Dimethyl sulphoxide, as solvent

A new synthesis of 2,3-disubstituted succinodinitriles (31), from aldehydes, has overcome a number of problems associated with older syntheses. With dimethyl sulphoxide as solvent, the entire synthesis can be carried out in a single reaction pot using the appropriate aldehyde and alkyl halide, together with potassium cyanide and ethyl cyanoacetate (Scheme 20). 

The use of dimethyl sulphoxide as a dipolar aprotic solvent is well known,7 and the present method can be regarded as a model procedure and has been applied to the preparation of a number of N-w-alkyl-pyrroles and N-w-alkyl indoles.8 The yield of N-benzylindole is considerably higher than in previously reported preparations and is as good as that reported for the preparation of N-methylindole in liquid ammonia.4 The present method is, however, less laborious and quicker to carry out. Very high yields are obtained in reactions using w-alkyl halides and moderately good yields with secondary alkyl halides. The reactions should be compared with those recently reported for pyrryl-thallium.9... 

Some time ago it was reported that rates of dimethyl sulphoxide exchange with nickel(ii) in dimethyl sulphoxide-dichloromethane and dimethyl sulphoxide-nitromethane solvent mixtures were almost independent of solvent composition. Recently, rates of dimethylformamide exchange at nickel(n) in dimethylformamide-nitromethane solvent mixtures have also been found to be remarkably insensitive to solvent-composition variation. Whereas in the dimethyl sulphoxide-dichloromethane solvent mixtures nickel(n) exists as [Ni(DMSO)e] +, in dimethylformamide-nitromethane mixtures the composition of the nickel(n) co-ordination shell varies with solvent composition, with preferential solvation by the nitromethane rather than by the dimethylformamide. These observations are difficult to explain in terms of an /d... 

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. 

Popova and colleagues47 carried out TLC of oxidation products of 4,4 -dinitrodiphenyl sulphide (the sulphoxide and sulphone) on silica gel + a fluorescent indicator, using hexane-acetone-benzene-methanol(60 36 10 l) as solvent mixture. Morris130 performed GLC and TLC of dimethyl sulphoxide. For the latter, he applied a 6% solution of the sample in methanol to silica gel and developed with methanol-ammonia solution(200 3), visualizing with 2% aqueous Co11 thiocyanate-methanol(2 1). HPLC separations of chiral mixtures of sulphoxides have been carried out. Thus Pirkle and coworkers131-132 reported separations of alkyl 2,4-dinitrophenyl sulphoxides and some others on a silica-gel (Porosil)-bonded chiral fluoroalcoholic stationary phase, with the structure ... 

Another marked physical difference between sulphides and sulphoxides (or sulphones) is that sulphoxides (and lower alkyl sulphones) are hygroscopic and dissolve quite readily in water or protic solvents such as alcohols, and even more so lower alkyl or alkyl aryl sulphoxides are almost freely miscible with water. This can be accounted for by the formation of the strong hydrogen bond between the S—O bond in the sulphoxides and water molecules. Moreover, lower alkyl sulphoxides and sulphones such as dimethyl sulphoxide (DMSO) or sulpholene can dissolve a number of metallic salts, especially those of alkali and alkaline earth metals, and hence these compounds have been widely utilized as versatile and convenient solvents in modern organic chemistry26 (Table 3). 

Solutions of potassium superoxide-crown ether in dimethyl sulphoxide have been shown to cause oxidation of the solvent to the sulphone75 such a reaction could possibly be used synthetically. In the presence of water the reaction probably proceeds as shown ... 

Parker37 defined class 4 as solvents "which cannot donate suitable labile hydrogen atoms to form strong hydrogen bonds with an appropriate species and proposed the designation dipolar aprotic solvents he extended their range down to s > 15 and quoted as examples acetone, acetonitrile, benzonitrile, dimethylformamide, dimethyl sulphoxide, nitrobenzene, nitromethane (41.8) and sulfolane (tetramethylene sulphone) (44), where e varies from 21 to 46.5, and the dipole moment p from 2.7 to 4.7 debye. 

Photolysis of sulphonyl azides in dimethyl sulphoxide with 2537 A light gives IV-sulphonylsulphoximines 12 in 15—50% yield 5>. The reaction was formulated as going via a nitrene intermediate which was trapped by the nucleophilic solvent... 

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 ... 

Dimethyl sulphoxide is a highly hygroscopic liquid and is miscible with water. Its m.p. is 18.5° and b.p. 189°C. It is one of those versatile compounds which is a solvent not only for many organic compounds but many inorganic salts as well. 

If the dimer mechanism interpretation is correct, addition of a HBA co-solvent, e.g. dimethyl sulphoxide (DMSO) (/> value = 0.76)178, in catalytic amounts should increase the reaction rate by forming a mixed aggregate RNH2 OS(CH3)2 (B DMSO), equation 35, where the amine acts now as a HBD, and therefore this mixed aggregation should increase its nucleophilicity. DMSO has been shown to increase the nitrogen electron density of primary and secondary amines161. 

An example of such a third competing step is the reaction of the intermediate aryl radical with H-atom donors present in the reaction medium, possibly the solvent itself. Indeed, aryl radicals are good H-atom scavengers and reduction of aryl halides is often carried out in organic solvents such as acetonitrile (ACN), lV,Af-dimethylformamide (DMF), dimethyl sulphoxide (DMSO), and ethers, that are good H-atom donors... 

Since their discovery in 1866, it has been known that sulphoxides are reducible by zinc and acid to the conesponding sulphide [63], fhe equivalent electrochemical process cannot be characterised because sulphoxides also decrease the hydrogen overpotential [64], Dialkyl sulphoxides are not reduced in absence of protons and dimethyl sulphoxide is used as a solvent for electrochemical reduction. Phenyl methyl sulphoxide gives a single two-electron wave on polarography in both ethanol (E./, = -2.17 V vs. see) and dimethylformamide (E./, = -2.32 V vs. see), forming phenyl methyl sulphide [65],... 

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