Sulphinic acids oxidation

As has been mentioned in an earlier section, aqueous chlorination of sulphoxides leads to sulphones. If excess reagents are used, sulphonyl chlorides may be formed directly from sulphoxides in good yields (equation 75)89,90,193. In order for this reaction to be synthetically useful, the sulphoxide used should be symmetrical. The product is presumably formed in a stepwise manner via the sulphinyl chloride [RS(0)C1] and the sulphinic acid [RS(0)0H]. In the case of chloromethyl dichloromethyl sulphoxide, the only sulphonyl chloride formed is chloromethanesulphonyl chloride (equation 76) and this may be readily separated from the other products by distillation90,193. Similarly, oxidation of dichloromethyl methyl sulphoxide and methyl trichloromethyl sulphoxide with chlorine in aqueous acetic acid leads to the formation of methanesulphonyl chloride in 75% and 86% yields respectively. Other species are also produced but these are much more volatile and thus easily removed (equations 77 and 78). In the absence of acetic acid the yields are somewhat reduced. 

Whilst the sulphonic adds themselves cannot, in practice, he reduced, their sulphochlorides may he brought to a lower state of oxidation, that of the sulphinic acids, by treatment with metals, preferably with zinc. In this way the zinc salts of these acids are produced directly ... 

The direct reaction of [TCO4] in ethanolic solution with dppe and oxalic acid produces the red Tc" complex [Tc(ox)(dppe)2] (552). Attempts to prepare similar complexes with succinic acid, phthalic acid, or salicylic acid failed, or the complexes were stable in solution only. " Similarly, cationic complexes of Tc" are produced by reaction of the versatile precursor [TcO(OH)(dppe)2] (204) with various dithiocarbamates, which produces several complexes of general formula [Tc(dtc)(dppe)2] (553). For this reaction the reductant formamidine sulphinic acid (510) was required in an alkaline solution. The X-ray crystal structure of [Tc(S2CNMe2)(dppe)2] (554) shows a distorted octahedral geometry. Cyclic voltammetry reveals a reversible reduction wave Tc"/Tc couple at —0.53 V, and a reversible oxidation at +0.3 V for the Tc" /Tc" couple. The same compound (554) was also prepared from the thiourea precursor [TcO(tmtu)4] + (91).The reaction of this precursor in dmf in the presence of dppe produced a mixture of brown [TcO(dtc)(tmtu)2] and the Tc" complex (553). The first compound is probably an intermediate... 

Sulphinic acids are unstable liquids passing readily into sulphonic acids on oxidation with alkaline permanganate. Where a mixture of isomeric sulphonic acids is formed by direct sulphonation the individual sulphonic acids may be prepared by this method from the corresponding sulphonic acids. For example, o-toluenesulphonic acid may be prepared from o-toluidine. 

Universal thiol precursor (X—SH) of oxidation products Cysteine sulphinic acid (X—SCFH), Cysteic acid (X-SO-jH) Cystine (X-S-S-X) ... 

Spinacia oleracea (Chenopodicaeae) animals thiol precursor (HC-SH) of oxidation products Homocysteine sulphinic acid (HC-SO9H) Homocvsteic acid (HCASO3H)... 

NMDA-Glu-R agonist [convulsions, excitotoxic, neurolathyrism, neurotoxic] [Oxidized to Cys sulphinic acid Cysteic acid (Aspartic acid analogues), NMDA-Glu-R agonists excitotoxins]... 

In the case of halogen-substituted hydrocarbons the principal method used is the mercuration of the sulphinic acid, and not the hydrocarbon itself, whilst the method acts equally well with nitrobenzene. The nitrotoluenes when mercurated by mercuric oxide in the presence of sodium hydroxide yield compounds containing mercury in the side chain, but with mercuric acetate at 140° C., in the absence of a solvent, the mercury enters the ring. If nitrotoluene sulphinic acids are used as starting-points, the acid group is replaced b mercury by prolonged boiling with 50 per cent, aqueous alcoholic mercuric chloride. 

Recently, the e.s.r. spectra of some arylsulphonyl radicals, ArS02, have been reported (McMillan and Waters, 1966) these unstable radicals were generated in a flow system by oxidation of the sulphinic acids with ceric ion. Similar radicals have been generated in the solid state by y-irradiation of sulphones (Ayscough et al., 1966). 

Taurine - A glyclne-like, sulphur containing amino acid, taurine (12) is found in reasonably high concentrations throughout the mammalian central nervous system and in heart.In brain, taurine is formed as a result of the decarboxylation of cysteine sulphinic acid (15) to hypotau-rlne (8 ), which in turn is oxidized to form taurine.Like other transmitter candidates, taurine is accumulated and released by brain tissue and the accumulation can be inhibited by ouabain. Clinically, significant alterations in taurine levels may be associated with retinitis pigmentosa, epilepsy, mongolism, and possibly heart disease. 

Reactivity is not limited to direct addition to the phenoxyl ring structure, and reactions with thiols, amines and olefmic compounds have been reported. Both HOBr and HOCl can elicit oxidation of cysteine residues, where oxidation of the thiol moiety to a sulphinic acid is associated with activation of the latent form of matrix metalloproteinase-7 [111]. Higher doses of HOCl cause inactivation of the enzyme through site-specific modification of tryptophan and the adjacent glycine to yield an unknown product that lacks four mass units [112]. 

The final part of this section covers the oxidation of sulphur(IV)-containing moieties to sulphonic acids. The functional groups covered here are sulphinic acids and their derivatives. 

The preparation of sulphonic acids by the oxidation of sulphinic acids and their derivatives has been studied, by many workers, for at least the last hundred years. Much... 

The only oxide of nitrogen that has been reported to oxidize sulphinic acids is dinitrogen tetraoxide. In the presence of dinitrogen tetraoxide, aromatic sulphinic acids are converted to sulphonic acids and novel sulphonyl nitrites265 (equation 53). 

Bromine has been used for the preparation of copper salts of sulphonic acids, by oxidation of the corresponding sulphinic acid salts279. 

It has been mentioned above that there are few naturally occurring sulphonic acids. One notable exception is taurine (6), which is formed biosynthetically in several steps. One of these steps involves the oxidation of either cysteine sulphinic acid or hypotaurine (both of which contain a sulphinic acid group) to sulphonic acids. This reaction is, of course,... 

Sulphinic acid esters have also been oxidized, to the sulphonic acid ester, with hydrogen peroxide although the reaction usually proceeds in poor yield345,346. This resistance to oxidation is also evident when other oxidants are used233,347. A much improved procedure for the oxidation of aromatic sulphinate esters uses potassium permanganate in aqueous solution, as oxidant345,348,349, as shown in equation 79. Mefa-chloroperbenzoic acid has also been used with success for the oxidative preparation of sulphonate esters. Indeed, it has resulted in the preparation of unstable sulphonate esters that are hard to form by other means350. 

Oxidative amidation of sulphinic acids occurs under rather forcing conditions (18% oleum) to give a sulphonamide as product (equation 109)446. The severity of the reaction conditions means that this approach is not one that is generally applicable for the conversion. A far preferable method involves the rather mild oxidation of the ammonium salts of arenesulphinic acids with either hypochlorite ions or chlorine, in aqueous solution (equation 110)447. 

As early as 1893, Limpricht566 showed that sulphinic acids may be oxidized to the corresponding sulphonyl bromides using bromine. More recently, workers have also indicated the synthetic utility of this reaction466,555 559 560 564,567, which is shown in equation 144. The product from this reaction is usually a sulphonyl bromide, although a sulphonic acid may be formed depending upon the reaction conditions. Methyl methanesulphinate has also been oxidized with bromine. In this reaction, at 0 °C, the products are methanesulphonyl bromide and bromomethane568. 

Iodine has also been used to oxidize sulphinic acids and their salts to sulphonyl iodides (equation 145)343,559,569- 572. Indeed, this was the first method by which alkanesulphonyl iodides were prepared and isolated571. 

An induction period was observed in the decomposition of cumyl hydroperoxide in chlorobenzene at 70 and 110 °C in the presence of phenolic sulphides CXCVIIa,b262). This was a substantial difference with respect to the behaviour of 4,4 -thio-bis(2,6-di-tert-butylphenol) CLXVIIIb which decomposed ROOH under the same conditions without induction period. The result indicates a mechanistic distinction in the action of both types of phenolic sulphides. In the mechanism of transformations of benzyl sulphide CXCVIIb, there are assumed (Scheme 24) the formation of sulphoxide CXCVIII and the intermediary formation of CIC followed by oxidation and formation of sulphinic acid CC. Further transformation of the acid CC depends on the character of R. If R = 3,5-di-tert-butyl-4-hydroxybenzyl, as it is in the formation of CC from CXCVIIa, the total elimination of the sulphurous part of molecule may occur and the transformation products of phenolic or quinoid character may be formed 3,5-di-tert-butyl-4-hydroxybenzyl alcohol XXXI, the corresponding aldehyde XXXII, and 2,6-di-tert-butyl-l,4-benzoquinone XXII were identified. Another possible sulphurless product is 4,4 -ethylenebis(2,6-di-tert-butyl-phenol) XXVIII, which was isolated in small amounts in its oxidized form as 3,5,3 ,5 -tetra-tert-butyl-4,4 -stilbenequinone (XXIX). Quinone methide XXX formed by thermolysis of sulphoxide CXCVIII, may be also the precursor in formation of XXIX. According to66), XXX is further oxidized by hydroperoxides to XXIX... 

If R is alkyl in sulphinic acid CC (obtained by transformation of CXCVIIb), S02 is readily eliminated and further oxidized to S03. This compound is according to2 9) the real catalyst of the decomposition of ROOH (Scheme 24). 

Chromones.- Enamines have previously been converted into chromones and in another approach, the enamine (104) reacted with thionyl chloride to give the chromone (105 n=2) in moderate yield. The sulphinic acid was readily oxidized to the sulphonic acid (105 n=3) by 3-chloroperoxybenzoic acid.110 A convenient synthesis has been described of 2-methylchromene-4-thione in 57% yield from 4-(2-hydroxyphenyl)butane-1,3-dione.111 The t-amino-methylchromones (106) have been synthesized and shown to be central nervous system depressants. A new synthesis of 2-substituted chromones (including flavones) uses 2-acetoxyphenacyl bromide (107) which is converted into its phosphorane (108). Heating this with an alkanoyl or aroyl chloride or anhydride in pyridine gave good yields of the chromone (109).113... 

The only thiol oxidation reaction to oxy-derivatives of general biochemical significance is that of cysteine to alanine 3-sulphinic acid (cysteine sulphinic add) . This is thought to be the initial reaction in the... 

In solution stable between pH 4-5 and 9-5 below pH 4-5 conversion to free Pyrithione which is very unstable in the presence of oxygen or light above pH 9-5 slow conversion to the sodium salt of Pyrithione sulphonic acid. Oxidizing agents such as peroxides and hypohalites will convert Pyrithione first to 2,2 -dithio-bis-pyridine-1,1 -dioxide (Section 11.1.5) and finally to inactive pyrithione sulphinic or sulphonic acid. 

The photosensitized oxidation of allylthiourea with erythrosin or eosin gave three products, the sulphinic acid (207), allyl cyanamide, and sulphuric... 

A possible route to 2- and 3-t-aminophenothiazines is afforded by the reaction of chloro-lO-alkylphenothiazines with sodium or lithium derivatives of secondary amines. Thus, treatment of 1-chloro- or 2-chloro-lO-methylphenothiazine with sodium amide-morpholine leads to the same product, i.e. 2-morpholino-lO-methylphenothiazine, presumably by way of the same phenothiazyne intermediate (121). 3-Chloro- and 4-chloro-lO-methylphenothiazine react similarly giving, as expected, the same 3-mor-pholino-derivative via an analogous phenothiazyne intermediate. The phenazathionium cation (122), generated oxidatively in situ with ferric chloride, reacts readily with toluene-p-sulphinic acid, nitrite, or thiourea to... 

Oxidation of sulphinic acids by air (under u.v. irradiation) gives sulphonic acids,but N2O4 leads to unstable sulphonyl nitrites RSO2NO rather than to oxidized products. ... 

Sulphonamides.— Oxidative amidation of sulphinic acids gives primary sulphon-amides, though the severe reaction conditions (18% oleum with NaNj) restrict the potential of this route. Selective amino sulphonation of anilines, using CISOjNCO and AlClj, depends on the formation of cyclic A-carbamoyl-sulphonamides. More conventional preparative methods are covered in the conversion of naphthalene-1-thiol into 4-(2-hydroxyethylsulphonyl)naphthalene-1-sulphonamide (an assessment of standard routes has been made), and in the preparation of alkanesulphonyl- and trifluoromethanesulphonyl-hydroxyl-amines from hydroxylamines and the sulphonyl chlorides. In the latter study,conditions favouring N- rather than 0-sulphonylation were established. 

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