2- -3-methyl-isothiazolium

Ethoxy-/3-methyl-amino-thioacrylic-(9-ethylester (R = Me, R2 = H) reacted with I2 or Br2 in pyridine to give 3,5-diethoxy-2-methyl-isothiazolium triiodide (85%) and tribromide (22%) (88AP863, see also Scheme 11). 

The treatment of 1,2-dithiolium salts 43 with methylamine gave 3-methyl-aminothiopropenones 44, which were oxidized by iodine to form the TV-methyl-isothiazolium salts 27a,45a, isolated as their perchlorates (73CJC3081). The yields of products were rather poor but the reaction is a very quick synthesis of TV-methyl-isothiazolium salts 27a,45a from the 1,2-dithiolium salts 43 (Scheme 12). 

Ethyl-4-methyl-1,2-dithiolium perchlorate 49, which crystallized from AcOH as colorless plates, was prepared and converted into the Vilsmeier salt 50 in 80% yield. The addition of aqueous methylamine to a solution of salt 50 in dimethylformamide at room temperature afforded the methylimine 51 in 92% as deep yellow needles. After heating with methyl iodide in acetonitrile, the dithiol 51 gave the S-methylated isothiazolium iodide 52a, which was treated with 70% perchloric acid to form the corresponding perchlorate 52b as yellow needles was received (69CC1314, Scheme 14). 

Table 3. Methylation of isothiazoles 74 to 2-methyl-isothiazolium salts 27,45 and 75... 

The 2-(imidazol-4-ylmethyl)- 81 and 2-(imidazol-3-ylmethyl)-3-methyl-isothiazolium salts 82 were prepared by N-alkylation of 3-methylisothiazole 80 in poor yields (26-27%). Similarly, the 2-(pyrimid-5yl-methyl)-3-methyl-isothiazolium bromides 83a and 83b were obtained (65JCS(C)4577, Scheme 25). 

Chloro-2-methyl-isothiazolium salts 75k,m,q,r were converted with malonodi-nitrile to 2-alkyl-3-(dicyanomethylen)-2,3-dihydroisothiazoles 410a-d by a condensation reaction (77DEP2851023, 78USP4281136, Scheme 138). 

Base-induced dimerization of isothiazolium salts containing an active methyl group in the 5-position provides a flexible approach for the synthesis of novel substituted 6aA4-thia-l,6-diazapentalenes. For example, salts 198 and 199 upon treatment with dicyclohexylamine in DMSO yielded the thiadiazapentalenes 200 as shown in Equation (51) and Table 27 <1996MOL142>. 

The synthesis of novel substituted 6aA4-thia-l,6-diazapentalenes 33 was achieved by a base-induced dimerization of two isothiazolium salts <2001PS(170)29>. It was shown that A -phenyl-substituted isothiazolium salts having active 5-methyl or 5-methylene groups can easily be obtained by reaction of (l-thiocyanatovinylaldehydes and substituted anilines <1995CZ175>. 

Recently, Schulze and coworkers synthesised a group of (2-aryl-4,5-diphenyl)isothiazol-3-ylidenes (see Figure 6.11) by deprotonation of the respective isothiazolium perchlorates with Bu OK as base [37], The compounds are yellow solids that dimerise readily and show typical carbene reactions like insertion into NH bonds. The tendency to dimerise follows the known electronic properties of substituents on the phenyl ring on nitrogen (< -methyl [Pg.317]

The methylation of the 1,2-dithiol 46 occurred at the sulfur atom with formation of the dithiolium salt 47, which could not be isolated and immediately reacted to form the isothiazolium iodide 48 (84JHC627, Scheme 13). 

The 4-chloromethyl isothiazole 86, which could be obtained from the isothiazolyl carbinol by treatment with thionyl chloride, was very reactive towards nucleophilic reagents. Thus 4-chloromethylisothiazole 86 underwent a self-quaternization to form the 4-chloromethyl-3-methyl-2-(3-methylisothiazol-4-ylmethyl)isothiazolium chloride 87 (68JCS(C)611, Scheme 27). 

Reaction of 2-alkyl/aryl isothiazol-3(2//)-thiones 90 with various alkyl-halogenides gave the 3-iS -alkyl-substituted isothiazolium salts 25a,91 in good-to-very-good yields (70BSF3076, 73CJC3081, 93JHC929, Scheme 29). Several isothiazolium iodides 25a,91a-n, perchlorate 25a and chlorides 91o-v were also synthesized. The structure of 2-methyl-5-aryl-isothiazolium chloride 91q, isolated in 60% yield, was confirmed by X-ray analysis. The S-alkylated isothiazolium salts 25a,91 with yields and references are represented in Table 5. 

Methoxy isothiazolium salts 75w and 102a-c were prepared in high yields by treating the isothiazolone 101 with an excess of methyl fluorosulfonate. In some... 

The 1-methyl 2,1-benzisothiazolium salts 169a-m were prepared by methylation of 2,1-benzisothiazole 168. The 1-alkylated isothiazolium salts 169 are presented with their yields and references in Table 9. These alkylation afforded a very simple... 

The H-3 proton of 4,5-diphenyl isothiazolium salt 63a is shifted to 10.00 ppm compared with 4,5-dimethyl- 57f,g or 4,5,6,7-tetrahydro perchlorates 1211, which are below 9.50 ppm. The salt 73n is an exception with a chemical shift of the H-3 proton at 8.54ppm. After an isomerization of 2-(4-methoxyphenyl)-4,5-dimethylisothiazolium perchlorate 57f to 2-(4-methoxyphenyl)-3,4-dimethylisothiazolium perchlorate 68d, described in this chapter, the 5-methyl group of 57g was transferred to the 3-position of the isothiazole ring and the H-5 proton of 68d is located at 9.25 ppm in contrast to the H-3 proton of 57g at 9.39 ppm. 

Especially, 2-phenyl-4,5,6,7-tetrahydro-l,2-benz- (121) and 5-methyl-2,4-diphenyl-isothiazolium salts 62 (R = H, 4-MeO, 2-C1, 2,6-Cl2) were studied with the HPLC-MS(MS) method to monitor the oxidation of isothiazolium salts with H202/acetic acid (96%) (03CG147). The strongly acidic reaction mixture was separated on a RP-18 column without any sample pretreatment and included intermediates, which were identified by API-MS(MS)-techniques. The aim of this work was to establish the reaction mechanism using several N-functionalized salts. 

Methyl-3-phenyl-isothiazolium salts 27a,b were attacked at the N-atom with the /V,A-binucleophile 2-aminoethanthiol to obtain thioethylaminothiones 290a,b in 48-57% yield (72JCS(P1)2305, Scheme 96). 

The isothiazolium salts with an active 5-methyl 57 and 62 or a 7-methylene group 121 reacted with DCHA depending on substituents R and R to thiadiazapentalenes 378. Salts 379 were obtained only as by-products (95JPR175, 95ZK73, Scheme 126). 

An interesting route to 4-imino-l,3-thiazines (406 X = CH) lies in the attack of unsaturated carbon nucleophiles (e.g. cyanide and methyl propiolate anion) upon the isothiazolium salt (405 X = CH), as shown in Scheme 158. The 1,2,5-thiadiazolium salt (405 X = N) reacts similarly, giving (406 X = N). " ... 

For example, the ethyl acetate anion 2, generated in situ by thermal decarboxylation of the K-salt of monoethyl malonate, cleaves the isothiazolium ion 1 by S-attack and formation of the ring-open iminothiolate 3, which cydizes to the 3-aminothiophene-2-carboxylate 5 by intramolecular aza-analogous aldol addition ( 4) and elimination of methyl mercaptan. 

For a comparative study of the rates of )V-methylation, see p. 344. Nucleophilic replacement of the halogeno-substituent in 2-ethyl-3-chloro-l,2-benziso-thiazolium chloride (52) by (thio)phenols readily yields quaternary isothiazolium... 

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