Sulphonates nucleophilic substitution

In Volume 13 reactions of aromatic compounds, excluding homolytic processes due to attack of atoms and radicals (treated in a later volume), are covered. The first chapter on electrophilic substitution (nitration, sulphonation, halogenation, hydrogen exchange, etc.) constitutes the bulk of the text, and in the other two chapters nucleophilic substitution and rearrangement reactions are considered. 

The hydroxy-nitro dye Naphthol Yellow S (6.233 Cl Acid Yellow 1) was discovered in 1879 by Caro and is still manufactured. It is produced by sulphonation of 1-naphthol to give l-naphthol-2,4,7-trisulphonic acid, followed by replacement of the 2- and 4-sulpho groups in nitric acid medium. Nucleophilic substitution of l-chloro-2,4-dinitrobenzene with 4-aminodiphenylamine-2-sulphonic acid gives Cl Acid Orange 3 (6.234). 

As an alternative to the oxidation of sulphides and sulphoxides (see Chapter 10), sulphones can be prepared by the nucleophilic substitution reaction of the sulphinite anion on haloalkanes. In the absence of a phase-transfer catalyst, the reaction times are generally long and the yields are low, and undesirable O-alkylation of the sulphinite anion competes with S-alkylation. The stoichiometric reaction of the preformed tetra-n-butylammonium salt of 4-toluenesulphinic acid with haloalkanes produces 4-tolyl sulphones in high yield [1], but it has been demonstrated that equally good... 

Polymeric phosphonium salt-bound carboxylate, benzenesulphinate and phenoxide anions have been used in nucleophilic substitution reactions for the synthesis of carboxylic acid esters, sulphones and C/O alkylation of phenols from alkyl halides. The polymeric reagent seems to increase the nucleophilicity of the anions376 and the yields are higher than those for corresponding polymer phase-transfer catalysis (reaction 273). 

Nucleophilic substitution of toluene- -sulphonates (tosy-lates) and other sulphonic esters of secondary steroidal alcohols has received much attention, both in studies of reaction mechanisms, and also as a route for the conversion of alcohols into their epimers. One of the most important practical objectives has been the synthesis of 3a-hydroxy-5a-steroids, which include androsterone and a wide variety of metabolites of the steroid hormones, Tosylates of equatorial 3jS-alcohols (15) give 3a-alcohols or their derivatives (16) in acceptable... 

Many steroid secondary alcohols are resistant to acid-catalysed dehydration, but can be converted into olefins by elimination reactions of their sulphonate esters, usually the toluene 3 -sulphonate ( tosylate ) or methanesulphonate ( mesylate ). These elimination reactions always accompany attempted nucleophilic substitution of the sulphonate (p. 41), and can be made to predominate by appropriate choice of reaction conditions. Activated alkaline alumina has been used to prepare A - and AH-olehns from the sulphonates of 3 - [131] and i2a-alcohols [132]. In the latter case the naphthalene-i-sulphonate was most effective, and the methanesulphonate distinctly less so, suggesting that steric acceleration occurs with the more bulky naphthalenesulphonate [ 132c]. This view is strengthened by the enhanced efficiency of elimination of a i2a-sulphonate in the presence of a 17a-methyl group, which increases the compression at C(i2) [132b]. The mechanism and stereochemical features of these heterogeneous reactions have not been described in detail. 

Reaction of nitrosyl disulphonate, 0N(S03), with hydroxylamine-N-sulphonate is reported to be subject to catalysis by ferric salts at low concentrations, and to depend on the alkalinity through the hydrolysis of the catalyst . In mildly alkaline solution (pH 6-11), the rates of decomposition of this sul-phonate have been shown to be consistent with the existence of two reaction paths, one forming NO and the other sulphite radicals . The processes are assumed to represent bimolecular nucleophilic substitution by water. 

II. NUCLEOPHILIC SUBSTITUTION A. Activating Effects for C—O Cleavage in Sulphonate Esters... 

Reactivities of brosylates, mesylates and tosylates are similar (Table 3), and show relatively small variations with solvent and alkyl group (R). Tosylate/mesylate rate ratios vary from 0.5 to 2.0 in S l solvolytic reactions of adamantyl sulphonates48. Slightly higher ratios may be observed for SN2 reactions in dipolar aprotic solvents, e.g. second-order rate constants for nucleophilic substitution in n-octyl sulphonates by thiocyanate anion show tosylate/mesylate rate ratios increasing from 0.7 in methanol to 1.5 in chlorobenzene and in cyclohexane, and to 4.4 in DMSO12. 

Nucleophilic substitution by a hydroxyl ion displaces a hydride ion. Alizarin plants were subsequently built in Germany and England [17-19]. The procedure developed by Koch (B.A.S.F.) is based on the sulphonation of the anthraquinone with oleum followed by alkali fusion under addition of an oxidising agent (Fig. (4)) [20]. 

Several compounds have been prepared by nucleophilic substitution of chlorine in 2-chloro-l,3-dithian with Grignard reagent (RMgBr), malonic esters, and phenols.A mechanism for the de-ethoxycarbonylation of the 2-(l,3-dithianyl)malonates by sodium chloride or sodium ethoxide has been studied. 2-Chlorotetrahydrofuran reacts with nucleophiles such as 2-lithio-2-phenyl-l,3-dithian (326) by three simultaneous mechanisms i.e. substitution, proton abstraction, and electron transfer) to give the products (327)—(330) (Scheme 12)/° When a dithian (331 R = H or COiMe) was treated with a sulphonyl chloride in pyridine, ring-expansion to the 5//-l,4-dithiepin (332) occurred instead of the expected formation of a sulphonate. ... 

The substituents at the least hindered, primary 6- and 6 -positions reacting preferentially and the other primary substituent, of the more crowded neo-pentyl type at the 1 -primary position, reacting more slowly them the more favorable, but secondary, 4-position. In accord with this mechanism, inversion of chirality is always observed when nucleophilic substitution occurs at a chiral centre, in this case at C-4. By this process, 4-sulphonate esters of sucrose are converted by substitution and inversion of configuration at C-4 into g-D-fructofuranosyl a-D-galactopyranoside (F)... 

Nucleophilic substitution of the sulphonyloxy substituents in these partially substituted sulphonate esters of sucrose readily affords 6,6 -di- and l, 6,6 -tri-substituted sucrose derivatives, such as the corresponding chlorides and azides, from which the deoxy- and amino-derivatives,respectively, can be prepared. 

The t-butylsulphonyl group readily undergoes nucleophilic displacement by RS and RO groups, making this a preparatively useful route. t-Butyl 3-thienyl sulphone is also easily dimetalated in the 2- and 5-positions. The dialdehyde formed upon reaction with DMF does not, however, undergo nucleophilic substitution. 

Ghosh and coworkers [109] have reported the development of a novel class of HIV-1 protease inhibitors which incorporate a cyclic sulphone moiety for binding to the P2 subsite. For the provision of cis-2-alkyl-3-hydroxy-tetrahydrothiophene building blocks (for example, 85), Sharpless epoxida-tions of ( )-4-methyl-2-penten-l-ol under catalytic conditions with (+)-diethyl L-tartrate and gave epoxy alcohol (86) of 90% ee (Scheme 5.37). Several steps were then required to access compound (85), including cyanide-induced Payne rearrangement and introdution of sulphur by a double nucleophilic substitution. The (5,S)-antipode of compound (85) was accessed via Sharpless epoxidation using (-)-diethyl D-tartrate. 

Nucleophilic substitution of octyl methane sulphonate by anions in biphasic chlorobenzene-water is catalysed by a lipophilic cryptand containing a ,4 alkyl side chain. Lipophilic cryptates exist as monomeric species in low-polarity solvents... 

Miscellaneous. 3-(Toluene-p-sulphonyl)azetidines provide a route to a variety of 3-alkyI-azetidines via nucleophilic substitution. The solvolysis of l-t-butyl-3-azetidinyl-3-toluene-p-sulphonate (181) has been investigated in... 

Nucleophilic substitution with sodium sulphide has been used to prepare thiapropellanes (Scheme 27), The sulphone of (129) was very unstable thermally and readily gave 1,4-dimethylenecyclohexane (see further Hoffman and Stohrer, /. Amer. Chem. Soc., 1972, 94, 779). Further salts of (130) and (131) are described. 

Nucleophilic substitution reactions of the secondary sulphonyloxy groups of sulphonate derivatives of cellulose have been investigated in hexamethyl phosphorus triamide using acetoxy-ions as the nucleophile. ... 

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