Quinuclidones are a class of bicyclic

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

s with

chemical formula In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...

C₇H₁₁NO with two

structural isomer In chemistry, a structural isomer (or constitutional isomer in the IUPAC nomenclature) of a chemical compound, compound is another compound whose molecule has the same number of atoms of each element, but with logically distinct chemical bond, b ...

s for the base skeleton 3-quinuclidone and 2-quinuclidone. 3-Quinuclidone (1-azabicyclo .2.2ctan-3-one) is an uneventful molecule that can be synthesized as the

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid Acid strength is the tendency of an acid, symbol ...

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...

in a

Dieckman condensation The Dieckmann condensation is the intramolecular chemical reaction of diesters with base to give β-keto esters. It is named after the German chemist Walter Dieckmann (1869–1925). The equivalent intermolecular reaction is the Claisen condensati ...

Organic reduction Organic reductions or organic oxidations or organic redox reactions are redox reactions that take place with organic compounds. In organic chemistry oxidations and reductions are different from ordinary redox reactions, because many reactions carr ...

of this compound gives the compound

quinuclidine Quinuclidine is an organic compound and a bicyclic amine and used as a catalyst and a chemical building block. It is a strong base with p''K''a of the conjugate acid of 11.0.{{cite journal , title=Azatriquinanes: Synthesis, Structure, and Reacti ...

, structurally related to DABCO, which has one additional bridgehead nitrogen atom. The other isomer, 2-quinuclidone, appears equally uneventful, but in fact it has defied synthesis until 2006. The reason is that this molecule is very unstable because its

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

group has the

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

lone pair In chemistry, a lone pair refers to a pair of valence electrons that are not shared with another atom in a covalent bondIUPAC ''Gold Book'' definition''lone (electron) pair''/ref> and is sometimes called an unshared pair or non-bonding pair. Lone ...

and the carbonyl group not properly aligned, as may be expected for an amide, as a result of steric strain. This behaviour is predicted by Bredt's Rule, and formal

group resembles in fact an

, as evidenced by the ease of salt formation. The

organic synthesis Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...

of the tetrafluoroborate

of 2-quinuclidone is a six-step affair starting from norcamphor the final step being an

azide In chemistry, azide is a linear, polyatomic anion with the formula and structure . It is the conjugate base of hydrazoic acid . Organic azides are organic compounds with the formula , containing the azide functional group. The dominant applic ...

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

Schmidt reaction In organic chemistry, the Schmidt reaction is an organic reaction in which an azide reacts with a carbonyl derivative, usually an aldehyde, ketone, or carboxylic acid, under acidic conditions to give an amine or amide, with expulsion of nitrogen ...

(38% yield): This compound rapidly reacts with water to the corresponding

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

with a

chemical half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...

of 15 seconds.

X-ray diffraction X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...

shows

pyramidalization In chemistry, trigonal planar is a molecular geometry model with one atom at the center and three atoms at the corners of an equilateral triangle, called peripheral atoms, all in one plane. In an ideal trigonal planar species, all three ligands ...

on the nitrogen atom (59° compared to 0 for reference

dimethylformamide Dimethylformamide is an organic compound with the formula ( CH3)2NC(O)H. Commonly abbreviated as DMF (although this initialism is sometimes used for dimethylfuran, or dimethyl fumarate), this colourless liquid is miscible with water and the majo ...

) and torsion around the carbon-nitrogen bond to an extent of 91°. Attempts to prepare the free-base lead to uncontrolled

polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer, monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are ...

. It is, nevertheless, possible to estimate its basicity in an experiment in which amine pairs (the quinuclidonium salt and a reference amine such as diethylamine or

indoline Indoline is an aromatic heterocyclic organic compound with the chemical formula C8H9N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing ring. The compound is based on the indole st ...

) are introduced into a mass spectrometer. The relative basicity is then revealed by collision-induced dissociation of the heterodimer. Further analysis via the extended kinetic method allows for the determination of the proton affinity and gas phase basicity of 2-quinuclidonium. This method has determined that quinuclidone ranks among secondary and tertiary amines in terms of proton affinity.''Synthesis of 2-Quinuclidonium by Eliminating Water: Experimental Quantification of the High Basicity of Extremely Twisted Amides'' Tony Ly, Michael Krout, Don K. Pham, Kousuke Tani, Brian M. Stoltz, and Ryan R. Julian

J. Am. Chem. Soc. The ''Journal of the American Chemical Society'' is a weekly peer-reviewed scientific journal that was established in 1879 by the American Chemical Society. The journal has absorbed two other publications in its history, the ''Journal of Analytic ...

; 2007; 129(7) pp 1864 - 1865; (Communication) This high basicity is hypothesized to be due to the loss of electron delocalization when the amide bond is twisted—this causes misalignment of the pi orbitals, resulting in loss of electron resonance.

References

{{reflist Quinuclidines Lactams