35421-08-0

Basic information

• Product Name: 4-Hydroxybenzyl chloride
• Synonyms: p-Choro-m-cresol;p-Hydroxybenzylchloride;4-Chloromethylphenol;4-Hydroxybenzyl chloride;alpha-Chloro-p-cresol;p-Chloromethylphenol;Phenol, 4-(chloromethyl)-
• CAS NO: 35421-08-0
• Molecular Formula: C₇H₇ClO
• Molecular Weight: 142.58
• EINECS: 215-309-8
• Mol File: 35421-08-0.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 257.4°Cat760mmHg
• Flash Point: 109.5°C
• Appearance: /
• Density: 1.233g/cm³
• Vapor Pressure: 0.00904mmHg at 25°C
• Refractive Index: 1.569
• PKA: 9.68±0.26(Predicted)
• CAS DataBase Reference: 4-Hydroxybenzyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Hydroxybenzyl chloride(35421-08-0)
• EPA Substance Registry System: 4-Hydroxybenzyl chloride(35421-08-0)

Safety Data

• Hazardous Substances Data: 35421-08-0(Hazardous Substances Data)

Usage

General Description

4-Hydroxybenzyl chloride is a chemical compound with the molecular formula C7H7ClO. It is a derivative of benzyl chloride in which the benzene ring has a hydroxyl group in the para position. The compound is a colorless to light yellow liquid with a strong, sweet odor. It is primarily used in organic synthesis as a reagent for the preparation of various organic compounds, including pharmaceuticals, agrochemicals, and dyes. It is also used as a building block in the synthesis of polymers and other specialty chemicals. Additionally, 4-Hydroxybenzyl chloride is used in the production of fragrances and flavors for the food and cosmetic industries.

InChI:InChI=1/C7H7ClO/c8-5-6-1-3-7(9)4-2-6/h1-4,9H,5H2

Synthetic route

4-tosyloxy-benzylchloride (169308-96-7) → 4-hydroxybenzyl chloride (35421-08-0)

Conditions	Yield
With potassium fluoride on basic alumina for 0.05h; Substitution; microwave irradiation;	83%

4-acetoxybenzyl chloride (39720-27-9) → 4-hydroxybenzyl chloride (35421-08-0)

Conditions	Yield
With sodium perborate In methanol at 25℃; for 0.5h;	81%

(4-hydroxyphenyl)methanol (623-05-2) → 4-hydroxybenzyl chloride (35421-08-0)

Conditions	Yield
With tetrachloromethane; potassium fluoride; triphenylphosphine In N,N-dimethyl-formamide at 50℃; for 0.0833333h; Microwave irradiation;	81%
With thionyl chloride In chloroform at 20℃; for 1h;	48%
With 1-chloro-1-(dimethylamino)-2-methyl-1-propene In chloroform at 20℃; Inert atmosphere;

methanol (67-56-1) + -chlorid (61661-14-1) → 4-hydroxybenzyl chloride (35421-08-0)

p-cresol (106-44-5) + n-C3H7X → 4-hydroxybenzyl chloride (35421-08-0)

Conditions	Yield
Multi-step reaction with 4 steps 2: PCl3, PhCONH2, (PhCO)2O2, SO2Cl2 / 135 °C View Scheme

p-chloromethyl-phenyl chloroformate (15451-04-4) → 4-hydroxybenzyl chloride (35421-08-0)

p-tolyl chloroformate (937-62-2) → 4-hydroxybenzyl chloride (35421-08-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: PCl3, PhCONH2, (PhCO)2O2, SO2Cl2 / 135 °C View Scheme

p-chloromethyl-phenyl chloroformate (15451-04-4) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 4-hydroxybenzyl chloride (35421-08-0)

Conditions	Yield
In methanol; acetonitrile
In methanol; acetonitrile

4-hydroxybenzyl chloride (35421-08-0) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → (3S)-3-[p-(chloromethyl)phenoxy]tetrahydrofuran

Conditions	Yield
Stage #1: 4-hydroxybenzyl chloride In dichloromethane at -5 - 0℃; for 3h; Stage #2: (S)-3-hydroxytetyrahydrofurane With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 4.5h; Reagent/catalyst; Reflux;	95.3%

4-hydroxybenzyl chloride (35421-08-0) → 4-methylphosphonomethyl phenol + diethyl (4-hydroxybenzyl)phosphonate (3173-38-4)

Conditions	Yield
In acetonitrile	A n/a B 93%
In acetonitrile	A 93% B n/a

4-hydroxybenzyl chloride (35421-08-0) + phenylacetylene (536-74-3) → 1-(p-hydroxybenzyl)-4-phenyl-1H-1,2,3-triazole (104951-50-0)

Conditions	Yield
With sodium azide In water at 20℃; for 6h; Inert atmosphere;	93%

4-hydroxybenzyl chloride (35421-08-0) + indole-2,3-dione (91-56-5) + 4-amino-phenol (123-30-8) → C21H16N2O3

Conditions	Yield
With potassium carbonate In acetonitrile for 0.05h; Microwave irradiation;	90%

4-hydroxybenzyl chloride (35421-08-0) + 2-dimethylamino-2-(thien-2-yl)-1-butanol (121048-66-6, 121048-79-1, 121048-81-5) → 4-(2-Dimethylamino-2-thiophen-2-yl-butoxymethyl)-phenol

Conditions	Yield
With potassium hydroxide In N,N-dimethyl-formamide for 1h; Ambient temperature;	85%

4-hydroxybenzyl chloride (35421-08-0) + 4-(chloromethyl)-2-methylquinoline (288399-19-9) → 4-[(2-methyl-4-quinolinyl)methoxy]benzyl chloride (676606-88-5)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide	81%

4-hydroxybenzyl chloride (35421-08-0) + 5-Bromo-1H-indole-2,3-dione (87-48-9) → N-(4-hydroxyphenylmethyl)-5-bromoindol-2,3-dione

Conditions	Yield
With potassium fluoride on basic alumina In acetonitrile Reflux;	80%

4-hydroxybenzyl chloride (35421-08-0) → 3-<(4-Hydroxyphenyl)methyl>pentane-2,4-dione (15451-07-7)

Conditions	Yield
In acetonitrile	78%
In acetonitrile	78%

4-chloropyridine N-oxide (1121-76-2) + 4-hydroxybenzyl chloride (35421-08-0) → 4-[(4-chlorobenzyl)oxy]pyridine 1-oxide (924311-88-6)

Conditions	Yield
Stage #1: 4-hydroxybenzyl chloride With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 4-chloropyridine N-oxide In tetrahydrofuran at 20℃; for 5h;	66%

N,N'-(propane-1,3-diyl)diformamide (16419-41-3) + 4-hydroxybenzyl chloride (35421-08-0) → N,N'-(propane-1,3-diyl)bis(4-hydroxybenzothioamide)

Conditions	Yield
With sulfur; sodium hydroxide at 100℃; for 8h; Schlenk technique;	66%

4-hydroxybenzyl chloride (35421-08-0) + descarboethoxyloratadine (100643-71-8) → 4-((4-(8-chloro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(6H)-ylidene)piperidin-1-yl)methyl)phenol

Conditions	Yield
Stage #1: descarboethoxyloratadine With triethylamine In dichloromethane at 0℃; Stage #2: 4-hydroxybenzyl chloride In dichloromethane Reflux;	63%

1-adamanthanol (768-95-6) + 4-hydroxybenzyl chloride (35421-08-0) → 2-(adamantan-1-yl)-4-(chloromethyl)phenol (1454334-47-4)

Conditions	Yield
With sulfuric acid; acetic acid In dichloromethane at 20℃; for 48h; Friedel-Crafts Alkylation;	60%

4-hydroxybenzyl chloride (35421-08-0) → 4-cyanomethylphenol (14191-95-8)

Conditions	Yield
In acetonitrile	45%
In acetonitrile	45%

4-hydroxybenzyl chloride (35421-08-0) → (4-hydroxyphenyl)methyl nitrate (1119076-12-8)

Conditions	Yield
With silver nitrate In acetonitrile at 20℃; for 1h; Darkness;	27%

4-hydroxybenzyl chloride (35421-08-0) + acetic anhydride (108-24-7) → 3-(diacetoxymethyl)-4-acetoxybenzyl chloride (64619-93-8)

Conditions	Yield
for 24h; Heating;

4-hydroxybenzyl chloride (35421-08-0) + sodium cyanide (143-33-9) → 4-cyanomethylphenol (14191-95-8)

4-hydroxybenzyl chloride (35421-08-0) + acetylacetone (123-54-6) → 3-<(4-Hydroxyphenyl)methyl>pentane-2,4-dione (15451-07-7)

Conditions	Yield
With triethylamine

4-hydroxybenzyl chloride (35421-08-0) + triethyl phosphite (122-52-1) → diethyl (4-hydroxybenzyl)phosphonate (3173-38-4)

Conditions	Yield
at 175℃;

4-hydroxybenzyl chloride (35421-08-0) + (2R,4R)-4-tert-butoxycarbonylamino-pyrrolidine-2,4-dicarboxylic acid dimethyl ester (238753-27-0) → (2R,4R)-4-tert-Butoxycarbonylamino-1-(4-hydroxy-benzyl)-pyrrolidine-2,4-dicarboxylic acid dimethyl ester (371979-21-4)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;

4-hydroxybenzyl chloride (35421-08-0) + C25H49BN2O5SSi → N-[1-butyl-1-(tert-butyl-dimethyl-silanyloxymethyl)-pentyl]-4-dimethylamino-2-(4-hydroxy-benzyl)-N-methyl-benzenesulfonamide (635752-70-4)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; toluene Suzuki coupling;

4-hydroxybenzyl chloride (35421-08-0) + C24H47BN2O5SSi → N-[1-butyl-1-(tert-butyl-dimethyl-silanyloxymethyl)-pentyl]-4-dimethylamino-2-(4-hydroxy-benzyl)-benzenesulfonamide (635752-88-4)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; toluene Suzuki coupling;

4-hydroxybenzyl chloride (35421-08-0) → 1-[4-(2-methyl-quinolin-4-ylmethoxy)-benzyl]-[1,3,5]triazinane-2,4,6-trione

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / Cs2CO3 / dimethylsulfoxide 2: 14 percent / DEAD; PPh3 / dimethylsulfoxide View Scheme

4-hydroxybenzyl chloride (35421-08-0) → 2-Amino-3-(3-formyl-4-hydroxy-phenyl)-2-methyl-propionic acid methyl ester (683196-30-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 24 h / Heating 2: sodium iodide / acetone / 6 h / Heating View Scheme

4-hydroxybenzyl chloride (35421-08-0) → 3-(diacetoxymethyl)-4-acetoxybenzyl iodide (64619-94-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 24 h / Heating 2: sodium iodide / acetone / 6 h / Heating View Scheme

Upstream product

• 623-05-2 (4-hydroxyphenyl)methanol 
• 15451-04-4 p-chloromethyl-phenyl chloroformate 
• 68-12-2 N,N-dimethyl-formamide 
• 937-62-2 p-tolyl chloroformate 
• 106-44-5 p-cresol 
• 39720-27-9 4-acetoxybenzyl chloride 
• 169308-96-7 4-tosyloxy-benzylchloride 
• 67-56-1 methanol 
• 61661-14-1 -chlorid 

Downstream Products

• 635752-70-4 N-[1-butyl-1-(tert-butyl-dimethyl-silanyloxymethyl)-pentyl]-4-dimethylamino-2-(4-hydroxy-benzyl)-N-methyl-benzenesulfonamide 
• 635752-88-4 N-[1-butyl-1-(tert-butyl-dimethyl-silanyloxymethyl)-pentyl]-4-dimethylamino-2-(4-hydroxy-benzyl)-benzenesulfonamide 
• 1119076-12-8 (4-hydroxyphenyl)methyl nitrate 
• 104951-50-0 1-(p-hydroxybenzyl)-4-phenyl-1H-1,2,3-triazole 
• 18951-43-4 4-Amino-4'-hydroxy-stilbene 
• 915095-94-2 (3S)-3-[4-[(2-chloro-5-iodophenyl)methyl]phenoxy]tetrahydrofuran 
• 924311-88-6 4-[(4-chlorobenzyl)oxy]pyridine 1-oxide 
• 1447910-94-2 4-((4-chlorobenzyl)oxy)-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one 
• 1447913-60-1 4-((4-chlorobenzyl)oxy)-1-(2-cyclopropyl-3-methylimidazo[1,2-a]pyrazin-6-yl)pyridin-2(1H)-one 
• 1447913-77-0 4-((4-chlorobenzyl)oxy)-1-(2-cyclopropyl-3-methylimidazo[1,2-a]pyrimidin-6-yl)pyridin-2(1H)-one 
• 1447913-74-7 4-((4-chlorobenzyl)oxy)-1-(2-cyclopropyl-3-methylimidazo[1,2-b]pyridazin-6-yl)pyridin-2(1H)-one 
• 191090-84-3 4-{[(4-chlorophenyl)methyl]oxy}-2(1H)-pyridinone 
• 1447911-27-4 4-((4-chlorobenzyl)oxy)-1-(2-cyclopropyl-1-propyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one 
• 1447911-17-2 4-((4-chlorobenzyl)oxy)-1-(2-cyclopropyl-1-ethyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one 

Relevant articles and documents

Practical and general method for the direct synthesis of alkyl fluorides from alcohols under mild conditions: A reinvestigation

In contrast to the results presented in a previous report, the direct conversion of alcohols to alkyl fluorides with triphenylphosphine and potassium fluoride in CCl4/DMF under mild conditions failed.

Synthesis and biological evaluation of nitric oxide-donating thalidomide analogues as anticancer agents

In search of more potent anticancer agents, 15 nitric oxide (NO)-donating thalidomide analogues, 6a, 6b, 8a-8e, and 13a-13h, were designed and synthesized. Cytotoxicity of these compounds was evaluated in vitro against three human tumor cell lines (HepG2, A549, and PC-3). The results indicated that 13a-13d exhibited notable anticancer activities comparable to or stronger than that of 5-fluorouracil (5-FU). Structure-activity relationships were also discussed, based on the experimental data obtained. Generally, the cytotoxic activity of target compounds is closely related to the type of NO donors, and the length of the spacers connecting to NO donors also appears important for the bioactivities.

Microwave assisted selective cleavage of sulfonates and sulfonamides in dry media

A simple and efficient method for the cleavage of Sulfonates and Sulfonamides has been achieved for the first time under microwave irradiation conditions using KF-Al2O3.