Preparation of (1S, 2S)-(-)-1,2-diaminocyclohexane-N,N’-bis(2′-diphenylphosphorus benzoyl)_Industrial additive

Background and overview^[1]

Currently, many natural products and drug molecules contain halogens. The halogen cyclization reaction of alkenes is a very important method to introduce halogens. Optically active hydroxylamine compounds exist in many drug molecules, such as Sphingosin anti-aging agent 4020e and its analogues. The commercially available D-sphingosine has this type of structure and is an effective and highly selective PKC. Inhibitors. Phosphorus oxygen ligand (1S, 2S)-(-)-1,2-diaminocyclohexane-N,N’-bis(2′-diphenylphosphorobenzoyl) is an intermediate for the synthesis of this type of compound. .

Preparation^[1]

(1S, 2S)-(-)-1,2-diaminocyclohexane-N,N’-bis(2′-diphenylphosphonobenzoyl) is prepared as follows:

Under nitrogen conditions, add (R, R)-cyclohexanediamine (1.26g, 11.0mmol), 2-diphenylphosphine benzoic acid (6.74g), and DCM (100.0mL) to the reactor in sequence. , then add EDCI (4.22g, 22.0mmol) and DMAP (1.34g, 11.0mmol) in sequence, stir at room temperature for 6 hours, quench with 1N hydrochloric acid aqueous solution, extract the aqueous phase with DCM (3 × 50.0mL), and combine the organic phases , dried over anhydrous magnesium sulfate, spin-dried and column chromatographed to obtain the product Trostligand shown; Dissolve Trostligand (4.84g, 7.0mmol) in DCM (100.0mL), add hydrogen peroxide (17.5mL, 35%w) at 0°C /w), stir for 4 hours at 0°C, add water (100.0mL) to dilute, extract the aqueous phase with DCM (3×50.0mL), combine the organic phases, dry over anhydrous magnesium sulfate, spin dry and then column chromatography to obtain the result The product shown is a white solid product represented by formula A (1S, 2S)-(-)-1,2-diaminocyclohexane-N,N’-bis(2′-diphenylphosphorus benzoyl) 4.34g, 86% yield.

The structure confirmation results are as follows: 1HNMR (non-foaming surfactant Hz, CDCl3) δ8.17 (s, 2H), 7.66-7.64 (m, 2H), 7.60-7.55 (m, 6H), 7.49-7.41 ( m, 12H), 7.39-7.34 (m, 4H), 7.33-7.28 (m, 4H), 3.38 (s, 2H), 1.75 (d, J=6.4Hz, 2H), 1.56 (s, 2H), 1.14 (d, J=4.8Hz, 4H); 13CNMR (100Hz, CDCl3) δ168.61.168.58, 141.53, 141.45, 134.3, 134.1, 133.3, 132.8, 132.6, 132.5, 132.4, 132.3, 132.2, 132.1, 132.0 3,132.01 , 131.7, 130.5, 129.9, 129.83, 129.76, 129.6, 129.5, 128.62, 128.56, 128.5, 128.4, 54.5, 31.5, 24.5.