Functional Sulphoxides

Sulphinyl-conjugated radicals R S(0)6r R , are formed from l,3-bis(alkane-sulphinyl)alkanes and HO radical, or from a sulphoxide with Ph radical. Discussion of structures and synthetic application of a-sulphinyl carbanions is in Chapter 2 in this volume. 

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Some limitations of the subject surveyed have been necessary in order to keep the size of the chapter within the reasonable bounds. Accordingly, to make it not too long and readable, the discussion of the methods of the sulphoxide synthesis will be divided into three parts. In the first part, all the general methods of the synthesis of sulphoxides will be briefly presented. In the second one, methods for the preparation of optically active sulphoxides will be discussed. The last part will include the synthetic procedures leading to functionalized sulphoxides starting from simple dialkyl or arylalkyl sulphoxides. In this part, however, the synthesis of achiral, racemic and optically active sulphoxides will be treated together. Each section and subsection includes, where possible, some considerations of mechanistic aspects as well as short comments on the scope and limitations of the particular reaction under discussion. 

Acylation of oc-sulphinyl carbanions. Synthesis of fS-oxosulphoxides. oi-Ketosulphoxides have found very broad application in organic synthesis (see, for example. Reference 532). For this reason, a great deal of examples of their syntheses appear in the chemical literature. The main approach to this class of functionalized sulphoxides involves the reaction of a-sulphinyl carbanions with carboxylic esters or acyl halides. 

The condensation reaction is promoted by certain polar solvents and of the many which have been tested dimethyl sulphoxide appears to be the most effective. As usual with linear condensation polymers molecular equivalence and near-absence of monofunctional material is necessary to ensure a high molecular weight. Moisture and alcohols can also have a devastating effect on the molecular weight. In the case of water it is believed that 4-chlorophenyl 4-hydroxyphenyl sulphone is formed which functions as an effective chain terminator. Gross contamination with air is also believed to reduce the maximum attainable molecular weight as well as causing intense discolouration. 

FIGURE 20. The free surface on the sulphur atom, S, (A2), as a function of ring strain for sulphide, sulphoxide and sulphone molecules. 

Some further chemical methods, mainly for detection of sulphoxides (e.g., in visualization), are based on reactions of other functional groups present in the molecule, or on the molecule as a whole. 

These results may easily be rationalized by assuming that the formation of hydroxy sulphoxides 91, 92 and 93 from hydroperoxysulphides 89 and 90 is an intramolecular oxidation-reduction reaction proceeding through a five-membered transition state 94. However, an alternative intermolecular mechanism in which the approach of the oxidant is directed by the hydroperoxy or the hydroxy function in the reductant cannot be excluded. 

Addition of heteroatomic nucleophiles to divinyl sulphoxides gives mono and bi-functionalized products as well as compounds resulting from their cyclization. For... 

Interestingly, comparison of the values of pAHB and the acidity constants pKa in a series of the same family of compounds, such as carbonyl compounds, amines, pyridines and sulphoxides, shows that a good correlation exists between p/CHB and pgiving straight lines in each series of compounds with parallel slopes. This enables one to calculate the difference of the several pKa values at the same p/CHB value, and vice versa. Thus, at p= 0, p/CHB values of various functional groups were determined and are shown in Table 13. 

This chapter deals with the reverse of these reactions. Since this is not a simple process, a brief discussion of the nature of the S—O bonds in sulphoxides and sulphones will be of assistance in understanding the requirements for reduction of these functional groups. 

Optically active peracids such as percamphoric acid have been used to oxidize selectively one sulphoxide enantiomer in a racemic mixture. These reactions involve the use of 0.5 molar equivalents of the peracid in either ether47 or chloroform48 as solvent. The presence of nitro groups causes the oxidant to be consumed without oxidation of the sulphoxide functionality. This method is usually used to obtain an optically active sulphoxide by recovery of the unreacted material after oxidation. 

Carbonyl oxides (formed by the reaction of diazo compounds with singlet oxygen) may also be used to oxidize sulphoxides74. The corresponding sulphone is formed in reasonable yields and the reaction may be carried out in the presence of the sulphide functionality. The reaction proceeds as shown in equation (21) and involves initial nucleophilic attack by the carbonyl oxide on the sulphoxide sulphur atom followed by the facile departure of the carbonyl compound yielding the required sulphone. 

There are many transition metal ion oxidants used in organic chemistry for the interconversion of functional groups. Those which have been used for the preparation of sulphones from sulphoxides will be discussed below. It is very interesting to note that this type of oxidant often reacts more rapidly with sulphoxides than with sulphides and so sulphoxides may be selectively oxidized with transition metal ion oxidants in the presence of sulphides. This is in direct contrast to the oxidation of sulphides and sulphoxides with peracids and periodate, for example, where the rate of reaction of the sulphide is more than 100 times that for the corresponding sulphoxide. 

If a mixture of diphenyl sulphide and the corresponding sulphoxide are treated with osmium tetroxide in boiling ether for 48 hours the sulphide is unchanged whilst the sulphoxide is converted into the sulphone in 96% yield with concomitant production of osmium trioxide140. It thus seems that this method would be useful synthetically for the preparation of sulphones from sulphoxides containing sulphide functionalities. Ruthenium tetroxide may be used in place of osmium(VIII) oxide148. 

Surprisingly there are relatively few data on the cathodic or anodic behaviour of sulfoxides 77. It is quite interesting to consider that the sulphoxide function is intermediate between the corresponding thioether and sulphone. Thus data concerning the cathodic properties of sulphoxides derive both from the basicity of the S=0 group and from their capability to allow the formation of the corresponding thioether, while cleavage reactions on the C—S bond are quite unusual. On the other hand, oxidation may provide sulphones. 

Data on the behaviour of a-ethylenic (82) and a, a-diethylenic (83) sulphoxides in aqueous-methanolic solutions are also available76. The sulphoxide function, when activated both by benzylic and propargylic moieties (as in 84), gives76 a reduction wave (E = — 1.44 V vs. SCE) in basic aqueous methanolic media. However, no results are available for cathodical reduction of activated sulphoxides. 

In a set of volumes on sulphur-containing functional groups, the volume on the sulphonium group appeared in 1981 (in two parts). The present volume deals with sulphones and sulphoxides and further volumes, one on derivatives of sulphinic acids and another on derivatives of sulphenic acids, are now in the course of preparation, with a volume on sulphonic acid derivatives planned for the more distant future. 

More definite evidence comes from an MO study of the S—O stretching in dimethyl sulphoxide , where three basis sets were employed a STO-3G one (I), a 4-3IG one (double-zeta, II) and a 3G -l- d one (III). Table 6 reports the main results the small effect of the double-zeta, and the dramatic effect of the 3d functions, are clearly visible. Notice also how the C—S bond length and the bond angles are by far less sensitive to basis set changes. 

An accurate MO study of the inversion barrier in dimethyl sulphoxide showed that the height of the calculated barrier is much more sensitive to the overall quality of the basis set, and to geometry optimization, than to the presence of 3d functions. This study predicts an S—O bond lengthening to 1.55 A, and the best estimate of the barrier is 39.9 kcal mol This was the difference in energy between optimum planar and pyramidal... 

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