Trithiazyl trichloride

Chloro-a,/3-unsaturated aldehydes condense with ammonium thiocyanate to give isothiazoles (76EGP122249). 2,3-Diphenylcyclopropenone reacts with iV-sulfinyl-cyclohexylamine in the presence of nickel tetracarbonyl to give the isothiazolin-3-one 1-oxide (197) (79SST(5)345). Cholesteryl acetate reacts with trithiazyl trichloride in pyridine to give the isothiazolo steroid (198) (77JCS(P1)916). 

The addition of trithiazyl trichloride (NSC1)3 to 2,5-disubstituted furans and to N-2,5-trisubstituted pyrroles has led to the formation of isothiazole derivatives <96JHC1419>. 

The 1,4-diketone 1,2-dibenzoylethane 151 can be transformed in one step into 3,4-dibenzoyl-l,2,5-thiadiazole 152 when treated either with preformed trithiazyl trichloride in tetrachloromethane (Equation 29) <1997J(P1)2831> or with urethane, thionyl chloride, and pyridine in benzene (Katz reagent) <2002ARK90> (see also Section 5.09.9.2.l(iii)(b)). Similarly, treatment of 1,3-diketones 153 with tetrasulfur tetranitride antimony pentachloride complex in toluene at 100 °C < 1998J(P 1 )2175 >, or trithiazyl trichloride in boiling tetrachloromethane < 1997J(P 1)2831 >, affords 4-substituted-3-aroyl-l,2,5-thiadiazoles 154 (Equation 30). 

Treatment of ethenes 158 with trithiazyl trichloride afforded 1,2,5-thiadiazoles 159 in moderate to good yields (Equation 32 Table 10). The reaction, however, suffers from the possibility of chlorination at allylic or benzylic positions, in particular if excess trimer is used. 

Table 10 Reaction of alkenes 158 with trithiazyl trichloride to give 1,2,5-thiadiazoles 159...

Similarly, conjugated dienes, enynes, and diynes such as ( , )-l,4-diphenylbuta-l,3-diene 162, fE)-l,4-diphenyl-but-l-en-3-yne 163, or l,4-diphenylbuta-l,3-diyne 164 on treatment with trithiazyl trichloride (2 equiv) afforded the bisthiadiazole 165 in moderate to good yield (40-60%), depending on the reaction conditions (Scheme 24) <1997CC1493, 1997J(P 1)3189, 1998CC1207>. 

Enamines 187 with electron-withdrawing groups in the /3-position are converted into thiadiazoles 188 in moderate yields (50-60%) on treatment with either tetrasulfur tetranitride antimony pentachloride complex <2000H(53)159> or trithiazyl trichloride <2001J(P1)662> (Equation 38 Table 12). Cyclization onto electrophilic /3-substituents was not observed, and thus the procedure offers a regiospecific synthesis of 4-substituted-3-aroyl-l,2,5-thiadiazoles. 

A-Alkylpyrroles undergo cycloaddition reactions with trithiazyl trichloride (NSC1)3 to afford, depending on the substituents R1, R2, and R3, thiadiazoles 216-218. The reactions are proposed to proceed by addition of the N-S(C1)-N fragment across the 2,3- and the 4,5-bonds of the A-alkylpyrrole, followed by a series of eliminations to give the observed products (Equation 49) <1997CC1493, 1997J(P 1)3189>. 

Electron-deficient 1,2,3-triazoles 222 can be converted into 1,2,5-thiadiazoles 223 with trithiazyl trichloride (Equation 51). The triazoles were proposed to react by initial ring opening to their diazoimine tautomers <2001J(P1)662>. 

In combination with the use of tetrasulfur tetranitride, trithiazyl trichloride, or any equivalent source of N-S-N , the technique of functionalizing a two-carbon source such as active methylene, alkene, or alkyne into thiadiazole (see Section 5.09.9.1.4) followed by reduction (see Section 5.09.5.6) provides a rapid route to 1,2-diamines. 

The reaction of 1,4-diphenylbuta-l,3-diene (2) with trithiazyl trichloride (3) yields a bi(thiadiazole) (4), an isothiazoloisothiazole (5), a dithiazolothiazine (6), and two thiazin-odithiatriazepines (7) and (8) by 1,2-, 1,3-, and 1,4-cycloaddition reactions (Scheme 2). The bridged-mode (/3-tether) tandem inter-[4 -E 2]/intra-[3 -E 2] cycloaddition of (ii)-2-methyl-2-nitrostyrene (9) with 1-butoxypenta-1,4-diene (10) produces stable tricyclic nitroso acetals (11) which afford, after reduction and protection, highly functionalized aminocyclopentanedimethanol triacetates (12) (Scheme 3). ... 

Trithiazyl trichloride (S3N3CI3) has been shown to be more electrophilic than S4N4. It will react... 

When N-substituted pyrrole 37 and trithiazyl trichloride (NSCfis are heated at reflux in carbon tetrachloride, IH-pyrrolo[2,3-r 4,5-. V-Substituted pyrrolo[2,3-f]-l,2,5-thiadi-azole 38 is believed to be an intermediate in this reaction (Equation 2). The enamine character of the carbon-carbon double bond of 38 is presumed to be enhanced compared to pyrrole 37, rendering 38 more reactive toward (NSCfis. 

Rees and co-workers in their study of the reactions of trithiazyl trichloride in the preparations of heterocyclic compounds have noted that the isothiazolo[5,4-, isothiazole compound 140 was produced in low yield on reaction with conjugated dienes, along with the other heterocyclic systems 142-145 in much higher yields (Equation 28). Since it is known that trithiazyl trichloride is in thermal equilibrium with its monomer NSCl (Equation 29), the authors propose the so-called criss-cross cycloaddition reaction (Equation 30) which has been reported for azabu-tadienes, but this represents the first example of such a criss-cross cycloaddition to an all-carbon diene <1998CC1207>. 

Nucleophilic attack at nitrogen is rare in these systems. However, the inorganic trithiazyl trichloride (87) acts as an apparent source of electrophilic nitrogen on reaction with certain organic substrates. Reaction with electron-rich alkenes such as stilbene gives 3,4-diphenyl-1,2,5-thiadiazole (77JCS(Pl)916>. 

Evidence has been presented for initial electrophilic substitution by thiazyl chloride (NSC1) in die reaction of trithiazyl trichloride with 2,5-diarylfurans (38) which eventually yields 5-aroyl-3-arylisothiazoles.86... 

Thiadiazoles have been prepared111 in a one-pot reaction of trithiazyl trichloride with alkynes (see Scheme 25). 

I )ithijzolc[4.5-r/]thiazinc. Y-oxidc 150 is formed in low yield by the reaction of trithiazyl trichloride ((NSC1)3>, which is in thermal equilibration with its monomer (N=S-C1), with l,4-diphenyl-l,3-buta-l,3-diene followed by oxidation with air (Scheme 28) <1998CC1207>. The structure of product 150 was confirmed by X-ray crystallography. The mechanism of this transformation involves an initial 1,4-cycloaddition process. 

The synthesis of 1,3,2-dithiazolidines from bis(sulfenylchlorides) and amines has been developed in the 1990s and 2000s (Equations 12 and 14). Trimethylsilyl azide confirmed its important role in the preparation of fused mono- and bis-l,3,2-dithiazolium cations (Equation 18). Oakley and co-workers showed that o-dimercapto derivatives can be used in the synthesis of these compounds if treated with trithiazyl trichloride (Equation 19). Synthesis of iV-substituted 1,3,2-benzodithazole tetraoxide has been successfully carried out from benzene-bis(sulfonylchloride) and aliphatic amines (Equation 15). An important feature in this reaction is the preparation of chiral derivatives from optically pure amines (Equations 16 and 17). 

Trithiazyl trichloride in synthesis of 5-membered N,S-heterocycles 92JHC639. 

Trithiazyl trichloride (S3N3C13) was shown to be much more electrophilic than S4N4. The trichloride reacts with acenaphthylene and trans-stilbene to produce moderate yields of acenaphtho[l,2-c][l,2,5]thiadiazole and 3,4-diphenylthiadiazole, respectively (77JCS(P1)916). 

Not only can S4N, be reduced as illustrated in the preceding example, but it can also be oxidized. When it is subjected to chlorine, trithiazyl trichloride i.s produced ... 

Thiadiazoles can be prepared by the oxidative cyclisation of 1,2-diamines or aminocarboxamides. Condensation of snlfamide (S02(NH2)2) with 1,2-diketones gives 1,2,5-thiadiazole 1,1-dioxides. A good general method is the reaction of trithiazyl trichloride with activated alkenes and alkynes this method is also useful for the fusion of a 1,2,5-thiadiazole onto other heterocycles, such as pyrroles. The reaction possibly proceeds via cycloaddition to an N-S-N unit in the trithiazine ring. "... 

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