PHENOXYACETIC ACID: SYNTHESIS, PROCEDURE, USES, RISKS - CHEMISTRY - 2024

The phenoxyacetic acid is a substance of organic nature, formed by the reaction between phenol and monochloroacetic acid in the presence of a solution of sodium hydroxide. The procedure used to obtain this product is called Williamson's ethers synthesis.

The synthesized phenoxyacetic acid is a white or colorless precipitate, formed by needle-shaped crystals, practically insoluble in water (solubility in water 12 g / l ^-1), but soluble in acetic acid, phenol and diethyl ether.

Chemical structure of phenoxyacetic acid. Source: «Phenoxyacetic acid». Wikipedia, the free encyclopedia. May 13, 2014, 5:21 pm UTC. May 13, 2014, 5:21 PM en.wikipedia.org. Edited image layout.

Its chemical name is 2-phenoxyethanoic and its molecular formula is C ₈ H ₈ O ₃. The molecular mass is 152.15 g.mol ^-1. This product behaves like a weak acid and has a melting point between 98 to 100 ° C and a boiling point of 285 ° C.

Phenoxyacetic acid is an intermediate product in the synthesis of substances with herbicidal properties. By itself, phenoxyacetic acid has antifungal properties against Candida albicans and Trichophyton rubrum. It is also useful as an exfoliative of the skin, eliminating excess keratin in calluses.

It is necessary to take precautions for its handling because when heated it emits toxic gases that are corrosive. Among the gases is hydrogen chloride.

Direct exposure with this product could cause mild irritation of the skin or mucosa, although not of great importance, except for the involvement of the ocular mucosa, it can be serious. It also causes irritation of the respiratory tract if inhaled and the gastric route if ingested.

It is a non-flammable substance and quite stable at room temperature, however, at high temperatures or pressures it could lose its stability, and when faced with water it can release a certain amount of energy but it will not do so violently.

Synthesis of phenoxyacetic acid

Phenol is an alcohol and as such it behaves like a weak acid, which is why it easily loses the acidic proton (H ⁺) to an alkali (sodium hydroxide) to become an alkoxide (phenolate). This later, through a bimolecular nucleophilic substitution, will form ether.

The alkoxide works as a nucleophile, that is, it is capable of giving up 2 electrons that are free to another substance. In the case of the reaction that concerns us, it is the alkyl halide (monochloroacetic acid), in such a way that it binds strongly through covalent bonds with it, forming a new substance that in this case is ether.

During the reaction, a displacement of the halide ion occurs, which is replaced by the alkoxide anion. This reaction is known as the Williamson ethers synthesis.

The amount of product obtained and the speed with which it is produced will depend on the concentration of the reactants involved, since this is a second-order kinetic reaction, where the collision of the molecules (nucleophile + alkyl halide) determines its effectiveness.

Process

Step 1

To begin the synthesis of phenoxyacetic acid, 0.5 g of phenol is carefully weighed and placed in a pear-shaped, single-mouth flask with a capacity of 50 ml. 2.5 ml of sodium hydroxide (NaOH) at 33% (p / v) is added to dissolve it.

Check the alkalinity of the solution with a pH indicator paper. Place a cork lid on the flask and mix vigorously for 5 minutes. A magnetic stirrer can be used for mixing.

Step 2

Subsequently, add 0.75 g of monochloroacetic acid and repeat the mixing procedure for 5 minutes.

If the mixture seeks to harden or become pasty, you can add water (between 1 to 3 ml), but this is added little by little until it returns to the previous texture, without diluting too much.

Step 3

Uncover the flask and place it in a water bath that has a reflux system for 10 minutes. If the flow system is not available, it is left for 40 minutes.

Step 4

Let the solution cool down and add 5 ml of water, then acidify with a concentrated HCl solution until reaching pH 1. (Measure pH with a paper for this purpose).

Step 5

Pass the mixture carefully through the separatory funnel and extract three times, using 5 ml of ethyl ether in each procedure.

Pool the organic extracts and place back into the separating funnel to run a water wash in triplicate, using 5 ml of water for each wash.

The aqueous fractions are separated to be discarded.

Step 6

Subsequently, the organic fraction is extracted with 3 ml of sodium carbonate (Na ₂ CO ₃) at 15% three times.

The alkaline aqueous extract obtained is placed in an ice bath and acidified with HCl until pH = 1, which generates the precipitation of the product. The acidification step must be carried out with great care adding drop by drop, because the reaction generates foam and if it is added abruptly it could splash.

The solid is obtained by vacuum filtration, the precipitate is washed and allowed to dry.

Step 7

The product obtained is weighed and the yield and melting point are observed.

Source: Sandoval M. (2015). Organic Chemistry Laboratory Practices Manual II. National Autonomous University of Mexico Faculty of Chemistry.

Applications

Phenoxyacetic acid alone has a fungicidal activity against certain fungi, such as Candida albicans and Trichophyton rubrum. This action was described in an investigation carried out by González et al.

The work revealed that the minimum inhibitory or fungistatic concentration (MIC) and the minimum fungicidal concentration (CMF) were the same (2.5 mg / ml) for 13 species of Candida albicans from clinical samples, specifically from patients suffering from onychomycosis..

While a Candida albicans ATCC 10231 strain presented a MIC of 2.5 mg / ml and a CMF of 5.0 mg / ml. For its part, Trichophyton rubrum presented a MIC of 0.313 mg / ml and a CMF of 1.25 mg / ml in 8 strains analyzed from infected nails.

In addition, phenoxyacetic acid has great utility as an exfoliative of keratin, therefore it is able to minimize calluses or pimples on skin affected with these characteristics.

On the other hand, phenoxyacetic acid is a raw material for the synthesis of pesticides, specifically herbicides, such as Astix and Duplosan.

Risks

If the product is accidentally ingested, it will cause irritation of the mucous membranes throughout the gastrointestinal tract (mouth, esophagus, stomach and intestines).

If inhaled, it will irritate the respiratory mucosa, causing respiratory failure and coughing.

On the skin it can cause slight irritation. While on the ocular mucosa the irritation will be more severe. In these cases, it is recommended to wash the affected area with plenty of water and soap and wash the eye mucosa with plenty of water.

This product has been associated as a predisposing factor for the development or appearance of adipose tumors. These tumors most often develop in the extremities or abdomen.

On the other hand, this product is classified as not dangerous to transport according to the criteria described by the transport regulations.

Pesticides derived from phenoxyacetic acid are usually toxic to the environment and have been associated with genetic mutations, specifically with the t-translocation present in non-Hodgkin's lymphoma in humans.

Precautions

- This product should be kept away from strong oxidizing agents and bases with which it can react violently.

- It is important to avoid heating this product.

- Handle using protective measures, such as gloves, gown, safety glasses.

References

1. González G, Trujillo R. Phenoxyacetic acid, identification and determination of its antifungal action in vitro against Candida albicans and Trichophyton rubrum. Rev. Peruana of the Faculty of Pharmacy, 1998; 34 (109). Available at: unmsm.edu
2. "Phenoxyacetic acid". Wikipedia, the free encyclopedia. May 13, 2014, 5:21 pm UTC. May 13, 2014, 17:21 wikipedia.org
3. Merck Laboratories. Safety data Sheet. 2017.Available at: ens.uabc.mx/
4. Aventis Laboratories. Aventis Safety Data Sheet. 2001. Available at: afipa.cl
5. Gutiérrez M. Phenoxyacetics in Toxicological Emergencies. CIATOX Toxicological Information and Advice Center. National university of Colombia. Available at: encolombia.com
6. Sandoval M. (2015). Organic Chemistry Laboratory Practices Manual II. National Autonomous University of Mexico Faculty of Chemistry.
7. Merck Laboratories. Safety data sheet according to EC regulation No. 1907/2006. 2015 Available at: ens.uabc.mx/
8. Berzal-Cantalejo M, Herranz-Torrubiano A, Cuenca-González C. Adipose tumor with alarm symptoms. Rev Clín Med Fam 2015, 8 (3): 246-250. Available at: scielo.isciii.es/scielo.
9. Matheus T, Bolaños A. Micronuclei: genotoxicity biomarker in those exposed to pesticides. Salus, 2014; 18 (2): 18-26. Available at: ve.scielo.org