Thiosulfonate synthesis

Synthesis. The method of synthesis for Methylene Blue described in reference 14 is stiU the stepwise method of choice for thiazine dyes. /V,/V-Dimethy1-y-pheny1ene diamine [99-98-9], CgH22N2, reacts with sodium thiosulfate [7772-98-7] to form the thiosulfonic acid which condenses with /V, /V-dimetby1 ani1 ine [121 -69-7], CgH N, in the presence of sodium dichromate [10588-01-9] to the indamine, then with copper sulfate [18939-61 -2] and sodium dichromate to Methylene Blue (26). 

Sulfur compounds with divalent sulfur functionalities are much more prone to dioxirane oxidation on account of their higher nucleophilicity compared to the above-presented oxygen-type nucleophiles. Examples of this type of dioxirane oxidation abound in the literature. Such a case is the oxidation of thiols, which may be quite complex and afford a complex mixture of oxidation products, e.g. sulfinic acids, sulfonic acids, disulfides, thiosulfonates and aldehydes , and is, therefore, hardly useful in synthesis. Nevertheless, the oxidation of some 9i/-purine-6-thiols in the presence of an amine nucleophile produces n >( -nucleoside analogs in useful yields (equation 19). This reaction also displays the general chemoselectivity trend that divalent sulfur functionalities are more reactive than trivalent sp -hybridized nitrogen compounds P. 

Methods using starting materials other than the 1,2-disubstituted benzene have also been developed, and a useful four-step route, equally applicable to the synthesis of (184) and (185), is shown in Scheme 22. Yields are quoted as being about 50% overall and as such compare favourably with those involving eliminations. The key features of the scheme are the intramolecular sulfenylation of the thiosulfonates in 73 and 76% yield, and the satisfactory yields, 76 and 78%, for the final dehydrogenation (75S451). 

Disulfides, diselenides, and ditellurides can be oxidized by hypervalent iodine compounds quite easily. Depending on the reaction conditions disulfides can be oxidized to sulfinic esters [59] or thiosulfonic S-esters [60,61]. Diselenides can be transformed into selenosulfonates [62]. Arenetellurinic mixed anhydrides are mild oxidants and can be obtained by oxidation of the corresponding ditellurides as shown in Scheme 9 [63]. Recently it was shown that a thioacetal based linker for solid-phase synthesis can be cleaved oxidatively using [bis(trifluoro-acetoxy)iodo]benzene 4 [64]. 

The sulfone moiety is a good acidifying group, so (methylsulfanyl)methyl sulfones 410 and 411 can be deprotonated and mono- or dialkylated with sodium hydroxide under PTC conditions or with sodium hydride619-622. The alkylated products can be easily hydrolyzed with hydrochloric acid in refluxing methanol, having been applied to the synthesis of acyclic and cyclic ketones. The acylation of compound 410 derived sodium anion has been performed with esters620. For the lithiation of a-thiosulfones 411622 and 412, n-BuLi, f-BuLi or LDA at —78 °C can be used. 

Use of thiirane 1,1-dioxide affords a useful synthesis of ethanesulfinates with the following functions in the 2-position thiol, disulfide, trisulfide, thiosulfate, thiosulfonate, and phos-phorthioate. Reaction of episulfone (83) with sodium p-toluenethiolate gives the sulfinate (84), which can be converted to the sulfone (85) (Scheme 35). Similarly, (83) is converted to the benzyl counterpart (86), which is desired for possible debenzylation to the thiol since the salt (86) is difficult to purify, it is converted to the ethyl ester (87) <86JOC5235>. 

The thiosulfonate derivative was prepared from cysteine to protect the thiol during the native chemical ligation method for peptide synthesis. It is prepared from sodium tetrathionate in DMSO with DIPEA. It can be removed with dithiothreitol. ... 

Fig. 2. Summary of the free and bound pathways of sulfate assimilation in plants. Some related reactions and points of entry of several forms of inorganic sulfur are also shown. The reaction sequence catalyzed by (1) ATP sulfurylase, (2) APS sulfotransferase, (3) thiosulfonate reductase, and (4) cysteine synthase constitutes the bound sulfate assimilation pathway. The synthesis of OAS is catalyzed by (5) serine transacetylase. The reaction sequence (I), (6)-(9)or (1), (2), (10), (8), (9) constitutes the free pathway reactims (7) and (10) are nonenzymatic, (6) is catalyzed by APS sulfotransferase, (8) by sulfite reductase, and (9) by cysteine synthase. APS and PAPS are interrelated via (11) APS kinase and (12) NDP phophohydrolase. APS can be hydrolyzed via (13) APS sulfohydrolase or (14) APS cyclase.

Synthesis of Sulfinate Ester. 5-Ethyl ethanethiosulfinate can be transformed to the stable sulfinate esters by replacement of the sulfenyl group with catalytic bromine and H2 O2 in the presence of an alcohol such as Isopropanol (eq 11). However, in absence of the alcohol, the thiosulfinate disproportionates rapidly under these conditions and forms a mixture of thiosulfonate and disulfide. 

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