Limonene

Limonene is a colorless liquid aliphatic hydrocarbon classified as a cyclic monoterpene. It is a major component in the essential oils of citrus fruit peels and is commonly used in various industries due to its distinct fragrance and versatile properties. Limonene can be found naturally in a variety of plants, particularly citrus fruits, where it contributes to their characteristic scent.

Names and Chemical Information

Limonene is known by several other names, including:

• 1-Methyl-4-(prop-1-en-2-yl)cyclohex-1-ene
• 1-Methyl-4-(1-methylethenyl)cyclohexene
• 4-Isopropenyl-1-methylcyclohexene
• p-Menth-1,8-diene
• Dipentene (racemic form)

It is categorized as a chiral molecule, with the principal isomer, the (+)-enantiomer (commonly referred to as the (R)-isomer), being the most prevalent in nature, especially in citrus fruits. The chemical structure of limonene consists of a cyclohexene ring with a methyl group and a prop-1-en-2-yl group attached to it. Limonene has the molecular formula C10H16 and a molar mass of 136.238 g·mol−1.

Identifiers

Limonene is identified by various chemical databases:

• CAS Number: 138-86-3 (R/S), 5989-27-5 (R), 5989-54-8 (S)
• ChEBI: CHEBI:15384
• ChemSpider: 20939 (R/S), 388386 (S), 389747 (R)
• PubChem CID: 22311 (R/S), 439250 (S)
• KEGG: D00194

Physical Properties

Limonene is a colorless liquid with a characteristic orange odor, which makes it a favored component in fragrances. The physical properties of limonene include:

• Melting point: −74.35°C (−101.83°F)
• Boiling point: 176°C (349°F)
• Density: 0.8411 g/cm³
• Solubility: Insoluble in water but miscible with organic solvents such as benzene, chloroform, ether, and oils
• Refractive index (nD): 1.4727
• Chiral rotation: 87–102° (optical rotation)

Hazards

Limonene, while widely used, has associated health and safety concerns. It is a skin sensitizer and may cause contact dermatitis upon prolonged exposure. When inhaled or aspirated, it can cause serious respiratory issues, including pulmonary oedema and pneumonitis. It is classified as a flammable substance, and its vapors can ignite, with a flash point of 50°C (122°F). In addition, limonene is toxic to aquatic life, posing environmental risks if improperly disposed of. Safety precautions include proper handling and storage to avoid contact with skin and eyes, and using it in well-ventilated areas to reduce inhalation risks.

Occurrence in Nature

Limonene is found predominantly in citrus fruit peels, where it contributes to the distinctive aroma of orange, lemon, and lime peels. The compound is commonly extracted from the waste products of orange juice production, where it is a byproduct of the essential oils obtained from the peel. It is also present in a variety of other plants, including various coniferous and broadleaved trees, such as red maple, cottonwood, pine, and juniper. In these plants, limonene is a significant component of their resins and aromatic oils.

Limonene is found in the essential oils of numerous plants, including:

• Citrus fruits (oranges, lemons, limes)
• Conifer species such as pines, spruce, and fir
• Cannabis (Cannabis sativa)
• Juniper bush (Juniperus spp.)

In citrus fruits, limonene is most abundant in the peel and accounts for the majority of the fruit’s essential oil. To optimize the extraction and recovery of valuable compounds from citrus peel waste, limonene is often isolated and purified through steam distillation or centrifugal separation.

Chemical Reactions and Synthesis

Limonene is a stable monoterpene and can be distilled without decomposition under normal conditions. However, when subjected to elevated temperatures or reactive chemicals, it can undergo several chemical reactions. For example:

• At high temperatures, limonene may crack to form isoprene.
• Limonene easily oxidizes in moist air, producing compounds such as carveol, carvone, and limonene oxide.
• With sulfur, it undergoes dehydrogenation to form p-cymene.
• In the presence of mineral acid, limonene can isomerize into the conjugated diene α-terpinene.

In synthetic chemistry, limonene can be selectively reacted at its double bonds to form various products. For instance, it undergoes Markovnikov addition of trifluoroacetic acid followed by hydrolysis to form terpineol. Another important transformation of limonene is its conversion into carvone, a compound with significant industrial and culinary applications.

Biosynthesis

In nature, limonene is synthesized from geranyl pyrophosphate (GPP), an intermediate in the terpenoid biosynthesis pathway. This process involves cyclization of the neryl carbocation (or its equivalent) to form the characteristic cyclohexene ring structure of limonene. The final step in the biosynthesis involves the loss of a proton from the cation, resulting in the formation of the alkene group characteristic of limonene.

The biosynthesis pathway of limonene is as follows:

• Geranyl pyrophosphate → Neryl carbocation → Cyclization → Limonene

Uses of Limonene

Limonene has a wide range of applications in both industrial and consumer products. Some of its most common uses include:

Fragrance and Flavoring

The pleasant citrus odor of limonene makes it a popular ingredient in perfumes, bath products, and personal care items such as aftershave lotions. It is also used as a flavoring agent in food products to mask undesirable tastes, especially in medicines and food additives.

Cleaning Products

Due to its ability to dissolve oils, limonene is widely used in cleaning products, particularly in hand cleaners, adhesive removers, and industrial solvents. It is also used in paint removers and as a substitute for turpentine, which is commonly used in the art and painting industries.

Pest Control

Limonene is effective as a botanical insecticide, used in organic herbicides and pest repellents. It is also incorporated into cleaning agents that are marketed as environmentally friendly alternatives to traditional chemical cleaners.

Solvent in 3D Printing

Limonene is used as a solvent in fused filament fabrication (FFF) 3D printing, especially for dissolving supports made from high impact polystyrene (HIPS). This makes it a useful solvent for post-processing printed objects, especially when support structures need to be removed easily.

Histological Use

In histology and pathology, D-limonene is commonly used as a less toxic alternative to xylene for clearing dehydrated specimens during tissue preparation for microscopic analysis.

Safety and Toxicology

While limonene is generally considered safe for use in food and cosmetics, it may cause contact dermatitis when applied to the skin, especially in individuals with sensitive skin. Prolonged exposure to limonene vapors may also irritate the respiratory system. Inhalation of large quantities of limonene can cause dizziness and nausea. As a flammable substance, proper safety measures should be followed to avoid accidents, especially when handling it in bulk quantities.

Limonene is considered to be toxic to aquatic life, and disposal of limonene-containing products should follow appropriate environmental safety guidelines to prevent contamination.

Cancer Research

There is currently no evidence to suggest that limonene, when consumed in moderate amounts as part of citrus fruit or citrus-derived products, has any significant effect on the onset or progression of cancer. Studies on limonene supplementation have shown no consistent evidence of a cancer-fighting benefit, although some studies suggest potential therapeutic effects in certain contexts.

Chemical Properties and Reactions

Limonene is a relatively stable monoterpene, making it suitable for various applications in the chemical and industrial sectors. Despite its stability, it can undergo several chemical reactions, which are vital for its commercial and scientific utility. Understanding the chemical properties of limonene allows for its use in synthetic chemistry, flavoring, and even pharmaceutical formulations.

Chemical Structure

The chemical structure of limonene is based on a cyclohexene ring with a methyl group and a prop-1-en-2-yl group attached to it. It is classified as a cyclic monoterpene, which means that it is formed from two isoprene units, each containing five carbon atoms, joined to form a ten-carbon ring structure.

The compound exists as two enantiomers: the (+)-limonene, also known as (R)-limonene, and the (−)-limonene, or (S)-limonene. These two isomers have distinct odorous characteristics and exhibit different properties in both their biological and chemical reactions.

Oxidation Reactions

Limonene is highly susceptible to oxidation in the presence of moisture and air. This chemical reaction results in the formation of various oxidation products, including:

• Carveol – A compound with a minty aroma, which is often produced as a secondary oxidation product of limonene.
• Carvone – A ketone compound with a characteristic minty scent, widely used in flavoring and fragrance applications.
• Limonene oxide – A highly reactive compound that plays an essential role in the formation of other derivatives like carvone.

The oxidation of limonene occurs readily when exposed to oxygen, especially in moist environments, contributing to the aroma changes in citrus peels and oils.

Dehydrogenation and Isomerization

Limonene can also undergo dehydrogenation reactions. When heated with sulfur or exposed to other suitable catalysts, limonene can lose hydrogen atoms to form other compounds, including p-cymene. This reaction is significant in the chemical industry, where p-cymene is used in the production of chemicals such as phenol and acetone.

Limonene is also known to undergo isomerization when exposed to acids. Specifically, it can be converted into the conjugated diene α-terpinene, which is another important intermediate in the synthesis of valuable compounds. The conversion of limonene into α-terpinene is often a reversible process, allowing the compound to shift between different isomeric forms under various conditions.

Reactions with Hydrogen Halides

Limonene reacts with hydrogen chloride (HCl) in a Markovnikov addition reaction. This reaction involves the addition of a hydrogen atom to one end of the double bond and the halide to the other, resulting in the formation of a chloroalkyl group. The resulting product can then undergo hydrolysis to form products such as terpineol, which is another compound with aromatic and medicinal properties.

Epoxidation and Selective Reactions

Limonene is also susceptible to selective epoxidation. The compound reacts with mCPBA (meta-chloroperbenzoic acid), a common oxidizing agent, to form an epoxide at the trisubstituted carbon in its double bond. This reaction is a valuable tool for synthetic chemists looking to create new functionalized derivatives of limonene.

In another selective reaction, limonene can undergo a Diels–Alder reaction with maleic anhydride in the presence of heat or a catalyst, forming a cyclohexene derivative. This reaction exemplifies the reactivity of limonene in forming complex structures that have applications in various organic syntheses.

Thermochemistry and Combustion

Limonene is combustible, with a flash point of approximately 50°C (122°F). It is essential to handle limonene with care in industrial environments where it may come into contact with heat sources or open flames. Upon combustion, limonene produces carbon dioxide and water, releasing significant amounts of energy.

The standard enthalpy of combustion (ΔcH⦵298) for limonene is approximately −6.128 MJ/mol, indicating that the substance releases a considerable amount of energy when burned. This property makes limonene a potential candidate for biofuels, as discussed in the "Uses" section of this article.

Stability and Storage

Limonene is relatively stable under normal storage conditions but is highly reactive in the presence of heat, light, and oxygen. To ensure the preservation of its chemical integrity, limonene should be stored in tightly sealed containers away from direct sunlight and high temperatures. In industrial and commercial applications, limonene is typically stored in cool, dry conditions to prevent degradation and oxidation.

Synthetic Routes and Industrial Applications

Limonene is synthesized primarily through the extraction of citrus peel oils or by chemical synthesis from other terpenes. The principal industrial method for obtaining limonene involves distillation from citrus peel, a byproduct of orange juice and citrus oil production. In chemical laboratories and industrial applications, limonene can be synthesized via the cyclization of geranyl pyrophosphate (GPP), a precursor in terpenoid biosynthesis.

Limonene serves as a valuable precursor in the synthesis of numerous chemical compounds, including:

• Carvone – A ketone with distinctive mint and caraway aromas, used in flavorings and fragrances.
• Terpineol – An alcohol with floral, lilac-like characteristics, used in perfumes and cleaning products.
• p-Cymene – An aromatic hydrocarbon used in the synthesis of phenols and acetones.
• Limonene oxide – A versatile compound used in the formation of other derivatives.

Use in the Production of Biofuels

Due to its renewable nature, limonene is being explored as a potential biofuel. The use of limonene extracted from citrus peel oil as an alternative energy source aligns with the growing demand for sustainable, environmentally friendly fuel alternatives. Research into the combustion properties of limonene, coupled with its extraction as a byproduct of the citrus industry, positions it as a valuable contributor to biofuel technologies.

Uses of Limonene

Limonene is a versatile compound with a wide range of applications across multiple industries, including food and beverage, pharmaceuticals, cosmetics, cleaning products, and even as a potential biofuel. Its unique fragrance, derived from citrus peels, makes it highly valuable in the production of perfumes and fragrances, while its solvent properties make it an essential component in cleaning products.

Flavoring Agent and Fragrance

One of the primary uses of (+)-limonene is as a flavoring agent in the food industry. It is commonly used to enhance the flavor of food products, particularly those with citrus-based flavors. D-limonene is widely added to soft drinks, candies, and baked goods, providing a fresh, citrusy taste. Its pleasant fragrance also makes it a favored ingredient in many perfumes, aftershave lotions, and other personal care products. Due to its natural origin, limonene is often preferred over synthetic fragrances, contributing to its increasing use in the growing natural and organic product market.

• Essential oils – Limonene is a major component of citrus essential oils, which are widely used in aromatherapy and as ingredients in cosmetic formulations.
• Flavorings – In addition to citrus-flavored foods, limonene is used to mask undesirable tastes, especially in medicines and supplements, where its flavor helps balance the bitterness of active ingredients.

Solvent Properties and Industrial Applications

Limonene's solvent properties are another reason for its widespread industrial use. It is often employed as a solvent in cleaning products, where it dissolves oils and grease. Limonene is used in products such as adhesive removers, hand cleaners, and paint strippers. Its effectiveness as a natural solvent makes it an environmentally friendly alternative to more hazardous synthetic solvents, such as turpentine and other petroleum-based chemicals.

Limonene is also used as a solvent in some industrial applications, such as the manufacture of model airplane glues and as a cleaning agent in various manufacturing processes. The fact that limonene is derived from renewable citrus oils makes it a preferred choice in industries that prioritize sustainability and eco-friendliness.

• Paint strippers – Limonene is used in place of harsher chemicals like methylene chloride, which is toxic and dangerous.
• Cleaning agents – Limonene-based products are used in the cleaning industry to remove grease, oil, and adhesives.
• Adhesive removers – Limonene's ability to dissolve sticky substances makes it effective for use in adhesive removers.

Insecticide and Herbicide Use

In addition to its solvent properties, limonene also serves as a natural botanical insecticide. The compound is toxic to a wide range of insects, and it is often used in organic pest control products. Limonene-based insecticides are particularly attractive for gardeners and farmers looking for non-toxic alternatives to chemical pesticides. Due to its natural origin, it is considered safer for humans and animals compared to many conventional chemical pesticides.

Limonene is also employed in herbicides for organic farming. It is used to control weeds and unwanted vegetation without the need for harsh chemicals, making it a preferred option for environmentally conscious farming practices.

• Insecticides – Limonene-based insecticides are effective in controlling pests, especially in agriculture and home gardens.
• Herbicides – Limonene is used as an active ingredient in organic herbicides to manage unwanted vegetation.

Pharmaceutical and Medical Uses

Limonene has found applications in the pharmaceutical and medical industries, both for its therapeutic properties and as a delivery agent for other medications. It has been studied for its potential medicinal benefits, including anti-inflammatory, antioxidant, and anticancer effects.

Limonene is believed to have potential as a treatment for conditions such as indigestion, nausea, and anxiety. It has been included in various formulations designed to alleviate these conditions, often as part of natural remedy products.

• Aromatherapy – Limonene is used in aromatherapy for its calming effects, particularly in reducing stress and promoting relaxation.
• Anti-inflammatory – Due to its purported anti-inflammatory properties, limonene is sometimes used in topical creams and oils designed to reduce swelling and pain.

Additionally, limonene's solubility in oils and its ability to penetrate the skin make it useful in transdermal delivery systems, where it can carry other active pharmaceutical ingredients into the body.

Biodegradable Solvent and Cleaner

Limonene is a biodegradable substance, which makes it an ideal solvent in applications where environmental impact is a concern. Unlike many synthetic solvents, which can persist in the environment and cause pollution, limonene breaks down naturally, reducing its long-term environmental footprint. This makes it a popular ingredient in eco-friendly cleaning products, which are in high demand due to growing consumer awareness of environmental issues.

Limonene-based cleaning agents are becoming more popular in households and businesses as people seek alternatives to harsh chemical cleaners. Its natural citrus scent also adds a pleasant fragrance to cleaning solutions, which enhances user experience.

Biofuel Potential

As a renewable resource, limonene has been investigated as a potential biofuel. Biofuels derived from limonene could offer a sustainable alternative to fossil fuels, contributing to a reduction in greenhouse gas emissions. Limonene’s combustion properties, along with its renewable source from citrus fruits, position it as a candidate for further research in biofuel production.

The use of limonene in biofuels also provides an innovative way to utilize the waste byproducts from the citrus industry. Instead of discarding the peel oils, which are typically a waste product of citrus juice production, these oils can be processed to extract limonene, which can then be used in biofuel applications. This contributes to reducing the waste produced by the citrus industry and can potentially create a circular economy.

Other Applications

In addition to the uses outlined above, limonene has other niche applications, including:

• 3D printing – Limonene is used as a solvent in the fused filament fabrication process for 3D printing, where it dissolves supports made of high impact polystyrene (HIPS).
• Histology – Limonene is used in histology as a safer alternative to xylene in tissue clearing procedures, making it useful in preparing tissue samples for microscopy.
• Stamp collectors – Limonene is used by stamp collectors to remove self-adhesive postage stamps from envelope paper, as its solvent properties help dissolve the adhesive without damaging the paper.

Safety Considerations

While limonene has a range of valuable uses, it is important to consider its potential hazards, particularly when used in industrial and pharmaceutical applications. Limonene is considered a skin sensitizer and may cause allergic reactions or contact dermatitis in some individuals. It is also flammable and should be handled with caution, especially in environments where heat or open flames are present.

Limonene should be stored in well-ventilated areas away from sources of ignition, and proper protective equipment should be worn when handling the compound in concentrated forms. Additionally, limonene is toxic to aquatic life, so care should be taken to prevent its release into water systems.

Toxicology and Regulatory Considerations

Regulatory bodies have evaluated limonene's safety for various applications. In the food and cosmetic industries, limonene is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration (FDA), provided it is used in appropriate concentrations. However, caution is advised for individuals with sensitive skin or those prone to allergic reactions.

In industrial settings, the Occupational Safety and Health Administration (OSHA) sets exposure limits for limonene to minimize risks related to inhalation or skin contact.

Cancer Research

There is no consistent evidence that limonene, either consumed in food or applied topically, has any significant impact on the onset or progression of cancer. While some studies have suggested a potential anticancer effect, these findings are not conclusive, and more research is needed. Health agencies, such as the National Cancer Institute (NCI), have stated that there is no reliable evidence to support the use of limonene as a cancer treatment.

Chemical Properties and Reactions

Limonene is a highly versatile compound with a variety of chemical properties that make it valuable in both natural and synthetic chemistry. As a cyclic monoterpene, limonene's chemical reactivity plays a significant role in its use in industry and its presence in biological processes. This chapter discusses the chemical characteristics, reactions, and transformations limonene undergoes.

Chemical Structure

Limonene is classified as a cyclic monoterpene with the chemical formula C10H16. It consists of a six-membered cyclohexene ring with one methyl group (-CH3) and a vinyl group (-CH=CH2) attached to the ring. The structure of limonene can exist in two enantiomeric forms: the (+)-limonene (R)-enantiomer and the (−)-limonene (S)-enantiomer.

The primary industrial source of limonene is the essential oil of citrus fruits, which predominantly contains the (+)-limonene (R) isomer. The two enantiomers of limonene, although chemically similar, exhibit distinct characteristics, with the (+)-form having a citrus scent and the (−)-form having a more turpentine-like odor.

The molecular structure of limonene allows it to undergo a wide range of chemical reactions, making it an important building block in chemical synthesis.

Chemical Reactions of Limonene

Limonene undergoes several important chemical reactions, which contribute to its uses in industrial and pharmaceutical applications. These reactions include oxidation, polymerization, and isomerization, among others.

Oxidation Reactions

Limonene readily undergoes oxidation in the presence of oxygen or air, forming various products, including carveol, carvone, and limonene oxide. This oxidation process is often initiated by moisture in the air, which triggers the formation of reactive oxygen species that interact with limonene.

• Carvone – One of the primary products of limonene oxidation, carvone has a distinctive odor, often described as minty or caraway-like. It is used in both the flavoring and fragrance industries.
• Limonene oxide – This compound is formed when limonene reacts with oxygen in air and is used in the production of specialty chemicals.

Thermal Decomposition

When heated to elevated temperatures, limonene undergoes cracking, a process in which it decomposes to form smaller molecules. This reaction produces isoprene, a compound that is a building block for various synthetic polymers such as rubber.

• Isoprene – Limonene can break down into isoprene at high temperatures, which is a key intermediate in the production of synthetic rubbers.

Electrophilic Addition Reactions

Limonene can also participate in electrophilic addition reactions, particularly with halogens and other reagents. For example, it can react with hydrogen chloride (HCl) in an addition reaction, resulting in the formation of chlorinated derivatives. This is often the first step in creating other chemical products, such as terpineol.

• Terpineol – By adding trifluoroacetic acid to limonene, a product known as terpineol is formed. This compound has a pleasant floral fragrance and is used in perfumes and as a solvent in various applications.

Diels-Alder Reactions

Limonene can participate in the Diels-Alder reaction, a chemical reaction that forms a six-membered ring from two reactants. In the case of limonene, it can react with maleic anhydride to form Diels–Alder adducts, demonstrating its potential for use in organic synthesis.

• Diels-Alder reaction – This reaction between limonene and maleic anhydride leads to the formation of a cyclic compound, which has applications in the synthesis of complex organic molecules.

Isomerization Reactions

Limonene undergoes isomerization, a process where the compound’s structure is rearranged without changing its molecular formula. One of the most important isomerization reactions is the conversion of limonene into α-terpinene, a conjugated diene that can further react with other chemicals.

• α-Terpinene – This conjugated diene is formed when limonene is heated in the presence of acid. It is a key intermediate in the production of other chemicals, such as p-cymene.

Polymerization Reactions

Limonene is used in the synthesis of various polymer materials. Through a process known as radical polymerization, limonene can be polymerized to form polylimonene, a synthetic polymer with applications in the creation of biodegradable plastics.

• Polylimonene – Polylimonene is a polymer that can be produced from limonene monomers. It is biodegradable, making it a promising material for eco-friendly plastic alternatives.

Reaction with Sulfur

Limonene also reacts with sulfur to undergo dehydrogenation, a reaction that produces p-cymene. This reaction is important in the production of aromatics used in the fragrance and chemical industries.

• p-Cymene – This aromatic compound is formed when limonene reacts with sulfur. p-Cymene is used in the synthesis of other chemicals and as a fragrance in perfumes and cleaning products.

Biosynthesis of Limonene

Limonene is synthesized in plants via the biosynthesis of the terpene pathway. The precursor to limonene is geranyl pyrophosphate, a molecule derived from the mevalonate pathway and isoprenoid biosynthesis. The biosynthesis of limonene involves a cyclization reaction, where the geranyl pyrophosphate molecule undergoes a rearrangement to form a neryl carbocation. This carbocation then undergoes further steps to form limonene.

The detailed biosynthesis of limonene from geranyl pyrophosphate is as follows:

1. The enzyme limonene synthase catalyzes the formation of limonene by cyclizing geranyl pyrophosphate. 2. The cyclization results in the formation of a cationic intermediate, which loses a proton to produce the final limonene product.

Enzyme-Driven Biosynthesis

The enzyme limonene synthase is essential in the final step of limonene production, converting geranyl pyrophosphate into limonene by facilitating the rearrangement and loss of a proton from the intermediate cation. This biosynthetic pathway is common in citrus fruits, where limonene is a primary component of essential oils.

Reactions Summary

Limonene is a versatile compound with a variety of chemical reactivities that allow it to be used in industrial, pharmaceutical, and chemical synthesis applications. The most common reactions include:

• Oxidation – Producing carveol, carvone, and limonene oxide.
• Thermal decomposition – Leading to the production of isoprene.
• Electrophilic addition – Forming products such as terpineol.
• Diels-Alder – Reacting with maleic anhydride to form cyclic compounds.
• Isomerization – Leading to the formation of α-terpinene.
• Polymerization – Producing polylimonene for biodegradable plastics.
• Dehydrogenation – Producing p-cymene.

See Also

• Monoterpenes
• Cyclic compounds
• Biosynthesis
• Geranyl pyrophosphate
• Terpene biosynthesis
• Diels-Alder reaction
• Limonene synthase
• Carvone
• p-Cymene
• Isoprene