Carbon-13 chemical shifts of 3-substituted thietanes,thietane 1-oxides and thietane 1,1-dioxides

Carbon-13 chemical shifts of the α- and β-carbon atoms for 12 thietane 1,1-dixides, 9 thietane 1-oxides and 7 thietanes with a variety of 3-substituents [H, CH(CO₂Et)₂, SEt, Br, SPh, Ph, Cl, NMe₂, OH, OSiMe₃, OAc, OEt] are correlated according to the nature of the sulfur atom (Y=sulfone, sulfoxide, sulfide) and the nature of the 3-substituent (X) by the equations δ_α= a_Y+b_X and δ_β=a_X+b_Y, where a and b are parameters characteristic of X and Y. One-bond coupling constants [J(CH)] are reported for 21 compounds. The chemical shifts for the α- and the β-carbon atoms of the sulfones show the ‘fore-membered ring sulfone effect’ (α-carbon unusually deshielded, β-carbon unusually shielded), but the α-carbon-hydrogen coupling constants are similar to those of the sulfoxides and sulfides; the β-carbon-hydrogen coupling constants are sensitive to the nature of the substituent (X) but no special β-effect is observed. Comparison of the chemical shifts of the α-methylene carbon atoms of 3-phenyl-, 3-(β-naphthyl)- and 3-(α-thienyl)-thietes with those of the coresponding sulfones also reveals the ‘four-membered ring sulfone effect’ cis- and trans-3-Substituted thietane 1-oxides may be distinguished by the greater downfield shift for the β-carbon atom in the trans-isomer.     

Substituent effects in mass spectrometry: The correlation of the ionisation potentials of substituted benzenes with σp+

It is demonstrated that the ionisation potentials of mono- and di-substituted benzenes are related to the sum of Brown's σ_p⁺ of the substituents for both the meta and para isomers. From this it is concluded that the charge, in substituted arenes, lies predominantly on the aromatic ring rather than on either of the substituents. An empirical equation relating the IP's of mono- and disubstituted benzenes to the sum of σ_p⁺ is presented.     

13C NMR of organosulphur compounds: I—the effects of sulphur substituents on the 13C chemical shifts of alkyl chains and of S-heterocycles

The ¹³C NMR spectra have been determined of: (i) aliphatic compounds having at one end a functionalized sulphur atom (? SH, ? S^?, ? SMe, ? S(O)Me, ? SO₂Me and ? S⁺Me₂) and (ii) saturated sulphur heterocycles variously substituted at the S-atom . The results are discussed in terms of the familiar deshielding effects for α- and β-carbons and shielding effects for γ-carbons, exerted by the sulphur atom itself and/or by the atoms or groups of which the sulphur function is made up. The γ-effect of the S-atom appears to be nearly independent of the nature of the S-function and of comparable magnitude to that of an aliphatic carbon (?2·5 + ?3·0 ppm). Surprisingly, however, a S? CH₃ group shields the carbon in γ position with respect to CH₃ by an amount (?5·4 ppm) which is more than twice that (?2·5 ppm) exerted by the aliphatic γ-carbon on the S-CH₃ carbon itself. As to the cyclic compounds, the shieldings of the α- and β-carbons can be rationalized in terms of the conformational orientation of the substituent at sulphur, and the equilibrium distribution of the conformers. The results confirm the great value of ¹³C NMR for configurational and conformational assignment of S-heterocycles.     

13C chemical shift subsitituent parameters for alkyllithium compounds in hydrocarbon solvents

¹³C chemical shift substituent parameters are presented for carbons α, β, γ, and δ to the lithium atom based on the chemical shifts of 14 ⁶Li-enriched alkyllithium compounds. The chemical shift of the carbon α to lithium depends on the branching of alkyl group at the α-carbon and on the aggregation state of the alkyllithium compound. Increased branching results in increased upfield shifts. This is interpreted in terms of the varying electronic nature of the alkyllithium compounds. The chemical shift of the carbon β to lithium substitution is shifted downfield approximately 5 ppm from the corresponding carbon in the parent hydrocarbon, irregardless of the alkyl group or the aggregation state of the alkyllithium compound. The chemical shift of the γ-carbon depends on the steric requirements of the alkyl group. Carbons four or more bonds from lithium have the same chemical shift as those of the parent hydrocarbon. The derived chemical shift parameters are used to assign the α-carbons of two alkyllithium compounds formed from the reaction of t-butyllithium and trimethylvinylsilane.     

13C NMR study of some polychloro-isobutane and -isobutene compounds

The ¹³C chemical shifts and the carbon–proton coupling constants have been determined for some chlorinated isobutane and isobutene compounds. The one-bond coupling constants in isobutane derivatives showed a regular increase with an increasing number of γ-chlorine substituents. The three-bond coupling constant of the methyl carbon decreased from 4.2 to 2.0 Hz as the number of chlorine substituents in the γ-position increased. In the isobutene compounds, the vicinal coupling of C-1 was larger to protons in a group that is trans with respect to a chlorine substituent on C-1 than to those in the corresponding group cis to the chlorine. The vicinal coupling constants between atoms in geminal groups (on C-2) seem to be affected by the orientation of the chlorine substituent on C-1.     

Konformationsuntersuchungen mit Hilfe der 13C-NMR-Spektroskopie. III. 13C-NMR-spektroskopische Verschiebungen durch sterisch gehinderte Methylgruppen

The ¹³C NMR chemical shifts of some cyclohexane derivatives containing 1,3-diaxial methyl groups are assigned. The resonance signals of the methyl carbon atoms 1 and 3 in these compounds are shifted on average by 4.5 ppm to lower field (δ-effect). The ring carbon atoms 1 and 3 also show shifts to lower field, averaging 0.7 ppm (γ-effect). In open-chain hydrocarbons, analogous shift effects are observed when the investigated compounds have the geometry of the g^Pg^M conformer of n-pentane.     

Carbon-13 NMR spectra of polybromoalkanes and polychlorobromoalkanes. Structural increments of halogens in polyhalogenated groups

The ¹³C NMR spectra of 48 polychlorobromoalkanes have been studied. Unlike the ¹³C signals of chlorine-containing groups (38–105 ppm), those of bromine-containing fragments, with the exception of CBr₂ (60–70 ppm), appear in a rather narrow range (25–50 ppm) and are shifted to higher field in relation to similar chlorine-containing groups. The spin–spin coupling constants in similar bromine- and chlorine-containing groups practically coinciEN. Calculation of the chemical shifts for the polyhaloalkanes under study according to the additivity scheme, as previously observed for polychloroalkanes, renders values which are in considerable discord with experimental values (up to –32 ppm for CBr₃). These discrepancies may be compensated for by corrections for the binary interaction of halogen atoms by grouping the halogen-containing fragments according to the geminal, vicinal, 1,3-, 1,3,5- and 1,2,3-arrangement of halogen atoms, and by introducing an increment for the position of the halogen at the secondary atom. It is established that as compared to 1-monohaloalkanes: (a) in the case of the geminal arrangement of halogen atoms the α- and γ-effects diminish (Δ α from –3.2 to –8 ppm; Δγ = 2.6 ppm), while the β-effect increases slightly (from 0 to 1.2 ppm); (b) in the case of a vicinal arrangement both the α- and β-effects diminish (by about –3.5 ppm) and the γ-effect remains constant, as if the vicinal system of the halogens was topologically insulated; (c) for the 1,3- and 1,3,5-arrangement of halogens their mutual influence is weak (about –0.5 ppm for each halogen atom in the α- and γ-positions); (d) the 1,2,3 system (serial arrangement of halogen atoms) is the sum of two vicinal fragments and hardly deviates from the additivity scheme; (e) the arrangement of a halogen at the secondary C atom enhances the α-effect (Δα = 2.8 and 1.0 for methyl and methylene, respectively, in the case of Cl, and 3.5 and 3.7 ppm in the case of Br); the variation of the β-effect has a different sign in relation to CH₃ and CH₂ groups (+1.2 and –1.7 for Cl, and +2.5 and –1.0 for Br). More distant effects of halogens (δ and ?) were not considered. The determined increments (Δα, Δβ and Δγ) for the α-, β- and γ-effects of chlorine and bromine atoms allow the prediction of the 13^C chemical shifts in polyhaloalkanes with an accuracy up to ±1.5 ppm. Some deviations of up to ±5 ppm may be connected with the influence of a three particle interaction of halogen atoms, which was taken into account only in the case of a geminal arrangement of halogen atoms.     

Zur Kenntnis des Chinoiden Zustandes—XX: 13CMR-Untersuchungen an Cyclohexadienonen

The ¹³C-NMR-chemical shifts of 19 para- and 5 ortho-cyclohexadienones are determined by ¹³C-Fourier-transformation spectroscopy and assigned. The effect of substituents on the chemical shift of the ring carbon atoms is discussed. The mutual dependence of the shifts of the olefinic ring carbons and the allylic carbon atom in the para-quinolid ring system is shown by computing regression lines. A frequently observed correlation between ¹³C-NMR and ¹H-NMR is examined in the case of cyclohexadienones.     

Carbon-13 chemical shifts of monosubstituted cyclohexanes

The carbon-13 chemical shifts of monosubstituted cyclohexane derivatives are compared with those of aliphatic compounds. The polar substituents exert a similar influence on the α-, β- and γ-carbons in both series of compounds. The δ-effect is shown to be characteristic mainly to the cyclic compounds, however. The appearance of a δ-effect is discussed as a possible consequence of electron delocalization in alicyclic molecules. A correlation of these δ-effects with inductive parameters of the substituents is presented.     

13C NMR study on the methoxy carbon chemical shifts in chloro-substituted anisoles and guaiacols

The ¹³C NMR chemical shifts of methoxy carbons in chlorinated anisoles and guaiacols have been measured for acetone-d₆ solutions. Multiple linear regression analysis, and also ‘simple sum rule’ calculations, have been used to estimate the effects of the chlorine atoms (the position and degree of substitution) on the chemical shifts. The most important effects have shown to be due to the chlorine atoms adjacent to the methoxy and hydroxy substituents. For chlorinated guaiacols, the greatest effect is due to the chlorine atom adjacent to the methoxy group. For chlorinated anisoles, the substituents adjacent to the methoxy group (2,6-disubstitution) cause large effects. For both groups of compounds, the chemical shifts are also greatly influenced by the number of chlorine substituents. Using the three most important independent variables, the average differences between the observed and calculated chemical shifts are ca 0.2 ppm for anisoles and 0.1 ppm for guaiacols. For chloroguaiacols, the corresponding difference was only 0.1 ppm when calculations were performed using single substituent effects.     

13C NMR study of the enol forms of β-diketones

Carbon-13 NMR spectra of a series of β-diketones in the enol form with various β-substituents have been studied. An additive influence of the β-substituents on the chemical shifts of the carbon atoms in the hydrogen bonded chelate ring has been found. It is shown that the α- and β-carbon chemical shifts can be calculated by means of a set of increments for arbitrary combinations of the X and Y substituents. Analysis of the experimental data enables the conclusions to be drawn that enol–enolic tautomerism with different populations of the forms (A) and (B) is absent in β-diketones and that the carbon chemical shift changes are caused by electron density redistribution in the hydrogen bonded chelate ring (C).     

13C NMR studies of reduced porphyrin compounds. Aromatic delocalization pathways

¹³C NMR spectra of ms-tetraphenylchlorins, new aminoalkyl- and hydroxy-pyrroline substituted ms-tetra-phenylchlorins, and ms-tetraphenylisobacteriochlorins are presented and discussed. Significant changes in the chemical shifts of the α-pyrrole, α-pyrroline and meso skeletal carbons are found in chlorins and isobacteriochlorins in comparison to porphyrins. In contrast, the chemical shifts of the β-pyrrole carbons are almost unaffected by the structural modifications in chlorin and isobacteriochlorin. The chemical shifts of the α-pyrrole carbons in the various chlorins and isobacteriochlorins are strongly affected by the substitutents of the pyrroline ring, or by the introduction of an additional pyrroline ring in isobacteriochlorins. The results show that most of the electron density is concentrated in the unreduced part of the molecule, i.e. in the pyrrole rings and, especially, on the α-pyrrole carbons and is transferred or removed through the aromatic pathway by substituents on the pyrroline ring. These observations are supporting evidence that the α-pyrrole, α-pyrroline and meso-carbons are in the aromatic pathway and favour the proposal of a 16 atom dianion as the preferred delocalization pathway in chlorins and isobacteriochlorins.     

The effects of substituents on the 5J long-range spin-spin coupling constants in substituted benzaldehydes

Proton magnetic resonance spectra of several mono- and disubstituted benzaldehydes were studied using CW, INDOR and double resonance techniques. It was verified that substitution in the para position has no effect on the long-range coupling of the aldehydic proton with the ring protons five bonds away. Substitution in the ortho and meta positions (with the exception of 2,4-dinitrobenzaldehyde) follows closely the additivity rule effects of the substituents.     

Conformations and 13C NMR shifts in tetralins

Force field (MM2) calculations, ¹³C NMR substituent-induced shifts (SIS) and epimeric shift differences (ESD) indicate a preference for equatorial substituents in the 2-position, but equal eq/ax populations in the 1-position of tetralines. Similar conclusions are reached from Yb(fod)₃-induced shifts, which are also used for signal assignments, e.g. in 1-tetralone. Configurational assignments are possible for 1,2- and 1,3-epimers (ESD up to 4 ppm) but, in line with the non-discriminating eq/ax conformations at C-I, not for 1,4-epimers (ESD<0.5 ppm). More than 50 compounds were measured, including functional derivatives which show regular SIS for substituents in the aromatic moiety only for m- and p-carbon atoms. OMe, but not OH or OAc substituents, induce o-carbon SIS varying from ?11 to ?19 ppm. Conversion of 1-hydroxytetralin to esters induces shielding variations at the aromatic carbon atoms which indicate the electrostatic origin of derivatization shifts.     

Saturated amine oxides: Part 8. Hydroacridines: Part 27. Effects of N-oxidation and of N-quaternization on the 15N NMR chemical shifts of N-methylpiperidine-derived mono-, bi-, and tricycloaliphatic tertiary amines

The (15)N chemical shifts of 13 N-methylpiperidine-derived mono-, bi- and tricycloaliphatic tertiary amines, their methiodides and their N-epimeric pairs of N-oxides were measured, and the contributions of specific structural parameters to the chemical shifts were determined by multilinear regression analysis. Within the examined compounds, the effects of N-oxidation upon the (15)N chemical shifts of the amines vary from +56 ppm to +90 ppm (deshielding), of which approx. +67.7 ppm is due to the inductive effect of the incoming N(+)--O(-) oxygen atom, whereas the rest is due to the additive shift effects of the various C-alkyl substituents of the piperidine ring. The effects of quaternization vary from -3.1 ppm to +29.3 ppm, of which approx. +8.9 ppm is due to the inductive effect of the incoming N(+)--CH(3) methyl group, and the rest is due to the additive shift effects of the various C-alkyl substituents of the piperidine ring. The shift effects of the C-alkyl substituents in the amines, the N-oxides and the methiodides are discussed.     

Steric effects in 31P NMR spectra: ‘Gamma’ shielding in aliphatic phosphorus compounds

An examination of published ³¹P NMR spectral data for aliphatic phosphorus compounds has revealed that chain lengthening and branching effects on the chemical shift can be interpreted in terms similar to those used for ¹³C and ¹⁵N shifts. For six families of phosphorus compounds, a β-carbon substituent was shown to deshield phosphorus, while a γ-carbon caused shielding. The effects are additive, and good agreement was obtained between ³¹P shifts calculated with the appropriate constants and the experimental values. Shielding by γ-carbon is indicative of the operation of a steric influence on ³¹P chemical shifts, not heretofore articulated. The γ-effect is also useful in explaining the unusually large shielding found in six-membered cyclic phosphines.     

Design,synthesis and biological evaluation of 2,4‐diamino‐6‐methyl‐5‐substitutedpyrrolo[2,3‐d]pyrimidines as dihydrofolate reductase inhibitors

Nine novel nonclassical 2,4‐diamino‐6‐methyl‐5‐mioarylsubstituted‐ 7H ‐pyrrolo[2,3‐d]pyrimidines 2‐10 were synthesized as potential inhibitors of dihydrofolate reductase and as antitumor agents. The analogues contain various electron donating and electron withdrawing substituents on the phenylsulfanyl ring of the side chains and were synthesized from the key intermediate 2,6‐diamino‐6‐methyl‐7H‐pyrrolo[2,3‐d]‐pyrimidine, 14 . Compound 14 , was in turn obtained by chlorination of 4‐position of 2‐amino‐6‐methylpyrrolo[2,3‐d]pyrimidin‐4(3H)‐one, 16 followed by displacement with ammonia. Appropriately substituted phenyl thiols were appended to the 5‐position of 14 via an oxidative addition reaction using iodine, ethanol and water. The compounds were evaluated against rat liver, rat‐derived Pneumocystis, Mycobacterium avium and Toxoplasma gondii dihydrofolate reductase. The most potent and selective inhibitor, (2) has a 1‐naphthyl side chain. In this series of compounds electron‐withdrawing and bulky substituents in the side chain afford marginally active dihydrofolate reductase inhibitors. The single atom sulfur bridge in the side chain of these compounds is not conducive to potent dihydrofolate reductase inhibition.     

Proton and boron-11 magnetic resonance studies of some potassium tetraarylborates

Proton and boron-11 magnetic resonance spectra for several potassium para-substituted tetraarylborate compounds [KB(C₆H₄-pX)₄, where X is H, OCH₃, CH₃, Br, Cl, F, CF₃] have been obtained. The chemical shift between the centers of the AA′ and XX′ multiplets for the ring proton multiplets, relative to a reference chemical shift of 0·39 ppm for potassium tetraphenylborate, correlated with the corresponding Hammett σ values for the para-substituent. Additionally, the boron-11 chemical shifts gave a good correlation with corresponding σ values for the substituents. Electronegativities of para-substituted phenyl rings were calculated and found to be approximately 2·70 for all compounds studied. It was shown that electronic substituent effects do not greatly influence the electron density surrounding the central boron atom in the tetraarylborate ions.     

13C NMR spectra and electronic structure of alkenylalanes

The parameters of¹³C NMR spectra of linear and cyclic alkenylalanes synthesized from mono- and disubstituted acetylene and the simplest alkylalanes have been obtained. A strong paramagnetic effect of the aluminum atom on shielding of α- and β-carbon atoms at the double bond has been observed for the dimeric form of organoaluminum compounds (OAC) in inert solvents, unlike that for the monomeric form solvated in electron-donor solvents (Et₂O, THF, and Et₃N). The results were interpreted in terms of the model of the electron density redistribution on going from the dimeric structure of OAC to the monomeric one. The PM3 method describes most adequately (as compared to MNDO and AM1) the equilibrium geometry of cyclic dimers of OAC.