Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

3-Fluoro-5-nitro-1-(pentafluorosulfanyl)benzene was prepared by three different ways: as a byproduct of direct fluorination of 1,2-bis(3-nitrophenyl)disulfane, by direct fluorination of 4-nitro-1-(pentafluorosulfanyl)benzene, and by fluorodenitration of 3,5-dinitro-1-(pentafluorosulfanyl)benzene. The title compound was subjected to a nucleophilic aromatic substitution of the fluorine atom with oxygen, sulfur and nitrogen nucleophiles affording novel (pentafluorosulfanyl)benzenes with 3,5-disubstitution pattern. Vicarious nucleophilic substitution of the title compound with carbon, oxygen, and nitrogen nucleophiles provided 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzenes substituted in position four.

S3 the mixture (see Figure 1, left). The crude mixture was poured onto ice, extracted with CH 2 Cl 2 (3 × 60 mL), the combined organic phase was dried (MgSO 4 ) and solvent was removed under reduced pressure. The amount of tar (28% by weight) was determined by Kugelrohr distillation.
2. Reaction in anhydrous HF followed by GC: A solution of 1 (4.50 g, 18.1 mmol) in anhydrous HF (100 mL) cooled to −15 °C was fluorinated with 10% F 2 /N 2 (v/v) at a rate of 3.6 L/h (at −15 to −10 °C). Samples were taken periodically and analyzed by GC to determine composition of the mixture (see Figure 1, right). The crude mixture after solvent evaporation was poured onto ice, extracted with CH 2 Cl 2 (3 × 60 mL), the combined organic phase was dried (MgSO 4 ) and solvent was removed under reduced pressure. The amount of tar (5% by weight) was determined by Kugelrohr distillation.
Preparative reaction: A solution of 1 (2.509 g, 10.08 mmol) in MeCN (60 mL) was added to a nitrogen flushed PFA reactor with a magnetic stirring bar. A mixture of 20% F 2 /N 2 (v/v) was bubbled for 11 h at a rate of 4.5 L/h while maintaining the temperature of the bath at -5 ºC. The mixture was flushed with N 2 for 10 min. and solvent was removed under reduced pressure yielding residue containing 40% of 2 (by GC-MS). Purification by flash chromatography (silica gel, Et 2 O/petroleum ether, 10:90) afforded 2 (466.3 mg, 17% yield, 26% yield based on recovered 1).

Synthesis of compounds 3 by S N Ar of fluorine
General procedure 1: To a solution of KOH (138.1 mg,2.46 mmol,5 equiv.) in the corresponding alcohol (4 mL), 2 (130.0 mg, 0.49 mmol, 1 equiv.) was added. The mixture was stirred at 80 °C for 30 min. If necessary, aqueous solution of NaOH (0.5 M) was added to pH ≈ 8 and the product was extracted into Et 2 O (4 × 10 mL). The combined organic phase was washed with water (15 mL), brine (15 mL), dried (MgSO 4 ) and solvent was removed under reduced pressure. Purification by flash chromatography afforded pure 3. General procedure 2: To a solution of NaH (3 equiv) in the appropriate solvent the corresponding alcohol was added and stirred for 30 min at rt. Then 2 (1 equiv) was added and the mixture was stirred at rt for the corresponding time. Water (5 mL) and aqueous solution of NaOH (10 mL, 0.5 M) were added and the product was extracted into Et 2 O (4 × 20). The combined organic phase was washed with water, brine, dried (MgSO 4 ) and solvent was removed under reduced pressure. If necessary, purification by flash chromatography afforded pure 3. 3c: Prepared according to the general procedure 2 from the mixture of NaH (26.0 mg, 0.65 mmol, 3 equiv) and dry iPrOH (2.5 mL) stirred for 30 min.

Synthesis of compounds 4 by VNS
General procedure 5: To a solution of t-BuOK (3 equiv) in the corresponding dry solvent, a mixture of the appropriate X-NuH (1-2 equiv) and 2 (1 equiv) were added dropwise. After stirring for appropriate temperature and time, aqueous solution of HCl (1 M) was added to pH ~ 3 and the product was extracted into EtOAc (4 × 10 mL). The combined organic phase was S8 washed with LiCl (40 mL, 1 M), dried (MgSO 4 ), and the solvent was removed under reduced pressure. Purification by flash chromatography afforded product 4. 4a: Prepared according to the general procedure 5 using t-BuOK (77.0 mg, 0.69 mmol, 3 equiv) in DMF (3 mL) and a mixture of 2 (50.4 mg, 0.19 mmol, 1 equiv) and ClCH 2 CO 2 Et (25.9 mg, 0.21 mmol, 1 equiv) in DMF (1.5 mL) at −30 °C for 10 min. No further purification of the product was carried out giving 4a as a pale yellow oil (47.5 mg, 71%