BENZYL BENZOATE: STRUCTURE, PROPERTIES, SYNTHESIS, USES - CHEMISTRY - 2025

The benzyl benzoate is an organic compound of formula C ₁₄ H ₁₂ O ₂. It appears as a colorless liquid or as a white solid in the form of flakes, with a characteristic weak balsamic odor. This enables benzyl benzoate to be used in the perfume industry as a scent fixing agent.

It was first studied as a medicine in 1918, and has been on the World Health Organization's essential medicines list ever since.

Source: Jynto, from Wikimedia Commons

It is one of the most used compounds in the treatment of scabies or scabies. A skin infection caused by the Sarcoptes scabei mite, characterized by severe itching that intensifies at night and can lead to secondary infections.

It is lethal to the scabies mite and is also used in pediculosis, a head and body lice infestation. In some countries it is not used as the treatment of choice for scabies due to the irritant action of the compound.

It is obtained by condensing benzoic acid with benzyl alcohol. There are other similar ways of synthesizing the compound. Likewise, it has been isolated in some species of plants of the genus Polyalthia.

Structure of benzyl benzoate

The upper image represents the structure of benzyl benzoate in a bar and sphere model. The dotted lines indicate the aromaticity of the benzene rings: one from benzoic acid (the left), and the other from benzyl alcohol (the right).

The Ar-COO and H ₂ C-Ar bonds rotate, causing the rings to rotate on those axes. Beyond these rotations, there are not many that can contribute (at first glance) with its dynamic characteristics; therefore, its molecules find fewer ways to establish intermolecular forces.

Interactions

Thus, it could be expected that the aromatic rings of neighboring molecules do not interact in an appreciable way, and neither do these with the ester group due to their difference in polarity (that of the red spheres, R-CO-OR).

Also, there is no likelihood of hydrogen bonding on either side of its structure. The ester group could accept them, but the molecule lacks the hydrogen donor groups (OH, COOH, or NH ₂) for such interactions to arise.

On the other hand, the molecule is slightly symmetric, which translates into a very low permanent dipole moment; therefore, their dipole-dipole interactions are weak.

And where would the region with the highest electron density be located? In the ester group, although not very pronounced due to the symmetry in its structure.

The prevailing intermolecular forces for benzyl benzoate are scattering or London forces. These are directly proportional to the molecular mass, and by grouping several of these molecules together, it can be expected that the formation of instantaneous and induced dipoles will occur with greater probability.

All of the above is demonstrated by the physical properties of benzyl benzoate: it only melts at 21 ° C, but in a liquid state it boils at 323 ° C.

Physical and chemical properties

Chemical name

Benzyl benzoate, or benzoic acid methyl ester. In addition, numerous names are assigned due to the manufacturers of the medical product, receiving among them the following: Acarosan, Ascabiol, Benzanil, and Novoscabin.

Molecular weight

212,248 g / mol.

Molecular formula

C ₁₄ H ₁₂ O ₂.

Physical appearance

Colorless liquid or white solid in the form of flakes.

Odor

It has a mild balsamic scent.

Taste

Sharp, burning to taste.

Boiling point

323.5 ° C.

Melting point

21 ºC.

Fire point

148 ° C (298 ° F).

Water solubility

It is practically insoluble in water (15.4 mg / L).

Solubility in organic solvents

Insoluble in glycerol, miscible with alcohol, chloroform, ether and oils. Soluble in acetone and benzene.

Density

1,118 g / cm ³ at 25 ° C.

Relative density with water

1.1 (with a water density of 1 g / cm ³).

Vapor density in relation to air

7.31 (air = 1).

Steam pressure

0.000224 mmHg at 25 ° C.

Stability

A 20% benzyl benzoate emulsion prepared in OS emulsifier and wool wax alcohol is stable. Maintains its effectiveness for approximately 2 years.

Auto ignition

480 ° C.

Viscosity

8,292 cPoise at 25 ° C.

Heat of combustion

-6.69 × 10 ⁹ J / Kmol.

pH

Practically neutral when the pH is estimated by wetting the litmus paper in the compound.

Surface tension

26.6 dynes / cm at 210.5 ° C.

Refractive index

1.5681 at 21 ° C.

Mechanism of action

Benzyl benzoate has toxic effects on the nervous system of the Sarcoptes scabiei mite, causing its death. It is also toxic to the mite's eggs, although the exact mechanism of action is unknown.

Benzyl benzoate would act by interrupting the function of voltage-gated sodium channels, causing a prolonged depolarization of the membrane potentials of nerve cells, and the interruption of the functioning of neurotransmitters.

It is pointed out that the selective neurotoxic effect of permethrin (a drug used in scabies) for invertebrates is due to structural differences between the sodium channels of vertebrates and invertebrates.

Synthesis

It is produced by the conjugation of benzyl alcohol and sodium benzoate in the presence of triethylamine. It is also produced by the transesterification of methylbenzoate, in the presence of benzyl oxide. It is a by-product of the synthesis of benzoic acid by oxidation with toluene.

Furthermore, it can be synthesized by the Tischenko reaction, using benzaldehyde with sodium benzylate (generated from sodium and benzyl alcohol) as a catalyst.

Applications

In the treatment of scabies

The compound has long been used in the treatment of scabies and pediculosis as well, being used as a 25% benzyl benzoate lotion. In the treatment of scabies, the lotion is applied to the whole body from the neck down, after a previous cleaning.

When the first application is dry, apply a second coat of the lotion with benzyl benzoate. Its use is considered low-risk for adult patients with scabies, and lethal for the mites that produce the disease, which are usually eliminated in five minutes. The use of benzyl benzoate in children is not recommended.

Typically two to three applications of the compound are required to cause skin irritation. An overdose of the compound can cause blisters, hives, or a rash.

There are no usable data on the percutaneous absorption of benzyl benzoate, there are studies that suggest this fact, but without quantifying its magnitude.

The absorbed benzyl benzoate is rapidly hydrolyzed to benzoic acid and benzyl alcohol. This is subsequently oxidized to benzoic acid. Subsequently, benzoic acid is conjugated with glycine to produce benzoylcholine (hipppuric acid), or with glucuronic acid to produce benzoylglucuronic acid.

In treating spasms

Benzyl benzoate has vasodilator and spasmolytic effects, being present in many medications for the treatment of asthma and pertussis.

Benzyl benzoate was used initially in the treatment of many conditions that affected people's health, including excessive intestinal peristalsis; diarrhea and dysentery; intestinal colic and enteroespasm; pylorospasm; spastic constipation; biliary colic; renal or urethral colic; urinary bladder spasm.

Also, spasms associated with contraction of the seminal vesicle; uterine colic in spastic dysmenorrhea; arterial spasm associated with high blood pressure; and bronchial spasm as in asthma. Currently it has been replaced in many of its uses by more effective drugs

As excipient

Benzyl benzoate is used as an excipient in some testosterone replacement drugs (such as Nebido) in the treatment of hypogonadism.

In Australia, a case of anaphylaxis occurred in a patient under treatment with testosterone replacement drugs, associated with the use of benzyl benzoate.

The compound is used in the treatment of some skin conditions such as ringworm, mild to moderate acne, and seborrhea.

In veterinary hospitals

Benzyl benzoate was used in veterinary hospitals as a topical miticide, scabicide, and pediculicide. At large doses, the compound can cause hyperarousal, loss of coordination, ataxia, seizures, and respiratory paralysis in laboratory animals.

Other uses

-It is used as repellants for chiggers, ticks and mosquitoes.

-It is a solvent for cellulose acetate, nitrocellulose and artificial musk.

-Used as a flavoring agent for candy, confectionery and chewing gums. Furthermore, it finds use as an antimicrobial preservative agent.

-Benzyl benzoate is used in cosmetology in the treatment of dry lips, through the use of a cream that contains it in conjunction with petroleum jelly and a perfume.

-It is used as a substitute for camphor in celluloid compounds, plastics and pyroxylin.

-Used as a dye carrier and plasticizer. Serves as a fragrance fixing agent. Although it is not an active fragrance ingredient, it helps to improve the stability and characteristic odor of the main ingredients.

References

1. University of Hertfordshire. (May 26, 2018). Benzyl benzoate. Recovered from: sitem.herts.ac.uk
2. Wikipedia. (2018). Benzyl benzoate. Recovered from: en.wikipedia.org
3. PubChem. (2018). Benzyl benzoate. Recovered from: pubchem.ncbi.nlm.nih.gov
4. Cosmetic, Medical and Surgical Dermatology. (2013). Scabies: a review. Recovered from: dcmq.com.mx
5. Saludmedin.es. (June 30, 2018). Instructions for use benzyl benzoate: emulsion and ointment. Recovered from: saludmedin.es