[44387-06-6]  · C2H7N3S  · S-Methylisothiosemicarbazide  · (MW 105.19)

(synthesis of substituted 1,2,4-triazines,1 tetrazoles,2 and guanylhydrazones3)

Alternate Names: methyl hydrazinecarboximido thioate; S-methylisothiocarbohydrazide; S-methylisothiosemicarbazone.

Physical Data: mp 140 °C (HI salt);2 mp 144-146 °C (TsOH salt).4

Preparative Methods: HI salt:2 prepared by refluxing thiosemicarbazide and methyl iodide in absolute ethanol for 45 min. Crystallized upon cooling the reaction mixture to give 90% yield. Recrystallized from absolute ethanol. TsOH salt:4 prepared by refluxing a mixture of 0.5 mol of thiosemicarbazide and 0.5 mol of methyl p-toluenesulfonate in 500 mL of methanol for 18 h. After reducing the volume to 250 mL in vacuo, the mixture was treated with 500 mL of ether to give 135 g of S-methylisothiosemicarbazide tosylate.

Handling, Storage, and Precautions: use in a fume hood.

S-Methylisothiosemicarbazide readily reacts with a-dicarbonyl compounds to afford the 3-methylthio derivatives of 1,2,4-triazines.1 a-Keto aldehydes exclusively gave the expected 5-substituted 3-methylthio-1,2,4-triazines (eq 1).1 Diethyl oxomalonate produces two isomers, depending on reaction conditions.4 In acetic acid at reflux, the reaction product was 3-methylthio-5-oxo-6-ethoxycarbonyl-4,5-dihydro-1,2,4-triazine. When the free S-methylisothiosemicarbazide was used in aqueous solution, in addition to the above product, a less polar isomer was formed in 3:2 ratio (eq 2).5 The condensation with an indole anhydride was reported to give only one product (eq 3).6 3-Amino-1,2,4-triazine 4-oxide was formed in modest yield when the HBr salt of S-methylisothiosemicarbazide was heated with an a-diketone monooxime under mild acidic conditions (eq 4).7

Formation of methylthiotetrazole was achieved by using the HCl salt of S-methylisothiosemicarbazide and potassium nitrite (eq 5).2 Isothiocyanates also react with S-methylisothiosemicarbazide to give an intermediate which upon heating yielded substituted triazoles (eq 6),8 but when the intermediate was heated in the presence of hydrochloric acid it afforded substituted thiadiazoles (eq 7).8 Substituted guanylhydrazones can be easily prepared by condensation with aldehydes followed by aminolysis (eq 8).3

Related Reagents.

N,N-Dimethyldithiocarbamoylacetonitrile; Dimethylthiocarbamoyl Chloride; Hydrazine; Methyl Glyoxylate; Semicarbazide; Sodium Trithiocarbonate; 1,1-Thiocarbonyldiimidazole.

1. Paudler, W. W.; Chen, T.-K. JHC 1970, 7, 767.
2. Freund, M.; Paradies, T. CB 1901, 34, 3110.
3. Foye, W. O.; Almassian, B.; Eisenberg, M. S.; Maher, T. J. JPS 1990, 79, 527.
4. Tai, A. W.; Lien, E. J.; Lai, M. M. C.; Khwaja, T. A. JMC 1984, 27, 236.
5. Huang, J. J. JOC 1985, 50, 2293.
6. Ali, M. I.; Abdel-Fattah, A. M.; Hussain, S. M.; El-Reedy, A. M. JHC 1982, 19, 993.
7. George, T.; Parthasarathy, P. C.; Anandan, L.; Rao, M. K. IJC(B) 1989, 28B, 556.
8. Indukumari, P. V.; Joshua, C. P.; Rajan, V. P. IJC(B) 1981, 20B, 384.

Seung Hoon Cheon

Sandoz Research Institute, East Hanover, NJ, USA

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