Efficient Syntheses of Thiophenol Derivatives

Abstract

The photochemical bromination of 4-methylthiophenol with N-bromosuccinimide is reported. Depending on the amount of NBS, mono or bis bromination of the methyl group was obtained. Conversion of brominated derivatives to dialdehydes is also discussed. Improvement of synthetic routes towards thiophenol derivatives is motivated by their key role for the functionalization of metal nanoparticles and surfaces.

Key words

photochemistry - halogenation - bromine - thiols - oxidation

References and Notes

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17

Procedure for the Synthesis of 1,2-Bis[4-(bromomethyl)-phenyl]disulfane (3; Table 1, Entry 4): NBS (0.8 g, 4.49 mmol) was added to a solution of 4-methylthiophenol (0.56 g, 4.49 mmol) in benzene (5 mL). The solution was deaerated with argon for 20 min during which time p-tolyl disulfide (4) formed. NBS (0.08 g, 0.449 mmol, 0.1 equiv) was added and the reaction mixture was irradiated for 1 h with a 250-W tungsten lamp, placed next to the flask, which provided sufficient energy to reflux the solvent. Two other portions of NBS (0.08 g, 0.449 mmol) were successively added followed by 1 h of irradiation after each addition. After cooling, succinimide precipitated and was removed by filtration. The filtrate was then concentrated under reduced pressure. The residue was diluted with CH₂Cl₂ (100 mL) and the organic phase was washed with diluted sodium thiosulfate until the brown color of bromine disappeared. The organic phase was washed twice with H₂O (2 × 20 mL), dried over MgSO₄ and the solvent was removed under reduced pressure. NMR spectrum of the brownish solid showed a mixture of 3 and 5 in a ratio of 92:8. Recrystallization from EtOH yielded 3 pure as a white solid (334 mg, 37% yield). ^¹H NMR (400 MHz, CDCl₃): δ = 4.46 (s, 4 H), 7.33 (d, 4 H, J = 8.3 Hz), 7.45 (d, 4 H, J = 8.3 Hz). ^¹³C NMR (100 MHz, CDCl₃): δ = 32.7, 127.5, 129.8, 136.9, 137.2. Anal. Calcd for C₁₄H₁₂Br₂S₂: C, 41.60; H, 2.99; S, 15.87. Found: C, 41.58; H, 3.10; S, 16.18.

18

Procedure for the Synthesis of 1,2-Bis[4-(dibromo-methyl)phenyl]disulfane (5; Table 2, Entry 1): NBS (0.8 g, 4.49 mmol) was added to a solution of 4-methylthiophenol (0.56 g, 4.49 mmol) in benzene (5 mL). The solution was deaerated with argon for 20 min during which time p-tolyl disulfide 4 formed. Then NBS (1.6 g, 8.98 mmol, 2 equiv) was added in one portion and the reaction mixture was irradiated for 1 h. After cooling, succinimide precipitated and was removed by filtration. The filtrate was then concentrated under reduced pressure. The residue was diluted with CH₂Cl₂ (100 mL) and the organic phase was washed with diluted sodium thiosulfate until the brown color of bromine disappeared. The organic phase was washed twice with H₂O (2 × 20 mL), dried over MgSO₄ and the solvent was removed under reduced pressure. NMR spectrum of the crude reaction mixture showed a mixture of 5:3 in the ratio 90:10. The residue was then purified by recrystallization from EtOH. Tetrabromide 5 was isolated pure as a light-brown solid (0.908 g, 72% yield). ^¹H NMR (400 MHz, CDCl₃): δ = 6.61 (s, 2 H), 7.47 (d, 4 H, J = 8.6 Hz), 7.52 (d, 4 H, J = 8.6 Hz). ^¹³C NMR (100 MHz, CDCl₃): δ = 39.9, 126.8, 127.3, 138.6, 140.8. Anal. Calcd for C₁₄H₁₀Br₄S₂: C, 29.92; H, 1.79; S, 11.41. Found: C, 30.19; H, 2.16; S, 11.61.

21

Procedure for the Synthesis of 1,2-Bis[4-(formyl)-phenyl]disulfane (2; Sommelet Reaction): aq AcOH (50%, 20 mL) was added to a mixture of 3 (0.50 g, 1.24 mmol), and hexamethylenetetramine (0.69 g, 4.8 mmol) in THF (10 mL). The mixture was refluxed overnight. The solution was then diluted with H₂O (20 mL) and extracted with CH₂Cl₂ (2 × 20 mL). The organic phases were combined, dried over MgSO₄ and the solvent was finally removed under reduced pressure. Purification by column chromatography (silica gel, CH₂Cl₂) afforded dialdehyde 2 as a colorless solid (0.254 g, 75% yield). NMR characterizations were consistent with the literature (see ref.^¹²). ^¹H NMR (400 MHz, CDCl₃): δ = 7.61 (d, 4 H, J = 8.4 Hz), 7.81 (d, 4 H, J = 8.4 Hz), 9.95 (s, 2 H, CHO). ^¹³C NMR (100 MHz, CDCl₃): δ = 126.2, 130.3, 135.1, 143.7, 190.9.