Cresol alkylation

The fert-butyl carbocation acts as an electrophile and alkylates p-cresol. Alkylation occurs ortho to the -OH group for both steric and electronic reasons. 

I ovolac Synthesis and Properties. Novolac resins used in DNQ-based photoresists are the most complex, the best-studied, the most highly engineered, and the most widely used polymers in microlithography. Novolacs are condensation products of phenoHc monomers (typically cresols or other alkylated phenols) and formaldehyde, formed under acid catalysis. Figure 13 shows the polymerization chemistry and polymer stmcture formed in the step growth polymerization (31) of novolac resins. 

Polymer-type antioxidants have been prepared by Eriedel-Crafts reaction of -cresol andp- and/or y -chloromethylstyrene in the presence of boron trifluoride-etherate (198). The oligomeric product resulting from the alkylation of phenyl-a-naphthylamine using C12—15 propylene oligomer in the presence of AlCl or activated white clays is used as an antioxidant additive for lubricating oils (199). 

PMMA is not affected by most inorganic solutions, mineral oils, animal oils, low concentrations of alcohols paraffins, olefins, amines, alkyl monohahdes and ahphatic hydrocarbons and higher esters, ie, >10 carbon atoms. However, PMMA is attacked by lower esters, eg, ethyl acetate, isopropyl acetate aromatic hydrocarbons, eg, benzene, toluene, xylene phenols, eg, cresol, carboHc acid aryl hahdes, eg, chlorobenzene, bromobenzene ahphatic acids, eg, butyric acid, acetic acid alkyl polyhaHdes, eg, ethylene dichloride, methylene chloride high concentrations of alcohols, eg, methanol, ethanol 2-propanol and high concentrations of alkahes and oxidizing agents. 

Phenol. Phenol monomer is highly toxic and absorption by the skin can cause severe blistering. Large quantities can cause paralysis of the central nervous system and death. Ingestion of minor amounts may damage kidneys, Hver, and pancreas. Inhalation can cause headaches, dizziness, vomiting, and heart failure. The threshold limit value (TLV) for phenol is 5 ppm. The health and environmental risks of phenol and alkylated phenols, such as cresols and butylphenols, have been reviewed (66). 

Substituted heat-reactive resins are most widely used in contact-adhesive appHcations and, to a lesser extent, in coatings (77,78) -butylphenol, cresol, and nonylphenol are most frequendy used. The alkyl group increases compatibiHty with oleoresinous varnishes and alkyds. In combination with these resins, phenoHcs reduce water sensitivity. Common appHcations include baked-on and electrical insulation varnishes, and as modifiers for baking alkyds, rosin, and ester gum systems. Substituted heat-reactive resins are not used for air-dry coatings because of theh soft, tacky nature in the uncured state substituted nonheat-reactive phenoHcs are the modifying resin of choice in this case. 

Laminates. Laminate manufacture involves the impregnation of a web with a Hquid phenoHc resin in a dip-coating operation. Solvent type, resin concentration, and viscosity determine the degree of fiber penetration. The treated web is dried in an oven and the resin cures, sometimes to the B-stage (semicured). Final resin content is between 30 and 70%. The dry sheet is cut and stacked, ready for lamination. In the curing step, multilayers of laminate are stacked or laid up in a press and cured at 150—175°C for several hours. The resins are generally low molecular weight resoles, which have been neutralized with the salt removed. Common carrier solvents for the varnish include acetone, alcohol, and toluene. Alkylated phenols such as cresols improve flexibiUty and moisture resistance in the fused products. 

Gymene. Methyhsopropylben2ene [25155-15-1] can be produced over a number of different acid catalysts by alkylation of toluene with propylene (63—66). Although the demand for cymene is much lower than for cumene, one commercial plant was started up in 1987 at the Yan Shan Petrochemical Company in the People s RepubHc of China. The operation of this plant is based on SPA technology offered by UOP for cumene. The cymene is an intermediate for the production of y -cresol (3-methylphenol) [108-59-4]. 

Alkylated phenol derivatives are used as raw materials for the production of resins, novolaks (alcohol-soluble resins of the phenol—formaldehyde type), herbicides, insecticides, antioxidants, and other chemicals. The synthesis of 2,6-xylenol [576-26-1] h.a.s become commercially important since PPO resin, poly(2,6-dimethyl phenylene oxide), an engineering thermoplastic, was developed (114,115). The demand for (9-cresol and 2,6-xylenol (2,6-dimethylphenol) increased further in the 1980s along with the growing use of epoxy cresol novolak (ECN) in the electronics industries and poly(phenylene ether) resin in the automobile industries. The ECN is derived from o-cresol, and poly(phenylene ether) resin is derived from 2,6-xylenol. 

The solubihty of alkylphenols in water falls off precipitously as the number of carbons attached to the ring increases. They are generally soluble in common organic solvents acetone, alcohols, hydrocarbons, toluene. Solubihty in alcohols or heptane follows the generalization that "like dissolves like." The more polar the alkylphenol, the greater its solubihty in alcohols, but not in ahphatic hydrocarbons likewise with cresols and xylenols. The solubihty of an alkylphenol in a hydrocarbon solvent increases as the number of carbon atoms in the alkyl chain increases. High purity para substituted phenols, through Cg, can be obtained by crystallization from heptane. 

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. 

Methylphenol is converted to 6-/ f2 -butyl-2-methylphenol [2219-82-1] by alkylation with isobutylene under aluminum catalysis. A number of phenoHc anti-oxidants used to stabilize mbber and plastics against thermal oxidative degradation are based on this compound. The condensation of 6-/ f2 -butyl-2-methylphenol with formaldehyde yields 4,4 -methylenebis(2-methyl-6-/ f2 butylphenol) [96-65-17, reaction with sulfur dichloride yields 4,4 -thiobis(2-methyl-6-/ f2 butylphenol) [96-66-2] and reaction with methyl acrylate under base catalysis yields the corresponding hydrocinnamate. Transesterification of the hydrocinnamate with triethylene glycol yields triethylene glycol-bis[3-(3-/ f2 -butyl-5-methyl-4-hydroxyphenyl)propionate] [36443-68-2] (39). 2-Methylphenol is also a component of cresyHc acids, blends of phenol, cresols, and xylenols. CresyHc acids are used as solvents in a number of coating appHcations (see Table 3). 

Toluenesulfonic Acid. Toluene reacts readily with fuming sulfuric acid to yield toluene—sulfonic acid. By proper control of conditions, /)i7n7-toluenesulfonic acid is obtained. The primary use is for conversion, by fusion with NaOH, to i ra-cresol. The resulting high purity i7n -cresol is then alkylated with isobutylene to produce 2 (i-dii-tert-huty -para-cmso (BHT), which is used as an antioxidant in foods, gasoline, and mbber. Mixed cresols can be obtained by alkylation of phenol and by isolation from certain petroleum and coal-tar process streams. 

Stabilization of Fuels and Lubricants. Gasoline and jet engine fuels contain unsaturated compounds that oxidize on storage, darken, and form gums and deposits. Radical scavengers such as 2,4-dimethyl-6-/ f2 butylphenol [1879-09-0] 2,6-di-/ f2 -butyl-/)-cresol (1), 2,6-di-/ f2 -butylphenol [128-39-2], and alkylated paraphenylene diamines ate used in concentrations of about 5—10 ppm as stabilizers. 

ButylatedPhenols and Cresols. Butylated phenols and cresols, used primarily as oxidation inhibitors and chain terrninators, are manufactured by direct alkylation of the phenol using a wide variety of conditions and acid catalysts, including sulfuric acid, -toluenesulfonic acid, and sulfonic acid ion-exchange resins (110,111). By use of a small amount of catalyst and short residence times, the first-formed, ortho-alkylated products can be made to predominate. Eor the preparation of the 2,6-substituted products, aluminum phenoxides generated in situ from the phenol being alkylated are used as catalyst. Reaction conditions are controlled to minimise formation of the thermodynamically favored 4-substituted products (see Alkylphenols). The most commonly used is -/ fZ-butylphenol [98-54-4] for manufacture of phenoHc resins. The tert-huty group leaves only two rather than three active sites for condensation with formaldehyde and thus modifies the characteristics of the resin. 

Nylons 46, 6, 66, 610, 11 and 12 are polar crystalline materials with exceptionally good resistance to hydrocarbons. Esters, alkyl halides, and glycols have little effect. Alcohols generally have some swelling action and may in fact dissolve some copolymers (e.g. nylon 66/610/6). There are few solvents for the nylons, of which the most common are formic acid, glacial acetic acid, phenols and cresols. 

While phenol is the most common monomer for novolac manufacture, it is far more common to see incorporation of other phenolic materials with novolacs than with resoles. Cresols, xylenols, resorcinol, catechols, bisphenols, and a variety of phenols with longer alkyl side chains are often used. While most resoles are made with a single phenolic monomer, two or more phenolic materials are often seen in novolac formulae. These additional monomers may be needed to impart special flow characteristics under heat, change a glass transition temperature, modify cure speed, or to adjust solubility in the application process among others. 

Thus, reduction of the Mannich reaction product (65) from acetophenone leads to alcohol 66. Replacement of the hydroxyl group by chlorine (67) followed by displacement of halogen with the anion from o-cresol affords the ether 68. Removal of one of the methyl groups on nitrogen by means of the von Braun reaction or its modem equivalent (reaction with alkyl chloroformate followed by saponification) leads to racemic 69 which is then resolved with L-(+)-mandelic acid to give the levorotary antidepressant tomoxetine (69) [16]. 

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

The kinetics of alkylation by triphenylmethyl compounds have been studied. Hart and Cassis353 found that the alkylation of phenol and o-cresol by triphenylmethyl chloride in o-dichlorobenzene gave non-linear kinetic plots which were, however, rendered linear by presaturation of the reaction mixture with hydrogen chloride, precise third-order kinetics, equation (182)... 

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