| | p-Cresol Chemical Properties |
| Melting point | 32-34 °C(lit.) | | Boiling point | 202 °C(lit.) | | density | 1.034 g/mL at 25 °C(lit.) | | vapor density | 3.72 (vs air) | | vapor pressure | 1 mm Hg ( 20 °C) | | refractive index | nD20 1.5395 | | FEMA | 2337 | P-CRESOL | | Fp | 193 °F | | storage temp. | Store below +30°C. | | solubility | 20g/l | | pka | 10.17(at 25℃) | | form | Crystalline Solid or Liquid | | color | Colorless to light yellow, may darken on exposure to light | | Specific Gravity | 1.0341 (20/4℃) | | Odor | at 0.10 % in dipropylene glycol. phenolic narcissus animal mimosa | | Odor Threshold | 0.000054ppm | | Odor Type | phenolic | | explosive limit | 1%(V) | | Water Solubility | 20 g/L (20 ºC) | | Sensitive | Light Sensitive | | Merck | 14,2579 | | JECFA Number | 693 | | BRN | 1305151 | | Henry's Law Constant | 6.17 at 20.00 °C, 9.31 at 25.00 °C (dynamic equilibrium system-GC, Feigenbrugel et al., 2004a) | | Exposure limits | NIOSH REL: TWA 2.3 ppm (10 mg/m3), IDLH 250 ppm; OSHA PEL: TWA 5
ppm (22 mg/m3); ACGIH TLV: TWA for all isomers 5 ppm (adopted). | | Stability: | Stable. Combustible. Incompatible with strong oxidizing agents. Air and light-sensitive. Hygroscopic. | | LogP | 1.94 | | CAS DataBase Reference | 106-44-5(CAS DataBase Reference) | | NIST Chemistry Reference | Phenol, 4-methyl-(106-44-5) | | EPA Substance Registry System | p-Cresol (106-44-5) |
| | p-Cresol Usage And Synthesis |
| 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 | 1. The mother liquor of using the para, m-cresol mixture for the extraction of m-cresol can be subject to recrystallization using oxalic acid addition method. 2. Toluene and sulfuric acid can be subject to sulfonation and neutralization to generate sodium p-toluenesulfonate followed by alkali melting, acidification and distillation to get the finished product p-cresol. In order to obtain high purity p-cresol, there are two processes: (1) the distilled p-cresol is subject to further crystallization and separation; (2) the p-toluenesulfonic acid after sulfonation is further subject to cooling, crystallization, filtration, and then neutralization, alkali melting, acidification and distillation to derive the products.
The Nanjing Jinyan Chemical Corporation has developed mature sulfonated alkali melting technology, being able to produce high purity p-cresol. With changing the process conditions, the same device can also enable the production of m-cresol, o-cresol, phenol, and naphthol.
There are several preparation methods as follows.
(1) Toluene sulfonation alkali melting method
The sulfonation reaction is carried out at 110-130 °C using toluene as raw material to produce intermediate toluene sulfonic acid. After neutralization, it further has alkali melting reaction with the molten sodium hydroxide at 340-365 °C to obtain Cresol sodium which further converts to crude cresol after the acidification, followed by distillation for separation of o-cresol and phenol, to get the mixed p-, m-cresol with p-cresol being the major part. The composition of isomers in cresol was determined by the temperature, the type of sulfonating agent and the ratio of toluene to sulfonating agent. Nanjing Jinyan Chemical Corporation can produce high purity p-cresol by sulfonation alkali fusion. Commonly used sulfonating agents also include fuming sulfuric acid and chlorosulfonic acid.
Preparation of p-cresol by toluene sulfonation is the earliest industrial process, this method is more mature, but need to consume a lot of acid, alkali, equipment corrosion problems. This method is currently still the main method of production of p-cresol.
The mother liquor of p-, m-cresol mixture after extraction of m-cresol can be subject to recrystallization using oxalic acid addition method. For example, the urea can be heated together with the filtered toluene solution to 95~100 ° C. Further add under stirring of oxalic acid for reaction of 2~3h, and then cooled at room temperature for about 16h, with vacuum filtration to obtain the white crystals, namely the p-cresol oxalic acid complex. The complex was decomposed with hot water. The supernatant oil layer was firstly distilled to toluene and steamed, followed by cutting the 93-104 ° C fraction at 0.094 MPa to obtain the p-cresol with a purity of 95%.
(2) p-toluidine diazo hydrolysis method
P-toluidine can react with sulfuric acid to form p-toluidine sulfate, further subject to sodium nitrite diazotization at 0~5 ℃. The diazonium salt is put into the dilute sulfuric acid for heating hydrolysis and the oil product is further separated out by the steam. The oil layer is further added into the 1% sodium hydroxide, followed by decolorization filtering. Add concentrated sulfuric acid to pH = 1, and then separate out the water layer, add zinc powder and sulfuric acid, and then neutralize to neutral with sodium carbonate; separate the oil product; wash, and then apply vacuum distillation to get the finished product.
(3) Separation of kerosene derived
Apply sulfuric acid for the sulfonation of toluene to obtain p-toluenesulfonic acid, followed by cooling, crystallization, filtration, and then addition of sodium sulfite for neutralization to obtain the sodium p-toluene sulfonate, with further sulfide acidification to derive the final product which is finally subject to distillation and crystallization separation. | | 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). | | Usage limit | FEMA (mg/kg): soft drinks 0.67; cold drinks 0.01 to 1.0; candies and baked goods 0.01 to 2.0. | | Chemical Properties | Colorless to pink crystals with a phenolic odor. Odor threshold concentration in water is 55 ppb
(Buttery et al., 1988). An experimentally determined odor threshold concentration of 1 ppbv was
reported by Leonardos et al. (1969) which exceeds the odor threshold concentration of 0.054 ppbv
reported by Nagata and Takeuchi (1990). | | Chemical Properties | Cresol is a mixture of the three isomeric cresols, o-, m-, and p-cresol. Cresols are slightly soluble in water. m-Isomer: Colorless or yellow liquid with characteristic odor. | | Chemical Properties | p-Cresol has a characteristics phenol-like odor. | | Physical properties | Colorless to pink crystals with a phenolic odor. Odor threshold concentration in water is 55 ppb
(Buttery et al., 1988). An experimentally determined odor threshold concentration of 1 ppbv was
reported by Leonardos et al. (1969) which exceeds the odor threshold concentration of 0.054 ppbv
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 | Intermediates of Liquid Crystals | | Uses | p-Cresol is used in the synthesis of Bupranolol (B689650), a non-selective beta blocker. | | Uses | For making synthetic resins; in disinfectants and fumigants; as industrial solvent; m-cresol in photographic developers, explosives. | | Definition | ChEBI: 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. | | 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. | | Aroma threshold values | Detection: 55 to 100 ppb. | | Synthesis Reference(s) | Journal of the American Chemical Society, 81, p. 4230, 1959 DOI: 10.1021/ja01525a028
Chemical and Pharmaceutical Bulletin, 31, p. 749, 1983 DOI: 10.1248/cpb.31.749
Tetrahedron Letters, 21, p. 3731, 1980 DOI: 10.1016/0040-4039(80)80164-X | | 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. | | Hazard | Questionable carcinogen. | | 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. | | Flammability and Explosibility | Notclassified | | 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). | | Environmental fate | Biological. Protocatechuic acid (3,4-dihydroxybenzoic acid) is the central metabolite in the
bacterial degradation of 4-methylphenol. Intermediate by-products include 4-hydroxybenzyl
alcohol, 4-hydroxybenzaldehyde, and 4-hydroxybenzoic acid. In addition, 4-methylphenol may
undergo hydroxylation to form 4-methylcatechol (Chapman, 1972). Chloroperoxidase, a fungal
enzyme isolated from Caldariomyces fumago, reacted with 4-methylphenol forming 4-methyl-2-
chlorophenol (Wannstedt et al., 1990). Under methanogenic conditions, inocula from a municipal sewage treatment plant digester degraded 4-methylphenol to phenol prior to being mineralized to
carbon dioxide and methane (Young and Rivera, 1985).
Photolytic. Photooxidation products reported include 2,2′-dihydroxy-4,4′-dimethylbiphenyl, 2-
hydroxy-3,4′-dimethylbiphenyl ether, and 4-methylcatechol (Smith et al., 1978). Anticipated
products from the reaction of 4-methylphenol with ozone or OH radicals in the atmosphere are
hydroxynitrotoluene and ring cleavage compounds (Cupitt, 1980). Absorbs UV light at a
maximum wavelength of 278 nm (Dohnal and Fenclová, 1995).
Chemical/Physical. Kanno et al. (1982) studied the aqueous reaction of 4-methylphenol and
other substituted aromatic hydrocarbons (toluidine, 1-naphthylamine, phenol, 2- and 3-
methylphenol, pyrocatechol, resorcinol, hydroquinone, and 1-naphthol) with hypochlorous acid in
the presence of ammonium ion. They reported that the aromatic ring was not chlorinated as
expected but was cleaved by chloramine forming cyanogen chloride. The amount of cyanogen
chloride formed was increased as the pH was lowered (Kanno et al., 1982). | | 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. |
| | p-Cresol Preparation Products And Raw materials |
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