Chemistry of Spontaneous Alkylation of Methimazole with 1,2-Dichloroethane
Spontaneous <i>S</i>-alkylation of methimazole (<b>1</b>) with 1,2-dichloroethane (DCE) into 1,2-bis[(1-methyl-1<i>H</i>-imidazole-2-yl)thio]ethane (<b>2</b>), that we have described recently, opened the question about its formation pathway(s). Results...
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| Autores principales: | , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/fd49ec461dd54c97a020001764d53e54 |
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| Sumario: | Spontaneous <i>S</i>-alkylation of methimazole (<b>1</b>) with 1,2-dichloroethane (DCE) into 1,2-bis[(1-methyl-1<i>H</i>-imidazole-2-yl)thio]ethane (<b>2</b>), that we have described recently, opened the question about its formation pathway(s). Results of the synthetic, NMR spectroscopic, crystallographic and computational studies suggest that, under given conditions, <b>2</b> is obtained by direct attack of <b>1</b> on the chloroethyl derivative 2-[(chloroethyl)thio]-1-methyl-1<i>H</i>-imidazole (<b>3</b>), rather than through the isolated stable thiiranium ion isomer, i.e., 7-methyl-2<i>H</i>, 3<i>H</i>, 7<i>H</i>-imidazo[2,1-<i>b</i>]thiazol-4-ium chloride (<b>4a</b>, orthorhombic, space group <i>Pnma</i>), or in analogy with similar reactions, through postulated, but unproven intermediate thiiranium ion <b>5</b>. Furthermore, in the reaction with <b>1</b>, <b>4a</b> prefers isomerization to the <i>N</i>-chloroethyl derivative, 1-chloroethyl-2,3-dihydro-3-methyl-1<i>H</i>-imidazole-2-thione (<b>7</b>), rather than alkylation to <b>2</b>, while <b>7</b> further reacts with <b>1</b> to form 3-methyl-1-[(1-methyl-imidazole-2-yl)thioethyl]-1<i>H</i>-imidazole-2-thione (<b>8</b>, monoclinic, space group <i>P</i> 2<sub>1</sub><i>/c</i>). Additionally, during the isomerization of <b>3</b>, the postulated intermediate thiiranium ion <b>5</b> was not detected by chromatographic and spectroscopic methods, nor by trapping with AgBF<sub>4</sub>. However, trapping resulted in the formation of the silver complex of compound <b>3</b>, i.e., bis-{2-[(chloroethyl)thio]-1-methyl-1<i>H</i>-imidazole}-silver(I)tetrafluoroborate (<b>6</b><sub>,</sub> monoclinic, space group <i>P</i> 2<sub>1</sub><i>/c</i>), which cyclized upon heating at 80 °C to 7-methyl-2<i>H</i>, 3<i>H</i>, 7<i>H</i>-imidazo[2,1-<i>b</i>]thiazol-4-ium tetrafluoroborate (<b>4b</b>, monoclinic, space group <i>P</i> 2<sub>1</sub><i>/c</i>). Finally, we observed thermal isomerization of both <b>2</b> and 2,3-dihydro-3-methyl-1-[(1-methyl-1<i>H</i>-imidazole-2-yl)thioethyl]-1<i>H</i>-imidazole-2-thione (<b>8</b>), into 1,2-bis(2,3-dihydro-3-methyl-1<i>H</i>-imidazole-2-thione-1-yl)ethane (<b>9</b>), which confirmed their structures. |
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