528-71-2

Basic information

• Product Name: 1-HYDROXYPHENAZINE
• Synonyms: 1-HYDROXYPHENAZINE;1-phenazinol;alpha-hydroxyphenazine;hemipyocyanin;hemipyocyanine;pyoxanthose;Hydroxyphenazine;1-HYDROXYPHENAZINE 95+%
• CAS NO: 528-71-2
• Molecular Formula: C₁₂H₈N₂O
• Molecular Weight: 196.2
• Mol File: 528-71-2.mol
• Article Data: 14

Chemical Properties

• Melting Point: 158°C
• Boiling Point: 333.09°C (rough estimate)
• Appearance: /
• Density: 1.1788 (rough estimate)
• Refractive Index: 1.6000 (estimate)
• PKA: 6.62±0.30(Predicted)
• Merck: 14,4645
• CAS DataBase Reference: 1-HYDROXYPHENAZINE(CAS DataBase Reference)
• NIST Chemistry Reference: 1-HYDROXYPHENAZINE(528-71-2)
• EPA Substance Registry System: 1-HYDROXYPHENAZINE(528-71-2)

Safety Data

• Safety Statements: 22-24/25
• RTECS: SG1647000
• Hazardous Substances Data: 528-71-2(Hazardous Substances Data)

Usage

Description

1-HYDROXYPHENAZINE, also known as Hemipyocyanine, is a phenazine metabolite carrying a hydroxy substituent at the 1-position. It is produced by several species of Pseudomonas and Streptomyces and exhibits broad-spectrum activity with weak antibacterial, antifungal, and antiviral properties. Due to its weak potency, it serves as an important dereplication standard in the search for novel active compounds.

Uses

Used in Biocontrol of Plant Diseases:
1-HYDROXYPHENAZINE is used as a biocontrol agent for the management of plant diseases, particularly by some Pseudomonas strains. It helps in the suppression of various pathogens, contributing to the overall health and productivity of plants.
Used in Pharmaceutical Research:
1-HYDROXYPHENAZINE is used as a dereplication standard in the pharmaceutical industry for the identification and elimination of leads with high amounts of weakly potent actives. This helps in the discovery of more potent and effective compounds for drug development.

Purification Methods

Purify the hydroxyphenazine by chromatography on acidic alumina with *benzene/ether and recrystallise it from aqueous EtOH, *benzene/heptane, then sublime it at 140o/1.5mm. [UV, IR: Badger et al. J Chem Soc 3204 1951, Hegedüs Helv Chim Acta 33 746 1950, Beilstein 23 II 360, 23 III/IV 2753.]

Synthetic route

phenazine methosulfate (299-11-6) → phenazin-1-ol (528-71-2)

Conditions	Yield
With water Flow reactor;	90%
Stage #1: phenazine methosulfate With water for 58.5h; Irradiation; Inert atmosphere; Stage #2: With sodium hydroxide In water for 36h; Inert atmosphere;	37%
Stage #1: phenazine methosulfate With water for 58.5h; Irradiation; Inert atmosphere; Stage #2: With sodium hydroxide In water for 36h; Inert atmosphere;	37%

1-methoxyphenazine (2876-17-7) → phenazin-1-ol (528-71-2)

Conditions	Yield
With hydrogen bromide; acetic acid In water for 8h; Reflux;	68%
With hydrogen bromide at 110 - 120℃;
With hydrogen bromide; acetic acid
With sodium methylate at 165℃;
With boron tribromide In dichloromethane

1-acetoxy-1,2,3,4-tetrahydrophenazine-5-oxide (16101-29-4) → phenazin-1-ol (528-71-2)

Conditions	Yield
With potassium hydroxide In methanol for 0.25h; Reflux;	37%

2-{[2-(phenyldiazenyl)phenyl]amino}phenol → phenazin-1-ol (528-71-2)

Conditions	Yield
With trifluoroacetic acid at 20℃;	37%

3-(2-nitrophenylamino)-2-cyclohexen-1-one (145657-29-0) → phenazin-1-ol (528-71-2)

Conditions	Yield
With carbon monoxide; 1,3-bis-(diphenylphosphino)propane; 1,10-phenanthroline hydrate; bis(dibenzylideneacetone)-palladium(0) In N,N-dimethyl-formamide at 120℃; under 4560.31 Torr; for 22h;	26%

Phenazin (92-82-0) → phenazin-1-ol (528-71-2)

phenazin-1-ylamine (2876-22-4) → phenazin-1-ol (528-71-2)

Conditions	Yield
With phosphoric acid at 150 - 160℃;

1-chlorophenazine (3577-37-5) → phenazin-1-ol (528-71-2)

Conditions	Yield
With sodium methylate at 165℃;
Multi-step reaction with 2 steps 1: methanol. sodium methylate / 140 °C 2: methanol. sodium methylate / 165 °C View Scheme

4-(2-amino-anilino)-3,5-dinitro-benzoic acid (860693-55-6) → phenazin-1-ylamine (2876-22-4) + phenazin-1-ol (528-71-2)

Conditions	Yield
With hydrogenchloride; water; tin(ll) chloride und Erhitzen des Reaktionsgemisches mit wss.HCl;
With hydrogenchloride; tin(ll) chloride Erhitzen des Reaktionsgemisches mit wss. HCl;

Anhydro [5-methyl-1-hydroxyphenazinium hydroxide] (15216-09-8, 392287-05-7) → phenazin-1-ol (528-71-2)

1,2-diamino-benzene (95-54-5) + 2-hydroxyresorcinol (87-66-1) → phenazin-1-ol (528-71-2)

Phenazin (92-82-0) → 1,4-dihydroxyphenazine (1790-81-4) + phenazin-1-ol (528-71-2) + 1-nitrophenazine (2876-24-6) + 2-nitrophenazine (3442-62-4)

Conditions	Yield
With water; Nitrate Kinetics; Nitration; Oxidation; Irradiation;

2-Nitroanisole (91-23-6) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOH; benzene 2: acetic acid; aqueous HBr View Scheme

o-nitroiodobenzene (609-73-4) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: K2CO3; copper; nitrobenzene 2: palladium/charcoal; ethanol / Hydrogenation.und Oxidation des Reaktionsprodukts mit FeCl3 in H2O 3: aqueous H3PO4 / 150 - 160 °C View Scheme

2,6-dinitroaniline (606-22-4) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: K2CO3; copper; nitrobenzene 2: palladium/charcoal; ethanol / Hydrogenation.und Oxidation des Reaktionsprodukts mit FeCl3 in H2O 3: aqueous H3PO4 / 150 - 160 °C View Scheme

(2,6-dinitro-phenyl)-(2-nitro-phenyl)-amine (56698-04-5) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium/charcoal; ethanol / Hydrogenation.und Oxidation des Reaktionsprodukts mit FeCl3 in H2O 2: aqueous H3PO4 / 150 - 160 °C View Scheme

2-methoxy-phenylamine (90-04-0) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOH; toluene 2: acetic acid; aqueous HBr View Scheme

nitrobenzene (98-95-3) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOH; toluene 2: acetic acid; aqueous HBr View Scheme

aniline (62-53-3) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOH; benzene 2: acetic acid; aqueous HBr View Scheme
Multi-step reaction with 4 steps 1: water / 2.5 h / 120 °C / Sealed tube; Microwave irradiation 2: triphenylphosphine / toluene / 0.17 h / 250 °C / Sealed tube 3: 1,2-dichloro-benzene / 0.14 h / 110 °C / Flow reactor 4: water / Flow reactor View Scheme
Multi-step reaction with 4 steps 1: copper(I) bromide; pyridine / toluene / 20 h / 60 °C / 760.05 Torr 2: N-Bromosuccinimide; palladium diacetate; toluene-4-sulfonic acid / acetonitrile / 20 h / 20 °C 3: tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; 1,1'-bis-(diphenylphosphino)ferrocene / toluene; water / 20 h / 80 °C 4: trifluoroacetic acid / 20 °C View Scheme
Multi-step reaction with 3 steps 1: tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate / toluene / 110 °C 2: sodium t-butanolate; sodium tetrahydroborate / ethanol / 60 °C 3: boron tribromide / dichloromethane View Scheme

1,2-diamino-benzene (95-54-5) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium acetate; aqueous ethanol 2: SnCl2; concentrated aqueous HCl / Erhitzen des Reaktionsgemisches mit wss. HCl View Scheme

4-chloro-3,5-dinitrobenzoic acid (118-97-8) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium acetate; aqueous ethanol 2: SnCl2; concentrated aqueous HCl / Erhitzen des Reaktionsgemisches mit wss. HCl View Scheme

3-methocycatechol (934-00-9) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: lead dioxide; benzene / man versetzt die filtrierte Reaktionsloesung mit o-Phenylendiamin in Eisessig + Benzol 2: hydrobromic acid / 110 - 120 °C View Scheme

benzofurazan oxide (480-96-6) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyrrolidine / acetonitrile 2: acetic acid / 12 h / 20 °C 3: potassium hydroxide / methanol / 0.25 h / Reflux View Scheme

1,2,3,4-tetrahydro-5,10-phenazine N,N'-dioxide (4121-35-1) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid / 12 h / 20 °C 2: potassium hydroxide / methanol / 0.25 h / Reflux View Scheme

cyclohexanone (108-94-1) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyrrolidine / acetonitrile 2: acetic acid / 12 h / 20 °C 3: potassium hydroxide / methanol / 0.25 h / Reflux View Scheme

pyocyanine (85-66-5) → phenazin-1-ol (528-71-2)

Conditions	Yield
With sodium hydroxide In aq. phosphate buffer

tubermycin B (2538-68-3) → phenazin-1-ol (528-71-2)

Conditions	Yield
With LaPhzS redox enzyme; oxygen; flavin adenine dinucleotide; NADH In aq. phosphate buffer at 20℃; for 0.5h; pH=7; Enzymatic reaction;

2-nitro-N-phenylaniline (119-75-5) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: triphenylphosphine / toluene / 0.17 h / 250 °C / Sealed tube 2: 1,2-dichloro-benzene / 0.14 h / 110 °C / Flow reactor 3: water / Flow reactor View Scheme

ortho-nitrofluorobenzene (1493-27-2) → phenazin-1-ol (528-71-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: water / 2.5 h / 120 °C / Sealed tube; Microwave irradiation 2: triphenylphosphine / toluene / 0.17 h / 250 °C / Sealed tube 3: 1,2-dichloro-benzene / 0.14 h / 110 °C / Flow reactor 4: water / Flow reactor View Scheme

phenazin-1-ol (528-71-2) + zinc bis(2,4-pentanedionate) monohydrate → C17H14N2O3Zn

Conditions	Yield
In methanol; dichloromethane at 20℃; for 0.25h;	100%

phenazin-1-ol (528-71-2) → 2,4-dibromo-1-hydroxyphenazine (1259015-00-3)

Conditions	Yield
With N-Bromosuccinimide In toluene at 50℃; for 5.5h; Inert atmosphere;	99%
With N-Bromosuccinimide In toluene at 50℃; for 5.5h; Inert atmosphere;	99%
With N-Bromosuccinimide In toluene at 50℃; for 8h;	93%
Multi-step reaction with 4 steps 1.1: potassium carbonate / acetone / 0.5 h / 20 °C / Inert atmosphere 1.2: 17 h / 20 °C / Inert atmosphere 2.1: N-Bromosuccinimide / dichloromethane / Inert atmosphere; Reflux 3.1: boron tribromide / dichloromethane / Inert atmosphere 4.1: N-Bromosuccinimide / dichloromethane / 1 h / 20 °C / Inert atmosphere View Scheme

phenazin-1-ol (528-71-2) + methyl iodide (74-88-4) → 1-methoxyphenazine (2876-17-7)

Conditions	Yield
Stage #1: phenazin-1-ol With potassium carbonate In acetone at 20℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In acetone at 20℃; for 17h; Inert atmosphere;	99%

phenazin-1-ol (528-71-2) + trifluoromethylsulfonic anhydride (358-23-6) → phenazin-1-yl trifluoromethanesulfonate

Conditions	Yield
With triethylamine In dichloromethane at -30 - 0℃; for 3h;	97%

phenazin-1-ol (528-71-2) + allyl bromide (106-95-6) → 1-(allyloxy)phenazine

Conditions	Yield
Stage #1: phenazin-1-ol With potassium carbonate In acetone at 20℃; for 0.5h; Inert atmosphere; Reflux; Stage #2: allyl bromide In acetone for 17h; Inert atmosphere; Reflux;	85%

phenazin-1-ol (528-71-2) + zinc bis(2,4-pentanedionate) monohydrate → C24H14N4O2Zn

Conditions	Yield
In methanol at 20℃;	77.5%

phenazin-1-ol (528-71-2) + trans-3-(trifluoromethyl)cinnamoyl chloride (60689-14-7) → phenazin-1-yl (E)-3-(3-(trifluoromethyl)phenyl)acrylate

Conditions	Yield
With pyridine In dichloromethane at 20℃;	57%

phenazin-1-ol (528-71-2) + (E)-3-(4-fluorophenyl)acryloyl chloride (13565-08-7) → phenazin-1-yl (E)-3-(4-fluorophenyl)acrylate

Conditions	Yield
With pyridine In dichloromethane at 20℃;	49%

phenazin-1-ol (528-71-2) → 2,4-dichloro-1-hydroxyphenazine (27205-77-2)

Conditions	Yield
With N-chloro-succinimide In dichloromethane at 20℃; for 2h; Inert atmosphere;	47%

phenazin-1-ol (528-71-2) + acryloyl chloride (814-68-6) → phenazin-1-yl acrylate

Conditions	Yield
With pyridine In dichloromethane at 20℃;	41%

phenazin-1-ol (528-71-2) → 2-bromo-1-hydroxyphenazine (855375-09-6)

Conditions	Yield
With N-Bromosuccinimide In toluene at 50℃; for 8h;	34%

phenazin-1-ol (528-71-2) → 2-bromo-1-hydroxyphenazine (855375-09-6) + 2,4-dibromo-1-hydroxyphenazine (1259015-00-3)

Conditions	Yield
With N-Bromosuccinimide In toluene at 50℃; for 5h; Inert atmosphere;	A 21% B 24%
With N-Bromosuccinimide In toluene at 50℃; for 5h; Inert atmosphere;	A 21% B 24%

phenazin-1-ol (528-71-2) → 2,4-diiodo-1-hydroxyphenazine

Conditions	Yield
With sodium periodate; potassium iodide; sodium chloride In water; acetic acid at 20℃; for 8h; Inert atmosphere;	19%

phenazin-1-ol (528-71-2) + dimethyl sulfate (77-78-1) → 1-hydroxy-3,5-dimethyl-phenazinium; methyl sulfate

Conditions	Yield
at 100℃;

phenazin-1-ol (528-71-2) → 5,10-dihydro-phenazin-1-ol (104621-61-6)

Conditions	Yield
With ethanol; nickel Hydrogenation;

phenazin-1-ol (528-71-2) → 1-methoxyphenazine (2876-17-7)

Conditions	Yield
With dimethyl sulfate

phenazin-1-ol (528-71-2) → phenazin-1-yl acetate (6033-10-9)

Conditions	Yield
With sodium acetate; acetic anhydride

phenazin-1-ol (528-71-2) → 1-hydroxyphenazine 5,10-dioxide (18274-55-0)

Conditions	Yield
With dihydrogen peroxide; acetic anhydride; benzene
Multi-step reaction with 2 steps 1: acetic acid anhydride; sodium acetate 2: acetic acid; aqueous H2O2 View Scheme

phenazin-1-ol (528-71-2) + N,N,N',N'-tetraisopropyl 2-cyanoethylphosphorodiamidite (102691-36-1) → phenazin-1-yl 2-cyanoethyl N,N-diisopropylphosphoramidite

Conditions	Yield
With N,N-diisopropylamine tetrazolide In dichloromethane for 1h; Ambient temperature; Yield given;

Upstream product

• 92-82-0 Phenazin 
• 2876-22-4 phenazin-1-ylamine 
• 3577-37-5 1-chlorophenazine 
• 2876-17-7 1-methoxyphenazine 
• 860693-55-6 4-(2-amino-anilino)-3,5-dinitro-benzoic acid 
• 15216-09-8 Anhydro [5-methyl-1-hydroxyphenazinium hydroxide] 
• 95-54-5 1,2-diamino-benzene 
• 87-66-1 2-hydroxyresorcinol 
• 91-23-6 2-Nitroanisole 
• 609-73-4 o-nitroiodobenzene 
• 606-22-4 2,6-dinitroaniline 
• 56698-04-5 (2,6-dinitro-phenyl)-(2-nitro-phenyl)-amine 
• 90-04-0 2-methoxy-phenylamine 
• 98-95-3 nitrobenzene 

Downstream Products

• 2876-17-7 1-methoxyphenazine 
• 6033-10-9 phenazin-1-yl acetate 
• 18274-55-0 1-hydroxyphenazine 5,10-dioxide 
• 39022-48-5 N-phenylphenazin-1-amine 
• 3225-16-9 1-phenylphenazine 
• 14994-67-3 1-hydroxyphenazine N′ 10-oxide 

Relevant articles and documents

Electrochemical Properties of Hydroxyphenazine-Coated Electrodes

Glass carbon and gold electrodes were coated with 1-hydroxyphenazine, and the electrochemical properties of these electrodes were tested using them as a rotating disc electrode to reduce Ru(bipy)33+, Fe3+, quinoxaline, O2, and to oxidize Eu2+.The fixed redox couple can be reversibly reduced and oxidized, and acts as an intermediate medium for the electron transfer.For example the Ru(bipy)33+ (E1/2= 1010 mV vs.SCE. (saturated calomel electrode) on a glassy carbon electrode in 1M H2SO4) is only reduced at 50 mV, whereas the oxidation of Eu2+( E1/2= -460 mV vs.SCE. on a Hg-electrode in 1M HCl) takes place at -100 mV.The heterogeneous rate constant depends on the second order reaction between the attached coating and the redox couple in solution.Depending on this rate constant, selectivity of the electrode is observed.

Synthesis of 1-substituted phenazines as novel antichlamydial agents

A novel series of 1-substituted phenazines 4a-4l were designed and synthesized via Palladium-catalyzed reactions from 1-phenazine trifluoromethanesulfonate. These phenazines showed antichlamydial activity with IC50 values from 1 to 10 μM. Among them, compounds 4c and 4i exhibited the best antichlamydial activity with IC50 values from 2.06 to 2.74 μM without apparent cytotoxicity to host cells.

Synthesis of phenazines from ortho-bromo azo compounds via sequential Buchwald-Hartwig amination under micellar conditions and acid promoted cyclization

Non-symmetric phenazines were synthesized via the Buchwald-Hartwig amination of ortho-bromoazobenzenes with anilines under micellar conditions, using the commercially available surfactant Kolliphor EL in water, followed by an acid-promoted 6π-electrocyclization-aromatization process. Two different synthetic pathways to obtain the ortho-bromo azo intermediates were explored, namely the palladium catalysed selective ortho bromination of azobenzenes and the diazo coupling of ortho-bromo diazonium salts with N,N-dimethylaniline, imidazole, phenol, sodium methanesulfinate and ethyl chloroformate.