Description
p-Cymene is a naturally occurring compound, although it has two further geometric isomers, m-cymene (with meta-substituted alkyl groups) and o-cymene (with ortho-substituted alkyl groups) which do not occur naturally. p-Cymene is related to the monoterpenes. Monoterpenes themselves belong to the “terpenes”, a larger class of organic compounds, which are the most representative components of essential oils. chemical structure of p-cymene, indicating the benzene ring with methyl and isopropyl substitutions.
chemical structure of p-cymene
Chemical Properties
p-Cymene has a citrusy aroma reminiscent of lemon. It is colorless liquid with a strong, characteristic odor reminiscent of carrot. It tends to darken with aging. It occurs naturally in orange peel oil, mandarin peel oil, satsuma mandarin peel oil, coldpressed lime peel oil, distilled lime peel oil, cinnamon leaf, etc. 4-isopropyltoluene has antimicrobial properties. It is used as a flavor ingredient permitted for direct addition to food for human consumption.
Uses
p-Cymene is an alkyl aromatic hydrocarbon mainly used to study oxidation reactions under various conditions to synthesize highly valuable intermediates and building-blocks such as cymene hydroperoxide, 4-methyl acetophenone, 4-isopropyl benzyl alcohol, 4-isopropyl benzaldehyde and 4-isopropyl benzoic acid etc.
Medicinally, p-cymene is used to prevent coughs and eliminate phlegm as well as being a flavouring agent, and being used in the production of fungicides and pesticides. It is considered to be “generally recognised as safe” (GRAS) by the U.S. Food and Drug Administration. Its potential in the prevention of protein glycation mediated diabetic complications has also been confirmed, and it has been suggested as an in vivo antioxidant compound due to its ability to reduce the formation of oxygen and nitrogen reactive species, acting as a potential neuroprotective agent in the brain. Therefore, it could be involved in the treatment of oxidative stress related diseases.
Production Methods
p-cymene is conventionally produced by the Friedel-Crafts alkylation of toluene with isopropanol, or of benzene with methyl or isopropyl halides.
References
[1] George A. Burdock, Encyclopedia of Food and Color Additives, Volume 1, 1996
[2] C.F. Bagamboula, M. Uyttendaele and J. Debevere, Inhibitory effect of thyme and basil essential oils, carvacrol, thymol, estragol, linalool and p-cymene towards Shigella sonnei and S. flexneri, Food Microbiology, 2004, vol. 21, 33-42
Chemical Properties
p-Cymene is a monoterpene that is found in a variety of plants, including C. sativa, and has diverse biological activities, including antimicrobial, anticancer, antioxidant, anti-inflammatory, antinociceptive, and anxiolytic properties.p-Cymene inhibits the growth of S. typhimurium, E. coli, L. monocytogenes, S. epidermidis, and S. aureus with MIC values ranging from 0.266 to 0.608% v/v.It decreases the invasive activity of HT-1080 human fibrosarcoma cells in vitro by 87% when used at a concentration of 600 μM.In mouse hippocampus, p-Cymene (50 mg/kg, i.p.) reduces lipid peroxidation and nitrite content by 65.5 and 71.2%, respectively, and increases superoxide dismutase (SOD) and catalase activities by 22.7 and 119.3%, respectively, compared to vehicle control animals.Formulations containing p-cymene have been used as flavoring agents.
Occurrence
Widespread in nature; reported in the oils of cypress, Artemisia cina Bg., Ceylon cinnamon, boldo leaf, cascarilla,
Cuminum cyminum L. and lemon; in the oils for seeds of coriander and Cicuta virosa; in the ether-extracted oils of Monarda
fisulosa and Monarda puncata; in the star anise and nutmeg essential oils. Note that p-cymene reported in essential oil may be
formed from the conversion of a cyclic terpene; its presence is indicative of aging in lemon essential oil. Reported found in citrus
juices and peel oils, guava, papaya, black currant, pineapple, blueberry, blackberry, carrot, tomato, celery seed, cumin seed, mace,
ginger, coriander seed, anise, nutmeg, mace, parsley, cardamom, cinnamon root and bark, pepper, peppermint oil, spearmint oil,
cassia leaf and Thymus vulgaris.
Uses
It is used in heat-exchange media, metal polishes, and thinners for lacquers/varnishes. Also used to make para-cresol, carvacrol, and synthetic resins. It is also used as a component of commercial terpene solvent mixtures.
Uses
As a diluent for lacquers, varnishes,
and dyes; in the production of resins; as a component
of fragrances; also found as a byproduct
in the manufacture of sulfite paper
pulp
Definition
ChEBI: A monoterpene that is toluene substituted by an isopropyl group at position 4.
Preparation
Obtained chiefly from the wash water of sulfite paper.
Aroma threshold values
Aroma characteristics at 1% EtoH: harsh chemical, woody and terpy-like with an oxidized citrus lemon
note. It has spicy nuances reminiscent of cumin, oregano and cilantro
Taste threshold values
Taste characteristics at 1 to 10 ppm: terpy and rancid with slightly woody, oxidized citrus notes. It has spice
nuances of green pepper and oregano.
Synthesis Reference(s)
Journal of the American Chemical Society, 95, p. 982, 1973
DOI: 10.1021/ja00784a090
General Description
Colorless liquid with a mild pleasant odor. Floats on water.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Vigorous reactions, sometimes amounting to explosions, can result from the contact between aromatic hydrocarbons, such as CYMENE, and strong oxidizing agents. They can react exothermically with bases and with diazo compounds. Substitution at the benzene nucleus occurs by halogenation (acid catalyst), nitration, sulfonation, and the Friedel-Crafts reaction.
Health Hazard
Inhalation causes impairment of coordination, headache. Contact with liquid causes mild irritation of eyes and skin. Ingestion causes irritation of mouth and stomach.
Fire Hazard
HIGHLY FLAMMABLE: Will be easily ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapor explosion hazard indoors, outdoors or in sewers. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water.
Flammability and Explosibility
Flammable
Chemical Reactivity
Reactivity with Water: No reaction; Reactivity with Common Materials: No reaction; Stability During Transport: Stable; Neutralizing Agents for Acids and Caustics: Not pertinent; Polymerization: Not pertinent; Inhibitor of Polymerization: Not pertinent.
Safety Profile
Mildly toxic by
ingestion. Humans sustain central nervous
system effects at low doses. A skin irritant.
Flammable liquid. Explosion Hazard:
Slight in the form of vapor. To fight fire,
use foam, CO2, dry chemical. When heated
to decomposition it emits acrid smoke and
fumes.
Metabolism
In this compound both an isopropyl and a methyl group occur together and the available evidence shows that only the methyl group is oxidized, cumic acid (pisopropylbenzoic acid) and its conjugate (cuminuric acid) being the main metabolites in dogs and in sheep (Williams, 1959). Following inhalation, only a small part is excreted unchanged, the remainder being oxidized to water-soluble metabolites. As early as 1873, Ziegler suggested that the readily oxidized propyl side-chain formed a -COO H group (Browning, 1965): The ultimate product in the case of dogs and sheep is cumic acid, which is probably excreted as a conjugate with glycine (Gerarde, 1960).
Purification Methods
Wash p-cymene with cold, conc H2SO4 until there is no further colour change, then repeatedly with H2O, 10% aqueous Na2CO3 and H2O again. Dry it over Na2SO4, CaCl2 or MgSO4, and distil it. Further purification steps include steam distillation from 3% NaOH, percolation through silica gel or activated alumina, and a preliminary reflux for several days over powdered sulfur. Store it over CaH2. [Beilstein 5 IV 1060.]
