270mmol) of compound 4, 0.11g (0.432mmol) of iodine, 0.19g (1.08mmol) of HIO3 in 5mL of dioxane, selleck chem Gemcitabine and 2.5mL of water was refluxed for 5 hours. After cooling to room temperature, the precipitate was formed, which was filtered and washed with water. Yield 0.152g (64%), colorless crystals, m.p. 180��C (decomposed, dioxane-water, 3:1). NMR 1H (DMSO-d 6), ��, ppm: 6.96 (2H, H3-Ph), 7.61 (s, 4H, H3-Pz), 7.75 (s, 4H, H5-Pz), 7.85 (2H, H5-Ph),7.91 (s, 2H, Pz2CH).3. Results and DiscussionPreviously unknown bitopic ligand 1 was prepared by the reaction of 4 equivalents of pyrazole (PzH) with neopentane tetrabromo derivative (1,3-dibromo-2,2-bis(bromomethyl)propane) (NTB) in a superbasic KOH-DMSO medium (Scheme 1).

The moderate yield of 36% could not be improved by varying the reagents ratio (PzH:NTB:KOH) or reaction temperature (from 20 to 120��C), which is probably due to steric reasons. In agreement with this, more bulky 3,5-dimethylpyrazole did not give substitution product at all and only starting materials were recovered.Scheme 1Synthesis of tetrakis[(pyrazol-1-yl)methyl]methane 1.In an attempt to improve product yield we tried to change the bromo leaving group to tosyloxy moiety. Unexpectedly, no tetra-pyrazolyl substituted product was obtained in this case. Instead, bis(pyrazolylmethyl) derivatives of oxetane were obtained, apparently as a result of intramolecular cyclization (Scheme 2). Similar cyclizations under the action of strong bases were reported previously for tri- and tetratosylates of pentaerythritol [11].Scheme 2Formation of 3,3-bis(pyrazol-1-ylmethyl)oxetanes 2, 3 as a result of intermolecular cyclization.

Synthesis of unsubstituted pyrazole compound 2 from potassium pyrazolidine and corresponding 3,3-dimethyloxetane derivative has been reported earlier [12]. The method of synthesis proposed here is more convenient and allowed to prepare previously unknown dimethyl derivative 3.Compounds 2 and 3 are interesting as ligands for coordination chemistry and as semiproducts for synthetic organic chemistry, since the reactive oxetane cycle can be opened by different basic agents with the formation of a variety of polyfunctional compounds.We have also prepared a new bitopic ligand with o-phenylene spacer. Compound 4 was obtained by the reaction of ��, ��, ����, ����-tetrabromo-o-xylene with pyrazole in a superbasic medium (Scheme 3).

Previously we have used this method for the preparation of ligands with p-phenylene spacer [13].Scheme 3Oxidative iodination of 1,2-bis[bis(pyrazol-1-yl)methyl]benzene.In case of p-xylene derivative, tetrapyrazolyl ligands were obtained for both unsubstituted and 3,5-dimethylsubstituted pyrazole [13]. In contrast, o-xylene Carfilzomib derivative reacted only with unsubstituted pyrazole, while in case of 3,5-dimethylpyrazole only starting materials were recovered, which is again due to steric reasons.