyl]imidazole → 1,1’-[1,3-phenylenebis(methylene)]bis{3-[3-(triethoxysilyl)propyl]-4,5-dihydro-1H-imidazol-3-ium} chloride

Conditions	Yield
In toluene for 48h; Inert atmosphere; Reflux;	92%

2,3-benzocarbazole (243-28-7) + 3-(chloromethyl)benzyl chloride (626-16-4) → 1,3-bis(benzo[b]carbazol-9-ylmethyl)benzene

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; potassium hydroxide at 80℃; for 10h;	91%
With potassium hydroxide 1.) DMSO, 50 deg C, 1 h, 2.) DMSO, 90 deg C, 1 h; Yield given. Multistep reaction;

2-(2-hydroxy-phenoxy)-ethanol (4792-78-3) + 3-(chloromethyl)benzyl chloride (626-16-4) → m-bis(2-ethoxyphenyloxy)xylene (1012793-41-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 7h;	91%

3-(chloromethyl)benzyl chloride (626-16-4) + potassium diphenylphosphine (15475-27-1, 4346-39-8) → 1,3-bis(diphenylphosphinomethyl)benzene (89756-88-7)

Conditions	Yield
In tetrahydrofuran at 20℃; for 6.16667h; Inert atmosphere;	90.1%

methanol (67-56-1) + carbon monoxide (201230-82-2) + 3-(chloromethyl)benzyl chloride (626-16-4) → dimethyl 2,2'-(1,3-phenylene)diacetate (36076-19-4)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); N-ethyl-N,N-diisopropylamine at 80℃; under 15514.9 Torr; for 8h;	90%
With tetrakis(triphenylphosphine) palladium(0); N-ethyl-N,N-diisopropylamine at 80℃; for 8h; Autoclave;	90%
With calcium oxide; methyl iodide; dicobalt octacarbonyl at 65℃; under 760 Torr; for 10h;	77%

3-(chloromethyl)benzyl chloride (626-16-4) → 1,3-bis(mercaptomethyl)benzene (41563-69-3)

Conditions	Yield
With thiourea In ethanol for 2h; Heating;	90%
With sodium hydroxide; thiourea In water 1.) reflux, 2 h, 2.) reflux, 5 h;
Stage #1: 3-(chloromethyl)benzyl chloride With thiourea In water for 2.5h; Inert atmosphere; Reflux; Stage #2: With water; sodium hydroxide at 40 - 70℃; for 2h; Temperature; Inert atmosphere;	55 g

Upstream product

• 128-09-6 N-chloro-succinimide 
• 108-38-3 m-xylene 
• 626-18-6 1,3-dimethanol benzene 
• 50-00-0 formaldehyd 
• 100-44-7 benzyl chloride 
• 7647-01-0 hydrogenchloride 
• 7446-70-0 aluminium trichloride 
• 1459-93-4 dimethyl Isophthalate 

Downstream Products

• 626-18-6 1,3-dimethanol benzene 
• 23189-85-7 1,3-Bis-<2,2-dicarbethoxy-penten-(4)-yl>-benzol 
• 85894-48-0 C₂₈H₂₄N₄⁽²⁺⁾*2Cl^(1-) 
• 82005-93-4 1,3-bis[(chlorodimethylsilyl)methyl]benzene 
• 19806-17-8 1,3-benzenediacetic acid 
• 155106-81-3 1-(3-Chloromethyl-benzyl)-4-(2-isopropoxy-phenyl)-piperazine 
• 122591-10-0 1,3-xylylenedimercaptoacetic acid 
• 620-19-9 1-chloromethyl-3-methyl-benzene 
• 4662-96-8 1,2-di-m-tolylethane 
• 15180-20-8 1,3-dibenzylbenzene 
• 195448-62-5 1,3-Di-prop-2-ynyl-benzene 
• 89756-88-7 1,3-bis(diphenylphosphinomethyl)benzene 

Relevant articles and documents

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