1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) 6674-22-2: A Key Catalyst in Synthesis

Introduction to 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (CAS 6674-22-2)

1,8-Diazabicyclo[5.4.0]undec-7-ene, commonly known by its acronym DBU, and identified by its CAS Number 6674-22-2, is a powerful organic compound widely recognized in the fields of organic synthesis and pharmaceutical manufacturing. It is a bicyclic amidine that functions as a strong, yet typically non-nucleophilic, base. This unique characteristic makes DBU an indispensable tool for chemists, enabling a variety of chemical transformations that would otherwise be difficult to achieve. Its high reactivity, coupled with relatively low volatility for an amine base, positions DBU (CAS 6674-22-2) as a preferred reagent in numerous industrial and research applications, particularly in the creation of complex molecules.

Chemical Properties of 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)

Understanding the chemical properties of 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) is key to appreciating its utility.

• Molecular Formula: C9​H16​N2​
• Molecular Weight: Approximately 152.24 g/mol
• Appearance: DBU is typically a colorless to pale yellow clear liquid at room temperature.
• Solubility: It is miscible with water and also soluble in many common organic solvents like ethanol, acetone, and toluene.
• Basicity: DBU is a strong base (the pKa of its conjugate acid is around 12-13), meaning it readily accepts protons from other compounds. However, it is considered “non-nucleophilic” due to the steric hindrance around its nitrogen atoms. This means it can remove protons (act as a base) without readily participating in other unwanted side reactions (acting as a nucleophile).
• Boiling Point: It has a relatively high boiling point (approximately 260-261 °C at atmospheric pressure, though often distilled at reduced pressure, e.g., 80-83 °C at 0.6 mmHg), contributing to its ease of handling in some industrial settings.
• Stability: DBU is stable under recommended storage conditions but is air-sensitive and hygroscopic (absorbs moisture from the air). It is incompatible with strong oxidizing agents, acids, acid chlorides, and acid anhydrides.
• Density: Approximately 1.01-1.02 g/mL.

Key Applications of 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (CAS 6674-22-2) in Synthesis

The primary role of 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (CAS 6674-22-2) is as a catalyst and a strong, non-nucleophilic base in organic synthesis. Its applications are diverse and crucial in many chemical processes:

• Pharmaceutical Manufacturing: DBU plays a significant role in the synthesis of numerous active pharmaceutical ingredients (APIs) and pharmaceutical intermediates. It is used in key steps for producing drugs like Rupatadine (an antihistamine), Ruxolitinib (a cancer treatment), Tipiracil (used in chemotherapy), Zonisamide (an anticonvulsant), and various cephalosporin antibiotics. The pharmaceutical uses of 1,8-Diazabicyclo[5.4.0]undec-7-ene are primarily as a reagent in these synthetic pathways.
• Dehydrohalogenation Reactions: DBU is exceptionally effective at promoting elimination reactions, particularly the removal of hydrogen halides (e.g., HCl, HBr) from molecules to form double bonds.
• Catalysis: It catalyzes a wide range of reactions, including:
  • Esterifications: Formation of esters from carboxylic acids and alcohols.
  • Transesterifications: Exchange of alkoxy groups in esters.
  • Condensation Reactions: Such as Knoevenagel and Claisen condensations, which are vital for carbon-carbon bond formation.
  • Alkylation and Acylation Reactions: Facilitating the addition of alkyl or acyl groups to molecules.
  • Isomerizations: Converting a molecule into one of its isomers.
• Polymer Chemistry: DBU is used as a catalyst in the production of polyurethanes and as a curing agent for epoxy resins, contributing to the formation of robust polymer materials.
• Agrochemical Synthesis: Similar to pharmaceuticals, DBU is also employed in the synthesis of complex organic molecules used in agriculture.

The versatility of DBU makes it a cornerstone reagent in developing efficient synthetic routes for a wide array of valuable chemical compounds.

Advantages of Using 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) in Chemical Processes

The widespread use of 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) stems from several distinct advantages it offers in chemical reactions:

• High Basicity: Its strong basic nature allows it to deprotonate even weakly acidic protons, initiating reactions that might not proceed with weaker bases.
• Non-Nucleophilic Character: Due to steric hindrance, DBU primarily acts as a base rather than a nucleophile. This selectivity is crucial as it minimizes unwanted side reactions, leading to cleaner reaction profiles and higher yields of the desired product.
• Mild Reaction Conditions: DBU often enables reactions to occur under milder conditions (e.g., lower temperatures) than might be required with other bases, which can be beneficial for sensitive substrates and energy efficiency.
• Catalytic Efficiency: Even in small (catalytic) amounts, DBU can effectively promote reactions, making processes more economical and reducing waste.
• Good Solubility: Its solubility in a range of organic solvents provides flexibility in choosing reaction media.
• Commercial Availability: DBU (CAS 6674-22-2) is readily available commercially, making it accessible for both research and large-scale industrial production.
• Operational Simplicity: Its use can simplify experimental procedures and workups in many instances.

These benefits of DBU contribute significantly to its role in developing more efficient, selective, and sometimes “greener” chemical syntheses.

Safety Profile and Handling Guidelines for 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)

While 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) is a valuable reagent, it is a hazardous chemical that requires careful handling.

• Hazards:
  • Toxic: DBU is harmful if swallowed and can be harmful in contact with skin.
  • Corrosive: It causes severe skin burns and serious eye damage.
  • Environmental Hazard: DBU can be harmful to aquatic life with long-lasting effects.
• Precautions and Handling:
  • Always use DBU in a well-ventilated area, preferably in a chemical fume hood.
  • Wear appropriate Personal Protective Equipment (PPE), including:
    • Chemical-resistant gloves (e.g., nitrile, neoprene).
    • Safety goggles and a face shield to protect against splashes.
    • Protective clothing or lab coat.
    • Respiratory protection may be necessary if ventilation is inadequate or if aerosols are generated.
  • Avoid breathing vapors or mists.
  • Prevent contact with skin, eyes, and clothing.
  • Do not eat, drink, or smoke when using this product.
  • Wash hands thoroughly after handling.
• Storage:
  • Store in a tightly closed container in a cool, dry, and well-ventilated place.
  • Keep away from incompatible materials such as acids, acid anhydrides, acid chlorides, and strong oxidizing agents.
  • Store under an inert atmosphere (e.g., nitrogen or argon) if possible, as DBU is air and moisture sensitive.
• First Aid:
  • If Swallowed: Rinse mouth. Do NOT induce vomiting. Seek immediate medical attention.
  • If on Skin (or hair): Take off immediately all contaminated clothing. Rinse skin with plenty of water for at least 15 minutes. Seek immediate medical attention.
  • If in Eyes: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. Seek immediate medical attention.
  • If Inhaled: Remove person to fresh air and keep comfortable for breathing. Seek medical attention if you feel unwell.

Always refer to the Safety Data Sheet (SDS) for 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (CAS 6674-22-2) before use for complete safety information.

Overview of 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) Manufacturing

The synthesis of 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) on an industrial scale is a multi-step chemical process. While specific proprietary methods may vary between manufacturers, a common approach involves starting materials like caprolactam (a cyclic amide) and acrylonitrile.

A simplified overview of a general synthetic route is:

1. Addition Reaction (Cyanoethylation): Caprolactam reacts with acrylonitrile. This step introduces a cyanoethyl group to the nitrogen atom of caprolactam. This reaction is typically catalyzed by a base.
2. Hydrogenation (Reduction): The nitrile group (-CN) of the intermediate formed in the first step is then reduced to a primary amine (-CH₂NH₂). This is usually achieved using hydrogen gas in the presence of a metal catalyst (e.g., Raney nickel).
3. Cyclization and Dehydration: The resulting amino compound undergoes an intramolecular cyclization reaction, often under heating, to form the bicyclic amidine structure of DBU, with the elimination of water.

The crude DBU obtained from these steps is then purified, typically through distillation under reduced pressure, to achieve the desired purity for its various applications in chemical synthesis, including the pharmaceutical uses of 1,8-Diazabicyclo[5.4.0]undec-7-ene. The entire DBU manufacturing process requires careful control of reaction conditions, such as temperature, pressure, and catalysts, to ensure high yield and purity.

Frequently Asked Questions (FAQ) about 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)

Q1: What makes 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) a “non-nucleophilic” base?

A1: DBU’s nitrogen atoms, which are responsible for its basicity, are sterically hindered (shielded) by the rest of the bicyclic molecule. This bulkiness makes it difficult for DBU to attack electron-deficient centers (act as a nucleophile), so it preferentially removes protons (acts as a base).

Q2: In what types of chemical reactions is 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) CAS 6674-22-2 commonly used?

A2: DBU (CAS 6674-22-2) is widely used in dehydrohalogenations, esterifications, transesterifications, alkylations, acylations, and various condensation reactions. It’s a key reagent in many organic synthesis protocols, particularly in pharmaceutical and polymer chemistry.

Q3: Is 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) safe to handle?

A3: No, DBU is a hazardous chemical. It is toxic if swallowed and corrosive, causing severe skin burns and eye damage. Safe handling requires appropriate personal protective equipment (PPE), use in a well-ventilated area, and adherence to all safety precautions outlined in its Safety Data Sheet (SDS).

Q4: How should 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) be stored?

A4: DBU should be stored in a tightly closed container in a cool, dry, well-ventilated place, away from incompatible materials like acids and strong oxidizing agents. Due to its air and moisture sensitivity, storage under an inert atmosphere (like nitrogen) is often recommended.

Q5: What are the main “pharmaceutical uses of 1,8-Diazabicyclo[5.4.0]undec-7-ene”?

A5: The pharmaceutical uses of 1,8-Diazabicyclo[5.4.0]undec-7-ene are not as a direct drug, but as a critical reagent and catalyst in the synthesis of various active pharmaceutical ingredients (APIs) and intermediates. It helps facilitate key chemical transformations in the manufacturing pathways of certain medications.