A Convenient and Efficient Synthesis of Trifluoromethyl Vinyl Sulfoxide and Its Reactivity in Addition Reactions

Abstract

We report a novel high-yielding approach to trifluoro­methyl vinyl sulfoxide from 2-mercaptoethanol and trifluoromethyl iodide. Additionally, the principal ability of this compound to react with N-, O-, and S-nucleophiles is demonstrated.

Key words

trifluoromethylation - oxidation - nucleophilic addition - bromination - vinyl sulfoxides

References and Notes

• 1 Hansch C. Leo A. Taft RW. Chem. Rev.  1991,  91:  165 
• 2 Knunyants IN. Rozhkov IN. Alexandrov AM. Yagupolskii LM. J. Gen. Chem. USSR (Engl. Transl.)  1967,  37:  1210 
• 3a Magnier E. Tordeux M. Goumont R. Magder K. Wakselman C. J. Fluorine Chem.  2003,  124:  55 
• 3b Moïse J. Goumont R. Magnier E. Wakselman C. Synthesis  2004,  2297 
• 4 Magnier-Bouvier C. Blazejewski J.-C. Larpent C. Magnier E. Tetrahedron Lett.  2006,  47:  9121 
• 5 de Castries A. Magnier E. Monmotton S. Fensterbank H. Larpent C. Eur. J. Org. Chem.  2006,  4685 
• 9 Harris JF. J. Org. Chem.  1967,  32:  2063 

6

2-[(Trifluoromethyl)thio]ethanol (5)
Reaction was carried out in the three-neck flask equipped by condenser (-80 ˚C), mechanical stirrer, and bubbler. To the stirred suspension of sodium sulfite (113.5 g, 0.9 mol) and sodium formate (93.6 g, 0.9 mol) in DMF-H₂O (600 mL:180 mL) mixture mercaptoethanol (70 g, 0.9 mol) in DMF (100 mL) was added in a single portion at 0 ˚C under argon. CF₃I (216 g, 1.1 mol) was bubbled into the reaction mixture for 2-3 h at r.t. After stirring at r.t. for 24 h the solution was poured into H₂O (300 mL). Product was extracted by Et₂O (5 × 300 mL), organic layer was washed by diluted HCl (3 × 50 mL), H₂O (5 × 200 mL) and dried (MgSO₄). Solvent was removed by distillation at atmospheric pressure, and product was purified by distillation. Yield 90 g, 68%; bp 124-126 ˚C. ^¹H NMR (299.5 MHz, DMSO-d ₆): δ = 3.06 (t, ^³ J = 6.2 Hz, 2 H, CH₂), 3.64 (t, ^³ J = 6.2 Hz, 2 H, CH₂), 5.01-5.35 (br s, 1 H, OH). ^¹9F NMR (282.2 MHz, DMSO-d ₆): δ = -39.96 (s, SCF₃). Anal. Calcd for C₃H₅F₃OS: C, 24.66; H, 3.45; S, 21.94. Found: C, 24.87; H, 3.40; S, 22.03.

7

2-Chloroethyl Trifluoromethyl Sulfide (6)
SOCl₂ (25 mL, 0.33 mol) was added dropwise to the alcohol 5 (45 g, 0.31 mol) at 0 ˚C over 30 min. The reaction mixture was stirred under reflux for 2 h. After cooling to r.t. H₂O (0.3 mL), followed by K₂CO₃ (2 g), was added, and the resulting mixture was allowed to stand overnight. Product 6 was purified by vacuum distillation (6.7˙10^-5 bar) over K₂CO₃ into cooled trap and following distillation at atmospheric pressure. Yield 49 g, 96%; bp 94-96 ˚C. ^¹H NMR (299.5 MHz, CDCl₃): δ = 3.21 (t, ^³ J = 7.5 Hz, 2 H, CH₂), 3.72 (t, ^³ J = 7.5 Hz, 2 H, CH₂). ^¹9F NMR (282.2 MHz, DMSO-d ₆): δ = -41.38 (s, SCF₃). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 31.8 (q, ^³ J _CF = 2.5 Hz, α-CH₂), 42.2 (s, β-CH₂), 130.7 (q, ^¹ J _CF = 306.9 Hz, CF₃).

8

Oxidation of Sulfide 6 to Sulfoxide 7 Using Oxone ^®
To the stirred mixture (mechanical stirrer) of SiO₂ (340 g) and H₂O (135 mL) Oxone^® (125 g, 0.41 mol of KHSO₅) and a solution of sulfide 6 (45 g, 0.27 mol) in CH₂Cl₂ (700 mL) were added in a single portion. The reaction mixture was stirred at r.t. for 120 h (monitoring by ^¹9F NMR). Silica gel was filtered off and washed with CH₂Cl₂ (ca 300 mL). The organic layer was washed with a FeSO₄ solution, dried (MgSO₄), and filtered. Solvent was removed at atmospheric pressure, and product was purified by distillation. Yield 47 g, 96%; bp 64 ˚C (9.3˙10^-³ bar). ^¹H NMR (299.5 MHz, CDCl₃): δ = 3.17-3.27 (m, 1 H, CH₂), 3.44-3.51 (m, 1 H, CH₂), 3.88-4.06 (m, 2 H, CH₂). ^¹9F NMR (282.2 MHz, CDCl₃): δ = -74.15 (s, SOCF₃). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 35.5 (s, β-CH₂), 51.4 (q, ^³ J _CF = 2.5 Hz, α-CH₂), 125.4 (q, ^¹ J _CF = 333.3 Hz, CF₃).