Sulfonation Routes

One of the earliest of the water soluble calixarenes was made by sulfonation of the upper rim, and this remains a frequently used procedure. Experimental details have been reported for the sulfonation of jh 4S9c 0H 4S9c 

The sulfonatocalixarenes are important in their own right as water soluble compounds but can also serve as intermediates for additional functionalization, generally by conversion to a sulfonamide. Treatment of p-sulfonatocalixarenes 

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Recently, a study of this rearrangement has been repeated and extended in order to determine the influence of a- and y-substitution on the position of the 68-69 equilibrium in the presence of silica, and the utility of this reaction for a novel and convenient synthesis of highly substituted a, / -unsaturated ketones, by subsequent treatment with CuCl2 in methanol-water136. An ion-pair mechanism can also be suggested for the facile rearrangement of sulfone 70 to 71, a key intermediate in the Hoffmann-La Roche Sulfone Route to Vitamin A137. 

Before 1970, there were five different processes used to make phenol in the United States the sulfonation route, chlorobenzene hydrolysis, the Raschig process, cumene oxidation, and the benzoic acid route. By 1978, the first three processes had essentially disappeared, and 98 percent of the remaining plant capacity was based on cumene oxidation. The oxidation process is shown in Fig. 10.33. 

The Julia olefination reaction is highly regioselective and ( )-stereoselective, providing a valuable alternative to the Schlosser reaction for making rrans -disubstituted olefins. The reaction involves condensation of a metalated alkyl phenyl sulfone with an aldehyde to yield a P-hydroxysulfone, which is then subjected to a reductive elimination to produce the alkene. There are limitations to the preparation of tri- and tetra-substituted alkenes via the sulfone route because the P-alkoxy sulfones derived from addition of the sulfone anion to ketones may be difficult to trap and isolate or they may revert back to their ketone and sulfone precursors. 

A major detraction to the p-silyl sulfone route to alkenes is its narrow scope, owing to the paucity of methods for preparing the requisite p-silyl sulfones. The method has so far been largely restricted to monosubstituted and 1,1-disubstituted ethylene derivatives because the P-silyl sulfones have usually been most conveniently and economically prepared by the alkylation of a sulfone anion with iodomethyl-trimethylsilane. Unfortunately higher haloalkylsilanes are difficult to prepare and their alkylation chemistry remains unexplored. 

Charles Adolphe Wurtz and August Kekule further improved the process in 1867. The sulfonation route was developed to technical maturity in particular by Bayer and Monsanto. The first stage in the synthesis is the sulfonation of benzene with sulfuric add, generally using a 100% excess of sulfuric acid. In the second stage, the sulfonation product is neutralized with sodium hydroxide or sodium sulfite. The resulting benzenesulfonate, in solid form or as a concentrated aqueous solution, is heated with sodium hydroxide at temperatures of 320 to 340 °C, in cast-iron pans. The alkaline sodium phenolate solution is neutralized ( saturated ) with CO2 or, in the Monsanto process, with SO2. When the water has been distilled off substantially pure phenol with a crystallizing point of 40.5 °C is obtained. 

As demand for phenol started to grow owing to the increased use of phenolie resins and the advent of polycarbonates, more eompanies looked for proeess improvements which gave economie benefits. Although avoidanee of waste was not a prime target it became a faetor in the overall production costs. With the discovery of the cumene route (Seheme 2.3) for the co-production of phenol and acetone (propanone), the benzene sulfonation route quickly became obsolete in developed countries. Today the most modem phenol plants produce very little waste, the initial alkylation step being carried out using zeolite eatalysts, and overall yields based on benzene are almost 90%. 

In 1969, VSgtle [17] first outlined the sulfone route for the preparation of [2.2.0]metacyclophane as one of the rare metacyclophanes containing three aromatic units, hi 1981, Vogtle etal. prepared the [2.2.2.2]biphenylophane 10 in 48% yield by sulfone pyrolysis at 600 °C/10 torr [18]. 

Scheme 2.75 The leaction of iV-aryl-2-nitrosoanilines with sulfones (route a), acetates (route b) and phosphonoacetates (route b)...

Acid rhodamines are made by the iatroduction of the sulfonic acid group to the aminoxanthene base. The preferred route is the reaction fluorescein (2) with phosphorous pentachloride to give 3,6-dichlorofluoran (fluorescein dichloride) (23), which is then condensed with a primary aromatic amine in the presence of 2inc chloride and quicklime. This product is then sulfonated. For example, if compound (23) (fluorescein dichloride) is condensed with aniline and the product is sulfonated. Acid Violet 30 Cl45186) (24) is produced. 

Even ia 1960 a catalytic route was considered the answer to the pollution problem and the by-product sulfate, but nearly ten years elapsed before a process was developed that could be used commercially. Some of the eadier attempts iacluded hydrolysis of acrylonitrile on a sulfonic acid ion-exchange resia (69). Manganese dioxide showed some catalytic activity (70), and copper ions present ia two different valence states were described as catalyticaHy active (71), but copper metal by itself was not active. A variety of catalysts, such as Umshibara or I Jllmann copper and nickel, were used for the hydrolysis of aromatic nitriles, but aUphatic nitriles did not react usiag these catalysts (72). Beginning ia 1971 a series of patents were issued to The Dow Chemical Company (73) describiag the use of copper metal catalysis. Full-scale production was achieved the same year. A solution of acrylonitrile ia water was passed over a fixed bed of copper catalyst at 85°C, which produced a solution of acrylamide ia water with very high conversions and selectivities to acrylamide. 

Esters. Most acryhc acid is used in the form of its methyl, ethyl, and butyl esters. Specialty monomeric esters with a hydroxyl, amino, or other functional group are used to provide adhesion, latent cross-linking capabihty, or different solubihty characteristics. The principal routes to esters are direct esterification with alcohols in the presence of a strong acid catalyst such as sulfuric acid, a soluble sulfonic acid, or sulfonic acid resins addition to alkylene oxides to give hydroxyalkyl acryhc esters and addition to the double bond of olefins in the presence of strong acid catalyst (19,20) to give ethyl or secondary alkyl acrylates. 

Direct, acid catalyzed esterification of acryhc acid is the main route for the manufacture of higher alkyl esters. The most important higher alkyl acrylate is 2-ethyIhexyi acrylate prepared from the available 0x0 alcohol 2-ethyl-1-hexanol (see Alcohols, higher aliphatic). The most common catalysts are sulfuric or toluenesulfonic acid and sulfonic acid functional cation-exchange resins. Solvents are used as entraining agents for the removal of water of reaction. The product is washed with base to remove unreacted acryhc acid and catalyst and then purified by distillation. The esters are obtained in 80—90% yield and in exceUent purity. 

The cumene oxidation route is the lea ding commercial process of synthetic phenol production, accounting for more than 95% of phenol produced in the world. The remainder of synthetic phenol is produced by the toluene oxidation route via benzoic acid. Other processes including benzene via cyclohexane, benzene sulfonation, benzene chlorination, and benzene oxychl orin ation have also been used in the manufacture of phenol. A Hst of U.S. phenol production plants and their estimated capacities in 1994 are shown in Table 2, and worldwide plants and capacities are shown in Table 3. 

PoIysuIfonyIa.tlon, The polysulfonylation route to aromatic sulfone polymers was developed independendy by Minnesota Mining and Manufacturing (3M) and by Imperial Chemical Industries (ICI) at about the same time (81). In the polymerisation step, sulfone links are formed by reaction of an aromatic sulfonyl chloride with a second aromatic ring. The reaction is similar to the Friedel-Crafts acylation reaction. The key to development of sulfonylation as a polymerisation process was the discovery that, unlike the acylation reaction which requires equimolar amounts of aluminum chloride or other strong Lewis acids, sulfonylation can be accompHshed with only catalytic amounts of certain haUdes, eg, FeCl, SbCl, and InCl. The reaction is a typical electrophilic substitution by an arylsulfonium cation (eq. 13). 

An alternative synthesis route for PES involves the partial hydrolysis of dichlorodiphenyl sulfone (2) with base to produce 4-chloro-4 -hydroxydiphenylsulfone [7402-67-7] (3) followed by the polycondensation of this difimctional monomer in the presence of potassium hydroxide or potassium carbonate (7). 

As a variation on the base-catalyzed nucleopbilic displacement chemistry described, polysulfones and other polyarylethers have been prepared by cuprous chloride-catalyzed polycondensation of aromatic dihydroxy compounds with aromatic dibromo compounds. The advantage of this route is that it does not require that the aromatic dibromo compound be activated by an electron-withdrawing group such as the sulfone group. Details of this polymerization method, known as the Ullmaim synthesis, have been described (8). 

The single-monomer route (eq. 5) is preferred as it proves to give more linear and para-linked repeat unit stmctures than the two-monomer route. Other sulfone-based polymers can be similarly produced from sulfonyl haUdes with aromatic hydrocarbons. The key step in these polymerisations is the formation of the carbon—sulfur bond. High polymers are achievable via this synthesis route although the resulting polymers are not always completely linear. 

Methylphenol. T -Cresol is produced synthetically from toluene. Toluene is sulfonated to yield T i ra-toluenesulfonic acid, which is then converted to 4-methylphenol via the caustic fusion route. A minor amount of 4-methylphenol is also derived from petroleum cmde and coal tars. 4-Methylphenol [106-44-5] is available in 55-gal dmms (208-L) and in bulk quantities as a molten material. 

When sulfonic acids are neutralized to sulfonic acid salts, the materials become relatively innocuous and low in toxicity, as compared to the parent sulfonic acid (see Table 4). The neutralized materials cause considerably less eye and skin irritation. The most toxic route of entry for sulfonic acid salts is ingestion (39). The toxicity of neutralized sulfonic acids, especially detergent sulfonates, has been directiy related to the foaming capabiUty of the material. 

Various processes have been disclosed wherein moist soHd sodium pyrosulfite [7681-57-4] is stirred in a steam-heated vessel with sodium carbonate. The exothermic reaction at 80—110°C results in the drying of the product. A lower grade of sodium sulfite is produced commercially in the United States as a by-product of the sulfonation—caustic cleavage route to resorcinol (333). 

SuIfona.tlon, Sulfonation is a common reaction with dialkyl sulfates, either by slow decomposition on heating with the release of SO or by attack at the sulfur end of the O—S bond (63). Reaction products are usually the dimethyl ether, methanol, sulfonic acid, and methyl sulfonates, corresponding to both routes. Reactive aromatics are commonly those with higher reactivity to electrophilic substitution at temperatures > 100° C. Tn phenylamine, diphenylmethylamine, anisole, and diphenyl ether exhibit ring sulfonation at 150—160°C, 140°C, 155—160°C, and 180—190°C, respectively, but diphenyl ketone and benzyl methyl ether do not react up to 190°C. Diphenyl amine methylates and then sulfonates. Catalysis of sulfonation of anthraquinone by dimethyl sulfate occurs with thaHium(III) oxide or mercury(II) oxide at 170°C. Alkyl interchange also gives sulfation. 

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