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Names | |
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IUPAC name 3,7-diazabicyclo[3.3.1]nonane | |
Identifiers | |
3D model (JSmol) | |
ChEMBL | |
ChemSpider | |
PubChem CID | |
CompTox Dashboard (EPA) | |
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Properties | |
C7H14N2 | |
Molar mass | 126.203 g/mol |
Melting point | 158-161 °C |
Boiling point | 190-195 °C (9 Torr) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Bispidine (3,7-diazabicyclo[3.3.1]nonane) is an organic compound that is classified as a bicyclic diamine. Although synthetic, it is related structurally to natural alkaloid sparteine. It is a white crystalline solid. It has been widely investigated as a chelating agent. Many derivatives are known.
Bispidine has a bicyclic scaffold consisting of two condensed piperidines. The unsubstituted bispidine backbone can assume three conformations: a chair-chair, boat-chair, and a boat-boat. In the gas phase, the chair-chair conformation predominates [1]
A convenient route to synthesize the bispidine molecule involves a pent-1-en-3-one and a prop-2-en-1-amine leading to a bis(carbethoxyethyl)allylamine which converts in 1-allylpiperidin-4-one by acid hydrolysis and decarboxylation. Then a Mannich reaction occurs, in particular a condensation of a 4-piperidone derivative with paraformaldehyde and allylamine in presence of acetic acid forms N,N’-diallylbispidin-9-one. This latter, results in the final bispidine after treatment with ethyl chloroformate in the presence of NaI, followed by alkaline hydrolysis. [2]
Reaction with formaldehyde gives a diazaadamantane. [3]
The bispidine unit can be chemically functionalized in several positions of its rigid bicyclic scaffold leading to a large number of bispidine-type ligands. [4]
The first bispidine-based ligands dates back to 1930, when Carl Mannich reported the synthesis of two different substituted bispidine molecules. [5] The common route to afford the bispidine derivatives is a variation of the Mannich reaction, in particular two steps are required to afford the final product. The first step includes a reaction between a compound containing acidic C-H hydrogens, an aldehyde and a primary amine, using a predefined molar ratio of 1:2:1, respectively, leading to a piperidone. Additionally, a second condensation between the piperidone, an aliphatic aldehyde and a primary amine, using a ratio of 1:4:2, yields the desired bispidine. The reaction conditions need to be controlled to avoid the competitive aldol reaction. [6] Indeed the reaction solution should be as concentrated as possible to afford maximum yield, using alcohols, THF or other solvents listed in literature. Whereas high temperatures are preferred for one-step condensations, the two-step reaction is generally carried out at 0 °C for the first and refluxed during the second one.
Chemical substitutions on the bispidine backbone can influence the equilibrium of conformers. Many computational studies and others based on nuclear magnetic resonance (1H and 13C NMR), X-ray crystallography and Raman spectroscopy have been done to investigate the different conformational entities of bispidine derivatives. [7]
Bispidine-based ligands have been mostly employed in coordination chemistry. [4] The first transition metal complex with bidentate bispidine dates back to 1957. [8] Indeed, by the addition of further metal binding sites in the basic bispidine scaffold, that has already two aliphatic aminic N donor atoms, efficient stable metal complexes can be selectively synthesized, thus obtaining tetra-, [9] penta-, [10] hexa- [11] and octa- [12] dentate species.
Because of the chemical versatility of the bispidine scaffold and due to the metal selectivity and complexes stability of these type of ligand, they have been proposed for many applications, although none have been commercialized
Cu(II)-bispidine complexes catalyze aziridations. [13] Amino acids-modified bispidine framework support catalysts for the enantio-selective aldol reaction of functionalized ketones. [14] Bispidine-based iron complexes have been investigated for the oxidation of olefin and unactivated C-H bonds. [15]
Several patents relate to the use of bispidine ligands for their antiarrhythmic [16] and analgesic activity. [17] It has been also found out that they exhibit high affinity and selectivity to ĸ-opioid receptors and many studies concerning the influence of structural variation towards their biological activity were also reported. [18]
Bispidine systems were also employed as bifunctional chelators for PET exams. [19] Fast complexation, availability of different functionalities for the linking to the targeting vectors, and a cost-effective way to synthesize them in the multigram scale are among these requirements. The functionalization and optimization of pentadentate bispidine derivatives and the evaluation of the potential of radiocopper−bispidine complexes as PET tracers have been done.
Bispidine derivatives have been used as ligands to build novel one-dimensional coordination polymers, showing an interesting influence on the dynamic behaviour of these hybrid systems. [20]
Ferrocene is an organometallic compound with the formula Fe(C5H5)2. The molecule is a complex consisting of two cyclopentadienyl rings bound to a central iron atom. It is an orange solid with a camphor-like odor, that sublimes above room temperature, and is soluble in most organic solvents. It is remarkable for its stability: it is unaffected by air, water, strong bases, and can be heated to 400 °C without decomposition. In oxidizing conditions it can reversibly react with strong acids to form the ferrocenium cation Fe(C5H5)+2. Ferrocene and the ferrocenium cation are sometimes abbreviated as Fc and Fc+ respectively.
In organic chemistry, the Mannich reaction is a three-component organic reaction that involves the amino alkylation of an acidic proton next to a carbonyl functional group by formaldehyde and a primary or secondary amine or ammonia. The final product is a β-amino-carbonyl compound also known as a Mannich base. Reactions between aldimines and α-methylene carbonyls are also considered Mannich reactions because these imines form between amines and aldehydes. The reaction is named after Carl Mannich.
DABCO (1,4-diazabicyclo[2.2.2]octane), also known as triethylenediamine or TEDA, is a bicyclic organic compound with the formula N2(C2H4)3. This colorless solid is a highly nucleophilic tertiary amine base, which is used as a catalyst and reagent in polymerization and organic synthesis.
A transition metal carbene complex is an organometallic compound featuring a divalent organic ligand. The divalent organic ligand coordinated to the metal center is called a carbene. Carbene complexes for almost all transition metals have been reported. Many methods for synthesizing them and reactions utilizing them have been reported. The term carbene ligand is a formalism since many are not derived from carbenes and almost none exhibit the reactivity characteristic of carbenes. Described often as M=CR2, they represent a class of organic ligands intermediate between alkyls (−CR3) and carbynes (≡CR). They feature in some catalytic reactions, especially alkene metathesis, and are of value in the preparation of some fine chemicals.
Tröger's base is a white solid tetracyclic organic compound. Its chemical formula is (CH
3C
6H
3NCH
2)
2CH
2. Tröger's base and its analogs are soluble in various organic solvents and strong acidic aqueous solutions due to their protonation. It is named after Julius Tröger, who first synthesized it in 1887.
The Petasis reaction is the multi-component reaction of an amine, a carbonyl, and a vinyl- or aryl-boronic acid to form substituted amines.
Cycloocta-1,5-diene is a cyclic hydrocarbon with the chemical formula C8H12, specifically [−(CH2)2−CH=CH−]2.
In organic chemistry, organocatalysis is a form of catalysis in which the rate of a chemical reaction is increased by an organic catalyst. This "organocatalyst" consists of carbon, hydrogen, sulfur and other nonmetal elements found in organic compounds. Because of their similarity in composition and description, they are often mistaken as a misnomer for enzymes due to their comparable effects on reaction rates and forms of catalysis involved.
NacNac is a class of anionic bidentate ligands. 1,3-Diketimines are often referred to as "HNacNac", a modification of the abbreviation Hacac used for 1,3-diketones. These species can exist as a mixture of tautomers.
Quinuclidine is an organic compound with the formula HC(C2H4)3N. It is a bicyclic amine that can be viewed as a tied back version of triethylamine. It is a colorless solid. It is used as a reagent (base) and catalyst. It can be prepared by reduction of quinuclidone.
In organometallic chemistry, a metallacycle is a derivative of a carbocyclic compound wherein a metal has replaced at least one carbon center; this is to some extent similar to heterocycles. Metallacycles appear frequently as reactive intermediates in catalysis, e.g. olefin metathesis and alkyne trimerization. In organic synthesis, directed ortho metalation is widely used for the functionalization of arene rings via C-H activation. One main effect that metallic atom substitution on a cyclic carbon compound is distorting the geometry due to the large size of typical metals.
Organoiron chemistry is the chemistry of iron compounds containing a carbon-to-iron chemical bond. Organoiron compounds are relevant in organic synthesis as reagents such as iron pentacarbonyl, diiron nonacarbonyl and disodium tetracarbonylferrate. While iron adopts oxidation states from Fe(−II) through to Fe(VII), Fe(IV) is the highest established oxidation state for organoiron species. Although iron is generally less active in many catalytic applications, it is less expensive and "greener" than other metals. Organoiron compounds feature a wide range of ligands that support the Fe-C bond; as with other organometals, these supporting ligands prominently include phosphines, carbon monoxide, and cyclopentadienyl, but hard ligands such as amines are employed as well.
The Petrenko-Kritschenko reaction is a classic multicomponent-name reaction that is closely related to the Robinson–Schöpf tropinone synthesis, but was published 12 years earlier.
In Lewis acid catalysis of organic reactions, a metal-based Lewis acid acts as an electron pair acceptor to increase the reactivity of a substrate. Common Lewis acid catalysts are based on main group metals such as aluminum, boron, silicon, and tin, as well as many early and late d-block metals. The metal atom forms an adduct with a lone-pair bearing electronegative atom in the substrate, such as oxygen, nitrogen, sulfur, and halogens. The complexation has partial charge-transfer character and makes the lone-pair donor effectively more electronegative, activating the substrate toward nucleophilic attack, heterolytic bond cleavage, or cycloaddition with 1,3-dienes and 1,3-dipoles.
Metal-catalyzed C–H borylation reactions are transition metal catalyzed organic reactions that produce an organoboron compound through functionalization of aliphatic and aromatic C–H bonds and are therefore useful reactions for carbon–hydrogen bond activation. Metal-catalyzed C–H borylation reactions utilize transition metals to directly convert a C–H bond into a C–B bond. This route can be advantageous compared to traditional borylation reactions by making use of cheap and abundant hydrocarbon starting material, limiting prefunctionalized organic compounds, reducing toxic byproducts, and streamlining the synthesis of biologically important molecules. Boronic acids, and boronic esters are common boryl groups incorporated into organic molecules through borylation reactions. Boronic acids are trivalent boron-containing organic compounds that possess one alkyl substituent and two hydroxyl groups. Similarly, boronic esters possess one alkyl substituent and two ester groups. Boronic acids and esters are classified depending on the type of carbon group (R) directly bonded to boron, for example alkyl-, alkenyl-, alkynyl-, and aryl-boronic esters. The most common type of starting materials that incorporate boronic esters into organic compounds for transition metal catalyzed borylation reactions have the general formula (RO)2B-B(OR)2. For example, bis(pinacolato)diboron (B2Pin2), and bis(catecholato)diborane (B2Cat2) are common boron sources of this general formula.
In chemistry, hexahydro-1,3,5-triazine is a class of heterocyclic compounds with the formula (CH2NR)3. They are reduced derivatives of 1,3,5-triazine, which have the formula (CHN)3, a family of aromatic heterocycles. They are often called triazacyclohexanes or TACH's but this acronym is also applied to cis,cis-1,3,5-triaminocyclohexane.
1,5-Diaza-3,7-diphosphacyclooctanes are organophosphorus compounds with the formula [R'NCH2P(R)CH2]2, often abbreviated PR2NR'2. They are air-sensitive white solids that are soluble in organic solvents. The ligands exist as meso and d,l-diastereomers, but only the meso forms function as bidentate ligands.
The Crabbé reaction is an organic reaction that converts a terminal alkyne and aldehyde into an allene in the presence of a soft Lewis acid catalyst and secondary amine. Given continued developments in scope and generality, it is a convenient and increasingly important method for the preparation of allenes, a class of compounds often viewed as exotic and synthetically challenging to access.
The nitro-Mannich reaction is the nucleophilic addition of a nitroalkane to an imine, resulting in the formation of a beta-nitroamine. With the reaction involving the addition of an acidic carbon nucleophile to a carbon-heteroatom double bond, the nitro-Mannich reaction is related to some of the most fundamental carbon-carbon bond forming reactions in organic chemistry, including the aldol reaction, Henry reaction and Mannich reaction.
The ketimine Mannich reaction is an asymmetric synthetic technique using differences in starting material to push a Mannich reaction to create an enantiomeric product with steric and electronic effects, through the creation of a ketimine group. Typically, this is done with a reaction with proline or another nitrogen-containing heterocycle, which control chirality with that of the catalyst. This has been theorized to be caused by the restriction of undesired (E)-isomer by preventing the ketone from accessing non-reactive tautomers. Generally, a Mannich reaction is the combination of an amine, a ketone with a β-acidic proton and aldehyde to create a condensed product in a β-addition to the ketone. This occurs through an attack on the ketone with a suitable catalytic-amine unto its electron-starved carbon, from which an imine is created. This then undergoes electrophilic addition with a compound containing an acidic proton. It is theoretically possible for either of the carbonyl-containing molecules to create diastereomers, but with the addition of catalysts which restrict addition as of the enamine creation, it is possible to extract a single product with limited purification steps and in some cases as reported by List et al.; practical one-pot syntheses are possible. The process of selecting a carbonyl-group gives the reaction a direct versus indirect distinction, wherein the latter case represents pre-formed products restricting the reaction's pathway and the other does not. Ketimines selects a reaction group, and circumvent a requirement for indirect pathways.