Ortho-methyl Substituent Research Articles

Stereoelectronic Effects and Gas-phase Affinities of Dicoordinated Borinium Cations

The relative affinities of the borinium cations (CH 3 O) 2 B + and CH 3 OB + H towards pyridines were determined by the kinetic method using a pentaquadrupole mass spectrometer and the absolute affinities of these ions towards pyridine itself were estimated with the aid of ab initio calculations at the MP2/6-31G(d,p)//6-31G(d,p) level to be 75.7 and 82.2 kcal mol -l , respectively (1 kcal = 4.184 kJ). The affinities were found to correlate linearly with the proton affinities of the meta- and para-substituted pyridines, but steric effects decrease the affinities for ortho-substituted pyridines. A set of gas-phase stereoelectronic parameters (s k ) for these isomers was measured from the deviation of the value of the logarithm of the experimentally measured ion abundance ratio from the regression line established for meta- and para-substituted pyridines. The S k value of 2,6-dimethylpyridine with (CH 3 O) 2 B + is smaller than that for other dimethylpyridines, owing to the stabilizing effects of auxiliary hydrogen bonding interactions between one hydrogen of each of the ortho-methyl substituents and the two oxygens of the (CH 3 0) 2 B + ion. The dimethoxy boron cation (CH 3 O) 2 B + is shown to have smaller steric effects than CH 3 OB + H, even though the former ion has two bulky methoxy groups. This is ascribed to the relatively longer B-N bond in (CH 3 O) 2 B + -Py as a result of reduced charge density on the boron atom due to resonance stabilization within the dimethoxy boron cation.

Stereoelectronic Effects and Gasphase Affinities of Dicoordinated Borinium Cations

The relative affinities of the borinium cations (CH3O)2B+ and CH3OB+H towards pyridines were determined by the kinetic method using a pentaquadrupole mass spectrometer and the absolute affinities of these ions towards pyridine itself were estimated with the aid of ab initio calculations at the MP2/6–31G(d,p)//6–31G(d,p) level to be 75.7 and 82.2 kcal mol-1, respectively (1 kcal=4.184 kJ). The affinities were found to correlate linearly with the proton affinities of the meta- and para-substituted pyridines, but steric effects decrease the affinities for ortho-substituted pyridines. A set of gas-phase stereoelectronic parameters (Sk) for these isomers was measured from the deviation of the value of the logarithm of the experimentally measured ion abundance ratio from the regression line established for meta- and para-substituted pyridines. The Sk value of 2,6-dimethylpyridine with (CH3O)2B+ is smaller than that for other dimethylpyridines, owing to the stabilizing effects of auxiliary hydrogen bonding interactions between one hydrogen of each of the ortho-methyl substituents and the two oxygens of the (CH3O)2B+ ion. The dimethoxy boron cation (CH3O)2B+ is shown to have smaller steric effects than CH3OB+H, even though the former ion has two bulky methoxy groups. This is ascribed to the relatively longer B—N bond in (CH3O)2B+—Py as a result of reduced charge density on the boron atom due to resonance stabilization within the dimethoxy boron cation. © 1997 by John Wiley & Sons, Ltd.

Sulfur trifluoride cation (SF 3+) affinities of pyridines determined by the kinetic method: Stereoelectronic effects in the gas phase

Ion/molecule reactions performed by pentaquadrupole mass spectrometry are used to generate cluster ions in which neutral pyridines are bound to the polyatomic cation SF3+. The dimeric ions Py1SF3+Py2, where Py1 and Py2 represent substituted pyridines, are shown to have loosely bound structures by collision-induced dissociation (MS3) experiments and by semiempirical AMI and ab initio RHF/6-31G(d, p) molecular orbital calculations. In the case of dimers comprised of meta- and/or para-substituted pyridines (unhindered pyridines), there is an excellent linear correlation between the logarithm of the fragment ion abundance ratio ln[Py1(SF3+)]/[Py(SF3+)] and the proton affinities (PA) of the constituent pyridines. Semiempirical calculations are used to estimate the SF3+ affinities of pyridines which are found to be in the range of 25–31 kcal/mol. The SF3+ affinities show an excellent linear correlation with the proton affinities of the pyridines, and the relationship SF3+ affinity (kcal/mol) = 0. 73PA — 135. 8 between the two affinities is derived. The effective temperature of the dimeric ions is determined to be 595 ± 69 K, which is in good agreement with values of around 600 K obtained experimentally in studies on many other systems activated under similar conditions. Ortho-substituted pyridines show lower than expected affinities due to stereoelectronic effects that decrease the cation affinities. Gas-phase Stereoelectronic parameters (Sk) are measured from the deviation from the PA correlation and are ordered as 2-MePy (−1.09) < 2,6-diMePy (−1.11) < 2-EtPy (−1.91) < 2,3-diMePy (−2. 15) < 2,5-diMePy (− 2. 25) < 2,4-diMePy (− 2. 40). Overall, the steric effects are larger than those in the corresponding Cl+-bound dimers but smaller than those in the bulky [OCNCO+] system. Calculations show evidence for agostic bonding that offsets the steric effects in some cases. The eclipsed conformation of 2-methylpyridine/SF3+ adduct is found to be more stable than the staggered form by 0. 8 kcal/mol, due to auxiliary agostic bonding between the hydrogen of the ortho methyl substituent and the sulfur atom. Calculations on atomic charge distribution reveal that the positive charge is mainly on the sulfur atom (+1. 99) and the charge on the bonding hydrogen S-H-C (+ 0. 07) is considerably lower than that on the other two methyl hydrogens ( + 0. 14), which appears to be a good indication of agostic binding. The most stable form of the 2-ethylpyridine/SF3+ adduct is found when the N-C1-Cα-Cβ dihedral angle is approximately 60 °, where the ethyl hydrogen is directed toward the SF3 group via an interesting six-membered ring alignment. The experiments show a remarkably small steric effect in 2,6-dimethylpyridine, probably due to strong agostic bonding enhanced by the buttressing effect that shortens the S-H distance. In addition, the face-to-face interactions of the F atoms and the H atoms further stabilize this form.

Thermal Variation of the EPR Linewidth of new Phosphoniumyl Free Radicals for NMR Magnetometers

AbstractThe temperature dependence of the EPR linewidth of two phosphoniumyl radicals is investigated between 193K and 353K. The observed behaviour is interpreted through a simple model which assumes that the main contribution to the EPR linewidth arises from the anisotropic component of the large hyperfine coupling of the unpaired electron with the phosphorus nucleus. However the non resolved hyperfine coupling with the protons of the ortho methyl substituents is shown to contribute significantly to the broadening of the EPR linewidths in the high temperature range. The EPR features of the two radicals are discussed to evaluate their usefulness in low field NMR magnetometers.

Derivatographic investigations of polycarbonates

Derivatographic non-isothermal investigations of the decomposition of PC in air provide useful information on the characteristic decomposition temperatures and the apparent activation energies of the observed steps of decomposition. The following sequence of apparent activation energies of the pyrolysis step was obtained: PC-M>PC-C>PC-A. The values ofE for PC-M are the highest, due to shielding of the ester linkages by the ortho-methyl substituents.

Structural features in epoxy networks from N, N-diglycidyl epoxies and amines: 2. Ether ring formation and polymer structure in the reactions of N, N-diglycidylaniline with aniline and substituted anilines

Intramolecular ether cyclization occurs much more readily than previously recognized in the cure of N, N-diglycidyl epoxies with aromatic amines. Even at a modest reaction temperature of 120°C, the polymer from N, N-diglycidylaniline (DGA) and aniline was shown by 13C n.m.r. spectroscopy to contain morpholinyl and perhydro-1,4-oxazepinyl end groups which accounted for 6 and 4%, respectively, of consumed epoxy groups, whereas intramolecular amine cyclization to give the simple perhydro-1,5-diazocine isomers accounted for 19%. ortho-Methyl substituents in the amine had little steric influence on the extent of ether cyclization, but electronegative substituents had a very marked effect such that it was increased to 28% with 2,4,6-trichloroaniline and 26% with 3,5-bis(trifluoromethyl)aniline. The polymer from DGA and aniline was linear and had a completely random tacticity: variation of reaction temperature and reactant ratio led to only modest improvements in molecular weight (maximum value about 3000) because of the relative ease of chain termination by ether cylization. Two new thermal reactions of the polymer are proposed to explain n.m.r. spectral and g.p.c. data, a cleavage reaction to give secondary amine and tetrahydroquinolyl end groups, and water elimination from adjacent hydroxyl groups to form an in-chain morpholine ring. The reactions were surface- and temperature-dependent. Polymer degradation also occurred slowly in tetrahydrofuran solution at room temperature.

Reactivity of heterocyclic nitrogen donors in systems containing the tetrachloroaurate(III) anion

A series of gold(III) complexes of the type [AuCl3(L)] has been prepared and characterised (L = oxazole, benzoxazole, thiazole, their benzo and methyl-substituted derivatives, or 2-methylbenzoselenazole). The five-membered N,O- N,S- and N,Se-heterocyclic bases are all bound to AuIII through nitrogen. The kinetics of the displacement of L by chloride to give [AuCl4]– has been studied in methanol–water (95:5, v/v) at 25.0°C and I= 0.20 mol dm–3(LiClO4). The equilibrium constants for the reversible processes have also been determined. The reactions of the corresponding pyridine, 4-chloro-, 4-cyano- and 2,6-bis(chloromethyl)-pyridine complexes have also been reexamined under the same conditions. The equilibrium constants, K2, depend upon the basicity of the nitrogen in the ligands and points for all ligands, irrespective of ring size and composition, lie roughly on the same log K2versus pKa curve. There is no significant systematic steric effect on the equilibrium constants of the sort found for the more basic methyl pyridines. The complexes of the five-membered heterocyclic ligands are approximately ten times less reactive than those of the six-membered N-heterocycles of comparable basicity and exhibit steric retardation from ortho-methyl substituents. The nucleophilicities of these ligands have been calculated and five-membered N,O- and N,S-heterocycles are considerably less reactive than six-membered N-heterocycles of similar basicity.

The fluxional behaviour of hexaphenylbenzene chromium tricarbonyl: A variable-temperature 13C NMR spectroscopic study

The 125 MHz 13C NMR spectrum of (C 6Ph 6)Cr(CO) 3 reveals that the metal is π-bonded to a peripheral ring. At −80°C this chromium-bonded phenyl exhibits slowed rotation on the NMR time-scale and is effectively orthogonal to the central ring. The fluxional process is shown to involve rotation of the Cr(CO) 3-complexed phenyl ring; the activation energy barrier is ≈ 12.2 kcal mol −1, a value much lower than those previously reported for non-complexed hexa-aryl benzenes bearing ortho or meta methyl or methoxy substituents.

Electron impact mass spectrometry of some 2,11‐diaza[3.3]cyclophane derivatives

AbstractThe most significant mass spectral features of thirteen title compounds are discussed with the aid of high‐resolution mass measurements and metastable peak analysis. The decomposition patterns of the compounds investigated are strongly affected by N‐substitution and by methyl substituents ortho to the bridging chains (ortho effects). A unique feature connected with symmetrical macrocycles, bearing at least two ortho methyl substituents on each phenyl ring, is the presence in their spectra of diagnostically important peaks, corresponding to [M  RNH2]+˙ and [M  2RNH2]+˙ (R = Ts, H, CH3). These daughter ions are proposed to be associated with the formation of cage compounds (multibridged cyclophanes), generated by an intramolecular [4 + 4] cycloaddition reaction of unstable linear bis‐(o‐xylylene) precursors.

ChemInform Abstract: Influence of ortho Methyl and Isopropyl Substituents on the Reactivity of N‐t‐Butyl P‐Arylphosphonamidic Chlorides with Isopropylamine and t‐Butylamine: Steric Acceleration of Metaphosphonimidate Formation by an Elimination‐Addition Mechanism; Contrasting Behavior of N,N‐Dimethyl P‐Arylphosphonamidic Chlorides.

AbstractTwo types of arylphosphonamidic chloride (III) and (IV) are prepared, mostly from the dichlorides (II).

Influence of ortho methyl and isopropyl substituents on the reactivity of N-t-butyl P-arylphosphonamidic chlorides with isopropylamine and t-butylamine: steric acceleration of metaphosphonimidate formation by an elimination addition mechanism; contrasting behaviour of N,N-dimethyl P-arylphosphonamidic chlorides

The two types of phosphonamidic chloride ArP(O)(Cl)NMe2(5) and ArP(O)(Cl)NHBut(7) have been prepared with Ar = Ph, o-MeC6H4, 2,4,6-Me3C6H2, and 2,4,6-Pri3C6H2. Both types give the expected phosphonic diamide substitution products with PriNH2 and ButNH2 in MeCN, but the two types display contrasting reactivity. With ButNH2 the NMe2 substrates (5) become progressively less reactive as the degree of steric crowding increases, and although the decrease is quite small (70-fold overall) it seems consistent with an associative [SN2(P)] mechanism. These substrates react 100 times faster with PriNH2, than with ButNH2 and in PriNH2–ButNH2 competitive experiments they give almost exclusively (99%) the product derived from the less hindered PriNH2. For the NHBut substrates (7) with ButNH2, there is little difference in reactivity between the Ph and o-MeC6H4 compounds, and between the 2,4,6-Me3C6H2 and 2,4,6-Pri3C6H2 compounds, but remarkably the more crowded pair of substrates is the more reactive, by a factor of ca. 100. Also, in competitive experiments these substrates display relatively little preference for reaction with PriNH2. Here a dissociative eliminationaddition mechanism, with a metaphosphonimidate intermediate, is seen to be important. A possible explanation of the steric acceleration is advanced. The ability of (7; Ar = Ph) to undergo substitution by elimination–addition makes possible the phosphonylation of unreactive nucleophiles such as ButOH and Pri2NH under mild conditions.

Structure and reactions of 4-(2,4,6-trimethyl)benzylidene-2-phenyloxazolin-5-one

The crystal structure of 4-(2,4,6-trimethyl)benzylidene-2-phenyloxazolin-5-one has been determined. Crystals of C19H17NO2, fw 291.35, are monoclinic, P21/c, a = 10.207(2), b = 8.977(2), c = 17.123(4) Å, β = 92.66(1)°. For 2435 observed independent reflections the final R = 0.039 and Rw = 0.042. The molecule has Z configuration about the exocyclic double bond, and the benzylidene ring is twisted 61.3° out of the oxazoline ring plane, thus relieving the overcrowding caused by the two ortho-methyl substituents. The reaction of this compound with benzylamine in acetonitrile occurs almost four times as fast as predicted using model reactions.

Mutagens and carcinogens formed during cooking.

In the late 1970s, Sugimura et al. (1977; 1983; 1986) noted that powerful mutagens were produced during flame or charcoal broiling of fish or meat. This observation started a new field of research in nutritional carcinogenesis. The mutagens were eventually identified as heterocyclic aromatic compounds with an exocyclic amino group and often an ortho-methyl group. The structure of the food mutagen 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) (I) mimicks that of the synthetic chemical 3,2’-dimethyl-4aminobiphenyl (DMAB) (II), a carcinogen for the colon, breast, and prostate (Figure 1). IQ contains both the quinoline ring system and the primary amine with an ortho-methyl substituent, which characterizes DMAB. Recent tests (Sugimura, 1985) show that the mutagens in this newly discovered class of mutagens, including IQ itself along with other IQ-type compounds, are potent carcinogens and deserve consideration as candidates for the genotoxic carcinogens implicated as the possible causative factors of the nutritionally-linked cancers (Weisburger and Horn, 1982). The key elements underlying this area will be described.KeywordsMammary GlandHeterocyclic AmineGenotoxic CarcinogenHeterocyclic Aromatic CompoundIslet Cell AdenomaThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Stabilities of Carbonium-Ions. IV. Steric Effects in the Solvolysis of Substituted Diphenylmethyl Chlorides

The replacement of ortho-hydrogen atoms by methyl groups in diphenylmethyl chloride has three distinguishable results upon the rate of solvolysis . Firstly, the alkyl groupactivates by its electronic effect; secondly, steric interactions diminish all observed substituent effects regardless of the position of the substituent in the aryl system; and thirdly, steric acceleration of the solvolysis can be seen in the rate of reaction of bis (2,6-dimethylphenyl)methyl chloride. The ortho-methyl substituents inhibit the formation of the planar transition state necessary to allow the greatest resonance stabilization by the aryl substituents of the incipient carbocation. Greater degrees of twist are reflected both in the variations in the rates of solvolysis of the poly(orthomethyl ) diphenylmethyl chlorides and in the consistent fall in the value of p+ with successive ortho-substitution.

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.

An X-Ray Analysis on Restricted Rotational Isomers of 2-Thioxo-4-oxazolidinone

Abstract The thermodynamically more stable diastereomeric rotational isomer I, of 3-(o-tolyl)-5-methyl-2-thioxo-4-oxazolidinone, which is first crystallized out in solution, shows that the ortho methyl substituent is cisoid to the methyl group of the hetero ring, and the thermodynamically less stable isomer II, crystallized later, has both methyl groups in transoid conformation, as is found in X-ray studies. The carbonyl and thiocarbonyl bonds are found to be longer in isomer II than in isomer I, which is attributed to the favored conjugation interaction of carbonyl, thiocarbonyl groups with the lone pair electrons of nitrogen, that may cause the lessened stability of isomer II.

Steric and electronic control of the dissociative hydrolysis of 4-hydroxybenzoate esters

The introduction of two ortho methyl substituents changes the propensity of 4-hydroxybenzoates to react via the oxo-ketene pathway by nearly one million-fold; the increased reactivity of the hindered conjugate base over that of the parent is assigned to enhanced internal nucleophilicity of the 4-oxyanion.

Effects of ortho-methyl substituents on the mutagenicity of aminobiphenyls and aminonaphthalenes

A series of aminobiphenyls and aminonaphthalenes were assayed for mutagenicity toward S. typhimurium, in the presence of rat liver 9000 g supernatant, to investigate the effects of positional isomerism and ortho-methyl substitution. Among the 3 possible aminobiphenyl isomers, only 4-aminobiphenyl was a potent mutagen, showing activity in S. typhimurium TA1538 and TA100, but not TA1535. 4-Amino-3-methylbiphenyl was a more potent mutagen in S. typhimurium TA1538 than was 4-aminobiphenyl, whereas both 3-amino-4-methylbiphenyl and 3-aminobiphenyl were inactive in this strain. 3-Amino-4-methylbiphenyl was mutagenic in S. typhimurium TA100, in contrast to 3-aminobiphenyl. These results demonstrate the enhancing effect of an ortho-methyl group on mutagenicity in the aminobiphenyls, which contrasts to the inhibitory effect of methyl substitution frequently observed in the 4-nitrobiphenyl system. Among the 2-aminonaphthalenes, 2-amino-3-methylnaphthalene was the most mutagenic compound in S. typhimurium TA1538, followed by 2-amino-1-methylnaphthalene and 2-aminonaphthalene. In S. typhimurium TA1535, however, 2-aminonaphthalene was a more potent mutagen than either of the ortho-methyl substituted derivatives. No significant mutagenic activity was observed for either 1-aminonaphthalene or 1-amino-2-methylnaphthalene in S. typhimurium TA1538 and TA1535. However, 1-aminonaphthalene was weakly mutagenic in S. typhimurium TA 100.

The loss of ortho halogeno substituents from substituted thiobenzamide ions

AbstractThe loss of ortho substituents (CH3, Cl, Br, I) from molecular ions of substituted thiobenzamides has been investigated by determination of the critical energy and kinetic energy released during this process to obtain some further insight into the corresponding reaction of N,N‐dimethylthiobenzamide ions. In contrast to the latter compounds the ortho methyl substituent is not eliminated from the molecular ions of o‐methylthiobenzamide, but the loss of ortho halogeno substituents occurs with identical reaction characteristics in both series of compounds. It is concluded that the loss of halogeno substituents from molecular ions in both series corresponds to a direct substitution reaction via a 4‐membered transition state.

Hydrolysis of diarylphosphinic amides in acidic solution: steric inhibition and mechanism

The pseudo-first-order rate constants for the hydrolysis of diphenylphosphinic amide Ph2P(O)NH2 and its di-p-tolyl, di-o-tolyl, and dimesityl analogues (106kψ 3 630, 2 340, 81.0, and 3.27 s–1 respectively with H+ 0.0662M and T 30.2 °C) in water–dioxan (9 : 1 v/v) containing perchloric acid show that reaction is sterically hindered by ortho-methyl substituents in the P-aryl groups. Steric inhibition is as great, or greater, in the hydrolysis of the corresponding (N-phenyl)diarylphosphinic amides (106kψ 5 440, 4 470, 54.9, and 0.88 s–1 respectively with H+ 1.36M and T 39.9 °C) and (N-p-nitrophenyl)diarylphosphinic amides (106kψ 724, 702, 6.57, and 0.098 s–1 respectively with H+ 2.58M and T 39.9 °C) even though the departing amine is less nucleophilic. Such sensitivity to steric hindrance is consistent with associative (A2) mechanisms for the hydrolysis of all the substrates.