Activated S-N bond

Microbiddes with an activated N-S bond as toxophoric structural element... 

Also haloalkylthio amides, e.g. Ar,A dimethyl-A/ -phenyl-A/ -dichlorofluoromethyl-thiosulphamide (Section 14.5) or A-triahalomethylthio-phthalimides (Sections 14.1 and 14.2) are well-known microbicides. They are electrophilic active agents with an activated N-S bond their role as an important class of microbicides is described separately in Section 14 (A -haloalkylthio compounds). 

Microbicides belonging to this substance class are used on a large scale they include certain N-haloalkylthio compounds (Lucken, 1966) and isothiazolinone derivatives (Crow and Leonard, 1965 Lewis et al., 1971) [Figure 12.]. In principle there is no difference in the first step in the mechanism of action of N-haloalkylthio compounds and isothiazolone derivatives with activated N-S bonds both may react with SH groups found in cell components, with the N-S bond being split off and the formation of disulfides. 

Figure 14 Formation of a N-haloalkylthio compounds containing an activated N-S bond.

Substances containing an isothiazolone ring, such as 2-methyl-isothiazolin-3-one (MI), benzisothiazolin-3-one (BIT), 2-methyl-4,5-trimethylene-isothiazolin-3-one, also contain activated N-S bonds which may react with nucleophilic cell entities with opening of the isothiazolone ring, thus exerting antimicrobial activity (Miller et ah, 1975). 

Also haloalkylthio amides are well-known microbicides they are electrophilic active agents disposing of an activated N-S bond. Their role as an important class of microbicides is described separately under 16. 

The pathway for biodegradation of Ml-cleavage of the activated N-S bond and further reactions - is discussed in Part I, Chapter 2. 

In comparision to 2-methyl-4-isothiazolin-3-one (15.1.), the antimicrobial activity of which bases merely on the availability of an activated N-S bond susceptible to nucleophilic attack, the 5-chloro-2-methyl-4-isothiazolin-3-one disposes additionally of a vinyl activated chloro atom and therefore can be characterized as a molecule with two toxophoric structural elements (Paulus, 1988). As a result CMI should exhibit stronger antimicrobial efficacy than the halogen-free MI. This is confirmed by examinations of Diehl and Chapman (1999) see Table 109. Applications for CMI are described under 15.3. 

Another example of the activation of N=S bonds is provided by the reaction of Fe COXi with RNSNR (R = Bul, 4-MeC6H4) which produces a number of compounds presented in die general Scheme 4.26 It is not useful to discuss this reaction scheme in detail, but it is relevant to mention that RNSNR is clearly fragmented by N=S bond rupture in such a way that nitrene (NR), S and RN=S moieties are formed which are captured in clusters. 

So far little information is available on electrophilic substitution reactions these are mainly expected to occur in the azine ring when activated by electron-releasing substituents. Nucleophilic substitution reactions, however, occur readily in either ring. The N—S bond may be cleaved by nucleophilic attack at sulfur and this may be the preferential reaction path in some cases. The N—S bond may also be cleaved as a result of proton abstraction from the azole ring. 

The Influence of Catalysts. The effect of ammonia has already been described above. At low pH the catalytic effect of ammonia is clearly due to chemical interactions between ammonia and sulfur dioxide, because in very concentrated solution, and in non-aqueous systems, N-S bonded compounds can be found and identified (10). At high pH, ammonia clearly catalyzes the decomposition of oxyacids, and, in liquid ammonia, even elemental sulfur is activated, even though N-S bonded products have not yet been clearly identified (11). 

Substituted 3,5-diimino-l,2,4-thiadiazolidines (512) are isomerized in acidic media to the corresponding 2-guanidinobenzothiazoles (516).3 Thus 2,4-dimethyl-3,5-bis(phepylimino)-l,2,4-thiadiazole(512 R = Me, Ar = Ph) yields 516 (R = Me, Ar = Ph, 82%) on being boiled in 1M hydrochloric acid for 45 min 48 The tetraphenyl homolog (512 R, Ar = Ph) reacts even more rapidly, isomerization being complete within a few minutes.59 The mechanism shown in Scheme 11 accounts for these results.59 Protonation at N2 of 512 and fission of the N—S bond generates the cation 514 electrophilic attack by the sulfur at the phenyl residue (which is activated by the amidino... 

Chiral N-sulfmyl imines (80) have emerged as an extremely powerful class of building blocks for asymmetric synthesis [24-27, 72). They are conveniently synthesized in high optical purity and there are numerous available procedures to cleave the N-S bond in order to remove the chiral auxiliary. The N-sulfonyl group is strongly electron-withdrawing and thus activates C=N towards nucleophilic attack. 

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