New Heterocyclic Organosulfur Compounds Derived from Dithioacetals

Abstract

The dithioacetalization of lactaldehyde derivatives with ethane-1,2-, propane-1,3-, butane-1,4-, and pentane-1,5-dithiols in the presence of 4 mol% of scandium triflate has been described. A series of cyclic dithioacetals were obtained with yields ranging from quantitative to 37%. The dithioacetalization of lactaldehyde derivatives with butane-1,4-dithiol and pentane-1,5-dithiol groups are accompanied by the formation of 14- and 16-membered macrocyclic sulfur structures with yields of 3% and 18%, respectively. In the case of a cyclic dithioacetal derivative with three methylene groups, a diastereoisomeric pair of enantiomers was obtained, the structure of which was confirmed by single-crystal X-ray diffraction analysis. Dithioacetals are useful building blocks in the synthesis of complex chemical structures. Macrocyclic compounds can be used to complex metal ions.

Key words

lactic aldehyde - chiral cyclic dithioacetals - scandium triflate - sulfur macrocycle - dithioacetalization

Publication History

Received: 20 August 2023

Accepted after revision: 01 February 2024

Accepted Manuscript online:
01 February 2024

Article published online:
20 February 2024

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• 18 A stirred solution of (S)-(1-(1,3-dithian-2-yl)ethoxy)(tert-butyl)dimethylsilane (4, 0.166 g, 0.60 mmol) in dry DCM (5 mL) was cooled to 7 °C, Sc(OTf)₃ (0.62 g, 1.25 mmol, 2.1 equiv) was added portion wise, and the resulting mixture was stirred for 72 h in 7 °C. (Note: the reaction mixture changed color from colorless to orange.) Then a mixture of water and a saturated water solution of NaHCO₃ (12 mL, 4:3) and DCM (8 mL) were added. (Note: decolorization of the reaction mixture occurred.) Phases were separated, the water layer was extracted with DCM (3 × 15 mL), organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and volatiles were removed under reduced pressure. A crude mixture of products was purified with column chromatography (180-fold silica gel excess, n-hexane–EtOAc, from 99:1 to 97:3). Dithiepane 5 was obtained as a colorless oil, which solidified during storage (22 mg, 22% yield). The product was further purified by recrystallization from DCM, affording product 5 as colorless crystals; mp 123.5–125.5 °C. IR (KBr): ν = 2927, 2903, 1464, 1443, 1416, 1379, 1296, 1273, 1229, 1185, 996, 904, 778, 743 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 4.95 (d, J = 2.25 Hz, 1 H, SCHS), 3.23 (qd, J = 6.9, 2.6 Hz, 1 H, CH₃CH(S)CH(S)), 3.14–3.04 (m, 2 H, SCH₂), 3.03–2.89 (m, 2 H, SCH₂), 2.89–2.82 (m, 2 H, SCH₂), 2.72 (dd, J = 10.0, 2.4 Hz, 1 H, SCH(CH₃)CH(S)CH(CH₃)), 2.63–2.57 (m, 2 H, SCH₂), 2.49 (dqd, J = 10.0, 6.8, 2.3 Hz, 1 H, CH₃CH(CH)CH), 2.14–2.10 (m, 1 H, SCH₂CH ₂), 1.98–1.93 (m, 2 H, SCH₂CH₂ ), 1.88–1.79 (m, 1 H, SCH₂CH ₂), 1.54 (d, J = 6.9 Hz, 3 H, CH₃ CH(S)), 1.19 (d, J = 6.8 Hz, 3 H, CH₃ CH(CH)₂) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 55.8, 53.3, 41.0, 38.3, 31.7, 31.2, 30.7, 26.4, 25.4, 24.2, 21.2, 14.6 ppm. MS (EI+): m/z (%) = 294 (77) [M]⁺, 187 (78), 175 (16), 148 (30), 147 (30), 119 (100), 106 (22), 73 (27), 41 (26). HRMS (EI+): m/z [M]⁺ calcd for C₁₂H₂₂S₄: 294.0604; found: 294.0605.