Methylene Insertion Research Articles

Direct spectroscopic evidence of the cross-coupling reaction between CH(2)(a) and CF(3)(a) on Ag(111).

The cross-coupling reaction between CH2 and CF3 on Ag(111) was studied with reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed reaction spectroscopy (TPRS). Adsorbed CF3CH2(a) was, for the first time, spectroscopically identified as an intermediate in the reaction to form CF2CH2. It is formed by migratory methylene insertion into Ag-CF3. CF3CH2(a) undergoes beta-fluoride elimination to form CF2CH2. Our results provide direct new fundamental insight into Fischer-Tropsch synthesis.

Ion-molecule reactions of [C, H(3), S](+) ions and evidence for long-lived triplet CH(3)S(+).

Gas-phase [C, H(3), S](+) ions obtained by electron impact from (CH(3))(2)S at 14 eV undergo two distinct low-pressure ion-molecule reactions with the parent neutral: proton transfer and charge exchange. The kinetics of these reactions studied by Fourier transform ion cyclotron resonance (FT-ICR) techniques clearly suggests the [C, H(3), S](+) species to be a mixture of isomeric ions. While proton transfer is consistent with reagent ions displaying the CH(2)SH(+) connectivity, the observed charge exchange strongly argues for the presence of thiomethoxy cations, CH(3)S(+), predicted to be stable only in the triplet state. Charge exchange reactions are also observed in the reaction of these same [C, H(3), S](+) ions with benzene, toluene and phenetole. For these substrates, the CH(2)SH(+) ions can promote proton transfer and electrophilic methylene insertion in the aromatic ring with elimination of H(2)S. The results obtained for the different substrates suggest that the fraction of long-lived fraction of thiomethoxy cations obtained at 14 eV by electron ionization of dimethyl sulfide amounts to ~(22 -/+ 4)% of the [C, H(3), S](+) fragments.

Design, synthesis, and development of novel caprolactam anticonvulsants

Epilepsy afflicts 1–2% of the world's population and often goes untreated; nearly 70% of those with a form of epilepsy fail to receive proper treatment. Therefore, there is great demand for the design of novel, effective anticonvulsants to combat epilepsy in its numerous forms. Previously, α-hydroxy-α-phenylcaprolactam was found to have rather potent antiepileptic activity [anti-maximal electroshock (MES) ED 50=63 mg/kg and anti-subcutaneous Metrazol (scMet) ED 50=74 mg/kg] when administered intraperitoneally in mice. We focused our attention on the development of this compound through traditional medicinal chemistry techniques—including the Topliss approach, isosteric replacement, methylene insertion, and rigid analogue approach—in the hopes of determining the effect of caprolactam α-substitution and other structural modifications on anticonvulsant activity. A number of the desired targets were successfully synthesized and submitted to the Anticonvulsant Screening Program of the National Institute of Neurological Disorders and Stroke (NINDS). Phase I results were quite promising for at least three of the compounds: α-ethynyl-α-hydroxycaprolactam ( 10), α-benzyl-α-hydroxycaprolactam ( 11), and α-hydroxy-α-(phenylethynyl)caprolactam ( 13). Phase II results for 11 strongly suggested it as a new structural class for further development, as it exhibited an anti-MES T.I. in excess of 4.0. Further, the potent activity of 13 in all models also pointed to the substituted alkynylcaprolactams as a new anticonvulsant structural class.

The Surface Chemistry of Hydrocarbon Fragments on Transition Metals: Towards Understanding Catalytic Processes

AbstractFor Abstract see ChemInform Abstract in Full Text.

Isolation and Characterization of Borane Complexes of Dimethylsulfoxonium Methylide

Trialkylboranes (R3B) catalyze the repetitive insertion of methylene from dimethylsulfoxonium methylide (1) to form polymethylene. A proposed intermediate in this reaction is a 1:1 complex between R3B and ylide 1. Following complexation, an alkyl group (boron-substituted) undergoes a 1,2-migration to the methylide carbon with displacement of a molecule of DMSO. A series of complexes of dimethylsulfoxonium methylide (1) and various organoboranes, X3B (X = H, Ph, F, C6F5), have been prepared and isolated. Molecular structures, obtained by single-crystal X-ray diffraction, for ylide·BF3 (3) and ylide·B(C6F5)3 (4) were found to contain geometries with potential migrating groups anti-periplanar to the carbon−sulfur bond. The stability of solutions of these complexes ranges considerably. For example, ylide·BPh3 (6) undergoes reaction at room temperature, while ylide·B(C6F5)3 (3) is stable to temperatures > 100 °C. All complexes can be prepared as solids stable at room temperature. The solid-state stability of ylide·BR3 complexes was evaluated by differential scanning calorimetry. The decomposition temperature increases across the series for R = H, Ph, C6F5, F. The heats of reaction of ylide·BR3 are R = H (−54.7), Ph (−15.7), C6F5 (−21.6), and F (−17.1) kcal mol-1, respectively.

Insertion of carbon fragments into P(III)-N bonds in aminophosphines and aminobis(phosphines): synthesis, reactivity, and coordination chemistry of resulting phosphine oxide derivatives. Crystal and molecular structures of (Ph(2)P(O)CH(2))(2)NR (R = Me, (n)Pr, (n)Bu), Ph(2)P(O)CH(OH)(n)()Pr, and cis-[MoO(2)Cl(2)((Ph(2)P(O)CH(2))(2)NEt-kappaO,kappaO)

Reactions of N-aryl and N-alicyclic derivatives of aminophosphines with paraformaldehyde lead to methylene insertion into P-N bond followed by oxidation of phosphorus from the P(III) to P(V) state. When N-alkyl derivatives are reacted with paraformaldehyde, dimerization takes place to afford bis(phosphine oxide)s of the type Ph(2)P(O)CH(2)N(R)CH(2)P(O)Ph(2) (R = Me, (n)Pr, (n)Bu). Aminobis(phosphines) also undergo methylene insertion when treated with paraformaldehyde to give bis(phosphine oxides) Ph(2)P(O)CH(2)N(R)CH(2)P(O)Ph(2) (R = Me, Et, (n)()Pr, (i)()Pr, (n)Bu) in good yield. The reaction of aminophosphines with aromatic aldehydes ArCHO leads to insertion of "ArCH" into the P-N bond to give Ph(2)P(O)CH(R)N(H)Ph (R = C(6)H(5), furfuryl, o-C(6)H(4)OH), but with aliphatic aldehydes such as butanal, P-N bond cleavage takes place to afford alpha-hydroxy phosphine oxide. The reaction of aminobis(phosphines) with both aromatic and aliphatic aldehydes leads to the formation of alpha-hydroxy phosphine oxides through P-N bond cleavage whereas the reaction with furfural leads to the P-N bond insertion. The structure of the alpha-hydroxy derivative Ph(2)P(O)CR(H)(OH)(n)()Pr shows intermolecular hydrogen bonding between OH and P=O oxygen. The phosphine oxide derivatives act as bidentate ligands and form chelate complexes with Co(II), Mo(VI), Th(IV), and U(VI) derivatives. The crystal structure of the molybdenum complex, cis-[MoO(2)Cl(2)((OPPh(2)CH(2))(2)NEt-kappaO,kappaO)], shows the distorted octahedral geometry around Mo with two oxo groups cis to each other.

The surface chemistry of hydrocarbon fragments on transition metals: towards understanding catalytic processes

In this review the surface chemistry of hydrocarbons on transition metal surfaces is discussed, with focus on the contributions from the surface science community, and specifically the author's group, to an understanding of the mechanism of this chemistry at a molecular level. The clean production of alkyl surface moieties on well characterized metals and the study of the thermal chemistry of those moieties are described. Alpha, beta and gamma hydride eliminations, reductive elimination with hydrogen or other alkyl groups, methylene insertions, and C—C bond breaking reactions, are all introduced. Particular emphasis is given to the discussion of catalytic hydrogenation processes.

Some evidence refuting the alkenyl mechanism for chain growth in iron-based Fischer–Tropsch synthesis

Recently, Maitlis et al. [J. Catal. 167 (1997) 172] proposed an alternative reaction pathway for chain growth in the Fischer–Tropsch synthesis. In this mechanism, chain growth is assumed to occur by methylene insertion into a metal–vinyl bond, forming an allyl species that will subsequently isomerise to a vinyl species. Organo-metallic allyl complexes, Fe{[η 5-C 5H 5](CO) 2CH 2CHCH 2} and Fe{[η 5-C 5(CH 3) 5](CO) 2CH 2CHCH 2} were synthesised. Under thermal treatment, the decomposition of these complexes was observed, instead of the isomerisation. In a hydrogen atmosphere, the reduction of the iron–carbon bonds and the hydrogenation yielding iron–alkyl species was observed. This clearly shows that the proposed vinyl–allyl isomerisation is unlikely to occur in mono-nuclear iron complexes. Hence, it might be expected that the reaction mechanism proposed by Maitlis et al. [J. Catal. 167 (1997) 172] is unlikely to be the main route for chain growth in the Fischer–Tropsch synthesis.

1-Boraadamantane blows its top, sometimes. The mono- and polyhomologation of 1-boraadamantane.

[reaction: see text] 1-Boraadamantane.THF (3) reacts with 1 equiv of dimethylsulfoxonium methylide (4) to afford a monohomologated product. The polyhomologation of 1-boraadamantane.THF by ylide 4 followed by oxidative cleavage generates star polymethylene polymers incorporating a cyclohexane core. However, only one-third of the initiators lead to product formation, resulting in an observed degree of polymerization three times higher than expected. The polyhomologation of 3 was found to contain branch points after the fourth and fifth methylene insertions. At the branch points, the propagating species either terminate in tricyclic trialkylborane cages with collapsed, pyramidal inverted boron centers that are unreactive toward ylide or they continue in uninterrupted polymerization and eventually result in the formation of giant "tube-like" structures such as 5.

First examples of methylene insertion into the phosphorus(III)–nitrogen bond

The reaction of N-substituted phosphinous amides with paraformaldehyde leads to methylene insertion into the P–N bond, followed by the oxidation of phosphorus from P(III) to P(V) state. The product, Ph 2P(O)CH 2NHPh was characterised by a single-crystal X-ray diffraction study. The reaction not only depends on the acidic proton on the nitrogen, but also on the oxidation state of phosphorus and it is considered to proceed through Staudinger–Wittig pathway.

Mechanism of Olefin Cyclopropanation by Diazomethane Catalyzed by Palladium Dicarboxylates. A Density Functional Study

The reaction of diazomethane with ethylene in the presence of palladium diformate has been studied through density functional calculations. Several mechanistic paths leading to the formation of cyclopropane have been studied. The results obtained show that the reaction of palladium diformate with diazomethane is more favorable than the reaction with ethylene. The reaction with diazomethane may lead to two different isomeric complexes: a methylene-inserted complex and a palladium-carbene complex. Insertion of methylene is the most favorable process, but the resulting complex is not suitable for cyclopropanation. The reaction with two additional diazomethane molecules makes the formation of the bismethylene-inserted palladium-carbene complex favorable. Attack of ethylene on this palladium-carbene complex leads to the formation of cyclopropane.

Synthesis of Bis(Alkyltelluro)Methanes and their Complexation with Cadmium(II)

A novel and convenient route for the synthesis of a series of bis(alkyltelluro)methanes (alkyl─ethyl, isopropyl, n-butyl and n-hexyl) is described by one pot methylene insertion reaction using dialkyl ditellurides, sodium borohydride and chloroform. The cadmium(II) complexes of bis(isopropyltelluro)methane were also synthesized. The bis(alkyltelluro)meth-anes were characterized by elemental analysis, 1H and 125Te NMR. The product of the complexation of bis(isopropyl telluro)methane with Cd(II) have been characterized by elemental analysis, 1H, TGA and FAB mass spectrometry. The dialkyltelluroether ligands may be useful in organic synthesis and their complexes with cadmium(II) can be considered a potential single source of metal-organic chemical vapor deposition (MOCVD) precursors for advanced electronic materials.

ChemInform Abstract: Organometallic Chemistry and Surface Science: Mechanistic Models for the Fischer-Tropsch Synthesis

Abstract The Fischer–Tropsch synthesis is an industrially important process for the conversion of synthesis gas (CO/H2) into hydrocarbons and oxygenates. Synthesis gas can be obtained from coal or natural gas. Organometallic model complexes and surface science techniques have been widely used to obtain mechanistic information about this heterogeneous process. A review of the mechanisms for the Fischer–Tropsch synthesis and the evidence for these mechanisms is presented. It is generally accepted that the Fischer–Tropsch reaction may be viewed as a polymerisation of surface methylene (CH2) species, which are formed by the dissociation and hydrogenation of CO on the catalyst surface. The alkyl mechanism proposes that the reaction is initiated by the formation of a surface methyl species, and that chain growth takes place by successive insertions of methylene into the metal-alkyl bond. The alkenyl mechanism proposes that the formation of a surface vinyl species (CHCH2) initiates chain formation, and that chain growth is facilitated by methylene insertion into the metal-vinyl bond to form an allyl species (CH2CHCH2). The allyl species isomerises to form a surface alkenyl (CHCHCH3) which may propagate further. These mechanisms are discussed.

Solid phase synthesis and biological activities of [Arg 8]-vasopressin methylenedithioether

Solid phase synthesis of [Arg 8]-vasopressin methylenedithioether, an analog of vasopressin which contains an extra methylene group between the two sulfur atoms of Cys 1 and Cys 6, is described. Methylene insertion occurred easily when the thiol free peptide on a solid support was treated with tetrabutylammonium fluoride in dichloromethane at room temperature for 3 h. The uterotonic in vitro, pressor, and antidiuretic activities of the compound were reduced in comparison to [Arg 8]-vasopressin by one order of magnitude.

Theoretical study of the fluorine effect on the methylene insertion reaction in the hydrogen molecule, hydrogen fluoride, and the fluorine molecule

Complete ab initio studies were performed with the goal of determining the reactivity of methylene and fluorinated methylene in an insertion reaction with the hydrogen molecule, hydrogen fluoride, and fluorine molecules. An energy profile for these reactions was computed, elucidating the reactants’ complex and the transition state structures. The complexation energies, activation barriers, and enthalpies of the reactions were used comparatively to determine the relative carbene stability and reactivity, as well as the influence of fluorine as a substituent on the reaction potential energy surface.

Surface Reactions of CH3I and CF3I with Coadsorbed CH2I2 on Ag(111) as Mechanistic Probes for Carbon−Carbon Bond Formation via Methylene Insertion

The insertion of methylene into metal−alkyl bonds has been studied on an Ag(111) surface under ultrahigh-vacuum conditions. Methyl (CH3) and methylene (CH2) groups are generated on Ag(111) by thermal scission of the C−I bonds in adsorbed methyl iodide (CH3I) and methylene iodide (CH2I2) below 200 K. When studying the bimolecular interaction of coadsorbed CH3 and CH2 moieties, propane and butane are detected in the temperature-programmed reaction (TPR) experiments, suggesting that CH2 inserts into the Ag−CH3 bond to produce metal-bound ethyl (CH2CH3) groups, followed by facile self-/cross-coupling of existing alkyl groups on the surface. In a separate approach, CF3 is used instead of CH3 as the target for CH2 insertion. TPR studies of the coadsorbed CF3 and CD2 show that CD2 also inserts into the Ag−CF3 bond to form a new C−C bond; however, a different chain termination step (β-fluoride elimination) is observed to produce 1,1-difluoroethylene-d2 (CF2CD2) in the gas phase. Two sequential methylene insertions are also implicated, as evidenced by the production of 1,1,1-trifluoropropyl iodide-2,3-d4 (CF3CD2CD2I) as a result of the recombination of CF3CD2CD2 groups with surface iodine. The relative rates of methylene insertion, alkyl coupling, and β-elimination involved in the reaction mechanisms are systematically compared. The effect of coadsorbed iodine on the reaction pathways is assessed. The methylene insertion rate is found to be more facile on silver than on copper surfaces.

A New Efficient Method for S–CH2–S Bond Formation and Its Application to a Djenkolic Acid-Containing Cyclic Enkephalin Analog

Abstract An efficient methylene insertion reaction to construct an S–CH2–S bridge between two cysteine residues occurred when the thiol-protecting dimethylphosphinothioyl (Mpt) group of Z–Cys(Mpt)–OMe was removed with tetrabutylammonium fluoride hydrate in CH2Cl2. The thiol-free form gave similar results, albeit the yields were somewhat lower. In both cases, the best yields were obtained using 2 molar amounts of the reagent. Higher amounts of the reagent reduced the yield because of dehydroalanine formation. In the case of penicillamine, the thiol-free form was better in reactivity than the S-Mpt form, which required double the amount of the reagent to give the same yield. The reaction was successfully used in a synthesis of a cyclic enkephalin analog with the S–CH2–S bridge.

Distinct Demonstration of Methylene Insertion into the Metal−Carbon Bond on Ag(111)

We provide a clear demonstration of the migratory insertion of methylene into the metal−carbon bond on a silver single-crystal surface. The insertion reaction is characterized by the interaction between methylene and perfluoromethyl groups coadsorbed on Ag(111). The CH2 insertion into the Ag−CF3 bond followed by β-fluoride elimination produces CH2CF2, which is our experimental evidence for the insertion mechanism. Our observations confirm the step concerning the propagation of the carbon chain in the Fischer−Tropsch processes.

Effects of Fluorination on Methylene Insertion Reactions

The potential energy surfaces for the insertion reactions of methylene and fluorinated methylenes into the H2, HF, and F2 molecules were studied by density functional, many body perturbation, and coupled-cluster theories. These methods predict the barrier for the CF2 insertion into the hydrogen molecule to be about 33 kcal/mol, that is, significantly lower than previous estimates. A new transition state was found in this system for the reaction path which leads to CHF + HF. However the transition state for this metathesis channel is about 25 kcal/mol higher than that of the insertion channel. For the fluoromethylene insertion into H2 the predicted activation energy is about 8 kcal/mol. The CH2 insertion into F2 proceeds without a barrier. The peculiarity of the insertion reactions between carbenes and HF involves formation of a hydrogen-bonded complex. The CH2···HF complex is bound by about 10 kcal/mol relative to CH2 + HF. Coupled-cluster methods predict a small (ca. 3 kcal/mol) barrier for transformatio...

Gas-Phase Reactions of Fe(CH2O)+ and Fe(CH2S)+ with Small Alkanes: An Experimental and Theoretical Study

The gas-phase reactions of Fe(CH2O)+ and Fe(CH2S)+ with a series of aliphatic alkanes were studied by Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. Like bare Fe+, C−C insertion, particularly terminal C−C insertion, is predominant for the reactions of Fe(CH2O)+, while C−H insertion is preferred for Fe(CH2S)+. About 90% of the Fe(CH2O)+ reaction products are formed by C−C insertion with small alkane loss. For Fe(CH2S)+, after initial C−H insertion, the proposed mechanism includes hydrogen transfer to sulfur, followed by migratory insertion of methylene into the metal−alkyl bond and formation of an activated H2S−Fe+−olefin complex, which dissociates by H2S elimination. The structures of the reaction products were probed by collision-induced dissociation, ion−molecule reactions, and use of labeled compounds, yielding information about the reaction mechanism. Collision-induced dissociation and ligand displacement reactions yield the brackets D0(Fe+−C3H6) = 37 ± 2 kcal/mol < D0(Fe+−CH2S) < D0(Fe+−C6H6) = 49.6 ± 2.3 kcal/mol and D0(Fe+−CH2O) < D0(Fe+−C2H4) = 34 ± 2 kcal/mol. The optimized geometry of Fe(CH2O)+, obtained by density functional calculations, has C2v symmetry with a nearly undisturbed formaldehyde unit. The Fe+−CH2O bonding is found to be predominantly electrostatic with a calculated bond energy of 32.2 kcal/mol. However, the optimized Fe(CH2S)+ structure has Cs symmetry with dative bonding between Fe+ and CH2S. D0(Fe+−CH2S) is calculated at 41.5 kcal/mol. The differences in geometry and chemical bonding between Fe(CH2O)+ and Fe(CH2S)+ are correlated with the different reaction pathways observed.