Sulphonylation methods

Another important aspect of Schotten-Baumann reaction is sulphonylation whereby benzene sulphonyl chloride, CgH SOgCl (i.e., the corresponding acid chloride of benzene sulphonic acid, CgH SOgOH) is employed instead of benzoyl chloride, and almost similar structural analogues may be obtained. 

It has been established experimentally that Schotten-Baumann sulphonylation holds good for two different types of organic compounds, namely (a) Phenols—i.e., OH moiety attached directly to an aromatic ring, and b) Aniline—i.e., primary aromatic amine. These reactions are dealt with separately as under  

Explanation. The sulphonylation with phenol takes place in two steps essentially first, is the formation of sodium phenolate by the interaction of phenol with an excess of 10% w v) NaOH solution and secondly, the reaction between sodium phenolate and a small excess of benzene sulphonyl chloride to give rise to the formation of phenyl benzene sulphonate (I). 

the crystalline ester (I) is separated and the excess of benzene sulphonyl chloride gets hydrolyzed by the alkali producing the soluble sodium benzene sulphonate. 

Explanation. A suspension of freshly redistilled aniline (straw-yellow colour liquid) in sodium hydroxide solution [10% (w/v)] when treated in a similar manner with benzene sulphonyl 

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The sulphonylation method may be used for the S3mtheses of dichloramine-T and chloramine-T starting from toluene-p-sulphonamide and dichloramine-T respectively. 

To convert the aryl sulphonyl chloride into the sulphonamide, use either of the following methods —... 

The procedure is not usually applicable to aminosulphonic acids owing to the interaction between the amino group and the phosphorus pentachloride. If, however, the chlorosulphonic acid is prepared by diazotisation and treatment with a solution of cuprous chloride in hydrochloric acid, the crystalline chlorosulphonamide and chlorosulphonanilide may be obtained in the usual way. With some compounds, the amino group may be protected by acetylation. Sulphonic acids derived from a phenol or naphthol cannot be converted into the sulphonyl chlorides by the phosphorus pentachloride method. 

The sulphonanilldes may be prepared by either of the following methods —(i) Reflux the solution of the sulphonyl chloride in benzene obtained as above, with 2 5 g. of aniline for 1 hour. Concentrate the benzene solution to half its volume and cool in ice. Collect the solid which separates on a filter, wash with hot water, and recrystallise from ethanol or dilute ethanol. 

One method of preparing sulphlnic acids has already been described (diazo reaction. Section IV,65). Reduction of a sulphonyl chloride with zinc powder and water affords the zinc salt of the sulphinic acid, converted by sodium carbonate to the sodium salt (in which form it is conveniently isolated), and by hydrochloric acid into the somewhat unstable sulphinic acid, for example ... 

An alternative method of purification consists in dissolving the crude sulphonyl chloride in the minimum volume of boiling chloroform, transferring rapidly to a warm separatory funnel, and separating the lower chloroform layer upon cooling the chloroform solution, the crystalline sulphonyl chloride separates, and is collected by filtration with suction. A further quantity is obtained by concentrating the mother liquor. 

A second paper161 describes the use of the same base in either THF or t-butanol for the elimination of a-acetoxy phenyl sulphones as outlined in equation (68), in essence a reaction sequence very similar to the Julia olefin synthesis (Section III.B.3) except in the method by which the sulphonyl group is finally removed. 

The use of chlorine as an oxidizing agent for the conversion of sulphoxides into sulphones is completely unsuccessful under anhydrous conditions. In aqueous solutions, the sulphone is formed but this is usually part of a complex mixture of chlorinated sulphoxides, chlorinated sulphones and sulphonyl chlorides89, so that the reaction is usually not very useful as a preparative method for alkyl sulphones. Dimethyl sulphone has however been obtained in 70% yield in one isolated case90. In methanol solution dibenzyl sulphoxide is cleanly oxidized to dibenzyl sulphone and benzyl sulphonyl chloride in reasonable overall yield91. 

Aromatic substitution by sulphonyl azides has been applied to the synthesis of cyclic sulphonamides not as readily available by other methods 16h For example, thermolysis of biphenyl-2-sulphonyl azide (60) in w-dodecane or in cyclohexane 78> at 150 °C gives high yields (partic-... 

In general, reductive removal of a sulphonyl group from vinyl sulphones is not a stereospecific reaction. However, two methods, both developed by Julia, result in stereospecific products. The first one involves reaction of the vinyl sulphone with n-BuMgCl in the presence of a transition metal catalyst such as Ni(acac)2. This method was used to synthesize a pheromone having a (Z, )-diene (equation 27)59. Palladium catalysts can also be used for... 

Dansyl chloride (dimethylaminonaphthalene-5-sulphonyl chloride) will react with free amino groups in alkaline solution (pH 9.5-10.5) to form strongly fluorescent derivatives (Figure 10.14). This method can also be used in combination with chromatographic procedures for amino acid identification in a similar manner to the FDNB reagent but shows an approximately 100-fold increase in sensitivity. This makes it applicable to less than 1 nmol of material and more amenable for use with very small amounts of amino acids liberated after hydrolysis of peptides. The dansyl amino acids are also very resistant to hydrolysis and they can be located easily after chromatographic separation by viewing under an ultraviolet lamp see Procedure 10.1. 

Dansyl chloride (5-dimethylaminonaphthlene-l-sulphonyl chloride) and the related dabsyl chloride (4-dimethyl-aminoazobenzene-4 -sulphonyl chloride) have also been used. Sensitivity of the latter method is poor and both suffer problems from interference with reagent excess. 

Another study employed CE for the determination of the stoichiometry of the conjugation reaction between immonuglobulin and Lissamine rhodamine-B sulphonyl chloride (LRSC). The chemical structure of the dye is shown in Fig. 3.162. Separation of the unconjugated dye from the conjugated end product was performed by CE using an uncoated fused-silica capillary column (60 cm X 75 //m i.d.). The running buffer consisted of 10 rnM borate and 0.5 mM sodium dodecyl sulphate. The separation voltage was 20 kV and analytes were detected by a fluorescence detector. It was concluded from the results that the CE method combined with... 

A -Sulphonylation of pyrroles and indoles, using a liquidtliquid two-phase procedure [3, 48, 50-54], is superior to the traditional methods, which frequently require preformation of the heteroaryl sodium derivative, whereas A-sulphonylation of indole using a sulphonyl chloride in the presence of pyridine leads to the formation of the l,4-dihydro-4-indol-3-ylpyridine [49], The liquid liquid two-phase procedure outlined below is suitable for most A -Sulphonylation reactions with heteroaromatic compounds, but it is sometimes advisable to add a second quantity of the sulphonyl chloride during the course of the reaction [22,47]. 

Method A The sulphonyl azide (50 mmol), PhH (200 g), NaHCO, (1.68 g) and Adogen (0.22 g, 5 mmol) are heated in an autoclave at 125°C for 3 h. The cooled reaction mixture is filtered, washed well with H,0, dried (Na2S04), and evaporated to yield the azepine, which is purified by chromatography on alumina. 

Method To a solution of (Et0)2P(0)TeNa (5 mmol) in EtOH (10 mL) is added a solntion of benzene sulphonyl chloride (0.88 g, 5 mmol) in THF (10 mL) under N2. An instantaneous reaction occurs and the colour of the mixture changes from colourless to deep black. After stirring for 20 min, a solution of benzyl chloride (0.64 g, 5 mmol) and catalytic amounts of BzEtjN Cr (0.01 g) in THE (10 mL) is added. The mixture is refluxed for 4 h. After evaporating the solvent nnder reduced pressure, the residue is treated with CHCI3 (50 mL). After filtration, the organic phase is evaporated to dryness. The crnde product is recrystallized from EtOH, giving the pure product (1.93 g (82.4%) m.p. 145-147°C). 

A further technique said to be useful on an industrial scale for the ECF conversion of alkanesulphonyl fluoride and tetramethyl sulphone to form per-fluoroalkane sulphonyl fluorides involves the continuous extraction of products from the electrolyte and hydrogen gas stream. The method claims high yields (93%) without recovery problems of prior art [151]. 

The bromonium ion may be generated by other methods than direct bromination solvolytic reaction of trans-2-bromo-[(4-bromophenyl)sulphonyl]cyclohexane (36) (and cyclopentane) forms (reaction 7) the bromonium ion94 (37). If Br- is present in the reaction mixture, the generation of Br2 (and olefin) is observed (Scheme 14). This confirms the reversibility of the bromonium ion formation in the usual bromination pathway. When other olefin scavengers are present, a formal Br+ transfer is observed94. This may occur without the formation of Bit. 

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