612-12-4

Basic information

• Product Name: 1,2-Bis(chloromethyl)benzene
• Synonyms: DICHLORO(ALPHA, ALPHA'-)-O-XYLENE;A,A'-DICHLORO-O-XYLENE;A,A-DICHLORO-O-XYLENE;ALPHA,ALPHA'-DICHLORO-O-XYLENE;1,2-BIS(CHLOROMETHYL)BENZENE;1,2-DI(CHLOROMETHYL)BENZENE;O-XYLYLENE CHLORIDE;O-XYLYLENE DICHLORIDE
• CAS NO: 612-12-4
• Molecular Formula: C₈H₈Cl₂
• Molecular Weight: 175.06
• EINECS: 210-291-8
• Product Categories: Pharmaceutical Intermediates;Aryl;Building Blocks;C8;Chemical Synthesis;Halogenated Hydrocarbons;Organic Building Blocks
• Mol File: 612-12-4.mol
• Article Data: 5

Chemical Properties

• Melting Point: 51-55 °C(lit.)
• Boiling Point: 239-241 °C(lit.)
• Flash Point: 226 °F
• Appearance: white to light beige/Crystals or Crystalline Powder
• Density: 1.3930
• Refractive Index: 1.5544 (estimate)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: soluble in Methanol
• Water Solubility: hydrolysis
• BRN: 2043675
• CAS DataBase Reference: 1,2-Bis(chloromethyl)benzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1,2-Bis(chloromethyl)benzene(612-12-4)
• EPA Substance Registry System: 1,2-Bis(chloromethyl)benzene(612-12-4)

Safety Data

• Hazard Codes: C,Xi
• Statements: 34-36/37-36/37/38-50/53-26-22-36
• Safety Statements: 26-27-28-36/37/39-45-24/25-61-29-28A
• RIDADR: UN 3261 8/PG 2
• WGK Germany: 2
• RTECS: ZE4085000
• F: 19
• TSCA: Yes
• HazardClass: 6.1
• PackingGroup: II
• Hazardous Substances Data: 612-12-4(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powde

Uses

Different sources of media describe the Uses of 612-12-4 differently. You can refer to the following data:
1. 1,2-Bis(chloromethyl)benzene is used in solid-phase synthesis of large combinatorial variations of fundamental peptide unit 1 .
2. α,α′?Dichloro-o-xylene was used in solid-phase synthesis of large combinatorial variations of fundamental peptide unit.

General Description

α,α′-Dichloro-o-xylene reacts with elemental tellurium and NaI in 2-methoxyethanol to form 1,1-diiodo-3,4-benzo-1-telluracyclopentane.

Safety Profile

Poison by intravenous route. Mutation data reported. See also CHLORINATED HYDROCARBONS, AROMATIC. When heated to decomposition it emits toxic Cl-.

Synthetic route

phthalyl alcohol (612-14-6) → 1,3-dihydroisobenzofuran (496-14-0) + o-Xylylene dichloride (612-12-4) + 2-(chloromethyl)-phenyl methanol (142066-41-9)

Conditions	Yield
With hydrogenchloride In water at 70℃; for 1h;	A n/a B n/a C 91%

Benzotrichlorid (98-07-7) + phthalyl alcohol (612-14-6) → benzylidene dichloride (98-87-3) + o-Xylylene dichloride (612-12-4)

Conditions	Yield
With TOP; phenylsilane In neat (no solvent) at 100℃; for 24h; Appel Halogenation; Inert atmosphere;	A n/a B 65%

o-xylene (95-47-6) → o-Xylylene dichloride (612-12-4) + α,α,α'-trichloro-o-xylene (30293-58-4) + α,α-dichloro-o-xylene (60973-59-3) + 1-chloromethyl-2-methylbenzene (552-45-4)

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); chlorine at 90℃; for 4h;	A 50.5% B n/a C n/a D n/a

N-chloro-succinimide (128-09-6) + o-xylene (95-47-6) → o-Xylylene dichloride (612-12-4)

Conditions	Yield
Irradiation.UV-Licht;

N-chloro-succinimide (128-09-6) + o-xylene (95-47-6) → o-Xylylene dichloride (612-12-4) + 1-chloromethyl-2-methylbenzene (552-45-4)

Conditions	Yield
UV-Licht.Irradiation;

o-xylene (95-47-6) → o-Xylylene dichloride (612-12-4)

Conditions	Yield
With phosphorus pentachloride at 190℃;
durch Chlorierung im Sonnenlicht;
With chlorine Irradiation;

phthalic acid dimethyl ester (131-11-3) → o-Xylylene dichloride (612-12-4)

Conditions	Yield
With lithium aluminium tetrahydride; diethyl ether Erhitzen des Reaktionsgemisches mit konz. wss. Salzsaeure;

bis-(2-ethoxymethyl-benzyl)-amine (861338-62-7) → o-Xylylene dichloride (612-12-4) + o-chloromethylbenzylamine (38379-25-8)

Conditions	Yield
With hydrogenchloride; ethanol

formaldehyd (50-00-0) + benzyl chloride (100-44-7) → o-Xylylene dichloride (612-12-4) + p-Xylylene dichloride (623-25-6)

Conditions	Yield
With zinc(II) chloride at 80℃; Einleiten von HCl;
With aluminium trichloride; 1,2-dichloro-ethane; zinc(II) chloride at 50℃; Einleiten von HCl;

phthalyl alcohol (612-14-6) → o-Xylylene dichloride (612-12-4)

Conditions	Yield
With hydrogenchloride
With acetyl chloride; zinc(II) chloride
With tetrachloromethane; triphenylphosphine

formaldehyd (50-00-0) + toluene (108-88-3) → o-Xylylene dichloride (612-12-4) + p-Xylylene dichloride (623-25-6)

Conditions	Yield
With hydrogenchloride at 80 - 90℃; Leiten von Chlor in das Reaktionsgemisch bei 125-135grad;
With hydrogenchloride at 80 - 90℃; Behandlung des Reaktionsgemisches mit Chlor bei 125-135grad;

o-xylene (95-47-6) → o-Xylylene dichloride (612-12-4) + α,α,α'-trichloro-o-xylene (30293-58-4) + 1-chloromethyl-2-methylbenzene (552-45-4)

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); benzyl(trimethyl)ammonium tetrachloroiodate In tetrachloromethane for 6h; Heating;	A 49 % Spectr. B 12 % Spectr. C 30 % Spectr.

hydrogenchloride (7647-01-0) + formaldehyd (50-00-0) + benzyl chloride (100-44-7) + ZnCl2 → o-Xylylene dichloride (612-12-4) + p-Xylylene dichloride (623-25-6)

Conditions	Yield
at 80℃;

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

o-xylene (95-47-6) → o-Xylylene dichloride (612-12-4) + 1-chloromethyl-2-methylbenzene (552-45-4)

Conditions	Yield
With chlorine In tetrachloromethane for 0.0833333h; Photolysis;
With 2,2'-azobis(isobutyronitrile); 1,3,4,6-tetrachloro-3α,6α-diphenyl glycoluril In tetrachloromethane at 81℃; for 2h; Temperature; Time; Inert atmosphere;	A 26 %Chromat. B 41 %Chromat.

Phthaloyl dichloride (88-95-9) → o-Xylylene dichloride (612-12-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: glacial acetic acid; sodium amalgam 2: concentrated hydrochloric acid View Scheme

1H-imidazole (288-32-4) + o-Xylylene dichloride (612-12-4) → C14H16N4

Conditions	Yield
Stage #1: 1H-imidazole With sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: o-Xylylene dichloride In N,N-dimethyl-formamide at 20℃; for 4h;	100%

bis{1,2-bis(methylphosphino)ethane}palladium(II) dichloride + o-Xylylene dichloride (612-12-4) → Pd(C6H4(CH2P(CH3)CH2CH2P(CH3)CH2)2C6H4)(2+)*2Cl(1-)=(Pd(C6H4(CH2P(CH3)CH2CH2P(CH3)CH2)2C6H4))Cl2

Conditions	Yield
With potassium carbonate In ethanol (under Ar); addn. of K2CO3 and the dihalogenide to a soln. of the Pd complex in EtOH, stirring at room temp. for 2 h; filtn., washing the ppt. with EtOH, evapn. of the solvent under vac. at 40°C, recrystn. from EtOH at -20°C;	99%

o-Xylylene dichloride (612-12-4) + aniline (62-53-3) → 2-phenylisoindoline (19375-67-8)

Conditions	Yield
With potassium carbonate In water at 105℃; for 0.333333h; Concentration; Microwave irradiation; Green chemistry;	99%

o-Xylylene dichloride (612-12-4) + 5,6-dibromo-4,7-dibutylbenzo[1,2,3]triselenole → 1,2-(o-xylylenediseleno)-3,6-dibutyl-4,5-dibromobenzene

Conditions	Yield
Stage #1: 5,6-dibromo-4,7-dibutylbenzo[1,2,3]triselenole With sodium tetrahydroborate In tetrahydrofuran; methanol for 0.0833333h; Stage #2: o-Xylylene dichloride With potassium carbonate In tetrahydrofuran; methanol at 20℃;	99%

o-Xylylene dichloride (612-12-4) + 4-bromo-aniline (106-40-1) → 2-(4-bromophenyl)isoindoline

Conditions	Yield
With potassium carbonate In water at 105℃; for 0.333333h; Concentration; Microwave irradiation; Green chemistry;	98%

bis{1,2-bis(methylphosphino)ethane}palladium(II) dichloride + o-Xylylene dichloride (612-12-4) → chloro(5,6,7,8,9,10,15,16,17,18,19,20-dodecahydro-6,9,16,19-tetramethyldibenzo{f,n}-{1,4,9,12}-tetraphosphacyclohexadecine-P,P',P'',P''')palladium(II)-hydrogencarbonate (102258-62-8)

Conditions	Yield
With K2CO3 In ethanol (N2); added K2CO3 and 1,2-bis(chloromethyl)benzene to soln. of Pd-compound; filtered after 1 h; washed with ethanol; elem. anal.;	97%

Methyl formate (107-31-3) + o-Xylylene dichloride (612-12-4) → o-xylyleneglycolbisformate (1933-00-2)

Conditions	Yield
With sodium chloride; sodium formate; triethylamine	96.5%

o-Xylylene dichloride (612-12-4) → bis(chloromagnesiummethyl)benzol (78499-87-3)

Conditions	Yield
With magnesium; ethylene dibromide In tetrahydrofuran	96%
With magnesium; iodine In tetrahydrofuran	91%
With polymer supported 'magnesium(anthracene)'	90%
With magnesium; ethylene dibromide In tetrahydrofuran at 20℃; for 20.25h;

o-Xylylene dichloride (612-12-4) → 1,3-dihydroisobenzofuran (496-14-0)

Conditions	Yield
With sodium hydroxide In water at 100℃; for 4h; pH=12;	96%
With aluminum oxide for 0.166667h; microwave irradiation;	69%

o-Xylylene dichloride (612-12-4) + phenylacetylene (536-74-3) → 1,1'-(o-phenylenedimethylene)bis<4-phenyl-1H-1,2,3-triazole> (137959-33-2)

Conditions	Yield
With copper(l) iodide; sodium azide In water at 100℃; for 10h;	96%
With sodium azide In water at 60℃; for 4h; Huisgen Cycloaddition;	85%

borane-THF (14044-65-6) + o-Xylylene dichloride (612-12-4) + methylphenylphosphine (6372-48-1) → 1,2-bis((methylphenylphosphino-borane)methyl)benzene (882176-74-1, 882176-75-2)

Conditions	Yield
With NaOCH(CH3)2CH2CH2; [RuH(1,2-bis(dimethylphosphino)ethane)((R)-MeO-BiPHEP)][tetraphenylborate] In tetrahydrofuran (N2); addn. of phosphine deriv. and benzyl chloride to THF soln. of sodium alcoholate deriv. and ruthenium compd., stirring at room temp. for 90min, addn. of THF soln. of borane deriv., stirring at room temp. for 30 min; addn. of water, extn. (ethyl acetate), washing with brine, drying over Na2SO4, filtration, concg., chromy. (silica gel, 75:25 hexanes/ethyl acetate);	96%
With NaOCH(CH3)2CH2CH2; [RuH((R)-iPr-PHOX)2][tetraphenylborate] In tetrahydrofuran treatment of phosphine deriv. with benzyl chloride deriv. and sodium alcoholate deriv. in THF in presence of ruthenium compd. at -30°C for 60 h, treatment with borane deriv.; chiral HPLC;	87%

o-Xylylene dichloride (612-12-4) → 1,2-bis(azidomethyl)benzene (102437-79-6)

Conditions	Yield
With sodium azide In water at 120℃; for 0.5h; microwave irradiation;	95%
With sodium azide In methanol; water at 100℃; for 48h;	88%
With sodium azide In N,N-dimethyl-formamide Ambient temperature;
With sodium azide; N-benzyl-N,N,N-triethylammonium chloride In water at 95℃; for 12h;

1-methyl-1H-imidazole (616-47-7) + o-Xylylene dichloride (612-12-4) → 3,3’-[1,2-phenylenebis(methylene)]bis(1-methyl-1H-imidazol-3-ium) chloride

Conditions	Yield
at 150℃; for 12h;	95%
In toluene for 16h; Reflux;	80%

o-Xylylene dichloride (612-12-4) + C12H22OSi → 2-cyclopropyl-3-(tert-butyldimethylsiloxymethyl)-1,4-dihydronaphthalene

Conditions	Yield
With manganese; tris<3,5-bis(trifluoromethyl)phenyl>phosphane; cobalt(II) bromide In acetonitrile at 50℃; for 20h; Inert atmosphere; Schlenk technique;	95%

1-lithio-2-tert-butyldimethylsilyl-1,2-dicarba-closo-dodecaborane(12) (361544-93-6) + o-Xylylene dichloride (612-12-4) → 1-(α-C,α'-chloro-o-xylyl)-2-(tert-butyldimethylsilyl)-1,2-dicarba-closo-dodecaborane (419562-77-9)

Conditions	Yield
In diethyl ether; benzene to soln. Li(tBuMe2Si-1,2-C2B10H10) in benzene-Et2O (2:1) at 0°C was added dropwise soln. α,α'-dichloro-o-xylene in benzene-Et2O (2:1), allowed to warm to room temp. and refluxed for 12 h; soln. was evapd. to dryness in vacuo, residue was triturated with EtOH, cooled to -10°C overnight, ppt. was filtered, washed with chilledMeOh and dried in vacuo; elem. anal.;	94%

N-(2,3,4,5,6-pentamethylbenzyl)imidazoline (1202027-87-9) + o-Xylylene dichloride (612-12-4) → C38H52N4(2+)*2Cl(1-)

Conditions	Yield
In N,N-dimethyl-formamide at 25 - 50℃; Inert atmosphere;	94%

o-Xylylene dichloride (612-12-4) + pseudothiohydantoin (556-90-1) → 5,10-dihydrobenzo[e]thiazolo[3,2-a][1,3]diazepin-3(2H)-one (20932-68-7)

Conditions	Yield
at 290℃; for 1.5h;	94%

o-Xylylene dichloride (612-12-4) → C8H10O5P2

Conditions	Yield
Stage #1: o-Xylylene dichloride With tri-n-butyl phosphite at 160℃; under 7.50075 Torr; for 11h; Stage #2: With water; hydrogen bromide at 100℃; for 12h;	94%

o-Xylylene dichloride (612-12-4) + meta-hydroxybenzaldehyde (100-83-4) → 3,3′-[benzene-1,2-diylbis(methanediyloxy)]dibenzaldehyde (95912-31-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 24h; Ambient temperature;	93%

para-xylene (106-42-3) + o-Xylylene dichloride (612-12-4) → 1,2-bis(2,5-dimethylbenzyl)benzene (32094-53-4)

Conditions	Yield
With silica gel; zinc(II) chloride at 30℃; for 0.5h;	93%

5,6-dimethylbenzotriazole (4184-79-6) + o-Xylylene dichloride (612-12-4) → 1-(2-((5,6-dimethyl-1H-benzo[d][1,2,3]triazol-1-yl)-methyl)benzyl)-5,6-dimethyl-1H-benzo[d][1,2,3]triazole

Conditions	Yield
Stage #1: 5,6-dimethylbenzotriazole With potassium carbonate; potassium iodide In acetone for 0.5h; Stage #2: o-Xylylene dichloride In acetone for 5h; Reflux;	93%

isovanillin (621-59-0) + o-Xylylene dichloride (612-12-4) → C24H22O6 (95912-30-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 24h; Ambient temperature;	92%

o-Xylylene dichloride (612-12-4) → 1,3-dihydroisobenzofuran (496-14-0) + phthalyl alcohol (612-14-6) + 2-(chloromethyl)-phenyl methanol (142066-41-9)

Conditions	Yield
With sodium hydroxide In water at 100℃; for 4h; pH=7;	A n/a B 92% C n/a
In water; dimethyl sulfoxide at 100℃; for 4h;	A n/a B 92% C n/a
In water at 100℃; for 4h;	A n/a B 90% C n/a

o-Xylylene dichloride (612-12-4) + phenethylamine (64-04-0) → 6,13‑diphenethyl‑5,6,7,12,13,14‑hexahydrodibenzo[c,h][1,6]diazecine

Conditions	Yield
With triethylamine In dichloromethane at 20℃; Solvent;	92%

o-Xylylene dichloride (612-12-4) + (trimethylsilyl)diphenylphosphine (17154-34-6) → 2,2-diphenyl-1,2-dihydro-2λ5-phosphonia-inden-chlorid

Conditions	Yield
In toluene for 13h;	91%

2,3-benzocarbazole (243-28-7) + o-Xylylene dichloride (612-12-4) → 1,2-bis[(2,3-benzocarbazol-9-yl)methyl]benzene

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; potassium hydroxide at 80℃; for 10h;	91%

o-Xylylene dichloride (612-12-4) + thiourea (17356-08-0) → 1,2-phenylenebis(methylene)dicarbamimidothioate dihydrochloride

Conditions	Yield
In ethanol for 0.5h; Heating;	91%
In ethanol for 7h; Reflux;	85%

o-Xylylene dichloride (612-12-4) + cyclohexylamine (108-91-8) → 2-cyclohexyl-isoindoline (117135-94-1)

Conditions	Yield
With potassium carbonate In water at 120℃; for 0.333333h; microwave irradiation;	91%
With potassium carbonate In water at 105℃; for 0.333333h; Concentration; Microwave irradiation; Green chemistry;	68%

o-Xylylene dichloride (612-12-4) + potassium thioacyanate (333-20-0) → 1,2-bis(thiocyanatomethyl)benzene (62855-78-1)

Conditions	Yield
In water at 110℃; for 0.333333h; microwave irradiation;	91%

Upstream product

• 95-47-6 o-xylene 
• 131-11-3 phthalic acid dimethyl ester 
• 50-00-0 formaldehyd 
• 100-44-7 benzyl chloride 
• 108-88-3 toluene 
• 7647-01-0 hydrogenchloride 
• 7446-70-0 aluminium trichloride 
• 88-95-9 Phthaloyl dichloride 
• 612-14-6 phthalyl alcohol 
• 98-07-7 Benzotrichlorid 
• 861338-62-7 bis-(2-ethoxymethyl-benzyl)-amine 
• 128-09-6 N-chloro-succinimide 

Downstream Products

• 23189-84-6 1,2-Bis-<2,2-dicarbethoxy-penten-(4)-yl>-benzol 
• 14019-65-9 1,2-bisbenzene 
• 71721-11-4 1-Benzenesulfonylmethyl-2-chloromethyl-benzene 
• 35180-29-1 o-xylylenebisurea 
• 73217-16-0 1-(2-chloromethyl-benzyl)-pyrrole-2-carbaldehyde 
• 129055-79-4 C₁₈H₁₆N₂O₂ 
• 89052-09-5 3-(2-Chloromethyl-benzyloxy)-4-methoxy-benzaldehyde 
• 95912-30-4 C₂₄H₂₂O₆ 
• 129055-88-5 [1-(2-Chloromethyl-benzyl)-1H-pyrrol-2-yl]-phenyl-methanone 
• 118066-99-2 1,2-bis<2-(2,6-di-t-butylpyridyl)ethyl>benzene 
• 129055-90-9 [1-(2-Chloromethyl-benzyl)-1H-pyrrol-2-yl]-(4-chloro-phenyl)-methanone 
• 129055-80-7 (1-{2-[2-(4-Chloro-benzoyl)-pyrrol-1-ylmethyl]-benzyl}-1H-pyrrol-2-yl)-(4-chloro-phenyl)-methanone 
• 124993-48-2 2-<<4-(2-quinolinylmethoxy)phenoxy>methyl>benzyl chloride 
• 78499-87-3 bis(chloromagnesiummethyl)benzol 

Relevant articles and documents

Improved Halogenation of Methyl Aromatics and Methyl Heteroaromatics: Unexpected Reactivity of Tetrahalogeno-diphenylglycolurils

1,3,4,6-Tetrachloro (TCDGU) and 1,3,4,6-tetrabromo-3α,6α-diphenylglycolurils smooth halogen oxidizers have been exploited in a new direction as reagents for free radical substitution toward some N-halosuccinimide nonreactive bis-heterocycles. An unexpected selectivity and reactivity were observed with methyl benzenes, methyl heterocycles, and methyl-bis-heterocycles of interest. A chemometric study has been performed to optimize five independent factors of the chlorination reaction with TCDGU. The predictive model was established either for the halogenation conversion and the ratio of monochlorination.

Interpretation of retention indices in gas chromatography for establishing structures of isomeric products of alkylarenes radical chlorination

By an example of previously uncharacterized products obtained by alkylarenes radical chlorination was demonstrated that combination of various interpretation methods applied to the retention indices (RI) in the gas chromatography on the standard nonpolar phases (comparison of RI of products and initial compounds, characteristics of succession of the chromatographic elution of the structural isomers with the use of estimation of molecular dynamic parameters, application of the additive schemes to RI calculation, and using of structural analogy CH3?Cl for testing the results obtained) permitted unambiguous identification of the structure even without data of mass spectrometry.