(S)-(-)-3-cyclohexene carboxylic acid is a colorless transparent liquid at room temperature and pressure, with significant acidity and solubility in most organic solvents. It is commonly used as a chiral building block in organic synthesis, particularly in the preparation of chiral cyclohexane functional organic molecules such as the synthesis of the biologically active molecule ibuprofen.

Physical and Chemical Properties

The structure of (S)-(-)-3-cyclohexene carboxylic acid contains an internal double bond and a carboxyl group, giving it high chemical reactivity. The carboxyl unit in the structure can undergo reduction reactions to yield corresponding alcohol derivatives under the action of strong reducing agents. The internal double bond unit can undergo hydrogenation reactions to yield corresponding cyclohexane carboxylic acid derivatives under metal catalysis.

Iodination Reaction

One of the most common applications of (S)-(-)-3-cyclohexene carboxylic acid in organic synthesis is its addition reaction with elemental iodine under basic conditions. The double bond unit within the molecule can undergo electrophilic addition with elemental iodine under basic conditions, forming iodide ions that are rapidly attacked by the carboxylic acid unit to generate bridged iodination derivatives. This reaction has important applications in the synthesis of complex natural products.

Figure 1 (S)-(-)-3-cyclohexene carboxylic acid iodination reaction

Adding iodine (125.4 g, 494 mmol) to a mixture of (1S)-3-cyclohexene-1-carboxylic acid (48.0 g, 380 mmol), dichloromethane (580 mL), potassium iodide (82.1 g), sodium bicarbonate (42.0 g), and water (530 mL), the resulting reaction mixture was stirred at room temperature for 3 hours. After the reaction, 1 N sodium thiosulfate solution (800 mL) was added to the reaction mixture, followed by extraction with dichloromethane (1 L, 500 mL). The organic layer was washed with sodium bicarbonate solution (300 mL), water (500 mL), and saturated brine (300 mL). The organic layer was dried over anhydrous magnesium sulfate, separated, and concentrated. The precipitate was collected by filtration, washed with hexane, and dried to obtain the target product molecule.[1]

Medical Applications

(S)-(-)-3-cyclohexene carboxylic acid plays a crucial role as a chiral building block in the preparation of chiral cyclohexane organic molecules and the synthesis of biologically active molecules. Its diverse chemical properties and reactivity provide rich possibilities for organic synthesis, such as being a key intermediate in the synthesis of the drug molecule ibuprofen.

References

[1] Skidmore, John; et al Journal of Medicinal Chemistry (2014), 57(24), 10424-10442