High Base Concentrations Research Articles

An E1cB mechanism for the alkaline hydrolysis of thiolesters of fluorene-9-carboxylic acid: effect of ester conjugate base structure on differential eliminative reactivity of oxygen and sulphur nucleofuges

The alkaline hydrolysis of a series of thiolesters of fluorene-9-carboxylic acid has been studied and pseudo-first-order rate constants, kobs(hydroxide ion in excess), showed saturation with respect to hydroxide ion concentration for any given ester. The kinetic expression describing such behaviour was found to be kobs=k′/(1 +Kw/Ka[HO–]) where k′ is the limiting rate constant at high base concentrations and Ka is the acid dissociation constant of the acidic ester. Values of log10k′ followed a Bronsted correlation (with the pKa of the conjugate acid of the appropriate leaving group) with equation log10k′= 6.10 – 1.14 pK1.g. (r 0.9700). There was no significant steric effect on k′ as the 2′-methoxythiophenyl ester obeyed the above relationship. Esters with poorer leaving groups (S-benzyl, S-n-propyl) deviated positively from the correlation. For active thiolesters of fluorene-9-carboxylic acid the highly negative value of β1.g. for the k′ term (slope of the Bronsted plot), along with the saturation kinetics and a positive/zero value (+4.6 ± 6.1 J K–1 mol–1) for the entropy of activation for the S-phenyl ester was evidence of an E1cB alkaline hydrolytic mechanism. In support of this were the low solvent deuterium kinetic solvent isotope effect on k′(kH/kD= 1.37) and the rate inhibition on 9-methylation. Comparison of fluorene-9-esters with acetoacetic esters showed that there was less difference in reactivity between oxygen and sulphur esters for the former, an effect explained as lying in the highly delocalised nature of the fluorene ester conjugate bases.

The Kinetics of the acid-catalysed dissociation of the macrocyclic complexes [Ni( trans-Me 6[18]dieneN 4)] 2+ [Cu( trans-Me 6[18]dieneN 4] 2+ and [Cu( cis-Me 6[18]dieneN 4)] 2+ and the kinetics of the base-catalysed dissociation of the copper(II) complexes

The acid-catalysed dissociation of the copper(II) and nickel(II) complexes of trans-Me 6[18]dieneN 4 (2,4,4,11,13,13-hexamethyltetra-azacyclo-octadeca-1,10-diene) and the copper(II) complex of cis-Me 6[18]dieneN 4 (2,4,4,11,11,13-hexamethyltetra-azacyclo-octadeca-1,13-diene) have been studied kinetically. For the complexes of trans-Me 6[18]dieneN 4, the observed rate constant at constant hydrogen ion concentration (k obs) is given by the expression (i), where k o represents the solvolytic dissociation path way ▪ The acid catalysed reactions of the trans-diene complexes involve a rapid pre-equilibrium protonation step, followed by a slow loss of the metal ion from the protonated complex. Activation parameters for the k and k o pathways have been determined. The acid-catalysed dissociation of the copper(II) complex of the cis-diene, which is known to have pseudo-tetrahedral stereochemistry, is very much faster than that of the trans-diene which is essentially planar. This reaction shows no solvolytic pathway, but both general and specific acid catalysed pathways. Thus in the presence of acetic acid (HA) the rate expression at constant pH is given by ▪ The kinetics of dissociation of the two copper(II) complexes in basic solution have also been studied in detail. For 1 X 10 −2 to 5 X 10 −2 M hydroxide, the reactions show a second order dependence on the hydroxide ion concentration and the dissociation can be represented by the equations. ▪ At high base concentrations the reactions show a first order dependence on [OH −] (as all CuL 2+ is converted to CuLOH +). Values of K and k have been determined. The equilibrium CuL 2+ + N − 3 ⇌ [CuLN 3] + has also been studied for the trans diene, the equilibrium constant is 7.3 M −1 compared with 0.27 M −1 for the reaction with hydroxide ion at 25 °C.

Meisenheimer adduct formation between 2,4-dinitrophenetole and ethanolic alkali ethoxide solutions: the course of the acidity function J E and thermodynamic solvent isotope effects

Spectrophotometric measurements of the equilibrium constant (Kapp) for formation of a Meisenheimer adduct from 2,4-dinitroanisole and ethanolic sodium and potassium ethoxide have been used to define an acidity function JE for alkoxide solutions in ethanol (analogous to the functions JM for methanol). Sodium and potassium ethoxide behave identically up to a concentration of ca. 0.3 mol dm–3; above this value solutions of sodium ethoxide are slightly less basic. The dependence of Kapp on base concentration is interpreted in terms of ion-pairing effects. The formation of a 1 : 2 adduct becomes significant at high base concentrations, and appears to involve cation-specific ion-pairing effects. The limiting value of log Kapp at low concentrations is -3.1. In EtOD solutions of the same alkoxide concentration, the equilibrium constant is greater than that in EtOH solutions by a factor of 2.5. This result and measurements in mixtures of EtOH and EtOD are consistent with the formulation of the ethoxide ion as an entity containing three hydrogen-bonded solvent molecules, and a deuterium fractionation factor of ca. 0.72–0.73 for the hydrogen-bonded positions.

Reaction of butylmercury nitrate with Lewis bases

The reaction of butylmercury nitrate with organic bases has been studied in four solvents. BuHgNO 3 is molecular in benzene and acetone but ionic in water; in acetonitrile there is an equilibrium between molecular and ionic species. In benzene solution bases form 1 : 1 adducts, 3-coordinate with pyridine, 4-methylpyridine, bipyridine, Et 3N, Bu 3N, PBu 3, PPh 3 or diphos, 4-coordinate with tetramethyldiaminoethane. Adduct stabilities and enthalpies of formation are reported. In acetone solution bases displace nitrate, in water bases displace coordinated water and in acetonitrile they displace nitrate or coordinated solvent; in all three solvents the end products are BuHg · base + and NO 3 -. Enthalpies are reported for these reactions. Distribution of BuHgNO 3 between benzene and water is concentration dependent. Addition of phosphines increases the proportion of the mercury in the benzene phase; addition of heterocyclic bases increases the proportion in the aqueous phase; addition of tertiary amines first increases the proportion in the benzene phase, then, with higher base concentrations, that in the aqueous phase.

Excited state acid–base equilibrium of tyrosine

Fluorescence attributable to the tyrosinate form of the amino acid tyrosine, previously only observed at pH > pK(S0) = 10.3 where tyrosinate exists in the ground state, has been observed at neutral pH in the presence of high buffer base concentrations. This observation is consistent with the large shift in pK(Sl) predicted from absorption measurements and confirms that proton transfer is indeed a mechanism by which carboxylate ions quench tyrosine fluorescence. The dependence of the fluorescence quantum yields of tyrosine and tyrosinate on pH does not fit a simple excited state acid–base equilibrium model but a more complicated system where carboxylate is also capable of simultaneously quenching tyrosine fluorescence by a mechanism not involving proton transfer. Kinetic analysis of the system allows calculation of pK(S1) = 4.2 for tyrosine. The quantum yield of tyrosinate fluorescence can be appreciably higher than that normally measured at alkaline pH where a separate quenching mechanism must operate. These results have significance in the interpretation of the fluorescence properties of proteins.

The mechanism of cleavage of 3-phenylallyl-silicon and -tin bonds by methanolic sodium methoxide

Summary The compounds trans -PhCH CHCH 2 MR′ 3 with M Si or Sn and R′ Me or Et have been cleaved in methanolic sodium methoxide at 50°C to give the products trans -PhCH CHCH 3 (I) and PhCH 2 CH CH 2 (II). (Small amounts of cis -PhCH CHCH 3 sometimes obtained are thought to come mainly or exclusively from cis -PhCH CHCH 2 MR′ 3 in the starting material.) At base concentrations of 0.02–0.40 M the I/II ratio is 1.53 for MR′ 3 SiMe 3 and 1.04 for MR′ 3 SnMe 3 , but the ratio rises somewhat in both cases at higher base concentrations. The values of the product isotope effect, PIE, given by the product ratio PhCH CHCH 3 /PhCH CHCH 2 D obtained on cleavage in 1 : 1 MeOH/MeOD at 50°C, for formation of product I are as follows: (MR′ 3 ) SiMe 3 , 1.26; SiEt 3 , 1.75; SnMe 3 , 2.1; SnEt 3 , 2.2. The corresponding values for the formation of II are 1.45, 2.0, 3.0 and 3.2. For formation of I the values of the rate isotope effect, RIE, given by the ratio of the rate in MeOH to that in MeOD, are 0.60 and 0.77 for MR′ 3 SiMe 3 and SnMe 3 , respectively, and the corresponding values for formation of II are 0.65 and 1.14. The RIE: PIE ratios for MR′ 3 SiMe 3 are 0.48 and 0.45 for formation of I and II, respectively, and the corresponding ratios for MR′ 3 SnMe 3 are 0.37 and 0.38. It is suggested that in all cases the cleavage proceeds by an electrophically-assisted mechanism in which the proton transfers from the solvent to the C(1) or C(3) carbon atoms of the phenylallyl group are concerted with the cleavage of the metal-carbon bond.

Evidence for rate-limiting deprotonation of a spiro-Meisenheimer intermediate during Smiles' rearrangement of 2-(p-nitrophenoxy)ethylamine

Kinetic studies of intramolecular nucleophilic aromatic displacement of alkoxide ion by the amino group in 2-(p-nitrophenoxy)ethylamine support a mechanism whereby, at low base concentrations, the rate of Smiles' rearrangement is dependent upon the rate of general base-catalysed deprotonation of a spiro-Meisenheimer intermediate; at high base concentrations the base independent rate of formation of the Meisenheimer intermediate becomes rate limiting.

Competitive pathways in the synthesis of cyclopropa[b]naphthalene

The product distribution obtained from dehydrochlorination of the benzobicycloheptene 1 is dependent on the reaction conditions. In tetrahydrofuran at high base concentration cyclopropa[b]naphthalene ( 2) predominates, whereas at low base concentration 6 - chlorobenzo[a]cyclohepta - 1,3,5 - triene ( 4) is the major product. In dimethyl sulphoxide 2 and 4 are formed in low yields, the ether 10 being the major product.

Base catalysis of nucleophilic aromatic substitution. The reactions of primary and secondary amines with nitrophenyl phosphates

The aromatic nucleophilic displacement of methyl phosphate dianion from the anion of methyl 4-nitrophenyl phosphate by dimethylamine and piperidine is compared with the corresponding displacement of inorganic phosphate, as the trianion, from the dianion of 4-nitrophenyl phosphate. The latter reaction is known to show a change in the rate-determining step with increasing base concentration, and the reaction at high base concentration is quantitatively closely similar to that of the diester. The results are interpreted in terms of the two-step mechanism for nucleophilic aromatic substitution, and it is shown that both steps are subject to catalysis by hydroxide ion.

A spectroscopic study of the reversible reactions of aromatic nitrocompounds with sulphur bases

The reversible reactions of 1,3,5-trinitrobenzene with sodium thioethoxide and thiophenoxide have been investigated in methanol and in methanol–dimethyl sulphoxide mixtures. At low concentrations of base, 1:1 adducts are formed by covalent addition of base at a ring carbon carrying hydrogen. With sodium thioethoxide a 1:2 adduct is also formed at higher base concentrations. The equilibrium constants for formation of the adducts in methanol have been determined and are compared with the values for oxygen bases. These values, which give a measure of the thermodynamic affinities (carbon basicities) of the bases for aromatic carbon, decrease in the order SEt– > OMe– > SPh– > OPh–. The effect of changing the solvent to dimethyl sulphoxide on these equilibria is examined. Measurements with nitroanilines indicates that, relative to sodium methoxide, the sulphur bases have a greater tendency to form covalently bound addition products rather than abstract an amine proton.

Studies on the Chemical Modification of Arginine: I. THE REACTION OF 1,2-CYCLOHEXANEDIONE WITH ARGININE AND ARGINYL RESIDUES OF PROTEINS

Abstract The guanido group of arginine condenses with 1,2-cyclohexanedione in alkaline aqueous medium to form a new α-amino acid. The product(1,2-cyclohexanedione-arginine) was shown by independent synthesis to be N5-(4-oxo-1,3-diazaspiro[4.4]non - 2 - ylidene) - l - ornithine. At hydroxide concentrations of 0.2 n or higher, this was the principal product, and the reaction with free arginine and with the arginyl residues of model proteins was completed in 3 hours. At lower base concentration or with salmine at high base concentrations, a heterogeneous mixture of ninhydrin-positive products was observed. The reaction appears to be specific for the guanido group. Peptide maps of tryptic digests of 1,2-cyclohexanedione-treated chains of hemoglobin showed blocking of hydrolysis at arginyl bonds with no change in positions of tryptic peptides not adjacent to arginyl residues.

Kinetic Studies of Solvolysis. XI. The Steric Course of the Phenolyses of Optically Active α-Phenylethyl Chloride in Mixtures of Various Phenols and Organic Solvents—A Mechanism for the SN1 Reaction with a Net Retention of Configuration

Abstract The SN1 phenolyses of optically active α-phenylethyl chloride in binary mixtures of organic solvents and certain substituted phenols (i. e., phenol, p-cresol, p-chloro- and p-nitro-phenol) proceed in the presence of aniline and of triethylamine to give the corresponding α-phenylethyl substituted-phenyl ethers with a predominantly-retained configuration. In binary mixtures of benzene and various phenols, the extents of retention for the ethers are slightly reduced at the higher base concentrations. However, in binary solvents of acetonitrile and certain phenols, the optical purities of the ethers with retained configurations decrease continuously with the base concentrations, while at the higher concentrations (∼0.4 m) the steric courses change to the inverted course. The C-alkylated (α-phenylethylated) derivatives of these phenols, isolated along with the phenyl ethers, have inverted configurations, irrespective of the configurations of the corresponding phenyl ethers. These results are all consistent with a mechanism in which a molecule of the phenol reacts with the SN1 ion-pair intermediate of the phenolysis to give a phenyl ether with a retained configuration, probably by SNi-like four-center substitution, whereas the reaction of a phenoxide anion with the SN1 intermediate proceeds predominantly by the Walden inversion mechanism yielding a phenyl ether and α-phenylethylated phenols with inverted configurations.

Some effects of cocatalyst structure on the anionic polymerization of -caprolactam

A study of the effect of catalyst (base) concentration and N-acylcaprolactam cocatalyst size and substitution on the fast anionic polymerization of caprolactam indicated that a steric effect due to cocatalyst size exists, and perhaps an electronic effect due to cocatalyst substitution was noted. The rate of polymerization, degree of polymerization, and yield of polymer are related to these effects. It was also noted that at high base concentrations, the rate and degree of polymerization along with the product yields all decrease. These latter observations suggest that reinterpretation of some of the reaction mechanism data may be important if polymer degradation is not an appreciable factor during the reaction.

THE TRANSPORT OF GAS BY THE BLOOD OF THE TURTLE

The chief characteristics of the blood of the turtle Pseudemys concinna, considered as a system for the transport of oxygen and carbon dioxide, are its low corpuscular content (10 to 22 per cent by volume) and its high concentration of base bound as bicarbonate. These characteristics account fully for the shape and position of the carbon dioxide dissociation curve, the effect of oxygenation and reduction of the hemoglobin upon the carbon dioxide-combining power of the blood, and the distribution of carbon dioxide between the corpuscles and plasma. The oxygen-combining capacity of the turtle corpuscles does not differ from that of an equal volume of human erythrocytes. The oxygen dissociation curve is similar to that of mammalian blood and is affected in like manner by the quantity of carbon dioxide present. Its exact shape and position depend in part upon the number of corpuscles in the blood; in part its characteristics cannot be attributed to known chemical factors.