4521-33-9

Basic information

• Product Name: 5-NITROTHIOPHENE-2-CARBOXALDEHYDE
• Synonyms: 5-Nitro-2-thiophenecarboxaldehyde 98%;LABOTEST-BB LT00112375;5-NITROTHIOPHENE-2-CARBALDEHYDE;5-NITROTHIOPHENE-2-CARBOXALDEHYDE;5-NITRO-2-THIOPHENECARBALDEHYDE;5-NITRO-2-THIOPHENECARBOXALDEHYDE;AKOS 93853;5-Nitrothiophene-2-carboxaldehyde,98%
• CAS NO: 4521-33-9
• Molecular Formula: C₅H₃NO₃S
• Molecular Weight: 157.15
• EINECS: 224-850-9
• Product Categories: Heterocycles;Building Blocks;Heterocyclic Building Blocks;Thiophenes
• Mol File: 4521-33-9.mol
• Article Data: 15

Chemical Properties

• Melting Point: 75-77 °C(lit.)
• Boiling Point: 297.2 °C at 760 mmHg
• Flash Point: 133.5 °C
• Appearance: yellow solid
• Density: 1.534 g/cm³
• Vapor Pressure: 0.00137mmHg at 25°C
• Refractive Index: 1.662
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: acetone: soluble1%, clear, yellow
• Water Solubility: Insoluble in water.
• Sensitive: Air Sensitive
• BRN: 120540
• CAS DataBase Reference: 5-NITROTHIOPHENE-2-CARBOXALDEHYDE(CAS DataBase Reference)
• NIST Chemistry Reference: 5-NITROTHIOPHENE-2-CARBOXALDEHYDE(4521-33-9)
• EPA Substance Registry System: 5-NITROTHIOPHENE-2-CARBOXALDEHYDE(4521-33-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 4521-33-9(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 4521-33-9 differently. You can refer to the following data:
1. 5-Nitrothiophene-2-carboxaldehyde is a reagent that is used in the activity of mefloquine-oxazolidine derivatives against multidrug-resistant Mycobacterium tuberculosis.
2. 5-Nitro-2-thiophenecarboxaldehyde was used in preparation of 2, 3-dihydro-2-(5-nitro-2-thienyl) quinazolin-4-(1H)-ones and various novel oxime ether derivatives, anti-protozoan agents.

General Description

Diastereoselectivity in [4+2] cycloaddition of 1-methoxy-2-methyl-3-(trimethylsiloxy)-1,3-pentadiene with 5-nitro-2-thiophenecarboxaldehyde was investigated.

InChI:InChI=1/C5H3NO3S/c7-3-4-1-2-5(10-4)6(8)9/h1-3H

Synthetic route

(5-nitrothiophen-2-yl)methanol (20898-85-5) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9)

Conditions	Yield
With silica-supported Jones reagent In dichloromethane for 0.00269444h;	99.8%

5-nitrothiophene-2-carboxaldehyde diacetate (14289-24-8) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9)

Conditions	Yield
With hydrogenchloride In methanol; water at 65℃; for 8h;	80%
With ethanol; sulfuric acid
With hydrogenchloride
With sulfuric acid

2-(chloromethyl)-5-nitrothiophene (20898-86-6) + 2-lithio-2-nitropropane (147225-22-7) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 2-isopropylidenemethyl-5-nitrothiophene (74786-70-2) + 2-(2-methyl-2-nitropropyl)-5-nitrothiophene + 1,2-bis-(5-nitro-2-thienyl)ethylene

Conditions	Yield
In methanol for 0.25h; Ambient temperature; Irradiation;	A n/a B 61% C 7% D 5%

2-(chloromethyl)-5-nitrothiophene (20898-86-6) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 2-isopropylidenemethyl-5-nitrothiophene (74786-70-2) + 2-(2-methyl-2-nitropropyl)-5-nitrothiophene + 1,2-bis-(5-nitro-2-thienyl)ethylene

Conditions	Yield
With lithium 2-nitropropane In methanol for 0.25h; Ambient temperature; Irradiation;	A n/a B 61% C 7% D 5%

thiophene-2-carbaldehyde (98-03-3) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 4-nitrothiophene-2-carbaldehyde (57500-53-5)

Conditions	Yield
With sulfuric acid; nitric acid at 0℃; for 0.5h;	A 13% B 46%
With sulfuric acid; nitric acid at -10℃; for 0.0833333h;	A n/a B 40%
With sulfuric acid; potassium nitrate at 0℃; for 0.5h; Inert atmosphere; Schlenk technique;	A n/a B 40%

2-(1'-chloro-2',2'-dimethylpropyl)-5-nitrothiophene (87207-17-8) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 2,2-dimethyl-1-(5'-nitro-2'-thienyl)-1-propanol (87207-23-6) + 2,2-dimethyl-1-(5'-nitro-2'-thienyl)-propane-1-one (83054-95-9)

Conditions	Yield
With 2-lithio-2-nitropropane In dimethyl sulfoxide at 20℃; for 1.1h;	A 7% B 7% C 42%
With 2-lithio-2-nitropropane In dimethyl sulfoxide at 20℃; for 1.1h; Mechanism; Irradiation;	A 7% B 5% C 42%

(5'-nitro-2'-thienyl)methyl acetate (20898-83-3) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9)

Conditions	Yield
With sodium thiophenolate In dimethyl sulfoxide for 0.2h;	15%

2-(chloromethyl)-5-nitrothiophene (20898-86-6) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9)

Conditions	Yield
With sodium thiophenolate In dimethyl sulfoxide for 0.166667h;	7%

thiophene-2-carbaldehyde (98-03-3) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9)

Conditions	Yield
With nitric acid; acetic anhydride at -14℃; Kinetics; Rate constant; Thermodynamic data; other temperatures, E, lg A, ΔH(excit.), ΔS(excit.);

thiophene-2-carbaldehyde (98-03-3) + sulfuric acid (7664-93-9) + nitric acid (7697-37-2) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 4-nitrothiophene-2-carbaldehyde (57500-53-5)

thiophene-2-carbaldehyde (98-03-3) + nitric acid (7697-37-2) + acetic anhydride (108-24-7) + acetic acid (64-19-7) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 4-nitrothiophene-2-carbaldehyde (57500-53-5)

Conditions	Yield
anschl. Hydrolyse;

thiophene-2-carbaldehyde (98-03-3) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 4-nitrothiophene-2-carbaldehyde (57500-53-5) + 3-nitrothiophene-2-carbaldehyde (58963-75-0)

Conditions	Yield
With sulfuric acid; nitric acid at 0℃; Title compound not separated from byproducts;

2,2-dimethyl-1-(2-thienyl)-1-propanone (20409-48-7) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9)

Conditions	Yield
Multi-step reaction with 4 steps 3: 95 percent / SOCl2 / pyridine 4: 7 percent / 2-lithio-2-nitropropane / dimethylsulfoxide / 1.1 h / 20 °C / Irradiation View Scheme

2,2-dimethyl-1-(5'-nitro-2'-thienyl)-1-propanol (87207-23-6) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / SOCl2 / pyridine 2: 7 percent / 2-lithio-2-nitropropane / dimethylsulfoxide / 1.1 h / 20 °C / Irradiation View Scheme

2,2-dimethyl-1-(5'-nitro-2'-thienyl)-propane-1-one (83054-95-9) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9)

Conditions	Yield
Multi-step reaction with 3 steps 2: 95 percent / SOCl2 / pyridine 3: 7 percent / 2-lithio-2-nitropropane / dimethylsulfoxide / 1.1 h / 20 °C / Irradiation View Scheme

2-thiophenecarboxaldehyde diacetate (63011-97-2) → 5-nitro-2-thiophenecarboxaldehyde (4521-33-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid anhydride; nitric acid; acetic acid 2: aqueous sulfuric acid View Scheme

methanol (67-56-1) + 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) → 5-(dimethoxymethyl)-2-nitrothiophene (17375-68-7)

Conditions	Yield
With hydrogenchloride for 0.75h; Heating;	100%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + trimethyl orthoformate (149-73-5) → 5-(dimethoxymethyl)-2-nitrothiophene (17375-68-7)

Conditions	Yield
With amberlyst-15 In acetonitrile for 1h; electroosmos;	99.8%
With amberlyst-15 In acetonitrile for 0.166667h;	97.5%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 4-allyl-3-thiosemicarbazide (3766-55-0) → 4-allyl-1-(5-nitrothenylidene)thiosemicarbazide (1198748-12-7)

Conditions	Yield
With toluene-4-sulfonic acid In toluene at 20℃;	99%

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%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + thiosemicarbazide (79-19-6) → 2-((5-nitrothiophen-2-yl)methylene)hydrazinecarbothioamide (5351-83-7)

Conditions	Yield
In methanol for 3h; Reflux;	98%
In ethanol for 2h; Reflux;	92%
With acetic acid In methanol for 2h; Reflux;	84.2%

4-amino-1,2,4-triazole (584-13-4) + 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) → (5-nitro-thiophen-2-ylmethylene)-[1,2,4]triazol-4-yl-amine (31539-41-0)

Conditions	Yield
With toluene-4-sulfonic acid In toluene Heating;	98%
In ethanol for 0.5h; heating on a steam bath;	69%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 3-trifluoromethylaniline (98-16-8) → N-(5-nitro-2-thienomethylidene)-3-trifluoromethylaniline (140436-71-1)

Conditions	Yield
In ethanol for 1h; Heating;	98%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + furan-2-ylmethanamine (617-89-0) → Furan-2-ylmethyl-[1-(5-nitro-thiophen-2-yl)-meth-(E)-ylidene]-amine (69819-72-3)

Conditions	Yield
Duolite A 101 D resin In 1,2-dimethoxyethane at -20 - 25℃; for 3h;	98%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 1,3-diaminoguanidine hydrochloride (36062-19-8) → 1,3-bis-((5-nitrothiophen-2-yl-methylidene)amino)guanidine hydrochloride (1206770-32-2)

Conditions	Yield
In methanol for 5h; Reflux;	98%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) → 5-nitrothiophene-2-carbaldehyde oxime (6030-18-8)

Conditions	Yield
With hydroxylamine hydrochloride; potassium carbonate In water Reflux;	98%
With pyridine; hydroxylamine hydrochloride In ethanol for 24h; Reflux;	85%
With hydroxylamine hydrochloride; sodium carbonate In dimethyl sulfoxide at 20℃;
With hydroxylamine hydrochloride In methanol at 25℃; for 0.25h;

2,4-imidazolidinedione (461-72-3) + 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) → (Z)-5-((5-nitrothiophen-2-yl)methylene)imidazolidine-2,4-dione

Conditions	Yield
With copper(II)-Para-aminobenzoic acid complex supported on Fe3O4 Magnetic nanoparticle In ethanol for 1.55h; Aldol Condensation; Reflux; Green chemistry;	98%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) → (5-nitrothiophen-2-yl)methanol (20898-85-5)

Conditions	Yield
With sodium tetrahydroborate In ethanol for 5h;	97.2%
Stage #1: 5-nitro-2-thiophenecarboxaldehyde With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 0 - 20℃; for 20h; Inert atmosphere; Stage #2: With sodium tetrahydroborate In 1,2-dichloro-ethane at 20℃; for 0.5h; Inert atmosphere;	96%
With sodium tetrahydroborate In methanol at 0 - 20℃; Inert atmosphere;	90%

Hippuric Acid (495-69-2) + 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) → 4-[1-(5-Nitro-thiophen-2-yl)-meth-(Z)-ylidene]-2-phenyl-4H-oxazol-5-one (31271-16-6, 89035-35-8)

Conditions	Yield
With sodium acetate; acetic anhydride at 100℃; for 2h;	97%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 4-chloro-aniline (106-47-8) → N-(5-nitro-2-thienomethylidene)-4-chloroaniline (64857-14-3)

Conditions	Yield
In ethanol for 1h; Heating;	97%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 3-amino-2-(4-chloro-2-ethylthio-5-methylbenzenesulphonyl)guanidine (519053-87-3) → 1-(4-chloro-2-ethylthio-5-methylbenzenesulfonyl)-3-(5-nitrothienylideneamino)guanidine

Conditions	Yield
In ethanol for 4h; Heating;	97%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 1,2-dichloro-ethane (107-06-2) → methyl 5-nitrothiophene-2-carboxylate (5832-01-9)

Conditions	Yield
With iodine; sodium hydrogencarbonate In methanol; n-heptane	96.5%

2,4-thiazolidinedion (2295-31-0) + 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) → (Z)-5-((5-nitrothiophen-2-yl)methylene)thiazolidine-2,4-dione

Conditions	Yield
With copper(II)-Para-aminobenzoic acid complex supported on Fe3O4 Magnetic nanoparticle In ethanol for 1.56667h; Aldol Condensation; Reflux; Green chemistry;	96%

2-amino-5-ethyl-1,3,4-thiadiazole (14068-53-2) + 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + phosphonic acid diethyl ester (762-04-9) → diethyl (((5-ethyl-1,3,4-thiadiazol-2-yl)amino)(5-nitrothiophen-2-yl)methyl)phosphonate

Conditions	Yield
With phospho sulphonic acid In neat (no solvent) for 0.15h; Kabachnik-Fields Reaction; Microwave irradiation; Green chemistry;	95.5%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 4-hydroxybenzoic acid hydrazide (5351-23-5) → 4-hydroxybenzoic acid (5-nitrothiophen-2-ylmethylene)hydrazide

Conditions	Yield
acetic acid In ethanol for 4h; Heating / reflux;	95%
In ethanol; water Heating;	86%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 4-Phenyl-3-thiosemicarbazide (5351-69-9) → (E)-4-phenyl-1-(5-nitrothienyl)thiosemicarbazide

Conditions	Yield
With toluene-4-sulfonic acid In toluene at 20℃; Inert atmosphere;	95%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + [{5-(4-benzylthio-2-chloro-5-sulfamoylphenyl)-1,3,4-oxadiazol-2-yl}methyl]triphenylphosphonium chloride → (E)-2-(benzylthio)-4-chloro-5-(5-(2-(5-nitrothiophen-2-yl)vinyl)-1,3,4-oxadiazol-2-yl)benzenesulfonamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 24h; Wittig Olefination; Inert atmosphere;	95%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + adamantane-1-carbohydrazide (17846-15-0) → E-N'-[(5-nitrothiophen-2-yl)methylidene]adamantane-1-carbohydrazide

Conditions	Yield
In ethanol for 1h; Reflux;	95%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + phenethylamine (64-04-0) → [1-(5-Nitro-thiophen-2-yl)-meth-(E)-ylidene]-phenethyl-amine (69819-75-6)

Conditions	Yield
Duolite A 101 D resin In 1,2-dimethoxyethane at -20 - 25℃; for 3h;	94%

(cyclohexa-2,4-dienyl-diphenyl-λ5-phosphanylidene)-acetic acid tert-butyl ester + 5-nitro-2-thiophenecarboxaldehyde (4521-33-9) → 3-(5-nitro-thiophen-2-yl)-acrylic acid tert-butyl ester

Conditions	Yield
In water at 20℃; for 1h; Wittig reaction;	94%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 2,5-diamino-thiophene-3,4-dicarboxylic acid diethyl ester (80691-81-2) → 2-amino-5-[(5-nitrothiophen-2-ylmethylene)amino]thiophene-3,4-dicarboxylic acid diethyl ester

Conditions	Yield
In toluene for 0.5h; Reflux;	94%
With trifluoroacetic acid In isopropyl alcohol for 0.5h; Heating;	87%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + dimedone (126-81-8) + 1,2-diamino-benzene (95-54-5) → 3,3-dimethyl-11-(5-nitrothiophen-2-yl)-2,3,4,5,10,11-hexahydro-1Hdibenzo[b,e][1,4]diazepin-1-one

Conditions	Yield
With silica-supported nickel oxide nanocomposites In ethanol at 70℃; for 0.25h; Microwave irradiation; Green chemistry;	94%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + p-toluic hydrazide (3619-22-5) → (E)-4-methyl-N′-((5-nitrothiophen-2-yl)methylene)benzohydrazide

Conditions	Yield
In ethanol; water Heating;	93%
With acetic acid In methanol for 6h; Reflux;	80%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 4-aminobenzohydrazide (5351-17-7) → C12H10N4O3S

Conditions	Yield
In ethanol; water Heating;	93%

5-nitro-2-thiophenecarboxaldehyde (4521-33-9) + 3-chlorobenzhydrazide (1673-47-8) → C12H8ClN3O3S

Conditions	Yield
In ethanol; water Heating;	93%

Upstream product

• 98-03-3 thiophene-2-carbaldehyde 
• 20898-86-6 2-(chloromethyl)-5-nitrothiophene 
• 147225-22-7 2-lithio-2-nitropropane 
• 7664-93-9 sulfuric acid 
• 7697-37-2 nitric acid 
• 108-24-7 acetic anhydride 
• 64-19-7 acetic acid 
• 20898-85-5 (5-nitrothiophen-2-yl)methanol 
• 63011-97-2 2-thiophenecarboxaldehyde diacetate 
• 83054-95-9 2,2-dimethyl-1-(5'-nitro-2'-thienyl)-propane-1-one 
• 87207-23-6 2,2-dimethyl-1-(5'-nitro-2'-thienyl)-1-propanol 
• 20409-48-7 2,2-dimethyl-1-(2-thienyl)-1-propanone 
• 87207-17-8 2-(1'-chloro-2',2'-dimethylpropyl)-5-nitrothiophene 
• 20898-83-3 (5'-nitro-2'-thienyl)methyl acetate 

Downstream Products

• 50832-68-3 1-acetyl-2-[2-(5-nitro-thiophen-2-yl)-vinyl]-1H-imidazole 
• 31271-16-6 4-[1-(5-Nitro-thiophen-2-yl)-meth-(Z)-ylidene]-2-phenyl-4H-oxazol-5-one 
• 107505-22-6 C₂₅H₂₉N₅O₂S 
• 140436-72-2 N-(5-nitro-2-thienomethylidene)-4-trifluoromethylaniline 
• 78374-26-2 (E)-2-(5-Nitro-thiophen-2-yl)-ethenesulfonic acid acetyl-phenyl-amide 
• 78374-31-9 (E)-2-(5-Nitro-thiophen-2-yl)-ethenesulfonic acid acetyl-(4-methoxy-phenyl)-amide 
• 78374-28-4 (E)-2-(5-Nitro-thiophen-2-yl)-ethenesulfonic acid acetyl-(2,4-dichloro-phenyl)-amide 
• 78374-29-5 (E)-2-(5-Nitro-thiophen-2-yl)-ethenesulfonic acid acetyl-(3-trifluoromethyl-phenyl)-amide 
• 74693-57-5 Acetic acid 1-methyl-3-[(E)-2-(5-nitro-thiophen-2-yl)-vinyl]-2-oxo-1,2-dihydro-quinolin-4-yl ester 
• 31167-35-8 5-acetylaminothiophen-2-aldehyde 
• 956-78-5 N-(4-hydroxyphenyl)-5-nitro-2-thiophenecarboxaldimine 
• 140436-71-1 N-(5-nitro-2-thienomethylidene)-3-trifluoromethylaniline 
• 85929-52-8 2-<5-Nitrothienyl-(2)>-5,5-dimethyl-thiazolidin-4-carbonsaeure-hydrochlorid 
• 85929-53-9 2-<5-Nitrothienyl-(2)>-5,5-dimethyl-thiazolidin-4-carbonsaeure 

Relevant articles and documents

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