3-Fluoro-1-H-1,5-benzodiazepine-2,4-dione

3-Fluoro-1-H-1,5-benzodiazepine-2,4-dione

 

 

 

o-Phenylenediamine (2.70 g, 25 mmol) was added to the solution of sodium (1.2 g, 53 mmol) in anhydrous ethanol (50 mL) and the mixture was heated to reflux. Diethyl 2-fluoromalonate (4.45 g, 25 mmol) was added dropwise over 10 minutes and the mixture was heated at reflux for 2 h. After cooling to room temperature, the solution was filtered, the residue was washed with ethanol (20 mL), dissolved in water (30 mL) and acidified with HCl to pH 1. The mixture was cooled in ice, filtered, washed with water (2 × 10mL) and dried in vacuo to afford 3-fluoro-1-H-1,5-benzodiazepine-2,4-dione (3.23 g, 68%) as a tan powder.

m.p.: >300 °C, ([M + H]⁺, 195.0567, C₉H₈FN₂O₂ requires: [M]⁺, 195.0570); 

IR (neat,cm⁻¹) 3084, 2951, 1727, 1681, 1500, 1159;  


δ_H (DMSO d₆, 400 MHz): 5.57 (1H, d, ²J_HF 46.4, CHF), 7.15–7.19 (2H, m, Ar–H), 7.22 (2H, dt, ³J_HH 6.6, ⁴J_HH 3.5, Ar–H), 10.81 (2H, bs N–H); δ_F (DMSO d₆, 376 MHz): – 207.99 (d, ²J_HF 46.4 C–F);

 δ_C (DMSO d₆, 100 MHz) 85.12 (d, ¹J_CF 184.5, C–F), 122.55, 125.52, 128.41, 163.36 (d, ²J_CF 23.2, CO), 164.59 (d, ²J_CF 13.4, CO); 

m/z (ASAP) 195 (100%, [M + H]⁺), 135 (23%, [M − COCHF]⁺)............   N. Ishikawa, A. Takaoka and M. K. Ibrahim, J. Fluorine Chem., 1984, 25, 203–212 CrossRef CAS.


 http://pubs.rsc.org/en/content/articlehtml/2015/gc/c5gc00402k





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7-Phenyl-1 3-diazaspiro[4.4]nonane-2,4-dione

7-Phenyl-1 3-diazaspiro[4.4]nonane-2,4-dione

The product from Preparation 83 (5.8 g), potassium cyanide (2.75 g) and ammonium carbonate (9.1 g) were heated in 80 mls of 50% aqueous EtOH for 7 h, and then at room temperature for 48 h. The mixture was filtered, and the solid washed thoroughly with water (3×50 mls). The filtrate was concentrated, the pH adjusted to 2 using concentrated HCl and the resulting suspension filtered off and washed with water (3×50 mls). The bulked solids were recrystallised from EtOH and water (300 ml:100 ml) to give the title product as 1:1 mixture of diatereoisomeric pairs (6.32 g); R_f 0.6 in EtOAc;

 ¹HNMR (300 MHz, CDCl₃) δ: 1.60-2.58 (m, 6H), 3.08-3.37 (m, 1H), 6.83-7.44 (m, 5H), 8.33 (d, 1H), 10.60 (s, 1H);