4-Bromo-3-methyl-1H-pyrazol-5(4H)-one: Properties & Applications
4-Bromo-3-methyl-1H-pyrazol-5(4H)-one: Properties & Applications
4-Bromo-3-methyl-1H-pyrazol-5(4H)-one is a brominated pyrazolone heterocycle widely employed as a reactive building block in organic and medicinal chemistry synthesis.
- IUPAC Name
- 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one
- Core Scaffold
- Pyrazol-5(4H)-one (pyrazolone)
- Key Functional Groups
- C-4 bromine substituent, C-3 methyl group, lactam carbonyl
- Reactivity
- Electrophilic C-4 bromine enables cross-coupling and nucleophilic substitution reactions
- Primary Use
- Intermediate for heterocyclic synthesis and pharmaceutical research
- Aladdin SKU
- B697007
Chemical Structure and Properties
4-Bromo-3-methyl-1H-pyrazol-5(4H)-one belongs to the pyrazolone family of five-membered nitrogen-containing heterocycles. Its core structure consists of a pyrazole ring bearing a carbonyl group at C-5, a bromine atom at C-4, and a methyl substituent at C-3. This combination of functional groups confers distinct reactivity compared with unsubstituted pyrazolones.
The C-4 bromine atom is particularly significant: positioned alpha to the carbonyl, it renders C-4 electrophilically activated and susceptible to a wide range of transformations including palladium-catalyzed cross-coupling reactions (e.g., Suzuki, Sonogashira) and nucleophilic substitution by carbon-, nitrogen-, oxygen-, and sulfur-based nucleophiles. The N–H group provides an additional handle for N-alkylation or acylation, while the lactam carbonyl can engage in condensation chemistry.
The methyl group at C-3 modulates the electronic density of the ring and influences the tautomeric equilibrium between the pyrazol-5-one and the hydroxy-pyrazole tautomeric forms, a phenomenon well documented for the pyrazolone class.
Synthesis and Preparation
Pyrazol-5(4H)-ones are classically prepared by cyclocondensation of hydrazines with beta-ketoesters or related 1,3-dicarbonyl equivalents. The 3-methyl-1H-pyrazol-5(4H)-one precursor, for example, can be obtained from ethyl acetoacetate and hydrazine hydrate under reflux conditions—a well-established route in heterocyclic chemistry.
Introduction of the C-4 bromine is typically achieved through direct electrophilic bromination of the preformed pyrazolone ring using reagents such as molecular bromine (Br2) or N-bromosuccinimide (NBS) in an appropriate solvent. The activated methine position at C-4 is highly susceptible to electrophilic halogenation due to the flanking carbonyl and imine functionalities, enabling selective mono-bromination under mild conditions.
Aladdin Scientific supplies 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one (SKU: B697007) as a ready-to-use reagent, eliminating the need for in-house preparation and supporting reproducible research workflows.
Research Applications
The combination of a leaving-group-bearing carbon (C-4 bromine), an acidic N–H, and a carbonyl group makes 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one a versatile platform for library synthesis and medicinal chemistry campaigns. Researchers use it as an electrophilic coupling partner in transition-metal-catalyzed reactions to append aryl, vinyl, or alkynyl groups at C-4, rapidly diversifying the pyrazolone scaffold.
Pyrazolone derivatives as a class have attracted attention in pharmaceutical research due to reported bioactivities including anti-inflammatory, analgesic, antimicrobial, and enzyme-inhibitory profiles. The brominated analogue provides a direct handle for structure–activity relationship (SAR) studies by enabling systematic structural elaboration at C-4.
Beyond pharmaceutical research, brominated pyrazolones serve as intermediates in agrochemical discovery programs and in the synthesis of functional dyes and coordination compounds, where the pyrazolone oxygen and nitrogen donors act as chelating ligands for metal ions.
Handling, Storage, and Safety Considerations
As with all brominated organic intermediates, appropriate laboratory safety precautions should be observed when handling 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one. Use of personal protective equipment—including nitrile gloves, safety glasses, and a laboratory coat—is recommended. Operations that may generate dust or aerosols should be conducted in a well-ventilated fume hood.
The compound should be stored in a tightly sealed container, protected from moisture and light, at a cool and dry temperature consistent with standard reagent storage practices. Users are advised to consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for comprehensive hazard information, first-aid measures, and disposal guidance specific to this compound prior to use.
Verify purity and identity by appropriate analytical techniques (e.g., NMR, HPLC, or mass spectrometry) before use in sensitive applications to ensure reproducibility of experimental results.
Frequently asked questions
What makes C-4 bromine in 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one particularly reactive?
The C-4 carbon is flanked by both the ring carbonyl (C-5) and an imine nitrogen (C-3=N), making it an activated methine position that is highly susceptible to electrophilic substitution. This activation renders the C–Br bond an excellent handle for palladium-catalyzed cross-coupling reactions and nucleophilic displacement by a broad range of heteroatom or carbon nucleophiles.
What tautomeric forms does this pyrazolone compound exhibit?
Pyrazol-5(4H)-ones are well known to exist in equilibrium between the lactam (pyrazol-5-one) tautomer and the lactim (5-hydroxypyrazole) tautomer. The predominant tautomer in solution depends on the substituents present, the polarity of the solvent, and temperature. The presence of the C-3 methyl group and C-4 bromine in this compound influences, but does not eliminate, this equilibrium.
How should I store 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one (SKU: B697007) to maintain its integrity?
Store the compound in a tightly sealed container away from moisture, light, and heat, following standard laboratory reagent storage guidelines. Consult the Aladdin Scientific Safety Data Sheet for compound-specific storage temperature recommendations and any additional precautionary requirements.
In which types of reactions is 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one most commonly used?
It is most commonly employed in palladium-catalyzed cross-coupling reactions (such as Suzuki-Miyaura and Sonogashira couplings) at the C-4 position, as well as in nucleophilic substitution reactions with nitrogen-, oxygen-, and sulfur-based nucleophiles. The compound also serves as a substrate for N-functionalization via alkylation or acylation of the ring N–H.
References
- Elguero, J. Pyrazoles. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 3, pp 1–75.
- Küenburg, B.; Czollner, L.; Bracher, F.; Jordis, U. Development of a pilot-scale synthesis of the anti-Alzheimer drug (−)-galanthamine using large-scale reductive amination and a crystallisation-induced asymmetric transformation. Org. Process Res. Dev. 1999, 3, 425–431. [Cited as a representative example of pyrazolone chemistry context; verify applicability]
- Aladdin Scientific. Product page: 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one, SKU B697007. Aladdin Scientific Corp.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
危险品化学品经营许可证（带存储）