Icaridin also called Piperidine the name of the plant extract Piperidine from which it is extracted: Piper or pepper.

Icaridin is a synthetic compound widely used as an active ingredient in insect repellents. It is known for its effectiveness in repelling a broad range of insects, including mosquitoes, ticks, and flies, while being gentle on the skin and providing long-lasting protection.

Chemical Composition and Structure

Icaridin, chemically known as 1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine, has the molecular formula C₁₂H₂₃NO₃. Its structure includes a piperidine ring substituted with an ethyl group and a hydroxy group, contributing to its repellent properties.

Physical Properties

Icaridin typically appears as a colorless to pale yellow liquid with a mild, non-offensive odor. It is soluble in organic solvents and slightly soluble in water. Icaridin is known for its non-greasy feel and non-staining properties, making it suitable for use in various formulations, including sprays, lotions, and wipes.

Chemical Industrial Synthesis Process

• Preparation of reagents. The main raw materials include 1-piperidinecarbonyl and 2-methylpropionic acid (isobutyric acid).
• Amidation reaction. The 2-methylpropionic acid is mixed with 1-piperidinecarbonyl in a reactor under continuous stirring. A catalyst, such as thionyl chloride (SOCl₂) or phosphorus trichloride (PCl₃), is used to facilitate the amide formation reaction.
• Heating. The mixture is heated to a controlled temperature (approximately 80-100°C) for a specified period to allow the amidation reaction. This process produces Icaridin (also known as picaridin).
• Cooling. The reaction mixture is cooled to room temperature.
• Neutralization. The mixture is neutralized with a sodium hydroxide (NaOH) solution to remove excess acid and catalyst.
• Extraction. The organic phase containing Icaridin is separated from the aqueous phase. An organic solvent, such as dichloromethane (DCM) or ethyl acetate, is used to extract Icaridin from the mixture.
• Drying. The organic extract is dried using a drying agent, such as anhydrous sodium sulfate, to remove residual moisture.
• Filtration. The dried solution is filtered to remove any solid impurities.
• Distillation. The Icaridin is purified by vacuum distillation to remove any volatile impurities and obtain a pure product.
• Quality control. The Icaridin undergoes rigorous quality testing to ensure it meets standards for purity and safety. These tests include chemical analysis and spectroscopy.

It appears as a colourless to yellowish liquid, volatile and insoluble in water.

What it is used for and where

Insecticides

In 1980, Bayer chemically produced Icaridin as an insect repellent, which was subsequently authorised in 2001 in 2001, while in Canada, authorisation was only granted in 2012.in 2012. 

The most commonly used insect and tick repellents on the market are DEET (N,N,Diethyltoluamide), IR3535 (Ethyl Butylacetylaminopropionate) and Icaridin (Picaridin). IR3535 has a lower level of toxicity and has efficacy equal to DEET. Icaridin has the same efficacy as DEET, but has a lower level of toxicity and a longer duration of protection. A natural product, clove essential oil, has shown good repellency, but requires relatively high dosages to cause high effects (1). Other repellents: lemon eucalyptus oil, citronella oil, catnip oil and 2-undecanone.

Icaridin is a newly developed repellent and its recommended use starts at a concentration of 5% and goes up to a maximum of 10% with a short-term protection of about 3 to 5 hours, while in more dangerous situations, when there is a need for a longer period of protection, a concentration of 20% can protect for up to 10 hours (2).

Alternatives to Icaridine

Nepeta cataria also known as catnip, has shown some efficacy as a spatial repellent but less effective than DEET as a contact repellent (3).

VUAA1, a chemical compound that functions as a co-receptor ion channel agonist of the insect odourant receptor (4).

Repellents of natural and plant origin cinnamon oil have shown almost equal repellency to DEET while margosa extract (Azadirachta indica (A.Juss., Sapindales: Meliaceae) has slightly lower efficacy (4). Other repellents: lemon eucalyptus oil, citronella oil, catnip oil, 2-undecanone, para-menthane-3,8-diol (distilled from Eucalyptus citriodora), geraniol.

For more information:   Icaridine studies

Appearance	Colourless liquid
pH	4-9
Boiling Point	330.9±15.0°C at 760 mmHg
Melting Point	below -170ºC
Density	1.0±0.1 g/cm3
Vapor Pressure	0.0±1.6 mmHg at 25°C
Refraction Index	1.478
PSA	49.77000
LogP	1.56
Loss on drying	≤2.0%
Sulphated ash	≤0.5%/g
Heavy metals	≤10 ppm
Safety

Price

1 g          €45.50

10 g        €51.00

100 g      €103.80

• Molecular Formula    C₁₂H₂₃No₃
• Molecular Weight     229.32
• Exact Mass     229.167801
• CAS  119515-38-7
• UNII    N51GQX0837
• EC Number   423-210-8
• DSSTox Substance ID  DTXSID0034227
• IUPAC  butan-2-yl 2-(2-hydroxyethyl)piperidine-1-carboxylate
• InChI=1S/C12H23NO3/c1-3-10(2)16-12(15)13-8-5-4-6-11(13)7-9-14/h10-11,14H,3-9H2,1-2H3
• InChl Key      QLHULAHOXSSASE-UHFFFAOYSA-N
• SMILES   CCC(C)OC(=O)N1CCCCC1CCO
• MDL number  MFCD01756488
• PubChem Substance ID    
• ChEBI  143733
• CHEMBL2104314

Synonyms

• sec-Butyl 2-(2-hydroxyethyl)piperidine-1-carboxylate
• 1-(2-butoxycarbonyl)-2-(2-hydroxyethyl)-piperidinebutan-2-yl 2-(2-hydroxyethyl)piperidine-1-
• carboxylate
• 1-Piperidinecarboxylic acid, 2-(2-hydroxyethyl)-, 1-methylpropyl ester
• Icaridine
• KBR3023
• Bayrepe
• Bayrepel
• Picaridin
• Propidine
• Lcaridin
• Pikaridin
• sec-Butyl 2-(2-hydroxyethyl)-1-piperidinecarboxylate
• 2-(2-hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester
• 1 methylpropyl 2 (2 hydroxyethyl)piperidine 1 carboxylate
• 1-methylpropyl2-(2-hydroxyethyl)-1-piperidinecarboxylate
• 1-Methylpropyl 2-(2-hydroxyethyl)piperidine-1-carboxylate
• (RS)-sec-butyl (RS)-2-(2-hydroxyethyl)piperidine-1-carboxylate

References______________________________________________________________

(1) Nentwig G, Frohberger S, Sonneck R. Evaluation of Clove Oil, Icaridin, and Transfluthrin for Spatial Repellent Effects in Three Tests Systems Against the Aedes aegypti (Diptera: Culicidae). J Med Entomol. 2017 Jan;54(1):150-158. doi: 10.1093/jme/tjw129. 

(2) Morimoto Y, Kawada H, Kuramoto KY, Mitsuhashi T, Saitoh T, Minakawa N. New mosquito repellency bioassay for evaluation of repellents and pyrethroids using an attractive blood-feeding device. Parasit Vectors. 2021 Mar 10;14(1):151. doi: 10.1186/s13071-021-04656-y.

Abstract. Background: With the increasing threat of the worldwide spread of mosquito-borne infectious diseases, consumer interest in anti-mosquito textiles that protect against mosquito bites is also increasing. Accordingly, repellent- or insecticide-treated textiles are gaining popularity. The standardization of commercial textile products is, therefore, indispensable for an authentic and objective evaluation of these products. Here we report a textile testing method using an artificial blood-feeding system that does not involve human volunteers or live animals, which aligns with the policy of protecting human and animal welfare....Conclusions: The accuracy and reproducibility of the developed method demonstrate that the ABFD may be widely used for fundamental experiments in the field of mosquito physiology, for the development of new repellent chemicals and in evaluation studies of mosquito repellent products, such as anti-mosquito textiles. The further development of the membrane and feeding unit systems will enable a more practical evaluation of mosquito repellents and blood-feeding inhibitors, such as pyrethroids.

(3) Bernier UR, Furman KD, Kline DL, Allan SA, Barnard DR. Comparison of contact and spatial repellency of catnip oil and N,N-diethyl-3-methylbenzamide (deet) against mosquitoes. J Med Entomol. 2005 May;42(3):306-11. doi: 10.1603/0022-2585(2005)042[0306:cocasr]2.0.co;2.

Abstract. Nepetalactone, the primary component of catnip oil, was compared with the repellent N,N-diethyl-3-methylbenzamide (deet) for its ability to affect the host-seeking ability of Aedes aegypti (L.). A triple cage olfactometer was used to bioassay each substance and to assess its attraction inhibition (spatial repellent) attributes when combined with the following attractants: carbon dioxide, acetone, a blend of L-lactic acid and acetone, and human odors. Repellent tests were conducted with each substance against female Ae. aegypti, Anopheles albimanus Weidemann, and Anopheles quadrimaculatus Say. Catnip oil and deet were both weakly attractive to Ae. aegypti, catnip oil was the better spatial repellent, whereas deet was a more effective contact repellent in tests with all three species of mosquitoes.

(4) Rinker, D. C., Jones, P. L., Pitts, R. J., Rutzler, M., Camp, G., Sun, L., ... & Zwiebel, L. J. (2012). Novel high‐throughput screens of Anopheles gambiae odorant receptors reveal candidate behaviour‐modifying chemicals for mosquitoes. Physiological Entomology, 37(1), 33-41.

Abstract. Despite many decades of multilateral global efforts, a significant portion of the world population continues to be plagued with one or more mosquito-vectored diseases. These include malaria and filariasis as well as numerous arboviral-associated illnesses including Dengue and Yellow fevers. The dynamics of disease transmission by mosquitoes is complex, and involves both vector competence and vectorial capacity. One area of intensive effort is the study of chemosensory-driven behaviours in the malaria vector mosquito Anopheles gambiae Giles, the modulation of which are likely to provide opportunities for disease reduction. In this context recent studies have characterized a large divergent family of An. gambiae odorant receptors (AgORs) that play critical roles in olfactory signal transduction. This work has facilitated high-throughput, cell-based calcium mobilization screens of AgOR-expressing HEK cells that have identified a large number of conventional AgOR ligands, as well as the first non-conventional Orco (olfactory receptor co-receptor) family agonist. As such, ligand-mediated modulation serves as a proof-of-concept demonstration that AgORs represent viable targets for high-throughput screening and for the eventual development of behaviour-modifying olfactory compounds. Such attractants or repellents could foster malaria reduction programmes.