Toluene, alkylation sulfonation

Oxazoles and benzoxazoles yield salts with acids, alkyl halides, methyl toluene-p-sulfonate, triethyloxonium fluoroborate, etc. Quaternization is subject to the well-known steric effect of bulky substituents 2-phenylbenzoxazole, for instance, does not react with ethyl iodide even at 240 °C. The weakly basic nature of oxazole (see Section 4.18.2.4) is reflected in the instability of its simple salts, such as hydrochlorides and picrates, which are readily hydrolyzed, even in air. 2-Aminooxazoles and 2-aminobenzoxazoles are alkylated at the ring nitrogen atom the anilinonaphthooxazole (124), on the other hand, reacts with methyl iodide to yield a mixture of methyl derivatives (equation 1). 

Hydrogenolysis of the toluene-4-sulfonate of an alcohol may be carried out with a nucleophilic hydride such as lithium aluminium hydride. There are also a series of radical methods based on the reduction of alkyl halides with tri- -butyltin hydride (BUjSnH). Finally, the source of the hydrogen may be the electrophilic proton, exemplified by the decomposition of organometallic reagents such as the Grignard reagent with water. 

Many of the convenient methods of preparing alkyl halides are based on the reactions of alcohols with reagents such as thionyl chloride and phosphorus pentachloride. These are dealt with in more detail in Section 2.3 on alcohols. The nucleophilic substitution of an alkyl methanesul-fonate or toluene-4-sulfonate with a sodium or potassium halide is a useful method. 

Alkoxides are nucleophiles and may be used to react with alkyl hahdes or alkyl toluene-4-sulfonates to form ethers (Scheme 2.1 Ic). 

The sulfonyl halides (ArSOjCl) convert the alcohol into a sulfonate (ArSOjOR), which is a better leaving group than the hydroxyl group. This allows a range of nucleophilic substitutions to be carried out, many of which parallel those found with alkyl halides. Alkyl halides such as iodides are formed by the nucleophilic substitution of the sulfonate by an iodide ion. The reaction in this case proceeds with inversion of configuration. Treatment of the sulfonate esters with bases such as sodium methoxide or collidine (2,4,6-trimethylpyridine), or even just heating them, can lead to the elimination of toluene-4-sulfonic acid and the formation of an alkene. 

Amines can displace a halide or a derivative of an alcohol, such as the methanesulfonate or toluene-4-sulfonate, with the eventual formation of a quaternary ammonium salt. Reaction with ammonia may lead to mixtures, since the initial alkylation increases the basicity of the nitrogen, and hence the primary amine reacts more rapidly than ammonia. Further reaction, although enhanced by the increase in basicity, may be impeded by steric hindrance arising from the additional alkyl groups. 

The Niki reaction (alkylation of dimedone by l,4-dibromo-2-methyl-2-butene, with formation of compound 218), applied to phloro-acetophenone and to 3-isopentyl-2,4,6-trihydroxyisobutyrophenone, leads respectively to 2,3-dihydrobenzofurans 219a and 219b. Furan 219b with toluene-p-sulfonic acid rearranges to the benzofuran 220b. 

Isopropylation of toluene by isopropyl halo- and alkyl-sulfonates (equation 54) has been performed by Olah et al. A variety of cattdysts, such as AlCb, AlCb-MeNOa and Nafion-H were employed, and the isomer distribution (o, m, p) in the product was determined. Sartori et al have recently reported an unusual Friedel-Crafts alkylation of lithium phenolates with ethyl pyruvate in the presence of AlCb to afford a-(2-hydroxyphenyl)ethyl lactates (22), which are the precursors of 3-methyl-2,3-dihydrobenzo-furan-3-ols (23 Scheme 6). 

The alkyl halides used in the Michaelis-Becker reaction (cf. page 728) may be replaced by other alkylating agents such as dialkyl sulfates326 or alkyl sulfonates 295,327 even the use of carboxylic esters for alkylation of sodium dialkyl phosphites is the subject of a patent.328 It is noteworthy that p-toluene-sulfonates often have advantages over alkyl halides in that alcohols are readily converted into these esters and, further, that the p-toluenesulfonate ion liberated, being a weak nucleophile, causes fewer side reactions. Alkyl p-toluene-sulfonates rank between alkyl chlorides and bromides in their reactivity towards sodium dialkyl phosphites.286 p-Toluenesulfonates of secondary alcohols give poor yields of phosphonate. 

Inhibiting Side Reactions. As stated in a preceding section, undesired by-product sulfone formation is pronounced in the mono- and disulfonation of ai matic hydrocarbons such as benzene, toluene, or xylene with SO or strong oleum. The addition of acetic acid (about 5 per cent by weight of the hydrocarbon) inhibits, but does not eliminate, sulfone formation. Sodium sulfate and sodium benzenesulfonate are also said to inhibit sulfone formation from benzene. In sul nating dodecylbenzene detergent alkylate with SO3, sulfone formation does not occur as it does with benzene or toluene, but sulfonic anhydride formation does occur. This objection-... 

Alkylation of enolate anions is achieved readily with alkyl halides or other alkylating agents. Both primary and secondary alkyl, allyl or benzyl halides may be used successfully, but with tertiary halides poor yields of alkylated product often result because of competing elimination. It is sometimes advantageous to proceed by way of the toluene-p-sulfonate, methanesulfonate or trifluoromethane-sulfonate rather than a halide. The sulfonates are excellent alkylating agents and can usually be obtained from the alcohol in a pure condition more readily than... 

Enamines and metalloenamines provide a valuable alternative to the use of eno-lates for the selective alkylation of aldehydes and ketones. Enamines are a,p-unsaturated amines and are obtained simply by reaction of an aldehyde or ketone with a secondary amine in the presence of a dehydrating agent, or by heating in benzene or toluene solution in the presence of toluene-/7-sulfonic acid (TsOH) as a catalyst, with azeotropic removal of water (1.31). Pyrrolidine and morpholine are common secondary amines useful for forming enamines. All of the steps of the reaction are reversible and enamines are readily hydrolysed by water to reform the carbonyl compound. All reactions of enamines must therefore be conducted under anhydrous conditions, but once the reaction has been effected, the modified carbonyl compound is liberated easily from the product by addition of dilute aqueous acid to the reaction mixture. 

The lone-pair electron on the nitrogen is responsible for electrophilic reactions on its side. Thus, heterocyclic nitrogen atom of quinoline and isoquinolines react with electrophiles, as alkyl halides, alkyl sulfates, alkyl-toluene-p-sulfonates, etc., providing quinolinium and isoquinolinium salts. 

Table 4. Relative Rates of Solvolysis of Methoxy phenyl-alkyl Toluene-p-sulfonates ...

Fusion of methyl or ethyl toluene-p-sulfonates with 4-hydroxy-6-methyl-l,3,3a,7-tetraazaindene (135) gives only one salt, which on treatment with alkali is converted into a N-alkyl-4-oxo derivative. 

Because halides are poorer leaving groups than p toluene sulfonate alkyl p toluene sulfonates can be converted to alkyl halides by 8 2 reactions involving chloride bro mide or iodide as the nucleophile... 

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. 

ALKYL, ARYL, or TOLUENE SULFONIC ACID, LIQUID containing more 2584 ... 

ALKYL,ARYL,OR TOLUENE SULFONIC ACID, SOLID containing more than 2585 ... 

---