4066-41-5

Basic information

• Product Name: 5-Acetylthiophene-2-carboxylic acid
• Synonyms: LABOTEST-BB LT00454683;BUTTPARK 121\06-15;AKOS MSC-0226;5-ACETYL-2-THIOPHENECARBOXYLIC ACID;5-ACETYLTHIOPHENE-2-CARBOXYLIC ACID;RARECHEM AL BO 0535;5-Acetylthiophene-2-CarboxylicAcid98%;5-Acetylthiophene-2-Carboxylic Acid 98%
• CAS NO: 4066-41-5
• Molecular Formula: C₇H₆O₃S
• Molecular Weight: 170.19
• EINECS: 1312995-182-4
• Product Categories: Thiophenes
• Mol File: 4066-41-5.mol
• Article Data: 8

Chemical Properties

• Melting Point: 210-212°C
• Boiling Point: 385.2 °C at 760 mmHg
• Flash Point: 186.8 °C
• Appearance: /
• Density: 1.383
• Vapor Pressure: 1.27E-06mmHg at 25°C
• Refractive Index: 1.591
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: soluble in Methanol
• PKA: 2.95±0.10(Predicted)
• BRN: 128897
• CAS DataBase Reference: 5-Acetylthiophene-2-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Acetylthiophene-2-carboxylic acid(4066-41-5)
• EPA Substance Registry System: 5-Acetylthiophene-2-carboxylic acid(4066-41-5)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-22
• Safety Statements: 26-36/37/39-36
• Hazardous Substances Data: 4066-41-5(Hazardous Substances Data)

Usage

Uses

5-Acetylthiophene-2-carboxylic acid is a intermediate used in the preparation of various 2,5-disubstituted thiophenes.

Synthesis Reference(s)

Journal of Heterocyclic Chemistry, 3, p. 104, 1966 DOI: 10.1002/jhet.5570030127

InChI:InChI=1/C7H6O3S/c1-4(8)5-2-3-6(11-5)7(9)10/h2-3H,1H3,(H,9,10)

Synthetic route

5-bromothiophene-2-carboxylic acid (7311-63-9) + acetyl chloride (75-36-5) → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

Conditions	Yield
Stage #1: 5-bromothiophene-2-carboxylic acid; acetyl chloride With isopropylmagnesium bromide In tetrahydrofuran at -40 - -10℃; for 12h; Solid phase reaction; Stage #2: In dichloromethane at 20℃; for 0.25h; Hydrolysis; Further stages.;	90%

2-Acetyl-5-methylthiophen (13679-74-8) → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

Conditions	Yield
With cerium(III) chloride; 1,1,1-trichloroethanol; oxygen In acetonitrile at 60℃; Irradiation;	81%
With oxygen; cobalt(II) acetate; sodium bromide In acetic acid at 95℃; for 1.5h; Kinetics; Rate constant;
With oxygen; cobalt(II) acetate; sodium bromide In acetic acid at 100℃; for 1.5h;

2-Acetylthiophene (88-15-3) + carbon dioxide (124-38-9) → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

Conditions	Yield
With 2,3,6,7-tetramethoxy-9(10H)-anthracenone; caesium carbonate In dimethyl sulfoxide at 25℃; under 2280.15 Torr; for 18h; Irradiation; Sealed tube; regioselective reaction;	39%

2-thiophenylcarboxylic acid (527-72-0) + malonic acid (141-82-2) → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

Conditions	Yield
With PPA at 60 - 80℃; for 2h; Acylation; Friedel-Crafts acylation;	10%

1-(5-ethanesulfonylmethyl-[2]thienyl)-ethanone (98954-61-1) → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

Conditions	Yield
With potassium permanganate

N'-tetramethylethylenediamine + 2-methyl-2-(thiophen-2-yl)-[1,3]dioxolane (5916-12-1) → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

Conditions	Yield
With hydrogenchloride; n-butyllithium; carbon dioxide In tetrahydrofuran; hexane

2-Acetylthiophene (88-15-3) + 5-(α-methoxyimino)ethyl-2-thiophenecarboxylic acid (1379398-60-3) → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

2-Acetylthiophene (88-15-3) → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium carbonate; acetic acid / methanol; water / 86 °C / pH 4 - 5 2: polyphosphoric acid / 100 °C 3: sodium hypochlorite / methanol / 10 - 70 °C 4: hydrogenchloride / water / 55 - 60 °C View Scheme
Multi-step reaction with 4 steps 1: acetic acid; sodium carbonate / water; methanol / 3 h / pH 5 / Heating 2: zinc(II) chloride; hydrogenchloride / water; chloroform / 12 h / 100 °C 3: sodium hypochlorite; hydrogenchloride / water; methanol / 4 h / 70 °C 4: hydrogenchloride / water / 12 h / 65 °C View Scheme

2-(α-methoxyimino)ethylthiophene (114773-97-6) → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: polyphosphoric acid / 100 °C 2: sodium hypochlorite / methanol / 10 - 70 °C 3: hydrogenchloride / water / 55 - 60 °C View Scheme
Multi-step reaction with 3 steps 1: zinc(II) chloride; hydrogenchloride / water; chloroform / 12 h / 100 °C 2: sodium hypochlorite; hydrogenchloride / water; methanol / 4 h / 70 °C 3: hydrogenchloride / water / 12 h / 65 °C View Scheme

2-acetyl-5-(α-methoxyimino)ethylthiophene (114774-08-2) → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hypochlorite / methanol / 10 - 70 °C 2: hydrogenchloride / water / 55 - 60 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hypochlorite; hydrogenchloride / water; methanol / 4 h / 70 °C 2: hydrogenchloride / water / 12 h / 65 °C View Scheme

5-(α-methoxyimino)ethyl-2-thiophenecarboxylic acid → 5-acetylthiophene-2-carboxylic acid (4066-41-5)

Conditions	Yield
With hydrogenchloride In water at 55 - 60℃;
With hydrogenchloride In water at 65℃; for 12h;

5-acetylthiophene-2-carboxylic acid (4066-41-5) + diazomethyl-trimethyl-silane (18107-18-1) → methyl 5-acetyl-2-thiophenecarboxylate (4101-81-9)

Conditions	Yield
In methanol; toluene at 0 - 20℃;	100%
With tetrafluoroboric acid In dichloromethane; water at 0℃; for 2h;	11%

methanol (67-56-1) + 5-acetylthiophene-2-carboxylic acid (4066-41-5) → methyl 5-acetyl-2-thiophenecarboxylate (4101-81-9)

Conditions	Yield
With sulfuric acid Reflux;	92.81%
With thionyl chloride In N,N-dimethyl-formamide for 5h; Reflux;

5-acetylthiophene-2-carboxylic acid (4066-41-5) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → 5-(3-dimethylaminoacryloyl)thiophene-2-carboxylic acid methyl ester (866523-73-1)

Conditions	Yield
In toluene at 110℃; for 16h;	91%
In N,N-dimethyl-formamide Reflux;	80%
In toluene for 15h; Heating / reflux;
In toluene Reflux;

5-acetylthiophene-2-carboxylic acid (4066-41-5) + ethanol (64-17-5) → 5-acetyl-thiophene-2-carboxylic acid ethyl ester (33148-82-2)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 3h; Reflux; Dean-Stark;	91%
With sulfuric acid for 72h; Heating / reflux;	84%

5-acetylthiophene-2-carboxylic acid (4066-41-5) + N-[2-amino-1-(3-amino-3-oxopropyl)-1H-benzimidazol-5-yl]-N-methylbenzamide (658700-12-0) → C25H23N5O4S (1092486-13-9)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	90%
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 24h;

5-acetylthiophene-2-carboxylic acid (4066-41-5) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → 5-Acetyl-N-methoxy-N-methylthiophene-2-carboxamide (844502-57-4)

Conditions	Yield
With 4-methyl-morpholine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dimethyl amine at 25℃; for 16h;	86%

5-acetylthiophene-2-carboxylic acid (4066-41-5) + methyl iodide (74-88-4) → methyl 5-acetyl-2-thiophenecarboxylate (4101-81-9)

Conditions	Yield
With sodium carbonate In DMF (N,N-dimethyl-formamide) at 20℃;	80%
With potassium carbonate In N,N-dimethyl-formamide at 23℃; for 72h;	72%
With potassium carbonate In N,N-dimethyl-formamide at 23℃;	72%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 60h;
With sodium carbonate In N,N-dimethyl-formamide at 20℃;

5-acetylthiophene-2-carboxylic acid (4066-41-5) + tert-butyl alcohol (75-65-0) → tert-butyl-5-acetylthiophene-2-carboxylate (844502-29-0)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dimethyl amine at 25℃; for 16h;	72%

5-acetylthiophene-2-carboxylic acid (4066-41-5) + N-(2-(pyridin-2-yl)propan-2-yl)benzamide → 2-(5-acetylthiophen-2-yl)-N-(2-(pyridin-2-yl)propan-2-yl)benzamide

Conditions	Yield
With copper (I) acetate; lithium carbonate; silver nitrate In N,N-dimethyl-formamide at 100℃; for 24h; Inert atmosphere; Sealed tube;	45%

5-acetylthiophene-2-carboxylic acid (4066-41-5) + (R)-1-phenyl-ethyl-amine (3886-69-9) + sodium ethyltrithiocarbonate (67715-76-8) → ethyl 2-oxo-2-[5-((R)-1-phenylethylcarbamoyl)thiophen-2-yl]ethyl trithiocarbonate (1039454-46-0)

Conditions	Yield
Stage #1: 5-acetylthiophene-2-carboxylic acid With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at 0℃; for 0.75h; Stage #2: (R)-1-phenyl-ethyl-amine In tetrahydrofuran at 20℃; for 18h; Stage #3: sodium ethyltrithiocarbonate Further stages;	44%

5-acetylthiophene-2-carboxylic acid (4066-41-5) + sodium ethyltrithiocarbonate (67715-76-8) + aniline (62-53-3) → ethyl 2-oxo-2-(5-phenylcarbamoylthiophen-2-yl)ethyl trithiocarbonate (1039454-48-2)

Conditions	Yield
Stage #1: 5-acetylthiophene-2-carboxylic acid With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at 0℃; for 0.75h; Stage #2: aniline In tetrahydrofuran at 20℃; for 18h; Stage #3: sodium ethyltrithiocarbonate Further stages;	22%

5-acetylthiophene-2-carboxylic acid (4066-41-5) + 3,5-dimethylbenzyl amine (78710-55-1) + sodium ethyltrithiocarbonate (67715-76-8) → 2-[5-(3,5-dimethylbenzylcarbamoyl)thiophen-2-yl]-2-oxoethyl ethyl trithiocarbonate (1039454-47-1)

Conditions	Yield
Stage #1: 5-acetylthiophene-2-carboxylic acid With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at 0℃; for 0.75h; Stage #2: 3,5-dimethylbenzyl amine In tetrahydrofuran at 20℃; for 18h; Stage #3: sodium ethyltrithiocarbonate Further stages;	21%

5-acetylthiophene-2-carboxylic acid (4066-41-5) + 2-hydrazino-1,3-thiazole (30216-51-4) → 5-[1-(Thiazol-2-yl-hydrazono)-ethyl]-thiophene-2-carboxylic acid (109793-48-8)

Conditions	Yield
In ethanol at 95℃; for 0.166667h;	20%

5-acetylthiophene-2-carboxylic acid (4066-41-5) + sodium ethyltrithiocarbonate (67715-76-8) + benzylamine (100-46-9) → 2-(5-benzylcarbamoylthiophen-2-yl)-2-oxoethyl ethyl trithiocarbonate (1039454-42-6)

Conditions	Yield
Stage #1: 5-acetylthiophene-2-carboxylic acid With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at 0℃; for 0.75h; Stage #2: benzylamine In tetrahydrofuran at 20℃; for 18h; Stage #3: sodium ethyltrithiocarbonate Further stages;	12%

5-acetylthiophene-2-carboxylic acid (4066-41-5) + (S)-1-phenyl-ethylamine (2627-86-3) + sodium ethyltrithiocarbonate (67715-76-8) → ethyl 2-oxo-2-[5-((S)-1-phenylethylcarbamoyl)thiophen-2-yl]ethyl trithiocarbonate (1039454-44-8)

Conditions	Yield
Stage #1: 5-acetylthiophene-2-carboxylic acid With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at 0℃; for 0.75h; Stage #2: (S)-1-phenyl-ethylamine In tetrahydrofuran at 20℃; for 18h; Stage #3: sodium ethyltrithiocarbonate Further stages;	6%

5-acetylthiophene-2-carboxylic acid (4066-41-5) → 5-ethyl-2-thiophenecarboxylic acid (23229-72-3)

Conditions	Yield
With hydrazine hydrate; ethylene glycol at 145℃; Erhitzen des Reaktionsgemisches mit Kaliumhydroxid bis auf 193grad;

5-acetylthiophene-2-carboxylic acid (4066-41-5) → 5-(1-hydroxyimino-ethyl)-thiophene-2-carboxylic acid (98279-55-1)

Conditions	Yield
With potassium hydroxide; ethanol; hydroxylamine hydrochloride

5-acetylthiophene-2-carboxylic acid (4066-41-5) + diazodiphenylmethane (908093-98-1) → 5-Acetyl-thiophene-2-carboxylic acid benzhydryl ester

Conditions	Yield
In methanol at 25℃; Rate constant;

5-acetylthiophene-2-carboxylic acid (4066-41-5) → 5-(2-Bromo-acetyl)-thiophene-2-carboxylic acid (96543-76-9)

Conditions	Yield
With bromine In acetic acid at 110℃; for 0.166667h;

5-acetylthiophene-2-carboxylic acid (4066-41-5) → [4-(5-amino-thiophen-2-yl)-pyrimidin-2-yl]-methyl-amine (866523-80-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: 91 percent / toluene / 16 h / 110 °C 2: NaOEt / 40 h / 70 °C 3: 87 percent / hydrazine / methanol / 16 h / 70 °C 4: 91 percent / aq. HCl; NaNO2 / acetic acid / 0.5 h / 0 °C 5: 30 percent / aq. HCl / 16 h / 100 °C View Scheme

5-acetylthiophene-2-carboxylic acid (4066-41-5) → [4-(5-isocyanato-thiophen-2-yl)-pyrimidin-2-yl]-methyl-amine

Conditions	Yield
Multi-step reaction with 5 steps 1: 91 percent / toluene / 16 h / 110 °C 2: NaOEt / 40 h / 70 °C 3: 87 percent / hydrazine / methanol / 16 h / 70 °C 4: 91 percent / aq. HCl; NaNO2 / acetic acid / 0.5 h / 0 °C 5: xylene / 0.42 h / 120 °C View Scheme

5-acetylthiophene-2-carboxylic acid (4066-41-5) → 5-(2-methylsulfanyl-pyrimidin-4-yl)-thiophene-2-carboxylic acid methyl ester (908834-77-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent / toluene / 16 h / 110 °C 2: 69 percent / pyridine / H2O / 68 h / 100 °C View Scheme

5-acetylthiophene-2-carboxylic acid (4066-41-5) → 5-(2-amino-pyrimidin-4-yl)-thiophene-2-carboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent / toluene / 16 h / 110 °C 2: NaOEt / 40 h / 70 °C View Scheme

5-acetylthiophene-2-carboxylic acid (4066-41-5) → 5-(2-methylamino-pyrimidin-4-yl)-thiophene-2-carboxylic acid ethyl ester (866523-74-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent / toluene / 16 h / 110 °C 2: NaOEt / 40 h / 70 °C View Scheme

Upstream product

• 98954-61-1 1-(5-ethanesulfonylmethyl-[2]thienyl)-ethanone 
• 13679-74-8 2-Acetyl-5-methylthiophen 
• 7311-63-9 5-bromothiophene-2-carboxylic acid 
• 75-36-5 acetyl chloride 
• 5916-12-1 2-methyl-2-(thiophen-2-yl)-[1,3]dioxolane 
• 88-15-3 2-Acetylthiophene 
• 124-38-9 carbon dioxide 
• 527-72-0 2-thiophenylcarboxylic acid 
• 141-82-2 malonic acid 
• 114774-09-3 5-(α-methoxyimino)ethyl-2-thiophenecarboxylic acid 
• 114774-08-2 5-acetyl-2-(α-methoxyimino)ethylthiophene 
• 114773-97-6 2-(α-methoxyimino)ethylthiophene 
• 1379398-60-3 5-(α-methoxyimino)ethyl-2-thiophenecarboxylic acid 

Downstream Products

• 23229-72-3 5-ethyl-2-thiophenecarboxylic acid 
• 1039454-44-8 ethyl 2-oxo-2-[5-((S)-1-phenylethylcarbamoyl)thiophen-2-yl]ethyl trithiocarbonate 
• 1039454-47-1 2-[5-(3,5-dimethylbenzylcarbamoyl)thiophen-2-yl]-2-oxoethyl ethyl trithiocarbonate 
• 1039454-48-2 ethyl 2-oxo-2-(5-phenylcarbamoylthiophen-2-yl)ethyl trithiocarbonate 
• 1039454-42-6 2-(5-benzylcarbamoylthiophen-2-yl)-2-oxoethyl ethyl trithiocarbonate 
• 862698-91-7 5-acetyl-N-(phenylmethyl)-2-thiophenecarboxamide 
• 925921-17-1 C₁₄H₁₃NO₃S 
• 52560-89-1 5-(2-mercapto-1,3-thiazol-4-yl)-2-thiophene carboxamide 
• 68257-90-9 5-(2-bromoacetyl)thiophene-2-carboxamide 
• 101540-26-5 arotinolol hydrochloride 
• 4101-81-9 methyl 5-acetyl-2-thiophenecarboxylate 
• 499770-66-0 5-(2-methyl-1,3-thiazol-4-yl)thiophene-2-carboxaldehyde 
• 4192-32-9 2-bromo-1-(5-methoxycarbonylthiophen-2-yl)-ethanone 
• 1332871-47-2 5-(1-{[(2-fluorophenyl)sulfonyl]amino}ethyl)-N-hydroxythiophene-2-carboxamide 

Relevant articles and documents

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