Fig 2.1: Suzuki Coupling Reaction – Aryl chloride (1.0mmol), Aryl boronic acid (1.2mmol), 0.5mol% catalyst, K2CO3 (2.0mmol), Tetrabutyl ammonium bromide (0.5mmol), 60°C Manufacture of 100 TPA of 2-Aminobiphenyl Page 5
Stille Coupling of aryl chlorides with organostannanes (Myung-Jong Jin and Dong-Hwan Lee, 2010) Stille Coupling is similar to Suzuki Coupling in terms of the catalyst used. The raw materials involved are aryl chlorides and organostannanes. The drawback with organostannanes is that they are extremely toxic and commercially unavailable. The chemical reaction involved is as follows:
Fig 2.2: Stille Coupling Reaction – Aryl chloride (1.0mmol), Organostannane (1.2mmol), 0.5mol% catalyst, CsF (2.0mmol), EtOH/H2O (2.0mL, 1:1), 50°C
Synthesis of 2-Aminobiphenyl using Palladium catalysed ortho-arylation of benzamides by aryl iodides (Dan-Dan Li, Ting-Ting Yuan, and Guan-Wu Wang, 2012 ) This method involves three steps which are briefly outlined below: a. Benzamide (0.5mmol) + Phenyl Iodide (1mmol) 2-Phenyl benzamide
Fig 2.3: Chemistry of conversion of Benzamide to 2-Phenyl benzamide
Conditions: Pd(OAc)2 (0.025mmol / 5mol%) + 1mmol of Ag2O (additive) in 5mL of Acetic acid Manufacture of 100 TPA of 2-Aminobiphenyl Page 6
Literature Survey Temp: 120°C Reaction Time: 5hrs Yield: 74%
On a lab scale, this reaction was carried out in a stirred vessel, monitored by thin layer chromatography (TLC) and stopped at the desired time. The solvent was vacuum evaporated to dryness and the residual was separated on a silica gel column with ether/ethyl acetate (2:1) as the eluent. b. 2-Phenyl benzamide (49.3 mg, 0.25 mmol) + solution of KOH (35.3 mg, 0.63 mmol) in MeOH (2.5 mL) Methyl biphenyl-2-yl carbamate The reaction mixture was stirred at room temperature until a homogeneous solution was obtained, then cooled to 5−10 °C in an ice−water bath. Diacetoxyiodobenzene (80.9 mg, 0.25 mmol) was added in one portion and dissolved within 5 min. The reaction was stirred at ice-bath temperature for 15 min followed by warming to room temperature while stirring for an additional 45 min. Upon completion of the reaction (TLC monitored), the methanol was removed in vacuo and the reaction mixture was quenched with water and extracted with CH2Cl2 (10 mL × 3). The solvent was removed in vacuo and the residual was separated on a silica gel column with petroleum...