Effect Of Alkyl Substituents Research Articles

Adenosine analogs mediating depressant effects on synaptic transmission in rat hippocampus: structure-activity relationships for the N6 subregion.

Previous studies have shown that analogs of adenosine with substituents upon the N6-nitrogen (e.g., N6-[1-phenyl-2(R)-propyl]adenosine; R-PIA) are often much more potent than the parent compound in activating adenosine receptors, particularly those of the A1 subtype. The present investigation characterized the potencies of a number of N6-substituted adenosine analogs in depressing excitatory synaptic transmission in slices of rat hippocampus, an electrophysiological response mediated by receptors of the A1 subtype. These potencies correlated well with previously reported affinities of these analogs for A1 receptor sites in brain, but not with coronary vasodilation in the dog heart, an A2 receptor mediated response. Analogs with alkyl or aryl substituents at the N6 position were generally more potent than adenosine, although analogs with a tertiary carbon attached directly to the N6-nitrogen were usually only weakly active. Although it has been suggested that there may be a subregion of the A1 receptor with some specificity for aryl groups, these experiments did not suggest that this was the case. Analogs with chiral centers attached to the N6-nitrogen usually displayed stereoselectivity, with R-isomers more potent than the S-isomers. The mechanism underlying this selectivity appeared to be both a facilitating effect of alkyl substituents in the propyl C1 position of R-PIA, and a hindering effect of substituents in the position normally occupied by the hydrogen attached to propyl C2 of R-PIA. These results indicate that although there are some similarities in terms of requirements for activity at A1 and A2 receptors, differences between the N6 sub-regions of these receptors are sufficient to permit the development of selective analogs for these two receptor sites.

PMR spectra of monosubstituted cobalticinium salts

1. The heteroannular effect of alkyl groups in the PMR spectra of alkylcobalticinium salts increases with their increasing hyperconjugative effect. 2. As a consequence of the complex nature of the electronic effects of the alkyl substituents, the chemical shifts for the α- and β-protons of the substituted Cp ligand in the PMR spectra of alkylcobalticinium salts approach one another until they finally coalesce in the series Me, Et, i-Pr, t-Bu.

Kinetics and Thermodynamics of Drug Permeation Through Silicone Elastomers III. Effect of Alkyl Substituent (R) in (MeRSiO) Polymer

The effect of silicone polymer structure on the permeability of drug through silicone membranes was investigated in the capsule-type drug delivery system. The permeability, diffusivity and solubility of progesterone and testosterone through polymethylalkylsiloxane membranes, (MeCn H2n+1 SiO)x, where n = 1, 2, 3, 6 and 8, were determined at 25, 37 and 50°C respectively.As the size of the alkyl substituent was increased from methyl to octyl, the diffusivity decreased, whereas the solubility increased. As a result, the permeability of progesterone decreased initially but increased gradually thereafter, going from (Me2SiO)x to (MeOctSiO)x, in this series of polymer. The same results were obtained with testosterone; however, permeabilities of testosterone were found to be one order of magnitude lower than those of progesterone. This was attributed to the lower solubilities of testosterone in (MeRSiO)x polymers when compared to those for progesterone. The activation energies of permeation for progesterone in these polymers were found to be in the range of 13-15 Kcal/mol.

ChemInform Abstract: ACID‐CATALYZED HYDROLYSIS OF BENZENESULFONAMIDES. RATE ENHANCEMENTS BY ORTHO‐ALKYL SUBSTITUENTS

Pseudo-first-order rate constants have been measured for the acid-catalyzed hydrolysis of a series of N,N-dimethyl- and N-methyl-N-phenylbenzenesulfonamides in 70% (v/v) CF3CO2H/H2O at 99°C. Analysis of the effect of alkyl substituents in the benzene ring shows a remarkable rate enhancement by ortho-alkyl groups, in contrast with a rate retardation of similar substituents in the corresponding benzamides. The rate enhancement in the sulfonamides is attributed to relief of initial-state strain in the transition state for hydrolysis. When the sulfonamide moiety is contained in a five-membered ring fused to a phenyl ring, the rate of hydrolysis is markedly reduced by an ortho-methyl substituent.

Effects of alkylation upon the proton affinities of nitrogen and oxygen bases

AbstractThe protonation energies of alkylated derivatives of NH3 and OH2 are calculated at the Hartree–Fock level with the split‐valence 4‐31G basis set. The methyl, dimethyl, and ethyl amines are studied; oxygen bases include methanol, dimethylether, and ethanol. The geometries of each molecule and its protonated analog are fully optimized. It is found that protonation leads to significant changes in the molecular structures. In particular, the bonds to the N and O atoms are substantially elongated, especially when the other atom involved is C rather than H. The calculated absolute proton affinities are somewhat larger than the experimental values. However, the differences in protonation energies of the various molecules relative to one another agree quantitatively with experiment. Replacement of one H atom of the base by a methyl group induces an increase in proton affinity of some 10 kcal/mol. If a second methyl group is added to the N or O atom, a further increment of about 70% this amount is noted. On the other hand, placement of the second C atom on the first methyl group (to form an ethyl substituent) leads to a smaller increase (∼30%). The magnitudes of these alkyl substituent effects are somewhat larger for the oxygen bases than for the amines.

Stereo-Electronic Effects in Substituted Phosphines: a Molecular Orbital Study

Substituent effects from directly bonded and remote groups in phosphines have been studied by ab initio molecular orbital methods in an attempt to discriminate between the electronic and steric effects of attached groups and determine how they are transmitted to phosphorus. Results of calculations are compared with experimentally determined basicities and acidities, ionization energies, inversion barriers and 31P N.M.R. results. The electronic consequences of steric effects are comparable in importance to direct electronic effects; in the PHn(CH3)3-n, series steric effects account for about half of the substituent effect on basicities and ionization potentials. The effects of steric bulk, modelled by bond angle constraint, are concentrated in the HOMO; by contrast, electronic effects on the HOMO are often minimal. Conformational changes include changes in geometry but the electronic response exceeds what would be expected for geometrical change alone and in NH2- and OH-substituted model compounds of the PH2X and PX3 series may be as great as that produced by changing the substituent. In remote substitution the effects are mainly due to charge displacement at phosphorus. Directly bound groups more often exert their effects by altering the balance between s and p orbitals in the bonding and in the non-bonding parts of the electron distribution but in ways which preclude correlation with electronegativity or other single-parameter measures of substituent properties. Donor/acceptor interactions are weaker in phosphorus(III) compounds than in the first-row analogues but the response to substitution in the density profile is much stronger around the more polarizable second-row element which explains why the alkyl substituent effect is greater for the donor properties of phosphines than amines while the effects of fluoro-substitution are weaker.

Reaction of copper powder with tetraalkylthiuram disulphides

Copper powder reacts photochemically with tetraalkylthiuram disulphides [(R 2NCS 2) 2, TRTD] in chloroform. The effect of different alkyl substituents (R) on the reaction was studied systematically by means of both high-performance liquid chromatography (HPLC) and spectrophotometry. The results obtained show that the reactivity of (R 2NCS 2) 2 increases with increase of R in the order butyl > propyl > ethyl > methyl. In addition, this reaction is applicable to the analysis of the copper content in copper powder, copper oxides, copper(II) hydroxides, and basic copper carbonates.

Acid‐catalyzed hydrolysis of benzenesulfonamides. Rate enhancements by ortho‐alkyl substituents

AbstractPseudo‐first‐order rate constants have been measured for the acid‐catalyzed hydrolysis of a series of N,N‐dimethyl‐ and N‐methyl‐N‐phenylbenzenesulfonamides in 70% (v/v) CF3CO2H/H2O at 99°C. Analysis of the effect of alkyl substituents in the benzene ring shows a remarkable rate enhancement by ortho‐alkyl groups, in contrast with a rate retardation of similar substituents in the corresponding benzamides. The rate enhancement in the sulfonamides is attributed to relief of initial‐state strain in the transition state for hydrolysis. When the sulfonamide moiety is contained in a five‐membered ring fused to a phenyl ring, the rate of hydrolysis is markedly reduced by an ortho‐methyl substituent.

ChemInform Abstract: Effect of Alkyl Substituents on the Thermodynamics of the Self‐association of Purine in Aqueous Solution

Chemischer InformationsdienstVolume 15, Issue 52 Article ChemInform Abstract: Effect of Alkyl Substituents on the Thermodynamics of the Self-association of Purine in Aqueous Solution H. + LOENNBERG, H. + LOENNBERGSearch for more papers by this authorJ. YLIKOSKI, J. YLIKOSKISearch for more papers by this authorA. VESALA, A. VESALASearch for more papers by this author H. + LOENNBERG, H. + LOENNBERGSearch for more papers by this authorJ. YLIKOSKI, J. YLIKOSKISearch for more papers by this authorA. VESALA, A. VESALASearch for more papers by this author First published: December 25, 1984 https://doi.org/10.1002/chin.198452064Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume15, Issue52December 25, 1984 RelatedInformation

Rate constants for the reactions of OH radicals with alkyl substituted olefins

AbstractRelative rate constants for the reactions of hydroxyl radicals with a series of alkyl substituted olefins were measured by competitive reactions between pairs of olefins at 298 ± 2 K and 1 atmospheric pressure. Hydroxyl radicals were produced by the photolysis of H2O2 with 254‐nm irradiation. The obtained rate constants were (× 10−11 cm3 molecule−1 s−1): 2.53 ± 0.06, propylene; 5.49 ± 0.17, cis‐2‐butene; 5.47 ± 0.1, isobutene; 6.46 ± 0.13, 2‐methyl‐1‐butene; 6.37 ± 0.16, cis‐2‐pentene; 6.23 ± 0.1, 2‐methyl‐1‐pentene; 8.76 ± 0.14, 2‐methyl‐2‐pentene; 6.24 ± 0.08, trans‐4‐methyl‐2‐pentene; 10.3 ± 0.1, 2,3‐dimethyl‐2‐butene; 9.94 ± 0.1, 2,3‐dimethyl‐2‐pentene; 5.59 ± 0.07, trans‐4,4‐dimethyl‐2‐pentene. A trend in alkyl substituent effect on the rate constant was found, which is useful to predict kOH on the basis of the number of alkyl substituents on the double bond.

Effect of alkyl substituents on the thermodynamics of the self-association of purine in aqueous solution

The thermodynamic parameters for the self-association of several alkyl-substituted purines have been determined by applying the isodesmic model to the molar enthalpies of infinite dilution at different initial concentrations. Carbon-bonded alkyl groups have been shown to increase the tendency to association by making the association enthalpy more negative. In contrast, the increasing size of the N9-bonded alkyl groups appears to reduce the negative entropy contribution and thus stabilize the associated complexes. These findings are discussed in terms of dipole–induced-dipole interactions and hydrophobic bonding.

Alkyl substituent effects. Part 1. An analysis of alkyl inductive properties in terms of group connectivity

Formulae are derived which express the scales of the inductive substituent constants σI and σ*, the group electronegativities χR, and the polarisability constants P of alkyl groups in terms of base-constants and ‘connectivity characteristics,’ pure numbers the value of which depend only on the number of carbon atoms a group contains and the pattern of their bonding. The formulae are of predictive value in calculating σI, σ*, χR, or P for any alkyl group and in discerning what these scale of measurement have in common and where they differ. It is shown that alkyl σ* is not a artefact as has been claimed, that σI and σ* are linear functions of alkyl group electronegativity, and that P probably has a hyperconjugative element.

ChemInform Abstract: THE PYROLYSIS KINETICS OF ETHYL ESTERS IN THE GAS PHASE. THE ALKYL SUBSTITUENT EFFECT AT THE ACYL CARBON

Chemischer InformationsdienstVolume 14, Issue 37 Preparative Organic Chemistry ChemInform Abstract: THE PYROLYSIS KINETICS OF ETHYL ESTERS IN THE GAS PHASE. THE ALKYL SUBSTITUENT EFFECT AT THE ACYL CARBON G. CHUCHANI, G. CHUCHANISearch for more papers by this authorI. MARTIN, I. MARTINSearch for more papers by this author G. CHUCHANI, G. CHUCHANISearch for more papers by this authorI. MARTIN, I. MARTINSearch for more papers by this author First published: September 13, 1983 https://doi.org/10.1002/chin.198337081Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume14, Issue37September 13, 1983 RelatedInformation

The pyrolysis kinetics of ethyl esters in the gas phase. The alkyl substituent effect at the acyl carbon

AbstractThe gas‐phase elimination of ethyl 3‐methylbutanoate and ethyl 3,3‐dimethylbutanoate has been studied, in a static system, over the temperature range of 360–420°C and in the pressure range of 71–286 torr. The reactions are homogeneous, unimolecular, and follow a first‐order rate law. The temperature dependence of the rate coefficients is given by the following Arrhenius equations: for ethyl 3‐methylbutanoate, log k1 (s−1) = (12.70 ± 0.36) – (202.5 ± 4.4) kJ/mol/2.303RT, and for ethyl 3,3‐dimethylbutanoate, log k1 (s−1) = (13.04 ± 0.08) – (207.1 ± 1.0) kJ/mol/2.303RT. Alkyl substituents at the acyl carbon of ethyl esters yield very close values in rates. Consequently it is rather difficult to offer some conclusion concerning the effect of these substituents.

Gas‐phase elimination kinetics of 1‐substituted ethyl acetates. Effect of polar substituents at the α carbon of secondary acetates

AbstractThe gas‐phase elimination of several polar substituents at the α carbon of ethyl acetates has been studied in a static system over the temperature range of 310–410°C and the pressure range of 39–313 torr. These reactions are homogeneous in both clean and seasoned vessels, follow a first‐order rate law, and are unimolecular. The temperature dependence of the rate coefficients is given by the following Arrhenius equations: 2‐acetoxypropionitrile, log k1 (s−1) = (12.88 ± 0.29) – (203.3 ± 2.6) kJ/mol (2.303RT)−1; for 3‐acetoxy‐2‐butanone, log ±1(s−1) = (13.40 ± 0.20) – (202.8 ± 2.4) kJ/mol (2.303RT)−1; for 1,1,1‐trichloro‐2‐acetoxypropane, log ℜ1 (s−1) = (12.12 ± 0.50) – (193.7 ± 6.0) kJ/mol (2.303RT)−; for methyl 2‐acetoxypropionate, log ℜ1 (s−1) = (13.45 ± 0.05) – (209.5 ± 0.5) kJ/mol (2.303RT)−1; for 1‐chloro‐2‐acetoxypropane, log ℜ1 (s−1) = (12.95 ± 0.15) – (197.5 ± 1.8) kJ/mol (2.303RT)−1; for 1‐fluoro‐2‐acetoxypropane, log ℜ1 (s−1) = (12.83 ± 0.15)– (197.8 ± 1.8) kJ/mol (2.303RT)−1; for 1‐dimethylamino‐2‐acetoxypropane, log ℜ1 (s−1) = (12.66 ± 0.22) –(185.9 ± 2.5) kJ/mol (2.303RT)−1; for 1‐phenyl‐2‐acetoxypropane, log ℜ1 (s−1) = (12.53 ± 0.20) – (180.1 ± 2.3) kJ/mol (2.303RT)−1; and for 1‐phenyl−3−acetoxybutane, log ℜ1 (s−1) = (12.33 ± 0.25) – (179.8 ± 2.9) kJ/mol (2.303RT)−1. The CαO bond polarization appears to be the rate‐determining process in the transmition state of these pyrolysis reactions. Linear correlations of electron‐releasing and electron‐withdrawing groups along strong σ bonds have been projected and discussed. The present work may provide a general view on the effect of alkyl and polar substituents at the CαO bond in the gas‐phase elimination of secondary acetates.

Amino-Claisen rearrangement. III. The effects of alkyl substituents on the allyl group upon the rearrangement.

The effects of mono- and dimethylation of the allyl group upon tertiary and quaternary amino-Claisen rearrangements were investigated with 1, 2, 3, 4-tetrahydroquinoline as the framework for the rearrangement. The introduction of γ-methyl onto the allyl group accelerated the rearrangement and increased the yield of para rearrangement product. The introduction of two γ-methyls on the allyl group resulted in complex reactions, of which the major ones were para rearrangement and deprenylation. Two reaction pathways, sigmatropic and dissociative, were observed. The reaction conditions used strongly influenced the products pattern. The presence of a 6-methoxy group retarded the reaction but did not have a major effect upon the reaction pattern. Tertiary and quaternary N-Claisen rearrangements are effective for the migration of allyl and crotyl groups but seem not to be very useful for the migration of the prenyl group.

The Origin of Alkyl Substituent Effects on the Reactivity and Thermodynamic Stability of Alkenes. A Theoretical Study on Alkene Radical Cations

AbstractFully optimized STO‐3G SCF MO calculations were conducted on a series of methyl substituted ethylene radical cations. The stabilizing effect of a methyl group is found to be 14 kcal/mol using ethylene as a reference. Analysis of the orbital make‐up of the radical cations and their calculated geometry suggests that hyperconjugative 1‐, 2‐, and 3‐electron interactions between the alkyl groups and the π‐system is largely responsible for the stabilization. Analysis of hyperconjugation in propene suggests that 2‐electron stabilization outweighs 4‐electron destabilization energetically but that effects of the 2‐electron stabilization are manifested in a low‐lying MO (Φ1, Fig. 6).

Chemical and enzymatic oxidation of alkylated benzo[ a]pyrenes

The chemical and enzymatic oxidations of 6-, 7- and 10-methylbenzo[ a]pyrenes, 6,10- and 7,10-dimethylbenzo[ a]pyrenes and benzo[ a]pyrene (BP) itself have been investigated to study the effects of alkyl substitution on the pathways of oxidation. The chemical oxidizing systems employed were Fenton's reagent ( FeSO 4 H 2 O 2 ); trifluoroacetic acid-hydrogen peroxide (TFA/H 2O 2); thallium tristrifluoracetate in trifluoroacetic acid (TTFA/TFA) and H 2SO 4. The enzymatic systems were horseradish peroxidase (HRP/H 2O 2) and rat liver microsomes. The oxidations were investigated by electron paramagnetic resonance (EPR) spectroscopy to detect radical intermediates and by high performance liquid chromatography (HPLC) to separate the products. All the compounds studied produced radicals, identified as cationic species, in both H 2SO 4 and TTFA/TFA. In addition the 7-methyl-, 10-methyl- and 7,10-dimethyl-BP's produced 6-oxy radicals in some or all of the remaining oxidizing systems. Both chemically and enzymatically these same three compounds were observed to produce quinones as stable products. Microsomal oxidations gave the broadest range of products exhibiting HPLC peaks in the diol, quinone and phenol regions of the chromatograms, however, there were considerable differences between products from the individual derivatives and those from the parent molecule. 6-Methyl and 6,10-dimethyl-BP's showed no evidence of oxy radical intermediates or quinones under any set of conditions, the 6-substituent effectively blocking this oxidation pathway. The observations are consistent with the expected effects of alkyl substituents at particular positions and indicate that studies such as this one are potentially useful in better understanding oxidation and possible activation pathways of polycyclic aromatic hydrocarbons.

Conformational study of anticholinesterase carbamates in the furylbenzene series by 1H and 13C NMR spectroscopy

AbstractThe structural analysis of carbamates derived from 2‐(α‐furyl)benzaldoximes and 2‐(α‐furyl)benzyl alcohols was carried out by 1H and 13C NMR spectroscopy. The conjugative and steric effects of alkyl substituents introduced on the benzene rings were found to modify the relative orientation of the aromatic and furan rings. The existence of a close relationship between the stereochemistry of the studied compounds and their anticholinesterase activity has been proposed.

On the nature of haloform–aromatic complexes

AbstractA study of the correlation of haloform proton solvent shifts in 13 aromatichydrocarbons gives clear evidence that the nature of the interactions is predominantly dipole‐induced dipole and not specific acid‐base interactions. The presence of halogen bonding interactions between the halogen atoms and the π electrons are not detected for CHCl3 and CHBr3, and can only be present to a marginal extent for CHI3. The ASIS effect is not related to the molar concentration of the aromatic solvents, and the effect of alkyl substituents is explained in terms of exctuded zones around the aromatic ring.