2-Amino-5-iodonicotinic Acid: Properties & Research Uses
2-Amino-5-iodonicotinic Acid: Properties & Research Uses
2-Amino-5-iodonicotinic acid is a halogenated aminopyridinecarboxylic acid widely employed as a versatile building block in medicinal chemistry, heterocyclic synthesis, and palladium-catalyzed cross-coupling reactions.
- CAS Number
- 35364-39-7
- Molecular Formula
- C6H5IN2O2
- Molecular Weight
- 263.02 g/mol
- Appearance
- Light yellow to yellow crystalline solid
- Key Functional Groups
- Primary amine (C-2), iodo substituent (C-5), carboxylic acid (C-3)
- SKU
- A170905
Chemical Structure and Key Properties
2-Amino-5-iodonicotinic acid (CAS 35364-39-7) is a substituted pyridine derivative bearing three distinct functional groups on the aromatic ring: a primary amino group at the 2-position, a carboxylic acid at the 3-position, and an iodo substituent at the 5-position. Its molecular formula is C6H5IN2O2, with a molecular weight of approximately 263.02 g/mol.
The coexistence of the electron-donating amino group and the electron-withdrawing carboxylic acid on the pyridine ring creates a polarized electronic environment that influences reactivity at each position. The C–I bond at the 5-position is particularly activated toward oxidative addition in transition-metal-catalyzed reactions, making this compound a highly reactive partner in cross-coupling chemistry. The free carboxylic acid and amino groups further provide handles for amide bond formation, esterification, and cyclization reactions.
The compound typically presents as a light yellow to yellow crystalline solid. Storage under cool, dry conditions away from light is recommended to preserve stability, as aminoiodopyridines can be sensitive to prolonged light exposure.
Synthesis and Role as a Building Block
The iodo substituent in 2-amino-5-iodonicotinic acid is the primary driver of its value in synthetic chemistry. Carbon–iodine bonds are among the most reactive toward palladium(0)-catalyzed cross-coupling reactions, including Suzuki–Miyaura (with boronic acids), Sonogashira (with terminal alkynes), Negishi (with organozinc reagents), and Buchwald–Hartwig amination reactions. The high reactivity of aryl iodides compared to aryl bromides or chlorides often allows milder reaction conditions and higher yields.
The 2-amino group can participate in condensation reactions to form imidazopyridines, pyrimidopyridines, and other fused bicyclic or polycyclic heterocyclic scaffolds relevant to drug discovery programs. The carboxylic acid at C-3 enables straightforward formation of amides and esters, or it can be converted to an acyl azide for Curtius rearrangement to access 3-aminopyridine derivatives.
Together, these three functional groups allow multi-directional diversification from a single starting material, making 2-amino-5-iodonicotinic acid a highly efficient platform for generating focused compound libraries in high-throughput medicinal chemistry campaigns.
Applications in Medicinal Chemistry and Drug Discovery
Pyridine-based scaffolds are among the most prevalent heterocyclic systems in approved pharmaceuticals and clinical candidates. The nicotinic acid (pyridine-3-carboxylic acid) core imparts favorable physicochemical properties including moderate polarity, good aqueous solubility relative to pure carbocyclic analogs, and the ability to engage in hydrogen bonding with biological targets.
2-Amino-5-iodonicotinic acid is used as an intermediate in the synthesis of kinase inhibitors, where the pyridine nitrogen and amino group can form key hydrogen-bond interactions with hinge region residues of kinase active sites. It also serves as a precursor to radiolabeled tracers: the C–I bond can be exploited in radioiodination strategies (e.g., using 125I or 123I) for the preparation of probes for autoradiography or SPECT imaging, though standard cold chemistry applications in lead optimization are more common.
Additionally, derivatives obtained from this scaffold have been explored in the context of antimicrobial, antiviral, and anticancer research programs, reflecting the broad biological relevance of functionalized aminonicotinic acid systems. Researchers working in fragment-based drug discovery (FBDD) also employ this compound as a fragment hit or fragment elaboration starting point due to its compact, information-rich structure.
Handling, Storage, and Safety Considerations
As with most organoiodine compounds and aromatic amines, 2-amino-5-iodonicotinic acid should be handled with appropriate personal protective equipment (PPE), including nitrile gloves, safety glasses, and a laboratory coat. Work should be conducted in a well-ventilated area or fume hood to minimize inhalation of fine particulate dust.
For storage, the compound should be kept in a tightly sealed container at room temperature or at 2–8 °C, protected from moisture and direct light. Under recommended storage conditions, the material is expected to maintain specification-grade purity for an extended period; however, users should verify purity by HPLC or NMR prior to use in sensitive assays or key synthetic steps.
Disposal of waste material containing this compound should comply with local institutional and governmental regulations for chemical waste, particularly given the iodine content. Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific (SKU A170905) for full hazard classification, first-aid measures, and disposal guidance before use.
Frequently asked questions
What makes 2-amino-5-iodonicotinic acid useful in cross-coupling reactions?
The aryl C–I bond at the 5-position is highly reactive toward oxidative addition into palladium(0) catalysts, enabling efficient Suzuki–Miyaura, Sonogashira, Negishi, and Buchwald–Hartwig reactions under relatively mild conditions. This reactivity, combined with the orthogonal amino and carboxylic acid handles, allows selective and sequential functionalization of the molecule.
How should 2-amino-5-iodonicotinic acid (A170905) be stored to maintain purity?
The compound should be stored in a tightly sealed container, protected from moisture, heat, and direct light, ideally at 2–8 °C or room temperature as specified on the product label. It is advisable to confirm purity by HPLC or NMR before use in critical experiments, especially after prolonged storage.
Can 2-amino-5-iodonicotinic acid be used to synthesize fused heterocyclic compounds?
Yes. The 2-amino group adjacent to the ring nitrogen is well-suited for condensation with carbonyl-containing reagents (e.g., aldehydes, anhydrides, orthoformates) to construct fused bicyclic systems such as imidazo[1,2-a]pyridines, pyrido[2,3-d]pyrimidines, and related scaffolds that are of significant interest in medicinal chemistry and drug discovery.
What is the molecular weight and CAS number of 2-amino-5-iodonicotinic acid?
2-Amino-5-iodonicotinic acid has a molecular weight of approximately 263.02 g/mol and the CAS registry number 35364-39-7. Its molecular formula is C6H5IN2O2.
Is 2-amino-5-iodonicotinic acid suitable for radioiodination studies?
The structural motif of an aryl iodide is commonly exploited in radioiodination chemistry; isotopically enriched analogs bearing 125I or 123I can in principle be prepared from corresponding precursors using halogen-exchange or electrophilic iodination strategies. However, the standard Aladdin Scientific product (A170905) contains non-radioactive iodine and is intended for conventional synthetic chemistry applications. Researchers requiring radioactive analogs should consult specialist radiochemistry suppliers.
References
- Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. (General reference for pyridine and nicotinic acid derivative chemistry.)
- Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
- Sonogashira, K. Development of Pd–Cu catalyzed cross-coupling of terminal acetylenes with sp2-carbon halides. J. Organomet. Chem. 2002, 653, 46–49. doi:10.1016/S0022-328X(02)01158-0
- Meanwell, N. A. Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design. J. Med. Chem. 2011, 54, 2529–2591. (Context for pyridine scaffolds in medicinal chemistry.) doi:10.1021/jm1013693
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）