Showing papers on "Nucleophile published in 1973"

The alpha effect. A review

Abstract: Instances of high reactivity (as signaled by a positive Bronsted deviation) by nucleophiles bearing one or more unshared pairs of electrons on an atom adjacent to the nucleophilic center (the alpha effect) are surveyed in the context of possible explanations for this phenomenon. No single cause appears to account satisfactorily for all the data. However, four factors (ground-state destabilization of the nucleophile, transition-state stabilization, solvent effect differences for alpha and nonalpha nucleophiles, and product stability) may be involved in contributory roles. The response to proton basicity of a substrate is probably not related to its susceptibility to the alpha effect. Carbon electrophiles seem to be receptive to the alpha effect in the order digonal > trigonal > tetrahedral. The inconsistent behavior of alpha nucleophiles makes the prediction of alpha effects rather risky and confirms the complicated nature of nucleophilic substitutions.

Reactions of papain and of low-molecular-weight thiols with some aromatic disulphides. 2,2′-Dipyridyl disulphide as a convenient active-site titrant for papain even in the presence of other thiols

Abstract: 1. The u.v.-spectral characteristics of 5,5′-dithiobis-(2-nitrobenzoic acid) (Nbs2), 2,2′-dipyridyl disulphide (2-Py–S–S–2-Py), 4,4′-dipyridyl disulphide (4-Py–S–S–4-Py), 5-mercapto-2-nitrobenzoic acid (Nbs), 2-thiopyridone (Py–2-SH) and 4-thiopyridone (Py–4-SH) were determined over a wide range of pH and used to calculate their acid dissociation constants. 2. The reactions of l-cysteine, 2-mercaptoethanol and papain with the above-mentioned disulphides were investigated spectrophotometrically in the pH range 2.5–8.5. 3. Under the conditions of concentration used in this study the reactions of both low-molecular-weight thiols with all three disulphides resulted in the stoicheiometric release of the thiol or thione fragments Nbs, Py–2-SH and Py–4-SH at all pH values. The rates of these reactions are considerably faster at pH8 than at pH4, which suggests that the predominant reaction pathway in approximately neutral media is nucleophilic attack of the thiolate ion on the unprotonated disulphide. 4. The reaction of papain with Nbs2 is markedly reversible in the acid region, and the pH-dependence of the equilibrium constant for this system in the pH range 5–8 at 25°C and I=0.1 is described by: [Formula: see text] 5. Papain reacts with both 2-Py–S–S–2-Py and 4-Py–S–S–4-Py in the pH range 2.5–8.5 to provide release of the thione fragments, stoicheiometric with the thiol content of the enzyme. 6. Whereas the ratios of the second-order rate constant for the reaction at pH4 to that at pH8 for the cysteine–2-Py–S–S–2-Py reaction (kpH4/kpH8=0.015) and for the papain–4-Py–S–S–4-Py reaction (kpH4/kpH8=0.06) are less than 1, that for the papain–2-Py–S–S–2-Py reaction is greater than 1 (kpH4/kpH8=15). 7. This high reactivity of papain has been shown to involve reaction of the thiol group of cysteine-25, the enzyme's only cysteine residue, which is part of its catalytic site. 8. That this rapid and stoicheiometric reaction of the thiol group of native papain is not shown either by low-molecular-weight thiols or by the thiol group of papain after its active conformation has been destroyed by acid or heat denaturation, strongly commends 2-Py–S–S–2-Py as one of the most useful papain active-site titrants discovered to date. This reagent has been shown to allow accurate titration of papain active sites in the presence of up to 10-fold molar excess of l-cysteine and up to 100-fold molar excess of 2-mercaptoethanol.

6 Chemical Basis of Biological Phosphoryl Transfer

Abstract: Publisher Summary This chapter discusses the probable mechanisms involved in biological phosphoryl transfer reactions as disclosed by the studies of model systems and their extrapolation to the enzyme mediated processes. Various lines of evidence have led to a general acceptance of the dissociative monomeric metaphosphate mechanism for the hydrolysis of monoester monoanions derived from alcohols and phenols, thiols, and amines. The principal supporting data include: (a) a general observation of P–O, P–S, or P–N bond cleavage; (b) entropies of activation close to zero in contrast to bimolecular or associative solvolyzes where entropies of activation are usually more negative by 20 eu; (c) molar product compositions (methyl phosphate : inorganic phosphate) in mixed methanol–water solvent that approximate the molar ratio of methanol, water or favor methyl phosphate formation, inferring the presence of a highly reactive electrophilic species; and (d) the existence of linear free-energy relationships between the logarithmic rates of hydrolysis of the monoanions and the dissociation constants of the corresponding leaving group. This chapter describes the hydrolysis of acyclic phosphate esters. Nucleophilic reactions at acyclic phosphorus are discussed in the chapter. Catalysis of phosphoryl transfer or ligand loss is also discussed in the chapter.

Photoisomerization of Acylsilanes to Siloxycarbenes, and Their Reactions with Polar Reagents

Abstract: The photolysis of acylsilanes in a variety of polar reagents (alcohols, acetic acid, HCN, pyrrole, etc.) is shown to involve formation of isomeric siloxycarbenes which act as nucleophiles and inser...

Kinetics of the reaction of hydrogen peroxide with cysteine and cysteamine

Abstract: The rate of the reaction between hydrogen peroxide and cysteine or cysteamine is proportional to [H2O2] and [NH3+CHXCH2S–](X = H or CO2–) consistent with nucleophilic attack by the thiolate ions on peroxide oxygen. The rate decreases at higher pH where loss of the NH3+ proton occurs, and it is suggested that hydrogen bonding between this group and hydrogen peroxide facilitates the reaction.

Reactions of esters of N-hydroxy-2-acetamidophenanthrene with cellular nucleophiles and the formation of free radicals upon decomposition of N-acetoxy-N-arylacetamides.

Abstract: The sulfate ester of N -hydroxy-2-acetamidophenanthrene was prepared and was found to react significantly with methionine, adenosine, and guanosine. The adduct from the methionine reaction was characterized as 1-methylmercapto-2-acetamidophenanthrene. The levels of reaction with adenosine and guanosine were comparable, in contrast with the observation that N -acetoxy-2-acetamidofluorene shows a marked preference for guanosine as a substrate among the nucleosides. Although the level of reaction was lower, N -acetoxy-2-acetamidophenanthrene also reacted equally well with adenosine and guanosine. Molecular orbital calculations suggested that the previously studied adduct-forming abilities of N -acetoxy- N -arylacetamides might be related to their ability to form radical cations. On this basis, the abilities of these compounds to decolorize the stable free radical 2,2-diphenyl-1-picrylhydrazyl were tested. N -Acetoxy-2-acetamidofluorene rapidly decolorized 2,2-diphenyl-1-picrylhydrazyl in 20% ethanol at 45°, N -acetoxy-2-acetamidophenanthrene acted much more slowly, while N -acetoxy-4-acetamidobiphenyl and N -acetoxy-4-acetamidostilbene had almost negligible effects. These activities are closely related to the adduct-forming abilities of these compounds and may affect their carcinogenicities. We suggest that the chemistry of esters of N -hydroxy-2-acetamidophenanthrene shown here is typical of nonradical reactions of N -aryl- N -acetylnitrenium ions, while the reactivity of N -acetoxy-2-acetamidofluorene reflects a high percentage of radical cations among the ions formed upon decomposition of this ester.

Nucleophilic Competition in Some β‐Galactosidase‐Catalyzed Reactions

Abstract: A study of nucleophilic competition in β-galactosidase-catalyzed reactions has been performed with different substrates: o, m and p-nitrophenyl β-d-galactosides, phenyl β-d-galactoside, o-aminophenyl, β-d-galactoside, p-aminophenyl, β-d-galactoside, o-nitrophenyl α-l-arabinoside. For each substrate the limiting step and the individual rate constants have been determined. The rate of formation of the galactosyl-enzyme intermediate, k2, does not correlate with the Hammett values, suggesting that this step remains more complex than a single chemical reaction. A preliminary investigation of the effect of pH and Mg2+ concentration on each individual rate constant is presented. Both k2 and k3 seem to exhibit the same pH profile. The action of various nucleophilic compounds on the galactosyl-enzyme has been tested. A peculiar effect of 2-mercaptoethanol has to be emphasized; the behaviour of this nucleophile has been analyzed and discussed.

Organometallic complexes in synthesis. Part IV. Abstraction of hydride from some tricarbonylcyclohexa-1,3-dieneiron complexes and reactions of the complexed cations with some nucleophiles

Abstract: Isomeric 1- and 2-methoxy-derivatives of tricarbonylcyclohexa-1,3-dieneiron can frequently be separated by chromatography. The positions of removal of hydride from such complexes, relative to OMe and/or Me sub-stituents, have been examined. Some of the resulting mesomeric cations have been treated with the nucleophiles borohydride, hydroxide, and morpholine to define positions of reaction relative to substitution. Among other nucleophiles which react are enamines and ketones. Conditions for removal of the tricarbonyliron group from the resulting complexes have been examined.

Metal ions and complexes in organic reactions. Part XV. Copper-catalysed substitutions of aryl halides by phthalimide ion

Abstract: Copper-catalysed nucleophilic substitutions, ArHal → ArN(CO)2C6H4(and thence ArNH2 by hydrolysis) are effective with a wide range of aromatic bromo- or iodo-derivatives; they are preferably carried out with potassium phthalimide and copper(I) iodide in refluxing dimethylacetamide. Reductive substitution. ArHal → ArH, is rarely competitive, but accompanying decarboxylation occurs in the case of halogenocarboxylic acids. Rates of halide substitution are dependent on the ratio of potassium phthalimide to copper(I) iodide. These two reagents solubilise each other and are considered to associate in cuprate complexes which react with the halides. Rates of substitution of para-(or meta-)halogeno-compounds, XC6H4Hal, show relatively small dependence on the polar character of X. The substitutions are however very susceptible to steric inhibition, as is evidenced by the behaviour of polycyclic halides and of compounds of the type o-XC6H4Hal, particularly if polar effects in the substituents X do not provide partial compensation.

The synthesis of fluorinated carbohydrates

Abstract: Three types of reaction are of particular value in the synthesis of fluoro sugars, namely, nucleophilic displacements with fluoride salts, epoxide cleavage reactions, and glycal addition reactions. These reactions have been developed to the point where effective syntheses of a wide range of fluoro sugars can be planned on a rational basis. Nucleophilic displacement usually involves the treatment of sulphonates with fluoride salts. Reagents of the type tetrabutylammonium fluoride-dipolar aprotic solvent are particularly effective for the displacement of secondary sulphonates. An understanding of the steric and polar factors which can adversely influence the displacement of carbohydrate secondary sulphonates and of competing reaction pathways usually allows the evaluation of this route in designing effective syntheses of fluoro sugars. Selection of ring size (furanose, pyranose, septanose derivatives) is an important parameter in synthesis design. The cleavage of carbohydrate epoxides to give Trans-fluorohydrins can be effected with reagents such as HF or KHF2. The reactions usually occur stereo-specifically and predictably if the epoxide ring is part of a rigid molecular system such as 1, 6-anhydrohexopyranose. The reagent CF3OF, which is an effective source of electrophilic fluorine, readily adds to O-acetylated glycals to give 2-deoxy-2-fluoro derivatives. 2-Deoxy-2-fluoro-D-glucose can be converted into 3,4,6-tri-O-acetyl-2-fluoro-D-glucal and thence by treatment with CF3OF, into ‘2,2-difluoro-D-glucose.’

Nucleophilic Attack on Some Isothiazolium Salts

Abstract: A variety of isothiazolium salts has been prepared and allowed to react with sodium benzoylacetate 2-Benzoylthiophenes are obtained, suggesting that the position of initial nucleophilic attack is at the sulfur atom of the heterocyclic cation Reaction with hydrogen sulfide gave acyclic reduction products, or 1,2-dithiole derivatives, depending on the type of substituent on nitrogen in the isothiazolium salts

Preparation and some reactions of Group VI metal monodentate bis-phosphine carbonyl complexes. Mechanistic aspects of chelate-ring formation

Abstract: A series of complexes LM(CO)5[M = Cr, Mo, or W; L = Me2PCH2CH2PMe2(dmpe), Ph2PCH2PPh2(dpm), Ph2PCH2CH2PPh2(dpe), Ph2PCH2CH2CH2PPh2(dpp), or Ph2PCH2CH2AsPh2(ape)] has been prepared and characterised by analysis, and i.r., mass, and n.m.r. spectroscopy. The complexes can be methylated with Me3OBF4 to give [(MeL)M(CO)5]BF4. The acid-assisted nucleophilic substitution reaction used in the formation of the complexs can also be applied to their conversion into bridged complexes, L[M(CO)5]2. Variations in geminal complexes coupling constants 2JPCH and aromatic solvent induced shifts for the series of complexes(dmpe)M(CO)n(M = Cr, Mo, or W; n= 4 or 5) are discussed and compared with those in (Me2PXCH2)2(X = O or S) and [(Me3PCH2)2](BF4)2, whose syntheses are also reported. Changes in the 31P chemical shift are used to demonstrate that the chelation shift is comparable to the co-ordination shift. Kinetic studies of the rate of the chelation reaction, LM(CO)5→ LM(CO)4+ CO, have been used to elucidate details of its mechanism. The reaction follows first-order kinetics, as required for the intramolecular process. The magnitude of the enthalpy of activation (ca. 140 kJ mol–1) and the similarity in rate between phosphorus and arsenic nucleophiles, suggest a large dissociative component in the activation. The positive entropy of activation and particularly its large variation (+6 to +71 J K–1 mol–1) suggest a concerted process in the transition state. The smaller the potential chelate ring, the faster the reaction in the series L = Ph2P(CH2)nPPh2(n= 1, 2 or 3); this appears to be largely an entropy effect.

The chemistry of nitroso-compounds. Part VI. Direct and indirect transnitrosation reactions of N-nitrosodiphenylamine

Abstract: Transfer of the nitroso-function from N-nitrosodiphenylamine to N-methylaniline, sodium azide, and other nucleophilic species is reported for acidic 50% aqueous ethanol at 25 °C. Neutral N-nitrosodiphenylamine is unreactive and protonation is required to initiate these reactions. Transfer to N-methylaniline is not catalysed by added Cl–, which suggests that the nitroso-group is transferred without the intermediacy of nitrous acid (direct transnitrosation). Transfer to sodium azide under similar conditions does proceed via nitrous acid. For other nucleophiles, however, both direct and indirect transnitrosation reactions may compete. Reaction rates are independent of these nucleophilic species when their concentration is high. Solvent isotope effects for reaction under these circumstances are negligible which suggests that an intramolecular rearrangement of the conjugate acid rather than protonation of the N-nitrosodiphenylamine is rate-limiting.

An Addition Reaction of Diethylamine to Styrene Catalyzed by Lithium Diethylamide

Abstract: An addition reaction of diethylamine to styrene catalyzed by lithium diethylamide was found to proceed stoichiometrically to produce 1-diethylamino-2-phenylethane. The rate of the reaction was expressed by the equations: υ=k[Styrene][Et2NLi]1.3 and υ=k[Styrene][Et2NLi], the ratios of [Et2NH]0 to [Et2NLi]0 being 3.0 and 10 respectivly. On the basis of the kinetic studies, the mechanism of the addition reaction was elucidated. The nucleophilic character of this reaction was clearly demonstrated by the σ–ρ Hammett plot. The second-order rate constant for the addition reaction of styrene was found to be of the same order of magnitude as that of butadiene. The presence of butadiene in the reaction system showed no effect on the reactivity of styrene.