Elimination Products Research Articles

3-Substituted-1-(Trimethylsilylmethyl)cyclobutyl Cations: Stereochemistry of Solvent Capture of β-Trimethylsilyl Carbocations

3-tert-Butyl- or phenyl-substituted-1-(trimethylsilylmethyl)cyclobutyl trifluoroacetates react in methanol via β-trimethylsilyl carbocationic intermediates formed from loss of trifluoroacetate ion. These cationic intermediates react to give a significant amount of methyl ether substitution products along with the expected alkene elimination products. Different methyl ether substitution products are formed from isomeric trifluoroacetates, and complete retention of configuration of the ether group relative to the starting trifluoroacetates is observed. The proposed origin of this retention is the involvement of two different β-trimethylsilyl carbocation intermediates that form while utilizing backside participation of the trimethylsilyl group. Computational studies have located three classical 1-(trimethylsilylmethyl)cyclobutyl carbocation energy minima. Two of these cations have a significant barrier (13-16 kcal/mol) to interconversion. It is proposed that methanol can capture each of these cations from different sides, leading to isomeric methyl ether products. A third energy minimum, formed by cyclobutane ring inversion, is thought to be unimportant in determining the stereochemistry of the methyl ether substitution products.

Improved Procedures for the Synthesis of 9,9-Disubstituted 9,10-Dihydroacridines.

We found that a previously reported synthesis of 9,9-disubstituted 9,10-dihydroacridines (DHAs) that relied on an acid-catalyzed cyclization was plagued by a competing elimination reaction, resulting in some elimination products being incorrectly identified as their structural isomer DHAs. In this report, we provide improved synthetic procedures for 9,9-disubstituted DHAs, demonstrated by the synthesis of two 9,9-diethyl DHAs.

Synthesis and reactivity of Pd(II) imidoyl complexes obtained by insertion of isocyanoferrocene into the Pd-C bonds of orthopalladated precursors.

While the multifaceted reactivity of organic isocyanides has been extensively demonstrated, that of their organometallic analogue, isocyanoferrocene (FcNC; Fc = ferrocenyl), has not yet been adequately explored. This contribution describes the syntheses of novel chelating Pd(II) imidoyl complexes, [(YCH2C6H4C(NFc)-κ2Y,C)PdCl(PR3)], by insertion of FcNC into the Pd-C bond of cyclopalladated precursors [(YCH2C6H4-κ2Y,C)PdCl(PR3)] (Y = Me2N, MeS, R = Ph, Me). The imidoyl complexes underwent facile alkylation with [Me3O][BF4] to produce the cationic aminocarbene complexes [{YCH2C6H4C(N(Me)Fc)-κ2Y,C}PdCl(PR3)][BF4]. All compounds were fully characterised using a combination of spectroscopic methods (NMR, FTIR and ESI MS), cyclic voltammetry and single-crystal X-ray crystallography. In addition, DFT calculations were used to describe the bonding in the two compound families. Analyses with intrinsic bond orbitals (IBOs) and the quantum theory of atoms in molecules (QTAIM) consistently pointed to the transformation of an X-type imidoyl C-ligand (σ-organyl) into an L-type carbene donor upon alkylation, which has only a minor structural consequence. Also reported is the unexpected conversion of the imidoyl complex [(Me2NCH2C6H4C(NFc)-κ2N,C)PdCl(PPh3)] into (Z)-2,2-dimethyl-1-(ferrocenylimino)isoindolin-2-ium tetrafluoroborate as a reductive elimination product, which was induced by Lewis and Brønsted acids.

Deamination of 1-Aminoalkylphosphonic Acids: Reaction Intermediates and Selectivity.

Deamination of 1-aminoalkylphosphonic acids in the reaction with HNO2 (generated "in situ" from NaNO2) yields a mixture of substitution products (1-hydroxyalkylphosphonic acids), elimination products (vinylphosphonic acid derivatives), rearrangement and substitution products (2-hydroxylkylphosphonic acids) as well as H3PO4. The variety of formed reaction products suggests that 1-phosphonoalkylium ions may be intermediates in such deamination reactions.

Radical-Polar Crossover Catalysis with a d0 Metal Enabled by a Redox-Active Ligand.

Radical-polar crossover mechanisms are invoked in numerous late transition metal and photocatalyzed reactions. To the best of our knowledge, reductive radical-polar crossover mechanisms are not invoked for group 3 early transition metals due to their propensity to exist in high oxidation states. Through use of a redox-active (tris)amido ligand we have accessed this mechanism for use with early transition metals. This mechanism is showcased through enabling product formation for a wide variety of elimination products from α-halo substituted benzylic bromides. The mechanism of this new type of reactivity with Sc is explored, and Hammett analysis reveals an anionic intermediate. The wide functional group tolerance of this reaction is also demonstrated.

N‐Benzoyl‐4‐dimethylaminopyridinium Chloride: A Lewis Base Adduct for Efficient Poly and Monobenzoylation

AbstractN‐benzoyl‐4‐dimethylaminopyridinium chloride [DMAPBz]+Cl− was efficiently employed for polybenzoylation of triols and tetrols without epimerization and elimination products. This Lewis base adduct has also been employed for regioselective monobenzoylation of polyols obtained from D‐pentoses. Further an eco‐friendly monobenzoylation of phenols, amines and alcohols was achieved in water as a solvent without using a base and chromatographic purification of the products. Chemoselective monobenzoylation and recovery of the DMAP is an added advantage of our protocol.

Effects of sugar cane extract on steroidogenesis in testicular interstitial cells of male Japanese quail (Coturnix japonica)

Sugar cane extract (SCE) is the end product of glucose, fructose, and sucrose elimination in molasses. SCE has various biological effects, such as anti-inflammation and antioxidation, and it is commonly found in animal feed. The present research is aimed at investigating the reproductive endocrine influence of SCE in male Japanese quails (Coturnix japonica) by feeding SCE containing food. In addition, in vitro Leydig cell culture was conducted to clarify the mechanism of SCE's influence. Our results showed that SCE feed extended the latency to the first neck grab, decreased male quail testis and epididymis weights, cloaca gland size, and reduced serum testosterone concentrations. Steroidogenic enzymes 3βHSD, 17βHSD, P450c17, and P450scc gene expression in the testis were decreased in the SCE groups. Western blot analysis showed decreased 3βHSD in the testis after feeding SCE. Isolated testicular interstitial cells cultured with SCE and ovine-LH suppressed testosterone secretion and 3βHSD gene expression. In conclusion, SCE as a feed additive has an impact on the sexual behavior and reproductive function of male Japanese quail, with the suppression of steroidogenesis in the Leydig cell. Our results may provide beneficial information to the livestock management and the poultry industry.

Rapid Access to Arylated and Allylated Cyclopropanes via Brønsted Acid-Catalyzed Dehydrative Coupling of Cyclopropylcarbinols.

A regioselective protocol for the synthesis of cyclopropyl derivatives that relies on Brookhart acid-catalyzed dehydrative coupling over substituted cyclopropylcarbinols without rearrangement is reported herein. The reactions proceed promptly at 25 °C with only 2.0 mol % catalyst loading and produce the cyclopropyl derivatives in excellent yields. This method is well tolerated with a vast range of cyclopropylcarbinols including aliphatic cyclopropylcarbinols, where no elimination product was obtained, demonstrating the protocol's utility. Further, the Hammett correlation suggested the formation of a cyclopropylcarbinyl cation followed by a coupling reaction. An extremely effective gram-scale reaction has also been demonstrated with a high turnover number.

Direct UV photodegradation of herbicide triclopyr in aqueous solutions: A mechanistic study

Mechanism of direct UV photolysis of pyridine herbicide triclopyr (TRI) was revealed by the combination of nanosecond laser flash photolysis, steady-state photolysis coupled with high resolution LC-MS and DFT quantum-chemical calculations. Both the detection of short-lived intermediates and the detailed identification of final products were done for the first time. The quantum yield of TRI photodegradation is about 4% at both UVC (254 nm) and UVB (308 nm) excitation. The primary stage is the heterolytic cleavage of C–Cl bond in dissociative triplet state of TRI with the formation of phenyl cation followed by a fast nucleophilic attack by a solvent molecule. The minor channel is the photohydrolysis leading to the formation of 3,5,6-trichloropyridin-2-ol. Primary photoproducts undergo secondary photolysis by the mechanism similar to initial TRI with the formation of products of acetic group elimination, sequential substitution of chlorine atoms to hydroxyl groups and, finally, oxidation and opening of the pyridine ring. Obtained results can be important for understanding the fate of pyridine herbicides in the processes of UVC disinfection and in natural waters under action of the sunlight.

Synthesis of 6-chloro(dichloro-, trichloro-)-methyl-3-R-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]- quinazolin-2-ones and their modification in reactions with nucleophilic and non-nucleophilic bases

The synthesis of 6-chloro-(dichloro-, trichloro)methyl-3-R-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones and their modification under the action of nucleophilic and/or basic reagents are described in this article. It was shown that 6-chloro-(dichloro-, trichloro)methyl-3-R-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones can be prepared by cyclocondensation of 3-(aminophenyl)-6-R-1,2;4-triazine-5(2Н)-ones with chloro-(dichloro-)acetaldehyde or chloral hydrate. The reactivity of the synthesized compounds toward nucleophilic base morpholine and non-nucleophilic base diisopropylethylamine (DIPEA) under different conditions was studied. It was shown that the prepared compounds under the action of morpholine and/or DIPEA can be converted into the products of substitution, elimination or elimination followed by isomerization and substitution. Refluxing of 6-(chloromethyl)-3-R-6,7-dihydro-2Н-[1,2,4]triazino[2,3-с]quinazoline-2-ones with equimolar quantity of morpholine and 10% excess of DIPEA in ethylene glycol monoethyl ether (EGEE) yielded the products on N-alkylation. 6-(Morpholinomethyl)-3-R-2H-[1,2,4]triazino[2,3-с]quinazoline-2-ones were obtained by heating of 6-dichloromethyl-3-R-6,7-dihydro-2Н-[1,2,4]triazino[2,3-с]quinazoline-2-ones with five-fold excess of morpholine in EGEE. Reaction of 3-R-6-(trichloromethyl)-6,7-dihydro-2H-[1,2,4]triazino[2,3-с]quinazolin-2-ones with three-fold excess of DIPEA in EGEE yielded 3-R-2Н-[1,2,4]triazino[2,3-с]quinazoline-2-ones. The physicochemical and spectral characteristics of the prepared compounds were determined and discussed.

Extending the HSA-Cys34-Adductomics Pipeline to Modifications at Lys525.

We previously developed an adductomics pipeline that employed nanoflow liquid chromatography and high-resolution tandem mass spectrometry (nLC-HR-MS/MS) plus informatics to perform an untargeted detection of modifications to Cys34 in the tryptic T3 peptide of human serum albumin (HSA) (21ALVLIAFAQYLQQC34PFEDHVK41). In order to detect these peptide modifications without targeting specific masses, the pipeline interrogates MS2 ions that are signatures of the T3 peptide. The pipeline had been pilot-tested with archived plasma from healthy human subjects, and several of the 43 Cys34 adducts were highly associated with the smoking status. In the current investigation, we adapted the pipeline to include modifications to the ε-amino group of Lys525─a major glycation site in HSA─and thereby extend the coverage to products of Schiff bases that cannot be produced at Cys34. Because trypsin is generally unable to digest proteins at modified lysines, our pipeline detects miscleaved tryptic peptides with the sequence 525KQTALVELVK534. Adducts of both Lys525 and Cys34 are measured in a single nLC-HR-MS/MS run by increasing the mass range of precursor ions in MS1 scans and including both triply and doubly charged precursor ions for collision-induced dissociation fragmentation. For proof of principle, we applied the Cys34/Lys525 pipeline to archived plasma specimens from a subset of the same volunteer subjects used in the original investigation. Twelve modified Lys525 peptides were detected, including products of glycation (fructosyl-lysine plus advanced-glycated-end products), acetylation, and elimination of ammonia and water. Surprisingly, the carbamylated and glycated adducts were present at significantly lower levels in smoking subjects. By including a larger class of in vivo nucleophilic substitution reactions, the Cys34/Lys525 adductomics pipeline expands exposomic investigations of unknown human exposure to reactive electrophiles derived from both exogenous and endogenous sources.

Selenoxide Elimination Triggers Enamine Hydrolysis to Primary and Secondary Amines: A Combined Experimental and Theoretical Investigation.

We discuss a novel selenium-based reaction mechanism consisting in a selenoxide elimination-triggered enamine hydrolysis. This one-pot model reaction was studied for a set of substrates. Under oxidative conditions, we observed and characterized the formation of primary and secondary amines as elimination products of such compounds, paving the way for a novel strategy to selectively release bioactive molecules. The underlying mechanism was investigated using NMR, mass spectrometry and density functional theory (DFT).

Reversible C(sp3)-Si Oxidative Addition of Unsupported Organosilanes: Effects of Silicon Substituents on Kinetics and Thermodynamics.

The intermolecular oxidative addition of unactivated C(sp3)-Si bonds is reported for a family of organosilanes at a cationic pincer-supported iridium complex. To our knowledge, no examples of oxidative addition to give analogous unsupported (alkyl)metal silyl complexes have been previously reported. The generality of this transformation is excellent, with successful examples demonstrated for tetraorganosilanes, mono- and poly alkoxysilanes, and two siloxysilanes. Oxidative addition is found to be completely reversible, with the product of reductive elimination being subject to trapping by triethylsilane. The successful isolation of these metal silyl complexes has allowed for an in-depth kinetic analysis of C(sp3)-Si reductive elimination, a process with strong implications in both catalytic C-H silylation and olefin hydrosilylation. The apparent order of reactivity is SiMe3 > SiMe2(CF3) > SiMe2OSiMe3 > SiMe2OSiMe2OSiMe3 > SiMe2(OMe) > SiMe2(OEt) > SiMe(OMe)2. A DFT analysis of the oxidative addition products shows that the thermodynamic stability of the (alkyl)metal silyl complexes span a range of ca. 10 kcal·mol-1, which relate closely with the experimentally determined rates of C(sp3)-Si reductive elimination and trapping, though a clear kinetic distinction exists between methoxy- and siloxysilyl complexes.

Diethyl Ether Conversion to Ethene and Ethanol Catalyzed by Heteropoly Acids

The conversion of diethyl ether (DEE) to ethene and ethanol was studied at a gas–solid interface over bulk and supported Brønsted solid acid catalysts based on tungsten Keggin heteropoly acids (HPAs) at 130–250 °C and ambient pressure. The yield of ethene increased with increasing reaction temperature and reached 98% at 220–250 °C (WHSV = 2.2 h–1). The most active HPA catalysts were silica-supported H3PW12O40 and H4SiW12O40 and the bulk heteropoly salt Cs2.5H0.5PW12O40. The HPA catalysts outperformed zeolites HZSM-5 and USY reported elsewhere. A correlation between catalyst activity and catalyst acid strength was established, which indicates that Brønsted acid sites play an important role in DEE elimination over HPA catalysts. The results point to the reaction occurring through the consecutive reaction pathway: DEE → C2H4 + EtOH followed by EtOH → C2H4 + H2O, where ethene is both a primary product of DEE elimination and a secondary product via dehydration of the primary product EtOH. Evidence is provided that DEE elimination over bulk HPA and high-loaded HPA/SiO2 catalysts proceeds via the surface-type mechanism.

Lithium aluminum hydride reduction of 1-phenylbutane-1,3-dione, and acetylation of the products: NMR and GC-MS analysis

Reduction of ?-diketones with lithium aluminum hydride (LiAlH4, LAH) can lead to different products, depending on the tautomeric equilibrium: the reduction of diketo forms gives the corresponding diols and the reduction of ketoenol forms yields elimination products, saturated and unsaturated ketones and alcohols. Here, we report on the results of LAH reduction of 1-phenylbutane-1,3-dione. The products of reduction were further acetylated and separated by dry flash chromatography. The obtained products, phenylbut(en)ols, phenylbut(en)ones and phenylbut(en)yl acetates, were characterized by spectral (1H and 13C NMR, MS) and retention index (RI) data. It can be concluded that LAH preferentially reduces the carbonyl group more distant from the phenyl group of 1-phenylbutane-1,3-dione. The structure-retention index relationships between isomers were discussed. Proton splitting patterns were resolved by proton NMR simulations.

Low‐Energy Pathways Found for the NH3 Activation and H2 Elimination by the Werner‐Type Complexes M(NH3)4+ (M=Fe, Ru and Os).

AbstractThe interactions of NH3 with the transition metal complexes M(NH3)n+ (M=Fe, Ru, Os; n=0−4) were investigated theoretically with the aim of analyzing the factors that determine their reactivity patterns and product distributions. The reactions of ammonia with the low‐coordination complexes of the three metallic ions (n=1−3) lead only to the addition product M(NH3)n+1+. However, once the highest‐coordinated complex M(NH3)4+ is reached, each of the reactions evolves to metal‐inserted species through low energy channels. For osmium, the hydrogen abstraction from an additional NH3 molecule by the inserted intermediate H−Os(NH3)4‐NH2+ leads to H2 elimination products along a favorable pathway. The facile breaking of the strong N−H bond of ammonia by these Werner‐type complexes is by far the most striking finding emerging from this study. Hopefully, this could inspire future contributions in the areas of chemical and bioinorganic catalysis.

Nucleophilic Fluorination with KF Catalyzed by 18-Crown-6 and Bulky Diols: A Theoretical and Experimental Study.

The activation of potassium fluoride for nucleophilic fluorination of alkyl halides is an important challenge because of the high lattice energy of this salt and its low solubility in many polar aprotic solvents. Crown ethers have been used for increasing the solubilization of KF during several decades. Nevertheless, these macrocycles are not enough to produce a high reaction rate. In this work, theoretical methods were used for designing a synergic combination of bulky diols with crown ethers able to accelerate this kind of reaction. The calculations have predicted that the bulky diol 1,4-Bis(2-hydroxy-2-propyl)benzene, which has distant hydroxyl groups, is able to catalyze nucleophilic fluorination in combination with 18-crown-6 via two hydrogen bonds to the SN2 transition state. Experimental studies following the theoretical predictions have confirmed the catalytic effect and the estimated kinetic data point out that the bulky diol at 1 mol L-1 in combination with 18-crown-6 is able to produce an 18-fold increase in the reaction rate in relation to crown ether catalysis only. The reaction produces 46% yield of fluorination after 24 h at moderate temperature of 82 °C, with minimal formation of the side elimination product. Thus, this work presents an improved method for fluorination with KF salt.

Dialkyl Ether Formation at High-Valent Nickel.

In this article, we investigated the I2-promoted cyclic dialkyl ether formation from 6-membered oxanickelacycles originally reported by Hillhouse. A detailed mechanistic investigation based on spectroscopic and crystallographic analysis revealed that a putative reductive elimination to forge C(sp3)–OC(sp3) using I2 might not be operative. We isolated a paramagnetic bimetallic NiIII intermediate featuring a unique Ni2(OR)2 (OR = alkoxide) diamond-like core complemented by a μ-iodo bridge between the two Ni centers, which remains stable at low temperatures, thus permitting its characterization by NMR, EPR, X-ray, and HRMS. At higher temperatures (>−10 °C), such bimetallic intermediate thermally decomposes to afford large amounts of elimination products together with iodoalkanols. Observation of the latter suggests that a C(sp3)–I bond reductive elimination occurs preferentially to any other challenging C–O bond reductive elimination. Formation of cyclized THF rings is then believed to occur through cyclization of an alcohol/alkoxide to the recently forged C(sp3)–I bond. The results of this article indicate that the use of F+ oxidants permits the challenging C(sp3)–OC(sp3) bond formation at a high-valent nickel center to proceed in good yields while minimizing deleterious elimination reactions. Preliminary investigations suggest the involvement of a high-valent bimetallic NiIII intermediate which rapidly extrudes the C–O bond product at remarkably low temperatures. The new set of conditions permitted the elusive synthesis of diethyl ether through reductive elimination, a remarkable feature currently beyond the scope of Ni.

4-(3-Methoxyphenyl)-5-(2-thienylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-selone: Synthesis, structural characteristics and reactions

The title compound 4-(3-methoxyphenyl)-3-(2-thienylmethyl)-4,5-dihydro-3H-1,2,4-triazole-3-selone 2 was synthesized by two-step procedure including condensation of 1-isoselenocyanato-3-methoxybenzene with 2-(2-thienyl)acetohydrazide to selenosemicarbazide 1 and its intramolecular cyclization. Oxidation of selone 2 by atmospheric oxygen or hydrogen peroxide furnished corresponding diselenide 3 or product of elimination of selenium 1,2,4-triazole 4. Alkylation of compound 2 by benzyl chloride leads to the formation of selenide 5. The synthesized compounds have been characterized by spectroscopic techniques and the structures of 3,4 and 5 were confirmed by X-ray diffraction techniques and the supramolecular contacts were analyzed by Hirshfeld surface analyses.

Easier to Twist than Bend: The Scope of the Bridge Formation Approach to Naphthalenophane Synthesis

Twisting anthracene and higher acenes can alter their optical, magnetic, and electronic properties. To test the effect of twisting on the lower homologue, naphthalene, we synthesized tethered naphthalenophanes bearing alkyl bridges. Both X-ray structure and DFT calculations show that hexyl and butyl bridges induce a 6° and 12° end-to-end twist on the naphthalene unit, respectively. Attempts to increase the twisting further using shorter tethers resulted in an elimination product. Enantiomerically pure naphthalenophanes display strong chiroptical properties, which intensify with increasing twist. Attempts to induce bending, rather than twisting, using the same synthetic methodology, resulted in intermolecular dimerization, yielding macrocyclic naphthalenes. This work highlights the importance of steric hindrance in the synthesis of curved cyclophanes using the bridge formation approach.