Isabel Fonseca

Synthesis and Structure of New Pyrido[2,3-d]pyrimidine Derivatives with Calcium Channel Antagonist Activity

We gratefully acknowledge to ALTER S. A. for studentship (to A. P and R. A.) and financial support

A practical synthesis of ethynylferrocene from ferrocene carboxaldehyde: structure of 1,4-diferrocenyl-1,3-butadiyne

Abstract Ethynylferrocene was satisfactoryly obtained by a Wittig reaction between ferrocene carboxaldehyde and chloromethylentriph-enylphosphonium ylid to give an E/Z mixture of 2-chloro-1-ferrocenylethene. Both isomers were isolated pure by chemical methods. Reaction of the isomers mixture with n-butyllithium allowed ethynylferrocene to be obtained in good yield. The method was applied in one pot giving the ethynylferrocene and (E/Z)-1,4-diferrocenyl-but-1-en-3-yne as a secondary product. Oxidative coupling to 1,4-difeerrocenyl-1,3-butadiyne has been carried out in quantitative yields. A single-crystal analysis of t he diyne was carried out, but the compound is unreactive in solid state.

The hydrolysis of pentamethylcyclopentadienyltitanium trihalides and the formation of di-, tri-, and tetra-nuclear μ-oxo complexes. Crystal structure of [(C5Me5)TiBr(μ-O)]4CHCl3, which contains a Ti4O4 ring

Abstract Controlled hydrolysis of pentamethylcyclopentadienyltitanium trihalides Cp★TiX3 in toluene in the presence of NHEt2 leads to the isolation of compounds of the types [Cp★TiX2]2(μ-O) (X = Cl, Br, I), [Cp★TiX(μ-O)]n (X = Cl, n = 3; X = Br, n = 4] and finally [Cp★Ti]4(μ-O)6 depending upon the Ti/H2O stoichiometry. The crystal structure of [Cp★TiBr(μ-O)]4 has been determined: the compound crystallizes with one molecule of CHCl3 in the orthorhombic space group Pnca and contains a Ti4O4 ring of alternating Ti and O atoms. The four oxygen atoms lie in a plane, with the titanium atoms situated alternately ± 0.191(2) A above and below this plane.

Synthesis of ferrocene derivatives with π-extended conjugation

Abstract Synthesis of ( E )-1-ferrocenyl-2-( p -iodophenyl)ethene was carried out by means of the Wittig reaction between the p -iodobenzyl triphenylphosphonium ylid and the ferrocene carboxaldehyde, satisfactory as a mixture of E/Z isomers. Isomerization Z → E was induced by iodine—NBS in quantitative yield. The X-ray molecular structure of this ( E )-isomer indicates that the molecules are linked by charge transfer complexation between the iodine atom and the cyclopentadiene ring. The conjugation of the molecule of l-ferrocenyl-2-( p -iodophenyl)ethene was expanded to the ( Z,Z )- and ( E, E )-1,4-di[1-ferrocenyl-2( p -iodophenyl)ethenyl]biphenyl and to the ( Z,Z )- and ( E,E )-1,4-di(l-ferrocenyl-2-( p -phenylethenyl)-1,3-butadiyne, both as centrosymmetric structures.

Synthesis and X-ray structure of 1,4-bis[4-(N,N-dimethylamino)phenyl]buta-1,3-diyne: charge-transfer complex with acceptors

4-(N,N-dimethylamino)phenylethyne has been satisfactorily prepared by the Wittig reaction between chloromethylene(triphenyl)phosphine ylide and 4-(N,N-dimethylamino)benzaldehyde, followed by hydrochloric acid elimination. 1,4-Bis[4-(N,N-dimethylamino)phenyl]-buta-1,3-diyne was obtained by oxidative dimerization in good yield. The dimer forms a 1 : 1 charge-transfer complex with TCNE, an X-ray structure analysis of which is reported.

The 7-oxabicyclo[2.2.1]heptane system as a valuable starting material for the synthesis of modified a ring vitamin D3 analogues

Abstract A totally stereoselective synthesis of an analogue of the A ring fragment of vitamin D 3 has been achieved in optically pure form starting from a 7-oxanorbornenic disulfone. The key step is the alkylative cleavage of the oxygen bridge to produce a highly oxygenated cyclohexenyl sulfone.

The zwitterion structure of imidazol-1-ylacetic acids in the solid state and in solution

Abstract The crystal zwitterion structures of imidazol-1-ylacetic acid 1 and (±)-3-ethoxycarbonyl-2-imidazol-1-ylpropionic acid2 have been determined by X-ray diffraction analysis. Spectroscopic 13C NMR studies in the solid state, by the CP/MAS technique, and in solution have revealed the presence of the zwitterion structure in H2O and D2O solutions. Results have been complemented with 17O NMR and IR data.

Synthesis of 1,4-di(n-pyridyl)buta-1,3-diyne and formation of charge-transfer complexes. X-Ray structure of 1,4-di(3-pyridyl)buta-1,3-diyne

Ethynylpyridines have been satisfactorily prepared by two different routes: (a) the Wittig reaction between chloromethylene(triphenyl)phosphine ylide and a pyridinecarbaldehyde, followed by elimination of hydrogen chloride; (b) from the 2-methyl-4-(n-pyridyl)but-3-yn-2-ol intermediate, by elimination of acetone. 1,4-Di(n-pyridyl)buta-1,3-diynes are obtained by oxidative dimerization in good yield. An X-ray structure of the 3-substituted dimer is reported. Mono- and di-methyl salts of the 3-substituted diyne have been obtained and the charge-transfer complexes with tetramethyl-p-phenylenediamine (TMPD) are formed.

Synthesis, and structural, conformational and pharmacological studies of new fentanyl derivatives of the norgranatane system

A series of 9-phenethyl-3-α-(N-arylamido)norgranatanes have been synthesized and studied by 1H and 13C-NMR spectroscopy, and the crystal structure of 9-phenethyl-3-α-(N-p-tolyl-p-chlorobenzamido)norgranatane has been determined by X-ray diffraction. The compounds studied display in deuteriochloroform the same preferred chair–boat conformation with the disubstituted ring in a slightly distorted boat form. This bicycle conformation is similar to that found for compound 4f in the crystal state. In vivo pharmacological testing demonstrated that compounds 4a–h were inactive in the analgesic test, with the exception of compound 4b(the N-p-tolylpropanamido derivative) which showed an ED50 of 100 mg kg–1p.o.

Structural, conformational and pharmacological study of some esters derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9β-ol

Abstract A series of some esters derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9β-ol were synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of 3-methyl-2,4-diphenyl-9β(3,5-dimethyl-benzoyloxy)-3-azabicyclo[3.3.1]nonane (II) has been determined by X-ray diffraction. The compounds studied display, in deuterochloroform, a flattened chair-chair conformation with the cyclohexane ring more flattened than the piperidine moiety and the NCH3 groups in equatorial position. Pharmacological assays on mices were drawn to evaluate drug-induced behavioral alteration, peripheral or central acute toxicity analgesic and neuroleptic activity.