6317-37-9

Basic information

• Product Name: 5-Nitrothiophene-2-carboxylic acid
• Synonyms: RARECHEM AL BO 0544;5-Nitro-2-thenoic acid;5-NITRO-2-THIOPHENECARBOXYLIC ACID;5-NITROTHIOPHENE-2-CARBOXYLIC ACID;BUTTPARK 121\04-13;5-Nitro-2-ThiphenecarboxylicAcid;5-nitro-2-thiophenecarboxylic;2-Carboxy-5-nitrothiophene
• CAS NO: 6317-37-9
• Molecular Formula: C₅H₃NO₄S
• Molecular Weight: 173.15
• EINECS: 228-654-4
• Product Categories: Heterocycles;Carboxylic Acids;Thiophenes & Benzothiophenes;Thiophene&Benzothiophene;Carboxylic Acids;Thiophenes & Benzothiophenes;Building Blocks;Heterocyclic Building Blocks;Thiophenes
• Mol File: 6317-37-9.mol
• Article Data: 23

Chemical Properties

• Melting Point: 154-159℃
• Boiling Point: 367.2 °C at 760 mmHg
• Flash Point: 175.9 °C
• Appearance: Pale yellow/Solid
• Density: 1.676 g/cm³
• Vapor Pressure: 4.88E-06mmHg at 25°C
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: 2.69±0.10(Predicted)
• CAS DataBase Reference: 5-Nitrothiophene-2-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Nitrothiophene-2-carboxylic acid(6317-37-9)
• EPA Substance Registry System: 5-Nitrothiophene-2-carboxylic acid(6317-37-9)

Safety Data

• Hazard Codes: Xi
• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 6317-37-9(Hazardous Substances Data)

Usage

Chemical Properties

Solid

Uses

5-Nitrothiophene-2-carboxylic Acid is a reagent used in the preparation of benzothiophene amides which fuctions as nicotinamide ribosyltransferase inhibitors with potential antitumor and anticancer activities. It also functions as an intermediate in varying organic transformations.

Synthesis Reference(s)

Canadian Journal of Chemistry, 44, p. 2881, 1966 DOI: 10.1139/v66-428Journal of Medicinal Chemistry, 34, p. 2112, 1991

InChI:InChI=1/C5H3NO4S/c7-5(8)3-1-2-4(11-3)6(9)10/h1-2H,(H,7,8)/p-1

Synthetic route

(5-nitrothiophen-2-yl)methanol (20898-85-5) → 5-nitrothiophene-2-carboxylic acid (6317-37-9)

Conditions	Yield
With silica-supported Jones reagent In dichloromethane for 0.035h;	99.7%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) → 5-nitrothiophene-2-carboxylic acid (6317-37-9)

Conditions	Yield
With bromine; sodium acetate; acetic acid	98.5%
With hydrogenchloride; bromine; sodium hydroxide In water	98.2%
With sodium hypobromide; sodium acetate; acetic acid	92%

2-thiophenylcarboxylic acid (527-72-0) → 5-nitrothiophene-2-carboxylic acid (6317-37-9) + 4-nitro-2-thiophenecarboxylic acid (13138-70-0)

Conditions	Yield
With nitric acid; acetic anhydride; acetic acid at 20℃; for 4h; Nitration;	A 17% B 34%
With sulfuric acid; nitric acid at 0 - 10℃; for 1.25h;
With sulfuric acid; nitric acid at 10 - 20℃;	A n/a B 18.2 g
With sulfuric acid; nitric acid at 10 - 20℃; Overall yield = 18.2 g;

5-nitro-2-thienyl cyanide (16689-02-4) → 5-nitrothiophene-2-carboxylic acid (6317-37-9)

Conditions	Yield
With hydrogenchloride

2-acetyl-5-nitrothiophene (39565-00-9) → 5-nitrothiophene-2-carboxylic acid (6317-37-9) + (5-nitro-[2]thienyl)-glyoxylic acid

Conditions	Yield
With nitric acid

2-thiophenylcarboxylic acid (527-72-0) + nitric acid (7697-37-2) + acetic anhydride (108-24-7) → 2-nitrothiophene (609-40-5) + 5-nitrothiophene-2-carboxylic acid (6317-37-9) + 4-nitro-2-thiophenecarboxylic acid (13138-70-0)

Conditions	Yield
at -5℃;

2-thiophenylcarboxylic acid (527-72-0) → 5-nitrothiophene-2-carboxylic acid (6317-37-9) + 4-nitro-thiophene-2-carboxylic acid ; 2-nitro-thiophene

Conditions	Yield
With nitric acid; acetic anhydride at -5℃;

2-thiophenecarboxaldehyde diacetate (63011-97-2) → 5-nitrothiophene-2-carboxylic acid (6317-37-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid anhydride; nitric acid; acetic acid 2: aqueous sulfuric acid 3: aqueous potassium permanganate solution; aq. NaOH solution View Scheme

5-nitrothiophene-2-carboxaldehyde diacetate (14289-24-8) → 5-nitrothiophene-2-carboxylic acid (6317-37-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous sulfuric acid 2: aqueous potassium permanganate solution; aq. NaOH solution View Scheme
Multi-step reaction with 2 steps 1: ethanol; sulfuric acid 2: chromium (VI)-oxide; aqueous sulfuric acid / 110 °C View Scheme

2-thiophenylcarboxylic acid (527-72-0) → 5-nitrothiophene-2-carboxylic acid (6317-37-9)

sodium chlorite (7758-19-2) + 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + sodium dihydrogen phosphate → 5-nitrothiophene-2-carboxylic acid (6317-37-9)

Conditions	Yield
With dihydrogen peroxide; sodium thiosulfate In water; acetonitrile

sodium dihydrogenphosphate (10049-21-5) + 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + dihydrogen peroxide (7722-84-1) → 5-nitrothiophene-2-carboxylic acid (6317-37-9)

Conditions	Yield
With hydrogenchloride; NaClO2; sodium sulfite In water; acetonitrile

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + jones reagent → 5-nitrothiophene-2-carboxylic acid (6317-37-9)

Conditions	Yield
In water; isopropyl alcohol; acetone	967 mg (90%)

5-nitrothiophene-2-carboxylic acid (6317-37-9) → 5-nitrothiophene-2-carbonyl chloride (39978-57-9)

Conditions	Yield
With oxalyl dichloride Reflux;	100%
With thionyl chloride Reflux;	100%
With thionyl chloride

5-nitrothiophene-2-carboxylic acid (6317-37-9) + ethanol (64-17-5) → 5-nitro-2-thiophenecarboxylic acid ethyl ester (5751-84-8)

Conditions	Yield
With hydrogenchloride In water for 1.5h; Reflux;	98.3%
Stage #1: 5-nitrothiophene-2-carboxylic acid With thionyl chloride for 3h; Heating / reflux; Stage #2: ethanol for 3h; Heating / reflux;	96%
In methanol Reflux;

5-nitrothiophene-2-carboxylic acid (6317-37-9) → (5-nitrothiophen-2-yl)methanol (20898-85-5)

Conditions	Yield
With borane-THF In tetrahydrofuran at 20℃; for 16h; Inert atmosphere; Cooling with ice;	98%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + 4-isopropyl-1-methylcyclohex-3-en-1-amine → N-(4-isopropyl-1-methylcyclohex-3-en-1-yl)-5-nitrothiophene-2-carboxamide

Conditions	Yield
Stage #1: 5-nitrothiophene-2-carboxylic acid With thionyl chloride; N,N-dimethyl-formamide In dichloromethane Reflux; Stage #2: 4-isopropyl-1-methylcyclohex-3-en-1-amine With triethylamine In dichloromethane; N,N-dimethyl-formamide Reflux;	96.39%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + (S)-N-[[3-[3-fluoro-4-(1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (154590-66-6) → C21H22FN5O6S

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 18h;	93%

methanol (67-56-1) + 5-nitrothiophene-2-carboxylic acid (6317-37-9) → methyl 5-nitrothiophene-2-carboxylate (5832-01-9)

Conditions	Yield
With sulfuric acid for 48h; Heating;	91%
With hydrogenchloride
With thionyl chloride
In methanol Reflux;

5-nitrothiophene-2-carboxylic acid (6317-37-9) + dimethyl sulfate (77-78-1) → methyl 5-nitrothiophene-2-carboxylate (5832-01-9)

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide); acetone at 100℃; for 1h;	89%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + diethyl-L-glutamate hydrochloride (1118-89-4) → N-(5-nitro-2-thiophenecarbonyl)-L-glutamic acid diethyl ester (106585-64-2)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane for 2h; Ambient temperature;	88%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + 2-methoxy-6-pentadecylaniline → N-(2-methoxy-6-pentadecylphenyl)-5-nitrothiophene-2-carboxamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;	88%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + 2-methoxy-6-octylaniline → N-(2-methoxy-6-octylphenyl)-5-nitrothiophene-2-carboxamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;	87%

2-{1-[3,5-difluoro-4-(1,2,3,6-tetrahydro-pyridin-4-yl)-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-isoindole-1,3-dione (864145-50-6) + 5-nitrothiophene-2-carboxylic acid (6317-37-9) → 2-(1-{3,5-difluoro-4-[1-(5-nitro-thiophene-2-carbonyl)-1,2,3,6-tetrahydro-pyridin-4-yl]-phenyl}-1H-[1,2,3]triazol-4-ylmethyl)-isoindole-1,3-dione

Conditions	Yield
Stage #1: 5-nitrothiophene-2-carboxylic acid With thionyl chloride for 1h; Heating / reflux; Stage #2: 2-{1-[3,5-difluoro-4-(1,2,3,6-tetrahydro-pyridin-4-yl)-phenyl]-1H-[1,2,3]triazol-4-ylmethyl}-isoindole-1,3-dione With triethylamine In tetrahydrofuran at 0 - 35℃; for 12h;	80%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + L-glutamic acid diethyl ester (16450-41-2) → N-(5-nitro-2-thiophenecarbonyl)-L-glutamic acid diethyl ester (106585-64-2)

Conditions	Yield
Stage #1: 5-nitrothiophene-2-carboxylic acid With thionyl chloride for 3h; Reflux; Stage #2: L-glutamic acid diethyl ester With triethylamine In dichloromethane at 0 - 5℃; for 1h;	79.9%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + C13H12N4O4S → 5-nitro-N-(4-(5-(5-nitrothiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)thiophene-2-carboxamide

Conditions	Yield
With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 12h;	78%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + 2-(3,4-dimethoxyphenyl)-ethylamine (120-20-7) → N-(3,4-dimethoxyphenethyl)-5-nitrothiophene-2-carboxamide (93988-49-9)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide at 20℃; for 2h;	74%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + 4-(4-(tert-butyl)phenyl)-5-(4-fluorophenyl)thiazol-2-amine → N-(4-(4-(tert-butyl)phenyl)-5-(4-fluorophenyl)thiazol-2-yl)-5-nitrothiophene-2-carboxamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; Inert atmosphere;	74%

5-nitrothiophene-2-carboxylic acid (6317-37-9) → 4-amino-2-thiophenecarboxylic acid (89499-38-7)

Conditions	Yield
With hydrogenchloride; tin(ll) chloride at 20℃; for 6h; Reduction;	67%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + 1-(5-nitrothiazol-2-yl)piperidin-4-amine (1601751-76-1) → 5-nitro-N-(1-(5-nitrothiazol-2-yl)piperidin-4-yl)thiophene-2-carboxamide (1624309-47-2)

Conditions	Yield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In dichloromethane; ethyl acetate at 0 - 20℃; for 6h;	65.5%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + C14H19ClN2O3 (1312205-19-8) → C19H21N3O7S (1274572-94-9)

Conditions	Yield
With dmap In N,N-dimethyl-formamide at 80℃; for 6h;	64%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + (4-aminomethyl)aniline (4403-71-8) → 5-nitro-N-(4-(5-nitrothiophene-2-carboxamido)benzyl)thiophene-2-carboxamide

Conditions	Yield
With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0℃; for 24h;	63%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + N-tert-butylchloroacetamide (15678-99-6) → C11H14N2O5S (1274572-90-5)

Conditions	Yield
With dmap In N,N-dimethyl-formamide at 80℃; for 6h;	61%

3-(1H-imidazol-1-yl)propan-1-amine (5036-48-6) + 5-nitrothiophene-2-carboxylic acid (6317-37-9) → N-(3-(1H-imidazol-1-yl)propyl)-5-nitrothiophene-2-carboxamide

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide at 20℃; for 2h;	59%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + C14H19ClN2O3 (1312205-12-1) → C19H21N3O7S (1274572-93-8)

Conditions	Yield
With dmap In N,N-dimethyl-formamide at 80℃; for 6h;	58%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + 3-amino-6-trifluoromethylquinoxaline-2-carbonitrile-N1,N4-dioxide → C15H6F3N5O5S (1207614-18-3)

Conditions	Yield
Stage #1: 5-nitrothiophene-2-carboxylic acid; 3-amino-6-trifluoromethylquinoxaline-2-carbonitrile-N1,N4-dioxide In N,N-dimethyl-formamide at 20℃; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide Stage #3: With dmap	57.9%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + chloroacetone (78-95-5) → C8H7NO5S (1274572-95-0)

Conditions	Yield
With dmap In N,N-dimethyl-formamide at 80℃; for 6h;	56%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + 1-(4-fluorophenylmethyl)piperazine (70931-28-1) → [4-(4-fluorobenzyl)piperazin-1-yl](5-nitro-2-thienyl)methanone

Conditions	Yield
Stage #1: 5-nitrothiophene-2-carboxylic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 1-(4-fluorophenylmethyl)piperazine With triethylamine In N,N-dimethyl-formamide at 50℃; for 0.166667h; Microwave irradiation;	55%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + 3-amino-6-trifluoromethylquinoxaline-2-carbonitrile-N1,N4-dioxide → C15H6F3N5O5S (1207614-17-2)

Conditions	Yield
Stage #1: 5-nitrothiophene-2-carboxylic acid; 3-amino-6-trifluoromethylquinoxaline-2-carbonitrile-N1,N4-dioxide In N,N-dimethyl-formamide at 20℃; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide Stage #3: With dmap	51.8%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + 1-chloro-3,3-dimethyl-butan-2-one (13547-70-1) → C11H13NO5S (1274572-97-2)

Conditions	Yield
With dmap In N,N-dimethyl-formamide at 80℃; for 6h;	48%

5-nitrothiophene-2-carboxylic acid (6317-37-9) + C13H10N2O5S → 5-nitro-N-(4-((5-nitrothiophen-2-yl)carbamoyl)benzyl)thiophene-2-carboxamide

Conditions	Yield
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 0 - 20℃; for 2h;	46%

Upstream product

• 39565-00-9 2-acetyl-5-nitrothiophene 
• 527-72-0 2-thiophenylcarboxylic acid 
• 7697-37-2 nitric acid 
• 108-24-7 acetic anhydride 
• 4521-33-9 5-nitro-2-thiophenecarboxaldehyde 
• 10049-21-5 sodium dihydrogenphosphate 
• 7722-84-1 dihydrogen peroxide 
• 7758-19-2 sodium chlorite 
• 14289-24-8 5-nitrothiophene-2-carboxaldehyde diacetate 
• 63011-97-2 2-thiophenecarboxaldehyde diacetate 
• 20898-85-5 (5-nitrothiophen-2-yl)methanol 
• 16689-02-4 5-nitro-2-thienyl cyanide 

Downstream Products

• 5751-84-8 5-nitro-2-thiophenecarboxylic acid ethyl ester 
• 660-88-8 5-aminopentanoic acid 
• 89499-46-7 5-acetylaminothiophene-2-carboxylic acid 
• 89499-38-7 4-amino-2-thiophenecarboxylic acid 
• 5832-01-9 methyl 5-nitrothiophene-2-carboxylate 
• 891845-32-2 cyclohexyl 5-nitro-2-thiophenecarboxylate 
• 1498311-57-1 tert-butyl 5-aminothiophene-2-carboxylate 
• 112889-02-8 N-(5-methylamino-2-thiophenecarbonyl)-L-glutamic acid diethyl ester 

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