@article{SzatmariBelasriHeydenreichetal.2019, author = {Szatmari, Istvan and Belasri, Khadija and Heydenreich, Matthias and Koch, Andreas and Kleinpeter, Erich and Fulop, Ferenc}, title = {Ortho-Quinone methide driven synthesis of new O,N- or N,N-Heterocycles}, series = {ChemistryOpen : including thesis treasury}, volume = {8}, journal = {ChemistryOpen : including thesis treasury}, number = {7}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {2191-1363}, doi = {10.1002/open.201900150}, pages = {961 -- 971}, year = {2019}, abstract = {To synthesize functionalized Mannich bases that can serve two different types of ortho-quinone methide (o-QM) intermediates, 2-naphthol and 6-hydroxyquinoline were reacted with salicylic aldehyde in the presence of morpholine. The Mannich bases that can form o-QM and aza-o-QM were also synthesized by mixing 2-naphthol, 2-nitrobenzaldehyde, and morpholine followed by reduction of the nitro group. The highly functionalized aminonaphthol derivatives were then tested in [4+2] cycloaddition with different cyclic imines. The reaction proved to be both regio- and diastereoselective. In all cases, only one reaction product was obtained. Detailed structural analyses of the new polyheterocycles as well as conformational studies including DFT modelling were performed. The relative stability of o-QMs/aza-o-QM were also calculated, and the regioselectivity of the reactions could be explained only when the cycloaddition started from aminodiol 4. It was summarized that starting from diaminonaphthol 25, the regioselectivity of the reaction is driven by the higher nucleophilicity of the amino group compared with the hydroxy group. 12H-benzo[a]xanthen-12-one (11), formed via o-QM formation, was isolated as a side product. The proton NMR spectrum of 11 proved to be very unique from NMR point of view. The reason for the extreme low-field position of proton H-1 could be accounted for by theoretical calculation of structure and spatial magnetic properties of the compound in combination of ring current effects of the aromatic moieties and steric compression within the heavily hindered H(1)-C(1)-C(12b)-C(12a)-C(12)=O structural fragment.}, language = {en} } @article{NeuvonenFulopNeuvonenetal.2005, author = {Neuvonen, Kari and Fulop, Ferenc and Neuvonen, Helmi and Koch, Andreas and Kleinpeter, Erich and Pihlaja, Kalevi}, title = {Propagation of polar substituent effects in 1-(substituted phenyl)-6,7-dimethoxy-3,4-dihydro- and -1,2,3,4- tetrahydroisoquinolines as explained by resonance polarization concept}, year = {2005}, abstract = {Propagation of inductive and resonance effects of phenyl substituents within 1-(substituted phenyl)-6,7- dimethoxy-3,4-dihydro- and -1,2,3,4-tetrahydroisoquinolines were studied with the aid of C-13 and N-15 NMR chemical shifts and ab initio calculations. The substituent-induced changes in the chemical shift (SCS) were correlated with a dual substituent parameter equation. The contributions of conjugative (rho(R)) and nonconjugative effects (rho(F)) were analyzed, and mapping of the substituent-induced changes is given over the entire isoquinoline moiety for both series. The experimental results can be rationalized with the aid of the resonance polarization concept. This means the consideration of the substituent-sensitive balance of different resonance structures, i.e., electron delocalization, and the effect of the aromatic ring substituents on their relative contributions. With tetrahydroisoquinolines, the delocalization of the nitrogen lone pair (stereoelectronic effect) particularly contributes. Correlation analysis of the Mulliken atomic charges for the dihydroisoquinoline derivatives was also performed. The results support the concept of the substituent-sensitive polarization of the isoquinoline moiety even if the polarization pattern achieved via the NMR approach is not quite the same as that predicted by the computational charges. Previously the concepts of localized pi- polarization and extended polarization have been used to explain polar substituent effects within aromatic side-chain derivatives. We consider that the resonance polarization model effectively contributes to the understanding of the polar substituent effects}, language = {en} } @article{SchusterKochHeydenreichetal.2008, author = {Schuster, Ildik{\´o} and Koch, Andreas and Heydenreich, Matthias and Kleinpeter, Erich and Forr{\´o}, Enik{\"o} and L{\´a}z{\´a}r, L{\´a}szl{\´o} and Sillanp{\"a}{\"a}, Reijo and Fulop, Ferenc}, title = {Synthesis and Conformational Analysis of Tetrahydroisoquinoline-Fused 1,3,2-Oxazaphospholidines and 1,2,3- Oxathiazolidines}, year = {2008}, abstract = {The cyclizations of tetrahydroisoquinoline 1,2-amino alcohols with phenylphosphonic dichloride, bis(2- chloroethyl)phosphoramidic dichloride, thionyl chloride and sulfuryl chloride were utilized to synthesize 1,5,6,10b- tetrahydro-1,3,2-oxazaphospholo[4,3-a]isoquinolines (2, 3), 1,5,10,10a-tetrahydro-1,3,2-oxazaphospholo[3,4- b]isoquinolines (8, 9), 1,5,6,10b-tetrahydro-1,2,3-oxathiazolo[4,3-a]isoquinolines (4-6) anda 1,5,10,10a-tetrahydro- 1,2,3-oxathiazolo[3,4-b]isoquinoline (11), which are the first representatives of these ring systems. NMR spectroscopic analysis revealed the existence of conformational equilibria that are fast on the NMR timescale. Theoretical DFT calculations pointed to the participation of generally two preferred conformers in the conformational equilibria; the positions of the equilibria were indicated by the experimental NMR spectroscopic parameters, and they are in good agreement with the theoretically calculated energy differences of the participating conformers. For two compounds, which could be not isolated (10, 12), both the preferred conformers and the stereochemistry could be concluded from the DFT calculation results.}, language = {en} } @article{NeuvonenFulopNeuvonenetal.2008, author = {Neuvonen, Helmi and Fulop, Ferenc and Neuvonen, Kari and Koch, Andreas and Kleinpeter, Erich}, title = {Electronic effects of heterocyclic ring systems as evaluated with the aid of 13C and 15N NMR chemical shifts and NBO analysis}, doi = {10.1002/Poc.1271}, year = {2008}, abstract = {The electronic effects of the 5- and 6-membered heterocyclic rings on the C=N-N unit of five different hydrazone derivatives of pyridine-2-, -3- and -4-carbaldehydes, pyrrole-2-carbaldehyde, furan-2- and -3-carbaldehydes and thiophene-2- and -3-carbaldehydes have been studied with the aid of 13C and 15N NMR measurements together with the natural bond orbital (NBO) analysis. As model compounds are used the corresponding substituted benzaldehyde derivatives. The polarization of the C=N unit of the hydrazone functionality of the heteroaryl derivatives occurs in an analogous manner with that of phenyl derivatives. The electron-withdrawing heteroaryl groups destabilize and the electron-donating groups stabilize the positive charge development at the CN carbon while the effect on the negative charge development is opposite. The 15N NMR chemical shift of the C=N and C=N-N nitrogens and the NBO charges at C=N-N unit can be correlated with the replacement substituent constants of the heteroaryl groups. 13C NMR shifts of the C=N carbon of N,N- dialkylhydrazones of the heteroarenecarbaldehydes can be correlated with a dual parameter equation possessing the polar substituent constant ;* of the heteroaryl group and the electronegativity of the heteroatom as variables.}, language = {en} } @article{HeydenreichKochSzatmarietal.2008, author = {Heydenreich, Matthias and Koch, Andreas and Szatm{\´a}ri, Istv{\´a}n and Fulop, Ferenc and Kleinpeter, Erich}, title = {Synthesis and conformational analysis of naphth[1,2-e][1,3]oxazino[4,3-a][1,3]isoquinoline and naphth[2,1- e][1,3]oxazino[4,3-a]isoquinoline derivatives}, doi = {10.1016/j.tet.2008.05.025}, year = {2008}, abstract = {Through the cyclization of 1-(;-hydroxynaphthyl)-1,2,3,4-tetrahydroisoquinoline and 1-(;- hydroxynaphthyl)-1,2,3,4-tetrahydroisoquinoline with formaldehyde, phosgene, p-nitrobenzaldehyde or p-chlorophenyl isothiocyanate, 8-substituted 10,11-dihydro-8H,15bH-naphth[1,2-e][1,3]oxazino[4,3-a]isoquinolines (3 and 4) and 10,11- dihydro-8H,15bH-naphth[2,1-e][1,3]oxazino[4,3-a]isoquinolines (15 and 16) were prepared. Conformational analysis of both the piperidine and the 1,3-oxazine moieties of these heterocycles by NMR spectroscopy and an accompanying theoretical study revealed that these two conformationally flexible six-membered ring moieties prefer twisted chair conformers.}, language = {en} } @article{StarkeSchusterFulopetal.2008, author = {Starke, Ines and Schuster, Ildikk{\´o} and Fulop, Ferenc and Kleinpeter, Erich}, title = {Mass spectra of tetrahydroisoquinoline-fused 1,3,2-O,N,P- and 1,2,3-O,S,N-heterocycles: influence of ring size and fusion, of present heteroatoms, substituent effects and of the stereochemistry on fra}, year = {2008}, abstract = {The electron ionization (EI) mass spectra of a variety of stereoisomeric tricyclic 1,3,2-oxazaphosphino[4,3- a]isoquinolines (1-4), 1,2,3-oxathiazino[4,3-a]isoquinoline-4-oxides (5-7) and the -4,4-dioxides (8-10) of oxazaphospholo- and oxathiazolo[4,3-a]- (11, 12, 15 and 16) and -[3,4-b]isoquinolines (13, 14 and 17) were recorded. Ring size and fusion, the different heteroatoms (P and S) and substituents on the ring systems strongly influence the mass spectra. In addition, mass spectra of the stereoisomers of compounds 1, 2 and 13, 14 revealed stereochemically relevant differences which are not observed for the other pairs of isomers. Copyright © 2008 John Wiley \& Sons, Ltd.}, language = {en} } @article{HeydenreichKochKlodetal.2006, author = {Heydenreich, Matthias and Koch, Andreas and Klod, Sabrina and Szatmari, Istvan and Fulop, Ferenc and Kleinpeter, Erich}, title = {Synthesis and conformational analysis of naphth[1', 2':5,6][1,3]oxazino[3,2-c][1,3]benzoxazine and naphth[1', 2':5,6][1,3]oxazino[3,4-c][1,3]benzoxazine derivatives}, series = {Tetrahedron}, volume = {62}, journal = {Tetrahedron}, number = {48}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0040-4020}, doi = {10.1016/j.tet.2006.09.037}, pages = {11081 -- 11089}, year = {2006}, abstract = {A new functional group, the hydroxy group, was inserted into a Betti base by reaction with salicylaldehyde, and the naphthoxazine derivatives thus obtained were converted by ring-closure reactions with formaldehyde, acetaldehyde, propionaldehyde or phosgene to the corresponding naphth[1',2':5,6][1,3]oxazino[3,2-c][1,3]benzoxazine derivatives. Further, the conformational analysis of these polycyclic compounds by NMR spectroscopy and an accompanying molecular modelling are reported; especially, both quantitative anisotropic ring current effects of the aromatic moieties in these compounds and steric substituent effects were employed to determine the stereochemistry of the naphthoxazinobenzoxazine derivatives.}, language = {en} } @article{SzatmariMartinekLazaretal.2004, author = {Szatmari, Istvan and Martinek, T. A. and Lazar, L. and Koch, Andreas and Kleinpeter, Erich and Neuvonen, Kari and Fulop, Ferenc}, title = {Stereoelectronic effects in ring-chain tautomerism of 1,3-diarylnaphth[1,2-e][1,3]oxazines and 3-alkyl-1- arylnaphth[1,2-e][1,3]oxazines}, issn = {0022-3263}, year = {2004}, abstract = {The disubstitution effects of X and Y in 1-(Y-phenyl)-3-(X-phenyl)-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines on the ring-chain tautomerism, the delocalization of the nitrogen lone pair (anomeric effect), and the C-13 NMR chemical shifts were analyzed by using multiple linear regression analysis. Study of the three-component equilibrium B reversible arrow A reversible arrow C revealed that the chain reversible arrow trans (A reversible arrow B) equilibrium constants are significantly influenced by the inductive effect (sigma(F)) of substituent Y on the 1-phenyl ring. In contrast, no significant substituent dependence on Y was observed for the chain reversible arrow cis (A reversible arrow C) equilibrium. There was an analogous dependence for the epimerization (C reversible arrow B) constants of 1-(Y-phenyl)-3- alkyl-2,3-dihydro-1H-naphth[1,2-e] [1,3]oxazines. With these model compounds, significant overlapping energies of the nitrogen lone pair was observed by NBO analysis in the trans forms B (to sigma*(C1-C1'), sigma*(C1-C10b), and sigma*(C3-O4)) and in the cis forms C (to sigma*(C1-H), sigma*(C1-C10b), and sigma*(C3-O4)). The effects of disubstitution revealed some characteristic differences between the cis and trans isomers. However, the results do not suggest that the anomeric effect predominates in the preponderance of the trans over the cis isomer. When the C-13 chemical shift changes induced Y by substituents X and Y (SCS) were subjected to multiple linear regression analysis, negative rho(F)(Y) and rho(F)(X) values were observed at C-1 and C-3 for both the cis and trans isomers. In contrast, the positive rho(R)(Y) values at C-1 and the negative rho(R)(X) values at C-3 observed indicated the contribution of resonance structures f (rho(R) > 0) and g (rho(R) < 0), respectively. The classical double bond-no-bond resonance structures proved useful in explaining the substituent sensitivities of the donation energies and the behavior of the SCS values}, language = {en} } @article{KleinpeterSzatmariLazaretal.2009, author = {Kleinpeter, Erich and Szatm{\´a}ri, Istv{\´a}n and L{\´a}z{\´a}r, L{\´a}szl{\´o} and Koch, Andreas and Heydenreich, Matthias and Fulop, Ferenc}, title = {Visualization and quantification of anisotropic effects on the 1H NMR spectra of 1,3-oxazino[4,3- alpha]isoquinolines - indirect estimates of steric compression}, issn = {0040-4020}, doi = {10.1016/j.tet.2009.07.038}, year = {2009}, abstract = {The anisotropic effects of the phenyl, alpha- and beta-naphthyl moieties in four series of 1,3-oxazino[4,3- a]isoquinolines on the H-1 chemical shifts of the isoquinoline protons were calculated by employing the Nucleus Independent Chemical Shift (NICS) concept and Visualized as anisotropic cones by a through-space NMR shielding grid. The signs and extents of these spatial effects on the H-1 chemical shifts of the isoquinoline protons were compared with the experimental H-1 NMR spectra. The differences between the experimental delta (H-1)/ppm values and the calculated anisotropic effects of the aromatic moieties are discussed in terms of the steric compression that occurs in the Compounds studied.}, language = {en} } @article{SzatmariHeydenreichKochetal.2013, author = {Szatmari, Istvan and Heydenreich, Matthias and Koch, Andreas and Fulop, Ferenc and Kleinpeter, Erich}, title = {Unexpected isomerization of new naphth[1,3]oxazino[2,3-a] isoquinolines in solution, studied by dynamic NMR and supported by theoretical DFT computations}, series = {Tetrahedron}, volume = {69}, journal = {Tetrahedron}, number = {35}, publisher = {Elsevier}, address = {Oxford}, issn = {0040-4020}, doi = {10.1016/j.tet.2013.06.094}, pages = {7455 -- 7465}, year = {2013}, abstract = {Through the reactions of 1-aminomethyl-2-naphthol and substituted 1-aminobenzyl-2-naphthols with 3,4-dihydroisoquinoline or 6,7-dimethoxy-3,4-dihydroisoquinoline under microwave conditions, naphth[1,2-e][1,3]oxazino[2,3-a]-isoquinoline derivatives were prepared in good yields. The latter reaction was extended by using 2-aminoarylmethyl-1-naphthols, leading to isomeric naphth-[2,1-e][1,3]oxazino[2,3-a] isoquinolines. Beside the detailed NMR spectroscopic and theoretical study of both stereochemistry and dynamic behaviour of these new conformational flexible heterocyclic ring systems an unexpected dynamic process between two diastereomers was observed in solution, studied by variable temperature H-1 NMR spectroscopy and the mechanism proved by theoretical DFT computations.}, language = {en} }