16405-98-4

Basic information

• Product Name: 2,1,3-Benzothiadiazole-5-carboxylic acid
• Synonyms: TIMTEC-BB SBB007390;RARECHEM AL BE 1094;1,2,3-BENZOTHIADIAZOLE-5-CARBOXYLIC ACID;2,1,3-BENZOTHIADIAZOLE-5-CARBOXYLIC ACID;BENZO-2,1,3-THIADIAZOLE-5-CARBOXYLIC ACID;BENZO-1,2,3-THIADIAZOLE-5-CARBOXYLIC ACID;BENZO[1,2,5]THIADIAZOLE-5-CARBOXYLIC ACID;BUTTPARK 46\04-59
• CAS NO: 16405-98-4
• Molecular Formula: C₇H₄N₂O₂S
• Molecular Weight: 180.18
• Product Categories: Heterocycles series;API intermediates
• Mol File: 16405-98-4.mol
• Article Data: 3

Chemical Properties

• Melting Point: 229 °C
• Boiling Point: 368.748 °C at 760 mmHg
• Flash Point: 176.813 °C
• Appearance: /
• Density: 1.609 g/cm³
• Vapor Pressure: 4.35E-06mmHg at 25°C
• Refractive Index: 1.749
• PKA: 3.16±0.30(Predicted)
• CAS DataBase Reference: 2,1,3-Benzothiadiazole-5-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2,1,3-Benzothiadiazole-5-carboxylic acid(16405-98-4)
• EPA Substance Registry System: 2,1,3-Benzothiadiazole-5-carboxylic acid(16405-98-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-41-37/38
• Safety Statements: 26-36/37/39-24/25-39
• HazardClass: IRRITANT
• Hazardous Substances Data: 16405-98-4(Hazardous Substances Data)

Usage

General Description

2,1,3-Benzothiadiazole-5-carboxylic acid, also known as BTDA, is a chemical compound belonging to the class of organic compounds known as benzothiadiazoles. 2,1,3-Benzothiadiazole-5-carboxylic acid is characterized by a benzothiadiazole ring system, a structure that contains a benzene ring fused to a thiadiazole ring, a type of heterocyclic aromatic ring with a nitrogen and sulfur atom. BTDA commonly appears as a colorless to slightly yellow crystalline powder, and it is a solid at room temperature. The compound is primarily known for its use in the field of high-performance polymers and epoxy resins in addition to its capabilities as a curing agent. It provides enhanced thermal and dimensional stability, oxidation resistance, and exceptional resistivity to various chemicals. However, protection is necessary when handling this chemical due to its potential hazard risks.

InChI:InChI=1/C7H4N2O2S/c10-7(11)4-1-2-5-6(3-4)9-12-8-5/h1-3H,(H,10,11)

Synthetic route

methyl benzo-2,1,3-thiadiazole-5-carboxylate → benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4)

Conditions	Yield
Stage #1: methyl benzo-2,1,3-thiadiazole-5-carboxylate With sodium hydroxide; ethanol; water at 20℃; for 3h; Stage #2: With hydrogenchloride In water pH=2;	92%
With pyridine; lithium iodide Heating;

benzo[c][1,2,5]thiadiazole-5-carbaldehyde (71605-72-6) → benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4)

Conditions	Yield
With sodium hydroxide; silver nitrate

N-phenylsulfinylamine (222851-56-1) + 3,4-diaminobenzoic acid (619-05-6) → benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4)

Conditions	Yield
With xylene

5-methylbenzo[c][1,2,5]thiadiazole (1457-93-8) → benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: N-bromo-succinimide 3: aqueous acetic acid; hexamethylenetetramine 4: AgNO3; aqueous NaOH View Scheme

5-bromomethyl-benzo[1,2,5]thiadiazole (65858-50-6) → benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4)

Conditions	Yield
Multi-step reaction with 3 steps 2: aqueous acetic acid; hexamethylenetetramine 3: AgNO3; aqueous NaOH View Scheme

1-benzo[1,2,5]thiadiazol-5-ylmethyl-1,3,5,7-tetraaza-adamantanium; bromide → benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous acetic acid; hexamethylenetetramine 2: AgNO3; aqueous NaOH View Scheme

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) + N,0-dimethylhydroxylamine (1117-97-1) → benzo[1,2,5]thiadiazole-5-carboxylic acid methoxy-methyl-amide (937279-22-6)

Conditions	Yield
With triethylamine; HATU In dichloromethane at 20℃; for 3h; Inert atmosphere;	95%

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) + 4-(4-methoxybenzyl)-6-piperidin-4-ylpyrimidin-2-amine (198554-72-2) → 4-[1-(2,1,3-benzothiadiazol-5-ylcarbonyl)piperidin-4-yl]-6-(4-methoxybenzyl)pyrimidin-2-amine (1085916-69-3)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 20℃;	84%

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) → 2,1,3-benzothiadiazol-5-ylmethanol (89795-51-7)

Conditions	Yield
Stage #1: benzo[1,2,5]thiadiazole-5-carboxylic acid With triethylamine; isobutyl chloroformate In tetrahydrofuran at 0℃; for 0.5h; Stage #2: With sodium tetrahydroborate; water In tetrahydrofuran at 0℃; for 0.5h;	81%
Multi-step reaction with 2 steps 1: DIPEA / tetrahydrofuran / 1.5 h / 0 °C 2: 1.45 g / aq. NaBH4 / tetrahydrofuran / 2 h / 20 °C View Scheme

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) + tert-Butyl 2,2,2-trichloroacetimidate (98946-18-0) → tert-butyl 2,1,3-benzothiadiazole-5-carboxylate

Conditions	Yield
With boron trifluoride diethyl etherate In tetrahydrofuran; cyclohexane at 20℃; for 0.5h;	76%

6,6-difluoro-5-methyl-5-hexenyl methanesulfonate (509101-25-1) + benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) → 6,6-difluoro-5-methyl-5-hexenyl benzo[1,2,5]thiadiazole-5-carboxylate

Conditions	Yield
With sodium hydrogencarbonate In DMF (N,N-dimethyl-formamide) at 100℃; for 3h;	64%

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) → benzo[1,2,5]thiadiazole-5-carboxylic acid amide (99620-31-2)

Conditions	Yield
With thionyl chloride anschliessend Umsetzen mit NH3;

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) + chloroformic acid ethyl ester (541-41-3) → C10H8N2O4S

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0℃; for 1.5h;

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) + 4-{2-[1-methyl-4-(1-methyl-4-(4-amino-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine dihydrochloride → 4-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-(benzo[1,2,5]thiadiazole-5-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25 - 37℃; for 16h;

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) → 8-benzo[1,2,5]thiadiazol-5-ylmethyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one

Conditions	Yield
Multi-step reaction with 3 steps 1.1: DIPEA / tetrahydrofuran / 1.5 h / 0 °C 2.1: 1.45 g / aq. NaBH4 / tetrahydrofuran / 2 h / 20 °C 3.1: MeSO2Cl; DIPEA / CH2Cl2 / 0.5 h / 20 °C 3.2: tetrahydrofuran / 1 h / 20 °C View Scheme

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) → 4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]decane-8-carboxylic acid benzo[1,2,5]thiadiazol-5-ylmethyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1.1: DIPEA / tetrahydrofuran / 1.5 h / 0 °C 2.1: 1.45 g / aq. NaBH4 / tetrahydrofuran / 2 h / 20 °C 3.1: dimethylformamide; tetrahydrofuran / 2 h / 20 °C 3.2: 16.5 percent / dimethylformamide; tetrahydrofuran View Scheme

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → benzo[1,2,5]thiadiazole-5-carboxylic acid methoxy-methyl-amide (937279-22-6)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 42h; Inert atmosphere;

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) → 5-(benzo[c][1,2,5]thiadiazol-5-yl)-2,2-dimethylfuran-3(2H)-one (1202376-82-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine; HATU / dichloromethane / 3 h / 20 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C / Inert atmosphere 2.2: 3 h / -78 °C 3.1: toluene-4-sulfonic acid / dichloromethane / 2 h / 20 °C 4.1: diethylamine / ethanol / 20 °C View Scheme

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) → 5-(benzo[c][1,2,5]thiadiazol-5-yl)-4-bromo-2,2-dimethylfuran-3(2H)-one (1202376-83-7)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: triethylamine; HATU / dichloromethane / 3 h / 20 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C / Inert atmosphere 2.2: 3 h / -78 °C 3.1: toluene-4-sulfonic acid / dichloromethane / 2 h / 20 °C 4.1: diethylamine / ethanol / 20 °C 5.1: N-Bromosuccinimide / chloroform / 2 h / 20 °C View Scheme

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) → 1-(benzo[c][1,2,5]thiadiazol-5-yl)-4-hydroxy-4-methylpent-2-yn-1-one (1202376-81-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: triethylamine; HATU / dichloromethane / 3 h / 20 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C / Inert atmosphere 2.2: 3 h / -78 °C 3.1: toluene-4-sulfonic acid / dichloromethane / 2 h / 20 °C View Scheme

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) → 1-(benzo[c][1,2,5]thiadiazol-5-yl)-4-methyl-4-(trimethylsilyloxy)pent-2-yn-1-one (1202376-80-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine; HATU / dichloromethane / 3 h / 20 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C / Inert atmosphere 2.2: 3 h / -78 °C View Scheme

benzo[1,2,5]thiadiazole-5-carboxylic acid (16405-98-4) → 5-(benzo[c][1,2,5]thiadiazol-5-yl)-2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one (1202368-77-1)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: triethylamine; HATU / dichloromethane / 3 h / 20 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C / Inert atmosphere 2.2: 3 h / -78 °C 3.1: toluene-4-sulfonic acid / dichloromethane / 2 h / 20 °C 4.1: diethylamine / ethanol / 20 °C 5.1: N-Bromosuccinimide / chloroform / 2 h / 20 °C 6.1: caesium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; toluene / 12 h / Inert atmosphere; Reflux View Scheme

Upstream product

• 619-05-6 3,4-diaminobenzoic acid 
• 36692-49-6 Methyl 3,4-diaminobenzoate 
• 65858-50-6 5-bromomethyl-benzo[1,2,5]thiadiazole 
• 1457-93-8 5-methylbenzo[c][1,2,5]thiadiazole 
• 175204-21-4 methyl benzo-2,1,3-thiadiazole-5-carboxylate 
• 222851-56-1 N-phenylsulfinylamine 
• 71605-72-6 benzo[c][1,2,5]thiadiazole-5-carbaldehyde 

Downstream Products

• 1085916-69-3 4-[1-(2,1,3-benzothiadiazol-5-ylcarbonyl)piperidin-4-yl]-6-(4-methoxybenzyl)pyrimidin-2-amine 
• 321309-31-3 benzo[c][1,2,5]thiadiazole-5-carbonyl chloride 
• 937279-22-6 N-methoxy-N-methylbenzo[c][1,2,5]thiadiazole-5-carboxamide 
• 89795-51-7 2,1,3-benzothiadiazol-5-ylmethanol 

Relevant articles and documents

Substitution Effect on 2-(Oxazolinyl)-phenols and 1,2,5-Chalcogenadiazole -Annulated Derivatives: Emission-Color-Tunable, Minimalistic Excited-State Intramolecular Proton Transfer (ESIPT)-Based Luminophores

Minimalistic 2-(oxazolinyl)-phenols substituted with different electron-donating and -withdrawing groups as well as 1,2,5-chalcogenadiazole-annulated derivatives thereof were synthesized and investigated in regard to their emission behavior in solution as well as in the solid state. Depending on the nature of the incorporated substituent and its position, emission efficiencies were increased or diminished, resulting in AIE or ACQ characteristics. Single-crystal analysis revealed J- and H-type packing motifs and a so-far undescribed isolation of ESIPT-based fluorophores in the keto form.

From hit to lead. Combining two complementary methods for focused library design. Application to μ opiate ligands

Compound 1 obtained by random screening and displaying a micromolar activity on the μ opiate receptor was chosen as a starting point for optimization. Two complementary concepts of similarity were used for the design of analogues and compared. These are based, respectively, on a computer-aided comparison of pharmacophoric patterns and on topological similarity. The structure-activity relationships are discussed in light of both similarity concepts. Compound 40, an N-methyl-3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetamide derivative, designed by combining the structure-activity relationships enlightened by each method, has a subnanomolar affinity for μ (h) receptor (IC50=0.9 nM). It is a promising lead, allowing the design of a new series of analogues substituted at the N-3 of the spirocycle moiety.