939-69-5

Basic information

• Product Name: 2-CYANO-6-HYDROXYBENZOTHIAZOLE
• Synonyms: 2-CYANO-6-HYDROXYBENZOTHIAZOLE;2-Benzothiazolecarbonitrile, 6-hydroxy;6-Hydroxy-2-Benzothiazolecarbonitrile;6-Hydroxy-Benzothiazole-2-Carb;2-Benzothiazolecarbonitrile,6-hydroxy-(7CI,8CI,9CI);6-hydroxy-benzothiazole-2-carbonitrile;6-hydroxy-1,3-benzothiazole-2-carbonitrile;2-Cyano-6-hydroxy-1,3-benzothiazole
• CAS NO: 939-69-5
• Molecular Formula: C₈H₄N₂OS
• Molecular Weight: 176.2
• Product Categories: BENZOTHIAZOLE;Sulphur Derivatives
• Mol File: 939-69-5.mol
• Article Data: 24

Chemical Properties

• Melting Point: 211-213°C
• Boiling Point: 374.657 °C at 760 mmHg
• Flash Point: 180.387 °C
• Appearance: /
• Density: 1.53 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.744
• Storage Temp.: 2-8°C
• PKA: 7.52±0.40(Predicted)
• CAS DataBase Reference: 2-CYANO-6-HYDROXYBENZOTHIAZOLE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-CYANO-6-HYDROXYBENZOTHIAZOLE(939-69-5)
• EPA Substance Registry System: 2-CYANO-6-HYDROXYBENZOTHIAZOLE(939-69-5)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36
• Safety Statements: 26-36/37
• RIDADR: UN3439
• WGK Germany: 3
• Hazardous Substances Data: 939-69-5(Hazardous Substances Data)

Usage

General Description

2-Cyano-6-hydroxybenzothiazole is a chemical compound with the molecular formula C8H5NOS. It is commonly used as a reagent in the synthesis of pharmaceuticals and organic compounds due to its ability to act as a nucleophilic catalyst. 2-Cyano-6-hydroxybenzothiazole is known for its unique properties, including its distinctive odor and light yellow color. It also has applications in the rubber industry, where it is utilized as an accelerator for the vulcanization of rubber. Additionally, 2-Cyano-6-hydroxybenzothiazole has been studied for its potential as an antioxidant and its ability to inhibit the growth of certain microbial organisms.

InChI:InChI=1/C8H4N2OS/c9-4-8-10-6-2-1-5(11)3-7(6)12-8/h1-3,11H

Synthetic route

2-cyano-6-methoxybenzothiazole (943-03-3) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
With pyridine hydrochloride at 200℃;	99%
In methanol; hexane; ethyl acetate	95%
With pyridine hydrochloride In sulfolane at 180℃; Sealed tube; Inert atmosphere;	93%

potassium cyanide + diazonium tetrafluoroborate salt of 2-amino-6-hydroxybenzothiazole → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions

Yield

Stage #1: potassium cyanide With dibenzo-18-crown-6; copper(II) tetrafluroborate hexahydrate; copper(l) cyanide In acetonitrile for 0.25h; Sandmeyer Reaction; Stage #2: With N,N,N,N,-tetramethylethylenediamine In acetonitrile at 25℃; for 0.5h; Sandmeyer Reaction; Stage #3: diazonium tetrafluoroborate salt of 2-amino-6-hydroxybenzothiazole In acetonitrile at 25℃; for 1h; Catalytic behavior; Mechanism; Reagent/catalyst; Time; Sandmeyer Reaction; Sealed tube; Inert atmosphere;

90%

6-allyloxybenzothiazole-2-carbonitrile (1198094-60-8) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
With sodium tetrahydroborate; tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;	83%

N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-4-methoxyaniline (75318-49-9) → 2-cyano-6-hydroxybenzothiazole (939-69-5) + 2-cyano-6-methoxybenzothiazole (943-03-3)

Conditions	Yield
With pyridine hydrochloride In sulfolane at 180℃; for 1h;	A 61% B 20%

4-methoxy-aniline (104-94-9) + 4,5-dichloro-1,2,3-dithiazolium chloride (75318-43-3) → 2-cyano-6-hydroxybenzothiazole (939-69-5) + 2-cyano-6-methoxybenzothiazole (943-03-3)

Conditions	Yield
Stage #1: 4-methoxy-aniline; 4,5-dichloro-1,2,3-dithiazolium chloride In sulfolane at 40 - 180℃; for 3.33333h; Sealed tube; Inert atmosphere; Stage #2: With pyridine hydrochloride In sulfolane at 180℃; for 1h; Sealed tube; Inert atmosphere;	A 51% B 21%

2-chloro-6-(methyloxy)-1,3-benzothiazole (2605-14-3) + diisopropyl ether-tetrahydrofuran → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
With trimethylsilyl iodide In diethyl ether; chloroform; dimethyl sulfoxide	42%

6-ethoxy-benzothiazole-2-carbonitrile (91634-13-8) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
With pyridine hydrochloride at 185 - 195℃; for 2h;

6-methoxybenzothiazol-2-ylamine (1747-60-0) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) AcOH, aq. H2SO4, aq. NaNO2, 2.) NaHCO3 / 1.) 1 h, 2.) water, 30 min 2: 81 percent / pyridinium chloride / 0.75 h / 200 °C View Scheme
Multi-step reaction with 2 steps 1: sodium nitrite / copper(I) chloride / hydrogenchloride; methanol; formic acid; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; water; acetic acid; ethyl acetate 2: trimethylsilyl iodide / diethyl ether; chloroform; dimethyl sulfoxide View Scheme

6-ethoxybenzothiazole-2-sulfonamide (452-35-7) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethylsulfoxide / 2.5 h / 125 °C 2: Py*HCl / 2 h / 185 - 195 °C View Scheme

ethyl 4'-methoxyoxanilate (18522-99-1) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: (i) P2S5, xylene, (ii) K3, aq. NaOH 2: HCl 3: NH3 / methanol 4: POCl3 5: Py*HCl / 200 °C View Scheme
Multi-step reaction with 5 steps 1: (i) P2S5, xylene, (ii) K3, aq. NaOH 2: methanol; diethyl ether 3: NH3 / methanol 4: POCl3 5: Py*HCl / 200 °C View Scheme

6-methoxybenzothiazole-2-carboxamide (946-12-3) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: POCl3 2: Py*HCl / 200 °C View Scheme

6-methoxybenzo[d]thiazol-2-carboxylic acid (946-13-4) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: HCl 2: NH3 / methanol 3: POCl3 4: Py*HCl / 200 °C View Scheme
Multi-step reaction with 4 steps 1: methanol; diethyl ether 2: NH3 / methanol 3: POCl3 4: Py*HCl / 200 °C View Scheme

6-methoxy-benzothiazole-2-carboxylic acid methyl ester (884-22-0) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: NH3 / methanol 2: POCl3 3: Py*HCl / 200 °C View Scheme

(4-methoxyphenyl)carbamothioyl cyanide (4968-41-6) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(l) iodide; tetrabutylammomium bromide; palladium dichloride / dimethyl sulfoxide; N,N-dimethyl-formamide / 3 h / 120 °C / Inert atmosphere 2: pyridine hydrochloride / 1 h / 180 °C / Neat (no solvent); Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: palladium dichloride; copper(l) iodide; tetrabutylammomium bromide / N,N-dimethyl-formamide; dimethyl sulfoxide / 2 h / 120 °C 2: pyridine hydrochloride / sulfolane / 180 °C / Sealed tube; Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: palladium dichloride; copper(l) iodide; tetrabutylammomium bromide / Inert atmosphere 2: pyridine hydrochloride / Inert atmosphere View Scheme

4-methoxy-aniline (104-94-9) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: dichloromethane / 1 h / 20 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / -5 °C 3.1: copper(l) iodide; tetrabutylammomium bromide; palladium dichloride / dimethyl sulfoxide; N,N-dimethyl-formamide / 3 h / 120 °C / Inert atmosphere 4.1: pyridine hydrochloride / 1 h / 180 °C / Neat (no solvent); Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: sulfolane / 3.33 h / 40 - 180 °C / Sealed tube; Inert atmosphere 1.2: 1 h / 180 °C / Sealed tube; Inert atmosphere 2.1: pyridine hydrochloride / sulfolane / 180 °C / Sealed tube; Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: dichloromethane / 3 h / 20 °C / Inert atmosphere 2: pyridine hydrochloride / sulfolane / 1 h / 180 °C View Scheme
Multi-step reaction with 3 steps 1.1: acetonitrile; tetrahydrofuran / 1 h / Inert atmosphere 1.2: 3 h / 20 °C / Inert atmosphere 2.1: palladium dichloride; copper(l) iodide; tetrabutylammomium bromide / N,N-dimethyl-formamide; dimethyl sulfoxide / 2 h / 120 °C 3.1: pyridine hydrochloride / sulfolane / 180 °C / Sealed tube; Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: dichloromethane / 3 h / 20 °C / Inert atmosphere 2: pyridine hydrochloride / sulfolane / 1 h / 180 °C 3: pyridine hydrochloride / sulfolane / 180 °C / Sealed tube; Inert atmosphere View Scheme

N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-4-methoxyaniline (75318-49-9) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / -5 °C 2: copper(l) iodide; tetrabutylammomium bromide; palladium dichloride / dimethyl sulfoxide; N,N-dimethyl-formamide / 3 h / 120 °C / Inert atmosphere 3: pyridine hydrochloride / 1 h / 180 °C / Neat (no solvent); Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: pyridine hydrochloride / sulfolane / 1 h / 180 °C 2: pyridine hydrochloride / sulfolane / 180 °C / Sealed tube; Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / Inert atmosphere 2: palladium dichloride; copper(l) iodide; tetrabutylammomium bromide / Inert atmosphere 3: pyridine hydrochloride / Inert atmosphere View Scheme

(4-(((2-cyanobenzo[d]thiazol-6-yl)oxy)methyl)phenyl)boronic acid (1421277-81-7) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
With dihydrogen peroxide In aq. buffer Kinetics;

p-benzoquinone (106-51-4) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydrogenchloride / ethanol; water / 0.5 h 1.2: 24 h / 25 °C 2.1: sodium acetate / water 3.1: tetrafluoroboric acid; sodium nitrite / water / 1 h / 0 °C 4.1: dibenzo-18-crown-6; copper(II) tetrafluroborate hexahydrate; copper(l) cyanide / acetonitrile / 0.25 h 4.2: 0.5 h / 25 °C 4.3: 1 h / 25 °C / Sealed tube; Inert atmosphere View Scheme

2-amino-6-hydroxybenzothiazole hydrochloride salt (26278-78-4) → 2-cyano-6-hydroxybenzothiazole (939-69-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium acetate / water 2.1: tetrafluoroboric acid; sodium nitrite / water / 1 h / 0 °C 3.1: dibenzo-18-crown-6; copper(II) tetrafluroborate hexahydrate; copper(l) cyanide / acetonitrile / 0.25 h 3.2: 0.5 h / 25 °C 3.3: 1 h / 25 °C / Sealed tube; Inert atmosphere View Scheme

morpholine (110-91-8) + formaldehyd (50-00-0) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 6-hydroxy-7-[(morpholin-4-yl)methyl]-1,3-benzothiazole-2-carbonitrile

Conditions	Yield
Stage #1: morpholine; formaldehyd In acetonitrile at 80℃; for 1h; Stage #2: 2-cyano-6-hydroxybenzothiazole In acetonitrile at 80℃;	98%

allyl bromide (106-95-6) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 6-allyloxybenzothiazole-2-carbonitrile (1198094-60-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 20h; Inert atmosphere;	96%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere;	90%
Stage #1: 2-cyano-6-hydroxybenzothiazole With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.25h; Williamson Ether Synthesis; Stage #2: allyl bromide In N,N-dimethyl-formamide at 70℃;	82%

D-cysteine (921-01-7) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → D-luciferin (2591-17-5)

Conditions	Yield
In water at 20℃;	95%
With ammonia; sodium In methanol; water	94%
Stage #1: D-cysteine; 2-cyano-6-hydroxybenzothiazole In aq. buffer for 1h; Stage #2: With ATP; magnesium chloride; zinc(II) chloride; luciferase In aq. buffer	27%

formaldehyd (50-00-0) + 2-cyano-6-hydroxybenzothiazole (939-69-5) + 4-(piperidin-4-yl)morpholine (53617-35-9) → 6-hydroxy-7-[[4-(morpholin-4-yl)piperidin-1-yl]methyl]-1,3-benzothiazole-2-carbonitrile

Conditions	Yield
Stage #1: formaldehyd; 4-(piperidin-4-yl)morpholine In acetonitrile at 80℃; for 1h; Stage #2: 2-cyano-6-hydroxybenzothiazole In acetonitrile at 80℃;	95%

acryloyl chloride (814-68-6) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → C11H6N2O2S

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 5h; Cooling with ice;	94.8%

crotonyl chloride (10487-71-5) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 2-cyanobenzo[d]thiazol-6-yl but-2-enoate

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 5h; Cooling with ice;	94.7%
With triethylamine In dichloromethane at 20℃; for 1h;	94.7%

α-methyl-o-nitrobenzyl bromide (69642-00-8) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 2-cyano-6-(1-(2-nitrophenyl)ethoxy)benzothiazole (1186015-39-3)

Conditions	Yield
With potassium carbonate In acetone Reflux;	94.5%

4-bromomethylphenylboronic acid (68162-47-0) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → (4-(((2-cyanobenzo[d]thiazol-6-yl)oxy)methyl)phenyl)boronic acid (1421277-81-7)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 60℃;	94%

p-hydroxymethylphenylboronic acid (59016-93-2) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → (4-(((2-cyanobenzo[d]thiazol-6-yl)oxy)methyl)phenyl)boronic acid (1421277-81-7)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 60℃;	94%

methanol (67-56-1) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → methyl 6-hydroxybenzo[d]thiazole-2-carboxylate (129058-56-6)

Conditions	Yield
With potassium carbonate	94%
With potassium carbonate at 20℃; for 24h;	94%

t-butyl (S)-2-((t-butoxycarbonyl)amino)-5-((4-(hydroxymethyl)phenyl)amino)-5-oxopentanoate + 2-cyano-6-hydroxybenzothiazole (939-69-5) → C29H34N4O6S

Conditions	Yield
Stage #1: t-butyl (S)-2-((t-butoxycarbonyl)amino)-5-((4-(hydroxymethyl)phenyl)amino)-5-oxopentanoate With triethylamine; p-toluenesulfonyl chloride In dichloromethane at 0℃; for 2.5h; Inert atmosphere; Stage #2: 2-cyano-6-hydroxybenzothiazole With potassium carbonate; sodium iodide In acetonitrile at 85℃; for 5h; Inert atmosphere;	92%

formaldehyd (50-00-0) + dimethyl amine (124-40-3) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 7-[(dimethylamino)methyl]-6-hydroxy-1,3-benzothiazole-2-carbonitrile

Conditions	Yield
Stage #1: formaldehyd; dimethyl amine In acetonitrile at 80℃; for 1h; Stage #2: 2-cyano-6-hydroxybenzothiazole In acetonitrile at 80℃;	91%

propargyl bromide (106-96-7) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 6-(prop-2-ynyloxy)benzo[d]thiazole-2-carbonitrile (1429468-55-2)

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃;	91%

2-nitrophenylmethyl bromide (3958-60-9) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 2-cyano-6-(2-nitrobenzyloxy)benzothiazole (1186015-37-1)

Conditions	Yield
With potassium carbonate In acetone for 1h; Reflux;	90%

2,6-bis-(bromomethyl)pyridine (7703-74-4) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 6-((6-(bromomethyl)pyridin-2-yl)methoxy)benzo[d]thiazole-2-carbonitrile

Conditions	Yield
With caesium carbonate In tetrahydrofuran at 50℃;	89%
With caesium carbonate In tetrahydrofuran at 50℃; for 16h;	69%

6-nitroveratrylbromide (53413-67-5) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 2-cyano-6-(4,5-dimethoxy-2-nitrobenzyloxy)benzothiazole (1186015-38-2)

Conditions	Yield
With potassium carbonate In acetone Reflux;	88.6%

2-(trimethylsilyl)ethyl 4-(1-bromoethyl)-3-nitrobenzoate (1072106-27-4) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 2-(trimethylsilyl)ethyl-4-(1-(2-cyanobenzo[d]thiazol-6-yloxy)ethyl)-3-nitrobenzoate (1379604-39-3)

Conditions	Yield
With potassium carbonate In acetone for 2h; Reflux;	88%

levulinic acid (123-76-2) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 2-cyanobenzo[d]thiazol-6-yl 4-oxopentanoate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 2h;	87.3%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 2h;	67.3%

Hexanoyl chloride (142-61-0) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 2-cyano-6-(hexanoyloxy)benzothiazole

Conditions	Yield
With pyridine In dichloromethane for 0.333333h; Ambient temperature;	87%

2-cyano-6-hydroxybenzothiazole (939-69-5) → 2-(1H-tetrazol-5-yl)benzo[d]thiazol-6-ol (1609122-28-2)

Conditions	Yield
With sodium azide; water; zinc(II) chloride at 25℃; for 24h; Micellar solution;	87%
With sodium azide; zinc(II) chloride In water at 25℃; for 24h;	87%

D-cysteine hydrochloride (32443-99-5) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → D-luciferin (2591-17-5)

Conditions	Yield
With potassium carbonate In methanol; water for 0.333333h; Inert atmosphere;	86%
With potassium carbonate In water; acetonitrile at 20℃; for 0.333333h;	86%
With potassium carbonate In methanol; water for 0.0833333h; Yield given;
With potassium carbonate In methanol for 8h; Concentration; Reagent/catalyst; Inert atmosphere;	22.76g

2-cyano-6-hydroxybenzothiazole (939-69-5) + n-hexadecanoyl chloride (112-67-4) → 2-cyano-6-(palmitoyloxy)benzothiazole

Conditions	Yield
With pyridine In dichloromethane for 0.333333h; Ambient temperature;	86%

3-(dimethylamino)propyl chloride hydrochloride (5407-04-5) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 6-(3-dimethylaminopropoxy)-2-cyanobenzothiazole

Conditions	Yield
With potassium carbonate; sodium iodide In acetone Heating;	86%
With potassium carbonate; sodium iodide In acetone Reflux;	86%

bis(pentafluorophenyl)carbonate (59483-84-0) + N-[(CH2)3-COO-t-Bu]-N’-Boc-N’-methyl-ethylenediamine + 2-cyano-6-hydroxybenzothiazole (939-69-5) → N-[(CH2)3COO-t-Bu]-N’-Boc-N’-methyl-ethylenediamine 6-hydroxybenzo[d]thiazole-2-carbonitrilecarbamate

Conditions	Yield
Stage #1: bis(pentafluorophenyl)carbonate; 2-cyano-6-hydroxybenzothiazole With triethylamine In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: N-[(CH2)3-COO-t-Bu]-N’-Boc-N’-methyl-ethylenediamine In tetrahydrofuran at 20℃; for 2h;	86%

bromoacetic acid tert-butyl ester (5292-43-3) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → tert-butyl 2-((2-cyanobenzo[d]thiazol-6-yl)oxy)acetate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃;	86%
With potassium carbonate; sodium iodide In acetone Reflux;	78%

l-cysteine hydrochloride (52-89-1) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → D-luciferin (2591-17-5)

Conditions	Yield
Stage #1: l-cysteine hydrochloride; 2-cyano-6-hydroxybenzothiazole In methanol; water at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: With potassium carbonate In methanol; water at 20℃; for 0.333333h; Inert atmosphere;	86%
With potassium carbonate In methanol; dichloromethane; water for 0.166667h; Cooling with ice;	80%

5-nitro-2-toluenesulfonyl chloride (21320-90-1) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 2-cyanobenzothiazol-6-yl 2-methyl-4-nitrobenzenesulfonate

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 3h;	85%
With triethylamine In dichloromethane at 20℃; for 3h;	85%

2-nitro-5-methylbenzenesulfonyl chloride (173908-60-6) + 2-cyano-6-hydroxybenzothiazole (939-69-5) → 2-cyanobenzothiazol-6-yl 2-nitro-5-methylbenzenesulfonate (918400-80-3)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 3h;	85%

Upstream product

• 943-03-3 2-cyano-6-methoxybenzothiazole 
• 1198094-60-8 6-allyloxybenzothiazole-2-carbonitrile 
• 26278-78-4 2-amino-6-hydroxybenzothiazole hydrochloride salt 
• 106-51-4 p-benzoquinone 
• 75318-49-9 N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-4-methoxyaniline 
• 104-94-9 4-methoxy-aniline 
• 75318-43-3 4,5-dichloro-1,2,3-dithiazolium chloride 
• 1421277-81-7 (4-(((2-cyanobenzo[d]thiazol-6-yl)oxy)methyl)phenyl)boronic acid 
• 4968-41-6 (4-methoxyphenyl)carbamothioyl cyanide 
• 2605-14-3 2-chloro-6-(methyloxy)-1,3-benzothiazole 
• 884-22-0 6-methoxy-benzothiazole-2-carboxylic acid methyl ester 
• 946-13-4 6-methoxybenzo[d]thiazol-2-carboxylic acid 
• 946-12-3 6-methoxybenzothiazole-2-carboxamide 
• 18522-99-1 ethyl 4'-methoxyoxanilate 

Downstream Products

• 20240-21-5 D-luciferin 
• 34500-31-7 (R)-2-(6-hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid 
• 2591-17-5 D-luciferin 
• 20115-09-7 2-(6’-hydroxy-2'-benzothiazolyl)-thiazole-4-carboxylic acid 
• 1386983-05-6 C₂₇H₂₆N₂O₃S₂ 
• 1421277-81-7 (4-(((2-cyanobenzo[d]thiazol-6-yl)oxy)methyl)phenyl)boronic acid 
• 1426551-44-1 N-(4-(((2-cyanobenzo[d]thiazol-6-yl)oxy)methyl)phenyl)-3-methyl-3-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide 
• 1426551-50-9 2-cyanobenzo[d]thiazol-6-yl (3-(N,3-dimethyl-3-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamido)propyl)carbonate 
• 1426551-68-9 quinone trimethyllock N,N,2,2-tetramethylpropanediamine-2-cyanobenzothiazole carbamate 
• 1344979-77-6 6-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)benzo-[d]thiazole-2-carbonitrile 
• 1622311-98-1 (S)-2-( 6-(4-borono-3-fluorobenzyloxy)benzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid 
• 676460-32-5 Luciferin-6'-benzyl ether 

Relevant articles and documents

An allylated firefly luciferin analogue with luciferase specific response in living cells

An allylated firefly luciferin was successfully synthesized and its bioluminescence properties were evaluated. When applied to cellular imaging in combination with Eluc, which is one of the commercially available luciferases, this analogue displayed a luciferase-specific bioluminescence signal with prolonged emission (>100 min).

Reduction Triggered in Situ Polymerization in Living Mice

"Smart"biomaterials that are responsive to physiological or biochemical stimuli have found many biomedical applications for tissue engineering, therapeutics, and molecular imaging. In this work, we describe in situ polymerization of activatable biorthogonal small molecules in response to a reducing environment change in vivo. We designed a carbohydrate linker- and cyanobenzothiazole-cysteine condensation reaction-based small molecule scaffold that can undergo rapid condensation reaction upon physiochemical changes (such as a reducing environment) to form polymers (pseudopolysaccharide). The fluorescent and photoacoustic properties of a fluorophore-tagged condensation scaffold before and after the transformation have been examined with a dual-modality optical imaging method. These results confirmed the in situ polymerization of this probe after both local and systemic administration in living mice.

DERIVATIVES OF LUCIFERIN AND METHODS FOR THEIR SYNTHESIS

6-Thio derivatives of D-luciferin, also referred to as D-thioluciferins, having the general structure of Formula (I) are provided. Methods for synthesising D-luciferin, its derivatives, and their related 2-cyanobenzothiazole precursors are also provided. These compounds are commercially valuable due to their application in optical imaging, particularly in bioluminescence imaging.