MoS₂-Catalyzed Aerobic Synthesis of Tetraethylthiuram Disulfide in Batch and Continuous Flow

Abstract:

Tetraethylthiuram disulfide (TETD) is one of the most important thiuram-class rubber vulcanization accelerators and a ‘star molecule’ in other areas. The development of a mild, efficient, low-cost, safe, and sustainable approach to produce TETD is extremely desirable. Here, we developed a much-improved route to synthesize TETD using MoS₂ as the catalyst and ethanol as the solvent. A packed-bed microflow strategy was implemented to accelerate the catalytic process. TETD was obtained with an excellent yield and purity within a short residence time. Besides, this continuous process did not generate any waste salts, rendering it a sustainable method for producing thiuram-type compounds.

Key words

tetraethylthiuram disulfide - molybdenum disulfide - packed-bed microflow reactor - green solvent - aerobic oxidation - sustainability

Publication History

Received: 25 October 2022

Accepted after revision: 16 December 2022

Accepted Manuscript online:
16 December 2022

Article published online:
13 January 2023

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• 32 General Procedure for the Synthesis of Tetraethylthiuram Disulfide in Batch Carbon disulfide (144 μL, 2.4 mmol), dimethylamine (208 μL, 2.0 mmol), triethylamine (280 μL, 2 mmol, 1 equiv.), and MoS₂ (40 mg, 0.25 mmol) were stirred in ethanol (4 mL) under O₂ atmosphere at room temperature for 14 h. The resulting mixture was added styrene (internal standard, 1.0 mmol) and centrifuged at 10000 rpm. The supernatant (100 μL) was diluted with ethanol (1.50 mL) for HPLC analysis. HPLC analyses were performed on Wufeng LC 100 system with SHISEIDO CAPCELL PAK ADME S5 column (4.6 mm I.D. × 150 mm), at a detection wavelength of 254 nm and a flow rate of 0.8 mL/min, with water (pH 3, adjusted with formic acid, as phase A) and methanol (as phase B) as the eluents. The isocratic eluents conditions were A:B = 1:9. General Procedure for the Synthesis of Tetraethylthiuram Disulfide in Continuous Flow Carbon disulfide (1.8 mL, 30 mmol), dimethylamine (2.6 mL, 25 mmol), and triethylamine (3.5 mL, 25 mmol, 1 equiv.) were mixed in ethanol (50 mL). The packed bed (4.6 × 150 mm) was filled with MoS₂ (2.17g). Molecular oxygen was introduced in the reactor with a flow rate of 2.5 sccm via mass-flow controller (MFC) and mixed with solution-phase reactant introduced with a flow rate of 0.1 mL/min by a plunger pump at a T-mixer. An intermittent flow with a gas–liquid volume ratio of 2:1 was formed and flowed into packed-bed microreactor. The reaction mixture resided in the microflow reactor for 20–25 min and flowed to the collection tank through a backpressure regulator (40 psi). The pressure of the entire reactor system was controlled at approximately 0.6 MPa. TETD was isolated and purified by recrystallization, with an isolated yield of 88% in multigram scale (product: 3.92 g). The product was analyzed by NMR spectroscopy and HRMS. ¹H NMR (400 MHz, DMSO-d ₆): δ = 1.19 (t, 6 H, J = 8.0 Hz), 1.39 (t, 6 H, J = 8.0 Hz), 3.97 (quint, 8 H, J = 8.0 Hz) ppm. ¹³C NMR (110 MHz, DMSO-d ₆): δ = 190.84, 51.51, 47.24, 13.27, 11.16 ppm. HRMS: m/z calcd for C₁₀H₂₁N₂S₄ ⁺ [M + H]⁺: 297.0583; found: 297.0579.