Nucleophilic Attack at Ring Sulfur

Nucleophilic attack at ring sulfurs can proceed at S-l as well as S-2 atoms. The cleavage of the S-S bond in the 1,2,3-dithiazole ring and formation of sulfur heterocycles in the first case, or the formation of compounds with C=S group by the attack on S-2 atom, are the results of these reactions. 

Various reagents of a nucleophilic or reductive nature can attack at S-2 of 1,2,3-dithiazole ring. Treatment of arylimines 69 with NaOH in aqueous EtOH afforded thiocarbamoylamidines 70 in good to excellent yields (Equation 11) 1996T8413 . The formation of amidines 70 was explained by a nucleophilic attack of hydroxide ion at S-2 with the cleavage of S-S bond. 

56 and stable phosphoranes 72. However, the major products in this reaction were dithiomethylenephosphoranes 73, which unequivocally confirmed the initial attack at the S-2 atom 1996TL869 . 

Treatment of dicyanomethylenedithiazole 42 with an excess of Ph3P gives complex ylide 74 whose structure was confirmed by X-ray analysis (Equation 12) 1998J(P1)2765 . A mechanism for this ylide formation, involving an initial attack of Ph3P at S-2 atom, has been proposed. 

Opening of the dithiazole ring in imine 56 can occur by the action of Grignard reagent and is presumably initiated by attack at S-2. Further addition of a second molecule of Grignard reagent to the reaction mixture results in the formation of arylisothiocyanate 75 (Equation 13) 1998J(P1)889 . 

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For conjugated structures thermolytic reactions with loss of sulfur have been studied since 1980 and afford various types of cyclic and acyclic products (Section 4.11.5.1). Nucleophilic attack at ring carbon is very characteristic of 1,2,3-dithiazoles (Section 4.11.5.4). This type of reaction was especially prolific with Appel s salt, studied mostly by Appel, Rees and their co-workers. The preferential site of attack is C(5) but nucleophilic substitution may occur at C(4) when the C(5) site is blocked by poorly leaving substituents, see the first edition of Comprehensive Heterocyclic Chemistry (CHEC-I) for examples of 1,2,3-dithiazoles <84CHEC-I(6)924> and 1,2,3-oxathiazoles <84CHEC-l(6)930>. Nucleophilic attack at ring sulfur in 1,2,3-dithiazoles occurs on S(2) (Section 4.11.5.5), see... 

Nucleophilic attack may occur at the least hindered position, not necessarily where there is a good leaving group. In this case, ring opened products are obtained. Other possible reaction modes include loss of a proton (at C-3), nucleophilic attack at ring sulfur, or acceptance of electrons. 

Nucleophilic attack at ring sulfur may displace an exocyclic substituent, or lead to S—O or S—S bond cleavage and ring opening. An example of the former is conversion of the... 

Electrophilic attack at ring silicon, sulfur, selenium, and phosphorus Nucleophilic attack at ring silicon Nucleophilic attack at ring boron... 

Nucleophilic Attack at Ring Atoms 5.16.3.5.1 Oxygen, nitrogen and sulfur nucleophiles... 

Reactions in which the ring is cleaved or completely fragmented are fairly common in these systems. Ring contraction to form five-membered rings is also common especially where sulfur is extruded, and these reactions are considered separately, as are reactions which involve desulfurization or reduction. Reactions which lead to ring opening but are initiated by nucleophilic attack at ring carbons have already been discussed in Section 2.28.3.3.3. 

The thermolysis and photolysis of mesoionic phenyl-1,3,2-oxathiazolones were extensively investigated during the period 1980-1990 <1996CHEC-II(4)433>. Electrophilic and nucleophilic attack at ring atoms of 1,3,2-dithiazoles (nitrogen, carbon, and sulfur) occurs quite rarely and little attention was paid to it in CHEC-II(1996). A large part of the section was devoted to the transformation of 1,3,2-dithiazolium radicals to corresponding cations and vice versa. 

Treatment of 3-chloro-2-phenylbenzo[ ]thiophene with -butyllithium, followed by quenching with NH4C1, gave a 71% yield of the l-phenyl-2-(2- -butylthiophenyl)acetylene, which is obviously the result of nucleophilic attack at the sulfur with cleavage of the ring and elimination of chloride. 

Aromatic sultones, unlike the aliphatic analogues, react with nucleophiles at the electrophilic sulfur atom. As an illustration, naphthalene-1,8-sultone (169) reacts with sodium hydroxide, ammonia or a Grignard reagent to give the products (170)-(172) (Scheme 71). The mechanism of these reactions involves initial nucleophilic attack at the sulfur atom with opening of the sultone ring system (Scheme 71). 

Many reactions, which lead to ring cleavage, often followed by rearrangement and recyclization, are now explained by an initial nucleophilic attack at the sulfur atom rather than at C-3 or C-5. Thus, the reaction of carbanions with a variety of isothiozolium or 1,2-benzisothiazolium salts... 

Phosphorus nucleophiles appear to attack at ring sulfur (Section 3.11.6.4.2(v)). 

As was introduced earlier, once the sulfoxide is activated, the resulting sulfonium salt 102 can undergo nucleophilic attack at the sulfur atom This is known as an interrupted Pummerer reaction and is outlined in Scheme 20.24. The nucleophilic substitution on the sulfur atom yields a new sulfonium salt 103. Depending on the structure of R, Nu, and in 103, this can have three a electrophilic positions, which means that a nucleophilic substitution of sulfide will produce the loss of one of the three fragments. Usually, the first nucleophile is present in the same molecule, reacting in an intramolecular way. However, some exanples using interrupted Pummerer reactions in intermolecular processes are described in the literature, and inportantiy, the reaction can be used to activate relatively unreactive positions in heterocyclic rings. 

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