Theoretical study of the gas‐phase ion pairs SN2 reactions of LiX with CH3SY (X,Y = F,Cl, Br,I)

The gas‐phase ion pair S_N2 reactions at saturated sulfur LiX + CH₃SY → CH₃SX + LiY (X, Y = F, Cl, Br, I) are investigated using the CCSD(T) calculations. The calculated results show that the reactions LiX + CH₃SY are exothermic only when the nucleophile is a heavier lithium halide. Central barrier heights are found to depend primarily on the identity of nucleophile LiX, decreasing in the order LiF > LiCl > LiBr > LiI. Another interesting feature of the ion pair reactions at sulfur is the good correlation between the reaction barriers with geometrical looseness of Li? X and S? Y bonds in the transition state structures. The data for the reaction barriers show good agreement with the prediction of the Marcus equation and its modification. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Kinetics of chloride substitution in [Pt(bpma)Cl]+ and [Pt(gly-met-S,N,N)Cl] complexes by thiourea, nitrites, and iodides

Substitution of chloride in [PtCl(bpma)]⁺ and [PtCl(gly-met-S,N,N)], where bpma is bis(2-pyridylmethyl)amine and gly-met-S,N,N is glycyl-l-methionine, was studied as a function of the entering nucleophile concentration and temperature. Reactions between the platinum(II) complexes and thiourea (TU), iodides (I^?), and nitrites(III) (NO ₂ ^? ) were carried out in aqueous solutions using conventional UV-VIS spectrophotometry. Suitable ionic conditions were reached by an addition of 0.1 M NaClO₄ and 0.01 M NaCl (to suppress hydrolysis). The second-order rate constants, k ₂, for the studied reactions with NO ₂ ^? varied between 0.036–0.038 M^?1 s^?1, and for the reactions with TU between 0.095–1.06 M^?1 s^?1, respectively. The reaction between TU and the [PtCl(bpma)]⁺ ion is ten times faster than that of the [PtCl(gly-met-S,N,N)] complex. An analysis of the activation parameters, ΔH ^≠ and ΔS ^≠, for the selected reactions clearly shows their associative nature.     

On the reactivity of silylperoxides : Oxidation of thioxane and of n,n-dimethyl-para-anisidine by bis(trimethylsilyl)peroxide and by tert-butyl(trimethylsilyl)peroxide

Rates and rate-laws have been determined for the oxidation of 1-thia-4-oxacyclohexane 5 by bis(trimethylsilyl)peroxide 1 and tert-butyl-(trimethylsilyl) peroxide 2 in CHC1₃ at 25.0°; these are compared to the rates of oxidation of the same substrate by the more common oxidants, tert-butyl hydroperoxide 3 and di-tert-butyl peroxide 4 in the same solvent. The two silylperoxides give similar oxidations rates, which are over 50 times higher than that measured for t-BuOOH, while t-Bu₂O₂ is almost unreactive under the conditions adopted. Oxidation of N,N-dimethyl-p-anisidine 6, a nitrogen nucleophile, by silylperoxide 1 in CHCl₃ is ca. 1000 times slower than that of the sulphur nucleophile 5. The results are discussed in terms of a mechanism involving nucleophilic attack by the substrate on the peroxide, with the heterolysis of the OO bond being assisted by the migration of the Me₃Si- group.     

Asymmetric Au-catalyzed domino cyclization/nucleophile addition reactions of enynes in the presence of water, methanol and electron-rich aromatic derivatives

An efficient Au(I) catalytic system is described for the asymmetric domino cyclization/functionalization reactions of functionalized 1,6-enynes in the presence of an external nucleophile. The use of (R)-4-MeO-3,5-(t-Bu)₂-MeOBIHEP ligand associated with gold led to clean rearrangements implying the formal addition of an oxygen or carbon nucleophile to an alkene followed by a cyclization process. The enantiomeric excesses were highly dependant on the substrate/nucleophile combination. Very good enantiomeric excesses up to 98% were obtained in the case of substrates bearing larger groups (hindered diesters and disulfones) and in the case of hindered carbon nucleophiles.     

Reaktive E=C(p‐p)π‐Systeme. 54 [1] Reaktionen des Perfluor‐2‐arsapropens,F3CAs=CF2 (1), mit H‐aciden Verbindungen Me2EH (E = N,P, As) und MeE′H (E′ = O,S, Se)

Reactive E=C(p‐p)π‐Systems. 54 [1] Reactions of perfluoro‐2‐arsapropene, F₃CAs=CF₂ (1), with H‐acidic compounds Me₂EH (E = N, P, As) and MeE′H (E′ = O, S, Se) The reactions of the perfluoro‐2‐arsapropene ( 1 ) with H‐acidic compounds Me₂EH (E = N, P, As) and MeE′H (E′ = O, S, Se), respectively, proceed via addition to the As=C double bond yielding either secondary arsanes F₃C(H)AsCF₂X (X = NMe₂, PMe₂, OMe, SMe) or AsX derivatives (X = AsMe₂, SeMe). Me₂‐AsH is obviously a border case nucleophile because, besides the AsX derivative as main product, small amounts of the arsane are formed indicative for the reverse addition pathway. With the strong base Me₂NH, the addition is followed immediately by HF elimination producing the fairly stable arsaalkene F₃CAs=C(F)NMe₂ ( 4 ) which had already been obtained by reaction of HAs(CF₃)₂ with three equivalents of Me₂NH. The novel rather labile compounds were identified by spectroscopic (NMR, GC/MS) investigations. – Quantum chemical DFT calculations [B3LYP/6‐311+G(d,p)] were carried out to determine the relative energy of the isomeric products and the thermodynamics of the addition reactions.     

The influence of some steric and electron effects on the mechanism of aromatic nucleophilic substitution (SNAr) reactions in nonpolar solvent

Kinetic studies are reported for the reactions with aniline in benzene of a series of X‐phenyl 2,4,6‐trinitrophenyl ethers [X = H; 2‐, 3‐, 4‐CH₃; 2,4‐, or 2,6‐(CH₃)₂] a–f , and the results compared with those of the corresponding nitro derivatives. In the methyl series, kinetic data show that increasing substitution reduces drastically the rates of reactions indicative of the operation of some kind of steric effect. The unfavorable steric congestion at the reaction center appears to be unimportant in determining the kinetic order of the reactions. In general, the second‐order rate constants k_A depend linearly on the square of nucleophile concentration. The change in the kinetic form observed in the nitro derivatives may be largely due to the electron‐withdrawing effect of the group. With the 2,6‐dinitro derivative, however, the uncatalyzed pathway k₂ takes all the reaction flux. Steric hindrance to intermolecular proton transfer from base to the ethereal oxygen of the intermediate is sufficient to make the base‐catalyzed pathway insignificant relative to the k₂ pathway. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 744–750, 2005     

Palladium(II)‐catalyzed catalytic aminocarbonylation and alkoxycarbonylation of terminal alkynes: regioselectivity controlled by the nucleophiles

The aminocarbonylation and alkoxycarbonylation reactions of terminal alkynes took place smoothly and efficiently using a catalyst system Pd(OAc)₂–dppb–p‐TsOH? CH₃CN? CO under relatively mild experimental conditions. The catalytic system was tested and optimized using two different nucleophiles: alcohols and amines. Phenylacetylene (1a) was considered as an alkyne along with diisobutylamine (2b₁) and methanol (2c₁) as nucleophiles. The results showed significant differences in the conversion of 1a and in the selectivity towards the gem or trans unsaturated esters or amides with these nucleophiles. The effects of the type of palladium catalysts, the type of ligands, the amount of dppb and the solvents were carefully studied. With diisobutylamine (2b₁), excellent regioselectivity towards the 2‐acrylamides (gem isomer, 3ab₁) was almost always observed, while trans‐α,β‐unsaturated esters 4ac₁ was the predominant product with methanol (2c₁) as a nucleophile. This remarkable sensitivity in the selectivity of the reaction indicates two different possible mechanistic pathways for these carbonylation reactions. Copyright © 2009 John Wiley & Sons, Ltd.     

Kinetics of the reactions of halogenated methyl radicals (CF3, CF2Cl,CFCl2, and CCl3) with molecular chlorine

The kinetics of four gas-phase reactions involving halogenated methyl radicals (R ? CF₃, CF₂Cl, CFCI₂, and CCI₃) with molecular chlorine have been studied using a tubular reactor coupled to a photoionization mass spectrometer. The radicals were homogeneously generated by the pulsed photolysis of precursor molecules at 193 nm. The subsequent decays of the radical concentration were monitored in real-time experiments as a function of Cl₂ concentration to obtain the rate constants of these R + Cl₂ reactions. Where possible, the rate constants were measured as a function of temperature to determine Arrhenius parameters. Apparent discrepancies between these measured rate constants for CF₃ and CCl₃ with Cl₂ and ones obtained in prior indirect studies are explained. The higher activation energies for these R + Cl₂ reactions compared to that of the CH₃ + Cl₂ reaction are attributed in part to the different polarities of the transition states formed.     

A correlation between spin state and electrochemical electron-transfer rate for tris(N,N-disubtituted dithiocarbamato) iron(III) complexes

The electrochemical electron-transfer rate constants for the redox systems Fe(IV)L₃⁺/Fe(III)L₃ (L=N,N-disubstituted dithicarbamate ion) and Fe(III)L₃/Fe(II)L₃^? with a variety of substituents were measured at a platinum electrode in acetonitrile with the galvanostatic double-pulse method. It is known that each of the Fe(III) complexes exists both in a highspin state ⁶A₁ and a low-spin state ²T₂ in equilibirium of which position is widely changed by a subtle change in substituent. The standard rate constants for Fe(IV)L₃⁺/Fe(III)L₃ were larger or smaller than those for Fe(III)L₃/Fe(II)L₃^? according as the Fe(III)L₃ complexes are predominantly low- or high-spin complexes. Since the Fe(IV) and Fe(II) complexes are low-and high-spin complexes respectively, these findings suggest that electrochemical electron-transfer reactions accompanied by a spin-state change are slower than those without it. Such spin-state effect on electrode reactions has rarely been discussed so far.     

A Unified Framework for Understanding Nucleophilicity and Protophilicity in the SN2/E2 Competition

The concepts of nucleophilicity and protophilicity are fundamental and ubiquitous in chemistry. A case in point is bimolecular nucleophilic substitution (S_N2) and base-induced elimination (E2). A Lewis base acting as a strong nucleophile is needed for S_N2 reactions, whereas a Lewis base acting as a strong protophile (i.e., base) is required for E2 reactions. A complicating factor is, however, the fact that a good nucleophile is often a strong protophile. Nevertheless, a sound, physical model that explains, in a transparent manner, when an electron-rich Lewis base acts as a protophile or a nucleophile, which is not just phenomenological, is currently lacking in the literature. To address this fundamental question, the potential energy surfaces of the S_N2 and E2 reactions of X⁻+C₂H₅Y model systems with X, Y = F, Cl, Br, I, and At, are explored by using relativistic density functional theory at ZORA-OLYP/TZ2P. These explorations have yielded a consistent overview of reactivity trends over a wide range in reactivity and pathways. Activation strain analyses of these reactions reveal the factors that determine the shape of the potential energy surfaces and hence govern the propensity of the Lewis base to act as a nucleophile or protophile. The concepts of “characteristic distortivity” and “transition state acidity” of a reaction are introduced, which have the potential to enable chemists to better understand and design reactions for synthesis.     

Kinetic and mechanistic investigation into the influence of chelate substituents on the substitution reactions of platinum(II) terpyridine complexes

The substitution kinetics of the complexes [Pt{4′‐(o‐CH₃‐Ph)‐terpy} Cl]SbF₆ (CH₃PhPtCl(Sb)), [Pt{4′‐(o‐CH₃‐Ph)‐terpy}Cl]CF₃SO₃ (CH₃PhPtCl(CF)), [Pt(4′‐Ph‐terpy)Cl]SbF₆ (PhPtCl), [Pt(terpy)Cl]Cl·2H₂O (PtCl), [Pt{4′‐(o‐Cl‐Ph)‐terpy}Cl]SbF₆ (ClPhPtCl), and [Pt{4′‐(o‐CF₃‐Ph)‐terpy}Cl]SbF₆ (CF₃PhPtCl), where terpy is 2,2′:6′,2″‐terpyridine, with the nucleophiles thiourea (TU), N,N′‐dimethylthiourea (DMTU), and N,N,N′,N′‐tetramethylthiourea (TMTU) were investigated in methanol as a solvent. The substitution reactions of the chloride displacement from the metal complexes by the nucleophiles were investigated as a function of nucleophile concentration and temperature under pseudo‐first‐order conditions using the stopped‐flow technique. The reactions followed the simple rate law k_obs = k₂[Nu]. The results indicate that the introduction of substituents in the ortho position of the phenyl group on the ancillary ring of the terpy unit does influence the extent of π‐backbonding in the terpy ring. This controls the electrophilicity of the platinum center, which in turn controls the lability of the chloro‐leaving group. The strength of the electron‐donating or ‐withdrawing ability of the substituents correlates with the reactivity of the complexes. Electron‐donating substituents decrease the rate of substitution, whereas electron‐withdrawing substituents increase the rate of substitution. This was supported by DFT calculations at the B3LYP/LACVP+** level of theory, which showed that most of the electron density of the HOMO is concentrated on the phenyl ligand rather than on the metal center in the case of the strongest electron‐withdrawing substituent in CF₃PhPtCl. The opposite was found to be true with the strongest electron‐donating substituent in CH₃PhPtCl. Thiourea was found to be the best nucleophile with N,N,N′,N′‐tetramethylthiourea being the weakest due to steric effects. The temperature dependence studies support an associative mode of activation. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 808–818, 2008     

Kinetic and competition studies of substitution reactions of the trans-aquosulphitotetracyanocobalt complex,Co(CN)4(SO)3(OH2)3−

The relative nucleophile efficiencies predicted for NH₃, CH₃NH₂ and CN^? from their rates of reaction with trans-Co(CN)₄(SO)₃(OH₂)^3? are confirmed by competition experiments with similar nucleophiles (NH₃-CH₃NH₂) but not by experiments with contrasting nucleophiles (NH₃-CN^?). This system, though substantially dissociative in mechanism, (D), possesses some interchange properties, (I_d).     

Synthesis of epigallocatechin trimer, (epigallocatechin)2-epicatechin,and (epigallocatechin)2-catechin via a Lewis acid mediated one-pot condensation and their antitumor activities in prostate cancer cells

Syntheses of epigallocatechin trimer, (epigallocatechin)₂-epicatechin and (epigallocatechin)₂-catechin were achieved. The key condensation to form the proanthocyanidin trimer derivatives was accomplished in a one-pot procedure using a dimeric epigallocatechin electrophile, which was prepared in situ by self-condensation of an epigallocatechin derivative, and an epigallocatechin, epicatechin, or catechin derivative as the nucleophile in the presence of a Lewis acid. The epigallocatechin monomer to trimer compounds containing a pyrogallol group significantly suppressed cell proliferation in PC-3 prostate cancer cells.     

Zum nukleophilen Abbau von Tris(pentasulfido)platinat(IV), [Pt(S5)3]2−, und Bis(pentasulfido)platinat(II),[Pt(S5)2]2−

On the Nucleophilic Degradation of Tris(pentasulfido)platinum(IV), [Pt(S₅)₃]^2?, and Bis(pentasulfido)platinum(II), [Pt(S₅)₂]^2? The behaviour of [Pt(S₅)₃]^2?, ( I ), towards sulfite, arsenite, sulfide, hydroxide, and triphenylphosphine has been studied qualitatively and quantitatively. With stoichiometric amounts of nucleophile one ring is degraded; the reaction product [Pt(S₅)₂]^2?, ( II ), can be isolated. With excess of nucleophile all sulfur atoms are taken off from the platinum; with triphenylphosphine, however, (PPh₃)₂PtS₄, ( III ), is formed. A mechanistic interpretation of the course of the reaction is given and supported by kinetic studies.     

Kinetics and mechanism of the substitution reactions of some bifunctional palladium(II) complexes with different nitrogen-donor heterocycles

Substitution reactions of three Pd(II) complexes, [Pd(cbdca)Cl₂]^2? (cbdca = cyclobutane-1,1-dicarboxylato), [Pd(ox)Cl₂]^2? (ox = oxalato) and [Pd(mal)Cl₂]^2? (mal = malonato), with different five- and six-membered N-heterocycles, such as pyrazole, 3-amino-4-iodo-pyrazole (pzI), 5-amino-4-bromo-3-methyl-pyrazole (pzBr), 1,2,4-triazole, pyrazine, imidazole, pyridazine and pyrimidine, were investigated in aqueous 0.10 M NaClO₄ with the presence of 20 mM NaCl using variable-temperature stopped-flow spectrophotometry. Substitution of these complexes occurs in two consecutive reversible steps, and their reactivity decreases in order [Pd(cbdca)Cl₂]^2? > [Pd(mal)Cl₂]^2? > [Pd(ox)Cl₂]^2?. The most reactive nucleophile among the five-membered heterocycles is imidazole, while pyridazine is the most reactive among the six-membered heterocycles. Activation parameters were determined for all reactions, and negative values for entropy of activation, ΔS^≠, support an associative mode of substitution. The reaction between [Pd(mal)Cl₂]^2? complex and pzBr was investigated by ¹H NMR, and the obtained results confirm that substitution with nitrogen-donor nucleophile does not lead to decomposition of the complex.     

Oxidations of 4- and 3-Aminopyridinepentaammineruthenium(ii) Complexes by Ethylenediaminetetraacetatocobaltate(III)

Redox reactions of Co(edta)^? with Ru(NH₃)₅L²⁺ (L = 3- and 4-aminopyridine (AmPy)) were found to follow an outer-sphere electron transfer mechanism. The specific rate constants are (3.26 ± 0.03) × 10² and (3.07 ± 0.04) × 10₃ M^?1S^?1, for L = 3- and 4-AmPy, respectively, at μ, = 0.10 M LiClO₄, pH = 8.0 (tris) and T = 25 °C. The rate constants of oxidations for a series of Ru(NH₃)₅L²⁺ complexes are higher than those of the corresponding Fe(CN)₅L_3- complexes by factors of 4 to 15 even after corrections for differences in reduction potentials and in charges of the complexes. Nonadiabaticity in the reactions of Fe(CN)₅L3 complexes may account for the difference in the relative reactivities.     

Computational study on vapor phase coupling reaction between diiso(thio)cyanates with diamines,diols, and dithiols

Coupling between iso(thio)cyanates and amines, alcohols, and thiols to yield (thio)urea/urethane in the gas phase is important for the vacuum deposition processes of functional organic thin films such as molecular layer deposition or chemical vapor deposition. In this study, the kinetics and thermodynamics of 12 reactions between bifunctional reactants containing ? NCO/? NCS and ? NH₂/? OH/? SH moieties were calculated using double‐hybrid density functional theory to find systematic structure–reactivity relationships. The activation energy for the proton‐transfer step was correlated with the basicity of the nucleophile/Brønsted acid reactants, while the exothermicity of the coupling reaction depends on whether the other functionality is ? NCO or ? NCS. Analysis of the transition states revealed that the location of the transition state is affected by the basicity of the reactants. Vibrational and electronic spectra of the product were obtained to help future experimental investigations.     

Novel Transition‐Metal (M=Cr,Mo, W,Fe) Carbonyl Complexes with Bis(guanidinato)silicon(II) Ligands

The donor‐stabilized silylene 2 (the first bis(guanidinato)silicon(II ) complex) reacts with the transition‐metal carbonyl complexes [M(CO)₆] (M=Cr, Mo, W) to form the respective silylene complexes 7 – 10 . In the reactions with [M(CO)₆] (M=Cr, Mo, W), the bis(guanidinato)silicon(II ) complex 2 behaves totally different compared with the analogous bis(amidinato)silicon(II ) complex 1 , which reacts with [M(CO)₆] as a nucleophile to replace only one of the six carbonyl groups. In contrast, the reaction of 2 leads to the novel spirocyclic compounds 7 – 9 that contain a four‐membered SiN₂C ring and a five‐membered MSiN₂C ring with a M?Si and M?N bond (nucleophilic substitution of two carbonyl groups). Compounds 7 – 10 were characterized by elemental analyses (C, H, N), crystal structure analyses, and NMR spectroscopic studies in the solid state and in solution.     

Asymmetric phase-transfer catalytic sulfanylation of some 2-methylsulfinyl cyclanones. Modeling of the stereochemical course of the aldol reaction of (SS,2S)-2-methylsulfinyl-2-methylsulfanylcyclohexanone

Increased diastereoisomeric excesses are obtained for the sulfanylation reactions of some 2-methylsulfinyl cyclanones under phase-transfer catalysis using the chiral catalyst QUIBEC instead of TEBA. The optically pure (SS,2S)-2-methylsulfinyl-2-methylsulfanylcyclohexanone thus prepared reacts with ethyl acetate lithium enolate affording, after hydrolysis, (R)-2-[(ethoxycarbonyl)methyl]-2-hydroxycyclohexanone in 60% ee. Density functional theory calculations (at the B3LYP/6-311++G(d,p) level) can successfully explain the origin of this result as the kinetically favored axial attack of the nucleophile to the carbonyl group of the most stable conformer of the cyclanone, in which the CH₃SO and CH₃S groups are at the equatorial and axial positions, respectively.