Tetrachlorothiophene dioxide

Ludivine Jean-Gerard University of Pennsylvania, Philadelphia, PA, USA 

Preparative Methods the title reagent can be prepared by oxidation of tetrachlorothiophene with 3-chloroperbenzoic acid or with trifluoroperacetic acid.  

Purity recrystallization from hexane and sublimation at 60°C and 0.1 Torr. 

Handling, Storage, and Precaution can be stored in a refrigerator for weeks but should be sublimed before use. 

The cycloaddition of TCTD clearly shows an inverse electron demand but under harsher conditions it does add to maleic anhydride and to p-benzoquinone. In a study with p-substituted styrenes (eq 2) the addition of TCTD follows the Hammett equation log(k/kn)= donating substituents X.  

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Catalytic antibody 1E9, the first catalytic antibody discovered for Diels-Alder reaction, catalyzes the cycloaddition between tetrachlorothiophene dioxide and N-ethylmaleimide (Equation 4.15) [86]. 

Hilvert [33] has recently used this approach to catalyse the Diels-Alder reaction between tetrachlorothiophene dioxide (20) and A(-alkylmaleimides (21). a reaction that takes place in two steps i) initial formation of tricyclic adduct 22 and ii) cheletropic extrusion of sulfur dioxide to give dihydrophtalimide 23, which is spontaneously oxidised under the reaction conditions to 24 (see Scheme 11.6). 

Scheme 8 Imprinting approach used to catalyse the reaction between tetrachlorothiophene dioxide (43) and maleic anhydride (44) to give (45). The chlorendic anhydride (46), representing the TSA, is used as the template for imprinting.

In 1997 the same group developed the first imprinted polymer able to catalyse a Diels-Alder reaction between tetrachlorothiophene dioxide (43) and maleic anhydride (44) to give the product (45). The imprinting strategy was inspired by previous work carried out by Hilvert et al. in 1989 for the development of catalytic antibodies with Diels-Alder capabilities [26]. The chlorendic anhydride (46) was used as a template because of its structural analogy with the transition state of the reaction (TSA). The resulting imprinted polymer showed a Michaelis-Menten behaviour and a ratio kcal/kunca equal to 270 (Scheme 8). 

Scheme 4.2 Diels-Alder cycloaddition of tetrachlorothiophene dioxide (4) and /V-ethyI maleimide (5) yields a high energy intermediate (6) that decomposes spontaneously by elimination of sulfur dioxide. The initially formed product is subsequently oxidized in situ. Transition states for cycloaddition and chelotropic S02 elimination closely resemble the hexachloronorbornene derivative 3 used as a hapten to elicit antibody 1 E9.

Chlorendic anhydride Tetrachlorothiophen-dioxide + maleic anhydride ( imp - non-imp )/- non-imp = 270... 

Monocyclic thiophene 1,1-dioxides generally act as a 4n component toward di-enophiles. However, in some cases, thiophene 1,1-dioxides such as parent thiophene, 3,4-dichlorothiophene, and tetrachlorothiophene dioxides, 1 [132], 21 [133], and 53 [134], respectively,behave as a dienophile toward 47r components (Scheme 30). Examples are shown below. 

Cycloaddition of thiophene 1,1-dioxides with alkynic dienophiles leads to the formation of benzene derivatives with elimination of sulfur dioxide. Thus, the unstable parent thiophene 1,1-dioxide 1 reacts with diethyl acetylenedicar-boxylate and cyclooctyne to give diethyl phthalate and benzocyclooctene, although in low yields (Scheme 53) [132, 175]. Cycloadditions with alkenic and alkynic dienophiles had been used as evidence for the generation of 1 until spectroscopic evidence became available [46]. Tetrachlorothiophene dioxide 53 reacts with phenylacetylene [35] and a cyclic alkyne 92 [176] to give 1,2,3,4-tetrachloro-5-phenylbenzene and compound 93, respectively (Scheme 54). 

Careful hapten design also allowed the preparation of an antibody that catalysed the Diels-Alder reaction of tetrachlorothiophene dioxide 3 and A-ethylmaleimide. [20] Again, catalysis results simply from productive binding (an EM of > 110 m is estimated) turnover depends on the instability of the initial adduct 4, which loses SO2 very rapidly to give the aromatic product 5. This avoids product inhibition, which is a common problem with such potential catalytic systems the hapten 6 is a reasonable transition state analogue, but geometrically very different from the final product. 

Although the reaction of arynes with thiophenes as a route to naphthalenes leaves much to be desired, the reaction with thiophene-1,1 -dioxides is synthetically useful. An excess of benzyne precursor (benzenediazonium carboxylate) is used, and the solvent was refluxing 1,2-dichloroethane. Yields of naphthalenes are moderate and conversions are good. Thus 3-methylbenzyne and tetrachlorothiophene dioxide 296 gives naphthalene 297 in 65% yield (96% conversion). The thiophene dioxides may be prepared by m-CPBA oxidation of the corresponding thiophenes. 

Fig. 3 (A) [33] Sigrnatropic rearrangement of chorismate to prephenate catalyzed by antibody 11F1-2E11. The hapten is a shape mimic of the cyclic transition state. (B) Antibody 1E9 catalyzes a Diels-Alder reaction of tetrachlorothiophene dioxide and yV-ethylmaleimide. The hapten is comprised of the endo hexachloronorbornene unit. (C) Antibody 21H3A catalyzes the transesterification reaction between iec-phenethyl alcohol and an enolic ester to form a chiral ester. The hapten here is racemic phosphonate.

Figure 9 Chlorenic anhydride as the intermediate analogue of the Diels-Alder reaction between maleic anhydride and tetrachlorothiophene dioxide.

Cycloaddition with Alkenes. Tetrachlorothiophene dioxide (TCTD) undergoes a [4 + 2]cycloaddition with olefins to give an unstable 7-thiabicyclo[2.2.1]heptene dioxide which rapidly extrudes SO2 in a cheletropic reaction yielding a 1,2,3,4-tetrachloro-cyclohexa-1,3-diene (eq 1). The primary product has never been observed but it seems plausible as with 3,4-dichlorothiophene dioxide the analogous 7-thiabicyclo[2.2.1]heptene dioxide can be obtained. The broad scope of this reaction is given in the pioneering paper of Raasch. ... 

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