IR3535 is a natural product derived from Averrhoa bilimbi, a fruit tree belonging to the Oxalidaceae family, is an ethyl ester, a member of the acetamides and a tertiary carboxamide. It is also commonly identified as Ethyl butylacetylaminopropionate.

Ethyl Butylacetylaminopropionate is a synthetic compound primarily used as an insect repellent in cosmetic and personal care products. It is a safe and non-toxic ingredient that provides effective protection against mosquitoes, flies, and other insects. Known for being gentle on the skin, it has a lower risk of irritation compared to other insect repellents like DEET.

Chemical Composition and Structure

Ethyl Butylacetylaminopropionate is an ester derived from butylacetylaminopropionic acid and ethanol. Its chemical structure is specifically designed to interfere with the olfactory receptors of insects, repelling them without harmful effects on humans. This makes it a safe and effective option for use in insect repellent products for both children and adults.

Physical Properties

It appears as a colorless or slightly yellowish liquid with a mild characteristic odor. It is soluble in organic solvents and partially soluble in water. Ethyl Butylacetylaminopropionate has good stability across a range of temperatures and pH levels, making it suitable for use in a wide variety of cosmetic and insect repellent formulations.

Production Process

Ethyl Butylacetylaminopropionate is synthetically produced through an esterification reaction between butylacetylaminopropionic acid and ethanol. The synthesis process is carefully controlled to ensure the purity and effectiveness of the ingredient in insect repellent products.

The name defines the structure of the molecule:

• Ethyl. It refers to an ethyl group (C₂H₅), which is a functional group derived from ethane (C₂H₆). It consists of two carbon atoms and five hydrogen atoms.
• Butyl. Refers to the butyl group (C₄H₉), which is a functional group derived from butane (C₄H₁₀). It consists of four carbon atoms and nine hydrogen atoms.
• Acetyl. Refers to an acetyl group (CH₃CO-), which is a functional group derived from acetic acid (CH₃COOH). It consists of a methyl group (CH₃-) bonded to a carbonyl group (C=O).
• Amino. Refers to an amine group (-NH2), which is a functional group containing a nitrogen atom linked by single bonds to hydrogen atoms.
• Propionate. Refers to a propionate group (C₂H₅COO-), which is a functional group derived from propionic acid (C₂H₅COOH). It consists of a two-carbon propyl group attached to a carboxyl group (-COOH).

The synthesis process takes place in two steps:

• Butylacetylaminopropionic acid production. The process begins with the production of butylacetylaminopropionic acid . This can be synthesised through a series of reactions involving the condensation of butyraldehyde with aminopropanoic acid, followed by acetylation of the resulting compound.
• Esterification. Butylacetylaminopropionic acid is reacted with ethanol in a process called esterification. In this process, the carboxylic group (COOH) of butylacetylaminopropionic acid reacts with the hydroxyl group (OH) of ethanol to form an ester, releasing water as a by-product. The resulting compound is ethyl butylacetylaminopropionate.

It appears as a colourless to yellowish liquid.

What it is used for and where

Insecticides

Ethyl butylacetylaminopropionate, like all repellents in commercial use, tends to have, as a liquid form, low volatility, but has proven to be an effective and safe mosquito repellent (1).

Antiviral test results revealed that IR3535 showed antiviral effects against Poliovirus and Adenovirus and is therefore a promising agent for new therapeutic areas (2).

Due to its low allergenic potential, Ethyl butylacetylaminopropionate can also be used in products for children (3).

It is an ingredient that can be included in commercial mosquito and insect repellent products in the form of an emulsion, gel, solution, coating agent, microcapsule, aerosol, etc. (3).

Alternative a Ethyl butylacetylaminopropionate

Nepeta cataria also known as catnip, has shown some effectiveness as a spatial repellent but less effective than DEET as a contact repellent (4).

VUAA1, a chemical compound that functions as a co-receptor ion channel agonist of the insect odour receptor (5).

Icaridina, newly developed repellent and its recommended use starts at a concentration of 5% and goes up to a maximum of 10%. It is the least toxic compound although toxicity in these repellents is rather relative.

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 (6). Other repellents: lemon eucalyptus oil, citronella oil, catnip oil, 2-undecanone, para-menthane-3,8-diol (distilled from Eucalyptus citriodora), geraniol.

Health and Safety Considerations

Safety in Use
Ethyl Butylacetylaminopropionate is generally considered safe for use in cosmetic and personal care products. It is well tolerated by the skin and has a low risk of irritation, making it suitable for use on children and individuals with sensitive skin.

Allergic Reactions
Allergic reactions to this compound are rare, but as with any cosmetic ingredient, it is advisable to perform a patch test before using products on sensitive skin.

Toxicity and Carcinogenicity
There is no evidence to suggest that Ethyl Butylacetylaminopropionate is toxic or carcinogenic. It is considered safe for topical use and poses no known health risks when used at recommended concentrations.

Environmental and Safety Considerations
As a synthetic compound, Ethyl Butylacetylaminopropionate is relatively safe for the environment when used properly. It is not known to have a significant environmental impact, but it is always important to follow safe disposal guidelines for products containing repellents.

Regulatory Status
Ethyl Butylacetylaminopropionate is approved for use in insect repellents in many regions, including the European Union and the United States. It is subject to regulations that ensure its safety in products intended for human use.

For more information:  

Ethyl butylacetylaminopropionate studies

Typical commercial product characteristics BAAPE/Ethyl butylacetylaminopropionate 

Appearance	Light yellow or colorless clear liquid
pH	4.0-6.0
Boiling Point	314.8±25.0 °C at 760 mmHg
Purity	99%
Melting Point	<-20°C
Density	1.0±0.1 g/cm3
Vapor Pressure	0.0±0.7 mmHg at 25°C
Refraction Index	11.450
PSA	46.61000
LogP	1.65
Sulfated ash	≤0.1%
Water	≤0.5%
Free acid	≤1%
Shelf life	2 years
Safety

• Molecular Formula    C₁₁H₂₁NO₃
• PMolecular Weight     215.29
• Exact Mass    215.152145
• CAS  52304-36-6
• UNII    65GQA237EH
• EC Number   257-835-0
• DSSTox Substance ID  DTXSID9035753
• IUPAC  ethyl 3-[acetyl(butyl)amino]propanoate
• InChI=1S/C11H21NO3/c1-4-6-8-12(10(3)13)9-7-11(14)15-5-2/h4-9H2,1-3H3  
• InChl Key      VZRKEAFHFMSHCD-UHFFFAOYSA-N
• SMILES   CCCCN(CCC(=O)OCC)C(=O)C
• MDL number  MFCD00214076
• PubChem Substance ID    
• ChEBI  81991
• NCI    
• ICSC    
• NSC   
• RTECS   
• UN    

Synonyms

• Ethyl N-acetyl-N-butyl-β-alaninate
• IR3535
• Baape
• Ebaap
• Cleaneraddtion
• β-Alanine, N-acetyl-N-butyl-, ethyl ester
• N-Acetyl-N-butyl-β-alanine, ethyl ester

References________________________________________________________________

(1) WHO. Ethyl butylacetylaminopropionate (World Health Organisation, Geneva, 2006).

(2) Iyigundogdu Z, Kalayci S, Asutay AB, Sahin F. Determination of antimicrobial and antiviral properties of IR3535. Mol Biol Rep. 2019 Apr;46(2):1819-1824. doi: 10.1007/s11033-019-04632-x. 

Abstract. Insect repellent is a substance directly applied to skin or clothing in order to repel flies, mosquitoes, ticks etc. IR3535 or Ethyl butylacetylaminopropionate (EBAAP) is a relatively new repellent which is classified as a biopesticide due to exceptional skin tolerance and overall safety. The repellency against various insect and ticks, and the low toxicity of IR3535 are well acknowledged. However, there has been no attempt to investigate the effects on microorganisms or viruses up to now. In the present study, antimicrobial activity was investigated based on disc diffusion and micro-well dilution assays. Disc diffusion assays revealed IR3535 displayed remarkable antimicrobial activity on the microorganisms tested. MIC results showed that the antifungal efficiency of IR3535 is higher with respect to its antibacterial and anticandidal efficiency. Moreover, antiviral test results revealed that IR3535 showed antiviral effects against Poliovirus and Adenovirus. This is the first study that reveals IR3535's antimicrobial and antiviral properties against a broad range of microorganisms and viruses. In consideration of the antimicrobial and antiviral properties, IR3535 is a promising agent that could be used to develop novel therapeutic approaches, new application areas and formulations in the future.

(3) Pinto IC, Cerqueira-Coutinho CS, Santos EP, Carmo FA, Ricci-Junior E. Development and characterization of repellent formulations based on nanostructured hydrogels. Drug Dev Ind Pharm. 2017 Jan;43(1):67-73. doi: 10.1080/03639045.2016.1220564.

Abstract. Diseases caused by insects could lead to epidemic scenarios in urban areas and insect repellents are a shield against a wide range of insects, but they need to be safe without compromising efficacy. Ethyl butylacetylaminopropionate (EB) is a synthetic mosquito repellent, which could be used in products for adults and children due to its low-allergenic potential. The aim of this study was to develop and characterize EB and Poloxamer 407 nanoemulsions regarding their droplets mean size, pH, rheological properties, cytotoxicity and in vitro permeation profile. The developed formulations (F1 with 12.5% of EB and F2 with 25% of EB) were compared with a commercial formulation containing 12.5% of EB. Droplets mean size was determined by DLS, and for both nanoemulsions they were around 200 nm; however, the commercial formulation presented a droplets mean size of 10 nm, which could contribute to its high permeation. F1 and F2 presented a gel-like behavior, however F2 presented lower viscosity due to the presence of more EB between the polymer chains preventing them to interact with each other. Also, F2 was less retained by the epidermis when compared to F1 probably due to its lower viscosity. For the cytotoxicity assay only F2, which presented the highest concentration of EB was tested, and it was not toxic to the cells. This result could be also extended to F1 which presented half the EB concentration. The present study demonstrated that EB and Poloxamer 407 nanoemulsions are promising as new insect-repellent formulations.

(4) 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.

(5) 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.

(6)  Krüger A, Schmolz E, Vander Pan A. Methods for Testing Repellents Against Bed Bugs (Hemiptera: Cimicidae). J Econ Entomol. 2021 Feb 9;114(1):265-273. doi: 10.1093/jee/toaa304.