Piotr Fiedorow

An NMR and molecular mechanics structural study on some ethereal and Δ3,10 isomers of cinchona alkaloids

Abstract Z configurations have been ascribed to the ethylidene side chains of apocinchonine 2a and apoepiquinidine 2b . Unknown absolute configurations around C10 atoms, R for α-isocinchonine 4a and α-isoquinidine 4b and S for γ-isoquinidine 5 were determined. The C10 S arrangement for isoepiquinidine 6 and the C9 S for α-isocinchonine were confirmed. All the ethereal derivatives showed—in contrast with the parent alkaloids—the left-handed twist of their quinuclidine rings. The seven-membered intramolecular ethereal rings of the α and γ isomers adopt predominantly the ‘twist-chair’ conformation while in isoepiquinidine the ‘twist-boat’ form dominates. These conformations, deduced from NMR data, were confirmed by MM calculations. Both these methods allowed indication of the energetically most favourable positioning of the quinuclidine moiety in respect of the quinoline ring for the alkaloids investigated. ‘Anti-closed’ conformation I was found for isoepiquinidine whereas the remaining C10OC9 isomers prefer ‘anti-open’ forms VI, X, XIV . Minimum energy conformers ‘anti-closed’ XIX and ‘anti-open’ XVIII were found for Z -apocinchonine while Z -apoepiquinidine exists in prevailing ‘syn-open’ conformation XXV .

Synthesis of some 5-perfluoroalkenyl derivatives of uracil

Abstract 1,3-Dimethyl-5-iodouracil reacts smoothly with perfluorovinyl- (and E/Z-pentafluoropropenyl)-zinc iodides in the presence of Pd° as a catalyst yielding the appropriate 5-perfluoroalkenyl derivatives of uracil at high and moderate yield. In an analogous reaction, 1,3-dimethyl-6-iodouracils did not yield the expected coupling products.

Conformation of some sparteine N-16 oxides revisited

Sparteine N-16 oxides were thought to occur in all chair conformations with cis fusion between their C and D rings. NMR spectral analysis made possible indication of the chair – chair – boat– chair form with cis fussion of C, D rings for sparteine, 2phenyl- and 2-methylsparteine N-16 oxides. Molecular energy found by means of DFT, Hartree– Fock, AM1, PM3 methods supported this new shape of bisquinolizidine skeleton. q 2002 Elsevier Science B.V. All rights reserved.

Cinchona alkaloids: the structure of β-isocinchonicine revisited

Abstract Analysis of β-isocinchonicine — the enolo-ethereal derivative of cinchonine — by NMR, AM1 calculations, and X-ray diffraction resulted in the assignment of its structure as 1( S )-ethyl-3-(quinol-4-yl)-2-oxa-6( S )-9-azabicyclo[4.4.0]dec-3-ene contrary to the structure with seven-membered enolo-ethereal ring reported in the literature. The AM1 calculations also showed several energetically favorable conformations with the ethyl group equatorial in relation to the piperidine fragment. Four of these forms ( II , V , VIII , XI ), supported by NOEs and being the rotamers of the quinolyl and ethyl substituents, are most probable components of the conformational equilibrium mixture of β-isocinchonicine. Three of the rotamers have been observed by X-ray diffraction: two in the crystals of β-isocinchonicine hydroiodide monohydrate ( 7 ·HI·H 2 O) are linked into an asymmetric dimer by a pair of N–HN + hydrogen bonds and another rotamer in its hydroiodide dihydrate ( 7 ·HI·2H 2 O) where the cations are linked by N–HN + hydrogen bond into helices.

Structural studies of some 5-(perfluoroalkenyl) uracils

Abstract Structures of the most stable conformers of derivatives of 5-vinyluracil and fluorinated analogues have been determined using MM and semiempirical MNDO calculations. It has been found that the most stable conformers of 5-trifluorovinyl and 5- E / Z -pentafluoropropenyl groups are almost perpendicular to the plane of the uracil ring. These findings are in good agreement with X-ray data obtained for 1,3,6-trimethyl-5-trifluorovinyluracil. The calculated energy barrier for rotation of exocylic 5-substituents depends on the structure of the fluorinated fragments as well as on the nature of the substituent at the 6-position of uracil. A methyl group at the 6-position causes steric hindrance and significantly disturbs the rotation of fluorinated groups.

THE STRUCTURE OF INTERMEDIATE PRODUCTS OF 'FRAGMENTATION' OF 10-BROMODIHYDROCINCHONINE

Abstract 10-Bromodihydrocinchonine 1d , similarly to analogical derivatives of other main cinchona alkaloids, transforms into nicinquine and isonicinquine 2d formally loosing its C2 carbon atom in a form of formaldehyde. This reaction was found to proceed via the so-far unstudied intermediate compounds ( 5a ) 4- S -( Z -propenyl)- and ( 5 4- S -( E -propenyl)-6- R -7- S -(quinolyl-4)-8-oxa-1- R -azabicyclo[4.3.0]nonane which at the same time are products of a novel rearrangement of the parent cinchonine. The stereostructure of these compounds was determined using, mainly, NMR techniques. The energy minima of conformers 5 and 5a were supported by molecular mechanics calculations. The mechanisms for the 1d → 5 → 2d sequence have been discussed. The alkaloid 5 is sterically preferred to its Z -isomer. The accompanying nucleophilic substitution ( 1d → 6 ) and elimination ( 1d → 7 ) are also stereospecific.

Studies of the Surface of Fluorinated Carbon in the Aspect of its Catalytic Properties

Abstract Surface properties of fluorinated carbon were characterised from the point of view of its use as a material for catalytic purposes. Samples with different fluorine content (from 10 to 65 wt.%) were tested for their catalytic activity for a number of reactions of acid-base catalysis involving residual hydroxyl groups as active centres. It was found that they were capable of catalysing only such a reaction proceeding through the formation of carbenium ion for which the presence of very weak acid centres is sufficient. The generation of only weak acidity as a result of fluorination was unexpected, therefore calculations were performed using AM1 method to explain this fact. A simple molecule used as a model of fluorinated carbon surface enabled to predict acidity of residual OH groups which was in agreement with experimental findings.

X-ray and computational studies of some 5-(perfluoroalkenyl) uracils

Abstract X-ray structures of 1,3-dimethyl-5-trifluorovinyl-, 5- E - and Z -pentafluoroalkenyl uracils (compounds 1 , 2 , 3 ) were determined. In all cases planar ring of uracil was slightly distorted around C2, C4, N3 and C6 atoms. The exocyclic alkenyl group is not coplanar with uracil ring and exocyclic CC bond was shortened when compared with typical alkenes. Using semiempirical (MNDO, AM1, PM3) and ab initio (RHF 4-31 G) methods the structures of stable conformers were determined and obtained geometries were compared with those found experimentally.

Unusual reactivity of poly(trifluoromethyl)benzenes. Semiempirical reaction modelling

Abstract The reaction of methyllithium with 1,3,5-tris(trifluoromethyl)benzene, 1 , 1,2,4,5-tetrakis(trifluoromethyl)benzene, 2 , and 1,2,4-tris(trifluoromethyl)benzene, 3 , was analyzed using the semiempirical package mopac 6. It was shown that formation of lithium-hydrogen exchange products are favoured only in the case of compound 1 , whereas in the case of 2 and 3 the major products were those of nucleophilic substitution.

Conformational transformations of bis(trifluorovinyl) derivatives of napthalene and phenanthrene

Abstract Energetic barriers of conformational transformations of 1,2-bis(trifluorovinyl)-naphthalene and 9,10-bis(trifluorovinyl)phenanthrene were calculated by molecular mechanics (MM) methods and compared with experimental data obtained by NMR. It was found that simple MM methods can give results which are in good agreement with experimental data. The geometries of stable conformations of the above compounds were also calculated.