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3D model (JSmol) | |||
605387 | |||
ChEBI |
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ChemSpider |
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PubChem CID |
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CompTox Dashboard (EPA) |
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Properties | |||
CH2N2 | |||
Molar mass | 42.041 g·mol−1 | ||
Related compounds | |||
Related compounds | 1H-Diazirine | ||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
In organic chemistry, diazirines are a class of organic molecules consisting of a carbon bound to two nitrogen atoms, which are double-bonded to each other, forming a cyclopropene-like ring, 3H-diazirine (>CN2). They are isomeric with diazocarbon groups (>C=N=N), and like them can serve as precursors for carbenes by loss of a molecule of dinitrogen. For example, irradiation of diazirines with ultraviolet light leads to carbene insertion into various C−H , N−H, and O−H bonds. [1] Hence, diazirines have grown in popularity as small, photo-reactive, crosslinking reagents. [2] They are often used in photoaffinity labeling studies to observe a variety of interactions, including ligand-receptor, ligand-enzyme, protein-protein, and protein-nucleic acid interactions. [3]
A number of methods exist in the literature for the preparation of diazirines, which begin from a variety of reagents. [4]
Generally, synthetic schemes that begin with ketones (>C=O) involve conversion of the ketone with the desired substituents to diaziridines (>CN2H2). These diaziridenes are then subsequently oxidized to form the desired diazirines.
Diaziridines can be prepared from ketones by oximation, followed by tosylation (or mesylation), and then finally by treatment with ammonia (NH3). Generally, oximation reactions are performed by reacting the ketone with hydroxylammonium chloride (NH3OH−Cl+) under heat in the presence of a base such as pyridine. [5] [6] Subsequent tosylation or mesylation of the alpha-substituted oxygen with tosyl or mesyl chloride in the presence of base yields the tosyl or mesyl oxime. [7] The final treatment of the tosyl or mesyl oxime with ammonia produces the diaziridine. [1] [3] [7] [8]
Diaziridines can be also produced directly by the reaction of ketones with ammonia in the presence of an aminating agent such as a monochloramine or hydroxyl amine O-sulfonic acid. [9]
Diaziridines can be oxidized to diazirines by a number of methods. These include oxidation by chromium-based reagents such as the Jones oxidation, [10] oxidation by iodine and triethylamine, [5] oxidation by silver oxide, [11] oxidation by oxalyl chloride, [7] or even electrochemical oxidation on a platinum-titanium anode. [12]
Diazirines can be alternatively formed in a one-pot process using the Graham reaction, starting from amidines. [13] This reaction yields a halogenated diazirine, whose halogen can be displaced by various nucleophilic reagents. [14]
Upon irradiation with UV light, diazirines form reactive carbene species. The carbene may exist in the singlet form, in which the two free electrons occupy the same orbital, or the triplet form, with two unpaired electrons in different orbitals.
The substituents on the diazirine affect which carbene species is generated upon irradiation and subsequent photolytic cleavage. Diazirine substituents that are electron donating in nature can donate electron density to the empty p-orbital of the carbene that will be formed, and hence can stabilize the singlet state. For example, phenyldiazirine produces phenylcarbene in the singlet carbene state [15] whereas p-nitrophenylchlorodiazirine or trifluorophenyldiazirine produce the respective triplet carbene products. [16] [17]
Electron donating substituents can also encourage photoisomerization to the linear diazo compound [30], rather than the singlet carbene, and hence these compounds are unfavorable for use in biological assays. [18] On the other hand, trifluoroaryldiazirines in particular show favorable stability and photolytic qualities [18] and are most commonly used in biological applications. [1]
Carbenes produced from diazirines are quickly quenched by reaction with water molecules, [19] and hence yields for photoreactive crosslinking assays are often low. Yet, as this feature minimizes unspecific labeling, it is actually an advantage of using diazirines.
Diazirines are often used as photoreactive crosslinking reagents, as the reactive carbenes they form upon irradiation with UV light can insert into C-H, N-H, and O-H bonds. This results in proximity dependent labeling of other species with the diazirine containing compound.
Diazirines are often preferred to other photoreactive crosslinking reagents due to their smaller size, longer irradiation wavelength, short period of irradiation required, and stability in the presence of various nucleophiles, and in both acidic and basic conditions. [20] Benzophenones, which form reactive triplet carbonyl species upon irradiation, often require long periods of irradiation which can result in non-specific labeling, and moreover are often inert to various polar solvents. [21] Aryl azides require a low wavelength of irradiation, which can damage the biological macromolecules under investigation.
Diazirines are widely used in receptor labeling studies. This is because diazirine-containing analogs of various ligands can be synthesized and incubated with their respective receptors, and then subsequently exposed to light to produce reactive carbenes. The carbene will covalently bond to residues in the binding site of the receptor. The carbene compound may include a bioorthogonal tag or handle by which the protein of interest can be isolated. The protein can then be digested and sequenced by mass spectrometry in order to identify which residues the carbene containing ligand is bound to, and hence the identity of the binding site in the receptor.
Examples of diazirines used in receptor labeling studies include:
In a manner analogous to receptor labeling, diazirine containing compounds that are analogs of natural substrates have also been used to identify binding pockets of enzymes. Examples include:
Diazirines have been used in photoaffinity labeling experiments involving nucleic acids as well. Examples include:
Diazirines have also been used to study protein lipid interactions, for example the interaction of various sphingolipids with proteins in vivo. [29]
Benzophenone is the organic compound with the formula (C6H5)2CO, generally abbreviated Ph2CO. It is a white solid that is soluble in organic solvents. Benzophenone is a widely used building block in organic chemistry, being the parent diarylketone.
An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates.
In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural polymers.
In organic chemistry, a carbene is a molecule containing a neutral carbon atom with a valence of two and two unshared valence electrons. The general formula is R−:C−R' or R=C: where the R represents substituents or hydrogen atoms.
The Suzuki reaction is an organic reaction, classified as a cross-coupling reaction, where the coupling partners are a boronic acid and an organohalide, and the catalyst is a palladium(0) complex. It was first published in 1979 by Akira Suzuki, and he shared the 2010 Nobel Prize in Chemistry with Richard F. Heck and Ei-ichi Negishi for their contribution to the discovery and development of palladium-catalyzed cross-couplings in organic synthesis. This reaction is also known as the Suzuki–Miyaura reaction or simply as the Suzuki coupling. It is widely used to synthesize polyolefins, styrenes, and substituted biphenyls. Several reviews have been published describing advancements and the development of the Suzuki reaction. The general scheme for the Suzuki reaction is shown below, where a carbon-carbon single bond is formed by coupling a halide (R1-X) with an organoboron species (R2-BY2) using a palladium catalyst and a base. The organoboron species is usually synthesized by hydroboration or carboboration, allowing for rapid generation of molecular complexity.
Isoxazole is an electron-rich azole with an oxygen atom next to the nitrogen. It is also the class of compounds containing this ring. Isoxazolyl is the univalent radical derived from isoxazole.
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.
The Baeyer–Villiger oxidation is an organic reaction that forms an ester from a ketone or a lactone from a cyclic ketone, using peroxyacids or peroxides as the oxidant. The reaction is named after Adolf von Baeyer and Victor Villiger who first reported the reaction in 1899.
Affinity labels are a class of enzyme inhibitors that covalently bind to their target causing its inactivation. The hallmark of an affinity label is the use of a targeting moiety to specifically and reversibly deliver a weakly reactive group to the enzyme that irreversibly binds to an amino acid residue. The targeting portion of the label often resembles the enzyme's natural substrate so that a similar mode of noncovalent binding is used prior to the covalent linkage. Their usefulness in medicine can be limited by the specificity of the first noncovalent binding step whereas indiscriminate action can be utilized for purposes such as affinity labeling - a technique for the validation of substrate-specific binding of compounds.
In organic chemistry, umpolung or polarity inversion is the chemical modification of a functional group with the aim of the reversal of polarity of that group. This modification allows secondary reactions of this functional group that would otherwise not be possible. The concept was introduced by D. Seebach and E.J. Corey. Polarity analysis during retrosynthetic analysis tells a chemist when umpolung tactics are required to synthesize a target molecule.
Schwartz's reagent is the common name for the organozirconium compound with the formula (C5H5)2ZrHCl, sometimes called zirconocene hydrochloride or zirconocene chloride hydride, and is named after Jeffrey Schwartz, a chemistry professor at Princeton University. This metallocene is used in organic synthesis for various transformations of alkenes and alkynes.
Barrelene is a bicyclic organic compound with chemical formula C8H8 and systematic name bicyclo[2.2.2]octa-2,5,7-triene. First synthesized and described by Howard Zimmerman in 1960, the name derives from the resemblance to a barrel, with the staves being three ethylene units attached to two methine groups. It is the formal Diels–Alder adduct of benzene and acetylene. Due to its unusual molecular geometry, the compound is of considerable interest to theoretical chemists.
Organocopper chemistry is the study of the physical properties, reactions, and synthesis of organocopper compounds, which are organometallic compounds containing a carbon to copper chemical bond. They are reagents in organic chemistry.
In genetics, crosslinking of DNA occurs when various exogenous or endogenous agents react with two nucleotides of DNA, forming a covalent linkage between them. This crosslink can occur within the same strand (intrastrand) or between opposite strands of double-stranded DNA (interstrand). These adducts interfere with cellular metabolism, such as DNA replication and transcription, triggering cell death. These crosslinks can, however, be repaired through excision or recombination pathways.
Alcohol oxidation is a collection of oxidation reactions in organic chemistry that convert alcohols to aldehydes, ketones, carboxylic acids, and esters where the carbon carries a higher oxidation state. The reaction mainly applies to primary and secondary alcohols. Secondary alcohols form ketones, while primary alcohols form aldehydes or carboxylic acids.
An oxaziridine is an organic molecule that features a three-membered heterocycle containing oxygen, nitrogen, and carbon. In their largest application, oxaziridines are intermediates in the industrial production of hydrazine. Oxaziridine derivatives are also used as specialized reagents in organic chemistry for a variety of oxidations, including alpha hydroxylation of enolates, epoxidation and aziridination of olefins, and other heteroatom transfer reactions. Oxaziridines also serve as precursors to amides and participate in [3+2] cycloadditions with various heterocumulenes to form substituted five-membered heterocycles. Chiral oxaziridine derivatives effect asymmetric oxygen transfer to prochiral enolates as well as other substrates. Some oxaziridines also have the property of a high barrier to inversion of the nitrogen, allowing for the possibility of chirality at the nitrogen center.
An insertion reaction is a chemical reaction where one chemical entity interposes itself into an existing bond of typically a second chemical entity e.g.:
Fétizon oxidation is the oxidation of primary and secondary alcohols utilizing the compound silver(I) carbonate absorbed onto the surface of celite also known as Fétizon's reagent first employed by Marcel Fétizon in 1968. It is a mild reagent, suitable for both acid and base sensitive compounds. Its great reactivity with lactols makes the Fétizon oxidation a useful method to obtain lactones from a diol. The reaction is inhibited significantly by polar groups within the reaction system as well as steric hindrance of the α-hydrogen of the alcohol.
In organic chemistry, the Graham reaction is an oxidation reaction that converts an amidine into a diazirine using a hypohalite reagent. The halide of the hypohalite oxidant, or another similar anionic additive to the reaction, is retained as a substituent on the diazirine product. The reaction was first reported in 1965. Various reaction mechanisms have been proposed.
m-Terphenyls (also known as meta-terphenyls, meta-diphenylbenzenes, or meta-triphenyls) are organic molecules composed of two phenyl groups bonded to a benzene ring in the one and three positions. The simplest formula is C18H14, but many different substituents can be added to create a diverse class of molecules. Due to the extensive pi-conjugated system, the molecule it has a range of optical properties and because of its size, it is used to control the sterics in reactions with metals and main group elements. This is because of the disubstituted phenyl rings, which create a pocket for molecules and elements to bond without being connected to anything else. It is a popular choice in ligand, and the most chosen amongst the terphenyls because of its benefits in regards to sterics. Although many commercial methods exist to create m-terphenyl compounds, they can also be found naturally in plants such as mulberry trees.
30. S. M. Korneev: Valence Isomerization between Diazo Compounds and Diazirines. In: Eur. J. Org. Chem. (2011), Band 31, S. 6153–6175, doi:10.1002/ejoc.201100224