2-Bromo-3-pyridinecarboxaldehyde CAS 128071-75-0

2-Bromo-3-pyridinecarboxaldehyde(3-Pyridinecarboxaldehyde, 2-bromo-), chemical formula: C6H4BrNO, CAS 14533-22-9, molecular weight: 186.01 g/mol. It is a solid, usually in the form of a white or almost white crystalline powder. It has certain solubility in some common organic solvents (such as dichloromethane, ether, methanol, ethanol, etc.). However, please note that its solubility may vary depending on temperature, solvents, and other factors. As an important organic compound, it has a wide range of applications and uses. It plays an important role in the fields of drug synthesis, pesticide synthesis, coordination chemistry, and organic optoelectronic materials. Through synthesis and functionalization, compounds with specific structures and properties can be obtained to meet the needs of different fields and applications.

Molecular Features

2-Bromo-3-pyridinecarboxaldehyde consists of a six-membered pyridine ring (a nitrogen-containing aromatic heterocycle) with two substituents:

Bromine (Br): A strong electron-withdrawing group that activates the pyridine ring for nucleophilic substitution reactions (e.g., Suzuki, Heck, or Buchwald-Hartwig couplings).

Aldehyde (-CHO): A highly reactive functional group that participates in condensation reactions (e.g., imine formation, reductive amination) and oxidation/reduction processes.

Reaction Pathways

The compound's reactivity stems from the interplay between its two functional groups:

Nucleophilic Aromatic Substitution (SNAr): The bromine atom can be replaced by nucleophiles (e.g., amines, thiols, or boronic acids) under basic conditions, enabling the introduction of diverse substituents.

Condensation Reactions: The aldehyde group reacts with primary amines to form imines, which can be reduced to secondary amines using reducing agents like sodium borohydride (NaBH₄).

Oxidation/Reduction: The aldehyde can be oxidized to a carboxylic acid (using Jones reagent) or reduced to an alcohol (using NaBH₄).

Cross-Coupling Reactions: The bromine atom participates in palladium-catalyzed couplings (e.g., Suzuki, Sonogashira) to form carbon-carbon or carbon-heteroatom bonds.

These pathways make 2-bromo-3-pyridinecarboxaldehyde a linchpin in multi-step syntheses, where sequential functionalization is required.

It is a complex organic compound that can be synthesized through various pathways.

1. Hantzsch pyridine synthesis method:

The chemical reaction formula is as follows:

C₅H₄BrN+2C₃H₂N₂+CH₄N₂S → C₆H₄BrNO

This is a commonly used method for synthesizing 2-Bromo-3-pyridinecarboxaldehide, with the specific steps as follows:

Step 1: Prepare reactants:

Mix 2-bromopyridine and malononitrile in a molar ratio of 1:2, and add thiourea as a catalyst. The amount of reactants can be adjusted as needed.

Step 2: Reaction progress:

Add the reactants obtained from mixing in step 1 to the reaction flask and proceed with the reaction under appropriate reaction conditions. The reaction temperature is usually between 150 and 200 degrees Celsius, and dry nitrogen flow under solvent-free conditions can be used. The reaction time depends on specific experimental conditions, usually ranging from hours to days.

In this reaction, thiourea acts as a catalyst, promoting the progress of the reaction. Due to the high reaction temperature, the formation of C-C bonds can occur. The final product produced is 2-Bromo-3-pyridinecarboxaldehide.

Step 3: Cooling and crystallization:

After the reaction is completed, cool the reaction solution to room temperature or low temperature and proceed with crystallization. The crystallization of the product can be induced by slowly adding appropriate solvents (such as ethanol or ether solvents). During the crystallization process, the products precipitate from the solution in solid form.

Step 4: Purification and drying:

Centrifuge or filter the crystallized product to separate solid products. After separation, the product can be washed with appropriate solvents to remove impurities. Finally, the product was dried under appropriate conditions to obtain high-purity 2-Bromo-3-pyridine carboxaldehide.

2. Knoevenagel Condensation reaction:

The chemical reaction formula is as follows:

C₅H₄BrN+C₄H₈O₃+C₆H₁₅N → C₆H₄BrNO

In this reaction, acyl and carboxyl groups form C-C bond through Condensation reaction. The final product produced is 2-Bromo-3-pyridinecarboxaldehide.

The specific steps are as follows:

Step 1: Dissolve 2-bromopyridine and malonic acid (representative carboxylic acid) in an appropriate organic solvent. Ethanol is a commonly used solvent.

Step 2: add an alkaline catalyst, such as triethylamine, to promote the Condensation reaction.

Step 3: Heat the solution and conduct the reaction at an appropriate temperature. The commonly used reaction temperature is 80-100 degrees Celsius.

Step 4: After the reaction is completed, cool the solution and undergo acidification treatment to generate the target product 2-Bromo-3-pyridinecarboxaldehide.

Step 5: Purify and crystallize the product to obtain a high-purity compound.

These are just two common methods, and there are many other synthesis methods for 3-Pyridinecarboxaldehyde, 2-bromo-. It should be noted that each synthesis method has its specific advantages and applicability, and needs to be adjusted and optimized according to the specific situation in actual operation.

► Synthesis of a Kinase Inhibitor for Cancer Therapy

1)Background

Kinase inhibitors are a class of targeted anticancer drugs that block the activity of protein kinases, enzymes involved in cell signaling and proliferation. Pyridine-based scaffolds are common in kinase inhibitor design due to their ability to mimic ATP-binding sites. Researchers at a pharmaceutical company sought to develop a novel inhibitor targeting epidermal growth factor receptor (EGFR), a kinase overexpressed in many cancers.

2)Objective

Synthesize a pyridine-derived compound with high potency and selectivity for EGFR using 2-bromo-3-pyridinecarboxaldehyde as a key intermediate.

3)Experimental Approach

Synthesis of the Core Structure:

2-Bromo-3-pyridinecarboxaldehyde was reacted with aniline in ethanol under reflux to form an imine intermediate via condensation.

The imine was reduced using sodium borohydride (NaBH₄) to yield 2-bromo-N-phenylpyridin-3-amine, a critical building block for further functionalization.

Cross-Coupling Reaction:

The bromine atom at the 2-position underwent a Suzuki-Miyaura coupling with a boronic acid derivative (4-fluorophenylboronic acid) in the presence of palladium(II) acetate (Pd(OAc)₂) and a ligand (triphenylphosphine).

This step introduced a fluorophenyl group, enhancing lipophilicity and binding affinity.

Final Modification:

The aldehyde group was oxidized to a carboxylic acid using Jones reagent (chromic acid in sulfuric acid), yielding the target compound: N-(4-fluorophenyl)-2-(4-fluorophenyl)pyridine-3-carboxamide.

4)Results

Yield: 72% over three steps.

Biological Activity:

The compound inhibited EGFR kinase activity with an IC₅₀ of 12 nM in enzymatic assays.

In vitro studies on A431 cancer cells (overexpressing EGFR) showed a GI₅₀ (growth inhibition) of 0.8 μM.

Selectivity: The compound exhibited 50-fold selectivity over other kinases (e.g., VEGFR, CDK2), reducing off-target toxicity.

5)Implications

This case demonstrates how 2-bromo-3-pyridinecarboxaldehyde enables the rapid assembly of complex kinase inhibitors. Its aldehyde and bromine groups provide orthogonal reactivity for sequential functionalization, a strategy now widely adopted in medicinal chemistry.

► Functionalization of Graphene Oxide for Enhanced Composite Materials

1)Background

Graphene oxide (GO) is a popular reinforcement material in polymer composites due to its high mechanical strength and electrical conductivity. However, GO's hydrophilic nature limits its dispersion in non-polar polymers. Researchers sought to chemically modify GO using 2-bromo-3-pyridinecarboxaldehyde to improve compatibility with epoxy resins.

2)Objective

Covalently graft 2-bromo-3-pyridinecarboxaldehyde onto GO and evaluate the composite's thermal and mechanical properties.

3)Experimental Approach

GO Modification:

GO was dispersed in dimethylformamide (DMF) and sonicated for 2 hours.

2-Bromo-3-pyridinecarboxaldehyde (5 eq.) and sodium hydroxide (NaOH, 10 eq.) were added, initiating a nucleophilic substitution reaction between GO's epoxide groups and the aldehyde's α-carbon.

Composite Fabrication:

The modified GO (GO-Py) was mixed with an epoxy resin (diglycidyl ether of bisphenol A, DGEBA) and a hardener (triethylene tetramine, TETA).

The mixture was cured at 120°C for 4 hours to form a composite film.

Characterization:

Thermal stability was assessed via thermogravimetric analysis (TGA).

Mechanical properties were measured using tensile testing.

4)Results

Grafting Efficiency: Fourier-transform infrared spectroscopy (FTIR) confirmed the presence of pyridine rings on GO-Py.

Thermal Stability:

The onset degradation temperature of the composite increased by 35°C compared to unmodified GO/epoxy.

Mechanical Properties:

Tensile strength improved by 22%, from 45 MPa (unmodified) to 55 MPa (GO-Py).

Elongation at break increased by 15%, indicating better stress distribution.

5)Implications

This case illustrates how 2-bromo-3-pyridinecarboxaldehyde can bridge inorganic nanomaterials and organic polymers. The pyridine ring's aromaticity enhanced interfacial adhesion, a principle applicable to other 2D materials like molybdenum disulfide (MoS₂).

► Bioconjugation for Protein Labeling

1)Background

Site-specific protein labeling is essential for studying protein function, developing diagnostics, and creating biotherapeutics. The aldehyde group in 2-bromo-3-pyridinecarboxaldehyde can react with lysine residues in proteins via reductive amination, forming stable covalent bonds.

2)Objective

Label the N-terminus of green fluorescent protein (GFP) using 2-bromo-3-pyridinecarboxaldehyde and evaluate labeling efficiency.

3)Experimental Approach

Conjugation Reaction:

Recombinant GFP (1 mg/mL) was incubated with 2-bromo-3-pyridinecarboxaldehyde (10 eq.) in phosphate buffer (pH 7.4) for 2 hours at room temperature.

Sodium cyanoborohydride (NaBH₃CN, 5 eq.) was added to reduce the imine intermediate to a stable amine.

Purification:

The conjugate was purified using size-exclusion chromatography (SEC).

Characterization:

Labeling efficiency was quantified via UV-Vis spectroscopy (absorbance at 280 nm for protein, 340 nm for pyridine).

Fluorescence intensity was measured to assess GFP activity post-labeling.

4)Results

Labeling Efficiency: 85% of GFP molecules were conjugated, as determined by pyridine absorbance.

Fluorescence Retention: The conjugate retained 92% of native GFP's fluorescence, indicating minimal structural disruption.

Mass Spectrometry: ESI-MS confirmed a mass increase of 185 Da (consistent with one pyridinecarboxaldehyde moiety per GFP).

5)Implications

This study demonstrates the utility of 2-bromo-3-pyridinecarboxaldehyde in bioconjugation. Its small size and reactivity make it superior to larger fluorescent dyes, which often interfere with protein function. Similar strategies are now used to label antibodies for immunohistochemistry.

2-Bromo-3-pyridinecarboxaldehyde is a brominated aldehyde compound containing a pyridine ring, with the molecular formula C ₆ H ₄ BrNO and a molecular weight of 186. The 2-position of the pyridine ring in its structure is replaced by a bromine atom, and the 3-position is connected to an aldehyde group, giving it unique chemical properties. As an organic synthesis intermediate, it is widely used in drug research and development, pesticide synthesis, and materials science fields. For example, in drug synthesis, the aldehyde group can participate in condensation reactions to construct a heterocyclic skeleton, while the bromine atom can introduce functional groups through substitution reactions, providing flexibility for drug molecule design.

 

Skin contact: Direct contact can cause skin redness, itching, blisters, and in severe cases, contact dermatitis.
Mechanism: Aldehyde groups covalently bind with amino groups in skin proteins to form Schiff bases, disrupting the skin barrier function; The presence of bromine atoms may enhance its lipophilicity and promote penetration into the epidermal layer.
Eye contact: Severe eye irritation, manifested as conjunctival congestion, tearing, photophobia, and even corneal epithelial damage.
Mechanism: Aldehyde groups react with corneal proteins to cause protein denaturation, while bromine atoms may trigger oxidative stress reactions and damage corneal cells.

 

Respiratory irritation: Inhalation of vapor or dust can cause irritation to the nasopharynx, coughing, and difficulty breathing. Long term exposure may trigger asthma or chronic obstructive pulmonary disease (COPD). Aldehyde groups bind to proteins in respiratory mucosal epithelial cells, disrupting mucosal integrity; Bromine atoms may trigger inflammatory reactions by producing reactive oxygen species (ROS).

 

Digestive system reactions: nausea, vomiting, abdominal pain, diarrhea, and in severe cases, gastrointestinal bleeding or liver damage may occur. The direct corrosive effect of aldehyde groups on gastrointestinal mucosa, as well as the stimulation of the gastrointestinal tract by hydrogen bromide produced by the metabolism of bromine atoms in the body; The liver, as the main metabolic organ, may experience elevated transaminase levels due to oxidative stress.
Acute poisoning: Dizziness, fatigue, blurred consciousness, and in severe cases, coma, convulsions, and even respiratory and circulatory failure. Aldehyde groups interfere with nerve conduction by binding to neurotransmitter receptors; Bromine atoms may inhibit mitochondrial respiratory chain, leading to cellular energy metabolism disorders.

Hot Tags: 2-bromo-3-pyridinecarboxaldehyde cas 128071-75-0, suppliers, manufacturers, factory, wholesale, buy, price, bulk, for sale, Cerium sulfate powder, CHICAGO SKY BLUE 6B, Iridium III chloride, 1 AMINO 2 NAPHTHOL 4 SULFONIC ACID, Consumable