Reactions of Phenols

Show the mechanism of the reaction of p-methylphenol with 2-methylpropene and H3P04 catalyst to yield the food additive BHT. 

The hydroxyl group is a strongly activating, ortho- and para-directing substituent in electrophilic aromatic substitution reactions (Section 16.5). As a result, phenols are highly reactive substrates for electrophilic halogenation, nitration, sulfonation, and Friedel-Crafts reactions. 

Quinones are an interesting and valuable class of compounds because of their oxidation-reduction (redox) properties. They can be easily reduced to hydLroquinones (p-dihydroxybenzenes) by reagents such as NaBH4 and SnCl2, and hydroquinones can be easily reoxidized back to quinones by Fremy s salt. 

The redox properties of quinones are important to the functioning ( living cells, where compounds called ubiquinones act as biochemical ox dizing agents to mediate the electron-transfer processes involved in energ production. Ubiquinones, also called coenzymes Q, are components of tli cells of ail aerobic organisms, from the simplest bacterium to humans. They are so named because of their ubiquitous occurrence in nature. 

Ubiquinones function within the mitochondria of cells to mediate respiration process in which electrons are transported from the biological reducing agent NADH to molecular oxygen. Although a complex series of steps is involved in the overall process, the ultimate result is a cycle whereby NADH is oxidized to NAD, O2 is reduced to water, and energy is produced. Ubiquinone acts only as an intermediary and is itself unchanged. 

The transition state for Sn2 displacement of a benzylic halide is stabilized by conjugation with the pi electrons in the ring. 

Propose a mechanism for the reaction of benzyl bromide with ethanol to give benzyl ethyl 

Show how you would synthesize the following compounds, using the indicated starting materials. 

Much of the chemistry of phenols is like that of aliphatic alcohols. For example, phenols can be acylated to give esters, and phenoxide ions can serve as nucleophiles in the Williamson ether synthesis (Section 14-5). Formation of phenoxide ions is particularly easy because phenols are more acidic than water, aqueous sodium hydroxide depro-tonates phenols to give phenoxide ions. 

Aspirin inactivates two cyclooxygenases, named COX-1 and COX-2, and prevents the formation of critical prostaglandins in the body. Inhibition of COX-2 relieves the pain, while inhibition of COX-1 results in stomach irritation and upset. 

In addition to its use in making resins and adhesives, phenol is also the starting material for the synthesis of chlorinated phenols and the food preservatives BHT (butylated hydroxy toluene) and BHA (butylated hydroxyanisole). Penta-chlorophenol, a widely used wood preservative, is prepared by reaction of phenol with excess CI2. The herbicide 2,4-D (2,4-dichlorophenoxyacetic acid) is prepared from 2,4-dichlorophenol, and the hospital antiseptic agent hexa-chlorophene is prepared from 2,4,5-trichlorophenol. 

The food preservative BHT is prepared by Friedel-Crafts alkylation of p-methylphenol (p-cresol) with 2-methylpropene in the presence of acid BHA is prepared similarly by alkylation of p-methoxyphenol. 

Phenols don t undergo oxidation in the same way that alcohols do because they don t have a hydrogen atom on the hydroxyl-bearing carbon. Instead, oxidation of a phenol yields a cyclohexa-2,5-diene-l,4-dione, or quinone. Many different oxidizing agents will accomplish the transformation, with Na2Cr207 a common choice for simple phenols and potassium nitrosodisulfo-nate [(KS03)2N0], called Fremy s salt, used in more complex cases. 

Interactive to use a web-based palette to predict products from a variety of reactions involving phenols. 

Alcohols have a characteristic O-H stretching absorption at 33( 3600 cm in the infrared spectrum. The exact position of the absorption ] depends on the extent of hydrogen bonding in the sample. Unassociated alcohols show a fairly sharp absorption near 3600 cm 1, whereas hydrogen-1 

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Many of the reactions of phenols are frequently given also by their derivatives, e.g.f salicylic acid (p. 352) beha es like phenol towards a number of reagents. 

The evidence outlined strongly suggests that nitration via nitrosation accompanies the general mechanism of nitration in these media in the reactions of very reactive compounds.i Proof that phenol, even in solutions prepared from pure nitric acid, underwent nitration by a special mechanism came from examining rates of reaction of phenol and mesi-tylene under zeroth-order conditions. The variation in the initial rates with the concentration of aromatic (fig. 5.2) shows that mesitylene (o-2-0 4 mol 1 ) reacts at the zeroth-order rate, whereas phenol is nitrated considerably faster by a process which is first order in the concentration of aromatic. It is noteworthy that in these solutions the concentration of nitrous acid was below the level of detection (< c. 5 X mol... 

Electrophilic Aromatic Substitution Reactions of Phenols (Continued)... 

Reaction of phenol with 1 2 epoxypropane in aqueous sodium hydroxide at 150°C gives a single product C9H12O2 m 90% yield Suggest a rea sonable structure for this compound... 

Allyl phenyl ether is pre pared by the reaction of phenol with allyl bromide as described in Section 24 11... 

In the reaction of phenol with hydroxide ion the stronger acid (phenol) is on the left side of the equation and the weaker acid (water) is on the nght... 

Phenolic Resins. Phenohc resins (qv) are formed by the reaction of phenol [108-95-2] C H O, and formaldehyde [50-00-0] CH2O. If basic conditions and an excess of formaldehyde are used, the result is a resole phenohc resin, which will cure by itself Hberating water. If an acid catalyst and an excess of phenol are used, the result is a novolac phenohc resin, which is not self-curing. Novolac phenohc resins are typically formulated to contain a curing agent which is most often a material known as hexamethylenetetraamine [100-97-0] C H22N4. Phenohc resin adhesives are found in film or solution... 

Long-chain esters of pentaerythritol have been prepared by a variety of methods. The tetranonanoate is made by treatment of methyl nonanoate [7289-51-2] and pentaerythritol at elevated temperatures using sodium phenoxide alone, or titanium tetrapropoxide in xylene (12). PhenoHc esters having good antioxidant activity have been synthesized by reaction of phenols or long-chain aUphatic acids and pentaerythritol or trimethyl olpropane (13). 

Depending on the ring substituent, trifluoromethoxyben2enes can be made by the sequential chlorination—fluorination of anisole(s) (351—354). A one-step process with commercial potential is the BF (or SbF2)-cataly2ed reaction of phenol with carbon tetrachloride/hydrogen fluoride (355). Aryl trifluoromethyl ethers, which may not be accessible by the above routes,may be made by fluorination of aryl fluoroformates or aryl chlorothioformates with sulfur tetrafluoride (348) or molybdenum hexafluoride (356). 

The most important commercial chemical reactions of phenol are condensation reactions. The condensation reaction between phenol and formaldehyde yields phenoHc resins whereas the condensation of phenol and acetone yields bisphenol A (2,2-bis-(4-hydroxyphenol)propane). PhenoHc resins and bisphenol A [80-05-7] account for more than two-thirds of U.S. phenol consumption (1). 

PhenoHc resins are prepared by the reaction of phenol or substituted phenol with an aldehyde, especially formaldehyde, in the presence of an acidic or basic catalyst. Their thermosetting character and the exotherm associated with the reaction presented technical barriers to commercialization. In 1900, the first U.S. patent was granted for a phenoHc resin, using the resin in cast form as a substitute for hard mbber (10). 

Special resoles are obtained with amine catalysts, which affect chemical and physical properties because amine is incorporated into the resin. For example, the reaction of phenol, formaldehyde, and dimethylamine is essentially quantitative (28). 

In the reaction of phenol and bisphenol F with hexa, nmr spectra show the transient appearance of benzoxazine intermediates after 2 h at 103°C, all the benzoxazine decomposed to the diphenyknethylene and benzylamine intermediates (15). 

Methylphenol. This phenol, commonly known as o-cresol, is produced synthetically by the gas phase alkylation of phenol with methanol using modified alumina catalysis or it may be recovered from naturally occurring petroleum streams and coal tars. Most is produced synthetically. Reaction of phenol with methanol using modified zeoHte catalysts is a concerted dehydration of the methanol and alkylation of the aromatic ring. 2-Methylphenol [95-48-7] is available in 55-gal dmms (208-L) and in bulk quantities in tank wagons and railcars. 

Reactions. Saligenin [90-01-7] undergoes the typical reactions of phenols and benzyl alcohol. When heated above 100°C, it transforms into a pale yellow resinous material. Amorphous condensation products are obtained when saligenin reacts with acetic anhydride, phosphoms pentachloride, or mineral acids. Upon boiling with dilute acids, saligenin is converted into a resinous body, saliretin, a condensed form of saligenin. Condensation reactions of saligenin with itself in the absence of any catalysts and in the presence of bases have also been studied. 

Phenolic Resins. PhenoHc resins [9003-35 ] (qv) are thermosets prepared by the reaction of phenol with formaldehyde, through either the base-cataly2ed one-stage or the acid-cataly2ed two-stage process. The Hquid intermediate may be used as an adhesive and bonding resin for plywood, particle board, ftberboard, insulation, and cores for laminates. The physical properties for typical phenoHc laminates made with wood are Hsted in Table 1. 

Phenols. Phenols are unreactive toward chloroformates at room temperature and at elevated temperatures the yields of carbonates are relatively poor (< 10%) in the absence of catalysis. Many catalysts have been claimed in the patent Hterature that lead to high yields of carbonates from phenol and chloroformates. The use of catalyst is even more essential in the reaction of phenols and aryl chloroformates. Among the catalysts claimed are amphoteric metals or thek haUdes (16), magnesium haUdes (17), magnesium or manganese (18), secondary or tertiary amines such as imidazole (19), pyridine, quinoline, picoline (20—22), heterocycHc basic compounds (23) and carbonamides, thiocarbonamides, phosphoroamides, and sulfonamides (24). 

Other Coatings Resins. A wide variety of other resin types are used in coatings. PhenoHc resins, ie, resins based on reaction of phenols and formaldehyde, have been used in coatings for many years. Use has been declining but there are stUl significant appHcations, particularly with epoxy resins in interior can coatings. 

From Phenol. In the type of condensation discovered by von Pechmaim in 1883, coumarin is formed by reaction of phenol [108-95-2] with malic (34), maleic, or fumaric acids (35—38) in the presence of concentrated sulfuric acid. 

Coumarin can also be formed by the reaction of phenol with diketene (40). Similarly, diphenols can react with hydroxycarboxyUc acids or beta-ketoesters to give hydroxycoumaria derivatives. The reaction of resorciaol with malic acid produces umbeUiferone (7-hydroxycoumaria) and its reaction with ethyl acetoacetate gives beta-methylumbeUiferone (7-hydroxy-4-methylcoumaria). 

The express method of phenolic compounds determination was designed. It is based on heterogeneous azo-coupling reaction of phenols, which different extracts of fresh raw material contain, with aryldiazonium salts grafted on the silica surface. We can carry out phenols analysis on-site, as formation of immobilized azocompounds leads to a drastic change in the sorbent s color. Thus, we pui pose a new method, that allows to indicate herb phenols in aqueous and non-aqueous medias and to compare it with a well-known Folin-Ciocalteau method. 

The PVF is made by acidic reaction between poly(vinyl alcohol) (PVA) and formaldehyde. The poly(vinyl alcohol) is, in turn, made by hydrolysis of poly(vinyl acetate) or transesterification of poly(vinyl acetate). Thus, residual alcohol and ester functionality is usually present. Cure reportedly occurs through reaction of phenolic polymer hydroxyls with the residual hydroxyls of the PVA [199]. The ester residues are observed to reduce bond strength in PVF-based systems [199]. This does not necessarily extend to PVF-P adhesives. PVF is stable in strong alkali, so participation of the acetals in curing is probably unimportant in most situations involving resoles. PVF is physically compatible with many phenolic resins. 

Murray, G.S., An Investigation into the Chemistry of the Reactions of Phenol-Fonnaldehyde Compounds with Novel Crosslinking Agents, Ph.D. The.sis. Portsmouth University, Portsmouth, 1993. 

In the manufacture of pure resorcinol resins, the reaction can be violently exothermic unless controlled by the addition of alcohols. Because the alcohols perform other useful functions in the glue mix, they are left in the liquid adhesive. PRF adhesives are generally prepared firstly by reaction of phenol with formaldehyde to form a PF resol polymer, that has been proved to be in the greatest percentage, and often completely, linear [95], In the reaction step that follows the resorcinol chemical is added in excess to the PF-resol to react it with the PF-resin -CH2OH groups to form PRF polymers in which the resorcinol groups can be resorcinol chemical or any type of resorcinol-formaldehyde polymer. 

Verify that the position of equilibrium for the reaction between phenol and hydroxide ion lies to the right by comparing the pK of the acid on the left to the acid on the right. Which acid is stronger Do the same for the reaction of phenol with hydrogen carbonate ion. 

Chcmically, Bakelite is a phenolic resin, produced by reaction of phenol and formaldehyde. On heating, water is eliminated, many cross-links form, and the polymer sets into a rocklike mass. The cross-linking in Bakelite and other thermosetting resins is three-dimensional and is so extensive that we can t really speak of polymer "chains." A piece of Bakelite is essentially one large molecule. 

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