Phenol

Phenol, also known as carbolic acid, is an aromatic organic compound with the molecular formula C₆H₅OH. It is a white crystalline solid that is volatile. The molecule consists of a phenyl group (âˆ'C₆H₅) bonded to a hydroxyl group (âˆ'OH). It is mildly acidic and requires careful handling due to its propensity to cause chemical burns.

Phenol was first extracted from coal tar, but today is produced on a large scale (about 7 billion kg/year) from petroleum. It is an important industrial commodity as a precursor to many materials and useful compounds. Its major uses involve its conversion to plastics or related materials. Phenol and its chemical derivatives are key for building polycarbonates, epoxies, Bakelite, nylon, detergents, herbicides such as phenoxy herbicides, and numerous pharmaceutical drugs.

Although similar to alcohols, phenols have unique distinguishing properties. Unlike alcohols, where the hydroxyl group is bound to a saturated carbon atom, phenols have the hydroxyl group attached to an unsaturated aromatic (alternating double and single bond) hydrocarbon ring such as benzene. Consequently, phenols have greater acidity than alcohols due to stabilization of the conjugate base through resonance in the aromatic ring.

Properties

Phenol is appreciably soluble in water, with about 84.2 g dissolving in 1000 mL (0.88 M). Homogeneous mixtures of phenol and water at phenol to water mass ratios of ~2.6 and higher are also possible. The sodium salt of phenol, sodium phenoxide, is far more water soluble.

Acidity

Phenol is weakly acidic and at high pHs gives the phenolate anion C₆H₅O^âˆ' (also called phenoxide):

PhOH ⇌ PhO^âˆ' + H⁺          (K = 10^âˆ'10)

Compared to aliphatic alcohols, phenol is about 1 million times more acidic, although it is still considered a weak acid. It reacts completely with aqueous NaOH to lose H⁺, whereas most alcohols react only partially. Phenols are less acidic than carboxylic acids, and even carbonic acid.

One explanation for the increased acidity over alcohols is resonance stabilization of the phenoxide anion by the aromatic ring. In this way, the negative charge on oxygen is delocalized on to the ortho and para carbon atoms. In another explanation, increased acidity is the result of orbital overlap between the oxygen's lone pairs and the aromatic system. In a third, the dominant effect is the induction from the sp² hybridised carbons; the comparatively more powerful inductive withdrawal of electron density that is provided by the sp² system compared to an sp³ system allows for great stabilization of the oxyanion.

The pK_a of the enol of acetone is 10.9, comparable to that for phenol. The acidities of phenol and acetone enol diverge in the gas phase owing to the effects of solvation. About 1/3 of the increased acidity of phenol is attributable to inductive effects, with resonance accounting for the remaining difference.

Phenoxide anion

The phenoxide anion has a similar nucleophilicity to free amines, with the further advantage that its conjugate acid (neutral phenol) does not become entirely deactivated as a nucleophile even in moderately acidic conditions. Phenols are sometimes used in peptide synthesis to "activate" carboxylic acids or esters to form activated esters. Phenolate esters are more stable toward hydrolysis than acid anhydrides and acyl halides but are sufficiently reactive under mild conditions to facilitate the formation of amide bonds.

Tautomerism

Phenol exhibits keto-enol tautomerism with its unstable keto tautomer cyclohexadienone, but only a tiny fraction of phenol exists as the keto form. The equilibrium constant for enolisation is approximately 10^âˆ'13, meaning that only one in every ten trillion molecules is in the keto form at any moment. The small amount of stabilisation gained by exchanging a C=C bond for a C=O bond is more than offset by the large destabilisation resulting from the loss of aromaticity. Phenol therefore exists essentially entirely in the enol form.

Phenoxides are enolates stabilised by aromaticity. Under normal circumstances, phenoxide is more reactive at the oxygen position, but the oxygen position is a "hard" nucleophile whereas the alpha-carbon positions tend to be "soft".

Reactions

Phenol is highly reactive toward electrophilic aromatic substitution as the oxygen atom's pi electrons donate electron density into the ring. By this general approach, many groups can be appended to the ring, via halogenation, acylation, sulfonation, and other processes. However, phenol's ring is so strongly activatedâ€"second only to anilineâ€"that bromination or chlorination of phenol leads to substitution on all carbons ortho and para to the hydroxy group, not only on one carbon. Phenol reacts with dilute nitric acid at room temperature to give a mixture of 2-nitrophenol and 4-nitrophenol while with concentrated nitric acid, more nitro groups get substituted on the ring to give 2,4,6-trinitrophenol which is known as picric acid.

Aqueous solution of phenol is weakly acidic and turns blue litmus slightly to red. Phenol is easily neutralized by sodium hydroxide forming sodium phenate or phenolate, but it being weaker than carbonic acid cannot be neutralized by sodium bicarbonate or sodium carbonate to liberate carbon dioxide

C₆H₅OH + NaOH â†' C₆H₅ONa + H₂O

When a mixture of phenol and benzoyl chloride when shaken in presence of dilute sodium hydroxide solution, phenyl benzoate is formed. This is an example of Schotten-Baumann reaction:

C₆H₅OH + C₆H₅COCl â†' C₆H₅OCOC₆H₅ + HCl

Phenol is reduced to benzene when it is distilled with zinc dust or its vapour is passed over granules of zinc at 400 °C:

C₆H₅OH + Zn â†' C₆H₆ + ZnO

When phenol is reacted with diazomethane in the presence of boron trifluoride (BF₃), anisole is obtained as the main product and nitrogen gas

C₆H₅OH + CH₂N₂ â†' C₆H₅OCH₃ + N₂

Production

Because of phenol's commercial importance, many methods have been developed for its production. The dominant current route, accounting for 95% of production (2003), involves the partial oxidation of cumene (isopropylbenzene) via the Hock rearrangement:

C₆H₅CH(CH₃)₂ + O₂ â†' C₆H₅OH + (CH₃)₂CO

Compared to most other processes, the cumene-hydroperoxide process uses relatively mild synthesis conditions, and relatively inexpensive raw materials. However, to operate economically, there must be demand for both phenol, and the acetone by-product.

An early commercial route, developed by Bayer and Monsanto in the early 1900s, begins with the reaction of a strong base with benzenesulfonate:

C₆H₅SO₃H + 2 NaOH â†' C₆H₅OH + Na₂SO₃ + H₂O

Other methods under consideration involve:

• hydrolysis of chlorobenzene, using base (Dow's Process) or steam (Raschigâ€"Hooker process):

C₆H₅Cl + H₂O â†' C₆H₅OH + HCl

• direct oxidation of benzene with nitrous oxide, a potentially "green" process:

C₆H₆ + N₂O â†' C₆H₅OH + N₂

• oxidation of toluene, as developed by Dow Chemical:

C₆H₅CH₃ + 2 O₂ â†' C₆H₅OH + CO₂ + H₂O

In the Lummus Process, the oxidation of toluene to benzoic acid is conducted separately.

Phenol is also a recoverable byproduct of coal pyrolysis.

Uses

The major uses of phenol, consuming two thirds of its production, involve its conversion to precursors to plastics. Condensation with acetone gives bisphenol-A, a key precursor to polycarbonates and epoxide resins. Condensation of phenol, alkylphenols, or diphenols with formaldehyde gives phenolic resins, a famous example of which is Bakelite. Partial hydrogenation of phenol gives cyclohexanone, a precursor to nylon. Nonionic detergents are produced by alkylation of phenol to give the alkylphenols, e.g., nonylphenol, which are then subjected to ethoxylation.

Phenol is also a versatile precursor to a large collection of drugs, most notably aspirin but also many herbicides and pharmaceutical drugs. Phenol is also used as an oral anesthetic/analgesic in products such as Chloraseptic or other brand name and generic equivalents, commonly used to temporarily treat pharyngitis.

Niche uses

Phenol is so inexpensive that it attracts many small-scale uses. It once was widely used as an antiseptic, especially as carbolic soap, from the early 1900s to the 1970s. It is a component of industrial paint strippers used in the aviation industry for the removal of epoxy, polyurethane and other chemically resistant coatings.

Phenol derivatives are also used in the preparation of cosmetics including sunscreens, hair colorings, and skin lightening preparations.

Concentrated phenol liquids are commonly used in the surgical treatment of ingrown toenails to prevent a section of the toenail from growing back. This process is called phenolization.

Phenol is also used for permanent treatment of ingrown toe and finger nails, a procedure known as a chemical matrixectomy. The procedure was first described by Otto Boll in 1945. Since that time it has become the chemical of choice for chemical matrixectomies performed by podiatrists.

History

Phenol was discovered in 1834 by Friedlieb Ferdinand Runge, who extracted it (in impure form) from coal tar. Runge called phenol "Karbolsäure" (coal-oil-acid, carbolic acid). Coal tar remained the primary source until the development of the petrochemical industry. In 1841, the French chemist Auguste Laurent obtained phenol in pure form.

In 1836, Auguste Laurent coined the name "phène" for benzene; this is the root of the word "phenol" and "phenyl". In 1843, French chemist Charles Gerhardt coined the name "phénol".

The antiseptic properties of phenol were used by Sir Joseph Lister (1827â€"1912) in his pioneering technique of antiseptic surgery. Lister decided that the wounds themselves had to be thoroughly cleaned. He then covered the wounds with a piece of rag or lint covered in phenol, or carbolic acid as he called it. The skin irritation caused by continual exposure to phenol eventually led to the substitution of aseptic (germ-free) techniques in surgery.

Phenol is the active ingredient in some oral analgesics such as Chloraseptic spray and Carmex.

Phenol was the main ingredient of the Carbolic Smoke Ball, an ineffective device marketed in London in the 19th century as protecting against influenza and other ailments, and the subject of the famous law case Carlill v Carbolic Smoke Ball Company.

Second World War

The toxic effect of phenol on the central nervous system, discussed below, causes sudden collapse and loss of consciousness in both humans and animals; a state of cramp precedes these symptoms because of the motor activity controlled by the central nervous system. Injections of phenol were used as a means of individual execution by the Nazis during the Second World War. It was originally used by the Nazis in 1939 as part of Action T4. Although Zyklon-B pellets were used in the gas chambers to exterminate large groups of people, the Nazis learned that extermination of smaller groups was more economical via injection of each victim with phenol. Phenol injections were given to thousands of people, especially at Auschwitz-Birkenau. Approximately one gram is sufficient to cause death. One of the best known inmates to be executed with a phenol injection in Auschwitz was St. Maximilian Kolbe, a Polish Catholic priest who volunteered to undergo two weeks of starvation and dehydration in the place of another inmate.

Natural occurrences

It is a normal metabolic product, excreted in quantities up to 40 mg/L in human urine.

The temporal gland secretion of male elephants showed the presence of phenol and 4-methylphenol during musth.

It is also one of the chemical compounds found in castoreum. This compound is gathered from the plants the beaver eats.

Occurrence in whisky

Phenol is a measurable component in the aroma and taste of the distinctive Islay scotch whisky, generally ~30 ppm, but can be over 150 ppm in the malted barley used to produce whisky.

Biodegradation

Cryptanaerobacter phenolicus is a bacterium species that produces benzoate from phenol via 4-hydroxybenzoate. Rhodococcus phenolicus is a bacterium species able to degrade phenol as sole carbon sources.

Toxicity

Phenol and its vapors are corrosive to the eyes, the skin, and the respiratory tract. Its corrosive effect on skin and mucous membranes is due to a protein-degenerating effect. Repeated or prolonged skin contact with phenol may cause dermatitis, or even second and third-degree burns. Inhalation of phenol vapor may cause lung edema. The substance may cause harmful effects on the central nervous system and heart, resulting in dysrhythmia, seizures, and coma. The kidneys may be affected as well. Long-term or repeated exposure of the substance may have harmful effects on the liver and kidneys. There is no evidence that phenol causes cancer in humans. Besides its hydrophobic effects, another mechanism for the toxicity of phenol may be the formation of phenoxyl radicals.

Since phenol is absorbed through the skin relatively quickly, systemic poisoning can occur in addition to the local caustic burns. Resorptive poisoning by a large quantity of phenol can occur even with only a small area of skin, rapidly leading to paralysis of the central nervous system and a severe drop in body temperature. The LD₅₀ for oral toxicity is 300â€"500 mg/kg for dogs, rabbits, or mice; the minimum lethal human dose was cited as 140 mg/kg.

Chemical burns from skin exposures can be decontaminated by washing with polyethylene glycol, isopropyl alcohol, or perhaps even copious amounts of water. Removal of contaminated clothing is required, as well as immediate hospital treatment for large splashes. This is particularly important if the phenol is mixed with chloroform (a commonly-used mixture in molecular biology for DNA and RNA purification). Phenol is also a reproductive toxin causing increased risk of abortion and low birth weight indicating retarded development in utero.

Phenols

The word phenol is also used to refer to any compound that contains a six-membered aromatic ring, bonded directly to a hydroxyl group (-OH). Thus, phenols are a class of organic compounds of which the phenol discussed in this article is the simplest member.

See also

• Bamberger rearrangement
• Claisen rearrangement
• Cresols
• Fries rearrangement
• Polyphenol

References

External links

• International Chemical Safety Card 0070
• Phenol Material Safety Data Sheet
• National Pollutant Inventory: Phenol Fact Sheet
• NIOSH Pocket Guide to Chemical Hazards
• CDC - Phenol - NIOSH Workplace Safety and Health Topic
• IARC Monograph: "Phenol"
• Arcane Radio Trivia outlines competing uses for Phenol circa 1915