DL-2-Bromopropionic Acid (598-72-1): Uses & Safety

Introduction to DL-2-Bromopropionic Acid (598-72-1)

DL-2-Bromopropionic acid, identified by the CAS Number 598-72-1, is a significant chemical compound primarily utilized as an intermediate in the synthesis of various organic molecules. It is a racemic mixture, meaning it contains equal amounts of two enantiomers (mirror-image isomers). This compound plays a crucial role as a building block in the chemical industry, particularly in the development and production of pharmaceuticals and agrochemicals. Its reactivity, owing to the presence of both a carboxylic acid group and a bromine atom on an adjacent carbon, makes it a versatile reagent for creating more complex chemical structures.

Chemical Properties of DL-2-Bromopropionic Acid

DL-2-Bromopropionic acid is characterized by several key physical and chemical properties that are important for its handling and application. Understanding these traits helps in its effective use in various synthetic processes.

• Molecular Formula: C3​H5​BrO2​
• Molecular Weight: Approximately 152.97 g/mol
• Appearance: After melting, it is a clear, colorless to yellowish liquid. It has a reported melting point of around 25.7∘C (78.3∘F), meaning it can be solid at cooler room temperatures.
• Solubility: It is soluble in water. Furthermore, DL-2-Bromopropionic acid is miscible with common organic solvents such as alcohol, ether, chloroform, and benzene. This solubility profile is advantageous for its use in diverse reaction conditions.
• Density: It has a density of approximately 1.65 to 1.7 g/mL at 25∘C, making it denser than water.
• Boiling Point: The boiling point is around 203∘C (397.4∘F), though it may decompose at higher temperatures.
• Acidity (pKa): The carboxylic acid group gives it acidic properties, with a pKa value around 2.97, indicating it is a relatively strong organic acid.
• Reactivity & Stability: The bromine atom makes the alpha-carbon (the carbon atom next to the carboxyl group) susceptible to nucleophilic substitution reactions. This reactivity is key to its role as an intermediate. It should be stored away from strong bases and oxidizing agents to prevent unwanted reactions. Stability is best maintained in a cool, dry, dark, and well-ventilated environment, ideally below 15∘C (59∘F). It can be corrosive to metals.

These properties, especially its bifunctional nature (acid and bromo-alkyl group), allow DL-2-Bromopropionic acid (CAS 598-72-1) to be a versatile starting material or intermediate in multi-step organic syntheses.

Uses and Applications of DL-2-Bromopropionic Acid (598-72-1)

The primary significance of DL-2-Bromopropionic acid (CAS 598-72-1) lies in its role as a versatile chemical intermediate. Its reactive nature makes it invaluable in several industrial and research applications:

• Pharmaceutical Synthesis: This is a major application area. DL-2-Bromopropionic acid serves as a crucial building block in the synthesis of a wide range of active pharmaceutical ingredients (APIs). For example:
  • It is used in the preparation of certain amino acids (like alanine) and their derivatives, which are fundamental components of many drugs.
  • It can be an intermediate in the production of various drug categories, including some anti-inflammatory agents, antiviral compounds, and potentially anti-cancer drugs. Its structure allows for the introduction of specific chemical motifs into larger, more complex drug molecules.
• Agrochemical Production: Similar to its role in pharmaceuticals, it is used to synthesize active ingredients in agricultural products. This includes:
  • Herbicides: Such as quizalofop-ethyl, napropamide, and fenthiaprop.
  • Fungicides: Including metalaxyl, benalaxyl, and procymidone. These applications help in crop protection and management.
• Organic Synthesis Reagent: Beyond specific product classes, DL-2-Bromopropionic acid is employed as a general alkylating agent, particularly for mercaptans (thiols) and other sulfur-containing compounds. The bromine atom can be displaced by various nucleophiles, allowing for the formation of new carbon-sulfur, carbon-nitrogen, or carbon-oxygen bonds.
• Dye Industry: It has been mentioned as an intermediate in the production of certain dyes.
• Polymer Chemistry: It can be used in emulsion polymerization and in the preparation of reversible addition-fragmentation chain transfer (RAFT) agents, which are important in creating polymers with controlled architectures.

The utility of DL-2-Bromopropionic acid stems from its ability to participate in a variety of chemical reactions, facilitating the construction of complex molecules required for therapeutic, agricultural, and material science purposes.

Benefits of DL-2-Bromopropionic Acid in Pharmaceutical Applications

While DL-2-Bromopropionic acid (CAS 598-72-1) itself is not a therapeutic drug, its benefits in pharmaceutical applications are indirect but highly significant. They arise from its utility as a key chemical intermediate:

• Versatile Building Block: Its structure, featuring both a reactive bromine atom and a carboxylic acid group, allows for diverse chemical modifications. This versatility enables chemists to synthesize a wide array of complex pharmaceutical compounds and drug candidates.
• Introduction of Specific Moieties: It allows for the precise introduction of a propionic acid fragment or a 2-bromopropionyl group into a target molecule. This can be critical for achieving the desired pharmacological activity or modifying the properties of an existing drug molecule.
• Chiral Synthesis Potential: Although this article focuses on the DL- (racemic) form, related chiral versions (R or S enantiomers) of 2-bromopropionic acid are valuable chiral building blocks. These are essential for synthesizing enantiomerically pure drugs, which often have improved efficacy and reduced side effects compared to their racemic counterparts. The DL-form can also be a precursor to these chiral molecules or used where chirality is not a critical factor for the final product.
• Efficiency in Synthesis: As a readily available and reactive intermediate, DL-2-Bromopropionic acid can streamline synthetic routes to complex APIs, potentially making drug manufacturing more efficient and cost-effective.
• Scaffolding for Drug Discovery: Its ability to react with various nucleophiles makes it a useful tool in medicinal chemistry for creating libraries of related compounds. These libraries can then be screened for biological activity, aiding in the discovery of new drug leads. For instance, its use in synthesizing novel amino acid derivatives or modifying peptide structures can lead to new therapeutic agents.

In essence, the primary benefit of DL-2-Bromopropionic acid in pharmaceuticals is its role as an enabler – it provides chemists with a reliable and reactive tool to construct the sophisticated molecules that become life-enhancing or life-saving medicines.

Safety Profile: Understanding Hazards and Precautions for DL-2-Bromopropionic Acid

As DL-2-Bromopropionic acid (CAS 598-72-1) is primarily an industrial chemical intermediate rather than a medication taken by patients, its safety profile focuses on occupational hazards and handling precautions. It is crucial for personnel working with this chemical to be aware of its properties to prevent exposure and ensure safe use.

Key Hazards:

• Corrosive: DL-2-Bromopropionic acid is corrosive and can cause severe skin burns and serious eye damage upon contact.
• Irritant: It is a skin and eye irritant.
• Harmful if Swallowed: Acute oral toxicity is a concern.
• Skin Sensitizer: May cause an allergic skin reaction in some individuals.
• May be Corrosive to Metals: This is important for storage and handling equipment.

Potential Effects of Exposure:

• Skin Contact: Can cause redness, pain, and severe burns. Prolonged contact may lead to chemical burns.
• Eye Contact: Can cause severe irritation, pain, and burns, potentially leading to permanent eye damage. Immediate and thorough rinsing is critical.
• Inhalation: Vapors or mists can irritate the respiratory tract, causing coughing and shortness of breath. Higher exposures could lead to more severe respiratory issues.
• Ingestion: Harmful if swallowed. Can cause burns to the mouth, throat, and stomach, along with nausea, vomiting, and abdominal pain.

Contraindications for Handling (Situations to Avoid Unprotected Exposure):

While “contraindications” typically refer to medical use, in the context of this chemical, they relate to conditions or materials that make its handling particularly hazardous:

• Incompatible Materials: Avoid contact with strong bases, strong oxidizing agents, and metals (due to its corrosive nature). Reactions with these can be vigorous and produce heat or hazardous fumes.
• Poor Ventilation: Working with DL-2-Bromopropionic acid in poorly ventilated areas increases the risk of inhalation exposure.
• Lack of Personal Protective Equipment (PPE): Handling without appropriate PPE is a major contraindication to safe use.

General Safety Guidelines and Precautions:

• Engineering Controls: Work in a well-ventilated area, preferably under a chemical fume hood, especially when heating or agitating the material.
• Personal Protective Equipment (PPE):
  • Eye Protection: Wear chemical safety goggles and a face shield if splashing is possible.
  • Skin Protection: Wear chemical-resistant gloves (e.g., nitrile, neoprene), a lab coat, and other protective clothing to prevent skin contact.
  • Respiratory Protection: If ventilation is inadequate or if mists/vapors are generated, use an approved respirator with an appropriate cartridge for organic acids/vapors.
• Handling:
  • Avoid direct contact with skin, eyes, and clothing.
  • Do not breathe vapors or mists.
  • Wash hands thoroughly after handling.
  • Do not eat, drink, or smoke in areas where the chemical is handled or stored.
  • Keep containers tightly closed when not in use.
• Storage:
  • Store in a cool, dry, dark, well-ventilated place, away from incompatible materials.
  • Store in corrosion-resistant containers. Keep below 15∘C (59∘F) for optimal stability.
• Emergency Procedures:
  • Eye Contact: Immediately flush eyes with copious amounts of water for at least 15 minutes, lifting upper and lower eyelids occasionally.¹ Seek immediate medical attention.
  • Skin Contact: Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing² and shoes. Seek medical attention if irritation³ or burns occur.
  • Inhalation: Remove victim to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen.⁴ Seek immediate medical attention.
  • Ingestion: Do NOT induce vomiting.⁵ Rinse mouth with water. Give water to drink if conscious. Seek immediate medical attention.
• Spill Control: In case of a spill, wear appropriate PPE, contain the spill, and absorb with an inert material (e.g., vermiculite, sand). Collect and place in a suitable container for disposal according to local regulations.

It is essential to consult the Safety Data Sheet (SDS) for DL-2-Bromopropionic acid (CAS 598-72-1) before use for complete and detailed safety information. This chemical is intended for industrial and research use by trained personnel.

How DL-2-Bromopropionic Acid is Manufactured

The synthesis of DL-2-Bromopropionic acid (CAS 598-72-1) typically involves the bromination of propionic acid. While specific industrial processes can vary and are often proprietary, a general chemical approach suitable for a layperson’s understanding can be outlined.

The core principle is to introduce a bromine atom onto the carbon atom that is adjacent to the carboxylic acid group (the $\alpha$-carbon). A common laboratory and industrial method for achieving this is the Hell-Volhard-Zelinsky (HVZ) reaction.

Here’s a simplified overview of the steps involved, focusing on the general principles:

1. Starting Material: The primary starting material is propionic acid (CH3​CH2​COOH).
2. Activation/Catalysis: The reaction usually requires a catalyst, typically a small amount of phosphorus (e.g., red phosphorus or phosphorus tribromide, PBr3​). The phosphorus reacts with bromine to form phosphorus tribromide in situ if not added directly. This PBr3​ then reacts with the propionic acid to form an acyl bromide intermediate (CH3​CH2​COBr). This intermediate is more reactive towards bromination at the $\alpha$-carbon than the original carboxylic acid.
3. Bromination: Elemental bromine (Br2​) is then added. The bromine reacts with the acyl bromide intermediate, specifically at the $\alpha$-carbon (the carbon next to the C=O group). This step introduces the bromine atom onto that carbon, forming 2-bromopropionyl bromide (CH3​CHBrCOBr).
4. Hydrolysis: The final step is the addition of water (H2​O). The 2-bromopropionyl bromide (an acyl halide) reacts with water (hydrolyzes) to form DL-2-Bromopropionic acid (CH3​CHBrCOOH) and hydrobromic acid (HBr) as a byproduct.

In simpler terms:

Imagine you have propionic acid, and you want to replace one of the hydrogen atoms on the carbon next to the acid part with a bromine atom.

• First, you “activate” the acid part, often with the help of phosphorus and bromine, to make it more willing to undergo the next step.
• Then, you introduce more bromine, which attaches to that specific carbon.
• Finally, you add water to convert the “activated” intermediate back into an acid, now with the bromine atom attached in the desired position, yielding DL-2-Bromopropionic acid.

This process results in the racemic (DL) mixture because the bromination step typically does not favor the formation of one enantiomer over the other. Manufacturing of specific enantiomers (L- or D-2-Bromopropionic acid) would require different, more complex chiral synthesis strategies or resolution techniques. The resulting DL-2-Bromopropionic acid is then purified for use as a chemical intermediate in various industries, notably for pharmaceutical uses of DL-2-Bromopropionic acid.

Frequently Asked Questions (FAQ) about DL-2-Bromopropionic Acid

• What is DL-2-Bromopropionic acid primarily used for?

  DL-2-Bromopropionic acid (CAS 598-72-1) is primarily used as a chemical intermediate in the synthesis of pharmaceuticals (such as certain amino acids, anti-inflammatory drugs, and antiviral agents) and agrochemicals (like herbicides and fungicides). Its reactivity makes it a valuable building block in organic chemistry.

• Is DL-2-Bromopropionic acid dangerous to handle?

  Yes, DL-2-Bromopropionic acid is a hazardous chemical. It is corrosive and can cause severe skin burns and eye damage. It is also harmful if swallowed and may cause skin sensitization. Proper safety precautions, including the use of personal protective equipment (gloves, eye protection, lab coat) and working in a well-ventilated area (like a fume hood), are essential when handling this compound. Always refer to the Safety Data Sheet (SDS) before use.

• Is DL-2-Bromopropionic acid a medication?

  No, DL-2-Bromopropionic acid itself is not a medication that is administered to patients. Instead, it is a key raw material or intermediate used in the manufacturing process of various pharmaceutical drugs. The final drug products undergo extensive testing for safety and efficacy.

• What does “DL” mean in DL-2-Bromopropionic acid?

  The “DL” prefix indicates that the substance is a racemic mixture. This means it contains equal amounts of the D- (dextrorotatory) and L- (levorotatory) enantiomers, which are non-superimposable mirror images of each other. The “2” indicates that the bromine atom is attached to the second carbon atom of the propionic acid chain (the alpha-carbon, next to the carboxyl group).

• How should DL-2-Bromopropionic acid be stored?

  DL-2-Bromopropionic acid should be stored in a cool, dry, dark, and well-ventilated place, ideally below 15∘C (59∘F). It should be kept in tightly sealed, corrosion-resistant containers, away from incompatible materials such as strong bases, strong oxidizing agents, and metals.