Novel ferrocene imide derivatives: synthesis, conformational analysis and X-ray structure.

The synthesis and structural characterization of the ferrocene imide derivatives Fc-CO-NH-CO-Me (4), Fc-CO-NH-CO-Fc (7) and Fc-CO-NH-CO-Fn-CO-NH-CO-Fc (8) have been reported. The mononuclear, dinuclear and trinuclear ferrocene imides were prepared by the reaction of ferrocenecarboxamide (3), with acetyl chloride, ferrocenecarbonyl chloride (2) and ferrocene-1,1'-(dicarbonyl chloride) (6), respectively. IR spectroscopic analysis revealed the absence of intramolecular hydrogen bonds in solutions of imides 4, 7 and 8. The crystal packing of N-acetylferrocenecarboxamide (4) is characterized by N-H⋯O hydrogen bonds forming centrosymmetric dimers, while the molecules of its homologue N-methylferrocenecarboxamide (5) are self-assembled by intermolecular N-H⋯O bonds into infinite chains. A detailed conformational analysis (DFT study) suggests the cis-trans configuration of ferrocene imide derivative 7 in solution. The effect of different substituents attached to bridged imide nitrogen on conformational properties of bis-ferrocenyl imides was further investigated and results compared to the existing experimental data.

N,N-Dibenzoyl-ferrocenecarboxamide.

In the title compound, [Fe(C(5)H(5))(C(20)H(14)NO(3))], the cyclo-penta-dienyl rings deviate by 9.3 (2)° from an eclipsed conformation, defined by C-Cg(1)-Cg(2)-C pseudo-torsion angles ranging from 8.8 (1) to 9.85 (1)°. The coordination at the N atom is slightly pyramidal, as indicated by the angular sum around it of 352.6°. The amide group is inclined at 17.86 (9) and 27.27 (11)° with respect to the aromatic rings. In the crystal, mol-ecules are linked by one C-H⋯O hydrogen bond and one C-H⋯π inter-action into a two-dimensional framework parallel to the b axis.

The first ferrocene analogues of muramyldipeptide.

The two structurally interesting bioorganometallic analogues of muramyldipeptide (MDP) with potential immunomodulatory activity were synthesized starting from the O-protected N-acetylmuramic acid (MurNAc), L- or D-Ala and 1'-aminoferrocene-1-carboxylic acid (Fca). They were fully characterized by IR, (1)H NMR, (13)C NMR and CD spectroscopy as well as by FD mass spectrometry.

Methyl 4-(1'-carboxyferrocen-1-yl)butyrate.

The title compound, [Fe(C6H5O2)(C10H13O2)], contains a heteroannularly substituted ferrocene unit, with the two substituents, viz. 3-(methoxycarbonyl)propyl and carboxyl, both capable of forming O-H...O hydrogen bonds. The keto ester group is stereochemically hindered by the trimethylene spacer and does not participate in intramolecular hydrogen-bond formation. Instead, the carboxy groups form self-complementary intermolecular hydrogen bonds [O...O = 2.650 (2) A], which join the molecules into centrosymmetric dimers with a graph-set descriptor R(2)2(8).

Helically chiral ferrocene peptides containing 1'-aminoferrocene-1-carboxylic acid subunits as turn inducers.

We present a detailed structural study of peptide derivatives of 1'-aminoferrocene-1-carboxylic acid (ferrocene amino acid, Fca), one of the simplest organometallic amino acids. Fca was incorporated into di- to pentapeptides with D- and L-alanine residues attached to either the carboxy or amino group, or to both. Crystallographic and spectroscopic studies (circular dicroism (CD), IR, and NMR) of about two dozen compounds were used to gain a detailed insight into their structures in the solid state as well as in solution. Four derivatives were characterized by single-crystal X-ray analysis, namely Boc-Fca-Ala-OMe (16), Boc-Fca-D-Ala-OMe (17), Boc-Fca-beta-Ala-OMe (18), and Boc-Ala-Fca-Ala-Ala-OMe (21) (Boc=tert-butyloxycarbamyl). CD spectroscopy is an extremely useful tool to elucidate the helical chirality of the metallocene core. Unlike in all other known ferrocene peptides, the helical chirality of the ferrocene is governed solely by the chirality of the amino acid attached to the N terminus of Fca. Depending on the degree of substitution of both cyclopentadiene (Cp) rings, different hydrogen-bonding patterns are realized. (1)H NMR and IR spectroscopy, together with the results from X-ray crystallography, give detailed information regarding not only the hydrogen-bonding patterns of the compounds, but also the equilibria between different conformers in solution. Differences in chemical shifts of NH protons in dimethyl sulfoxide ([D(6)]DMSO) and CDCl(3), that is, the variation ratio (vr), is used for the first time as a measure of the hydrogen-bonding strength of individual COHN bonds in ferrocenoyl peptides. In dipeptides with one intramolecular hydrogen bond between the pendant chains, for example, in dipeptide 16, an equilibrium between hydrogen-bonded and open forms is observed, as testified by a vr value of around 0.5. Higher peptides, such as tetrapeptide 21, are able to form two intramolecular hydrogen bonds stabilizing one single conformation in CDCl(3) solution (vr approximately 0). Due to the low barrier of Cp-ring rotation, new and unnatural hydrogen-bonding patterns are emerging. The systematic work described herein lays a solid foundation for the rational design of metallocene peptides with unusual structures and properties.

The first oligopeptide derivative of 1'-aminoferrocene-1-carboxylic acid shows helical chirality with antiparallel strands.

The unnatural organometallic amino acid 1'-aminoferrocene-1-carboxylic acid (Fca) induces a turn structure in a tetrapeptide with anti-parallel strands which is stabilized by two intra-molecular hydrogen bonds in the solid state and in solution.

Ferrocene compounds. XXXIX. 1-Ferrocenylisochromane.

In the title compound, [Fe(C(5)H(5))(C(14)H(13)O)], the plane of the heterocyclic ring is almost perpendicular to the plane of the substituted cyclopentadienyl ring, and the heterocyclic ring adopts a half-chair conformation. The conformation of the nearly parallel cyclopentadienyl (Cp) rings [the dihedral angle between their planes is 2.7 (1) degrees ] is almost halfway between eclipsed and staggered, and the rings are mutually twisted by about 19.4 (2) degrees (mean value). The mean lengths of the C-C bonds in the substituted and unsubstituted cyclopentadienyl ring are 1.420 (2) and 1.406 (3) A, respectively, and the Fe-C distances range from 2.029 (2) to 2.051 (2) A. The phenyl and unsubstituted cyclopentadienyl rings are involved in C-H.pi interactions, with intermolecular H.centroid distances of 2.85 and 3.14 A for C-H.pi(Ph), and 2.88 A for C-H.pi(Cp). In two of these interactions, the C-H bond points towards one of the ring bonds rather than towards the ring centroid. In the crystal structure, the C-H.pi interactions connect the molecules into a three-dimensional framework.

Ferrocene compounds. XXXVIII. Dimethyl ferrocene-1,1'-dicarboxylate.

In the title compound, [Fe(C(7)H(7)O(2))(2)], the cyclopentadienyl rings and the two attached methoxycarbonyl groups, in an anti arrangement, form an extended pi-conjugated system. The Fe-C distances range from 2.035 (3) to 2.061 (3) A and the average value of the C-C bond lengths in the two cyclopentadienyl rings is 1.419 (5) A. The rings are almost parallel to one another [1.0 (2) degrees ] and are mutually twisted from an eclipsed conformation by only 1.8 (3) degrees (average value). The methoxycarbonyl groups are twisted out of the plane of the cyclopentadienyl rings by 6.5 (4) and 15.7 (4) degrees, respectively. The molecules are joined into dimers by intermolecular C-H.O hydrogen bonds that form ten-membered rings. The same types of hydrogen bonds form eight-membered rings and infinite chains along the b axis.

Ferrocene compounds. XXXIV. 1'-(tert-butoxycarbonylamino)ferrocene-1-carboxylic acid.

Heteroannularly substituted ferrocene derivatives can act as model systems for various hydrogen-bonded assemblies of biomolecules formed, for instance, by means of O-H...O and N-H...O hydrogen bonding. The crystal structure analysis of 1'-(tert-butoxycarbonylamino)ferrocene-1-carboxylic acid, [Fe(C(10)H(14)NO(2))(C(6)H(5)O(2))] or (C(5)H(4)COOH)Fe(C(5)H(4)NHCOOC(CH(3))(3), reveals two independent molecules within the asymmetric unit, and these are joined into discrete dimers by two types of intermolecular hydrogen bonds, viz. O-H...O and N-H...O. The -COOH and -NHCOOR groups are archetypes for dimer formation via two eight-membered rings. The O-H...O hydrogen bonds [2.656 (3) and 2.663 (3) A] form a cyclic carboxylic acid dimer motif. Another eight-membered ring is formed by N-H...O hydrogen bonds [2.827 (3) and 2.854 (3) A] between the N-H group and an O atom of another carbamoyl moiety. The dimers are assembled in a herring-bone fashion in the bc plane.