Reijo Kauppinen

Self-Organization of 2-Acylaminopyridines in the Solid State and in Solution

Aggregation of 2-acylaminopyridines and their 6-methyl derivatives in chloroform solution was studied by (1)H, (13)C, and (15)N NMR spectroscopies. The results were compared with (13)C and (15)N CPMAS NMR and IR spectral as well as with X-ray structural data. Intermolecular interactions in solution and in solid state were found to have a similar nature. Relatively strong N(amide)-H···N(pyridine) intermolecular hydrogen bonds enable dimerization to take place. Steric interactions in N-pivaloyl- and N-1-adamantylcarbonyl as well as that caused by the 6-methyl group hinder formation of the dimeric aggregates stabilized by the N(amide)-H···N(pyridine) intermolecular hydrogen bonds. In general, the DFT optimized geometries of the aggregates in chloroform solution are in agreement with the X-ray crystal structures. Wavenumbers of the stretching vibration band of the C═O group were also found indicative of the type of hydrogen bond present in the solid state.

Multinuclear 1H, 13C and 15N NMR study of some substituted 2-amino-4-nitropyridines and their N-oxides.

1H, 13C and 15N NMR chemical shift assignments based on pulsed field gradient selected PFG 1H,X (X = 15C and 15N) HMQC and HMBC experiments are reported for three 4-nitropyridine N-oxides and four 4-nitropyridines. It was found that an ortho effect of a methyl group inhibits the deshielding effect of the 4-nitro group and that this effect and the so-called back donation is influenced by electronegativity and position of substituents in the multisubstituted pyridine N-oxides. The shielding effect of N-oxide group is most pronounced in the 15N NMR chemical shifts of the studied compounds. This effect is further modified by methylamino, methylnitramino, 5- or 3-methyl and 4-nitro groups. Among them the 4-nitro group exerts the highest influence on the shielding effect of the N-oxide functionality. Experimental 1H, 13C and 15N NMR chemical shifts and GIAO/DFT theoretical calculations are consistent with each other and supported by the reactivity on nucleophilic substitution, the UV spectral and the dipole moment data.

Complexation of 2,6-Bis(acylamino)pyridines with Dipyridin-2-ylamine and 4,4-Dimethylpiperidine-2,6-dione

Intermolecular hydrogen bonds between 2,6-bis(acylamino)pyridines and dipyridin-2-ylamine as well as 4,4-dimethylpiperidine-2,6-dione are responsible for relatively strong interactions between these species. Association has been found to be significantly affected by the size of acyl substituent (chemical shift of the NH proton was used as the main probe in determination of the association constants). Calculations at the DFT level of theory are in line with the experimentally observed results. Calculated energies of the interactions between the complex congeners also show the size of the substituent to affect the association. Conformational changes in the dipyridin-2-ylamine molecule are shown to adapt a geometry suitable for formation of efficient hydrogen bonding.

NMR SPECTROSCOPY IN ENVIRONMENTAL CHEMISTRY : 1H AND 13C NMR CHEMICAL SHIFT ASSIGNMENTS OF CHLORINATED DIBENZOTHIOPHENES BASED ON TWO-DIMENSIONAL NMR TECHNIQUES AND AB INITIO MO AND DFT/GIAO CALCULATIONS

1H and 13C NMR spectra for seven chlorinated dibenzothiophenes (DBTs) were measured. Complete 1H and 13C NMR chemical shift assignments for 2,8‐ and 3,7‐dichloro‐ and 2,3,6,8‐, 2,3,7,8‐ and 2,4,6,8‐tetrachloro congeners are based on z‐gradient selected inverse (proton detected) two‐dimensional heteronuclear chemical shift correlation experiments, 1H,13C HMQC and HMBC. For 1,2,3,4,6,7,8‐heptachloro‐DBT and octachloro‐DBT, where polarization transfer techniques from proton to (all) carbons are not possible, the 13C NMR chemical shift assignments are based on theoretical calculations using ab initio MO and DFT/GIAO methods at the HF/6–311G* and BPW91/6–311G* levels. The observed HMBC correlations for the heptachloro congener are in good agreement with a theoretically predicted shift order, providing evidence for the reliability of the theoretical method. Copyright

1H, 13C NMR spectroscopy and conformational properties of 18 halogenated diphenyl ethers

Abstract 18 Polyhalogenated diphenyl ethers (DEs) were synthesized and their 1 H and 13 C NMR spectra measured and analyzed. As far as we know, most NMR data are reported for the first time. The assignments of the 1 H and 13 C NMR spectra of one congener were ascertained by 2-D 13 C- 1 H COSY measurements. 13 C chemical shift differences between ortho and meta positions indicate the varying conjugational extent of the ether oxygen with the phenyl groups. All theoretical and experimental results show that the coplanarity of DEs is impossible. Thermodynamical and kinetical considerations suggest the free internal motion of DEs around their C-O bond at ambient temperatures.

Substituent and temperature controlled tautomerism: multinuclear magnetic resonance, X-ray, and theoretical studies on 2-phenacylquinolines

Proton-transfer equilibria in chloroform solution of twelve 2-phenacylquinolines were studied by 1H, 13C and 15N NMR spectroscopies. The (Z)-enaminone form stabilized by an intramolecular hydrogen bond was found to prevail in all cases. Electron-donating substituents in the phenacyl part of the molecule lead to an increase of the ketimine form (to 33% for p-NMe2). Variable temperature 1H NMR measurements show that higher temperatures have the same effect. The negative logarithm values of the equilibrium constant, pKT, were found to be linearly dependent on Hammett σ substituent constants. The pKTvs. temperature correlation also has a linear character. In general, strong electron-withdrawing substituents cause transformation of the ketimine to the enaminone form to become more exothermic but values of the heat of reaction for 2-phenacylquinolines studied are not linearly dependent on σ. X-Ray data show that the strength of the internal hydrogen bond in the enaminone form increases for strong electron-withdrawing substituents. Rough estimation shows this bond to be stronger in chloroform solution than in the crystalline state. π-Electron delocalization in the six-membered quasi-ring involving the H⋯O bond is very strong. This effect is responsible for the predominance of the tautomeric enaminone form in 2-phenacylquinolines. On the other hand, semiempirical AM1 and PM3 calculations show that in the gas phase the ketimine tautomer is energetically favored in most cases.

Structural, Thermoanalytical and Molecular Modeling Studies on N-(3-hydroxypropyl) 3α,12α-Dihydroxy-5β-cholan-24-amide and Its Monohydrates

The synthetic method for preparing N-(3-hydroxypropyl) 3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-amide can lead to formation of at least three different crystal forms - an anhydrous compound and two monohydrates. The structural and thermal properties of these forms have been characterized by 13C-CP/MAS-NMR and IR spectroscopy, thermo- gravimetry, differential scanning calorimetry and by powder and single crystal x-ray crystallography. In addition, theoretical 13C-NMR chemical shift calculations were also performed for the anhydrous compound and for the first monohydrate, starting from single crystal structures and the structures of these species have now been verified. The first monohydrate, C27H47NO4 x H2O, crystallizes in orthorhombic space group P2(1)2(1)2(1) with cell parameters: a = 7.1148(2), b = 18.1775(5), c = 20.1813(6), Z = 4.

Tuning the hydrogen-bonding strength in 2,6-bis(cycloalkylcarbonylamino)pyridine assemblies by variable flexibility. Association constants measured by hydrogen-bonded vs. non-hydrogen-bonded protons

The association of 2,6-bis(cycloalkylcarbonylamino)pyridines with rigid and non-rigid counterparts in chloroform solution was studied using 1H NMR and computational methods. The angles within the cycloalkyl ring and the rotation of these substituents determine the strength of the association via triple hydrogen bonding. The dimerisation and methyl–methyl repulsion have been addressed as mechanisms restricting heterocomplexation of diacetamide. The association constants obtained by the shift changes of hydrogen-bonded protons are in agreement with those of methine protons. This ‘dual shift’ method was proposed as an additional verification of association constants obtained generally by amino protons.

Macrocycles prepared from lithocholic acid, piperazine and isomeric pyridine dicarboxylic acids and their selective affinities towards sodium and potassium

Abstract Two novel macrocycles prepared from lithocholic acid, piperazine and pyridine dicarboxylic acids (2,6- and 3,5-isomers), have been characterized by 13C NMR and ESI–MS techniques. In case of the pyridine-2,6-dicarboxylate derivative, the molecular formula of the cycle was C59H87O6N3 (I), while the pyridine-3,5-dicarboxylate derivative (II) was a trimeric structure by molecular mass when compared with I. Furthermore, cycle I showed a special affinity towards potassium cation, while II possessed significant proton and sodium cation recognition properties.

Oxygen-containing bicyclic monoterpenes. 1H, 13C and 17O NMR Spectroscopic and X-ray diffraction studies of seven oxidation products of (+)-3-carene

Seven oxidation products of (1S,6R)-(+)-3,7,7-trimethylbicyclo[4.1.0]hept-3-ene [naturally abundant terpene, (+)-3-carene)]1; (1S,6R)-3,7,7-trimethylbicyclo[4.1.0]hept-3-en-2-one (3-caren-2-one)2, (1S,6R)-3,7,7-trimethylbicyclo[4.1.0]hept-3-en-5-one (3-caren-5-one)3, (1S,6R)-3,7,7-tri-methylbicyclo[4.1.0]hept-3-ene-2,5-dione (3-carene-2,5-dione)4, (1S,3S,4R,6R)-(+)-3,7,7-trimethylbicyclo[4.1.0]heptene 3,4-trans-oxide (trans-3,4-epoxy-3-carene)5, (1S,3R,4R,6R)-3,7,7-trimethylbicyclo[4.1.0]heptane-3-exo-4-endo-diol (carane-3-exo-4-endo-diol)6 and (1S,2R,4R,5R)-1-methyl-4-exo-(1-hydroxy-1-methylethyl)bicyclo[3.1.0]hexan-2-endo-ol 7 and (1S,6R)-3-endo-7,7-trimethylbicyclo[4.1.0]heptan-4-one (trans-4-caranone)8 have been obtained by oxidation with tert-butylchromate, selenium dioxide, hydrogen peroxide and peracetic acid. The 1H, 13C and 17O NMR spectra of the purified oxidation products have been recorded and assigned. In addition to C,H-COSY spectra, the 1J(C,H) coupling constants were especially useful in 13C NMR spectral assignment. The differentiation between isomeric ketones 2 and 3 is based on a clear difference in the 13C NMR shifts of the double bond methyl. The stereochemical structure elucidation of oxide 5 is based on lanthanide shift reagent [Eu(dpm)3] induced effects. For ketone 8, molecular mechanics (MM) calculations and comparison of experimental and theoretical 3J(H,H) coupling constants are needed for a final structure elucidation. The assignment of 17O NMR lines of diols 6 and 7 is based on literature values. The crystal structures and absolute configurations of pure enantiomers of diols 6 and 7 have been determined by X-ray diffraction. Crystal data: a= 7.659(2), b= 10.804(3), c= 25.509(4)A, orthorhombic, space group C 2221, Z= 8 (6) and a= 8.076(4), b= 8.836(2), c= 12.487(3)A, orthorhombic, space group P212121, Z= 4 (7).