[76847-41-2] · C17H17BrN2O2 · 3-Bromo-4,5-dihydro-5-hydroperoxy-4,4-dimethyl-3,5-diphenyl-3H-pyrazole · (MW 361.24)
(oxygen-atom transfer reagent; heteroatom and alkene oxidation2)
Physical Data: mp 77-80 °C (dec).
Solubility: sol CHCl3, CH2Cl2, ether, acetone.
Analysis of Reagent Purity: 3 gravimetric analysis gives 96% of bromine theoretical yield. Analysis of gaseous products (thermolysis) shows an N2 to O2 ratio of 1:1. IR (KBr): stretching absorptions for OOH and N=N at 3250 and 1540 cm-1, respectively. 1H NMR (CDCl3): -0.05 (s, 3H), 1.68 (s, 3H), 7.2-7.8 (m, 11H). 13C NMR (CDCl3): 19.9, 23.0, 25.8, 48.6, 102.4, 119.7, 125.7, 128.2, 128.3, 129.1, 132.1, 135.4, 138.9.
Preparative Method: 3 to a slurry of 2.0 g (8.0 mmol) of 4,4-dimethyl-3,5-diphenyl-4H-pyrazole in anhydrous ether at 0 °C is carefully added in small portions 6 g (159 mmol) of 90% Hydrogen Peroxide (caution: danger of explosion!). The solution is allowed to warm to rt and 1.17 g (4.1 mmol) of 1,3-Dibromo-5,5-dimethylhydantoin is added as a powder, portionwise, over a 20-30 min period in the dark. The resulting solution is kept at -20 °C for 48 h, after which it is washed with cold 10% sodium bicarbonate and dried over anhydrous magnesium sulfate. Filtration and removal of the solvent under reduced pressure at 0 °C affords the crude product as a yellow oil; recrystallization from CH2Cl2/petroleum ether (below -20 °C) yields white crystals of the desired reagent in 75% yield.
Handling, Storage, and Precautions: should be stored at low temperature. Crystals have been kept at -30 °C for years with little or no detectable decomposition. Solutions of the hydroperoxide must contain small amounts of cis- or trans-3-hexene to prevent self-induced decomposition. Addition of 2 mL of the unreactive alkene per 1 mL of solvent stabilizes the reagent. All normal precautions used in the handling of peroxidic materials should be followed.
3-Bromo-4,5-dihydro-5-hydroperoxy-4,4-dimethyl-3,5-diphenyl-3H-pyrazole (1) is one of the most reactive organic hydroperoxides known.1 As an electrophilic oxygen-atom transfer reagent, its reactivity in heteroatom oxidation (eq 1)2 is similar to that of flavin hydroperoxides and ca. two orders of magnitude faster than acyclic azo hydroperoxides.4 Both N- and S-oxidation have been found to be first order in (1) and in substrate, respectively. No external proton source was required. The reactivity of (1) can be estimated1 to be ca. 105 that of Hydrogen Peroxide and t-Butyl Hydroperoxide for N-oxidation. Heteroatom oxidation has been found4b to be an order of magnitude slower in acetone-d6 than in CDCl3.
Azo hydroperoxide (1) has been found to be of sufficient reactivity to epoxidize alkenes (eq 2) in good yield under mild conditions.2 The selectivity is essentially identical to that of peroxy acids. The reactivity of (1) is comparable to that of 2-Hydroperoxyhexafluoro-2-propanol and roughly two orders of magnitude lower than that of Peracetic Acid.1 Representative product yields and second order rate constants for heteroatom and alkene oxidation are listed in Table 1.
Oxygen-atom transfer reagent (1) offers the following advantages: (a) high reactivity with normal selectivity; (b) mild reaction conditions with
neutral products; and (c) long-term storage. Limitations for this reagent center on its synthesis. The procedure3 must be followed in detail and the method has not been extended to additional compounds. Conc H2O2 is required in the preparation which greatly increases the difficulty in the preparation of labeled reagent. The newer generation4b,5 of cyclic azo hydroperoxides are of equal reactivity but are prepared by the reaction of oxygen with 3,4-dihydro-2H-pyrazoles (eq 3). Thus these compounds can be prepared readily with 17O or 18O enriched oxygen for use as labeling reagents.4a
Alfons L. Baumstark & Pedro C. Vasquez
Georgia State University, Atlanta, GA, USA