5-Benzylhexahydro-1,3,5-triazine-2-thione synthesis

Yield:42170-02-5 81%

Reaction Conditions:

with magnesium(II) perchlorate in chloroform; for 3 h;Reflux;

Steps:

1,3,5-Triazinanes 4-6; Typical Procedure Method a (MulticomponentApproach)

General procedure: Paraformaldehyde (90 mg, 3.00 mmol; 94.3 mg, 3.14 mmol inthe case of thiourea derivatives) (based of formaldehyde) andMg(ClO4)2 (36 mg, 0.157 mmol) were added to a solution theappropriate amide (1.57 mmol) in CHCl3 (5 mL). The appropriateamine (0.8 mmol; 1.60 mmol in the case of thiourea) wasthen added, and the mixture stirred under reflux for 3 h in airor under argon. (A sealed vessel at 66 ° in oil bath was used inthe case of t-BuNH2 or i-PrNH2. Refluxing for 4.5 h was requiredfor derivative 6). The mixture was then cooled to r.t. and filteredthrough a thin layer of silica gel. In the case of compounds 4uand 4v, the reaction was quenched with hot acetone (25 mL),due to the low solubility of corresponding compounds in CHCl3,and filtered through a fritted glass filter with minimal porosity.The filtrate was concentrated to approximately 0.5-0.7 mLunder reduced pressure, and Et2O (5 mL) was added. The resulting resultingsolution was cooled to -20 °C and the precipitate was collectedby filtration, washed with a small amount of cold EtOHand dried, initially in air and then in a vacuum desiccator overP2O5. Workup for products 4l, 4p, and 4w after concentration ofthe filtrate included extraction of the crude viscous productwith boiling hexane-Et2O (1:2), followed by slow evaporation ofthe resulting extract, initially at r.t. and then at 0 °C, resulting inslow precipitation of the products as white solids. The resultingsolids were collected by filtration and dried in air and then in avacuum desiccator over P2O5. Compound 5e precipitated fromCHCl3. The crude product was collected by filtration, washedwith acetone, and dissolved in EtOH. The solution was filteredthrough a fritted glass filter with minimal porosity, evaporated,and treated with CHCl3 (5 mL). The precipitate was collected byfiltration and dried in air and then in a vacuum desiccator overP2O5. In the case of 3,5-di-tert-butyl-1,3,5-triazinane-1-carbaldehyde(6), 2.05 equivalents of the amine were used under theoptimal conditions, as the use of equimolar combinations offormamide and tert-butylamine gave 6 in a lower yield. Purecompound 6 was obtained immediately after evaporation of thefiltrate under reduced pressure. The use of an argon atmospheredid not generally affect the yields of the products, butdid reduce the slight coloration of the reaction mixtures and thecrude products.

References:

Bunev, Alexander S.;Frontera, Antonio;Grigoriev, Mikhail S.;Grudova, Mariya V.;Kletskov, Alexey V.;Presnukhina, Sofia;Shetnev, Anton;Sinelshchikova, Anna A.;Zaytsev, Vladimir P.;Zubkov, Fedor I. [Synlett,2020,vol. 31,# 11,p. 1067 - 1072] Location in patent:supporting information