36157-40-1

Basic information

• Product Name: 3-Acetyl-2,5-dichlorothiophene
• Synonyms: AKOS 1010;3-ACETYL-2,5-DICHLOROTHIOPHENE;2,5-DICHLORO-3-THIENYL METHYL KETONE;1-(2,5-DICHLORO-3-THIENYL)-1-ETHANONE;1-(2,5-DICHLORO-3-THIENYL)ETHAN-1-ONE;1-(2,5-Dichloro-3-thienyl)ethanone;1-(2,5-Dichloro-thiophen-3-yl)-ethanone;Ethanone, 1-(2,5-dichloro-3-thienyl)-
• CAS NO: 36157-40-1
• Molecular Formula: C₆H₄Cl₂OS
• Molecular Weight: 195.07
• EINECS: 252-893-3
• Product Categories: Sulphur Derivatives;Heterocycles series;Thiophene&Benzothiophene;Miscellaneous;Heterocycle-oher series
• Mol File: 36157-40-1.mol
• Article Data: 8

Chemical Properties

• Melting Point: 37-40 °C(lit.)
• Boiling Point: 120-122°C 4mm
• Flash Point: >230 °F
• Appearance: /solid
• Density: 1.4514 (estimate)
• Vapor Pressure: 0.0543mmHg at 25°C
• Refractive Index: 1.575
• Storage Temp.: Refrigerator
• BRN: 121288
• CAS DataBase Reference: 3-Acetyl-2,5-dichlorothiophene(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Acetyl-2,5-dichlorothiophene(36157-40-1)
• EPA Substance Registry System: 3-Acetyl-2,5-dichlorothiophene(36157-40-1)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 20/21/22-36/37/38
• Safety Statements: 26-36-36/37/39-22-36/37
• WGK Germany: 3
• Hazardous Substances Data: 36157-40-1(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powder

Uses

3-Acetyl-2,5-dichlorothiophene may be used in the following syntheses:substituted chalconesAL-4623A and AL-4862 (brinzolamide), inhibitors of topical carbonic anhydrase2,5-dichlorothiophene-3-carboxylic acid, which is the starting reagent required for the synthesis of 2,5-dichloro-N-(substituted amino-carbonothioyl)thiophene-3-carboxamides and 2-(substituted amino)-4H-thieno[3,2-e]-1,3-thiazin-4-ones

InChI:InChI=1/C6H4Cl2OS/c1-3(9)4-2-5(7)10-6(4)8/h2H,1H3

Synthetic route

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%

1-methyl-4-chlorobutenal (61170-81-8) + thioacetyl chloride (16911-84-5) → 3-acetyl-2,5-dichlorothiophene (36157-40-1)

Conditions	Yield
Stage #1: 1-methyl-4-chlorobutenal With sodium hydrogencarbonate In acetone at -15 - 10℃; for 1h; Stage #2: thioacetyl chloride In acetone at 75℃; for 4h; Solvent; Temperature; Reagent/catalyst;	117.6 g

3-acetyl-2,5-dichlorothiophene (36157-40-1) → 2-bromo-1-(2,5-dichlorothien-3-yl)ethanone (59160-46-2)

Conditions	Yield
	100%
With bromine; acetic acid at 15 - 25℃;	85%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → 1-(2,5-dichloro-3-thienyl)-3-(dimethylamino)prop-2-en-1-one (166196-79-8)

Conditions	Yield
Reflux;	100%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + benzyl chloride (100-44-7) → 3-Acetyl-2-(phenylmethyl)thio-5-chlorothiophene (160982-09-2)

Conditions	Yield
Stage #1: benzyl chloride With thiourea In ethanol; water for 2h; Reflux; Large scale; Stage #2: 3-acetyl-2,5-dichlorothiophene With sodium hydroxide In ethanol; water for 3h; Reflux; Large scale; regioselective reaction;	97%
With sodium hydroxide; sodium hypochlorite; thiourea In ethanol; water

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 2-chloro-6-methoxyquinolin-3-carboxaldehyde (73568-29-3) → (2E)-3-(2-chloro-6-methoxyquinolin-3-yl)-1-(2,5-dichlorothien-3-yl)prop-2-en-1-one (1253278-28-2)

Conditions	Yield
With sodium hydroxide In methanol; water at 20℃; for 2h; Claisen Schmidt condensation;	96%
With sodium hydroxide In ethanol; water

3-acetyl-2,5-dichlorothiophene (36157-40-1) → C6H4ClO4S2(1-)*Na(1+) (1245550-94-0)

Conditions	Yield
With sodium sulfite In ethanol at 25 - 110℃; Reflux;	95.5%
With sodium sulfite In ethanol; water at 25 - 110℃; Reflux;	95.5%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 2,4-Dimethoxybenzaldehyde (613-45-6) → (E)-1-(2,5-dichlorothiophen-3-yl)-3-(2,4-dimethoxyphenyl)prop-2-en-1-one

Conditions	Yield
With potassium hydroxide In methanol at 20℃; for 10h; Claisen-Schmidt Condensation;	95%

morpholine (110-91-8) + 3-acetyl-2,5-dichlorothiophene (36157-40-1) → 3-acetyl-5-chloro-2-(4-morpholino)thiophene (210098-03-6)

Conditions	Yield
	94%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 3-bromo-4-methoxybenzylaldehyde (34841-06-0) → (E)-3-(3-bromo-4-methoxyphenyl)-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-one

Conditions	Yield
With potassium hydroxide In methanol at 20℃; for 10h; Claisen-Schmidt Condensation;	94%

4-hydroxy-3-ethoxybenzaldehyde (121-32-4) + 3-acetyl-2,5-dichlorothiophene (36157-40-1) + ethyl 2-cyanoacetate (105-56-6) → 6-(2,5-dichlorothiophen-3-yl)-1,2-dihydro-4-(3-ethoxy-4-hydroxyphenyl)-2-oxopyridine-3-carbonitrile

Conditions	Yield
With ammonium acetate; potassium hydroxide In ethanol for 6h; Reflux;	92%

3-acetyl-2,5-dichlorothiophene (36157-40-1) → 1-(5-Chlor-3-thienyl)-ethanon (58119-67-8)

Conditions	Yield
With zinc In water; acetic acid for 2.5h; Heating;	91%

3-acetyl-2,5-dichlorothiophene (36157-40-1) → (R)-1-(2,5-dichlorothiophen-3-yl)ethan-1-ol

Conditions	Yield
With (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidine; dimethylsulfide borane complex In tetrahydrofuran at 25℃; for 2h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	91%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 3-phenyl-propenal (104-55-2) → C15H10Cl2OS

Conditions	Yield
With sodium hydroxide In ethanol Claisen-Schmidt condensation;	88%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + benzyl bromide (100-39-0) → 3-Acetyl-2-(phenylmethyl)thio-5-chlorothiophene (160982-09-2)

Conditions	Yield
With sodium hydroxide; thiourea In tetrahydrofuran; water	88%
With sodium hydroxide; thiourea In tetrahydrofuran; water	88%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 4-fluorobenzaldehyde (459-57-4) + ethyl 2-cyanoacetate (105-56-6) → 6-(2,5-dichlorothiophen-3-yl)-4-(4-fluorophenyl)-1,2-dihydro-2-oxopyridine-3-carbonitrile

Conditions	Yield
With ammonium acetate; potassium hydroxide In ethanol for 6h; Reflux;	88%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 4-methoxy-benzaldehyde (123-11-5) → (E)-1-(2,5-dichlorothiophen-3-yl)-3-(4-methoxy)prop-2-en-1-one

Conditions	Yield
With sodium hydroxide In ethanol Claisen-Schmidt condensation;	86%
With potassium hydroxide In methanol Claisen-Schmidt Condensation;
With sodium methylate In methanol

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 4-chlorobenzaldehyde (104-88-1) → C13H7Cl3OS

Conditions	Yield
With sodium hydroxide In ethanol Claisen-Schmidt condensation;	86%
With sodium methylate In methanol

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 4-tert-Butylbenzaldehyde (939-97-9) + ethyl 2-cyanoacetate (105-56-6) → 4-(4-tert-butylphenyl)-6-(2,5-dichlorothiophen-3-yl)-1,2-dihydro-2-oxopyridine-3-carbonitrile

Conditions	Yield
With ammonium acetate; potassium hydroxide In ethanol for 6h; Reflux;	86%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 5-chloro-3-phenyl-1H-indole-2-carboxyhydrazide (25434-84-8) → C21H14Cl3N3OS (1504554-95-3)

Conditions	Yield
In methanol Reflux;	85%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 3-nitro-benzaldehyde (99-61-6) → C13H7Cl2NO3S

Conditions	Yield
With sodium hydroxide In ethanol Claisen-Schmidt condensation;	84%
With sodium methylate In methanol

3-acetyl-2,5-dichlorothiophene (36157-40-1) + ethyl 2-cyanoacetate (105-56-6) + 2,4-Dimethoxybenzaldehyde (613-45-6) → 6-(2,5-dichlorothiophen-3-yl)-1,2-dihydro-4-(2,4-dimethoxyphenyl)-2-oxopyridine-3-carbonitrile

Conditions	Yield
With ammonium acetate; potassium hydroxide In ethanol for 6h; Reflux;	84%

5-bromo-2-thiophencarboxaldehyde (4701-17-1) + 3-acetyl-2,5-dichlorothiophene (36157-40-1) → (E)-3-(5-bromothiophen-2-yl)-1-(2,5-dichlorothiophen-3-yl)-2-propen-1-one

Conditions	Yield
With sodium hydroxide In water at 20℃;	83.6%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + benzaldehyde (100-52-7) → C13H8Cl2OS

Conditions	Yield
With sodium hydroxide In ethanol Claisen-Schmidt condensation;	83%
With sodium methylate In methanol

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 9-anthracene aldehyde (642-31-9) → (E)-3-(anthracen-9-yl)-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-one

Conditions	Yield
With potassium hydroxide In methanol at 20℃; for 10h; Claisen-Schmidt Condensation;	83%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + ethyl 2-cyanoacetate (105-56-6) + 4-dimethylamino-benzaldehyde (100-10-7) → 6-(2,5-dichlorothiophen-3-yl)-4-[4-(dimethylamino)-phenyl]-1,2-dihydro-2-oxopyridine-3-carbonitrile

Conditions	Yield
With ammonium acetate; potassium hydroxide In ethanol for 6h; Reflux;	82%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 3-bromo-4-methoxybenzylaldehyde (34841-06-0) + ethyl 2-cyanoacetate (105-56-6) → 4-(3-bromo-4-methoxyphenyl)-6-(2,5-dichlorothiophen-3-yl)-1,2-dihydro-2-oxopyridine-3-carbonitrile

Conditions	Yield
With ammonium acetate; potassium hydroxide In ethanol for 6h; Reflux;	82%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 4-methyl-benzaldehyde (104-87-0) → C14H10Cl2OS

Conditions	Yield
With sodium hydroxide In ethanol Claisen-Schmidt condensation;	81%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 5-bromo-3-phenylindole-2-carboxyhydrazide (70070-24-5) → C21H14BrCl2N3OS (1504554-96-4)

Conditions	Yield
In methanol Reflux;	80%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + 3,5-dibromo-4-hydroxybenzaldehyde (2973-77-5) → (E)-3-(3,5-dibromo-4-hydroxyphenyl)-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-one

Conditions	Yield
With potassium hydroxide In methanol at 20℃; for 10h; Claisen-Schmidt Condensation;	80%

3-acetyl-2,5-dichlorothiophene (36157-40-1) + ethyl 2-cyanoacetate (105-56-6) + (4-isopropylbenzaldehyde) (122-03-2) → 6-(2,5-dichlorothiophen-3-yl)-1,2-dihydro-4-(4-isopropylphenyl)-2-oxopyridine-3-carbonitrile

Conditions	Yield
With ammonium acetate; potassium hydroxide In ethanol for 6h; Reflux;	79%

Upstream product

• 3172-52-9 2,5-diclorothiophene 
• 75-36-5 acetyl chloride 
• 61170-81-8 1-methyl-4-chlorobutenal 
• 16911-84-5 thioacetyl chloride 

Downstream Products

• 36157-41-2 2,5-dichlorothiophene-3-carboxylic acid 
• 160982-09-2 3-Acetyl-2-(phenylmethyl)thio-5-chlorothiophene 
• 1353877-68-5 (2E)-1-(2,5-dichlorothiophen-3-yl)-3-(4-piperidin-1-ylphenyl)prop-2-en-1-one 
• 138890-62-7 brinzolamide 
• 160982-10-5 3-acetyl-5-chloro-2-thiophenesulfonamide 
• 160982-11-6 3-(2-Bromoacetyl)-5-chloro-thiophene-2-sulfonamide 
• 160982-16-1 (S)-3,4-dihydro-6-chloro-4-hydroxy-4H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide 
• 160982-13-8 (S)-3,4-dihydro-6-chloro-4-hydroxy-2-(3-methoxypropyl)-4H-thieno[3,2-e]-1,2-thiazine 1,1-dioxide 
• 154127-42-1 (S)-3,4-dihydro-4-hydroxy-2(3-methoxypropyl)-4H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide 
• 1313405-90-1 2-chloro-3-[3-(2,5-dichlorothiophen-3-yl)-4,5-dihydro-1H-pyrazol-5-yl]-8-methylquinoline 

Relevant articles and documents

Synthesis, characterization and biological evaluation of new 4-Aryl-6-(2,5-dichlorothiophen-3-yl)-1,2-dihydro-2-oxopyridine-3-carbonitrile

Condensation of 3-acetyl-2,5-dichlorothiophene with different aldehydes in presence of ethyl cyanoacetate led to the formation of the new oxopyridine derivatives containing a thiophene moiety (3a-j) in high yields. All newly synthesized compounds were characterized by standard spectroscopic techniques. Antibacterial evaluation for all new compounds shows no activity against four different types of bacteria.

Facile synthesis of 2-(substituted amino)-4H-thieno[3,2-e]-1,3-thiazin-4- ones

Interaction between 2,5-dichlorothiophene-3-carbonyl isothiocyanate, accessible via 2,5-dichlorothiophene-3-carbonyl chloride, and model heterocyclic amines produced the respective 2,5-dichloro-N-(substituted aminocarbonothioyl) thiophene-3-carboxamides. Upon heating, the deprotonated form of the latter underwent intramolecular cyclization to deliver the corresponding 2-(substituted amino)-4H-thieno[3,2-e]-1,3-thiazin-4-ones. The structures of these new bicyclic derivatives and their acyclic precursors are based on microanalytical and spectral (IR, MS, and NMR) data.

Synthesis method of 3-acetyl-2,5-dichlorothiophene

The invention discloses a synthesis method of 3-acetyl-2,5-dichlorothiophene and belongs to the field of organic synthesis. 1-methyl-4-chlorobutenal is added to a methanol solution, sodium methoxide is added after cooling, after thioacetylchloride is dropwise added, and a heating reaction is conducted to obtain the 3-acetyl-2,5-dichlorothiophene. The synthesis method is simple and convenient to operate, is green and environmentally friendly in production, the yield of the obtained product is higher, and the synthesis method is more suitable for mass production.

Synthesis, characterization and antimicrobial activity of new chalcones and their 6-aryl-4-(2,5-dichlorothiophen-3-yl)-6H-1,3-thiazin-2-amine derivatives

Chalcones (5a-h) were prepared in high yields via the condensation of 3-acetyl-2,5-dichlorothiophene (3) with aryl aldehydes (4a-h). The reaction of the resulting chalcones with thiourea in the presence of a catalytic amount of hydrochloric acid provided the 1,3-thiazin-2-amine derivatives (6a-g) in moderate yields. All new compounds were characterized by extensive NMR analysis data, including 1D NMR experiments (1H and 13C) and 2D NMR experiments (COSY, HMBC, HSQC), as well as ESIMS and HRESIMS data. The newly synthesized compounds were evaluated for their biological activities, which demonstrate a very good to low bioactivities as antibacterial and antifungal, respectively.