Sulfonyl halides substitution reactions

Sulfonate esters are especially useful substrates in nucleophilic substitution reactions used in synthesis. They have a high level of reactivity, and, unlike alkyl halides, they can be prepared from alcohols by reactions that do not directly involve bonds to the carbon atom imdeigoing substitution. The latter aspect is particularly important in cases in which the stereochemical and structural integrity of the reactant must be maintained. Sulfonate esters are usually prepared by reaction of an alcohol with a sulfonyl halide in the presence of pyridine ... 

Besides radical additions to unsaturated C—C bonds (Section III.B.l) and sulfene reactions (see above), sulfonyl halides are able to furnish sulfones by nucleophilic substitution of halide by appropriate C-nucleophiles. Undesired radical reactions are suppressed by avoiding heat, irradiation, radical initiators, transition-element ion catalysis, and unsuitable halogens. However, a second type of undesired reaction can occur by transfer of halogen instead of sulfonyl groups283-286 (which becomes the main reaction, e.g. with sulfuryl chloride). Normally, both types of undesired side-reaction can be avoided by utilizing sulfonyl fluorides. 

Nucleophilic substitution at RSO2X is similar to attack at RCOX. Many of the reactions are essentially the same, though sulfonyl halides are less reactive than halides of carboxylic acids. The mechanisms are not identical, because a tetrahedral intermediate in this case (148) would have five groups on the central atom. Though this is possible (since sulfur can accommodate up to 12 electrons in its valence shell) it seems more likely that these mechanisms more closely resemble the Sn2 mechanism, with a trigonal bipyramidal transition state (148). There are two major experimental results leading to this conclusion. 

The reactions represented by (191) are all nucleophilic substitutions occurring at a sulfonyl sulfur. Besides cpdisulfones substitutions of this kind are also of frequent occurrence in the chemistry of many other types of sulfonyl derivatives such as sulfonyl halides, aryl esters of sulfonic acids, etc., and many of the general aspects of their behaviour and mechanism have been examined in considerable detail. Most of the remainder of this section will be devoted to consideration of the results of such studies. 

Other reactions have been studied for synthesizing these polymers, including the electrophilic aromatic substitution of acyl and sulfonyl halides on aromatic reactants and the nickel-catalyzed aromatic coupling of aromatic dihalides [Yonezawa et al., 2000]. 

Reaction between sulfonyl halides and ammonia or amines 3-17 Vicarious substitution of aryl nitro compounds... 

Esters of aliphatic and aromatic sulfonic acids are conveniently prepared in high yields from alcohols and sulfonyl halides. A basic medium is required. By substituting sodium butoxide for sodium hydroxide in butanol, the yield of n-butyl p-toluenesulfonate is increased from 54% to 98%. Ethyl benzenesulfonate and nuclear-substituted derivatives carrying bromo, methoxyl, and nirro groups are prepared from the corresponding sulfonyl chlorides by treatment with sodium ethoxide in absolute ethanol the yields are 74-81%. Pyridine is by far the most popular basic medium for this reaction. Alcohols (C -Cjj) react at 0-10° in 80-90% yields, and various phenols can be converted to aryl sulfonates in this base. "... 

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. 

Sulfenyl halides (1) will also undergo nucleophilic addition with alkenes (Scheme 1) to yield the episulfides (7), which can suffer a further nucleophilic addition to give the sulfides (8). The nucleophilic substitutions of sulfenyl (1) (see Chapter 4, p. 54) and sulfonyl (3) chlorides (see Chapter 7, p. 106) probably generally proceed by the SN2 reaction mechanism, which with the sulfonyl halide (3) involves the trigonal bipyramidal transition... 

In a so-called vicarious nucleophilic substitution of hydrogen,75 2,3-diphenylpyrido[2,3-6]-pyrazine is alkylated in the 8-position by [(chloromethyl)sulfonyl]benzene. This reaction proceeds by addition of the carbanion to the electron-deficient ring position of a nitroarene or electrophilic heteroaromatic system, followed by base-induced -elimination of the corresponding hydrogen halide.76,77 As with quinoxalines and naphthyridines, the reaction with pyrido[2,3-6]pyrazines also affords products bisannulated at the pyrazine or the pyridine moiety, depending on the kind of 2/3-substitution (cf. Section 7.2.3.1.2.2.2.). 

With the exception of propadiene, the addition of sulfonyl halides and seleno-sulfonates to allenes can be totally regioselective (equation (57)) [116], The attack of sulfony] radical on the central carbon atom, which leads to a stabilized ally] radical, is probably less reversible, if at all, than the addition to the terminal carbon. The ensuing atom or group transfer occurs at the less substituted end of the allyl radical. Therefore, the reaction results in 1,2-addition to the less substituted double bond. Subsequent oxidation of the adducts when X = SePh gives rise to allylic alcohols since the [2, 3]-sigmatropic rearrangement of selenoxide is much faster than the elimination of PhSeOH. 

ALkah-metal compounds of indole undergo reactions with haloalkanes, acyl halides, sulfonyl halides, and trialkylchlorosilanes to give the corresponding 1-substituted indoles 30 ... 

Organic sulfonate esters, like sulfonyl halides, also readily undergo nucleophilic substitution reactions as previously mentioned (p 23). For example, oxygen-labelled (-)menthyl phenylmethanesulfonate 18 reacted with / -tolylmagnesium bromide to give labelled benzyl p-tolyl sulfone 19 with inversion of stereochemical configuration at the chiral sulfur atom (Equation 16). 

Polysulfonylation. The polysulfonylation route to aromatic sulfone polymers was developed independently by Minnesota Mining and Manufacturing (3M) and by Imperial Chemical Industries (ICI) at about the same time (81). In the polymerization 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 polymerization process was the discovery that, unlike the acylation reaction which requires equimolar amounts of aluminum chloride or other strong Lewis acids, sulfonylation can be accomplished with only catalytic amounts of certain halides, eg, FeQ3, SbQ, and InCl3. The reaction is a typical electrophilic substitution by an arylsulfonium cation (eq. 13). 

As in catalytic ylide epoxidation (see Section 10.2.1.1), an alternative catalytic cycle can be based on generation of the ylide in situ by reaction of a sulfide with an alkyl halide to form a salt, which can then be deprotonated [76]. In 2001, Saito et al. reported the asymmetric version of this cycle using a 3 1 ratio of alkyl halide to sulfonyl imine (see Scheme 10.18) [81]. Good yields and ee-values were reported for aryl- and styryl-substituted aziridines using stoichiometric amounts of sulfide 24, and the diastereoselectivities ranged from 1 1 to 4 1. Unfortunately, when loadings were reduced the reaction times became longer and lower yields were reported (see Table 10.2). 

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