ANISOLE: STRUCTURE, PROPERTIES, NOMENCLATURE, RISKS AND USES - CHEMISTRY - 2024

The anisole or methoxybenzene is an organic compound consisting of an aromatic ether having the chemical formula C ₆ H ₅ OCH ₃. Its physical state is that of a colorless liquid, which may present yellowish colorations. It is easily recognized by its characteristic anise smell.

It is then a volatile compound and not very high cohesion forces; typical characteristics of light ethers, which are stored in small sealed containers. Specifically, anisole is the simplest of the alkyl aryl ethers; that is, those with an aromatic component (Ar) and another alkyl component (R), Ar-OR.

Anisole molecule. Source: Ben Mills via Wikipedia.

The group C ₆ H ₅ - comes to denote Ar, and -CH ₃ to R, thus having C ₆ H ₅ -O-CH ₃. The aromatic ring, and the presence of -OCH ₃ as a substituent group called methoxy, gives anisole a nucleophilicity superior to that of benzene and nitrobenzene. Therefore, it serves as an intermediate molecule for the synthesis of compounds with pharmacological activity.

Its characteristic anise smell has been used to add anisole to cosmetic and hygiene products that demand a pleasant fragrance.

Anisole structure

The upper image shows the molecular structure of anisole using a spheres and bars model. The aromatic ring can be seen, whose carbons are sp ² and therefore it is flat, like a hexagonal sheet; and attached to it is the methoxy group, whose carbon is sp ³, and its hydrogens are above or below the plane of the ring.

The importance of the -OCH ₃ group in the structure goes beyond breaking the plane geometry of the molecule: it gives it polarity, and consequently, the non-polar benzene molecule acquires a permanent dipole moment.

Dipole moment

This dipole moment is due to the oxygen atom, which attracts the electron densities of both the aromatic and methyl rings. Thanks to this, anisole molecules can interact through dipole-dipole forces; although, it lacks any possibility of forming hydrogen bonds, as it is an ether (ROR does not have H linked to oxygen).

Its high boiling point (154ºC), experimentally certifies the strong intermolecular interactions that govern its liquid. Likewise, the London dispersion forces are present, dependent on the molecular mass, and the π-π interactions between the rings themselves.

Crystals

The structure of anisole, however, does not allow it to interact strongly enough to adopt a solid at room temperature (mp = -37ºC). This may also be due to the fact that when the intermolecular distances are reduced, the electrostatic repulsions between the electrons of neighboring aromatic rings begin to gain a lot of force.

Therefore, and according to crystallographic studies, the anisole molecules in crystals at a temperature of -173ºC, cannot be arranged in such a way that their rings are facing each other; that is, their aromatic centers are not aligned one on top of the other, but rather a -OCH ₃ group is above or below a neighboring ring.

Properties

Physical appearance

Colorless liquid but that may present slight shades of straw color.

Odor

Smells slightly similar to anise seeds.

Taste

Sweet; however, it is moderately toxic, so this test is dangerous.

Molecular mass

108.140 g / mol.

Density

0.995 g / mL.

Vapor density

3.72 (relative to air = 1).

Melting point

-37 ° C.

Boiling point

154 ° C.

ignition point

125ºC (open cup).

Autoignition temperature

475 ° C.

Viscosity

0.778 cP at 30 ° C.

Surface tension

34.15 dynes / cm at 30 ° C.

Refractive Indicator

1.5179 at 20 ° C.

Solubility

Poorly soluble in water (around 1mg / mL). In other solvents, such as acetone, ethers and alcohols, it is however very soluble.

Nucleophilicity

The aromatic ring of anisole is rich in electrons. This is because oxygen, despite being a very electronegative atom, contributes with the electrons from its π cloud to delocalize them through the ring in numerous resonance structures. Consequently, more electrons flow through the aromatic system and therefore its nucleophilicity increases.

The increase in nucleophilicity has been experimentally demonstrated by comparing its reactivity, against aromatic electrophilic substitutions, with that of benzene. Thus, the remarkable effect of the -OCH ₃ group on the chemical properties of the compound is evidenced.

Likewise, it should be noted that the electrophilic substitutions occur in the positions adjacent (-orto) and opposite (-para) to the methoxy group; that is, it is ortho-para director.

Reactivity

The nucleophilicity of the aromatic ring of anisole already allows a glimpse of its reactivity. The substitutions can occur either in the ring (favored by its nucleophilicity), or in the methoxy group itself; in the latter the O-CH ₃ bond is broken to replace the -CH ₃ with another alkyl group: O-alkylation.

Therefore, in an alkylation process, anisole can accept an R group (fragment of another molecule) by substituting an H of its ring (C-alkylation), or substituting the CH ₃ of its methoxy group. The following image illustrates what has just been said:

Alkylation of anisole. Source: Gabriel Bolívar.

In the image the R group is located in the -orto position, but it may also be in the -para position, opposite to the -OCH ₃. When O-alkylation happens, a new ether with another -OR group is obtained.

Nomenclature

The name 'anisole' is the best known and most accepted, most likely derived from its anise-like smell. However, the name 'methoxybenzene' is quite specific, since it establishes at once what is the structure and identity of this aromatic ether; this is the name governed by the systematic nomenclature.

Another less used, but equally valid name is 'phenyl methyl ether', which is governed by traditional nomenclature. This is perhaps the most specific name of all, since it directly indicates which are the two structural portions of the ether: phenyl-O-methyl, C ₆ H ₅ -O-CH ₃.

Risks

Medical studies have not yet been able to demonstrate the possible deadly effects of anisole in the body at low doses. However, like most chemicals, it irritates the skin, throat, lungs, and eyes when exposed for too long and in moderate concentrations.

Also, due to the nucleophilicity of its ring, a part of it is metabolized and therefore is biodegradable. In fact, as a result of this property, simulations showed that it cannot concentrate on aqueous ecosystems since its organisms first degrade it; and therefore, rivers, lakes or seas can accumulate anisole.

In soils, given its volatility, it evaporates quickly and is carried away by air currents; being so, it does not significantly affect the plant masses or plantations either.

On the other hand, atmospherically it reacts with free radicals, and therefore does not represent a risk of contamination for the air we breathe.

Applications

Organic syntheses

From anisole other derivatives can be obtained by aromatic electrophilic substitution. This makes it possible for it to be used as an intermediate for the synthesis of drugs, pesticides and solvents, to which it is desired to add its characteristics. Synthetic routes can consist of mostly C-alkylation or O-alkylation.

Fragrances

In addition to its use for organic synthesis, it can be used directly as an additive for creams, ointments and perfumes, incorporating anise fragrances to such products.

References

1. Morrison, RT and Boyd, R, N. (1987). Organic Chemistry. 5th Edition. Editorial Addison-Wesley Interamericana.
2. Carey FA (2008). Organic Chemistry. (Sixth edition). Mc Graw Hill.
3. Graham Solomons TW, Craig B. Fryhle. (2011). Organic Chemistry. Amines. (10th edition.). Wiley Plus.
4. National Center for Biotechnology Information. (2019). Anisole. PubChem Database, CID = 7519. Recovered from: pubchem.ncbi.nlm.nih.gov
5. Wikipedia. (2019). Anisole. Recovered from: en.wikipedia.org
6. Pereira, Cynthia CM, de la Cruz, Marcus HC, & Lachter, Elizabeth R. (2010). Liquid phase alkylation of anisole and phenol catalyzed by niobium phosphate. Journal of the Brazilian Chemical Society, 21 (2), 367-370. dx.doi.org/10.1590/S0103-50532010000200025
7. Seidel RW and Goddard R. (2015). Anisole at 100 K: the first crystal structure determination. Acta Crystallogr C Struct Chem. Aug; 71 (Pt 8): 664-6. doi: 10.1107 / S2053229615012553
8. Chemical Formulation. (2018). Methoxybenzene Recovered from: formulacionquimica.com