88-04-0

Hazards Identification

Pictogram(s):

Signal:

Warning

GHS Hazard Statements:

H302: Harmful if swallowed [Warning Acute toxicity, oral]
H315: Causes skin irritation [Warning Skin corrosion/irritation]
H317: May cause an allergic skin reaction [Warning Sensitization, Skin]
H319: Causes serious eye irritation [Warning Serious eye damage/eye irritation]

Precautionary Statement Codes:

P261, P264, P264+P265, P270, P272, P280, P301+P317, P302+P352, P305+P351+P338, P321, P330, P332+P317, P333+P313, P337+P317, P362+P364, and P501

Hazard Classes and Categories:

Acute Tox. 4 *
Skin Irrit. 2
Eye Irrit. 2
Skin Sens. 1
Acute Tox. 4 (99.91%)
Skin Irrit. 2 (100%)
Skin Sens. 1 (100%)
Eye Irrit. 2 (100%)
Acute toxicity - category 4
Eye irritation - category 2
Skin irritation - category 2
Skin sensitisation - category 1

Hazards Summary:

Chloroxylenol is a very popular household and hospital disinfectant, and the authors have seen housekeepers who developed allergic contact dermatitis from this preservative in liquid soaps. [Marks, p. 141]

Usage

Chemical Properties

Different sources of media describe the Chemical Properties of 88-04-0 differently. You can refer to the following data:
1. 4-Chloro-3,5-dimethylphenol is white or cream crystalline powder with a characteristic odour
2. White or cream-colored crystals or crystalline powder with a characteristic phenolic odor. Volatile in steam.

Originator

Septiderm ,Fougera ,US,1960

Uses

Different sources of media describe the Uses of 88-04-0 differently. You can refer to the following data:
1. antibacterial, topical and urinary antiseptic
2. 4-Chloro-3,5-dimethylphenol is an antiseptic and germicide. Chloroxylenol is used for mildew prevention. Chloroxylenol is also an antibacterial; antiseptic (topical and urinary).
3. Antiseptic and germicide; for mildew prevention. Claimed to be about 60 times as potent as phenol.

Production Methods

Chloroxylenol is prepared by treating 3,5-dimethylphenol with chlorine or sulfuryl chloride (SO2Cl2).

Manufacturing Process

546 g of intermediate xylenol fraction having a crystallizing point of 45°C mixed with an equal weight of m-5-xylenol are placed in a suitable vessel, equipped with stirring gear, and 273 g of sulfuryl chloride are added slowly. The temperature rises in the course of the reaction to about 40°C. When all the sulfuryl chloride is added the reaction mixture is heated to 80°C and theacid gases removed as far as possible by air-blowing or any other suitable means. On cooling a quantity of the required chlor-xylenol separates out and is removed from the mother liquor. Further quantities of the material required can be isolated by vacuum distillation of the mother liquors and further crystallization. In all, 200 to 208 g of material substantially 2-chlor-m-5- xylenol can be obtained having a melting point of 112°C to 115°C. The material can be purified if desired by crystallization from a solvent such as a hydrocarbon.

Therapeutic Function

Topical antiseptic; Disinfectant

General Description

The degradation of 4-chloro-3,5-dimethylphenol (PCMX) by Fenton-like process using nanoparticulate zero-valent iron (nZVI) and hydrogen peroxide (H2O2) was studied.

Agricultural Uses

Microbiocide: 4-Chloro-3,5-dimethylphenol was first registered in the U.S. for use as a fungicide and is now applied as an antimicrobial for control of bacteria, algae and fungi in adhesives, emulsions, paints and wash tanks. It is registered for use in household and domestic dwellings, laundry equipment, bathrooms, diaper pails and in industrial water and aqueous systems. Not listed for use in EU countries. Registered for use in the U.S. There are 64 global suppliers.

Pharmaceutical Applications

4-Chloro-3,5-dimethylphenol is a common constituent of many proprietary disinfectants used for skin and wound disinfection. As a pharmaceutical excipient, 4-Chloro-3,5-dimethylphenol is commonly used in low concentrations as an antimicrobial preservative in topical formulations such as creams and ointments. 4-Chloro-3,5-dimethylphenol is also used in a number of cosmetic formulations. Therapeutically, 4-Chloro-3,5-dimethylphenol has been investigated as a treatment for acne vulgaris, for treating infected root canals, and as an antifungal agent when impregnated into medical devices. 4-Chloro-3,5-dimethylphenol is included in drug products approved for topical antifungal, topical acne and topical dandruff/seborrheic dermatitis/psoriasis treatments.

Trade name

BAR-FUNGAL PLUS?[C]; BIO SLIME?[C]; DESSON?; DETTOL?; ECOTRU?; ESPADOL?; HUSEPT?; HUSEPT EXTRA?; NIPACIDE?; OTTASEPT?[C]; OTTASEPT? EXTRA[C]; PCMX; RBA 777?

Clinical Use

p-Chloro-m-xylenol (PC-MX; Metasep) is a nonirritating antiseptic agent with broad-spectrum antibacterial and antifungal properties. It is marketed in a 2% concentration as a shampoo. It has also been used topically for the treatment of tinea (ringworm) infections such as athlete s foot (tinea pedis) and jock itch (tinea cruris).

Safety Profile

Poison by intraperitoneal route. Moderately toxic by ingestion. An experimental teratogen. An eye irritant. An antimicrobial agent. See also CHLOROPHENOLS and CHLORINATED HYDROCARBONS, AROMATIC. When heated to decomposition it emits toxic fumes of Cl-.

Safety

Chloroxylenol is generally regarded as a relatively nontoxic and nonirritant material when used as an excipient in topical products. However, chloroxylenol has been placed in Toxicity Category I for eye irritation effects. In addition, allergic skin reactions have been reported. Taken orally, chloroxylenol is mildly toxic and ingestion of a chloroxylenol-containing disinfectant product has been associated with reports of fatal or severe instances of selfpoisoning. LD50 (mouse, IP): 0.115 g/kg LD50 (rat, dermal): >2.0 g/kg LD50 (rat, oral): 3.83 g/kg

storage

Chloroxylenol is stable at normal room temperature, but is volatile in steam. Contact with natural rubber should be avoided. Aqueous solutions of chloroxylenol are susceptible to microbial contamination and appropriate measures should be taken to prevent contamination during storage or dilution. Chloroxylenol should be stored in polyethylene, mild steel or stainless steel containers, which should be well-closed and kept in a cool, dry place. Chloroxylenol does not absorb at wavelengths >290 nm and has been reported to be stable to sunlight for up to 24 hours.

Purification Methods

Crystallise the phenol from *benzene or toluene. [Beilstein 6 IV 3152.]

Incompatibilities

4-Chloro-3,5-dimethylphenol has been reported to be incompatible with nonionic surfactants and methylcellulose.

Regulatory Status

Included in the FDA Inactive Ingredients Database (otic preparations; topical creams and emulsions). Included in nonparenteral medicines licensed in the UK. Approved in Europe as a preservative in cosmetics with a maximum authorized concentration of 0.5%.

Synthetic route

3,5-Dimethylphenol (108-68-9) → 4-Chloro-3,5-dimethylphenol (88-04-0)

Conditions	Yield
With N-chloro-N-(benzenesulfonyl)benzenesulfonamide In acetonitrile at 20 - 25℃; for 0.166667h; Green chemistry;	98.9%
With hydrogenchloride; copper(II) choride dihydrate; oxygen; sodium chloride In 1,2-dichloro-ethane at 80℃; under 3750.38 Torr; Temperature; Solvent; Reagent/catalyst; Autoclave;	97.2%
With iron(III) chloride; N-chloro-succinimide; 1-butyl-3-methylimidazolium trifluoromethanesulfonimide In tetrahydrofuran at 60℃; for 12h; Inert atmosphere; regioselective reaction;	76%

4-chloro-3,5-dimethylanisole (6981-15-3) → 4-Chloro-3,5-dimethylphenol (88-04-0)

Conditions	Yield
Kaninchen-Organismus;
With boron tribromide In dichloromethane at 0℃; for 2h;

4-chloro-3, 5, dimethyl phenyl acetate (22012-58-4) → 4-Chloro-3,5-dimethylphenol (88-04-0)

Conditions	Yield
Kaninchen-Organismus;

3,5-Dimethylphenol (108-68-9) → 4-Chloro-3,5-dimethylphenol (88-04-0) + o-chloro-m-xylenol (5538-41-0)

Conditions	Yield
With sulfuryl dichloride; chloroform
With iron(III) chloride; 1,2-dithiacyclooctane; sulfuryl dichloride In dichloromethane at 20℃; for 4h; Reagent/catalyst; regioselective reaction;	A 89 %Chromat. B 7.6 %Chromat.
With 1,3-dichloro-5,5-dimethylhydantoin; diisopropylamine hydrochloride In toluene at 0℃; for 4h; Darkness; Overall yield = 86 %; regioselective reaction;

4-chloro-3,5-dimethylphenyl phosphate monoester → 4-Chloro-3,5-dimethylphenol (88-04-0)

Conditions	Yield
With hydrogenchloride at 98℃; Kinetics; Mechanism; Thermodynamic data; E(activ.), ΔS(excit.);

N,N,N',N'-Tetramethyl-acridine-3,6-diamine; compound with 4-chloro-3,5-dimethyl-phenol → 4-Chloro-3,5-dimethylphenol (88-04-0) + acridine orange (494-38-2)

Conditions	Yield
In benzonitrile at 25℃; Equilibrium constant; ionic strength 0.1 M;

N,N,N',N'-Tetramethyl-acridine-3,6-diamine; compound with 4-chloro-3,5-dimethyl-phenol → 4-Chloro-3,5-dimethylphenol (88-04-0) + acridine orange (494-38-2)

Conditions	Yield
In benzonitrile at 25℃; Equilibrium constant; ionic strength 0.1 M;

3,5-Dimethylphenol (108-68-9) → 4-Chloro-3,5-dimethylphenol (88-04-0) + 2,4-dichloro-3,5-dimethylphenol (133-53-9)

Conditions	Yield
With N-chlorotriethylammonium chloride In trifluoroacetic acid Ambient temperature; Yield given. Yields of byproduct given;

chlorine (7782-50-5) + acetic acid (64-19-7) + 3,5-Dimethylphenol (108-68-9) → 4-Chloro-3,5-dimethylphenol (88-04-0)

chloroform (67-66-3) + 3,5-Dimethylphenol (108-68-9) + sulfuryl chloride (1 mol) → 4-Chloro-3,5-dimethylphenol (88-04-0) + o-chloro-m-xylenol (5538-41-0)

5-(2-ethoxy)-2-chloro-1,3-dimethylbenzene (23399-89-5) + rabbit-organism → 4-Chloro-3,5-dimethylphenol (88-04-0)

ethanol (64-17-5) + (4-chloro-3,5-dimethyl-phenyl)-chloromethyl ether (855950-62-8) → formaldehyd (50-00-0) + 4-Chloro-3,5-dimethylphenol (88-04-0) + ethoxy-<4-chloro-3,5-dimethyl-phenoxy>-methane

Conditions	Yield
at 25℃; Rate constant; Solvolyse;

3,5-dimethylmethoxybenzene (874-63-5) → 4-Chloro-3,5-dimethylphenol (88-04-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-chloro-succinimide 2: boron tribromide / dichloromethane / 2 h / 0 °C View Scheme

3,5-Dimethylphenol (108-68-9) → 4-Chloro-3,5-dimethylphenol (88-04-0) + 2,4-dichloro-3,5-dimethylphenol (133-53-9) + o-chloro-m-xylenol (5538-41-0)

Conditions	Yield
With iron(III) chloride; sulfuryl dichloride; 1,3-bis(methylthio)propane In dichloromethane at 20℃; for 4h; Reagent/catalyst; regioselective reaction;	A 75 %Chromat. B 9 %Chromat. C 10 %Chromat.

4-Chloro-3,5-dimethylphenol (88-04-0) + 4-fluorobenzonitrile (1194-02-1) → 4-(4-chloro-3,5-dimethylphenoxy)benzonitrile (938300-53-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 16h;	100%
With potassium carbonate In dimethyl sulfoxide Microwave irradiation;

4-Chloro-3,5-dimethylphenol (88-04-0) + 4-fluorobenzaldehyde (459-57-4) → 4-(4-chloro-3,5-dimethylphenoxy)benzaldehyde

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 16h;	100%
With potassium carbonate In N,N-dimethyl-formamide at 110℃; Inert atmosphere;	70%

4-Chloro-3,5-dimethylphenol (88-04-0) + Cinnamoyl chloride (102-92-1) → 4-chloro-3,5-dimethylphenylcinnamate (89329-16-8)

Conditions	Yield
With pyridine In benzene for 1h; Heating;	99%

4-Chloro-3,5-dimethylphenol (88-04-0) + trans-p-methylcinnamic acid (1866-39-3) → 6-chloro-5,7-dimethyl-4-(p-tolyl)-3,4-dihydrochromen-2-one

Conditions	Yield
With trifluoroacetic acid at 100℃; for 23h;	99%

4-Chloro-3,5-dimethylphenol (88-04-0) + 2-methoxycinnamic acid (1011-54-7) → 6-chloro-4-(2-methoxyphenyl)-5,7-dimethyl-3,4-dihydrochromen-2-one

Conditions	Yield
With trifluoroacetic acid at 100℃; for 16h;	99%

4-Chloro-3,5-dimethylphenol (88-04-0) + (E)-3,4,5-trimethoxy-cinnamic acid (20329-98-0, 20329-99-1, 90-50-6) → 6-chloro-5,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydrochromen-2-one

Conditions	Yield
With trifluoroacetic acid at 100℃; for 16h;	99%

4-Chloro-3,5-dimethylphenol (88-04-0) + 3,4-methylenedioxy-trans-cinnamic acid (2373-80-0) → 4-(benzo[d][1,3]dioxol-5-yl)-6-chloro-5,7-dimethyl-3,4-dihydrochromen-2-one (850496-03-6)

Conditions	Yield
With trifluoroacetic acid for 23h;	99%
With trifluoroacetic acid

4-Chloro-3,5-dimethylphenol (88-04-0) + 3,4-(methylenedioxy)cinnamic acid (2373-80-0) → 4-(benzo[d][1,3]dioxol-5-yl)-6-chloro-5,7-dimethyl-3,4-dihydrochromen-2-one (850496-03-6)

Conditions	Yield
With acetyl chloride at 25℃; for 10h; Inert atmosphere;	99%

4-Chloro-3,5-dimethylphenol (88-04-0) + 3-(4'-methoxyphenyl)propenoic acid (830-09-1) → 6-chloro-5,7-dimethyl-4-(4-methoxyphenyl)-3,4-dihydrochromen-2-one (850496-00-3)

Conditions	Yield
With acetyl chloride at 25℃; for 1h; Inert atmosphere;	99%

4-Chloro-3,5-dimethylphenol (88-04-0) + diphenyl acetylene (501-65-5) → (Z)-(1-(4-chloro-3,5-dimethylphenoxy)ethene-1,2-diyl)dibenzene

Conditions	Yield
With [{Au(IPr)}2(μ-OH)][BF4] In toluene at 80℃; for 6h; regioselective reaction;	98%

4-Chloro-3,5-dimethylphenol (88-04-0) + 4-(1H-1,2,3-benzotriazol-1-yl)-5-nitrophthalonitrile (274924-71-9) → 4-benzotriazol-1-yl-5-(4-chloro-3,5-dimethyl-phenoxy)-phthalonitrile

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 20℃;	96%

4-Chloro-3,5-dimethylphenol (88-04-0) + propionic acid (802294-64-0) → 6-chloro-2-ethyl-3,5,7-trimethyl-4H-chromen-4-one

Conditions	Yield
With titanium tetrachloride In neat (no solvent) at 100℃; for 3h; Inert atmosphere;	96%

4-Chloro-3,5-dimethylphenol (88-04-0) + p-Chlorothiophenol (106-54-7) → 4-chloro-2-((4-chlorophenyl)thio)-3,5-dimethylphenol

Conditions	Yield
With nitronium tetrafluoborate; oxygen In sulfolane at 20℃; for 24h; Sealed tube;	96%

4-Chloro-3,5-dimethylphenol (88-04-0) + (E)-3-(4-methoxyphenyl)acrylic acid (943-89-5) → 6-chloro-5,7-dimethyl-4-(4-methoxyphenyl)-3,4-dihydrochromen-2-one (850496-00-3)

Conditions	Yield
With trifluoroacetic acid for 16h;	95%

trifluoromethylsulfonic anhydride (358-23-6) + 4-Chloro-3,5-dimethylphenol (88-04-0) → 4-chloro-3,5-dimethylphenyl trifluoromethanesulfonate (1242759-17-6)

Conditions	Yield
Stage #1: 4-Chloro-3,5-dimethylphenol With triethylamine In dichloromethane at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: trifluoromethylsulfonic anhydride In dichloromethane at -78 - 20℃; for 12h; Inert atmosphere;	95%
With triethylamine In dichloromethane at 0 - 20℃;	78%
Inert atmosphere;
With pyridine In dichloromethane at 0 - 20℃; for 5h;

4-methylcinnamic acid (1866-39-3) + 4-Chloro-3,5-dimethylphenol (88-04-0) → 6-chloro-5,7-dimethyl-4-(p-tolyl)-3,4-dihydrochromen-2-one

Conditions	Yield
With acetyl chloride at 25℃; for 10h; Inert atmosphere;	95%

4-Chloro-3,5-dimethylphenol (88-04-0) + 1,3,6,8-tetraazatricyclo[4.4.1.13,8]dodecane (51-46-7) → 1,3-bis[2′-hydroxy-5′-chloro-4′,6′-dimethylbenzyl]imidazolidine (1423170-05-1)

Conditions	Yield
at 150℃; for 0.333333h; Mannich Aminomethylation;	94%

m-bromobenzoic aldehyde (3132-99-8) + 4-Chloro-3,5-dimethylphenol (88-04-0) → 3-(4-chloro-3,5-dimethylphenoxy)benzaldehyde (1426937-26-9)

Conditions	Yield
With copper(l) iodide; dimethylaminoacetic acid; caesium carbonate In 1,4-dioxane at 180℃; for 16h;	94%

4-Chloro-3,5-dimethylphenol (88-04-0) → 4-chloro-3,5-dimethyl-2-nitrophenol (54582-90-0)

Conditions	Yield
With nitric acid; acetic acid at 5 - 25℃; for 1h;	93.2%
With nitric acid In acetic acid at 5 - 20℃; for 1h;	90.1%
With bismuth (III) nitrate pentahydrate In acetone at 56℃; for 6h;	80%

4-Chloro-3,5-dimethylphenol (88-04-0) + 2-(trifluoromethyl)-10H-phenothiazine (92-30-8) → 4-chloro-3,5dimethyl-2-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)phenol

Conditions	Yield
With Trimethylacetic acid at 150℃; Sealed tube;	92.3%
With oxygen; sodium nitrite In toluene at 0 - 20℃; Sealed tube;	74%

4-Chloro-3,5-dimethylphenol (88-04-0) + toluene-4-sulfonic acid (104-15-4) → 4-chloro-3,5-dimethylphenyl p-toluenesulfonate (19545-94-9)

Conditions	Yield
Fe(3+)-exchanged montmorillonite clay In 1,2-dichloro-ethane at 80℃; for 24h;	92%

4-Chloro-3,5-dimethylphenol (88-04-0) → 3,5-Dimethylphenol (108-68-9)

Conditions	Yield
With potassium carbonate; isopropyl alcohol; palladium diacetate; triphenylphosphine at 90℃; for 14h;	92%
In isopropyl alcohol for 15h; Irradiation; Inert atmosphere;	100 %Chromat.

4-Chloro-3,5-dimethylphenol (88-04-0) + methyl iodide (74-88-4) → 4-chloro-3,5-dimethylanisole (6981-15-3)

Conditions	Yield
	92%
With potassium carbonate In acetone for 3h; Inert atmosphere; Reflux;	84%
With potassium carbonate In acetone for 3h; Heating / reflux;	77%
With potassium carbonate In acetone for 6h; Reflux;

4-Chloro-3,5-dimethylphenol (88-04-0) + propionic acid (802294-64-0) → 4-chloro-3,5-dimethylphenyl propionate (100126-79-2)

Conditions	Yield
With tin(IV) chloride In neat (no solvent) at 100℃; for 8h; Inert atmosphere; chemoselective reaction;	92%

Octanoic acid (124-07-2) + 4-Chloro-3,5-dimethylphenol (88-04-0) → 6-chloro-2-heptyl-3-hexyl-5,7-dimethyl-4H-chromen-4-one

Conditions	Yield
With titanium tetrachloride In neat (no solvent) at 100℃; for 6h; Inert atmosphere;	91%

phenylacetic acid (103-82-2) + 4-Chloro-3,5-dimethylphenol (88-04-0) → 4-chloro-3,5-dimethylphenyl 2-phenylacetate

Conditions	Yield
With tin(IV) chloride In neat (no solvent) at 100℃; for 8h; Inert atmosphere; chemoselective reaction;	91%

4-Chloro-3,5-dimethylphenol (88-04-0) → 2,2'-dihydroxy-5,5'-dichloro-4,4',6,6'-tetramethyl-1,1'-biphenyl (188348-50-7, 188348-52-9, 155566-46-4)

Conditions	Yield
With air; Cu-exchange montmorillonite In chlorobenzene at 140℃; for 6h;	90%
With aluminum (III) chloride; propionic acid In nitromethane at 50℃; for 18h; Reagent/catalyst; Inert atmosphere;	86%
With clay; oxygen; copper In chlorobenzene for 10h; coupling; Heating;	63%
With iron(III) chloride	30%
With Cu-exchanged clay In chlorobenzene at 140℃; for 6h;	27%

4-Chloro-3,5-dimethylphenol (88-04-0) + (E)-3-methylcinnamic acid (3029-79-6, 14473-89-3, 16642-82-3) → 6-chloro-5,7-dimethyl-4-(m-tolyl)-3,4-dihydrochromen-2-one

Conditions	Yield
With trifluoroacetic acid at 100℃; for 40h;	90%

N,N-diisopropylcarbamoyl chloride (19009-39-3) + 4-Chloro-3,5-dimethylphenol (88-04-0) → 4-chloro-3,5-dimethylphenyl diisopropylcarbamate

Conditions	Yield
With potassium carbonate In acetonitrile	90%

Upstream product

• 6981-15-3 4-chloro-3,5-dimethylanisole 
• 22012-58-4 4-chloro-3, 5, dimethyl phenyl acetate 
• 108-68-9 3,5-Dimethylphenol 
• 7782-50-5 chlorine 
• 64-19-7 acetic acid 
• 67-66-3 chloroform 
• 64-17-5 ethanol 
• 855950-62-8 (4-chloro-3,5-dimethyl-phenyl)-chloromethyl ether 
• 874-63-5 3,5-dimethylmethoxybenzene 
• 23399-89-5 5-(2-ethoxy)-2-chloro-1,3-dimethylbenzene 

Downstream Products

• 101263-50-7 4-chloro-3,5-dimethyl-2-pyrrolidinomethyl-phenol 
• 46824-94-6 4-chloro-3,5-dimethyl-2-(N-morpholinyl)methylphenol 
• 47348-42-5 4-chloro-3,5-dimethyl-2,6-bis-morpholinomethyl-phenol 
• 108849-27-0 4-chloro-3,5-dimethyl-2-(4-methyl-piperazinomethyl)-phenol 
• 22002-38-6 4-chloro-2,6-bis-hydroxymethyl-3,5-dimethyl-phenol 
• 16085-23-7 4,4'-dichloro-3,5,3',5'-tetramethyl-2,2'-methanediyl-di-phenol 
• 132982-42-4 2-(4-chloro-3,5-dimethyl-phenoxymethyl)-5-methoxy-pyran-4-one 
• 91308-29-1 oxalic acid bis-(4-chloro-3,5-dimethyl-phenyl ester) 
• 18980-16-0 2-sec-butyl-4-chloro-3,5-dimethyl-phenol 
• 18980-17-1 2-sec-Amyl-3,5-dimethyl-p-Chlorophenol 
• 18980-18-2 2-Diethylmethyl-3,5-dimethyl-p-Chlorophenol 
• 133-53-9 2,4-dichloro-3,5-dimethylphenol 
• 17387-53-0 4,4',6'-trichloro-3,5-dimethyl-2,2'-methanediyl-di-phenol 
• 54582-90-0 4-chloro-3,5-dimethyl-2-nitrophenol 

Relevant academic research and scientific papers

Activator free, expeditious and eco-friendly chlorination of activated arenes by N-chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI)

N-Chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI) has been explored for the first time as a chlorinating reagent for direct chlorination of various activated arenes and heterocycles without any activator. A comparative in-silico study was performed to determine the electrophilic character for NCBSI and commercially available N-chloro reagents to reveal the reactivity on a theoretical viewpoint. The reagent was prepared by an improved method avoiding the use of hazardous t-butyl hypochlorite. This reagent was proved to be very reactive compared to other N-chloro reagents. The precursor of the reagent N-(phenylsulfonyl)benzene sulfonamide was recovered from aqueous spent, which can be recycled to synthesize NCBSI. The eco-friendly protocol was equally applicable for the synthesis of industrially important chloroxylenol as an antibacterial agent.

Method for preparing 4-chloro-3, 5-dimethylphenol

The invention relates to a method for preparing 4-chloro-3, 5-dimethylphenol. The method comprises the following specific steps: fully dissolving 3, 5-dimethylphenol by using a protonic solvent, and dropwise adding sulfuryl chloride to perform chlorination reaction under the action of a directional chlorination catalyst to obtain the 4-chloro-3, 5-dimethylphenol, wherein the directional chlorination catalyst is Fe-MOFs. A directional catalyst/protic solvent combined system adopted by the method is applied to directional chlorination of 3, 5-dimethylphenol, so that the selectivity of chlorination reaction is effectively improved, and a 4-chloro-3, 5-methylphenol product is efficiently prepared; and a final product with the content of 94% and the purity of 99.7% is obtained through one-step synthesis without purification. The method has the characteristics of simplicity and convenience in operation, high product selectivity and the like, and has very high industrial application value.

Method for preparing 4 -chloro -3 and 5 -dimethylphenol by low-temperature chlorination

The invention discloses a method for preparing 4 -chloro -3-5 -dimethylphenol by low-temperature chlorination, which comprises (1) 3,5 -dimethylphenol and a chlorination agent carrying out chlorination reaction at low temperature, and carrying out solid-liquid separation to obtain the solid crude product 1 and the intermediate mother liquor. (2) The mother liquor is further subjected to chlorination reaction at low temperature, and the final solid-liquid separation is carried out after the reaction is completed to obtain the solid crude product 2 and the final mother liquor. The solid crude product 1 and the solid crude product 2 are post-treated to give said 4 - chloro -3, 5 - dimethylphenol. To the method, the precipitated crystals are separated in time in the reaction process, the wrapping of the raw materials is reduced on the one hand, and the conversion rate is improved.

para-Selective chlorination of cresols and m-xylenol using sulfuryl chloride in the presence of poly(alkylene sulfide)s

Chlorination of o-cresol, m-cresol, and m-xylenol using sulfuryl chloride in the presence of a range of poly(alkylene sulfide)s and a Lewis acid (aluminum or ferric chloride) has been studied. The sulfur containing catalysts used led to the production of para-chlorophenols in high yields and higher para/ortho ratios than for reactions in the absence of such poly(alkylene sulfide)s. The effectiveness of the polymers was found to be dependent on the length of the spacer groups between the sulfur atoms. For example, polymers with shorter spacers provided high yields of 4-chloro-o-cresol (ca. 97%), while polymers with at least one longer spacer provided high yields of both 4-chloro-m-cresol (up to 94.6%) and 4-chloro-m-xylenol (up to 97.6%).

Synthesis method of 4-chloro-3, 5-dimethylphenol

The invention provides a synthesis method of 4-chloro-3, 3, 3-tetrafluoropropene. A bivalent copper salt is used as a catalyst, 3, 5-dimethylphenol reacts with a chlorinating agent and an oxidizing agent under the condition of an organic solvent to obtain 4-chloro-3, 5-dimethylphenol, and the synthesis method is good in reaction selectivity, high in yield, recyclable in solvent, easy to separate the catalyst, capable of being repeatedly used, mild in reaction condition, environmentally friendly and quite beneficial to industrial production in the production process.

Method for preparing 4-chloro-3, 5-dimethylphenol

The invention discloses a method for preparing 4-chloro-3, 5-dimethylphenol. The method comprises the following step: carrying out a chlorination reaction on a 3, 5-dimethylphenol by taking phosgene as a chlorination reagent and a saturated nitrogen-oxygen heterocyclic compound as an accelerant to obtain 4-chloro-3, 5-dimethylphenol. The method has the advantages of no generation of gas sulfide, high para-position selectivity, simplicity and convenience in operation and the like.

Regioselective chlorination of phenols in the presence of tetrahydrothiopyran derivatives

Four six-membered cyclic sulfides, namely tetrahydrothiopyran, 3-methyltetrahydrothiopyran, 4-methyltetrahydrothiopyran and 4,4-dimethyltetrahyrdrothiopyran have been used as moderators in chlorination reactions of various phenols with sulfuryl chloride in the presence of aluminum or ferric chloride. On chlorination of phenol, ortho-cresol and meta-cresol the para/ortho chlorination ratios and yields of the para-chloro isomers are higher than when no cyclic sulfide is used for all of the cyclic sulfides, but chlorination of meta-xylenol is less consistent, with some cyclic sulfides producing higher p/o ratios and others producing lower ratios than reactions having no sulfide present.

Ammonium Salt-Catalyzed Highly Practical Ortho-Selective Monohalogenation and Phenylselenation of Phenols: Scope and Applications

An ortho-selective ammonium chloride salt-catalyzed direct C-H monohalogenation of phenols and 1,1′-bi-2-naphthol (BINOL) with 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) as the chlorinating agent has been developed. The catalyst loading was low (down to 0.01 mol %) and the reaction conditions were very mild. A wide range of substrates including BINOLs were compatible with this catalytic protocol. Chlorinated BINOLs are useful synthons for the synthesis of a wide range of unsymmetrical 3-aryl BINOLs that are not easily accessible. In addition, the same catalytic system can facilitate the ortho-selective selenylation of phenols.

Regioselective synthesis of important chlorophenols in the presence of methylthioalkanes with remote SMe, OMe or OH substituents

Various methylthio alcohols, methoxy(methylthio)alkanes and bis(methylthio)alkanes have been used as regioselectivity modifiers in the chlorination reactions of various phenols at room temperature. The process involves the use of a slight excess of sulfuryl chloride in the presence of aluminum or ferric chloride as an activator. Methylthio alcohols, methoxy(methylthio)alkanes and bis(methylthio)alkanes having 2 and 3 methylene groups as a spacer were found to be good for the para-selective chlorination of o-cresol and phenol. On the other hand, methylthio alcohols, methoxy(methylthio)alkanes and bis(methylthio)alkanes having 6 and 9 methylene groups were found to be good for the selective para-chlorination of m-xylenol and m-cresol. Calculations using density functional theory on bis(methylthio)alkanes have suggested two different types of stable chlorinated intermediates depending on the number of methylene units as a spacer.

Iron(III)-Catalyzed Chlorination of Activated Arenes

A general and regioselective method for the chlorination of activated arenes has been developed. The transformation uses iron(III) triflimide as a powerful Lewis acid for the activation of N-chlorosuccinimide and the subsequent chlorination of a wide range of anisole, aniline, acetanilide, and phenol derivatives. The reaction was utilized for the late-stage mono- and dichlorination of a range of target compounds such as the natural product nitrofungin, the antibacterial agent chloroxylenol, and the herbicide chloroxynil. The facile nature of this transformation was demonstrated with the development of one-pot, tandem, iron-catalyzed dihalogenation processes allowing highly regioselective formation of different carbon-halogen bonds. The synthetic utility of the resulting dihalogenated aryl compounds as building blocks was established with the synthesis of natural products and pharmaceutically relevant targets.