25984-63-8

Basic information

• Product Name: 4-HYDROXYTHIOBENZAMIDE
• Synonyms: 4-HYDROXYTHIOBENZAMIDE;4-Hydroxy Thiobenzamide p-Hydroxy Thiobenzamide;p-HydroxyThioBenzamide;4-hydroxybenzothioamide;4-HYDROXY THIOBENZAMIDE 98.0%MIN;4-Hydroxybenzene-1-carbothioamide;4-hydroxy thiobenzam;HydroxythiobenzaMide
• CAS NO: 25984-63-8
• Molecular Formula: C₇H₇NOS
• Molecular Weight: 153.2
• EINECS: 1308068-626-2
• Product Categories: chemical additive;pharmaceutical intermediate;Febuxostat intermediate;Febuxostat Intermediates
• Mol File: 25984-63-8.mol
• Article Data: 24

Chemical Properties

• Melting Point: 181-185℃
• Boiling Point: 320.394 °C at 760 mmHg
• Flash Point: 147.57 °C
• Appearance: Grey white powder
• Density: 1.339 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.702
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 9.24±0.26(Predicted)
• CAS DataBase Reference: 4-HYDROXYTHIOBENZAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-HYDROXYTHIOBENZAMIDE(25984-63-8)
• EPA Substance Registry System: 4-HYDROXYTHIOBENZAMIDE(25984-63-8)

Safety Data

• Hazard Codes: Xi
• Statements: 20/21/22-36/37/38-43-22
• Safety Statements: 26-36/37/39-36/37
• Hazardous Substances Data: 25984-63-8(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 25984-63-8 differently. You can refer to the following data:
1. 4-Hydroxythiobenzamide is used in the synthesis of PPARα agonists used in increasing HDLc levels. Also used in the synthesis of potent CDK5 inhibitors in the treatment of Alzheimer’s disease.
2. febuxostat intermediate

InChI:InChI=1/C7H7NOS/c8-7(10)5-1-3-6(9)4-2-5/h1-4,9H,(H2,8,10)

Synthetic route

4-cyanophenol (767-00-0) → 4-hydroxythiobenzamide (25984-63-8)

Conditions	Yield
Stage #1: 4-cyanophenol With sodium hydrogensulfide In water at 20℃; for 0.5h; Stage #2: With hydrogen sulfide at 70℃; under 2068.65 - 2896.11 Torr; for 5.91667 - 6h;	97.57%
With sodium monohydrogen sulfide x-hydrate; ammonium chloride In water; N,N-dimethyl-formamide at 40℃; for 22h; Product distribution / selectivity;	94%
With sodium hydrogen sulfide; triethylamine hydrochloride; triethylamine In ethanol at 5 - 50℃; for 12h; Reagent/catalyst; Solvent; Temperature;	92%

4-hydroxybenzaldehyde oxime (699-06-9, 60221-52-5, 60221-53-6) → 4-hydroxythiobenzamide (25984-63-8)

Conditions	Yield
With tetraphosphorus decasulfide In toluene at 80 - 85℃; Reagent/catalyst; Temperature; Beckmann Rearrangement;	91.3%

diethylthiophosphoric acid + 4-cyanophenol (767-00-0) → 4-hydroxythiobenzamide (25984-63-8)

Conditions	Yield
In water; ethyl acetate	87%

p-hydroxybenzamide (619-57-8) → 4-hydroxythiobenzamide (25984-63-8)

Conditions	Yield
With Lawessons reagent In tetrahydrofuran at 20℃; for 6h;	87%
With Lawessons reagent In 2-methyltetrahydrofuran at 0 - 30℃; for 12h;

4-cyanophenol (767-00-0) + O,O-Diethyl hydrogen phosphorodithioate (298-06-6) → 4-hydroxythiobenzamide (25984-63-8)

Conditions	Yield
In water at 80℃; for 1h;	78%

thiocarbamoyl chloride (16890-86-1) + phenol (108-95-2) → 4-hydroxythiobenzamide (25984-63-8)

4-cyanophenol (767-00-0) + thioacetamide (62-55-5) → 4-hydroxythiobenzamide (25984-63-8)

Conditions	Yield
With polyphosphoric acid In water at 40 - 80℃;
With hydrogenchloride In water at 60℃; for 2h; Time; Temperature; Green chemistry;

4-hydroxy-benzaldehyde (123-08-0) → 4-hydroxythiobenzamide (25984-63-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; formic acid; sodium formate / 2 h / 105 °C / Green chemistry 2: hydrogenchloride / water / 2 h / 60 °C / Green chemistry View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide; hydroxylamine hydrochloride / water; methanol / 20 - 25 °C 2: tetraphosphorus decasulfide / toluene / 80 - 85 °C View Scheme

4-hydroxythiobenzamide (25984-63-8) + acetic acid 4-(2-bromoacetyl)phenyl ester (41104-10-3) → acetic acid 4-[2-(4-hydroxyphenyl)-1,3-thiazol-4-yl]phenyl ester

Conditions	Yield
In acetonitrile for 1h; Reflux;	99%

4-hydroxythiobenzamide (25984-63-8) + ethyl 2-chloro-3-oxo-butyrate (609-15-4) → (2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester) (161797-99-5)

Conditions	Yield
In ethanol at 65 - 70℃; for 3h;	98%
In spirit at 60 - 65℃; for 2.5h;	90.7%
In isopropyl alcohol at 55 - 85℃; for 3h;	58%

4-hydroxythiobenzamide (25984-63-8) + ethyl 2-bromoacetoacetate (84911-18-2, 609-13-2) → (2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester) (161797-99-5)

Conditions	Yield
In ethanol for 3h; Reflux;	91%
In ethanol for 2h; Reflux;	84%

4-hydroxythiobenzamide (25984-63-8) + C21H28O3 → (1S,2R,13R,14S,17R,18S)-17-ethynyl-7-(4-hydroxyphenyl)-2,18-dimethyl-8-thia-6-azapentacyclo[11.7.0.02,10.05,9.014,18]icosa-5(9),6,10-trien-17-ol

Conditions	Yield
With acetic acid at 100℃; for 8h;	91%

4-hydroxythiobenzamide (25984-63-8) + 2-bromoethylamine hydrobromide (2576-47-8) → 2-(4-hydroxyphenyl)-4,5-dihydro-1,3-thiazole (90563-68-1)

Conditions	Yield
Stage #1: 4-hydroxythiobenzamide; 2-bromoethylamine hydrobromide In water at 60 - 70℃; for 2.5h; Stage #2: With sodium carbonate In water	90%

4-hydroxythiobenzamide (25984-63-8) + 2-bromoethan-1-amine hydrohalide → 2-(4-hydroxyphenyl)-4,5-dihydro-1,3-thiazole (90563-68-1)

Conditions	Yield
With water for 2.5h;	90%

4-hydroxythiobenzamide (25984-63-8) + 2-bromoethanamine hydrogen halide salt → 2-(4-hydroxyphenyl)-4,5-dihydro-1,3-thiazole (90563-68-1)

Conditions	Yield
In water for 2.5h;	90%

4-hydroxythiobenzamide (25984-63-8) + ethyl Bromopyruvate (70-23-5) → ethyl 2-(4-hydroxyphenyl)thiazole-4-carboxylate

Conditions	Yield
In ethanol at 70℃; for 2h;	90%
In ethanol at 80℃; for 4h;	89%
In ethanol at 80℃; for 4h;	89%
In ethanol at 80℃; for 4h; Temperature;	88.56%
In ethanol; water at 80℃; for 4h;

4-hydroxythiobenzamide (25984-63-8) → 4-cyanophenol (767-00-0)

Conditions	Yield
With methylene blue; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 25℃; Sealed tube; Irradiation;	88%
With iodine; triethylamine In dichloromethane at 20℃; for 0.5h;	80%
With manganese(IV) oxide In acetone under 760.051 Torr; for 0.5h;	82 %Chromat.

4-hydroxythiobenzamide (25984-63-8) + 3-chloroacetyl acetone (7660-21-1) → 2-(4-hydroxyphenyl)-4-methy-5-acetylthiazole

Conditions	Yield
In ethanol for 5h; Reflux;	85%

4-hydroxythiobenzamide (25984-63-8) + ethyl 2-bromoacetoacetate (84911-18-2, 609-13-2) → 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylic acid ethyl ester hydrobromide

Conditions	Yield
In ethanol at 70 - 80℃; for 3h;	82.8%

4-hydroxythiobenzamide (25984-63-8) + 1H-1-(1'-phenylethynyl)-5-methyl-1,2,3-benziodoxathiole 3,3-dioxide (152716-92-2) → 2-(4-methoxyphenyl)-4-phenylthiazole + potassium 2-iodo-5-methylbenzenesulfonate (1093215-92-9)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 45℃; Inert atmosphere;	A 82% B n/a

4-hydroxythiobenzamide (25984-63-8) + 1,3-Diamino-2-hydroxypropane (616-29-5) → 4-(1,4,5,6-tetrahydro-5-hydroxy-2-pyrimidinyl)phenol

Conditions	Yield
In 1,2-dimethoxyethane for 18h; cycloamination; Heating;	80%

4-hydroxythiobenzamide (25984-63-8) + 4-bromocrotonic ethyl ester (6065-32-3) → ethyl 2-(2-(4-hydroxyphenyl)-4,5-dihydrothiazol-4-yl)acetate

Conditions	Yield
With 1,1,1,3',3',3'-hexafluoro-propanol; sodium acetate for 8h; Reflux;	80%
In tetrahydrofuran at 65℃; Inert atmosphere;	62%

2-bromo-1-(3-methylphenyl)-2-(4-pyridyl)ethanone hydrobromide + 4-hydroxythiobenzamide (25984-63-8) → 4-[4-(3-methylphenyl)-5-(4-pyridyl)-1,3-thiazol-2-yl]phenol

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 14h;	78%

4-hydroxythiobenzamide (25984-63-8) + α-bromoacetophenone (70-11-1) → 2-(4-methoxyphenyl)-4-phenylthiazole

Conditions	Yield
In methanol; ethanol; dichloromethane; ethyl acetate	78%

4-hydroxythiobenzamide (25984-63-8) + (3-bromo-2-oxopropyl)((tert-butyldiphenylsilyl)imino)(phenyl)-λ6-sulfanone → C16H14N2O2S2

Conditions	Yield
In isopropyl alcohol at 20℃; Inert atmosphere;	78%

4-hydroxythiobenzamide (25984-63-8) + artesunic acid (88495-63-0) → C26H33NO8S

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;	78%

4-hydroxythiobenzamide (25984-63-8) + 1H-1-(1'-octynyl)-5-methyl-1,2,3-benziodoxathiole 3,3-dioxide (152716-87-5) → 2-(4-methoxyphenyl)-4-hexylthiazole + potassium 2-iodo-5-methylbenzenesulfonate (1093215-92-9)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 20℃; for 5h;	A 72% B n/a

4-hydroxythiobenzamide (25984-63-8) + 1H-1-(1'-hexynyl)-5-methyl-1,2,3-benziodoxathiole 3,3-dioxide (152716-85-3) → 2-(4-methoxyphenyl)-4-butylthiazole + potassium 2-iodo-5-methylbenzenesulfonate (1093215-92-9)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 20℃; for 5h;	A 70% B n/a

Phenylpropargyl aldehyde (2579-22-8) + 4-hydroxythiobenzamide (25984-63-8) + ethanol (64-17-5) → 4-(5-(ethoxy(phenyl)methyl)thiazol-2-yl)phenol

Conditions	Yield
With bromotris(triphenylphosphine)copper(I); Trimethylacetic acid at 60℃; for 8h; Schlenk technique; regioselective reaction;	64%

4-hydroxythiobenzamide (25984-63-8) + 2-(5-fluoro-2-methyl-1-(4-(methylsulfinyl)benzylidene)-1H-inden-3-yl)acetic acid (38194-50-2, 49627-22-7, 53933-60-1, 61812-46-2, 149116-77-8, 32004-68-5) → C27H22FNO3S2

Conditions	Yield
Stage #1: 2-(5-fluoro-2-methyl-1-(4-(methylsulfinyl)benzylidene)-1H-inden-3-yl)acetic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-hydroxythiobenzamide In acetonitrile at 20℃; for 4h; Inert atmosphere;	62.5%

4-hydroxythiobenzamide (25984-63-8) + ethanolamine (141-43-5) → 4-(4,5-dihydro-2-oxazolyl)phenol (81428-58-2)

Conditions	Yield
With potassium carbonate In water at 90℃; for 6h;	60%

4-hydroxythiobenzamide (25984-63-8) + 1-bromo-2,2-dimethoxyethane (7252-83-7) → 2-(4-hydroxyphenyl) thiazole (81015-49-8)

Conditions	Yield
With toluene-4-sulfonic acid In ethanol at 20 - 90℃; for 24h;	60%
With toluene-4-sulfonic acid In ethanol at 20 - 90℃; for 24h;	60%
With toluene-4-sulfonic acid In ethanol at 20 - 90℃; for 24h;	60%
With toluene-4-sulfonic acid In ethanol at 90℃; for 24h;

4-hydroxythiobenzamide (25984-63-8) + acipimox (51037-30-0) → C13H11N3O3S

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 12h; Inert atmosphere;	59%

Upstream product

• 767-00-0 4-cyanophenol 
• 62-55-5 thioacetamide 
• 699-06-9 4-hydroxybenzaldehyde oxime 
• 123-08-0 4-hydroxy-benzaldehyde 
• 619-57-8 p-hydroxybenzamide 
• 298-06-6 O,O-Diethyl hydrogen phosphorodithioate 
• 16890-86-1 thiocarbamoyl chloride 
• 108-95-2 phenol 

Downstream Products

• 1174737-78-0 4-(5-acetyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)phenol 
• 1174737-83-7 2-(4-hydroxyphenyl)-6,7-dihydro[1,3]thiazolo[4,5-b]pyridin-5(4H)-one 
• 1174738-02-3 ethyl 2-[4-hydroxyphenyl]-5,6-dihydro-4H-cyclopenta[d][1,3]thiazole-5-carboxylate 
• 407582-47-2 2-[3-cyano-4-(2-hydroxy-2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid 
• 407582-49-4 2-[4-(2-carboxypropoxy)-3-cyanophenyl]-4-methylthiazole-5-carboxylic acid 

Relevant articles and documents

Phenylthiazole antibiotics: A metabolism-guided approach to overcome short duration of action

Antibacterial resistance is a pressing global health challenge that necessitates the development of new therapeutic agents. Phenylthiazole antibacterial agents have been extensively studied, by our group, as a potential novel class of antibiotics to circumvent the scourge of antibacterial resistance. Previously, the phenylthiazole lead compound 1 was shown to possess potent activity against clinical isolates of methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA). The promising activity of this novel class of antibiotics is hampered by their short half-life due to rapid hepatic metabolism. In the present study, a metabolic methylene soft spot in the lead 1 was identified and replaced with an oxygen atom. The newly developed phenylthiazoles, with alkoxy side chains, demonstrate high metabolic stability (t1/2> 4 h), while maintaining their potent anti-MRSA activity. Furthermore, compound 5p demonstrated a selective advantage over vancomycin with its ability to kill intracellular MRSA.

New preparation method of febuxostat intermediate

The invention relates to a new preparation method of a febuxostat intermediate. The method includes: taking cheap 4-hydroxybenzaldehyde as an initial raw material, firstly preparing aldoxime from 4-hydroxybenzaldehyde and hydroxylamine hydrochloride, then adding a corresponding thio reagent, and preparing a compound 4-hydroxythiobenzamide (152A1-00) by Beckmann rearrangement reaction; utilizing one-pot process, adopting cheap 4-hydroxybenzaldehyde as an initial raw material, carrying out a series of reactions, and then performing cyclization with 2-halogenated ethyl acetoacetate to obtain ethyl 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate or different salt forms (152A2x) thereof; and using isobutyl sulfonate (152H1x) with more easily controllable quality to replace bromo-isobutane soas to prepare ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate (152A4-00). In conclusion, the method provided by the invention is more beneficial to safe, simple and cost-efficientindustrial scale preparation of the febuxostat intermediate with higher purity.

Synthesis, molecular docking, DFT study of novel N-benzyl-2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxamide derivatives and their antibacterial activity

A series of febuxostat based new chemical entities was synthesized using microwave method and characterized by NMR, mass and FT-IR spectral studies. Molecular docking of febuxostat amide nucleus substitution compounds 8c (-7.91kcal/mol), 8g (-7.94 kcal/mol) exhibiting high binding energy against ALK receptors. Theoretical investigation of MEPs, HOMO, LUMO and energy gap of HOMO-LUMO were calculated by B3LYP/6-31G method. Among the tested compounds, methoxy substituted compound 8g showed highest antibacterial activity against S. aereus and B. subtilis.