Sulphoxides nucleophilic substitution reactions

Finally it should be mentioned that a number of nucleophilic substitution reactions of unactivated halides can be made to proceed in bipolar non-protic solvents such as dimethyl sulphoxide (DMSO), Me2S —Oe. No hydrogen-bonded solvent envelope, as in for example MeOH, then needs to be stripped from Ye before it can function as a nucleophile AG is thus much lower and the reaction correspondingly faster. Rate differences of as much as 109 have been observed on changing the solvent from MeOH to Me2SO. Chlorobenzene will thus react readily under these conditions with Me3COe ... 

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... 

On the other hand, in the case of a-halogenoethyl sulphoxides 503 an SN2-type displacement occurs with mercaptide anions and leads to a-alkylthioethyl sulphoxides 504, while the elimination-addition mechanism is operative with alkoxide anions, affording jS-alkoxyethyl sulphoxides577,596 505 (equation 306). Finally, the reaction of 1-halogeno-l-methylethyl derivatives with both nucleophiles mentioned above occurs via the elimination-addition mechanism596 (equation 307). The substitution reaction can also take place intramolecularly (equation 308) and it proceeds very easily (cf. Section IV.A.2.C)484,600. 

Concomitant formation of the dimerized compounds 76 and 77 with 56% and 26% yields, respectively, was observed with methyl p-toluensulphinate (07T10479). Previously these dimers were obtained in lower yields as secondary compounds in lithiation reactions (04T5785, 98T15287). The higher yield of dimerized side products may be due to a higher reactivity of the in situ generated sulphoxide, which reacts with the lithiated intermediates by nucleophilic substitution. (Scheme 15). 

Three-co-ordinate sulphur. The most inorganic example has been the study of the kinetics and mechanism of hydrolysis of dithionites. Kinetics of attack of iodide and of thiourea at the 55 -dimethylsulphinium cation (M62S-NH2+) in water and in aqueous dimethyl sulphoxide indicate pre-equilibrium protonation followed by a rate-determining associative process. The overall activation entropy is negative. Nucleophilic substitution, by vinyl-lithium, at the triphenylsulphonium cation (PhaS ) is also associative. Indeed the species (30) is an intermediate rather than a transition state. Comparison of the stereochemical courses of reactions at tetrahedral phosphorus and at three-co-ordinate sulphur, which is... 

The tetrakis-sulphoxides (67) have been reported as a new type of PT catalyst in a solid-liquid mode, for example in 5n reactions of 1-bromo-octane. Nucleophilic substitutions of 1-bromo-octane and benzyl bromide are again the test reactions in a report on the use of the sucrose-ethylene oxide adducts (68a) as PT catalysts in both solid-liquid and liquid-liquid modes. The methacrylate ester derivative (68b) has been polymerized to a cross-linked gel that acts in a TC capacity for the same reactions. In a related approach some modified dextran anion exchangers carrying lipophilic substituents, such as the modified hydroxypropylated dextran gel shown in (69), have been synthesized and shown to catalyse displacement reactions including the alkyl bromide to iodide transformation under TC conditions. ... 

Halogenovinyl sulphoxides 551 react with nucleophiles to give -substituted vinyl sulphoxides 552. The first step in the reaction is a Michael addition, followed by an elimination of a halide anion605,627 (equation 351). 

It is interesting to note that the oxidation of sulphoxides by peracids is faster in alkaline than in acidic solution. This is in contrast to the oxidation of sulphides and amines with the same reagents " . The oxidation rate of ortho-substituted aryl alkyl sulphoxides with aromatic peracids is less than the corresponding meta- and para-substituted species due to steric hindrance of the incoming peracid anion nucleophiles . Steric bulk in the alkyl group also has some effect . Such hindrance is not nearly so important in the oxidation reaction carried out under acidic conditions . 

Dimethyl sulphoxide has recently been used for tosylate elimination reactions [131 ], It is not clear whether this is a simple Ei process. The nucleophilic reactivity of dimethyl sulphoxide (p. 46) suggests the possibility of an indirect mechanism, with preliminary Sn2 substitution of the tosylate group by the oxygen atom of the reagent. This would permit elimination of an equatorial tosylate via the more favourably oriented axial oxysulphonium ion (c/. p. 47). 

In their study of the reactions of organotin compounds, Gielen et al [Gi 62-72] divided the solvent effect into two factors. They showed that whereas in polar solvents (methanol, dimethyl sulphoxide, dimethylformamide, etc.) the reactivity is governed by the steric effects of the substituents on the organotin compound, in apolar solvents (carbon tetrachloride, chlorobenzene, cyclohexane, etc.) inductive effects of these same substituents are manifested. Hence, the reactivity sequence of organotin compounds substituted in various ways is controlled by the solvent. According to this concept, in a polar medium the solvent behaves as a nucleophilic catalyst. 

Allenmark s work on anchimerically assisted reactions of sulphoxides" continues with a study of the rates of reduction of the syn- and anti-forms of e fo-cis-3-benzenesulphinylbicyclo[2,2,l]heptane-2-carboxylic acids. The syn-was more reactive than the an/i-isomer by a factor of more than 3.2 x 10 . The relative ease of formation of the acyloxysulphonium ion resulting from nucleophilic attack by the carboxy-group on sulphur accounts for this result, and also for the relative racemization rates of jS-carboxy-substituted sulphoxides. Pummerer reaction of one enantiomer of a benzyl o-carboxyphenyl sulphoxide in the presence of DCCI leads to 2-phenyl-3,l-benzoxathian-4-one (47) in an optically active form, indicating the transfer of chirality from S to C. ... 

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