Substrate Substituents Research Articles

Synthesis and Structural and Reactivity Studies of Thiatitanacyclopropane Complexes [Cp†Ti(SCHCH2CH2S)]2 (Cp† = Cp, MeCp)

The complexes [Cp†Ti(SCHCH2CH2S)]2 (Cp† = Cp (3), MeCp (4)) are readily prepared from reaction of Cp†Ti(SCH2CH2CH2S)Cl (Cp† = Cp (1), MeCp (2)) with MeLi, AlMe3, or t-BuLi. Both compounds are centrosymmetric dimers in the solid state containing strained thiatitanacyclopropane rings. PMe3 cleaves these dimers, establishing equilibria between 3 and 4 and Cp†Ti(SCHCH2CH2S)(PMe3) (Cp† = Cp (5), MeCp (6)), while compound 3 undergoes facile acidolysis with HCl, acetic acid, PhSH, and propanedithiol affording CpTiCl3, CpTi(O2CMe)3 (7), CpTi(SCH2CH2CH2S)(SPh), and H+[CpTi(SCH2CH2CH2S)2]-·THF (8), respectively. The thiametallacycles react with benzophenone to give Cp†Ti(SCH(CPh2O)CH2CH2S) (Cp† = Cp (9); MeCp (10)) while reaction with cyclohexanone gives the dimeric species [Cp†Ti(SCH(C6H10O)CH2CH2S)]2 (Cp† = Cp (11); MeCp (12)). Analogous reactions with 2-methylcyclohexanone, menthone, and nopinone give related addition products with varying degrees of diastereoselectivity. The complex 3 also reacts with a series of imines to give complexes of the form CpTi(SCH(CHRNR)CH2CH2S), where the diastereoselectivity observed is a function of the steric demands of the substrate substituents. Reaction of 3 with nitriles, methyl isocyanate, dicyclohexylcarbodiimide, and phenyl thioisocyanate results in insertion of the substrate and subsequent enolization to give species of the form CpTi(SC=(C(R)NH)CH2CH2S). The analogous reaction with phenyl isocyanate yields the bimetallic complex CpTi(SC(PhNCO)CH2CH2S)TiCp(SCH2CH2CH2S) (27). Crystallographic characterization of a number of these reaction products is reported. Kinetic studies of the formation of 10 and 12 are consistent with initial formation of ketone complex adducts and subsequent intra- and intermolecular C−C bond formation reactions. The nature of the products, reaction mechanisms, and reactivity of strained thiatitanacyclopropane rings are discussed in the light of EHMO calculations.

Rhodium-catalysed hydroformylation of branched 1-alkenes; bulky phosphite vs. triphenylphosphine as modifying ligand

The influence of alkyl substituents in 1-alkene substrates in the rhodium-catalysed hydroformylation in the presence of tris(2-tert-butyl-methylphenyl) phosphite has been studied and compared with that observed for the reaction involving the conventional PPh 3-modified catalyst. Hindered alkenes underwent hydroformylation at good rates (i.e. 1300 mol (mol Rh) −1 h −1 for 3,3-dimethyl-1-butene as T = 70°C and P = 20 bar (H 2CO)); under mild conditions the rates were only slightly affected by the alkyl substituents. The selectivity towards the linear aldehyde increases progressively with substitution, from 66% for 1-octene up to 100% for 3,3-dimethyl-1-butene, and the proportion of isomerized alkenes remained substantial (up to 17.4% for allylcyclohexane). The differences between the two systems are explained in terms of the different kinetics observed for them.

A structural basis for the interaction of urea with lysozyme.

The effect of urea on the crystal structure of hen egg-white lysozyme has been investigated using X-ray crystallography. High resolution structures have been determined from crystals grown in the presence of 0, 0.7, 2, 3, 4, and 5 M urea and from crystals soaked in 9 M urea. All the forms are essentially isomorphous with the native type II crystals, and the derived structures exhibit excellent geometry and RMS differences from ideality in bond distances and angles. Comparison of the urea complex structures with the native enzyme (type II form, at 1.5 A resolution) indicates that the effect of urea is minimal over the concentration range studied. The mean difference in backbone conformation between the native enzyme and its urea complexes varies from 0.18 to 0.49 A. Conformational changes are limited to flexible surface loops (Thr 69-Asn 74, Ser 100-Asn 103), the active site loop (Asn 59-Cys 80), and the C-terminus (Cys 127-Leu 129). Urea molecules are bound to distinct sites on the surface of the protein. One molecule is bound to the active site cleft's C subsite, at all concentrations, in a fashion analogous to that of the N-acetyl substituent of substrate and inhibitor sugars normally bound to this site. Occupation of this subsite by urea alone does not appear to induce the conformational changes associated with inhibitor binding.

A novel method for the generation of 2,3-naphthoquinodimethanes utilizing samarium(II) iodide-promoted allene synthesis

2,3-Naphthoquinodimethanes are easily generated from o-bis(α-acetoxypropargyl)benzene derivatives with SmI 2 in the presence of palladium catalyst under mild conditions. The reactions of the quinodimethane intermediates were found to follow the different paths depending on the acetylenic substituents of substrates.

ChemInform Abstract: Regio‐ and Stereoselective Control in the Alkylation of 1‐Alkoxy‐1,4‐cyclohexadienes by the Chiral Auxiliary Approach. Enantioselective Synthesis of Precursors for cis‐Hydrindans.

AbstractAn enantioselective variant of the title reaction is developed, based on a number of preliminary experiments ‐ e.g. a study of the effect of substituents in substrates (I) and alkylating agents such as (II), as well as a comparison of various chiral auxiliaries.

Structure-reactivity correlations on the kinetics of substituted 2-phenylethyl m-nitrobenzenesulfonates with substituted pyridines

The rates of the substituted 2-phenylethyl m-nitrobenzenesulfonate(2-PNS) with pyridines were determined in acetonitrile. The reaction was accelerated by an electron - donating substituent on both substrate and nucleophlie. Substitutent effects 2-PNS and pyridine are correlated by Brønsted and Hammett equations, respectively. The sensitivity parameters, β and ϱ, obtained from the free-energy relationships, are inter-related and are themselves sensitive to the reactivity of the system. Thus, β varies from 0.246 for p-MeO 2-PNS to 0.284 for p-NO 2PNS, and are linearly related to the α values for 2-PNS substituents. Likewise the ϱ z (Z is a substituent of substrate) values are linearly related to pKa of the pyridines and ϱ y (Y is a substituent of pyridine) values are also correlated to the β values. These data show that electron-withdrawing substituents in 2-PNS increse bond formation between C and N atoms and such subsituents in the pyridines also lead to increased bond formation relatively to bond breaking in the transition state. The More O'Ferral and Swain, Thornton, and Harris approaches were applied for the prediction of substituent effects on above interpretation.

Compound I formation with turnip peroxidases and peroxybenzoic acids.

The kinetics of formation of the compounds I of the turnip peroxidase isoenzymes 1 and 7 with peroxybenzoic acid and a series of substituted peroxybenzoic acids (p‐OCH3, p‐CH3, p‐Cl, m‐Cl, m‐NO2 and p‐NO2) were studied at 25°C. The pH profiles of the observed second‐order rate constants, after correction for the alkaline transitions of the enzymes, indicate that isoenzyme 1 reacts exclusively with unionized peroxy acids whereas with isoenzyme 7, although the major contribution involves reaction with unionized peroxy acid, an additional reaction with peroxy anion is observed. In contrast to the behaviour of horse‐radish peroxidase, (where the rate constants for unhindered unionized peroxybenzoic acids exceed that with H2O2 and the reactions are probably diffusion controlled) the rate constants, kHA, for isoenzyme 1 reaction with unionized peroxy acids are all lower than that with H2O2 and the activation energies indicate chemical control. For isoenzyme 7 the value of kHA with the most weakly acidic peroxybenzoic acids exceeds the rate constant with H2O2. For both isoenzyme 1 and isoenzyme 7 the values of kHA are very sensitive to peroxy acid acidity and in both cases log kHA shows good correlation with pKHA.The results are compared with each other and with previous data for both turnip and horse radish peroxidases. It is suggested that the multifactorial influences upon the kinetics of compound I formation include (a) diffusion, (b) substrate hydrophobicity, the hydrophobic binding affinity of the active sites of the enzymes and perhaps hydrogen bonding interactions, (c) a substrate‐charge‐type discrimination elicited by the protein at the entrance to the active site, (d) substrate substituent inductive effects which suggest the importance of the generation of highly nucleophilic peroxy anions from neutral hydroperoxides within the active site. These influences are of very variable relative importance in enzymes from different sources and in different isoenzymes from the same source.

Design of substrate-site-directed inhibitors of adenylate kinase and hexokinase. Effect of substrate substituents on affinity for the adenine nucleotide sites

Nineteen derivatives of adenosine 5'-phosphate (AMP) bearing acylaminomethyl, acetoxy, or alkylaminomethyl substituents on the phosphate-ribose bridge (5' and O-5' positions) of AMP together with 2',3'-O-ethylidene, 2',3',-O-isopropylidene, and 2',3'-di-O-acetyl derivatives of AMP have been synthesized. Their substrate and/or competitive inhibitor properties with pig rabbit muscle AMP kinases indicate that all the substituents except 2',3'-O-ethlidene with the pig enzyme permitted binding of AMP at its enzymic site. Determination of enzyme-inhibitor dissociation constants showed that several compounds with substituents on the ribose-phosphate bridge bind as well or better than AMP. The affinity is ascribed in part to interaction between substituents and a lipophilic region of the enzymes adjacent to the ribose-phosphate bridge in the enzyme-AMP complexes. The enzyme-inhibitor dissociation constants reveal a structural dissimilarity between the pig and rabbit enzymes in the vicinity of the lipophilic region. The substrate and inhibitor properties of eight ATP derivatives gave evidence that affinity of ATP for its substrate site on the AMP kinases is compatible with acetyl- or chloroacetylaminomethyl groups at the phosphate-ribose bridge or with 2',3'-O-ethylidene or isopropylidene residues. The yeast hexokinase-ATP complex tolerated an acetylaminomethyl group at C-5' or a benzoylaminomethyl group adjacent to O-5'. The present findings regarding substituent tolerance could be used in the design of adenine nucleotide site-directed irreversible inhibitors.

Design of substrate-site-directed irreversible inhibitors of adenosine 5'-phosphate aminohydrolase. Effect of substrate substituents on affinity for the substrate site

Derivatives of adenosine 5'-phosphate (AMP) have been synthesized in which the phosphoester (POCH2) grouping of AMP is replaced by PCH(R)CH2 where R is OC(O)Me, CH2NHCOMe, CH2NHCOEt, and CH2NHCOOR' (R' = Me, Et, and Pr). The 2',3'-O-isopropylidene and 2', 3'-di-O-acetyl derivatives of AMP were also prepared. All compounds were competitive inhibitors of rabbit muscle AMP aminohydrolase with enzyme-inhibitor dissociation constants (Ki values) of 330, 20, 17, 19, 16, 14, 260, and 105 muM, respectively. All compounds were substrates except those in which R was CH2NHCOEt and CH2NHCOOR' (R'=Me, Et, and Pr). The previously described allo and talo epimers of 5'-C-acetylaminomethyl-AMP and the allo epimer of 5'-C-propionylaminomethyl-AMP were substrates and competitive inhibitors with Ki values of 18, 47, and 42 muM, respectively. The talo epimer of 5'-C-propionylaminomethyl-AMP was not a substrate and was a noncompetitive inhibitor, Ki

Catalytic Vapor-Phase Ammoxidation of Substituted Toluenes over Chromium Oxide

Abstract Ammoxidation of substituted toluenes over a chromium oxide catalyst has been studied in a flow system at atmospheric pressure. The reactions give satisfactory yields (ca.70%) of corresponding nitriles at high conversion of toluenes. The rate constant for the reaction of substrate adsorbed on the catalyst surface, kT0, is independent of the substituent of substrate, while the adsorption equilibrium constant of gaseous substrate, KT depends on the substituent, affording Hammett’s ρ of −0.9 for σ+. These results support our mechanism reported previously for the analogous oxidation of toluene and ethylbenzene over Cr2O3, which involves an electron transfer from adsorbed hydrocarbons to dissociated oxygen.

Effects of substituents on chain‐transfer reactivities of p‐substituted cumenes in radical polymerization of p‐substituted styrenes

AbstractIn order to study the effects of the substituents in both substrate and attacking radical on the chain‐transfer reactivities of nuclear‐substituted cumenes toward substituted polystyryl radicals, the polymerizations of p‐substituted styrenes in the presence of p‐substituted cumenes were carried out with α,α′‐azobisisobutyronitrile as an initiator at 60°C, and their chain‐transfer constants were determined. The relative chain transfer reactivities of p‐substituted cumenes toward given p‐substituted polystyryl radicals did not follow the Hammett equation, but were correlated with the modified Hammett equation, log(k/k0) = pρ + γER, which was proposed by the present authors for evaluating the substituent effects in radical reactions. On the other hand, the relative reactivities of poly‐(p‐substituted styrene) radicals toward given p‐substituted cumenes were correlated by the Hammett equation. Thus, it was concluded that the effects of the substituents in substrate cumene depended upon the contributions of both polar and resonance factors, while those in attacking polystyryl radical depended upon only a polar factor.