description
p-Cresol is a low-molecular-weight compound, is a starting material in the synthesis of bupranolol which is a non-selective beta blocker.
p-cresol is found in extracts from the plants Mentha pulegium and Hedeoma pulegioides, commonly known as pennyroyal oil and pennyroyal tea. These extracts are popular as unconventional herbal therapeutic agents and are applied as abortiva, diaphoretics, emmenagogues, and psychedelic drugs. Pennyroyal oil is extensively used for its pleasant mint-like smell in the flavoring industry.
It is also used in the production of antioxidants like butylated hydroxytoluene. Furthermore, it is used as an adhesive and a sealant in chemicals, dyes, intermediates, odor agents, plasticizers, plating agents and surface treating agents. It acts as an antioxidant and a disinfectant in pharmaceuticals.
Chemical properties
It appears as colorless to pink crystal with smoked and herbal smell. The relative density (d420) is 1.0178; the refractive index (nD20) is 1.5312; the melting point is 34.8 °C; the boiling point is 201.9 °C and the flash point is 86.1 °C. It is soluble in water (2.3%/40 ℃), easily soluble in caustic soda and common organic solvents.
Natural products exist in ylang oil, strawberry, cheese, coffee and cocoa and so on.
Uses
1. It can be used as germicide, fungicide. Used for organic Synthesis.
2. This product is the raw material for the manufacture of antioxidant 2,6-di-tert-butyl-p-cresol and rubber antioxidant. At the same time, it is also an important fundamental raw material for the production of pharmaceutical TMP and dyes para-Cresidine sulfonic acid.
3. P-cresol is the intermediate for the manufacturing of fungicide methylphosophos, an insecticide flufenvalerate, and Etofenprox, but also the intermediate of antioxidant additives 2, 6-di-tert-butyl-4-methyl phenol and p-hydroxybenzene formaldehyde.
4. It can be used as raw materials for the preparation of antioxidant 264 (2, 6-di-tert-butyl-p-cresol) and rubber antioxidant. In the plastics industry, it can produce phenolic resin and plasticizer. In medicine, it can be used as a disinfectant. In addition, it can be used as the raw materials of dyes and pesticides.
Production method
Production method of p-Cresol: sulfonate toluene with sulfuric acid to get p-toluenesulfonic acid, after cooling, crystallization, filtration, and then add sodium sulfite to neutralize to get sodium p-toluenesulfonate, and then sodium hydroxide alkaline melting to get sodium p-toluene phenol, and then acidified by sulfurous acid to become. Finally, it is separated by distillation and crystallization.
Toxicity
Central nervous system: toxic effects with being fatal in severe cases.
LD50:1800 mg/kg (rat, oral);
As fragrances, it can be safely used in food (FDA, §172.515, 2000);
GRAS (FEMA).
Chemical Properties
Cresol is a mixture of three isomeric forms: o-, m-, and p-cresol. These compounds are slightly soluble in water. The m-isomer is a colorless or yellow liquid with characteristic odor. The p-cresol is a colorless to pink crystals with a characteristics phenol-like odor. The concentration at which the odor becomes detectable in water is 55 parts per billion (Buttery et al., 1988). Another study by Leonardos et al. (1969) reported an experimental odor threshold concentration of 1 parts per billion, which is higher than the 0.054 parts per billion reported by Nagata and Takeuchi (1990).
Occurrence
Has been found in a score of essential oils including ylang ylang and oil of jasmine (Gildemeister & Hoffman, 1966).
Uses
p-Cresol is utilized in the production of artificial resins, liquid crystal intermediates, disinfectants, fumigants, and as an industrial solvent. It is also involved in the manufacturing of Bupranolol, a non-selective beta blocker.
Production Methods
The cresols (cresylic acids) are methyl phenols and generally
appear as a mixture of isomers. p-Cresol is a 4-methyl
derivative of phenol and is prepared from m-toluic acid
or obtained from coal tar or petroleum. Crude
cresol is obtained by distilling “gray phenic acid” at a
temperature of ～180–201°C. p-Cresol may be separated
from the crude or purified mixture by repeated fractional
distillation in vacuo. It can also be prepared synthetically by
diazotization of the specific toluene or by fusion of the
corresponding toluenesulfonic acid with sodium hydroxide.
Preparation
It can be prepared by fractional distillation of coal tar where it occurs together with the ortho- and para- isomers.
Definition
ChEBI: P-cresol is a cresol that consists of toluene substituted by a hydroxy group at position 4. It is a metabolite of aromatic amino acid metabolism produced by intestinal microflora in humans and animals. It has a role as a uremic toxin, a human metabolite and an Escherichia coli metabolite.
Aroma threshold values
Detection: 55 to 100 ppb.
General Description
Colorless solid with a tar like odor. Sinks and mixes slowly with water.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
p-Cresol is sensitive to heat. p-Cresol is also sensitive to light. p-Cresol is incompatible with strong oxidizers and strong alkalis. p-Cresol will attack some forms of plastics, coatings and rubber.
Health Hazard
INHALATION: Irritation of nose or throat. EYES: Intense irritation and pain, swelling of conjunctiva and corneal damage may occur. SKIN: Intense burning, loss of feeling, white discoloration and softening. Gangrene may occur. INGESTION: Burning sensation in mouth and esophagus. Vomiting may result. Absorption by all routes may cause muscular weakness, gastroenteric disturbance, severe depression and collapse. Effects are primarily on central nervous system, edema of lungs, injury of spleen and pancreas may occur.
Safety Profile
Poison by ingestion,
skin contact, subcutaneous, intravenous, and
intraperitoneal routes. A severe skin and eye
irritant. Questionable carcinogen with
experimental neoplastigenic data by itself
and with 7,12-dirnethyl benz(a)anthracene.
Combustible when exposed to heat or
flame. Moderately explosive in the form ofvapor when exposed to heat or flame. To
fight fire, use CO2, dry chemical, alcohol
foam. See also other cresol entries and
PHENOL.
Potential Exposure
Cresol is used as a disinfectant and fumigant; as an ore flotation agent, and as an intermediate in the manufacture of chemicals, dyes, plastics, and antioxidants. A mixture of isomers is generally used; the concentrations of the components are determined by the source of the cresol.
Carcinogenicity
o-Cresol has been induced a few
papillomas but no carcinomas in tumor studies.
Source
As 3+4-methylphenol, detected in distilled water-soluble fractions of 87 octane gasoline
(6.03 mg/L), 94 octane gasoline (0.60 mg/L), Gasohol (1.76 mg/L), No. 2 fuel oil (1.84 mg/L), jet
fuel A (0.43 mg/L), diesel fuel (1.318 mg/L), and military jet fuel JP-4 (0.92 mg/L) (Potter, 1996).
A high-temperature coal tar contained 4-methylphenol at an average concentration of 0.27 wt %
(McNeil, 1983).
Occurs naturally in brown juniper, Spanish cedar, peppermint (2 to 20 ppb), tarragon, asparagus
shoots, ylang-ylang, jasmine, tea leaves, coffee beans, Japanese privet, white mulberries,
raspberries, vanilla, blueberries, sour cherries, anise, and tamarind (Duke, 1992).
A liquid swine manure sample collected from a waste storage basin contained 4-methylphenol
at a concentration of 4.9 mg/L (Zahn et al., 1997).
Metabolism
p-Cresol is oxidized at the methyl group in both dogs and rabbits to yield ρ-hydroxybenzoic acid. In the rabbit up to 10% of oral doses of 0.25-0.5 g is excreted as free and conjugated p-hydroxybenzoic acid (Williams, 1959).
Shipping
UN2076 Cresols, liquid, Hazard class: 6.1; Labels: 6.1-Poisonous materials, 8-Corrosive material. UN3455 Cresols, solid, Hazard class: 6.1; Labels: 6.1- Poisonous materials, 8-Corrosive material.
Purification Methods
It can be separated from m-cresol by fractional crystalisation of its melt. Purify it by distillation, by precipitation from *benzene solution with pet ether, and via its benzoate, as for phenol. Dry it under vacuum over P2O5. It has also been crystallised from pet ether (b 40-60o) and by conversion to sodium p-cresoxyacetate which, after crystallisation from water is decomposed by heating with HCl in an autoclave [Savard Ann Chim (Paris) 11 287 1929]. The 3,5-dinitrobenzoate (prepared with 3,5-dinitrobenzoyl chloride in dry pyridine, and recrystallised from EtOH or aqueous Me2CO) has m 189o. [Beilstein 6 II 2093.]
Incompatibilities
Vapors may form explosive mixture with air. Incompatible with strong acids; oxidizers, alkalies, aliphatic amines; amides, chlorosulfonic acid; oleum. Decomposes on heating, producing strong acids and bases, causing fire and explosion hazard. Liquid attacks some plastics and rubber. Attacks many metals.
Waste Disposal
Wastewaters may be subjected to biological treatment. Concentrations may be further reduced by ozone treatment. High concentration wastes may be destroyed in special waste incinerators.
