Pyrazoles. 19. Selective thermolysis reactions of bromo-1-nitro-1H-pyrazoles. Formation of 3-nitro-1H- vs. 4-nitro-1H-pyrazoles

Abstract

1833 with Z > 3u(O were retained for solution and refinement of the structure. The large number of unmeasured reflections stems from the small crystal size of 0.020 X 0.175 X 0.325 mm. The structure was solved by direct methods and refined to a final R value of 0.069. In the final refinement Fe and C1 atoms were assigned anisotropic thermal parameters and hydrogen atoms were included a t calculated positions using a riding model and U(H) = 1.2U(bonded C). The largest feature in a final difference map was 0.5, the size of a hydrogen and of no possible chemical significance. H(45) is the largest peak on a difference map computed with it omitted. Tables of anisotropic thermal parameters, hydrogen atom coordinates, and complete tables of bond distances and angles are available as supplementary material.Refluxing 3,4,5,-tribromo-l-nitro-1H-pyrazole (la) in benzene results in the evolution of bromine and NO2 and gives the 4-nitro-1H-pyrazole 2 and the 1-phenyl-1H-pyrazoles 4 and 5, while heating la in toluene gives 2 and benzyl bromide. Thermolysis of la in refluxing acetonitrile affords both 2 and the isomeric 5-nitro-1H-pyrazole 6a. Refluxing la mixed with the electron-rich 3,5-dimethyl-lH-pyrazole (7) in all three solvents gives 6a and 4-bromo-3,5-dimethyl-lH-pyrazole (8), whereas refluxing la mixed with anisole in benzene solution gives 2 and bromoanisoles. 3,5-Dibromo-l-nitro-lH-pyrazole (lb) in refluxing acetonitrile gives mainly 3,4-dibromo-5-nitro-1H-pyrazole (6a) and 3,5-dibromo-IH-pyrazole (3b), but refluxing l b mixed with 7 affords 3-bromo-5-nitro-1H-pyrazole (6b). Possible mechanisms are discussed involving intramolecular rearrangements to intermediates 3-bromo-3-nitro-3H-pyrazoles 9a,b and 4-bromo-4-nitro-4H-pyrazole 10 responsible both for the loss of bromine and NOP as well as for the electrophilic bromination of 7 and anisole. (1) Pyrazoles Studies. Part 19. Part 18: Berbee, R. P. M.; Habraken, C. L. J. Heterocycl. Chem. 1981, 18, 559-560. (2) Janssen, J. W. A. M.; Habraken, C. L.; Louw, R. J. Org. Chem. 1976, 41, 1758-1762 and earlier publications cited therein. (3) (a) Habraken, C. L.; Cohen-Fernandes, P. J. Chem. SOC., Chem. Commun. 1972, 38. (b) Pevzner, M. S.; Kulibabina, T . N.; Loffe, S. L.; Maslina, I. A,; Gidaspov, B. V.; Tartakovskii, V. A. Khim. Geterotsikl. Soedzn. 1979, 15, 550-554. Fernandes, P.; Habraken C. L. J . Org. Chem. 1984, 49, 3310-3314. (4) Zibuck, R.; Stahl, M. A.; Barchiesi, B.; Waalwijk, P. S.; Cohen-0 1986 American Chemical Society Selective Thermolysis Reactions Scheme I1

Novel Synthesis and Structural Characterization of a High-Affinity Paramagnetic Kinase Probe for the Identification of Non-ATP Site Binders by Nuclear Magnetic Resonance

“…Therefore, our synthetic efforts became focused on synthesizing this key intermediate whereby a convergent and flexible synthesis allowing for late stage diversity at both the headpiece and the tailpiece of the pyrazolo[1,5-α]pyrimidines could be achieved. These efforts resulted in the first report of the synthesis of 3-bromo-1 H -pyrazol-5-amine, 17 , obtained from the concomitant debromination and nitro reduction of the previously reported 16 , shown in Scheme . The regiochemistry of the reduction product was confirmed by spectroscopic comparison of 17 with commercially available 4-bromo-1 H -pyrazol-5-amine (Scheme ).…”

Preparation and Chemistry of 3/5-Halogenopyrazoles

“…The course of the rearrangement of 1-nitro-3,4,5-tribromopyrazole ( 227 ) can be shifted toward either the 4- or the 5-nitro isomer 228 or 230 . Indeed, upon heating the 1-nitropyrazole 227 in the presence of 3,5-dimethylpyrazole, 62% of the 5-nitro isomer 228 was obtained along with the 4-brominated pyrazoles 229 . Alternatively, the 4-nitro isomer 230 was prepared by heating compound 227 in toluene, and yields up to 65% were subsequently reported with this method .…”

“…Indeed, upon heating the 1-nitropyrazole 227 in the presence of 3,5-dimethylpyrazole, 62% of the 5-nitro isomer 228 was obtained along with the 4-brominated pyrazoles 229 . Alternatively, the 4-nitro isomer 230 was prepared by heating compound 227 in toluene, and yields up to 65% were subsequently reported with this method . An iodine atom on carbon 4 is also turning out to be quite labile as, for instance, the sulfo-nitric treatment of compounds 232 – 233 or 236 led to the 4-nitrated derivatives 234 – 235 or 237 . , …”

New approach to the synthesis of benzo[e]pyrazolo[5,1-b][1,3]oxazines

“…A mixture of 3,4,5-tribromopyrazole [4] (1 g, 3.3 mmol), salicyl alcohol (0.41 g, 3.3 mmol), and K 2 CO 3 (1.38 g, 10 mmol) in DMF (10 ml) was heated at reflux for 6 h with stirring. The mixture was cooled and poured into 50 ml water.…”