4231-68-9

Basic information

• Product Name: 3-Hydroxy-1-phenyl-1,2,4-triazole
• Synonyms: BUTTPARK 62\07-51;1-PHENYL-1,2,4-TRIAZOL-3-OL;1-PHENYL-1H-1,2,4-TRIAZOL-3-OL;1-PHENYL-3-HYDROXY-1,2,4-TRIAZOLE;1,2-dihydro-1-phenyl-3H-1,2,4-triazol-3-one;3-Hydroxy-1-Phenyl-1H-1,2,4-Triazole;1-Phenyl-2H-1,2,4-triazol-3-one;3-Hydroxy-1-phenyl-1,2,4-triazole
• CAS NO: 4231-68-9
• Molecular Formula: C₈H₇N₃O
• Molecular Weight: 161.16
• EINECS: 224-187-5
• Mol File: 4231-68-9.mol
• Article Data: 5

Chemical Properties

• Melting Point: 277-280
• Boiling Point: 392.2 °C at 760 mmHg
• Flash Point: 191 °C
• Appearance: White to pale yellow crystal powder.
• Density: 1.32 g/cm³
• Vapor Pressure: 1.03E-06mmHg at 25°C
• Refractive Index: 1.665
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 9.13±0.20(Predicted)
• CAS DataBase Reference: 3-Hydroxy-1-phenyl-1,2,4-triazole(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Hydroxy-1-phenyl-1,2,4-triazole(4231-68-9)
• EPA Substance Registry System: 3-Hydroxy-1-phenyl-1,2,4-triazole(4231-68-9)

Safety Data

• Hazard Codes: Xi
• HazardClass: IRRITANT
• Hazardous Substances Data: 4231-68-9(Hazardous Substances Data)

Usage

General Description

3-Hydroxy-1-phenyl-1,2,4-triazole, also known as 3-H-1,2,4-triazole, is a chemical compound with the molecular formula C8H7N3O. It is a triazole derivative and a member of the phenyltriazole class of compounds. This chemical has been found to have several pharmaceutical properties, including antifungal and herbicidal activities. It can also be used as a building block in the synthesis of various pharmaceuticals and agrochemicals. Additionally, 3-Hydroxy-1-phenyl-1,2,4-triazole has potential applications in the fields of medicinal chemistry and drug development due to its unique structural characteristics and biological activities.

InChI:InChI=1/C8H7N3O/c12-8-9-6-11(10-8)7-4-2-1-3-5-7/h1-6H,(H,10,12)

Synthetic route

orthoformic acid triethyl ester (122-51-0) + 1-phenylsemicarbazide (103-03-7) → 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9)

Conditions	Yield
With toluene-4-sulfonic acid for 16h; steam bath temperature;	91%

phenylhydrazine (100-63-0) → 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9)

Conditions	Yield
With formic acid; sulfuric acid; urea In 5,5-dimethyl-1,3-cyclohexadiene

phenylhydrazine (100-63-0) → 1-phenyl-1-hydroxy-1,2,4-triazole + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9)

Conditions	Yield
With formic acid; sulfuric acid; urea In hydrogenchloride; 5,5-dimethyl-1,3-cyclohexadiene

1-phenylsemicarbazide (103-03-7) → 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9)

Conditions	Yield
With formic acid; sulfuric acid

formic acid (64-18-6) + 1-phenylsemicarbazide (103-03-7) → 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9)

Conditions	Yield
With sulfuric acid In water at 90 - 125℃;
With sulfuric acid

formic acid (64-18-6) + phenylhydrazine (100-63-0) + urea (57-13-6) → 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9)

Conditions	Yield
Stage #1: phenylhydrazine; urea With hydrogenchloride In water at 135℃; for 4h; Stage #2: formic acid With sulfuric acid at 690℃; for 6h;

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + 2-chlorobenzyl halide → 3-(2-chlorobenzyloxy)-1-phenyl-1H-1,2,4-triazole (1332370-70-3)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 2-chlorobenzyl halide With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	89%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + 4-fluorobenzyl halide → 3-(4-fluorobenzyloxy)-1-phenyl-1H-1,2,4-triazole (1332370-68-9)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 4-fluorobenzyl halide With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	89%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + 2,4-difluorobenzyl halide → 3-(2,4-difluorobenzyloxy)-1-phenyl-1H-1,2,4-triazole (1332370-67-8)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 2,4-difluorobenzyl halide With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	88%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + 3-chlorobenzyl halide → 3-(3-chlorobenzyloxy)-1-phenyl-1H-1,2,4-triazole (1332370-71-4)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 3-chlorobenzyl halide With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	87%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + 2,4-dichlorobenzyl halide → 3-(2,4-dichlorobenzyloxy)-1-phenyl-1H-1,2,4-triazole (1332370-66-7)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 2,4-dichlorobenzyl halide With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	86%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + 4-chlorobenzyl halide → 3-(4-chlorobenzyloxy)-1-phenyl-1H-1,2,4-triazole (874798-69-3)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 4-chlorobenzyl halide With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	86%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + 3,4-dichlorobenzyl halide → 3-(3,4-dichlorobenzyloxy)-1-phenyl-1H-1,2,4-triazole

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 3,4-dichlorobenzyl halide With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	85%

4-chloro-3-cyanonitrobenzene (16588-02-6) + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 5-nitro-2-((1-phenyl-1H-1,2,4-triazol-3-yl)oxy)benzonitrile

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With sodium hydroxide In dimethyl sulfoxide at 50℃; for 0.333333h; Stage #2: 4-chloro-3-cyanonitrobenzene In dimethyl sulfoxide at 80℃; for 8h;	79%

2-(tert-butoxycarbonylamino)ethyl bromide (39684-80-5) + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → N-Boc-2-(1-phenyl-1H-1,2,4-triazol-3-oxy)ethylamine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	75.1%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + hexadecanyl bromide (112-82-3) → 3-(hexadecyloxy)-1-phenyl-1H-1,2,4-triazole (1332370-75-8)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: hexadecanyl bromide With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	67%

1-bromo-octane (111-83-1) + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 3-(octyloxy)-1-phenyl-1H-1,2,4-triazole (1332370-73-6)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 1-bromo-octane With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	66%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 3-hydroxy-1-(4-nitrophenyl)-1H-1,2,4-triazole (22354-77-4)

Conditions	Yield
With sulfuric acid; nitric acid at 0℃; for 5h;	65%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + Ethyl 2-bromopropionate (535-11-5, 41978-69-2) → 3-(1-ethoxycarbonylethoxy)-1-phenyl-1,2,4-1H-triazole (110607-55-1)

Conditions	Yield
With sodium methylate In methanol; dimethyl sulfoxide for 4h; at steam bath temperature;	62%

5-chloro-3-methyl-1-phenyl-1H-pyrazole-4‑carboxylic acid (1140-38-1) + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 1-phenyl-1H-1,2,4-triazol-3-yl5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carboxylate

Conditions	Yield
Stage #1: 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4‑carboxylic acid With dmap; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 25℃; for 1h; Stage #2: 3-hydroxy-1-phenyl-1,2,4-1H-triazole In N,N-dimethyl-formamide at 25℃; for 3h;	62%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + dimethyl sulfate (77-78-1) → 3-methoxy-1-phenyl-1H-1,2,4-triazole (167275-99-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 48h;	57%

C11H8Cl2N2O2 + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 1-phenyl-1H-1,2,4-triazol-3-yl5-chloro-1-(4-chlorophenyl)-3-methyl-1H-pyrazole-4-carboxylate

Conditions	Yield
Stage #1: C11H8Cl2N2O2 With dmap; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 25℃; for 1h; Stage #2: 3-hydroxy-1-phenyl-1,2,4-1H-triazole In N,N-dimethyl-formamide at 25℃; for 3h;	57%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + 2-bromoethanol (540-51-2) → 2-(1-phenyl-1H-1,2,4-triazol-3-yloxy)ethanol (181418-30-4)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 2-bromoethanol With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	56%

1-dodecylbromide (143-15-7) + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 3-(dodecyloxy)-1-phenyl-1H-1,2,4-triazole (1332370-74-7)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 1-dodecylbromide With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	54%

C11H8ClFN2O2 + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 1-phenyl-1H-1,2,4-triazol-3-yl5-chloro-1-(4-fluorophenyl)-3-methyl-1H-pyrazole-4-carboxylate

Conditions	Yield
Stage #1: C11H8ClFN2O2 With dmap; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 25℃; for 1h; Stage #2: 3-hydroxy-1-phenyl-1,2,4-1H-triazole In N,N-dimethyl-formamide at 25℃; for 3h;	54%

C12H11ClN2O2 + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 1-phenyl-1H-1,2,4-triazol-3-yl5-chloro-3-methyl-1-(p-tolyl)-1H-pyrazole-4-carboxylate

Conditions	Yield
Stage #1: C12H11ClN2O2 With dmap; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 25℃; for 1h; Stage #2: 3-hydroxy-1-phenyl-1,2,4-1H-triazole In N,N-dimethyl-formamide at 25℃; for 3h;	52%

1-bromo-butane (109-65-9) + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 3-butoxy-1-phenyl-1H-1,2,4-triazole (1332370-72-5)

Conditions	Yield
Stage #1: 3-hydroxy-1-phenyl-1,2,4-1H-triazole With potassium carbonate In acetonitrile at 65℃; for 0.5h; pH=7.5 - 8.5; Stage #2: 1-bromo-butane With tetra-(n-butyl)ammonium iodide In acetonitrile at 70 - 75℃;	50%

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) + epichlorohydrin (106-89-8) → 1-fenylo-3-(2,3-epoksypropoksy)-1,2,4-triazol (156453-54-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide at 100℃; for 20h;	40%

2,3,4,6-tetra-O-acetyl-5-thio-D-glucopyranose (137886-82-9) + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 1'-phenyl-1'H-1',2',4'-triazol-3'-yl 2,3,4,6-tetra-O-acetyl-5-thio-β-D-glucopyranoside (777864-43-4)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran; toluene at 0 - 20℃; for 2h; Mitsunobu reaction;	38%

tert-butyldimethylsilyl chloride (18162-48-6) + 3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 1-phenyl-3-t-butyldimethylsilyloxy-1H-1,2,4-triazole (167275-93-6)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 80℃; for 48h;

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 1-phenyl-3-hydroxy-1H-1,2,4-triazol-5-ylphosphonic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: Et3N / dimethylformamide / 48 h / 80 °C 2: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 2 h, 2.) THF, hexane, -78 deg C, 1 h 3: 1.) trimethylsilyl bromide, Et3N, 2.) H2O / 1.) 40 deg C, 4 h, 2.) THF, RT View Scheme

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 1-phenyl-3-methoxy-1H-1,2,4-triazol-5-ylphosphonic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: 57 percent / K2CO3 / dimethylformamide / 48 h / 80 °C 2: 1.) n-BuLi, N,N,N',N'-tetramethylethylene diamine / 1.) THF, hexane, -78 deg C, 2 h, 2.) THF, hexane, RT, overnight 3: 1.) trimethylsilyl bromide, 2.) H2O / 1.) 50 deg C, 3 h, 2.) THF, RT, 1 h View Scheme

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 1-phenyl-3-hydroxy-1H-1,2,4-triazol-5-ylphosphonic acid, diethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / dimethylformamide / 48 h / 80 °C 2: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 2 h, 2.) THF, hexane, -78 deg C, 1 h View Scheme

3-hydroxy-1-phenyl-1,2,4-1H-triazole (4231-68-9) → 1-phenyl-3-methoxy-1H-1,2,4-triazol-5-ylphosphonic acid, diethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 57 percent / K2CO3 / dimethylformamide / 48 h / 80 °C 2: 1.) n-BuLi, N,N,N',N'-tetramethylethylene diamine / 1.) THF, hexane, -78 deg C, 2 h, 2.) THF, hexane, RT, overnight View Scheme

Upstream product

• 122-51-0 orthoformic acid triethyl ester 
• 103-03-7 1-phenylsemicarbazide 
• 64-18-6 formic acid 
• 100-63-0 phenylhydrazine 
• 57-13-6 urea 

Downstream Products

• 167275-93-6 1-phenyl-3-t-butyldimethylsilyloxy-1H-1,2,4-triazole 
• 167275-99-2 3-methoxy-1-phenyl-1H-1,2,4-triazole 
• 110607-63-1 3-(1-ethoxycarbonylpentoxy)-1-phenyl-1,2,4-1H-triazole 
• 1332370-72-5 3-butoxy-1-phenyl-1H-1,2,4-triazole 
• 1332370-73-6 3-(octyloxy)-1-phenyl-1H-1,2,4-triazole 
• 1332370-74-7 3-(dodecyloxy)-1-phenyl-1H-1,2,4-triazole 
• 1332370-75-8 3-(hexadecyloxy)-1-phenyl-1H-1,2,4-triazole 
• 181418-30-4 2-(1-phenyl-1H-1,2,4-triazol-3-yloxy)ethanol 
• 1332370-66-7 3-(2,4-dichlorobenzyloxy)-1-phenyl-1H-1,2,4-triazole 
• 1332370-67-8 3-(2,4-difluorobenzyloxy)-1-phenyl-1H-1,2,4-triazole 
• 1332370-70-3 3-(2-chlorobenzyloxy)-1-phenyl-1H-1,2,4-triazole 
• 1332370-71-4 3-(3-chlorobenzyloxy)-1-phenyl-1H-1,2,4-triazole 
• 874798-69-3 3-(4-chlorobenzyloxy)-1-phenyl-1H-1,2,4-triazole 
• 1332370-68-9 3-(4-fluorobenzyloxy)-1-phenyl-1H-1,2,4-triazole 

Relevant articles and documents

Discovery of novel triazole-containing pyrazole ester derivatives as potential antibacterial agents

To develop new antibacterial agents, a series of novel triazole-containing pyrazole ester derivatives were designed and synthesized and their biological activities were evaluated as potential topoisomerase II inhibitors. Compound 4d exhibited the most potent antibacterial activity with Minimum inhibitory concentration (MIC) alues of 4 μg/mL, 2 μg/mL, 4 μg/mL, and 0.5 μg/mL against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella gallinarum, respectively. The in vivo enzyme inhibition assay 4d displayed the most potent topoisomerase II (IC50 = 13.5 μg/mL) and topoisomerase IV (IC50 = 24.2 μg/mL) inhibitory activity. Molecular docking was performed to position compound 4d into the topoisomerase II active site to determine the probable binding conformation. In summary, compound 4d may serve as potential topoisomerase II inhibitor.

Synthesis of novel halobenzyloxy and alkoxy 1,2,4-triazoles and evaluation for their antifungal and antibacterial activities

A new class of halobenzyloxy or alkoxy 1,2,4-triazoles and their hydrochlorides were synthesized through cyclization starting from commercially available phenylhydrazine. The structures were characterized by MS, IR and 1H NMR spectra as well as elemental analyses. All the synthesized compounds were screened for their antibacterial activities in vitro against Staphylococcus aureus (ATCC29213), methicillin-resistant Staphylococcus aureus (N315), Bacillus subtilis, Escherichia coli (ATCC25922), Pseudomonas aeruginosa, Shigella dysenteriae, Eberthella typhosa, and antifungal activities against Candida albicans (ATCC76615), Aspergillus fumigatus by broth microdilution assay method. The results of preliminary bioassay indicated that 3-(2,4- difluorobenzyloxy)-1-phenyl-1H-1,2,4-triazole hydrochloride exhibited the best inhibitory activity with an MIC value of 56.25 μM against P. aeruginosa superior to Chloramphenicol, and showed comparable activity with Chloramphenicol against E. coli (ATCC25922).

Process for the manufacture of substituted 3-hydroxy-1,2,4-triazoles

Manufacture of 3-hydroxy-1,2,4-triazoles by cyclization of corresponding semicarbazides by formic acid in the presence of an inorganic acid or halide thereof.