2-((5-Bromopyrimidin-2-yl)thio)acetic Acid: Properties & Uses
2-((5-Bromopyrimidin-2-yl)thio)acetic Acid: Properties & Uses
2-((5-Bromopyrimidin-2-yl)thio)acetic acid is a halogenated pyrimidine-based thioether building block widely employed as a versatile intermediate in medicinal chemistry and heterocyclic synthesis.
- CAS-style IUPAC Name
- 2-((5-Bromopyrimidin-2-yl)thio)acetic acid
- SKU
- B193765
- Core Functional Groups
- Aromatic C–Br (electrophilic handle), thioether (C–S–C) linkage, carboxylic acid (–COOH)
- Molecular Framework
- Pyrimidine ring substituted at C-2 via sulfur and bearing bromine at C-5
- Key Reactivity
- Suzuki/Sonogashira cross-coupling at C–Br; amide/ester coupling at –COOH; potential S-oxidation or S-alkylation
- Supplier
- Aladdin Scientific
Chemical Structure and Properties
2-((5-Bromopyrimidin-2-yl)thio)acetic acid is a bifunctional heterocyclic compound combining three distinct reactive sites within a compact molecular framework. The pyrimidine ring, a six-membered aromatic nitrogen heterocycle, carries a bromine substituent at the 5-position and is connected at the 2-position through a sulfur atom to a methylene (–CH2–) group bearing a terminal carboxylic acid.
The electron-deficient nature of the pyrimidine ring is reinforced by the two ring nitrogen atoms, rendering the C-5 bromine particularly amenable to transition-metal-catalyzed cross-coupling reactions. The thioether linkage (C–S–C) is chemically stable under mild conditions yet can be selectively oxidized to a sulfoxide or sulfone under appropriate reagent conditions, offering further structural elaboration. The acetic acid moiety provides an ionizable handle suitable for salt formation, amide bond formation, or ester synthesis, enhancing the molecule's utility as a diversifiable scaffold.
As a solid organic acid, the compound is expected to exhibit moderate lipophilicity due to the combination of the lipophilic bromopyrimidine core and the hydrophilic carboxylic acid group, making it suitable for incorporation into drug-like molecules that must balance aqueous solubility with membrane permeability.
Synthesis and Preparation Routes
The most straightforward synthetic route to 2-((5-Bromopyrimidin-2-yl)thio)acetic acid involves the nucleophilic aromatic substitution (SNAr) reaction of 2-chloro-5-bromopyrimidine (or the corresponding 2-mercaptopyrimidine precursor) with thioglycolic acid (mercaptoacetic acid, HSCH2COOH) under basic conditions. The electron-deficient pyrimidine ring strongly activates the C-2 position toward SNAr, permitting displacement of a suitable leaving group by the thiolate nucleophile generated in situ under mild base.
Alternatively, 2-mercapto-5-bromopyrimidine can be S-alkylated with a haloacetic acid derivative (e.g., chloroacetic acid or its sodium salt) in the presence of a base such as potassium carbonate in a polar aprotic or protic solvent. This approach is operationally simple and scalable, providing the target compound in good yields after acidic workup to liberate the free carboxylic acid.
The bromine at C-5 is introduced either by direct electrophilic bromination of the pyrimidine precursor or by using commercially available 5-bromopyrimidine starting materials, avoiding harsh halogenation conditions on the final product. Researchers should handle the compound with standard laboratory precautions appropriate for organobromine compounds and carboxylic acids.
Research and Medicinal Chemistry Applications
The multi-functional architecture of 2-((5-Bromopyrimidin-2-yl)thio)acetic acid makes it a prized building block in drug discovery and synthetic medicinal chemistry. The C-5 aryl bromide serves as an entry point for palladium-catalyzed cross-coupling reactions—including Suzuki–Miyaura (boronic acids/esters), Sonogashira (terminal alkynes), Buchwald–Hartwig (amines), and Negishi (organozinc) couplings—enabling rapid diversification of the aromatic periphery of the scaffold.
The carboxylic acid group allows amide bond formation with a broad array of amines using standard coupling reagents (e.g., HATU, EDC/HOBt, T3P), facilitating the construction of amide-containing pharmacophores that are ubiquitous in approved pharmaceuticals. Esterification under Fisher or DCC-mediated conditions provides protected or prodrug forms of the molecule. These transformations can be orchestrated in either sequential or parallel fashion in library synthesis workflows.
Pyrimidine-2-thioether motifs are recognized in the literature as biologically relevant scaffolds appearing in kinase inhibitors, antiviral agents, antimicrobial compounds, and other bioactive small molecules. The bromine substituent at C-5 introduces a heavy-atom handle useful not only for coupling chemistry but also in X-ray crystallographic studies (anomalous dispersion phasing). Consequently, B193765 is suitable for researchers engaged in target-based drug discovery, fragment-based screening library construction, and structure–activity relationship (SAR) campaigns.
Handling, Storage, and Safety Considerations
As with all organobromine compounds and carboxylic acid derivatives, appropriate personal protective equipment (PPE) should be worn when handling 2-((5-Bromopyrimidin-2-yl)thio)acetic acid, including nitrile gloves, safety glasses, and a laboratory coat. Operations should be conducted in a well-ventilated fume hood, particularly during weighing and dissolution steps.
For storage, the compound should be kept in a tightly sealed container away from moisture, light, and incompatible materials (strong oxidizers, strong bases). Storage at controlled room temperature or under refrigeration (2–8 °C) in a dry environment is generally recommended for solid organic acids of this class to maintain long-term stability, though researchers should consult the certificate of analysis (CoA) provided with each lot for specific storage conditions confirmed by Aladdin Scientific.
The compound should be disposed of in accordance with local institutional and governmental regulations governing halogenated organic waste. Users should consult the Safety Data Sheet (SDS) supplied by Aladdin Scientific for complete hazard classifications, first-aid measures, and disposal guidelines before use.
Frequently asked questions
What are the primary coupling reactions possible with 2-((5-Bromopyrimidin-2-yl)thio)acetic acid?
The aryl C–Br bond at the 5-position of the pyrimidine ring is well-suited for palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura (with boronic acids or esters), Sonogashira (with terminal alkynes), Buchwald–Hartwig (with amines), and Negishi (with organozinc reagents) couplings. The carboxylic acid group can simultaneously or sequentially undergo amide or ester bond formation using standard activation chemistry.
How should 2-((5-Bromopyrimidin-2-yl)thio)acetic acid be stored to maintain stability?
The compound should be stored in a tightly sealed container, protected from moisture, heat, and direct light, preferably at 2–8 °C or at controlled room temperature in a dry environment. Researchers should always consult the lot-specific Certificate of Analysis (CoA) provided by Aladdin Scientific for confirmed storage recommendations.
In which therapeutic or biological research areas is this compound most relevant?
Pyrimidine-2-thioether acetic acid derivatives are recognized scaffolds in medicinal chemistry programs targeting kinases, antimicrobial targets, and antiviral mechanisms. As a versatile bifunctional building block, B193765 is particularly useful for fragment-based drug discovery, SAR library synthesis, and the preparation of novel heterocyclic pharmacophores in these and related therapeutic areas.
Can the thioether sulfur in this compound be further functionalized?
Yes. The thioether (C–S–C) linkage in 2-((5-Bromopyrimidin-2-yl)thio)acetic acid can be selectively oxidized to the corresponding sulfoxide or sulfone using appropriate oxidants such as mCPBA or hydrogen peroxide under controlled conditions. These oxidized derivatives often display distinct physicochemical and biological profiles, making sulfur oxidation a useful strategy in SAR studies.
References
- March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Wiley-Interscience. General reference for nucleophilic aromatic substitution and cross-coupling reactions.
- Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed. Oxford University Press. General reference for thioether chemistry and carboxylic acid activation.
- Aladdin Scientific. Product page and Certificate of Analysis for 2-((5-Bromopyrimidin-2-yl)thio)acetic acid, SKU B193765. https://www.aladdinsci.com
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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