Thiolate anions, reactions

No thiyl radicals were detected in these studies, possibly because such radicals could react with thiolate anions, reaction (13), and that the... 

Schemes 110-113 outline the most common general methods for accomplishing the synthesis of thiiranes by formation of a C—S bond (75RCR138,66CRV297, 64HC(19-1)576). The methods in Schemes 111-113 are variations of Scheme 110 they differ in the details of the generation of the thiolate anion which effects the ring closure by a displacement reaction. The methods of converting oxiranes to thiiranes, to be discussed separately (Section 5.06.4.3), involve a displacement like thafof Scheme 110 as the final step.

Alkylation of thiolate anions by bromochlorodifluoromethane generally follows this mechanism [55, 57] However, depending on the nature of the nucleophile and reaction condibons, disubstimtion can arise by a SET process [57] (equation 49)... 

Treatment of a thiol with a base, such as NaH, gives the corresponding thiolate ion (RS-), which undergoes reaction with a primary or secondary alkyl halide to give a sulfide. The reaction occurs by an Sn2 mechanism, analogous to the Williamson synthesis of ethers (Section 18.2). Thiolate anions are among... 

Thiols, the sulfur analogs of alcohols, are usually prepared by Sjv 2 reaction of an alkyl halide with thiourea. Mild oxidation of a thiol yields a disulfide, and mild reduction of a disulfide gives back the thiol. Sulfides, the sulfur analogs of ethers, are prepared by an Sk2 reaction between a thiolate anion and a primary or secondary alkyl halide. Sulfides are much more nucleophilic than ethers and can be oxidized to sulfoxides and to sulfones. Sulfides can also be alkylated by reaction with a primary alkyl halide to yield sulfonium ions. 

From Acylated Glycosyl Halides by Reaction with Thiolate Anion. 181... 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

Potential energy sections were calculated for R = CH3 and R = Ph, and X = F, Cl, Br, I, in the geometrical scheme shown in Fig. 16 a. The relative ease of approach of the thiolate anion in the xy plane was discussed in terms of the relative energies and positions of potential energy minima, possibly corresponding to reaction intermediates. Fig. 16b and 16c show, for a-attack, the positions and relative energies of these minima. No such minima were found for /3-attack, while hints for a possible linear RCC—X. .. SH intermediate were found for bromo- and iodophenylacetylene only. The conclusions drawn were a) a-attack is favoured over /3-attack, and b) the order of reactivity with respect to the... 

Bis(benzotriazol-lyl)methanethione 974 is easily prepared from thiophosgene and l-(trimethylsilyl)benzotriazole <1978JOC337>. In reactions with thiols and triethylamine, thiones 974 are converted to derivatives 973 in modest yields the main side products result from nucleophilic attacks of the thiolate anions on the thione sulfur atom to produce disulfides <2005JOC7866>. In reactions with amines, compounds 974 are smoothly converted to l-(thiocarbamoyl)benzotriazoles 975 <2004JOC2976>. Substitution of one of the benzotriazolyl groups in 974 by phenolate anions yields l-(aryloxythioacyl)benzotriazoles 978 (Scheme 161) <2005JOC7866>. 

Other postulated routes (Jourd heuil et al., 2003) to RSNO formation include the reaction between NO and 02 to yield N02 via a second-order reaction. NO and thiolate anion, RS, react giving rise to thiyl radical, (RS ) [e]. RS then reacts with NO to yield RSNO [f]. The reaction between RS and RS- can also be the source of non-enzymatic generation of superoxide anion (02 ) [g], [h]. 02 reacts with NO to produce peroxynitrite (ONOO ) [i] (Szabo, 2003). Thiols react with ONOOH to form RSNOs [k] (van der Vliet et al.,1998). 

The attack by the thiolate anion on the N-oxide oxygen of 62 produces the intermediate sulfenic acid derivative 65, which, in the presence of thiols, further reacts with the thiolate anion, to give the oxime 66, which has been isolated among the reaction products. By contrast, spontaneous loss of the halide anion from 65 affords the ni-troso intermediate 67 that, by losing NO and the thiyl radical directly, or through 68, produces the a-nitrosoolefm 69. By a Michael type reaction with water this last product immediately yields the final oxime 70, which has been isolated among the reaction products. 

Pyrimidine thioethers may also be synthesized via direct Pd-catalyzed C—S bond formation between halopyrimidines and thiolate anions. For very unreactive thiol nucleophiles such as 2-thiopyrimidine, both a strong base and a palladium catalyst are essential. Without a palladium catalyst or replacing f-BuONa with K2C03, the reaction failed to furnish the desired pyrimidine thioether [49]. 

The reactivity of thiols has been studied in connection with the catalytic function of sulfhydryl enzymes. When nucleophilic reactions of thiolate anions towards PNPA were compared, the thiolate reactivity in vitro was always very small relative to those observed in vivo. Although the details of enzymatic activation mechanisms are far from clear, there is general agreement that this large difference can be attributed to differing microenvironments around the SH group. 

Haloarene chromium tricarbonyl complexes are activated to nucleophilic attack by thiolate anions [58, 59]. High yields of the thioethers are obtained under liquiddiquid two-phase conditions, but optimum yields are achieved under soliddiquid conditions. In many cases the thioether is produced directly but, where the reaction mixture contains thioether and its chromium complex, the thioether can be isolated by degradation of the complex with iodine or an excess of the thiol. Both 1,2- and 1,4-dichlorobenzenes yield only monothioethers, even when an excess of thiolate anion is used. In contrast, 1,3-dichlorobenzenes produce a mixture of the mono- and dithioethers [59]. Aryl allyl thioethers have been produced under catalysed Heck reaction conditions from S-allyl thiocarbamates and iodobenzene [60]. 

Selected examples of the reaction of haloarene chromium tricarbonyl complexes [Cr(CO)jArX] with thiolate anions... 

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

In a one-pot synthesis of thioethers, starting from potassium 0-alkyl dithiocarbonate [36], the base hydrolyses of the intermediate dialkyl ester, and subsequent nucleophilic substitution reaction by the released thiolate anion upon the unhydrolysed 0,5-dialkyl ester produces the symmetrical thioether. Yields from the O-methyl ester tend to be poor, but are improved if cyclohexane is used as the solvent in the hydrolysis step (Table 4.13). In the alternative route from the 5,5-dialkyl dithiocarbonates, hydrolysis of the ester in the presence of an alkylating agent leads to the unsymmetrical thioether [39] (Table 4.14). The slow release of the thiolate anions in both reactions makes the procedure socially more acceptable and obviates losses by oxidation. 

As indicated above, the traditional base-catalysed hydrolysis of 0,5-dialkyl thio-carbonates for the synthesis of thiols is generally unsatisfactory, as oxidation leads to the formation of disulphides. Under phase-transfer conditions, the procedure produces thioethers to the virtual exclusion of the thiols, as a result of the slow release of the thiolate anions in the presence of the electrophilic ester. However, a simple modification of the reaction conditions provides an efficient one-pot reaction [50] from haloalkanes (Table 4.15) via the intermediate formation of the thermally labile (9-/ert-butyl-5-alkyl dithiocarbonates (Scheme 4.8). 

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