Addition-elimination Reaction Research Articles

Quinone-Catalyzed Selective Oxidation of Organic Molecules.

Quinones are common stoichiometric reagents in organic chemistry. Para-quinones with high reduction potentials, such as DDQ and chloranil, are widely used and typically promote hydride abstraction. In recent years, many catalytic applications of these methods have been achieved by using transition metals, electrochemistry, or O2 to regenerate the oxidized quinone in situ. Complementary studies have led to the development of a different class of quinones that resemble the ortho-quinone cofactors in copper amine oxidases and mediate the efficient and selective aerobic and/or electrochemical dehydrogenation of amines. The latter reactions typically proceed by electrophilic transamination and/or addition-elimination reaction mechanisms, rather than hydride abstraction pathways. The collective observations show that the quinone structure has a significant influence on the reaction mechanism and has important implications for the development of new quinone reagents and quinone-catalyzed transformations.

The mechanism of carboxyl activated-transfer reactions and its applications in chemistry and biology

The activation and transfer reaction on carboxyl group is not only an important topic in organic chemistry, but also a vital issue in biochemical systems. Understanding the details of these reactions could help investigators develop new synthetic methods, syntheze functional proteins and design new drugs or inhibitors. In this article, potential energy surfaces based on general physical organic and biochemical princeples are employed to analyze the structures and properties the transition states or intermediates in these reactions, as well as catalysts involved situations. A tetrahedron intermediate mediated two-step addition-elimination reaction mechanism is propused to be the most possible reaction process and Hammond postulate is used to determine the relative energy value of different transition states and intermediates. During the reaction, those activating groups which can effectively stablized the tetrahedron intermediates and eliminating from the centra carbon atom easily are illustrated to be better carboxyl group activating reagents, as the similar situations in catalysts of carboxyl activated reactions. Different cases in chemistry and biology of carboxyl activated-transfer reactions are compared and proved to be follow the same rules. And the applications of carboxyl activated-transfer reactions in chemical synthesis of peptides and biochemical process are also discussed. The analysis and comments of this review might serve researchers as meaningful reference on devoloping new carboxyl activated-transfer reactions.

Quantum chemical studies of azoles 4. A novel elimination–addition mechanism of tetrazole and 1,2,4-triazole electrophilic substitution

Thermodynamic parameters of the addition–elimination and elimination–addition electrophilic substitution reactions of 1H-tetrazole and 1,2,4-1H-triazole obtained from DFT B3LYP/ 6-31G(d,p) quantum chemical calculations with proton as model electrophile are compared. According to calculations, the elimination–addition reactions can proceed without preliminary formation of N-protonated azolium salts.

Synthesis and Characterization of Partially Fluorinated Polybenzoxazine Resins Utilizing Octafluorocyclopentene as a Versatile Building Block

Two new fluorinated diamine-based benzoxazines using octafluorocyclopentene (OFCP) as a building block have been developed. Monomers were synthesized via two distinct synthetic procedures utilizing the facile nucleophilic addition–elimination reaction of OFCP with phenols amenable to a multigram scale-up. The structure elucidation of both monomers was confirmed by 1H, 19F, and 13C NMR, ATR-FTIR, and high-resolution mass spectrometry. Benzoxazine networks were prepared by a thermally mediated ring-opening polymerization. ATR-FTIR analysis was utilized to monitor the ring-opening reaction of the monomers. The resulting two cured resins exhibit the combined excellent properties of low dielectric constants (k = 3.2–2.6), excellent thermal stability, and high char yields which are suitable for many applications such as flame-resistant materials as well as aerospace and microelectronic industries.

Colorimetric and fluorimetric detection of cysteine: Unexpected Michael addition–elimination reaction

The synthesis of three isomers based on Michael addition mechanism for the detection of sulfur-containing species in aqueous solution is described. These compounds are constructed by conjugating an enone to a coumarin fluorophore. A substituted-phenyl (o, m, or p-) was appended at the carbonyl carbon to adjust the reactivity. The experimental results showed that (E)-7-(diethylamino)-3-(3-(3-hydroxyphenyl)-3-oxoprop-1-en-1-yl)-2H-chromen-2-one (m-QPS) and (E)-7-(diethylamino)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)-2H-chromen-2-one (p-QPS) barely react with sulfur-containing nucleophiles, while (E)-7-(diethylamino)-3-(3-(2-hydroxyphenyl)-3-oxoprop-1-en-1-yl)-2H-chromen-2-one (o-QPS) exhibited a fast response toward sulfite, sulfide and thiols in DMSO/phosphate buffer (2:1). The above results are probably due to the intramolecular H-bonding activated Michael addition. More interestingly, cysteine triggered unusual photophysical responses of o-QPS: the original absorption (488 nm) and emission peaks (573 nm) underwent significant blue shifts initially and then recovered, which might be caused by the Michael addition and elimination reaction, respectively.

Experimental and theoretical studies of the products of addition-elimination reactions between benzil dihydrazone and three isomeric chlorobenzaldehydes.

A series of mono- and di-Schiff bases formed between benzil dihydrazone {BDH; systematic name: (1Z)-[(2E)-2-hydrazinylidene-1,2-diphenylethylidene]hydrazine} and three isomeric chlorobenzaldehydes were designed and synthesized to be used as model compounds to help to explain the reaction mechanisms for the formation of Schiff bases. These compounds are 1-(2-chlorobenzylidene)-2-{2-[2-(2-chlorobenzylidene)hydrazin-1-ylidene]-1,2-diphenylethylidene}hydrazine (BDHOCB), and the 3-chloro (BDHMCB) and 4-chloro (BDHPCB) analogues, all having the formula C28H20Cl2N4. Surprisingly, only di-Schiff bases were obtained; our attempts to push the reaction in favour of the mono-Schiff bases all failed. Density functional theory (DFT) calculations were performed to explain the trend in the experimental results. In the case of the systems studied, the type of Schiff base produced exhibits a clear dependence on the HOMO-LUMO energy gaps (ΔE(HOMO-LUMO)), i.e. the product is mainly governed by its stability. The compounds were characterized by single-crystal X-ray diffractometry, elemental analysis, melting point, (1)H NMR and (13)C NMR spectroscopy. The structural features of the three new Schiff bases are similar. For instance, they have the same chemical formula, all the molecules have a symmetrical double helix structure, with each Ph-C=N-N=C-Ph arm exhibiting an anti conformation, and their supramolecular interactions include intermolecular π-π and weak C-H...π stacking interactions. The crystal systems are different, however, viz. triclinic (space group P1¯) for BDHPCB, monoclinic (space group P2(1)/n) for BDHOCB and orthorhombic (space group Pnna) for BDHMCB.

Reactions of stabilized aliphatic carbanions with esters of formic acid in the gas phase.

The reactions of nitromethane, acetonitrile, and ethyl acetate carbanions with formic acid esters were investigated in the gas phase by mass spectrometry and quantum chemical calculations. It was found that the carbanion of nitromethane practically does not react with formic acid esters and only traces of the Claisen- type addition-elimination reaction product were observed. In the case of the deprotonated acetonitrile, the Claisen-type condensation that yielded the carbanion of cyanoacetaldehyde proceeded almost quantitatively for all the studied formates. Other products, like the Riveros reaction product, were observed in minor amounts. The ethyl acetate carbanion reacts with formates in a much more complex way because it decomposes in a collision cell, yielding the deprotonated ketene anion, which also can react with formic acid esters. Consequently, the Claisen condensation reaction products of both anions were observed as well as the products of other reactions. All the proposed reaction pathways were confirmed by quantum chemical calculations, including the transition-state energies.

Synthesis of Vinyl Sulfoxides Using Sulfinyl Chlorides and Olefins

A general method for synthesis of vinyl sulfoxides, using sulfinyl chlorides and olefins as starting materials and DBU as an HCl scavenger, has been developed. Vinyl sulfoxides were obtained from the ZnCl2 catalysed addition of sulfinyl chlorides to olefins followed by the elimination with DBU. However, the direct reaction of sulfinyl chlorides with olefins in the presence of DBU, usually leads to generation of vinyl sulfones. The sulfonyl radicals generated from the DBU-mediated disproportionation of the sulfinyl radicals undergo addition-elimination reaction with olefins to give vinyl sulfones.

Amine-promoted asymmetric [4+2] cycloadditions of α-acetoxymethyl allenoate and dual activated alkenes: stereoselective synthesis of poly-substituted cyclohexenes

A chiral secondary amine-promoted asymmetric [4+2] cycloadditions of α-acetoxymethyl allenoate 1 and electron-deficient alkenes 2 have been developed. The reaction features the utilization of addition–elimination reaction between allenoate 1 and the secondary amine to generate the key 2-aminobutadiene intermediate, which subsequently undergoes [4+2] cycloaddition with alkenes in a stepwise fashion, delivering the substituted cyclohexenes with good stereoselectivity.

ChemInform Abstract: The Metal Tin Promoted Cascade Reaction of Ketones in Aqueous Media for the Construction of 2‐Bromo‐4‐aryl‐1,3‐pentadiene.

A novel type of transformation was discovered serendipitously during the Barbier-type allenylation reaction of aromatic ketones promoted by the metal, tin, in aqueous media. Additionally, a series of new, highly functionalized 2-bromo-4-aryl-1,3-pentadienes could be obtained with good yields in this reaction. This cascade reaction shows the unique properties of the metal, tin. Furthermore, it is actually a cascade reaction which involves two steps: one is the Barbier-type allenylation of the carbonyl compound, and the other is an SN2′ type addition–elimination reaction. Notably, this reaction has the advantages of simple, mild conditions and is easy to operate. Furthermore, the corresponding product could be applied to various coupling reactions or other diversified transformations.

Synthesis and characterization of a novel fluorinated bismaleimide via a nucleophilic addition–elimination reaction and its polymeric networks

A novel fluorinated bismaleimide, OFCP-BMI, was designed and readily synthesized via the nucleophilic addition–elimination reaction of octafluorocyclopentene with maleimide-functionalized phenol.

Theoretical study of the degradation mechanism on the reactions 2,3,7,8-tetrachlorinated dibenzo-p-dioxins with hydrogen and chlorine atoms

The mechanism of the multiple-pathway and multiple-step degradation reactions of 2,3,7,8-tetrachlorinated dibenzo-p-dioxins with H and Cl atoms is investigated using the density functional theory. The electronic structures and the minimum energy path (MEP) are calculated at the B3LYP/6-311+G(d,p) level, and energetic information (single-point) is further refined at the B3LYP/6-311++G(3df,2p) level. The main possible ring opening reaction pathways of the C-O bond breakdown include indirect cleavage ring opening reaction, hydrogen addition reaction, hydrogen addition elimination reaction, and chlorine addition elimination reaction. Ten reaction steps of the six reaction pathways are considered. Our calculations indicate that hydrogen addition reaction step TS1c is of the smallest barrier height, and indirect cleavage ring opening reaction channel has the largest barrier height and is the most endothermic.

New solventless and metal-free synthesis of the antiepileptic drug 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide (Rufinamide) and analogues

This work presents a new synthesis of the antiepileptic drug rufinamide—1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide) in chemical form—and some analogue compounds, through a one-pot reaction employing a solventless, metal-free catalysis and without any reducing reagent. The great novelty presented is the synthesis of 4-trichloroacetyl-1-(2,6-difluorobenzyl/benzyl/4-methoxybenzyl)-5-methyl(phenyl)-1H-1,2,3-triazoles as new precursors from a regioselective 1,3-dipolar cycloaddition reaction between 1,1,1-trichloro-4-alkoxyalk-3-en-2-ones and some benzyl azides, which are converted into rufinamide and the analogues by an addition–elimination reaction with an aqueous solution of NH4OH in good yields (42–52%).

Addition-elimination versus Tishchenko reaction in the gas phase.

Gas phase reactions of the substituted phenide ions with methyl formate have been studied. It was found that the results of these reactions depend mainly on the basicity of the phenide ion, which is related to the presence of the electron-accepting or electron-donating substituents in the benzene ring. It was shown that the phenide ions substituted with electron-withdrawing groups react with methyl formate in the gas phase in a two-step reaction. The first step that proceeds according to the typical addition-elimination mechanism results in the formation of the anion of the respective benzaldehyde derivative with the negative charge located either in the aldehyde group (acyl anion) or in the benzene ring (phenide anion) in position ortho to an aldehyde moiety. In the second step, the preliminary-formed anion reacts with the second molecule of methyl formate yielding formally product of the second addition-elimination reaction. Theoretical calculations as well as collision induced dissociation spectra of the model compounds suggest that this reaction proceeds according to the Tishchenko reaction mechanism yielding the respective phthalide anion. According to our knowledge, this is the first example of the Tishchenko-type reaction in the gas phase.

ChemInform Abstract: Supra‐molecular Synthons Based on Gold....π(arene) Interactions

AbstractReview: 56 refs.

A concise synthesis of tunable fluorescent 1,3-dihydroisobenzofuran derivatives as new fluorophores

A convenient potassium tert-butoxide catalyzed addition–elimination reaction has been achieved using exo-cyclic enol ethers and aryl aldehydes as the starting materials. The transition-metal free reaction proceeded smoothly to afford 1,3-dihydroisobenzofuran derivatives with good to excellent yields. More importantly, the resulting products were discovered as novel fluorophores with good fluorescence properties and remarkable Stokes shifts. Changing the nature of the substituents in 1,3-dihydroisobenzofurans derivatives allowed the maximum emission wavelengths to be tuned between 438 and 597 nm and the Stokes shifts varied between 63 and 166 nm. In particular, derivative C27 containing a piperidyl and a cyano group showed the maximum emission wavelength of 597 nm and a Stokes shift of 166 nm.

Three overlooked chemical approaches toward 3-naphthalimide amonafide N-derivatives

Three efficient strategies for derivatization of the anticancer drug candidate amonafide (Quinamed, originally AS1413) are described. Unprecedented reductive amination of aryl aldehydes, SNAr, and addition–elimination reactions, while using readily available starting materials, give quick entry to potential libraries of novel 3-aryl, 3-benzyl N-derivatives of amonafide. The selective anticancer activity of this important DNA intercalation agent is expected to be enhanced by expanding the diversity of amonafide N-derivatives. The synthetic routes reported in this work are general and readily applicable.

(S)-Binaphthalene-based fluorescence polymer sensors for direct and visual F− detection

(S)-binaphthalene-based polymer sensors P-1 and P-2 could be synthesized by the polymerization of 5,5′-((2,5-dibutoxy-1,4-phenylene)bis(ethyne-2,1-diyl))bis-(2-hydroxy-3-(piperidin-1-ylmethyl) benzaldehyde (M-1) with (S)-2,2′-dimethoxy-(1,1′-binaphthalene)- 6,6′-diamine (M-2) and (S)-2,2′-dimethoxy-(1,1′-binaphthalene)-3,3′-diamine (M-3) via nucleophilic addition–elimination reaction. The fluorescence emission of P-1 and P-2 could exhibit gradual enhancement behavior upon the addition of F−. Compared with other anions, such as Cl−, Br−, I−, HSO4−, ClO4−, H2PO4−, AcO−, and NO3−, F− could lead to the most remarkable fluorescence enhancement as high as 3.67-fold for P-1 and 12.85-fold for P-2, respectively. More importantly, both two polymer sensors P-1 and P-2 can display a bright yellow fluorescence color change for F− under a commercially available UV lamp, which could be clearly observed by the naked eyes for direct visual detection of F−.

Ionic Liquid Effects on Nucleophilic Aromatic Substitution Reactions from QM/MM Simulations

Nucleophilic aromatic substitution (SNAr) reactions are particularly sensitive to medium effects and have been reported to benefit from ionic liquids. The SNAr reaction between cyclic secondary amines (i.e., piperidine, pyrrolidine, and morpholine) and the 2-L-5-nitrothiophene (para-like) and 2-L-3-nitrothiophene (ortho-like) isomers, where L = bromo, methoxy, phenoxy, and 4-nitrophenoxy, has been computationally investigated in 1-butyl-3-methylimidazolium tetrafluoroborate and hexafluorophosphate [BMIM][BF4] and [BMIM][PF6], respectively. QM/MM Monte Carlo simulations utilizing free-energy perturbation theory were used to characterize the solute-solvent interactions over the addition-elimination reaction pathway. Energetic and structural analyses determined that the improved SNAr reactivity in [BMIM][BF4] and [BMIM][PF6] can be attributed to (1) an enhanced nucleophilicity of the cyclic amines in the ionic liquids with an order of Pyr ≥ Pip > Mor, (2) beneficial π(+)-π interactions between the BMIM cations and the aromatic rings present on the substrate that enhanced coplanarity between the thiophene ring and the aromatic substituents, resulting in a larger positive charge on the reacting ipso carbon, and (3) a highly ordered ionic liquid clathrate formation that, despite an entropy penalty, provided reduced activation free-energy barriers derived from an increasing number of solvent ions favorably interacting with the emerging charge separation at the rate-limiting addition step.

Hg(2+) -induced in situ generated radical cation of (S)-BINOL-based polymer for highly enantioselective recognition of phenylalaninol.

Phenylalaninol enantiomers are one of the most important chiral compounds due to its presence in biologically active molecules and pharmaceutical products. In this paper, a novel chiral fluorescence polymer sensor incorporating (S)-BINOL and oligomeric aniline via a nucleophilic addition-elimination reaction is designed and synthesized. Polymer sensor exhibits "turn-off" fluorescence quenching response upon the addition of Hg(2+) , and "turn-on" moderate fluorescence enhancement behavior towards phenylalaninol enantiomers. Meanwhile, this kind of (S)-BINOL-based polymer sensor can exhibit highly selective enantioselective recognition response towards (L)-phenylalaninol upon the addition of Hg(2+) and the value of ef can reach as high as 5.4, which can be attributed to the formation of in situ generated radical cation arisen from oligomeric aniline moiety by Hg(2+) induction.