Multidentate ligands from N -hydroxy-and N -aminopyrazole

The reaction between hexafluorobenzene and the anion of 1-hydroxypyrazole affords a mixture of the products of bis-, tetrakis-and hexakis-substitution. On the other hand the anion of 1-aminopyrazole affords only the product of monosubstitution probably due to the acidity of the remaining NH. Finally, in the case of hexakis(bromomethyl)benzene, its reaction with 1-hydroxypyrazole lead to the hexakis-substituted product. All compounds have been characterized by NMR ( 1 H and 13 C) and mass spectrometry


Introduction
The ligands with the N-pyrazolylbenzene structure belong to two families, that where the pyrazole is directly linked to the phenyl ring and that where there is a spacer between the pyrazole and the benzene (Scheme 1).The first family is represented by the compounds I we called "propellenes", [1][2][3][4][5][6][7][8][9][10][11][12] such as hexakis(pyrazol-1-yl)benzene.There are many possibilities for the second family but the most significant representatives are compounds II [CH 2 as a linker, poly(pyrazol-1-ylmethyl)benzenes] studied by Steel and others (the black circles represent 1pyrazolyl substituents, from 1 to six).

13-20
The second class, owing to their increased flexibility, is more suitable as metal ligands in coordination chemistry as well as guests in host-guest chemistry.We report in the present publication our attempts to replace the CH 2 "ball-and-socket joint" of II by an O atom or a NH group or even by a CH 2 -O spacer.The presence of a supplementary O or N atom with their lone pairs could modify or even improve the above mentioned properties.

Results and Discussion
The reaction of 1-hydroxypyrazole 1 in basic conditions (1-hydroxypyrazolate 2) with hexafluorobenzene in THF/DMF in different conditions always affords a mixture of three compounds 3, 4 and 5 (Scheme 2).

Scheme 2
Mass spectrometry (exact mass) or elemental analyses, and 1 H and 13 C NMR (see NMR discussion) identified the three compounds.The reaction was carried out with ratios 1hydroxypyrazole/hexafluoro-benzene of 6/1 and 12/1 and with different reaction times (Table 1).The relative amounts were determined by 1 H NMR including the non reacted pyrazolate 2 and then converted to relative amounts not considering 2 (see note a in Table 1).We have underlined the most regio-selective conditions.Note that in all conditions there is a large amount of pyrazolate 2. It should be noted that hexafluorobenzene is a very volatile compound.Other conditions (see Experimental Part) have not improved the results.
The same reaction with the sodium salt of 1-aminopyrazole 7 affords exclusively the product of monosubstitution 8 (Scheme 3).When compound 8 was made to react with 7 no reaction was observed.We assign this lack of reactivity to the formation of the anion 9, which is much less reactive than the neutral molecule.When mixing 7 and 8 probably it results in a mixture of 6 and 9.

Scheme 3
The last reaction we carried out involves hexakis(bromomethyl)benzene 10 and 1hydroxypyrazole 1 (Scheme 4): in this case we isolated only the full substituted derivative 11 with 73% yield.The behavior of 1 towards hexafluorobenzene (a mixture of compounds with much starting 1) and with 11 (only a compound in high yield) may be due either to steric effects (11 is less hindered than 5) or to electronic effects (each introduced OPz group diminished the leaving group ability of the remaining fluorines) or even, to the volatility of hexafluorbenzene., the most representative features being δH 4 < δH 3 < δH 5 , J 45 ≥ J 34 > J 35 , δC 4 < δC 5 < δC 3 and 1 J(C 4 H 4 ) < 1 J(C 3 H 3 ) < 1 J(C 5 H 5 ).In the case of 11 the 1 H and 13 C NMR data of N-benzyloxypyrazole 12 24 were considered.For the benzene quaternary carbons the multiplicity of the signals due to carbonfluorine couplings has been taken into account.Finally, NMR heteronuclear bidimensional experiments permitted the complete assignment of the signals and confirmed our proposal for the structures of the products (within the molecular formulae corresponding to exact masses).

Conclusions
We have proved that N-hydroxypyrazole yields hexakis-substituted compounds when reacting with hexakis(bromomethyl)benzene and hexafluorobenzene, in the latter case together with bisand tetrakis-substituted derivatives.In contrast, the reaction of N-aminopyrazole with hexafluorobenzene affords only the monosubstitution product due to acidity of the remaining NH.These new compounds, where there is a spacer between the pyrazole and the benzene moieties, will certainly prove to be useful in host-guest chemistry and for metal coordination complexes.

Experimental Section
General Procedures.Melting points were determined on a microscope hot stage apparatus and are uncorrected.The R f values were measured on aluminum backed TLC plates of silicagel 60 F254 (Merck, 0.2 mm) with the indicated eluent.Column chromatography was performed on silica gel (Merck 60, 70-230 mesh).NMR spectra were recorded on a Bruker AC-200 spectrometer at 298 K working at 200.13 for 1 H and 50.32 for 13 C.Chemical shifts are expressed in ppm/TMS for 1 H and 13 C. Solvents were CDCl 3 and DMSO-d 6 .Signals of 1 H and 13 C NMR spectra were assigned with the help of XH-CORR ( 1 H-13 C) bidimensional experiments.Exact masses were determined using electron impact technique and PFK as reference for volatile samples, or FAB-MS positive spectra for the non-volatile derivatives, accuracy ± 0.0025 daltons (VG AutoSpec).
Reaction of 1-hydroxypyrazole with hexafluorobenzene.In a round flask, 1 g (0.12 mmol) of 1 25 was dissolved in 10 mL of anhydrous THF and Ar was flowed during 20 min.Then, a suspension of 476 mg (12 mmol) of 60% NaH in 10 mL of anhydrous THF was added.The mixture was refluxed under Ar atmosphere for 2 h (in this way the sodium salt 2 was obtained).The reaction was allowed to cool down to room temperature and 0.  (12).This compound was prepared as reported in reference. 27

Table 2 .
1H chemical shifts in ppm and coupling constants in Hz of the compounds described in

Table 3 .
13C chemical shifts in ppm and coupling constants in Hz of the compounds described in