Preparative resolution of (±)-trans-1,2-diaminocyclohexane by means of preferential crystallization of its citrate monohydrate

Even if (±)-trans-1,2-diaminocyclohexane crystallizes as a conglomerate, its low melting point (−10 °C) and its sensitivity to light, CO2, O2, and moisture make this molecule difficult to resolve. It has been shown that the citrate monohydrate of this compound crystallizes as a stable conglomerate with a high thermal stability (up to 163 °C) with no drawbacks as to those listed above for the pure diamine. The crystal structure of this salt, resolved by single crystal X-ray diffraction, reveals structural features consistent with the thermal stability of this phase. Several preferential crystallization attempts (AS3PC) have been performed at a 100 ml scale and at a one liter scale in water with and without additives. Finally a productivity of 40 g per batch per liter of solvent per hour was achieved with a crude enantiomeric purity better than 90%. A simple recrystallization of the crude crops gives quantitatively the crystalline compound with an ee >99% proving the absence of partial solid solution at room temperature.

Crystalline structure of (+)DACH, citrate monohydrate.Figure optionsDownload as PowerPoint slide

(1R,2R)-(−)-trans-1,2-Diaminocyclohexane citrate monohydrate[C6H16N2]2+, [C6O7H6]2−, H2O[α]36525=-21.2 (c 1.0, H2O)[α]43625=-14.4 (c 1.0, H2O)[α]54625=-9.0 (c 1.0, H2O)Source of chirality: (1R,2R)-(−)-trans-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R)