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

Description

5-NITROTHIOPHENE-2-CARBOXALDEHYDE is an organic compound that serves as a reagent in the synthesis of various pharmaceutical compounds. It is characterized by its nitro and thiophene groups, which contribute to its chemical properties and reactivity.

Uses

Used in Pharmaceutical Industry:
5-NITROTHIOPHENE-2-CARBOXALDEHYDE is used as a reagent for the synthesis of mefloquine-oxazolidine derivatives, which exhibit activity against multidrug-resistant Mycobacterium tuberculosis. Its presence in the synthesis process aids in the development of new treatments for drug-resistant tuberculosis.
Used in Organic Chemistry:
5-NITROTHIOPHENE-2-CARBOXALDEHYDE is used in the preparation of 2,3-dihydro-2-(5-nitro-2-thienyl)quinazolin-4(1H)-ones and various novel oxime ether derivatives. These compounds have potential applications as anti-protozoan agents, contributing to the development of treatments for parasitic infections.

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

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

Downstream Products

• 18922-31-1 3-(5-nitro-thiophen-2-yl)-1-phenyl-propenone 
• 61464-24-2 (5-Nitro-thiophen-2-yl)-phenyl-methanol 

Relevant articles and documents

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Synthesis method of 5-nitrothiophene-2-formaldehyde

The invention relates to the technical field of chemistry, in particular to a synthesis method of 5-nitrothiophene-2-formaldehyde. The method comprises the steps of mixing 2-thiophenecarboxaldehyde and acetic anhydride, carrying out nucleophilic addition reaction to generate (acetyloxy) (2-thiophene) methyl acetate, and adding a nitrating agent to carry out nitration reaction to prepare 5-nitrothiophene-2-yl methylene diacetate; and carrying out a hydrolysis reaction on the obtained 5-nitrothiophene-2-yl methylene diacetate in a solvent to prepare 5-nitrothiophene-2-formaldehyde. The method has the beneficial effects that (1) cheap and easily available raw materials are used, the process is simple, the production cost is low, and the method is suitable for industrial production; and (2) the total yield and the total purity of the product are high.

Ethylammonium nitrate (EAN)/Tf2O and EAN/TFAA: Ionic liquid based systems for aromatic nitration

Acting as in situ sources of triflyl nitrate (TfONO2) and trifluoroacetyl nitrate (CF3COONO2), the EAN/Tf 2O and EAN/TFAA systems, generated via metathesis in the readily available ethylammonium nitrate (EAN) ionic liquid as solvent, are powerful electrophilic nitrating reagents for a wide variety of aromatic and heteroaromatic compounds. Comparative nitration experiments indicate that EAN/Tf2O is superior to EAN/TFAA for nitration of strongly deactivated systems. Both systems exhibit low substrate selectivity (K T/KB = 5-10) in (Figure presented) between values reported for covalent nitrates and preformed nitronium salts.