Three-Component Reaction of Tautomeric Amidines with 3-Ferrocenylmethylidene-2,4-pentanedione. Formation of Polymeric Coordination Complexes of Potassium Ferrocenyl-(hexahydro)pyrimidoxides

Acetamidine hydrochloride and p-aminobenzamidine dihydrochloride interact with 3-ferrocenylmethylidene-2,4-pentanedione at 80–82 °C in the presence of K2CO3 in the water–alcohol medium in two tautomeric forms (the amidoimine and enediamine ones) with formation of mixtures of pyrimidine and piperidone derivatives and polymeric coordination complexes of potassium ferrocenyl(hexahydro)pyrimidoxides. The structure of the resultant compounds is elucidated on the basis of IR, 1H- and 13C-NMR spectroscopy, mass spectrometry and elemental analysis data. The crystal structures of 6-ferrocenyl-4-hydroxy-4-methyl-2-piperidone, potassium 6-ferrocenyl-4-methyl-2-methylidene(hexahydro)pyrimidin-4-oxide and 2-(4-aminophenyl)-4-ferrocenyl-6-methyl-pyrimidine were determined by X-ray analysis of suitable single crystals.

The structure of compounds 4-7 was elucidated on the basis of elemental analysis, mass spectrometry, 1 H and 13 C-NMR spectroscopy data, as well as X-ray diffraction analysis of single crystals of compounds 6 and 7.According to 1 H-NMR findings, 4-ferrocenyl-3-butenone (4) is generated solely in the form of the trans-isomer according to the J = 15.9Hz spin-spin coupling constant of the olefin protons.The 1 H-NMR spectrum of ferrocenylpyrimidine 5 contains signals from hydrogen atoms of two methyl groups and one ferrocene substituent, as well as one singlet from the olefinic hydrogen atom of the heterocycle.Additionally, in the 13 C-NMR spectrum of compound 5, there are three signals from the C 1 , C 3 and C 5 carbons of the heterocyclic ring and one signal from C ipso Fc, thus unambiguously confirming the structure of the resultant ferrocenylpyrimidine 5.
The structure of hydroxypiperidone 6 was established on the basis of IR, 1 H-NMR, and 13 C-NMR spectroscopy.The IR spectrum of compound 6 contains characteristic absorption bands of the NH, OH, C=O, and Fc groups (see the Experimental section).The 1 H-NMR spectrum contains signals from protons of one methyl and one ferrocene substituents, one hydroxyl group, one NH-fragment, two doublets from protons of the methylene fragment in the heterocycle, and also an ABX pattern of signals from protons of the -CH 2 -CH-fragment in the heterocycle.The 13 C-NMR data also confirm the structure of compound 6.
In addition to spectral data, the spatial configuration of piperidone 6 was further confirmed by X-ray diffraction analysis of single crystals obtained by crystallization from CH 2 Cl 2 .The general view of molecule 6 is shown in Figure 1, while the principal geometric parameters are listed in the Table 1.
The six-membered cycle in structure 6 has a boat conformation, where the ferrocene and methyl substituents occupy the axial-equatorial positions.Compound 7 is a water-and alcohol-soluble yellow crystalline substance, storage-stable in the crystalline form and in solutions, it decomposes during melting (~286 °C), a property that is characteristic of ionic products.Using crystallization from aqueous methanol, we have managed to grow single crystals of 7 that were suitable for X-ray diffraction studies of the spatial structure of 7. The general view of molecule 7 is shown in Figure 2, and the main geometrical parameters are listed in Table 1.Table 1.Selected bond lengths and bond angles for compounds 6, 7 and 8.

Selected bond lengths (Å) Selected bond angles (°)
As follows from the results of this analysis, compound 7 has the structure of potassium 6-ferrocenyl-4-methyl-2-methylidene(hexahydro)pyrimidin-4-oxide.The central fragment of the molecule is a six-membered ring with two nitrogen atoms.A characteristic feature of the crystal structure of 7 is that the unit cell contains two molecules with oppositely oriented ferrocene fragments and methylene fragments oriented so as to be brought closer to each other (Figure 3). Figure 4 shows the nature of coordination interactions of the potassium cation with three adjacent molecules 7, forming the polymeric structure of compound 7 and determining its high stability.Compounds 4, 8-11 were separated using column chromatography (Al 2 O 3 , grade III).The structure of each compound was determined on the basis of IR, 1 H and 13 C-NMR spectra, mass spectra, and elemental analysis, which are described in the Experimental section.
X-ray analysis of single crystals of compound 8 obtained by crystallization from CH 2 Cl 2 confirmed the structure of 8 to be that of 2-(4-aminophenyl)-4-ferrocenyl-6-methylpyrimidine (Figure 5).The Xray analysis data show that the N-C bonds in pyrimidine 8 have virtually equal lengths [d = 1.347 (5), 1.340 (5) Å].The lengths of Fe-C bonds and the geometry of the ferrocene sandwich are the same as in related compounds [19].Compound 11 is a yellow powder, which is soluble in water, methanol, and DMSO; it decomposes upon heating (~310 °C).The mass spectrum of compound 11 contains the peak of a molecular ion with m/z = 429 [M] + .The IR spectrum of compound 11 contains the characteristic absorption bands of the Fc, C=O, and NH groups.The 1 H and 13 C-NMR spectroscopy data are provided in the Experimental section.As follows from the 1 H-NMR spectra, compound 11 was obtained in the form of one diastereomer, presumably with a,e-trans-oriented Fc and Me groups.On the basis of our data and by analogy with the structure of potassium pyrimidoxide 7, product 11 was assumed to have the structure of potassium 6-ferrocenyl-4-methyl-2(4-oxo-2,5-cyclohexadienylidene)-hexahydropyrimid-4-oxide.Unfortunately, we failed to obtain single crystals of compound 11 that would be suitable for confirming its spatial structure by X-ray diffraction analysis.
To prove this statement, we studied the interaction of 4-ferrocenyl-3-buten-2-one 1 with amidines 2 and 3 under similar conditions (EtOH/H 2 O, K 2 CO 3 , 80-82 °C) and found that enone under these conditions does not cyclocondense with amidines 2 and 3 (Scheme 4).The reaction almost quantitatively yielded the initial chalcone 4, even after boiling of the reaction mixture for 24 h.

Posible Mechanisms of the Reactions of Acetamidine and p-Aminobenzamidine with 3-Ferrocenylmethylidene-2,4-pentanedione
On the basis of the results, we can make the following conclusions: (1) Chalcone 4 is formed in the studied reactions as a result of one-pot nucleophilic attack of amidine nitrogens on the carbonyl carbon of the acetyl group in β-diketone 1 (Scheme 5a).( 2

General
Column chromatography was carried out on alumina (Brockmann activity III).The 1 H-and 13 C-NMR spectra were recorded on a Unity Inova Varian spectrometer (300 and 75 MHz) for solutions in CDCl 3 (for compounds 4-6 and 8-10) and D 2 O (for compounds 7 and 11), with Me 4 Si as the internal standard.The IR spectra were measured with a Perkin-Elmer Instruments Spectrum RXI FTIR spectrophotometer using KBr pellets.The mass spectra were obtained on a Varian MAT CH-6 instrument (EI MS, 70 eV).The melting pointa were determined with w micro melting point apparatus (Boëtius or Fisher) and the uncorrected values were used.An Elementar Analysensysteme LECO CHNS-900 apparatus was used for the elemental analyses.The following reagents were purchased from Aldrich (Toluca, Mexico): ferrocenecarbaldehyde, 99%; acetylacetone, 99+%; acetamidine hydrochloride, 95%; 4-aminobenzamidine dihydrochloride, 95%.3-Ferrocenyl-methylidenepentane-2,4-dione (1) was prepared by condensation of ferrocenecarbaldehyde with acetylacetone in benzene in the presence of piperidinium acetate.The physical and 1 H-NMR spectroscopic characteristics of compound 1 were all in accordance with the literature data [18,20,21].

Crystal Structures of 6, 7 and 8
Single crystals of 6 and 8 were obtained by crystallization from CH 2 Cl 2 , while crystals of 7 were obtained by crystallization from H 2 O.The unit cell parameters and the X-ray diffraction intensities of 6, 7 and 8 were recorded on a Gemini (detector Atlas CCD, Cryojet N 2 ) diffractometer.The crystallographic data, the parameters of the X-ray diffraction experiments, and refinements are listed in

Figure 3 .
Figure 3. Structure of the fragment of unit cell of 7.

Figure 4 .
Figure 4. Fragment of X-ray crystal structure of 7.