Thiocarbonyl group, nucleophilicity

The sulfur atom of the thiocarbonyl group is a good nucleophile, and reaction between benzyl bromide and l-(2-thiazolyl)thiourea yields the isothiouronium salt (496). The sulfur atom may also be engaged in a chelate, as exemplified by the Cu chelate of 2-thioureido-4-methylthiazole (491). These chelates with metal ions were thoroughly studied in acidic, neutral, and alkaline media for 66 metal ions in order to define their analytical use. They are formed in the molar ratio of 1 2 for metal II compounds (498). 

The rearrangement discovered by Kolosova et al. probably involves such reactivit (159). This reaction provides a good preparative method for various 5-amino-methylthiazoles (Scheme 43). No mechanism is proposed in the report, and it is not easy to understand how the C-5 enamine-like position competes with the very nucleophilic thiocarbonyl group of the formed A-4-thiazoline-2-thione. An alternative mechanism could start with ethanol addition at C-2. leading to the A-4-thiazoline (90) (Scheme 44). In this intermediate, C-5 nucleophilic reactivity would be favored bv the true enaminic structure. After alkylation on C-5,... 

In these a-phosphorylated dithioesters, the electron-withdrawing effect of the phosphono group, which strongly increases the electrophilic character of the thiocarbonyl group, makes the latter more prone to the thiophilic attack of nucleophiles and stabilizes the resulting carbanion. The main reactions of 1 with nucleophiles are summarized in Scheme 2. 

Many examples of the nucleophilic attack of organometallic compounds at the sulfur atom of thiocarbonyl groups were reported in the 1970s by Beak, Vialle, Ohno, Schaumann and their co-workers [119, 120, 327-329]. This thiophilic addition opens the way for a new method of preparation of carbanions a to sulfur. 

As discussed in Section II, thiocarbonyl compounds differ from their carbonyl counterparts in at least two important characteristics. Because of the higher energy of the sulfur p orbitals, they are much more reactive as electron donors. On the other hand, the C=S bond is also much less polarized than the C=0 bond, due to the smaller difference in electronegativities between carbon and sulfur. The latter fact leads to the reactions of the thiocarbonyl group being less selective than those of the carbonyl group. This happens, for instance, in the case of nucleophilic additions (see Section IV.C), and an enhanced reactivity against dipoles has also been observed (see Section IV.E.3). 

In addition to the typical behavior exhibited in a wide array of reactions by the carbonyl group, attack by nucleophiles and reactions leading to C—S single bonds are generally favored. The energetic reasons for this behavior have been discussed in Section II. Likewise, thiocarbonyl groups show a rich variety of cycloaddition reactions, ranging from... 

The important 2-alkylthio-2-arylthio-carbapenems are usually prepared by nucleophilic displacement of the ester group from the enol ester derived from 2-oxocarbapenam. This procedure is discussed in more detail in Section 2.04.7.2. An account of the procedure and an example of the reactivity of a thiocarbonyl group are given in CHEC-11(1996) <1996CHEC-II(1B)659>. No new examples of the reaction of a thiocarbonyl group in fused /3-lactams have been found. 

The need for a variety of organofluorine molecules has encountered difficulties with oxygenated substitutes such as carboxylic esters due to their poor nucleophilicity towards electrophilic fluorinating reagents. This has led several groups to explore the conversion of the thiocarbonyl group into the CF2 moiety. It was successful with thioamides [174], dithioesters [175-177] and thionoesters [178, 179], providing new routes to difluoro-sulfides, amines, ethers and alkenes. 

Important reactions have included sulfur as nucleophile and leaving group in the Sn2 reaction (illustrated here see also Chapter 17), sulfonation of aromatic rings (Chapter 22), formation and reduction of thioacetals (Chapter 24) and La wesson s reagent for converting carbonyl groups to thiocarbonyl groups (Chapter 44). 

The nucleophilic property of the thiocarbonyl group in enaminothiones give rise to a different manner of reaction with bifunctional groups. For example, a-bromoketones lead to thienoazepines with spiro-heterocycles as isolable intermediates. The reaction also takes place with benzo-fused heterocycles345 (equation 262). 

Transformation of a thione into a carbonyl group [Eq. (1)] is today a standard technique in sulfur chemistry and generally proceeds in very good yields with widely different classes of compounds. Efficient methods are based on hydrolysis, alcoholysis, or oxidation. Hydrolysis involves nucleophilic attack at the thiocarbonyl group, followed by elimination of H2S [Eq. (2)]. Factors tending to shift the equilibrium... 

The next step then would be nucleophilic reaction of the carbanion with the electrophilic carbon of the thiocarbonyl group. This reaction joins carbons 1 and 3, as was predicted from the numbering scheme. 

With the exception of a few examples of nucleophilic attack on the thiocarbonyl group, including a more recently published method using sodium hydroxide under phase transfer conditions,most conversions are carried out with oxidative reagents. Sodium peroxide, dimethyl sulfoxide with acid or iodine,selenium-derived reagents and bis(p-methoxyphenyl)telluroxide have been used. 

IJC(B)109>. A mechanistic rationale (Scheme 6), which involves initial attack by hydrazine at the thiocarbonyl group followed by intramolecular nucleophilic attack at the ring sulfur by the terminal nitrogen of the hydrazine so formed accompanied by loss of hydrogen sulfide, is proposed. Attack by hydrazine at the ester carbonyl centre is discounted as the methyl and ethyl esters (37 R = Me or Et) yield different products, both of which show the appropriate alkyl resonances in... 

The majority of the reactions of this type that lead to the heterocyclic systems discussed in this chapter involve formation of a bond between a carbon and a heteroatom. Intramolecular nucleophilic attack by the oxime oxygen on the dithiocarbonate thiocarbonyl group in (103) gives the... 

Five-membered cyclic thiocarbamates have also been reported to originate during the reduction of v/c-azidolhiocarbonates, nucleophilic attack of the intermediate amine to the thiocarbonyl group being faster than reduction of the ester.96 312... 

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