5989-54-8

Usage

Uses

Used in Clinical Applications:
(S)-(-)-Limonene is used as a cholesterol solvent for dissolving cholesterol-containing gallstones. It also aids in relieving heartburn and gastroesophageal reflux disorder (GERD) due to its gastric acid neutralizing properties and support for normal peristalsis. Additionally, it has chemo-preventive activity against various types of cancers, as demonstrated in phase 1 clinical trials for breast and colorectal cancer patients. Furthermore, it is used to maintain regular bowel movements, particularly in cases caused by Candida albicans infection, and as a mild appetite suppressant to help manage weight, especially in individuals with unhealthy blood sugar levels.
Used in Personal Care:
(S)-(-)-Limonene serves as a flavoring agent to mask the bitter taste of alkaloids and as a fragrance in perfumery. It is also used in bath products, aftershave lotions, and other personal care products. (S)-(-)-LIMONENE is commonly added to cleaning products, such as hand wash solutions, to provide an orange or lemon fragrance.
Used in the Food Industry:
(S)-(-)-Limonene is utilized as a fragrance and flavoring agent in the manufacture of foods, chewing gums, and beverages.
Used in Agricultural Applications:
(S)-(-)-Limonene is employed as a botanical insecticide and is also a component of the organic herbicide "Aenger."
Used in Industrial Purposes:
As a natural product derived from citrus oil and byproducts during orange juice manufacturing, (S)-(-)-Limonene is used as a solvent for cleaning purposes, such as removing oil from machine parts. It is also used as a paint stripper, an alternative fragrance to turpentine, a solvent in glues and paints for some airplane models, and in commercial air fresheners. Additionally, it is used to remove self-adhesive postage stamps from envelopes by philatelists and has been considered as a biofuel due to its combustibility.
Used in Printing:
(S)-(-)-Limonene is used as a solvent for filament in 3D printing, allowing printers to erect binders and supports from HIPS, a polystyrene plastic that can easily dissolve in (S)-(-)-Limonene.
Used in Therapeutic Applications:
(S)-(-)-Limonene possesses therapeutic properties such as antimicrobial, antianaemic, antiseptic, and anti-sclerotic. It also has carminative, bactericidal, depurative, cicatrizant, diuretic, rubefacient, hyposensitive, vermifuge, and tonic characteristics.
Used in Histology:
Due to its less toxic nature compared to xylene, (S)-(-)-Limonene is often used in preparing tissues, particularly when cleaning dehydrated specimens, for histology.
Other Applications:
(S)-(-)-Limonene is also used for treating wounds and sores, in aromatherapy, douching, cataract treatment, mouth ulcers, varicose veins, and spots. Furthermore, it is used to inhibit the proliferation of colon cancer cells and in the production of artificial essential oils, such as (+)-carvone. It is an active component of turpentine and finds application as a solvent and wetting agent, as well as in the production of resins.

Chemical Composition and Reactions

The main D-Limonene’s compositions include camphene, a-pinene, a-terpene, b-pinene, b-bisabolene, trans-a-bergamotene, limonene, neral, and nerol. It chemically belongs to the family of cycloalkane known as terpenes. Notably, its IUPAC name is 4-isopropeny–1–methylcyclohexane. D-limonene can be distilled without decomposing and is a typically stable monoterpene, but can crack in high temperatures to form isoprene. D-limonene oxidizes easily in moist air to generate limonene oxide, carvone, and carveol. It dehydrates when reacted with Sulphur to form p-cymene. D-limonene isomerizes to conjugated diene α-terpinene when heated with mineral acid.

Safety and Side Effects

D-limonene is considered to have low toxicity; therefore, does not pose a carcinogenic, mutagenic, or nephrotoxic risk to humans. In proportional food amounts, d-limonene is safe. When taken orally for up to one year in correct medical amounts, d-limonene appears safe for most people. However, there is no enough information or research regarding the effect of d-limonene on pregnant and breast feeding women when taken in larger medical amounts. As such, it is vital to stay on the safer side until more research is done.

Dosing

The correct dosage for d-limonene is dependent on numerous factors, such as user’s health, age, as well as other conditions.

Flammability and Explosibility

Flammable

Contact allergens

Limonene is a racemic form of dand l-limonene. d-Limonene is contained in Citrus species such as citrus, orange, mandarin, and bergamot. l-Limonene is contained in Pinus pinea.

Safety Profile

A skin irritant. When heated to decomposition it emits acrid smoke and irritating fumes.

InChI:InChI=1/C10H16/c1-8(2)10-6-4-9(3)5-7-10/h4,10H,1,5-7H2,2-3H3

Upstream product

• 7785-26-4 (-)-α-pinene 
• 18172-67-3 beta-pinene 
• 80-26-2 (4S)-(-)-α-terpinyl acetate 
• 22567-21-1 (1S,2S,5S)-5-isopropenyl-2-methylcyclohexan-1-ol 
• 85-52-9 2-Benzoylbenzoic acid 
• 77287-34-4 formamide 
• 16789-26-7 (±)-linalyl diphosphate 
• 763-10-0 geranyl diphosphate 
• 7785-26-4 2,6,6-trimethylbicyclo[3.1.1]hept-2-ene 
• 97150-55-5 linalyl diphosphate 
• 130814-75-4 (-)-{1-(R)-[(1E)-2-methylbuta-1,3-dienyloxy]ethyl}benzene 
• 78-79-5 isoprene 
• 136476-14-7 [(S)-2,2-Dimethyl-1-((E)-2-methyl-buta-1,3-dienyloxy)-propyl]-benzene 
• 175522-76-6 [(R)-2,2-Dimethyl-1-((E)-2-methyl-buta-1,3-dienyloxy)-propyl]-benzene 

Downstream Products

• 856187-11-6 p-mentha-6,8-dien-2-yl-succinic acid 
• 138-86-3 limonene. 
• 96-08-2 (4S)-1-methyl-4-(2-methyloxiran-2-yl)-7-oxabicyclo[4.1.0]-heptane 
• 499-94-5 (S)-carvomenthene 
• 82470-90-4 2-Bromo-4-isopropenyl-1-methoxy-1-methyl-cyclohexane 
• 105631-52-5 Trimethyl-[2-((S)-4-methyl-cyclohex-3-enyl)-allyl]-silane 
• 79466-78-7 4,5-dihydro-5-(4-methyl-3-cyclohexenyl)-3-(phenylsulfonyl)isoxazole 
• 99-49-0 Carvone 
• 1195-32-0 1-methyl-4-isopropenylbenzene 
• 308363-12-4 L-carveol 
• 18031-40-8 (S)-(-)-perillaldehyde 
• 61585-35-1 p-menth-1-ene 
• 1678-82-6 trans-1,4-menthane 
• 6069-98-3 cis-1-isopropyl-4-methyl-cyclohexane 

Relevant academic research and scientific papers

Electro-mediated PhotoRedox Catalysis for Selective C(sp3)–O Cleavages of Phosphinated Alcohols to Carbanions

We report a novel example of electro-mediated photoredox catalysis (e-PRC) in the reductive cleavage of C(sp3)?O bonds of phosphinated alcohols to alkyl carbanions. As well as deoxygenations, olefinations are reported which are E-selective and can be made Z-selective in a tandem reduction/photosensitization process where both steps are photoelectrochemically promoted. Spectroscopy, computation, and catalyst structural variations reveal that our new naphthalene monoimide-type catalyst allows for an intimate dispersive precomplexation of its radical anion form with the phosphinate substrate, facilitating a reactivity-determining C(sp3)?O cleavage. Surprisingly and in contrast to previously reported photoexcited radical anion chemistries, our conditions tolerate aryl chlorides/bromides and do not give rise to Birch-type reductions.

Enantioselective Tail-to-Head Cyclizations Catalyzed by Dual-Hydrogen-Bond Donors

Chiral urea derivatives are shown to catalyze enantioselective tail-to-head cyclization reactions of neryl chloride analogues. Experimental data are consistent with a mechanism in which ?-participation by the nucleophilic olefin facilitates chloride ionization and thereby circumvents simple elimination pathways. Kinetic and computational studies support a cooperative mode of catalysis wherein two molecules of the urea catalyst engage the substrate and induce enantioselectivity through selective transition state stabilization.

Upcycling a plastic cup: One-pot synthesis of lactate containing metal organic frameworks from polylactic acid

Waste PLA can be upcycled to metal organic frameworks of potential high value in a one-pot synthesis scheme, where PLA depolymerisation occurs in situ. Three homochiral lactate based frameworks were successfully synthesised and characterised from PLA as a feed source, including ZnBLD. The chiral separation ability of ZnBLD was maintained.

Converting S-limonene synthase to pinene or phellandrene synthases reveals the plasticity of the active site

S-limonene synthase is a model monoterpene synthase that cyclizes geranyl pyrophosphate (GPP) to form S-limonene. It is a relatively specific enzyme as the majority of its products are composed of limonene. In this study, we converted it to pinene or phellandrene synthases after introducing N345A/L423A/S454A or N345I mutations. Further studies on N345 suggest the polarity of this residue plays a critical role in limonene production by stabilizing the terpinyl cation intermediate. If it is mutated to a non-polar residue, further cyclization or hydride shifts occurs so the carbocation migrates towards the pyrophosphate, leading to the production of pinene or phellandrene. On the other hand, mutant enzymes that still possess a polar residue at this position produce limonene as the major product. N345 is not the only polar residue that may stabilize the terpinyl cation because it is not strictly conserved among limonene synthases across species and there are also several other polar residues in this area. These residues could form a “polar pocket” that may collectively play this stabilizing role. Our study provides important insights into the catalytic mechanism of limonene synthases. Furthermore, it also has wider implications on the evolution of terpene synthases.

Photocatalytic Transfer Hydrogenolysis of Allylic Alcohols on Pd/TiO2: A Shortcut to (S)-(+)-Lavandulol

We report herein a regio- and stereoselective photocatalytic hydrogenolysis of allylic alcohols to form unsaturated hydrocarbons employing a palladium(II)-loaded titanium oxide; the reaction proceeds at room temperature under light irradiation without stoichiometric generation of salt wastes. Olefin and saturated alcohol moieties tolerated the reaction conditions. Hydrogen atoms were selectively incorporated into less sterically congested carbons of the allylic functionalities. This protocol allowed a short-step synthesis of (S)-(+)-lavandulol from (R)-(?)-carvone by avoiding otherwise necessary protection/deprotection steps.

Isotope sensitive branching and kinetic isotope effects to analyse multiproduct terpenoid synthases from Zea mays

Multiproduct terpene synthases TPS4-B73 and TPS5-Delprim from Zea mays exhibit isotopically sensitive branching in the formation of mono- and sesquiterpene volatiles. The impact of the kinetic isotope effects and the stabilization of the reactive intermediates by hyperconjugation along with the shift of products from alkenes to alcohols are discussed.

Metal-organic framework Co(D-cam)1/2(bdc)1/2(tmdpy) for improved enantioseparations on a chiral cyclodextrin stationary phase in gas chromatography

Initial efforts to combine a chiral metal-organic framework (MOF), Co(D-Cam)1/2(bdc)1/2(tmdpy) (D-Cam=D-camphoric acid, bdc=1,4-benzenedicarboxylic acid, tmdpy=4,4′-trimethylenedipyridine), with peramylated β-cyclodextrins to investigate whether the use of a MOF can enhance enantioseparations on a cyclodextrin stationary phase are reported. Compared with columns of peramylated β-cyclodextrin incorporated in a MOF containing sodium chloride, the column of peramylated β-cyclodextrin+MOF shows excellent selectivity for the recognition of racemates, and higher resolutions are achieved on the peramylated β-cyclodextrin+MOF stationary phase. Experimental results indicate that the use of Co(D-Cam) 1/2(bdc)1/2(tmdpy) can improve enantioseparations on peramylated β-cyclodextrins. This is the first report that chiral MOFs can improve enantioseparations on a chiral stationary phase for chromatography. Copyright

Oxidation of α-pinene by atmospheric oxygen in the supercritical CO2-ethyl acetate system in the presence of Co(II) complexes

The reactivity of monoterpene α-pinene in a flow reactor in the presence of cobalt catalyst in a complex supercritical solvent consisting of CO2 and ethyl acetate is studied over the temperature range of 190-320°C and a pressure range of 110-125 atm. It was found that the main isomerization products include compounds with bicyclo[2.2.1]heptane and p-menthane backbones; the reaction is accompanied by partial racemization. The formation of oxidation products is observed in the presence of air, with epoxydation rather than allylic oxidation being the predominant process at the first stage. The oxidized products (campholenic aldehyde, verbenone, pinocamphone) are shown to be formed with a high enantioselectivity; the formation of acetoxylation products is observed at temperatures above 200°C.

Comparative thermolysis of β-and α-pinenes in supercritical ethanol: The reaction characterization and enantiomeric ratios of products

The thermolysis of β-pinene and the co-thermolysis of an equimolar mixture of β-and α-pinenes in supercritical ethanol were carried out. The reaction of β-pinene affords β-myrcene as the major product (>70%). Considerable differences in the temperature dependence of the reaction rate were revealed for the transformations of β-pinene into β-myrcene and of α-pinene into limonene. The pre-exponential factors and the activation energies were calculated. The enantiomeric ratios of the thermolysis products of β-and α-pinenes and limonene were estimated. The starting monoterpenes do not undergo racemization during thermolysis. The thermolysis of enantiomerically pure α-pinene affords racemic (±)-limonene, whereas (-)-β-pinene gives (-)-limonene. The enantiomeric ratio in the latter remains equal to the enantiomeric purity of the starting β-pinene.

The kinetics, stereochemistry, and deuterium isotope effects in the α-pinene pyrolysis. Evidence for incursion of multiple conformations of a diradical

Pyrolysis of optically active α-pinene gave 95% racemic limonene (dipentene), alloocimine, racemic α-pinene, α-pyronene. Activation parameters are reported. Pyrolysis of (S) syn-6-trideuteriomethyl α-pinene at 256.7°C for 2400s gave dipentene with twice as much deuterium as hydrogen transfer with kH/kD=1.49 and alloocimine with a Z and E trideuteriomethyl ratio of ca. 5 with kH/kD=0.89. The isotope effect on loss of starting material was 1.16. Separation of the enantiomers of α-pinene from 3600s pyrolyses at 256.7°C followed by NMR analysis revealed that the ratio of the R-syn to R-anti to S-anti isomers is 4.6:3.7:1 at roughly two half-lives. Kinetic analysis reveals that the previously proposed mechanism for all conversions involving slow interconversion of two diradicals with Cs symmetry is not consistent with the distribution of the ??-pinene isomers, particularly the formation of more suprafacial-retention product (R-anti) than bond-rotated isomer (S-anti). Inclusion of another Cs species (ignoring the deuteriums) that would be intermediate between the originally proposed Cs species, appears more consistent with the observations.