Meta-substituted Derivatives Research Articles

Metathesis copolymerization of norbornene with phenylacetylene and its ring-substituted derivatives catalysed by WCl 6: 2. Reactivity of monomers

Effects of ring substituents of phenylacetylene (PA) were studied in the metathesis copolymerization of norbornene (NBE) with PA catalysed by WCl 6. The shape of copolymer composition curves indicated the formation of random copolymers in the copolymerizations of NBE with PA and its para- or meta-substituted derivatives. The more electron-withdrawing the substituent, the less reactive the PA; the Hammett plot of these systems gave a straight line with a negative slope ( ϱ = −1.1). In contrast, some composition curves for the copolymerizations of NBE with ortho-substituted PAs were sigmoidal. This difference is explained in terms of the steric hindrance of ortho-substituents, i.e. the propagation reaction between the ortho-substituted PA end and the NBE monomer seems sterically difficult.

Nucleophilic substitution at a trigonal carbon. Part 5. Substituent effects in the reactions of aromatic acyl bromides with methanol in acetonitrile

The kinetics of the methanolysis of benzoyl bromide and eight para- or meta-substituted derivatives in acetonitrile at 25.0 °C can be analysed in terms of the simultaneous operation of overall second- and third-order processes. In turn, each of these processes can be analysed in terms of the simultaneous operation of two reaction channels, which are proposed to involve a carbonyl addition–elimination mechanism (favoured for electron-withdrawing substituents) and a process (SN2–SN1) proceeding through a loose SN2-type transition state. For the p-methoxybenzoyl bromide substrate, a third reaction channel is observed, but only for the overall second-order process (first-order in methanol), and this is tentatively described as involving electrophilic assistance by a methanol molecule to an ionization (SN1) pathway.

Samarium diiodide / hexamethylphosphoramide promoted dimerization of benzaldehydes

Benzaldehyde, its ortho- and meta-substituted derivatives and acetophenone underwent dimerization reactions on treatment with samarium(II) iodide in the presence of HMPA. Intramolecular phenyl-carbonyl coupling reactions were similarly carried out.

Reactions of polyfluoroalkylsulfenyl chlorides with phenols

Polyfluoroalkylsulfenyl chlorides thiolate phenol and its ortho- and meta-substituted derivatives regiospecifically at the para-position in the absence of a catalyst and of a hydrogen chloride acceptor. Ortho thiolation occurs with significantly greater difficulty in the para-substituted phenols, and is only possible with the strong electron-donor properties of the substituent. Polyfluoroalkylthiolation of phenols is rendered more difficult with the increase in the steric impediments at the sulfur atom of the sulfenyl chloride and the volume of the substituents by the OH group of the phenol.

Addition and lithiation reactions of N-(1-phenylalkylidene)anilines with lithium dialkylamides

Lithium diisopropylamide undergoes an addition reaction to the methyleneamino moiety of the title Schiff's bases substituted with a cyano group at the ortho or para position of the aniline, but mediates tautomerization of the unsubstituted and meta-substituted derivatives into secondary enamines. Only the tautomerization is observed for lithium 2,2,6,6-tetramethylpiperidide-mediated reactions.

Electron reorganization induced by intramolecular hydrogen bonding in phenol derivatives: relationship between proton chemical shifts and the hydroxylic electron populations

Intramolecular hydrogen-bonding effects in ortho-substituted phenols have been studied by 1H n.m.r. and i.r. spectroscopy and CNDO/2 calculations. Full geometry optimization using the CNDO/2 method indicates definite variations of the OH bond length in intramolecular hydrogen-bonded phenols whereas these lengths remain nearly constant in para- or meta-substituted derivatives. There is a good linear relationship between the OH bond length and the i.r. νOH frequency shift, considered as reflecting the intramolecular association strength. Comparison of ortho- and para-substituted phenols shows that intramolecular hydrogen-bond formation induces important δ electron transfer from the substituent X to the hydroxylic oxygen via the bonded hydrogen atom whereas the electron population of this hydrogen atom decreases. This transfer results in π-electron reorganization of the X–C(1)–C(2)–OH fragment, and thereby increases the electron-releasing character of the OH group and the electron-withdrawing power of acceptor X groups, but the remaining atoms of the ring are little affected. With such an unusual electron reorganization, the chemical shifts of the phenolic hydrogen in ortho-, meta-, and para-substituted phenols can be simultaneously correlated with the electron population only if we consider both the proton investigated and the oxygen atom bearing it. The correlation Δδ=–31.6ΔqHM+ 16.1ΔQσO+ 0.08 satisfactorily reflects the proton shifts for the 22 compounds investigated.

195Pt, 119Sn and 31P NMR studies of alkyl, aryl and acyl trichlorostannate complexes of platinum(II). The crystal structure of trans-[Pt(SnCl 3)(COC 6H 5)(PEt 3) 2

195Pt, 119Sn and 31P NMR characteristics of the complexes trans-[Pt(SnCl 3)(carbon ligand)(PEt 3) 2] ( 1a- 1e) are reported, (carbon ligand = CH 3 ( 1a), CH 2Ph ( 1b), COPh ( 1c), C 6Cl 5 ( 1d), C 6Cl 4Y ( e); Y = meta- and para-NO 2, CF 3, Br, H, CH 3, OCH 3, or Pt(SnCl 3)(PEt 3) 2. The values of 1 J( 195Pt, 119Sn) vary from 2376 to 11895 Hz with the COPh ligand having the smallest and the C 6Cl 5 ligand the largest value, making a total range for this coupling constant, when the dimer syn- trans-[PtCl(SnCl 3)(PEt 3)] 2 is included, of ca. 33000 Hz. In the meta- and para-substituted phenyl complexes 1 J( 195Pt, 119Sn) (a) is greater for electron-withdrawing substituents, (b) varies more for the meta-substituted derivatives (5634 to 7906 Hz) than for the para analogues (6088 to 7644 Hz) and (c) has the lowest values when the Pt(SnCl 3)(PEt 3) 2 group is the meta- or para-substituent. The direction of the change in 1 J( 195Pt, 119Sn) is opposite to that found for 1 J( 195Pt, 119P). For the aryl complexes linear correlations are observed between δ( 119Sn), 1 J( 195Pt, 119Sn), 1 J( 195Pt, 31P), 1 J( 119Sn, 31P) and the Hammett substituent constant σ n . δ( 119Sn) and 1 J( 195Pt, 119Sn) are related linearly to v(Pt-H) in the complexes trans-[PtH(C 6H 4Y)(PEt 3) 2]; δ( 119Sn) and δ( 1H) (hydride) are also linearly related. Based on 1 J( 195Pt, 119Sn), the acyl ligand is suggested to have a very large NMR trans influence. The differences in the NMR parameters for ( 1a-e) are rationalized in terms of differing σ- and π-bonding abilities of the carbon ligands. The structure of 1c has been determined by crystallographic methods. The complex has a slightly distorted square planar geometry with trans-PEt 3 ligands. Relevant bond lengths (Å) and bond angles (°) are: PtSn, 2.634(1), PtP, 2.324(4) and 2.329(4), PtC, 2.05(1); PPtP, 170.7(6), SnPtC, 173.0(3), SnPtP, 92.1(1), 91.7(1), PPtC, 88.8(4) and 88.3(4). The PtSn bond separation is the longest yet observed for square-planar platinum trichlorostannate complexes, and would be consistent with a large crystallographic trans influence of the benzoyl ligand. The PtSn bond separation is shown to correlate with 1 J( 195Pt, 119Sn).

Fungicidal action and structure correlation of monosubstituted phenyl isothiocyanates.

The fungicidal activity of 10 monosubstituted phenyl isothiocyanates was observed with four plant pathogens. The ortho- and meta-substituted derivatives possessed a fair activity while the para-substituted ones proved to be highly fungicidal when compared to the control Agrosan GN.

ChemInform Abstract: (IMIDAZOLYLPHENYL)FORMAMIDINES. A STRUCTURALLY NOVEL CLASS OF POTENT HISTAMINE H2 RECEPTOR ANTAGONISTS

AbstractAus den Imidazolen (I) erhält man über die Cyanamidine (II) die Amidine (III).

(Imidazolylphenyl)formamidines. A structurally novel class of potent histamine H2 receptor antagonists.

Structure-activity considerations of N alpha-guanylhistamine, the first compound found with detectable H2-antagonist activity, led to the synthesis of a series of conformationally rigid guanylhistamine analogues, namely, (imidazolylphenyl)guanidines, imidazolylbenzamidines, and (imidazolylphenyl)formamidines. It was found that in the guanidine and benzamidine classes, the meta-substituted derivatives (3, 4, 7, and 8) possessed H2-antagonist activity, whereas in the class of formamidines, only the para-substituted derivative 10 was found active. A subsequent increase in the size of the substituent at the formamidino group of 10 led to compounds (15-20) of high H2-antagonist affinity, which was related to the gastric antisecretory effect. Members of this structurally novel class of H2 antagonists were 20- to 50-fold more potent than cimetidine both "in vitro" and "in vivo". Structure-activity relationships are discussed in terms of ionization properties, partitioning behavior, conformational aspects of the selected compound 17, and of possible modes of interaction with the histamine H2 receptor. It was found that the formamidine moiety was an important structural feature and that H2-antagonist activity requires correct steric and electronic properties. Compound 17 (DA 4577), owing to its pharmacological profile and demonstrated safety in animals, was selected to be clinically investigated.

Substituent–substituent interactions in carbon-13 substituent chemical shifts of phenols and phenoxides

The non-additive behaviour of 13C shifts observed for 4-X-substituted phenols or phenoxides are evidence for large substituent–substituent interactions (up to 5 p.p.m.;i.e., 75% of the substituent shifts observed in monosubstituted benzenes). X-Induced para-substituent shifts on C(1) are analysed by non-linear Dual Substituent Parameter correlations or by proportionality relationships with the corresponding shifts in monosubstituted benzenes (provided that for phenoxides electron donor or acceptor groups are treated separately). Similar proportionality relationships are also established for ipso SCSs [on C(4)]. Extension of this data treatment to various families of para-substituted benzenes leads to a general approach to the effect of substituent interactions on SCS values. In the factorisation model proposed, deviations from additivity are expressed via the product of ipso and para-SCS values, derived from the corresponding monosubstituted benzenes. The strict additivity of SCS values in meta-substituted derivatives is obeyed for phenols, whereas for phenoxides minute substituent–substituent interactions are observed.

Formation of arenediazonium ion in oxidation of N,N-dimethyl-4-aminobenzene and some meta-substituted derivatives with cerium(IV) ion in acid medium

Oxidation has been studied of an experimental hepatocarcinogene N,N-dimethyl-4-aminoazobenzene and some its meta-substituted derivatives with cerium(IV) ion in 1M hydrochloric acid medium with potentiometric indication. It has been possible to prove formation of more than 50 per cent arenediazonium ion and N,N-dimethylbenzoquinonimine besides the known metabolites. Furthermore, five meta-substituted derivatives of N,N-dimethyl-4-aminoazobenzene have been studied, and the amount of the arenediazonium ion formed has been found to depend critically on character of the 3'-substituent.

Structure-activity studies on nifedipine in isolated cardiac muscle.

1. The effects on contractile activity of 2 series of nifedipine-derivatives were investigated in isolated, isotonically contracting cat papillary muscles. 2. For structure-activity studies the lipophilicity of all compounds was determined by means of reversed phase thin-layer chromatography. 3. Neither the ortho-NO2 group in a series of arylderivatives nor the methyl-esters in a series of esterderivatives were found to be essential for the typical effect of the nifedipine molecule on myocardial contractility. 4. Generally ortho-substituted derivatives induce a greater negative inotropic activity than meta-substituted derivatives. Para-substituted derivatives are the least active compounds. 5. In the group of ester-derivatives activity decreases when lipophilicity and/or volume of the substituent increases. 6. The quantitative analysis (Hansch analysis) revealed significant correlations between the negative inotropic effect and steric substituent parameters. Best correlations were obtained with:

Reactivity of vinyl sulphonic esters. Part X. Effect of the substituents on the cyclisation of arylthiovinyl sulphonates to benzo[b]thiophens

Cyclisation of either meta- and para-phenylsulphonyl-substituted 2-arylthio-1,2-diphenylvinyl 2,4,6-trinitro-benzenesulphonate in dichloromethane with boron trifluoride as catalyst affords 2,3-diphenyl-5-phenylsulphonyl-benzo[b]thiophen. The position of the substituent in the product indicates that a rearrangement occurs in the cyclisation of the meta-substituted derivative, whereas with the para-derivative the position of the substituent in respect to the sulphur atom is retained. The results are discussed in terms of the meta-directing effect of the phenylsulphonyl-group. A close connection is found with the cyclisation of vinyl sulphonates having ortho,para-directing substituents in the arylthio-residue.

Cis–trans Equilibrium in meta-chlorophenyl aldehydes, ethers, ketones, and carboxylic esters from dipole moment studies

Comparison of dipole moments of meta-chloro-, para-chloro-, and 3,5-dichloro-substituted compounds with parents enable the calculation of group dipole directions, of interaction moments, and of cis–trans conformational equilibria in the meta-substituted derivatives.

Reactivity of Monochlorobenzene and Its Derivatives toward Solvated Electrons in Lower Aliphatic Alcohols

Monochlorobenzene and its para- or meta-substituted derivatives were irradiated with -γ-rays in methanol, ethanol and n-propanol containing nitrous oxide to elucidate the reactivities of these organic solutes toward solvated electrons, and also the effect of the substituent for the aromatic nucleus on the reactivities of these solutes. The value of G (N2) is seen to decrease with increasing concentration of the organic solute. Relative rate constants of these organic solutes toward solvated electrons have been determined from the competition with nitrous oxide by observing the G(N2) in there systems. Based on the results, the rate constants of the reactions of these derivatives of monochlorobenzene with solvated electrons relative to monochlorobenzene can be related to Hammett's σ function. The ρ value has been observed to be 3.3, 2.1 and 1.8 for methanol, ethanol and n-propanol respectively. The present data, together with that by Sherman(1) for 2-propanol, indicates that the ρ value is correlated linear...

The separation of polar and steric effects. Part X. Kinetics of the reactions of phenylacetic acid and meta- or para-substituted phenylacetic acids with diazodiphenylmethane in various alcohols

Rate coefficients have been determined for the reactions at 30° of diazodiphenylmethane with phenylacetic acid and various meta- or para-substituted phenylacetic acids (substituents : m- or p-Me, p-F, m- or p-Cl, p-Br, p-l, or m- or p-NO2) in methanol, ethanol, propan-2-ol, 2-methylpropan-1-ol, 2-methylpropan-2-ol, and 2-methylbutan-2-ol. For phenylacetic acid and the meta-substituted derivatives rate coefficients have also been determined for the reactions in propan-1-ol, benzyl alcohol, and in 2-methoxyethanol. Log k0 and Hammett ρ-values have been calculated for the reactions in the nine solvents. The reactions of phenylacetic acid in butan-1-ol, butan-2-ol, dimethyl sulphoxide, and ethyl acetate have also been studied, and those of p-nitrophenylacetic acid in propan-1-ol and in benzyl alcohol.The reactions of phenylacetic acid with diazodiphenylmethane in ten of the alcohols show a good linear free-energy relationship with the corresponding reactions of benzoic acid. The solvent effect can be interpreted in terms of the effect of the dielectric constant, and the influence of hydrogen bonding. Multiple linear correlation of log k with groups of three suitable solvent parameters is shown to be quite successful.The Hammett ρ-values for the reactions of phenylacetic acids (ρ2) with diazodiphenylmethane in eight alcohols are related to the ρ-values for the corresponding reactions of benzoic acids (ρ1) by the equation ρ2= 0·68ρ1– 0·235. This expression is interpreted in terms of Bowden, Chapman, and Shorter's treatment of the transmission of polar effects through side-chains. The correlation of ρ with pairs of solvent parameters is also examined.The calculated Hammett σ-constants for the substituents in para-substituted phenylacetic acids, when the acids react with diazodiphenylmethane, show considerable variation with the polarity of the alcoholic solvent. Two possible interpretations of this are discussed.‘Internal’ linear free-energy relationships, i.e., those involving only log k for reactions of phenylacetic acid or substituted phenylacetic acids with diazodiphenylmethane, are examined. Also a careful examination of the kinetic order for certain reactions is presented; rate coefficients at 37·0° and 48·0° and Arrhenius parameters are also recorded for the reactions of selected phenylacetic acids with diazodiphenylmethane in some of the alcohols.

On the reactivity of organophosphorus compounds. Part III: Application of the Hammett relation to the rates of alkaline hydrolysis of a number of diethyl substituted phenyl phosphates

As part of our program on the reactivity of organophosphorus compounds in nucleophilic substitution reactions the rates of alkaline hydrolysis have been determined for a number of diethyl substituted phenyl phosphates (diethyl phenyl phosphate and eight ortho-, five meta- and thirteen para-nuclear-substituted derivatives). The following relationships were observed: — an excellent ϱσ correlation between the log kOH values of diethyl phenyl phosphate and four meta-substituted derivatives and the “primary” σ values of van Bekkum et al. for meta-substituents; — a satisfactory correlation between the log kOH values of some ortho-substituted compounds and Taft's σ* values for ortho-substituents. Calculated σ values have been compared with van Bekkum's σn values concluding very weak and no mesomeric para interactions for − M and + M substituents respectively.

CORRELATIONS BETWEEN ACIDITY OF SUBSTITUTED PHENYLAMIDES AND INHIBITION OF THE HILL REACTION.

Relative acidities of substituted phenylamides were determined by potentiometric titration with 0.1 N tetrabutylammonium hydroxide methoxide in n-butylamine and expressed as half-neutralization potentials (HNP). The HNP's were correlated with inhibitory potency expressed against the Hill reaction. Of the phenylamide families studied, i.e., phenylureas, N-phenylcarbamates, and acylanilides, the phenylureas were the most acidic. Within each family, increased acidity was correlated with increased inhibition for the unchlorinated, 3- or 4-monochloro-, and 3,4-dichloro-derivatives, respectively. A peak occurred in the activity-acidity curve for various meta-substituted derivatives of 2-propyl N-phenylcarbamate which may be related to an optimum charge on the imino nitrogen required for high inhibitory activity. Variations in length of the side chain did not markedly affect the HNP. Substitution of a hydroxyl group for the imino hydrogen, replacement of the carbonyl oxygen with a sulfur atom, and chlorination and/or unsaturation in the alkyl group increased acidity, but in general decreased inhibitory activity. A correlation between charge on the imino nitrogen and inhibition of the Hill reaction is apparent if consideration are restricted to a comparison of derivatives in which electronic rather than steric influences predominate. Steric influences are considered to control the fit, as well as the ease, with which the inhibitor approaches the active site. Electronic influences conceivably control chemical reactivity and binding of the inhibitor at the active center.

The formation of meta-substituted derivatives of benzene in the alkylation of aromatic hydrocarbons with unsaturated hydrocarbons

The formation of meta-substituted derivatives of benzene in the alkylation of aromatic hydrocarbons with unsaturated hydrocarbons