On the synthesis of heterocyclic dendrons

The synthesis of dendrons 1 – 7 bearing azole (pyrazole, imidazole and 1,2,4-triazole) moieties is described. The synthesis of these compounds was carried out using different approaches: functionalisation of the methylene bridge of bispirazol-1-ylmethane derivates; double Michael addition of 1,2,4-triazole to methyl propiolate, nucleophilic substitution of halide from the corresponding 2,6-dichloro-4-methylpyridine or 1,3-bis(bromomethyl)benzene derivatives, and nucleophilic substitution on p -hydroxybenzaldehyde dimethylacetal. Schotten-Baumann reaction with 1,3,5-trischlorocarbonylbenzene and Sonogashira coupling with 1,3,5-triethynylbenzene were used for the synthesis of G0-dendrimers.


Introduction
Metallodendrimers, 1 i.e. dendrimers that contain metal atoms or cations, constitute a special class of dendrimer whose redox, 2 catalytic, 3 ion recognition, 4 sensor, 5 and light harvesting 6 properties are well documented.Metallodendrimers can act as homogeneous catalysts but are significantly larger than reactants and products, a situation that allows membrane separation techniques to be applied.Other advantages of these dendritic catalysts have been demonstrated and are described in the review by van Leeuwen.3a The active catalytic centre in a metallodendrimer can be situated in three different areas: (i) metal atom as the dendrimer core, (ii) metal atoms in the dendrimer branches, (iii) metal atoms in the periphery.The synthesis of the third type of metallodendrimer may be envisaged by two strategies.Firstly, it is possible to build the dendrimer and then incorporate the metal atoms in the final stage or, secondly, the metal atoms can be incorporated within the molecular fragments used to build the dendrimer.Regardless of the choice of route, it is necessary to obtain appropriate dendrons that have the ability to coordinate the catalytically active metal atom.In addition, dendrons have to bear different functional groups as focal points.In terms of complex formation or the coordination of metal atoms, the azoles are excellent candidates due to the presence of lone pairs on the nitrogen atoms 7 and the possibility of transformation into nucleophilic carbenes. 8he preparation of a catalyst with different catalytic centres requires the following: (i) cores with two or more different functional groups, (ii) dendrons with different focal points and (iii) dendrons having different metal atoms.As the first step in the preparation of a multi-centred catalyst we envisaged the synthesis of dendrons bearing different azoles on the periphery and having different focal points.

Results and Discussion
We describe the preparation of new dendrons bearing 1,2,4-triazole, pyrazole and imidazole systems and having different focal points (Figure 1).These compounds are suitable for the convergent synthesis of dendrimers with peripheral azole moieties.

Figure 1
Compound 1 was prepared from 3,5-dimethylpyrazole by following the route outlined in Scheme 1, the conditions of which are described in the experimental section.Phase Transfer Catalysis (PTC) 9 alkylation of 3,5-dimethylpyrazole with dichloromethane afforded bis(3,5dimethylpyrazol-1-yl)methane.Deprotonation with n-BuLi in THF at low temperature and subsequent reaction with carbon dioxide yielded the corresponding lithium carboxylate. 10This lithium salt was reduced with BH 3 •Me 2 S in THF 11 (Scheme 1).

Scheme 1
Compound 2 was synthesized by a double Michael addition of 1,2,4-triazole to methyl propiolate in THF using the azole/base/Michael acceptor molar ratio indicated (Scheme 2).The use of the appropriate molar ratio guarantees the presence of both the azolate anion and azole, the latter of which protonates the resulting enolate.This situation is necessary to perform the second Michael addition.Although the addition reactions between the 1,2,4-triazole anion and alkyl acrylates, acrylamide and acrylonitrile are known, 12 results concerning Michael addition to activated alkynes have not been reported to date.2,6-Bis(imidazol-1-yl)-4-methylpyridine (3) was prepared by reaction of imidazole, 2,6dichloro-4-methylpyridine and potassium hydroxide using solid-liquid PTC (without solvent) nucleophilic substitution conditions.The starting material, 2,6-dichloro-4-methylpyridine, was prepared by alkylation (n-BuLi/MeI) of 2,6-dichloropyridine according to a literature procedure 13 (Scheme 3).
In conclusion, several heterocyclic dendrons were synthesized bearing pyrazole, imidazole and 1,2,4-triazole systems and with different focal points.The possibility of building dendrimers from these systems has also been demonstrated.The ability of this kind of dendron to form complexes with catalytic metal atoms is known.The synthetic routes reported here therefore provide a promising way to develop multi-centred dendrimeric catalysts.

Experimental Section
General Procedures.Solvents were purified by distillation from appropriate drying reagents before use.Melting points were determined in capillary tubes on a Gallenkamp apparatus and are uncorrected.Elemental analyses were performed on a Perkin-Elmer 2400 CHN microanalyzer.NMR spectra were recorded on a Varian Unity operating at 299.980 MHz for 1 H and 75.423MHz for 13 C.Chemical shifts are expressed in parts per million (δ) relative to TMS as internal standard.The resonances of compounds were assigned by difference NOE and Hetcor experiments.