What Is Quinuclidine?
Quinuclidine is a heterocyclic amine with the chemical formula C7H13N. It is also known as 1,4-ethanopiperidine. Its molecular weight is 111.18, CAS number is 100-76-5, density is 1.025 g/cm3, and melting point is 158°C (316°F).
Its IUPAC name is 1-azabicyclo[2.2.2]octane. It is a sublimable, colorless to milky solid. As a natural product, quinuclidine is categorized as an alkaloid, prominently featured in the molecular structure of quinine, a well-known anti-malarial alkaloid.
Uses of Quinuclidines
1. Starting Material
Quinuclidine serves as a foundational material for pharmaceuticals and functional materials, embodying many natural products that incorporate the quinuclidine structure. A prime example is quinine, celebrated for its anti-malarial properties.
Quinine, commonly administered as quinine hydrochloride or quinine sulfate to enhance solubility in water, exhibits specific toxicity towards Plasmodium falciparum. This parasite metabolizes hemoglobin in erythrocytes for nutrition. However, the resultant heme is toxic to the parasite, which it counteracts by polymerizing heme into a nontoxic form using heme polymerase. Quinine’s anti-malarial action is theorized to stem from its inhibition of heme polymerase.
Beyond quinine, numerous natural products featuring the quinuclidine structure exhibit diverse bioactivities. Recent years have seen significant interest in their asymmetric synthesis, with quinuclidine utilized as a key starting material.
2. Catalyst
Quinuclidine’s strong nucleophilic properties make it a valuable catalyst in chemical reactions, such as the addition of alkenes to aldehydes in the Morita-Baylis-Hillman reaction. The potential for functionalization to introduce a chiral point into compounds underscores its significance in the development of asymmetric synthetic catalysts.
Properties of Quinuclidines
1. Physical Properties
The [2.2.2]bicyclooctane ring endows quinuclidine with distinctive physical properties, enhancing its solubility compared to conventional amine compounds due to its unique structure.
2. Chemical Properties
Quinuclidine exhibits unique chemical behaviors not common to typical amides, including increased reactivity due to its steric structure. This structure limits electron pair conjugation with the pi orbitals of carbonyl carbon and oxygen, rendering the carbonyl carbon more susceptible to nucleophilic attack. Its pronounced nucleophilicity can be attributed to the fixed position of the non-covalent electron pair by the ring structure and the minimal steric hindrance around the nitrogen atom.
Other Information on Quinuclidines
Hazards of Quinuclidines
Despite its acute toxicity and potential to cause skin and eye irritation, quinuclidine is not subject to regulation under major safety and health legislations. Its handling requires careful consideration of its hazardous properties.