Dibenzyl azodicarboxylate, Molecular formula C16H14N2O4, CAS 2449-05-0. It appears as yellow to orange crystalline powder at room temperature and pressure. It is a type of compound that contains both azo and carboxyl functional groups. Due to its unique electronic and structural properties, azodicarboxylic acid dialkyl esters have been widely used as multifunctional reagents in organic synthesis, especially in MChemical bookitsunobu reactions, ammonification of carbonyl compounds, ammonification of unsaturated hydrocarbons, and synthesis of heterocyclic compounds. In addition, azodicarboxylic acid esters can also serve as oxidants for dehydrogenation oxidation reactions of alcohols and amines. Widely used in Mitsunobu reactions and carboxyl functionalization reactions, it can be applied to the modification and derivatization of drug molecules, bioactive molecules, and pesticide molecules.
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Chemical Formula |
C16H14N2O4 |
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Exact Mass |
298 |
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Molecular Weight |
298 |
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m/z |
298 (100.0%), 299 (17.3%), 300 (1.4%) |
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Elemental Analysis |
C, 50.44; H, 5.75; N, 12.61; O, 26.40; S, 4.81 |
DBAD has a wide range of applications, covering multiple fields such as organic synthesis, medicinal chemistry, materials science, sugar chemistry, and asymmetric catalysis. Its core value lies in its unique reactivity as a bifunctional reagent.
DBAD plays the role of a "molecular connector" in organic synthesis, and its azo and carboxyl ester groups can participate in various key reactions to achieve the construction of carbon carbon and carbon nitrogen bonds, as well as the modification of the molecular skeleton.
1. Mitsunobu reaction
DBAD is the core reagent of the Mitsunobu reaction, which converts alcohol hydroxyl groups into good leaving groups (such as phosphonates) through the synergistic effect of triphenylphosphine (PPh3) and DBAD, thereby achieving stereoselective coupling of alcohols with nucleophilic reagents such as carboxylic acids, phenols, thiols, etc.
For example, in the synthesis of chiral drug intermediates, the Mitsunobu reaction can efficiently construct key structures such as β - amino alcohols and α - hydroxy acids, with high yield and excellent stereoselectivity.
2. Carboxyl functionalization reaction
DBAD can convert carboxylic acids into more active mixed anhydrides (such as benzyloxycarbonyl anhydride) for modification of amino acids, peptides, and nucleosides. For example, in peptide synthesis, DBAD serves as a protective group reagent that can selectively protect amino or carboxyl groups, avoiding side reactions and improving synthesis efficiency.
3. [4+2] cycloaddition reaction
DBAD can undergo [4+2] cycloaddition reaction with carbohydrate derivatives (such as glycerol) to generate 2-aminoglycoside compounds. This type of reaction is of great significance in glycochemistry and can be used to synthesize bioactive glycoconjugates, such as antibiotics and antiviral drugs.
4. Asymmetric series addition cyclization reaction
Under the catalysis of copper (Cu) or palladium (Pd), DBAD can participate in the asymmetric tandem addition cyclization reaction of 2- (2 ', 3' - dienyl) - β - ketoesters with organic halides, efficiently constructing optically active pyrazole derivatives. These compounds have potential applications in medicinal chemistry, such as as as enzyme inhibitors or receptor ligands.
Medicinal Chemistry: A Key Tool for Drug Molecular Modification
The application of DBAD in the pharmaceutical field focuses on the structural modification and derivatization of drug molecules, by introducing benzyloxycarbonyl (Cbz) protecting groups or participating in key reaction steps, to enhance the stability, activity, and bioavailability of drugs.
1. Amino acid and peptide protectants
DBAD, as a source of Cbz protecting groups, can selectively protect the amino or carboxyl groups of amino acids to prevent side reactions during peptide synthesis. For example, in solid-phase peptide synthesis (SPPS), Cbz protecting groups can be removed under mild conditions (such as hydrogenolysis) to avoid damage to other parts of the peptide chain.
2. Synthesis of drug intermediates
DBAD can be used to synthesize heterocyclic derivatives such as indole and azacene, which have potential activities such as inhibiting phospholipase production, antibacterial, and treating diabetes and atherosclerosis. For example, through the cycloaddition reaction involving DBAD, heterocyclic skeletons with specific stereoconfigurations can be constructed, providing structurally diverse candidate molecules for drug screening.
3. Bioactive molecule modification
DBAD can modify the functional groups of bioactive molecules (such as nucleosides and sugars) to enhance their binding ability with target molecules. For example, in the development of antiviral drugs, DBAD mediated glycosylation reactions can optimize the stereoconfiguration of nucleoside analogs and enhance their inhibitory activity against viral polymerases.
Materials Science: Functional Modification of Polymer Materials
The application of DBAD in materials science mainly focuses on the synthesis and modification of polymer materials. By introducing azo groups or benzyloxycarbonyl groups, the materials are endowed with unique photoresponsivity, thermal stability, and mechanical properties.
1. Polymer catalyst
DBAD can be used as a free radical initiator for the polymerization reaction of thermoplastic synthetic fibers such as polyacrylonitrile and polyester. Its azo group decomposes under heating or light conditions to generate free radicals, triggering monomer polymerization. At the same time, benzyloxycarbonyl can regulate the molecular weight distribution and stereoregularity of the polymer.
2. Foam polymer foaming agent
DBAD can be used as foaming agent to prepare low-density foam polymers (such as polyurethane and polystyrene). During heating, DBAD decomposes to produce nitrogen and other gases, which expand the polymer melt to form a porous structure. At the same time, the degradation products of benzyloxycarbonyl can improve the mechanical properties and heat resistance of foam.
3. Functional Polymer Synthesis
The cycloaddition reaction involving DBAD can be used to synthesize polymer materials with photoresponsiveness. For example, through the [4+2] cycloaddition reaction between DBAD and diene monomers, polymer chains containing azobenzene structures can be constructed. Such materials can undergo cis trans isomerization under light irradiation and are used in fields such as photo controlled drug release and photochromic devices.
Glycochemistry: Efficient Synthesis of Carbohydrate Derivatives
DBAD plays the role of a "glycosylation reagent" in glycochemistry, achieving precise modification of glycation structures and synthesis of sugar conjugates through cycloaddition reactions with sugar derivatives.
1. Synthesis of 2-Aminoglycosides
The [4+2] cycloaddition reaction between DBAD and glycerol (such as 1,2-unsaturated sugars) is a classic method for synthesizing 2-aminoglycosides. This type of reaction has mild conditions, high yields, and can introduce diverse protective groups (such as benzyloxycarbonyl), providing key intermediates for the synthesis of carbohydrate drugs.
2. Construction of C-glycosylated amino acids
DBAD, as an electrophilic reagent, can participate in the proline catalyzed α - amination reaction of C-glycosylaldehyde to synthesize C-glycosyl α - amino acids. These compounds have important value in the total synthesis of natural products and drug development, such as serving as analogs of glycopeptide antibiotics, which can enhance their antibacterial activity and stability.
3. Modification of sugar conjugates
DBAD can be used for coupling reactions between sugars and biomolecules such as proteins and nucleic acids, by forming glycosidic or amide bonds to construct sugar conjugates (such as glycoproteins and nucleic acids). This type of modification can regulate the biological activity, stability, and pharmacokinetic properties of biomolecules, providing important tools for biopharmaceuticals.
Dibenzyl azodicarboxylate (DBAD) is a widely used compound in organic synthesis, commonly used in photopolymerization, crosslinking reactions, and ester exchange reactions. The synthesis method is usually based on the hydrolysis of azodicarbonamide (ADCA) and subsequent esterification reaction.
Dibenzyl azodicarboxylate, also known as dibenzyl azodicarboxylate, is a yellow or orange solid at room temperature and pressure. Azodicarboxylate dibenzyl ester belongs to azo derivatives and can be used as organic synthesis reactions and medicinal chemical condensation agents. It is widely used in Mitsunobu reactions and carboxyl functionalization reactions, and can be applied to the modification and derivatization of drug molecules, bioactive molecules, and pesticide molecules.
Application Conversion
Add 13.6 mmol of dibenzyl azodicarboxylate to a solution of 6.79 mmol of 2-iodo-allyl alcohol and 13.6 mmol of triphenylphosphine in tetrahydrofuran (35 mL), stir the reaction mixture at zero temperature for 30 minutes, then slowly raise the reaction to room temperature and stir for 36 hours. After stirring for 36 hours, the reaction mixture was concentrated under vacuum, and the resulting residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate, 8:1) to obtain the target product.
Dissolve chiral catalyst and acetaldehyde (2.0 mmol) in dichloromethane (0.5 mL), cool the reaction system to 0 ° C, and add 0.5 mmol of dibenzyl azodicarboxylate to the mixture at 0 ° C while stirring. After confirming the consumption of dibenzyl azodicarboxylate by TLC spot plate, a methanol solution of sodium borohydride (0.5 mmol, 20 mg) was added to the reaction system while stirring at 0 ° C. After stirring for 5 minutes, 1.0 mL of NH4Cl aqueous solution was added to the system to quench the reaction. Extract the reaction mixture with ethyl acetate (2 × 10 mL), rinse the organic layer with brine, and dry the organic layer with anhydrous MgSO4. Filter the organic layer, concentrate the filtrate under vacuum, and purify the crude product by silica gel column chromatography using ethyl acetate/n-hexane (1:8 to 1:4) to obtain the target product.
The hazards of dibenzyl azodicarboxylate are a complex and multifaceted issue, involving multiple aspects such as human health, environmental safety, and potential risks during operation. The following is a detailed expansion of its harmfulness:
Harm to human health
Skin irritation and allergic reactions:
Azodicarboxylate dibenzyl ester may cause irritation reactions such as redness, swelling, pain, itching, etc. when in direct contact with the skin.
Long term or repeated exposure may cause skin sensitization and increase the risk of allergic reactions to other substances.
Respiratory system stimulation:
Inhaling the vapor or dust of dibenzyl azodicarboxylate may cause respiratory irritation, resulting in symptoms such as coughing, difficulty breathing, and throat discomfort.
Long term inhalation may cause chronic damage to the respiratory system.
Health impact:
Long term exposure or inhalation of this substance may cause damage to organs such as the liver and kidneys in the human body.
Studies have shown that dibenzyl azodicarboxylate or its metabolites may be carcinogenic and pose a potential threat to human health.
Eye irritation:
After entering the eyes, this substance can cause strong irritation, leading to eye pain, tearing, redness, and even damage to the cornea.
Environmental hazards
Azodicarboxylate dibenzyl ester is difficult to degrade in the environment and may cause pollution to water, soil, and air.
Once it enters the water body, the substance may accumulate and amplify through the food chain, causing harm to aquatic organisms.
Accumulation in soil may lead to soil pollution, affecting plant growth and soil ecological balance.
Potential risks during the operation process
Explosion risk:
The molecule of dibenzyl azodicarboxylate contains azo groups, which are sensitive to light and pose a potential risk of explosion in severe collisions.
During storage, transportation, and use, it is necessary to strictly follow safety operating procedures to prevent explosion accidents.
Leakage risk:
Container rupture, leakage, or improper operation may lead to the leakage of dibenzyl azodicarboxylate into the environment, causing environmental pollution and personal injury.
Safety precautions
In order to reduce the hazards of dibenzyl azodicarboxylate, the following safety precautions need to be taken:
Personal protection:
Wear appropriate personal protective equipment during use, storage, and transportation, such as protective gloves, goggles, respiratory protective equipment, etc.
Storage and transportation:
Store in a cool, dry, well ventilated place, away from sources of fire and heat.
During transportation, ensure that the container is sealed to prevent leakage and collision.
Operating standards:
Strictly follow the product safety instructions and operating procedures to avoid unauthorized operations.
During the operation, keep the work area clean and promptly clean up any leaks.
Training and Awareness Enhancement:
Provide safety training to relevant personnel to enhance their awareness and prevention ability of the hazards of dibenzyl azodicarboxylate.
Regularly conduct emergency drills to enhance the ability to respond to unexpected events.
In summary, the harmfulness of dibenzyl azodicarboxylate cannot be ignored. In order to ensure human health, environmental safety, and safety during operation, strict safety precautions and operating procedures need to be taken.
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