3172-52-9

Basic information

• Product Name: 2,5-Dichlorothiophene
• Synonyms: DICHLOROTHIOPHENE;2,5-DICHLOROTHIOPHENE;2,6-DICHLOROTHIOPHENE;2,5-dichloro-thiophen;thiophene,2,5-dichloro-;2,5-Dichlorothiophenene;2,5-Dichlorothiophene,97%;5-chloro-2-thienyl chloride
• CAS NO: 3172-52-9
• Molecular Formula: C4H2Cl2S
• Molecular Weight: 153.03
• EINECS: 221-638-8
• Product Categories: Thiophenes;Organics;Thiophene&Benzothiophene;Miscellaneous;Thiophens;Halogenated Heterocycles;Heterocyclic Building Blocks;ThiophenesBuilding Blocks;Heterocycle-oher series
• Mol File: 3172-52-9.mol
• Article Data: 10

Chemical Properties

• Melting Point: -41--40°C
• Boiling Point: 162 °C
• Flash Point: 59 °C
• Appearance: /liquid
• Density: 1.442 g/mL at 25 °C(lit.)
• Vapor Pressure: 3.33mmHg at 25°C
• Refractive Index: 1.561-1.563
• Storage Temp.: 0-6°C
• BRN: 109887
• CAS DataBase Reference: 2,5-Dichlorothiophene(CAS DataBase Reference)
• NIST Chemistry Reference: 2,5-Dichlorothiophene(3172-52-9)
• EPA Substance Registry System: 2,5-Dichlorothiophene(3172-52-9)

Safety Data

• Hazard Codes: T+,Xn
• Statements: 40-26/27/28-36/37/38-20/21/22
• Safety Statements: 45-36/37-28A-36-26
• RIDADR: 2929
• WGK Germany: 3
• TSCA: T
• HazardClass: 6.1
• PackingGroup: II
• Hazardous Substances Data: 3172-52-9(Hazardous Substances Data)

Usage

Chemical Properties

clear colorless to slightly yellow liquid

Uses

2,5-Dichlorothiophene is mainly used as a pharmaceutical intermediate. It is used in the synthesis of 3,4-disubstituted thiophenes.

InChI:InChI=1/C4H2Cl2S/c5-3-1-2-4(6)7-3/h1-2H

Synthetic route

thiophene (188290-36-0) → 2,5-diclorothiophene (3172-52-9)

Conditions	Yield
With N-chloro-succinimide In tetrachloromethane for 4h; Time; Reflux;	95%
With N-chloro-succinimide; perchloric acid In tetrachloromethane for 24h; Ambient temperature;	82%
With lead(IV) acetate; tin(IV) chloride In ethyl acetate for 0.25h;	75%
With N-chloro-succinimide; perchloric acid In chloroform for 0.5h; Heating;	67%
With chlorine anschliessend Erhitzen mit Kaliumhydroxid und Natriumhydroxid;

2-thienyl chloride (96-43-5) → 2,5-diclorothiophene (3172-52-9)

Conditions	Yield
With N-chloro-succinimide; perchloric acid In tetrachloromethane for 24h; Ambient temperature;	82%
With chlorine anschliessend Erhitzen mit Kaliumhydroxid und Natriumhydroxid;
With chlorine Yield given;

thiophene (188290-36-0) → 2-thienyl chloride (96-43-5) + 2,5-diclorothiophene (3172-52-9)

Conditions	Yield
With ammonium nitrate; N-chloro-succinimide In acetonitrile for 1h;	A 59% B 10%
With hydrogenchloride; sodium peroxide In toluene; benzene at 28 - 30℃; for 0.5h; Product distribution; var. reagents; var. temperatures, var. reaction times;	A 67 % Chromat. B 11 % Chromat.
With chlorine; potassium carbonate

2,5-dichlorothiophene-3-carboxylic acid (36157-41-2) → 2,5-diclorothiophene (3172-52-9) + 2,2',5,5'-tetrachloro-3,3'-bithiophene (57308-99-3)

Conditions	Yield
With palladium(II) trifluoroacetate; silver carbonate In dimethyl sulfoxide; N,N-dimethyl-formamide at 120℃; for 16h; Inert atmosphere;	A n/a B 57%

thiophene (188290-36-0) → 2,5-diclorothiophene (3172-52-9) + 2,3,5-trichlorothiophene (17249-77-3)

Conditions	Yield
With N-chloro-succinimide In acetic acid for 2h; Chlorination; Heating;	A 26% B 26%

thiophene (188290-36-0) + N-chloroacetamide (598-49-2) → 2-thienyl chloride (96-43-5) + 2,5-diclorothiophene (3172-52-9)

Conditions	Yield
at 60℃;

2-thiophenylcarboxylic acid (527-72-0) → 2,5-diclorothiophene (3172-52-9) + 5-Chlorothiophene-2-carboxylic acid (24065-33-6)

Conditions	Yield
With alkaline aqueous sodium hypochlorite solution anschliessend Erwaermen mit wss. Salzsaeure;

2,2,3,4,5,5-hexachloro-tetrahydro-thiophene (18614-15-8) → 2,5-diclorothiophene (3172-52-9)

Conditions	Yield
With water; zinc

2,3,4,5-tetrachloro-tetrahydro-thiophene (64048-11-9) → 2,4-dichlorothiophene (17249-75-1) + 2,5-diclorothiophene (3172-52-9) + 2,3-Dichlorothiophene (17249-79-5)

Conditions	Yield
Erhitzen auf 180grad; optically inactive stereoisomer(ic) of mp: 113 degree;

2-(methyldichlorosilyl)thiophene (18243-72-6) → 2-thienyl chloride (96-43-5) + 2,5-diclorothiophene (3172-52-9) + Methyltrichlorosilane (75-79-6)

Conditions	Yield
With chlorine; iron(III) chloride at 20℃; for 5h; Product distribution; other temperatures; various reaction times; other reagents: SO2Cl2, antimony trichloride, iodine.;

trichloro-thiophen-2-yl-silane (18145-51-2) → thiophene (188290-36-0) + 2,5-diclorothiophene (3172-52-9) + trichloro-(5-chloro-thiophen-2-yl)-silane (18145-49-8) + Trichloro-(4-chloro-thiophen-2-yl)-silane + Trichloro-(3-chloro-thiophen-2-yl)-silane + 3,5-dichloro-2-(trichlorosilyl)thiophene

Conditions	Yield
With chlorine at 20℃; for 6h; Product distribution; other temperatures; various reaction times; presence of catalysator: ferric chloride; UV irradiation; other reagent: SO2Cl2.;

trichloro-thiophen-2-yl-silane (18145-51-2) → 2,5-diclorothiophene (3172-52-9) + trichloro-(5-chloro-thiophen-2-yl)-silane (18145-49-8) + Trichloro-(4-chloro-thiophen-2-yl)-silane + Trichloro-(3-chloro-thiophen-2-yl)-silane

Conditions	Yield
With chlorine at 20℃; for 6h; Irradiation; Further byproducts given;	A 6.6 g B n/a C n/a D n/a

2,2,3,4,5,5-hexachloro-tetrahydro-thiophene (18614-15-8) + water (7732-18-5) + zinc → 2,5-diclorothiophene (3172-52-9)

Conditions	Yield
Erwaermen;

thiophene (188290-36-0) + chlorine (7782-50-5) → 2-thienyl chloride (96-43-5) + 2,5-diclorothiophene (3172-52-9)

thiophene (188290-36-0) + acetic acid chloroamide (3 mol) → 2-thienyl chloride (96-43-5) + 2,5-diclorothiophene (3172-52-9)

ethanol (64-17-5) + 2,3,4,5-tetrachloro-tetrahydro-thiophene (64048-11-9) + potassium hydroxide → 3,4-dichlorothiophene (17249-76-2) + 2,4-dichlorothiophene (17249-75-1) + 2,5-diclorothiophene (3172-52-9)

Conditions	Yield
optically inactive stereoisomer(ic) of mp: 113 degree;

thiophene (188290-36-0) → 2,5-diclorothiophene (3172-52-9) + 2-chloro-thiophene C4H3ClS

Conditions	Yield
With chlorine; potassium carbonate

2,5-diclorothiophene (3172-52-9) + N-(2,2,2-trichloroethylidene)-4-chlorobenzenesulfonamide (81924-15-4) → N-[2,2,2-trichloro-1-(2,5-dichlorothiophen-3-yl)ethyl]-4-chlorobenzenesulfonamide

Conditions	Yield
With sulfuric acid In Trichloroethylene	93%

2,5-diclorothiophene (3172-52-9) + S-methyl benzenethiosulfonate (1125-25-3) → 2,5-dichloro-3-(methylthio)thiophene (1097189-64-4)

Conditions	Yield
Stage #1: 2,5-diclorothiophene With 2,2,6,6-tetramethylpiperidinylmagnesium chloride In tetrahydrofuran at 25℃; for 0.5h; Inert atmosphere; Stage #2: S-methyl benzenethiosulfonate In tetrahydrofuran for 0.5h; Inert atmosphere;	92%

2,5-diclorothiophene (3172-52-9) + chloroacetyl chloride (79-04-9) → 2-chloro-1-(2,5-dichlorothiophen-3-yl) ethanone (13668-93-4)

Conditions	Yield
With aluminium trichloride In carbon disulfide for 1h; Heating;	91%
	91%
With carbon disulfide; aluminum (III) chloride at 20℃; for 17h; Friedel-Crafts Acylation; Inert atmosphere; Reflux;	91%
With aluminum (III) chloride In carbon disulfide Friedel Crafts acylation;

2,5-diclorothiophene (3172-52-9) + acetyl chloride (75-36-5) → 3-acetyl-2,5-dichlorothiophene (36157-40-1)

Conditions	Yield
With aluminum (III) chloride In carbon disulfide at 20℃; for 25h; Friedel-Crafts Acylation;	90%
With aluminum (III) chloride In carbon disulfide at 20℃;	76.7%
With aluminium trichloride In chloroform at 20℃; for 5h;	52%

2,5-diclorothiophene (3172-52-9) + phenylboronic acid (98-80-6) → 2,5-Diphenyl-thiophene (1445-78-9)

Conditions	Yield
With 4-di-tert-butylphosphanyl-1-phenyl-5-(2,6-dimethoxyphenyl)-1H-[1,2,3]triazole; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0) In toluene at 100℃; for 12h; Suzuki coupling; Inert atmosphere;	90%

2,5-diclorothiophene (3172-52-9) + 4-chlorobenzaldehyde (104-88-1) → (4-chlorophenyl)(2,5-dichlorothiophen-3-yl)methanol

Conditions	Yield
Stage #1: 2,5-diclorothiophene With 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex In tetrahydrofuran at 25℃; for 0.05h; Stage #2: 4-chlorobenzaldehyde In tetrahydrofuran at 25℃; for 0.00166667h;	88%

2,5-diclorothiophene (3172-52-9) + N-(2,2,2-trichloroethylidene)benzenesulfonamide (55596-11-7) → N-[2,2,2-trichloro-1-(2,5-dichlorothiophen-3-yl)ethyl]benzenesulfonamide

Conditions	Yield
With sulfuric acid In Trichloroethylene	87%

2,5-diclorothiophene (3172-52-9) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 2,5-dichlorothiophene-4-carboxaldehyde (61200-60-0)

Conditions	Yield
Stage #1: 2,5-diclorothiophene With 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex In tetrahydrofuran at 25℃; for 0.05h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at 25℃; for 0.00361111h;	87%

2,5-diclorothiophene (3172-52-9) + 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane (25015-63-8) → 2-(2,5-dichlorothiophen-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (942070-18-0)

Conditions	Yield
With 4,4'-di(tert-butyl)-2,2'-dipyridyl; [Ir(μ2-OMe)(1,4-cyclooctadiene)]2 In hexane at 20℃; for 20h;	86%

2,5-diclorothiophene (3172-52-9) + 1-Naphthalenethiol (529-36-2) → 2-Chloro-5-(1-naphthylthio)thiophene

Conditions	Yield
at 162 - 190℃; for 8h;	85%

2,5-diclorothiophene (3172-52-9) → 2,5-dichloro-3,4-dinitrothiophene (51584-21-5)

Conditions	Yield
With sulfuric acid; nitric acid at 70℃;	83%
With sulfuric acid; nitric acid for 3h;	82%
With sulfuric acid; nitric acid 1) 5 deg C, 2) r.t., 12 h;	77%
With sulfuric acid; nitric acid

2,5-diclorothiophene (3172-52-9) + di-tert-butyl dicarbonate (24424-99-5) → tert-butyl 2,5-dichlorothiophene-3-carboxylate (1097189-65-5)

Conditions	Yield
Stage #1: 2,5-diclorothiophene With 2,2,6,6-tetramethylpiperidinylmagnesium chloride In tetrahydrofuran at 25℃; for 0.5h; Inert atmosphere; Stage #2: di-tert-butyl dicarbonate In tetrahydrofuran at -20℃; Inert atmosphere;	82%

2,5-diclorothiophene (3172-52-9) + dibenzothiophenium bismethoxycarbonylmethylide (34297-79-5) → 2,5-dichlorothiophenium-1-bis(methoxycarbonyl)methylide (66946-86-9)

Conditions	Yield
UV-irradiation;	81%

2,5-diclorothiophene (3172-52-9) + o-cyanobromobenzene (2042-37-7) → 2-(2,5-dichlorothiophen-3-yl)benzonitrile (1552295-09-6)

Conditions	Yield
With PdCl(C3H5)(1,4-bis(diphenylphosphino)butane); potassium acetate In N,N-dimethyl-formamide at 150℃; for 20h; Inert atmosphere; Schlenk technique; regioselective reaction;	81%

2,5-diclorothiophene (3172-52-9) + 4-aminotiophenol (1193-02-8) → 2,5-bis(4-aminophenylenesulfanyl)thiophene (211238-27-6)

Conditions	Yield
Stage #1: 4-aminotiophenol With potassium carbonate In toluene at 140℃; for 4h; Dean-Stark; Inert atmosphere; Stage #2: 2,5-diclorothiophene at 120℃; Inert atmosphere;	80%

2,5-diclorothiophene (3172-52-9) + benzoyl chloride (98-88-4) → (2,5-dichloro-3-thienyl)(phenyl)methanone (99971-87-6)

Conditions	Yield
Stage #1: 2,5-diclorothiophene With 2,2,6,6-tetramethylpiperidinylmagnesium chloride In tetrahydrofuran at 25℃; for 0.5h; Inert atmosphere; Stage #2: With copper(I) cyanide*2 lithium chloride In tetrahydrofuran for 0.25h; Inert atmosphere; Stage #3: benzoyl chloride In tetrahydrofuran at -30 - 25℃;	78%
With carbon disulfide; aluminium trichloride

2,5-diclorothiophene (3172-52-9) → 2,5-dichloro-3,4-diiodothiophene (57308-89-1)

Conditions	Yield
With sulfuric acid; iodine; acetic acid; periodic acid at 90℃;	78%

2,5-diclorothiophene (3172-52-9) + 4-bromoisoquinoline (1532-97-4) → 4-(2,5-dichlorothiophen-3-yl)isoquinoline (1552295-11-0)

Conditions	Yield
With PdCl(C3H5)(1,4-bis(diphenylphosphino)butane); potassium acetate In N,N-dimethyl-formamide at 150℃; for 20h; Inert atmosphere; Schlenk technique; regioselective reaction;	78%

2,5-diclorothiophene (3172-52-9) + Ethyl oxalyl chloride (4755-77-5) → ethyl 2,5-dichloro-3-thienylglyoxylate (32766-64-6)

Conditions	Yield
With aluminium trichloride In nitromethane 1.) 10 deg C, 1 h, 2.) room temp., 1 h;	77%

2,5-diclorothiophene (3172-52-9) + 2-Thiophenecarbonyl chloride (5271-67-0) → 2,5-dichloro-3-(2-thiophenecarbonyl)thiophene (57248-31-4)

Conditions	Yield
With aluminium trichloride In nitromethane at 20℃; for 24h;	76%
With carbon disulfide; aluminium trichloride

2,5-diclorothiophene (3172-52-9) → 2,5-dichlorothiophene 1,1-dioxide (72541-87-8)

Conditions	Yield
With dihydrogen peroxide; trifluoroacetic anhydride In acetonitrile at 0 - 20℃;	76%
With trifluoroacetyl peroxide In acetonitrile for 4h;	76%
With water; fluorine In acetonitrile for 0.333333h; Ambient temperature;	70%
With HOF* CH3CN In chloroform; water for 0.5h; Ambient temperature;	70%

Thiophene-2-thiol (7774-74-5) + 2,5-diclorothiophene (3172-52-9) → bis(thien-2-yl)sulfide (3988-99-6) + 2-thienyl disulfide (6911-51-9) + 5-Chloro-2-(2-thienylthio)thiophene

Conditions	Yield
at 162 - 186℃; for 11h;	A 76% B 9% C 45%
at 162 - 186℃; for 10h;	A 28% B 9% C 52%

2,5-diclorothiophene (3172-52-9) + ethyl cyanoformate (623-49-4) → ethyl 2,5-dichlorothiophene-3-carboxylate (130562-95-7)

Conditions	Yield
Stage #1: 2,5-diclorothiophene With 2,2,6,6-tetramethylpiperidinylmagnesium chloride In tetrahydrofuran at 25℃; for 0.5h; Inert atmosphere; Stage #2: ethyl cyanoformate In tetrahydrofuran at 0℃; Inert atmosphere;	76%

2,5-diclorothiophene (3172-52-9) + chloromethyl methyl ether (107-30-2) → ether chloromethylique au dichloromethyl-3,4-thiophene (10095-90-6)

Conditions	Yield
With tin(IV) chloride	75%
With tin(IV) chloride In carbon disulfide at 0 - 20℃; for 3h;	69%

2,5-diclorothiophene (3172-52-9) + pivaloyl chloride (3282-30-2) → 1-(2,5-dichloro-3-thienyl)-2,2-dimethylpropan-1-one (1097189-66-6)

Conditions	Yield
Stage #1: 2,5-diclorothiophene With 2,2,6,6-tetramethylpiperidinylmagnesium chloride In tetrahydrofuran at 25℃; for 0.5h; Inert atmosphere; Stage #2: With copper(I) cyanide*2 lithium chloride In tetrahydrofuran for 0.25h; Inert atmosphere; Stage #3: pivaloyl chloride In tetrahydrofuran at -20 - 25℃;	75%

2,5-diclorothiophene (3172-52-9) + P-toluenesulfonyl cyanide (19158-51-1) → 2,5-dichlorothiophene-3-carbonitrile (1097189-67-7)

Conditions	Yield
Stage #1: 2,5-diclorothiophene With 2,2,6,6-tetramethylpiperidinylmagnesium chloride In tetrahydrofuran at 25℃; for 0.5h; Inert atmosphere; Stage #2: P-toluenesulfonyl cyanide In tetrahydrofuran at -20℃; Inert atmosphere;	73%

2,5-diclorothiophene (3172-52-9) + dimethyl diazomalonate (6773-29-1) → 2,5-dichlorothiophenium-1-bis(methoxycarbonyl)methylide (66946-86-9)

Conditions	Yield
With dirhodium tetraacetate	72%
With dirhodium tetraacetate

2,5-diclorothiophene (3172-52-9) + N-(methoxycarbonyl)aspartic anhydride (79686-90-1) → 4-(2,5-dichlorothiophen-3-yl)-2-methoxycarbonylamino-4-oxobutanoic acid (166764-46-1)

Conditions	Yield
In 1,2-dichloro-ethane for 4h; Ambient temperature;	71%

Upstream product

• 188290-36-0 thiophene 
• 598-49-2 N-chloroacetamide 
• 18614-15-8 2,2,3,4,5,5-hexachloro-tetrahydro-thiophene 
• 18243-72-6 2-(methyldichlorosilyl)thiophene 
• 18145-51-2 trichloro-thiophen-2-yl-silane 
• 7732-18-5 water 
• 7782-50-5 chlorine 
• 64-17-5 ethanol 
• 64048-11-9 2,3,4,5-tetrachloro-tetrahydro-thiophene 
• 36157-41-2 2,5-dichlorothiophene-3-carboxylic acid 
• 527-72-0 2-thiophenylcarboxylic acid 
• 96-43-5 2-thienyl chloride 

Downstream Products

• 99971-87-6 (2,5-dichloro-3-thienyl)(phenyl)methanone 
• 36157-40-1 3-acetyl-2,5-dichlorothiophene 
• 408351-15-5 3-benzenesulfonyl-2,5-dichlorothiophene 
• 99979-31-4 1-(2,5-dichloro-[3]thienyl)-2-phenyl-ethanone 
• 24065-33-6 5-Chlorothiophene-2-carboxylic acid 
• 40477-45-0 2,5-dichloro-3,4-dibromothiophene 
• 17019-32-8 2-tert.Butoxy-5-chlorthiophen 
• 61200-60-0 2,5-dichlorothiophene-4-carboxaldehyde 
• 120413-98-1 4-[(4-ethyl)phenyl]-2-chlorothiophene 
• 90454-54-9 phenyl N-(2,5,5-trichloro-2,5-dihydro-2-thienyl)-carbamate 
• 90454-56-1 phenyl N-(3,5-dichloro-2-thienyl)-carbamate 
• 32766-64-6 ethyl 2,5-dichloro-3-thienylglyoxylate 
• 54095-29-3 2-chloro-4-(p-methoxyphenyl)thiophene 
• 62497-30-7 2,4-bis(4-methoxyphenyl)thiophene 

Relevant articles and documents

2, 5-dichloro thiophene preparation method

The present invention discloses a 2, 5-dichloro thiophene preparation method comprising the following steps: (1) an organic solvent and thiophene are added into a reaction vessel and warmed to reflux, under reflux conditions, batches of added N-chlorosucc

Synthesis and structural characterization of 2,5-dihalo-3,4- dinitrothiophenes

Using new nitration protocols, we have been able to efficiently dinitrate 2,5-dihalothiophenes with yields of ～80-95%. The resulting products 2,5-dibromo-3,4-dinitrothiophene (1), 2,5-dichloro-3,4-dinitrothiophene (2), 2-bromo-5-chloro-3,4-dinitrothiophene (3), as well as the analogous 2-bromo-3,4-dinitrothiophene (4), all crystallize easily allowing their characterization via X-ray crystallography. Crystallization of 1 occurs in the monoclinic space group C2/c with a=14.547(3)A, b=7.3534(15)A, c=10.775(2)A, β=128.89(3)°, and Z=4. Crystallization of 2 occurs in the tetragonal space group I-42d with a=9.9398(14)A, b=9.9398(14)A, c=16.866(3)A, and Z=8. Crystallization of 3 occurs as a pseudo-merohedral twin in the triclinic space group P-1 with a=7.340(5)A, b=8.094(5)A, c=9.112(5)A, α=82.059(5)°, β=66.232(5)°, γ=63.021(5)°, and Z=2. Crystallization of 4 occurs in the triclinic space group P-1 with a=7.1787(14)A, b=7.4092(15)A, c=8.3151(17)A, α=101.67(3)°, β=96.00(3)°, γ=116.13(3)°, and Z=2. The structures of all compounds exhibit the formation of interesting solid-state assemblies due to halogen-bonding interactions between the halogen and nitro groups. Springer Science+Business Media, LLC 2007.

Chlorinated thiophenes. Part 2. Trihalogenated hydroxythiophenes; preparation, reactions and tautomeric properties

2-Hydroxy-3,4,5-trichlorothiophene (4), 3-hydroxy-4-bromo-2,5-dichlorothiophene (5) and 3-hydroxy-2,4,5-trichlorothiophene (6) have been synthesised. It was found that 4 exists in a carbonyl form, whereas 5 and 6 the hydroxy forms were the major tautomers