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DBU Phenolate (CAS 57671-19-9) for High-Yield Production in Fine Chemicals

admin 3月 27th, 2025 News

DBU Phenolate (CAS 57671-19-9): The Unsung Hero in High-Yield Production of Fine Chemicals

Introduction

In the world of fine chemicals, where precision and efficiency reign supreme, one compound has quietly risen to prominence: DBU Phenolate (CAS 57671-19-9). This unsung hero, often overshadowed by more glamorous molecules, plays a crucial role in enhancing the yield and quality of various chemical reactions. DBU Phenolate, derived from 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) and phenol, is a versatile catalyst that has found applications in numerous industries, from pharmaceuticals to polymers.

This article aims to provide a comprehensive overview of DBU Phenolate, delving into its structure, properties, synthesis, and applications. We will explore how this compound can significantly boost the productivity of fine chemical processes, making it an indispensable tool for chemists and engineers alike. So, buckle up as we embark on a journey through the fascinating world of DBU Phenolate!

Structure and Properties

Chemical Structure

DBU Phenolate, with the chemical formula C12H17N2O, is a salt formed by the reaction of DBU and phenol. The structure of DBU Phenolate can be visualized as follows:

DBU (1,8-Diazabicyclo[5.4.0]undec-7-ene): A bicyclic organic compound with two nitrogen atoms in its ring system. DBU is known for its strong basicity, which makes it an excellent base for deprotonation reactions.
Phenol (C6H5OH): A simple aromatic alcohol with a hydroxyl group attached to a benzene ring. Phenol is a weak acid, and its conjugate base, the phenolate ion, is a resonance-stabilized anion.

When DBU reacts with phenol, the resulting DBU Phenolate consists of the DBU cation and the phenolate anion. The strong basicity of DBU allows it to effectively deprotonate phenol, forming a stable salt that can act as a powerful catalyst in various reactions.

Physical and Chemical Properties

Property	Value
Molecular Weight	203.28 g/mol
Appearance	White to off-white crystalline solid
Melting Point	160-162°C
Solubility	Soluble in polar solvents like DMSO, DMF, and ethanol; insoluble in nonpolar solvents like hexane and toluene
pKa	~9.9 (for phenol)
Basicity	Strongly basic due to the presence of DBU
Stability	Stable under normal conditions, but may degrade in acidic environments or at high temperatures

Safety and Handling

While DBU Phenolate is generally considered safe for laboratory use, it is important to handle it with care. The compound is moderately toxic if ingested or inhaled, and it can cause skin and eye irritation. Therefore, appropriate personal protective equipment (PPE), such as gloves, goggles, and a lab coat, should be worn when handling DBU Phenolate. Additionally, it is advisable to work in a well-ventilated area or under a fume hood to minimize exposure.

Synthesis of DBU Phenolate

The synthesis of DBU Phenolate is relatively straightforward and can be carried out using a variety of methods. The most common approach involves the reaction of DBU with phenol in the presence of a polar solvent. Below is a step-by-step guide to the synthesis process:

Method 1: Direct Reaction of DBU and Phenol

Reagents:
- 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)
- Phenol
- Dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) as solvent
Procedure:
- Dissolve DBU in DMSO or DMF in a round-bottom flask equipped with a magnetic stirrer.
- Slowly add phenol to the solution while stirring. The reaction mixture will become cloudy as the DBU Phenolate precipitates out.
- Continue stirring for 1-2 hours at room temperature.
- Filter the solid product and wash it with cold DMSO or DMF to remove any unreacted starting materials.
- Dry the product under vacuum to obtain pure DBU Phenolate.
Yield: Typically, this method yields 80-90% of the theoretical amount of DBU Phenolate.

Method 2: In Situ Generation in Reaction Mixtures

In some cases, it may be more convenient to generate DBU Phenolate in situ during a catalytic reaction. This approach eliminates the need for isolating the catalyst beforehand and can simplify the overall process. For example, in a typical esterification reaction, DBU and phenol can be added directly to the reaction mixture, where they will react to form DBU Phenolate, which then catalyzes the desired transformation.

Advantages of In Situ Generation

Simplicity: No need for separate synthesis and purification steps.
Cost-Effective: Reduces the amount of reagents and solvents required.
Versatility: Can be adapted to a wide range of reactions, including esterifications, amidations, and carbonylations.

Challenges and Considerations

While the synthesis of DBU Phenolate is generally straightforward, there are a few challenges to keep in mind:

Solubility: DBU Phenolate is only soluble in polar solvents, which can limit its use in certain reaction conditions. However, this can also be an advantage, as it allows for easy separation of the catalyst from the reaction mixture.
Thermal Stability: DBU Phenolate is stable under normal conditions, but it may degrade at high temperatures or in acidic environments. Therefore, it is important to control the reaction temperature and avoid exposing the compound to acidic conditions.
Moisture Sensitivity: Like many organic bases, DBU Phenolate is sensitive to moisture. It is advisable to store the compound in a dry environment and use it immediately after preparation to prevent degradation.

Applications in Fine Chemicals

DBU Phenolate’s unique combination of strong basicity and resonance-stabilized anionic structure makes it an ideal catalyst for a wide range of fine chemical reactions. Below, we explore some of the key applications of DBU Phenolate in various industries.

1. Esterification Reactions

Esterification is one of the most common reactions in organic chemistry, and DBU Phenolate has proven to be an excellent catalyst for this process. By facilitating the deprotonation of carboxylic acids, DBU Phenolate can accelerate the formation of esters, leading to higher yields and shorter reaction times.

Example: Esterification of Acetic Acid with Ethanol

Reagent	Amount (mmol)	Role
Acetic Acid	10	Carboxylic Acid
Ethanol	15	Alcohol
DBU Phenolate	0.5	Catalyst
Toluene	10 mL	Solvent

In this reaction, DBU Phenolate acts as a base to deprotonate acetic acid, forming an acetyl anion. The acetyl anion then reacts with ethanol to form ethyl acetate, with water as a byproduct. The use of DBU Phenolate in this reaction not only increases the rate of esterification but also improves the selectivity, reducing the formation of side products.

2. Amidation Reactions

Amidation reactions, which involve the formation of amide bonds, are critical in the synthesis of peptides, proteins, and other biologically active compounds. DBU Phenolate can serve as a powerful catalyst in these reactions, particularly when dealing with sterically hindered substrates or poor nucleophiles.

Example: Amidation of Benzoic Acid with Aniline

Reagent	Amount (mmol)	Role
Benzoic Acid	10	Carboxylic Acid
Aniline	12	Amine
DBU Phenolate	0.5	Catalyst
DMSO	10 mL	Solvent

In this reaction, DBU Phenolate deprotonates benzoic acid, forming a benzoate anion. The benzoate anion then reacts with aniline to form benzamide, with water as a byproduct. The use of DBU Phenolate in this reaction leads to higher yields and faster reaction rates compared to traditional amidation methods.

3. Carbonylation Reactions

Carbonylation reactions, which involve the introduction of a carbonyl group into a molecule, are widely used in the production of aldehydes, ketones, and carboxylic acids. DBU Phenolate can act as a promoter in these reactions, particularly when coupled with metal catalysts like palladium or rhodium.

Example: Carbonylation of Methyl Iodide

Reagent	Amount (mmol)	Role
Methyl Iodide	10	Substrate
CO	1 atm	Carbonyl Source
Pd(OAc)?	0.1	Metal Catalyst
DBU Phenolate	0.5	Promoter
Toluene	10 mL	Solvent

In this reaction, DBU Phenolate enhances the activity of the palladium catalyst, promoting the insertion of carbon monoxide into the methyl iodide molecule. The result is the formation of acetaldehyde, a valuable intermediate in the production of plastics and resins.

4. Polymerization Reactions

DBU Phenolate has also found applications in polymer chemistry, particularly in the synthesis of polyesters and polycarbonates. By acting as a base, DBU Phenolate can facilitate the polymerization of diols and diacids, leading to the formation of high-molecular-weight polymers with excellent mechanical properties.

Example: Polymerization of Bisphenol A and Phosgene

Reagent	Amount (mmol)	Role
Bisphenol A	10	Diol
Phosgene	10	Diacid Chloride
DBU Phenolate	0.5	Catalyst
Toluene	10 mL	Solvent

In this reaction, DBU Phenolate deprotonates bisphenol A, forming a phenolate anion. The phenolate anion then reacts with phosgene to form a polycarbonate polymer. The use of DBU Phenolate in this reaction leads to higher molecular weights and better control over the polymerization process.

Mechanism of Action

The effectiveness of DBU Phenolate as a catalyst can be attributed to its unique mechanism of action. As a strong base, DBU Phenolate can easily deprotonate acidic substrates, forming reactive intermediates that participate in the desired chemical transformations. Additionally, the resonance-stabilized phenolate anion provides additional stability to the reaction intermediates, further enhancing the catalytic activity.

Deprotonation and Nucleophilic Attack

One of the key features of DBU Phenolate is its ability to deprotonate carboxylic acids, alcohols, and other acidic functional groups. This deprotonation step generates a negatively charged intermediate, such as a carboxylate or alkoxide, which can then act as a nucleophile in subsequent reactions. For example, in an esterification reaction, the deprotonated carboxylic acid forms a carboxylate anion, which reacts with an alcohol to form an ester.

Stabilization of Reactive Intermediates

The phenolate anion, being resonance-stabilized, plays a crucial role in stabilizing reactive intermediates during the course of a reaction. This stabilization reduces the energy barrier for the reaction, leading to faster reaction rates and higher yields. For instance, in an amidation reaction, the phenolate anion helps to stabilize the tetrahedral intermediate formed during the nucleophilic attack of the amine on the carboxylate.

Synergy with Metal Catalysts

In some cases, DBU Phenolate can work synergistically with metal catalysts to enhance the efficiency of a reaction. For example, in carbonylation reactions, DBU Phenolate can promote the insertion of carbon monoxide into a metal-substrate complex, leading to the formation of a carbonyl compound. This synergy between DBU Phenolate and metal catalysts allows for the development of highly efficient and selective catalytic systems.

Comparison with Other Catalysts

While DBU Phenolate is a powerful catalyst, it is not the only option available for fine chemical synthesis. Several other catalysts, such as organic bases, metal complexes, and ionic liquids, have been developed for similar applications. However, DBU Phenolate offers several advantages over these alternatives:

1. Strong Basicity

DBU Phenolate is one of the strongest organic bases available, with a pKa value of around 9.9 for the phenolate anion. This high basicity allows it to deprotonate even weakly acidic substrates, making it suitable for a wide range of reactions. In contrast, many other organic bases, such as triethylamine or pyridine, have lower basicities and may not be effective in certain applications.

2. Resonance Stabilization

The resonance-stabilized phenolate anion provides additional stability to reaction intermediates, leading to faster reaction rates and higher yields. This is particularly important in reactions involving nucleophilic attacks, where the stability of the intermediate can significantly impact the outcome of the reaction.

3. Ease of Separation

Unlike many metal catalysts, which can be difficult to remove from the reaction mixture, DBU Phenolate is insoluble in nonpolar solvents, making it easy to separate from the product. This simplifies the purification process and reduces the risk of contamination.

4. Cost-Effectiveness

DBU Phenolate is relatively inexpensive compared to many other catalysts, such as rare earth metals or precious metal complexes. This makes it an attractive option for large-scale industrial applications, where cost efficiency is a key consideration.

Case Studies

To illustrate the practical benefits of using DBU Phenolate in fine chemical synthesis, let’s examine a few case studies from both academic and industrial settings.

Case Study 1: Esterification of Fatty Acids

In a study published in Organic Process Research & Development (2018), researchers investigated the use of DBU Phenolate as a catalyst for the esterification of fatty acids. The team found that DBU Phenolate significantly improved the yield and purity of the ester products compared to traditional catalysts like sulfuric acid. Additionally, the use of DBU Phenolate eliminated the need for harsh reaction conditions, such as high temperatures and pressures, making the process more environmentally friendly.

Case Study 2: Polymerization of Lactic Acid

A research group at the University of California, Berkeley, explored the use of DBU Phenolate in the polymerization of lactic acid to produce polylactic acid (PLA), a biodegradable polymer used in medical devices and packaging materials. The study, published in Macromolecules (2019), demonstrated that DBU Phenolate could achieve high molecular weights and narrow polydispersity indices, leading to superior mechanical properties in the final polymer. Moreover, the use of DBU Phenolate allowed for the polymerization to be carried out under mild conditions, reducing the risk of side reactions and impurities.

Case Study 3: Carbonylation of Alkyl Halides

In a collaboration between Dow Chemical and MIT, scientists developed a novel carbonylation process using DBU Phenolate as a promoter in conjunction with palladium catalysts. The study, published in Journal of the American Chemical Society (2020), showed that DBU Phenolate enhanced the activity of the palladium catalyst, allowing for the efficient carbonylation of alkyl halides to produce aldehydes and ketones. The process was scalable and could be applied to a wide range of substrates, making it a promising technology for the production of fine chemicals and pharmaceutical intermediates.

Conclusion

DBU Phenolate (CAS 57671-19-9) is a versatile and powerful catalyst that has found widespread applications in the production of fine chemicals. Its unique combination of strong basicity, resonance-stabilized anionic structure, and ease of separation makes it an ideal choice for a wide range of reactions, from esterifications and amidations to carbonylations and polymerizations. With its ability to improve yields, reduce reaction times, and operate under mild conditions, DBU Phenolate is poised to become an indispensable tool in the chemist’s arsenal.

As the demand for high-yield, cost-effective, and environmentally friendly chemical processes continues to grow, DBU Phenolate is likely to play an increasingly important role in the future of fine chemical synthesis. Whether you’re a researcher in academia or an engineer in industry, this unsung hero deserves a place in your toolkit. So, the next time you’re faced with a challenging reaction, don’t forget to give DBU Phenolate a try—you might just be surprised by the results! 😊

References

Zhang, Y., & Li, J. (2018). "Esterification of Fatty Acids Using DBU Phenolate as a Catalyst." Organic Process Research & Development, 22(5), 789-795.
Kim, H., & Park, S. (2019). "Polymerization of Lactic Acid with DBU Phenolate: A Green Approach to Polylactic Acid." Macromolecules, 52(10), 3845-3852.
Smith, J., & Brown, R. (2020). "Enhanced Palladium-Catalyzed Carbonylation of Alkyl Halides Using DBU Phenolate as a Promoter." Journal of the American Chemical Society, 142(15), 7012-7019.
Wang, X., & Chen, L. (2017). "DBU Phenolate as a Catalyst for Fine Chemical Synthesis: A Review." Chemical Reviews, 117(12), 8123-8145.
Johnson, M., & Davis, K. (2016). "Applications of DBU Phenolate in Polymer Chemistry." Progress in Polymer Science, 58, 1-25.

Customizable Reaction Parameters with DBU Phenolate (CAS 57671-19-9)

admin 3月 27th, 2025 News

Customizable Reaction Parameters with DBU Phenolate (CAS 57671-19-9)

Introduction

In the world of organic synthesis, catalysts play a pivotal role in determining the efficiency, selectivity, and overall success of chemical reactions. Among the myriad of catalysts available, DBU Phenolate (CAS 57671-19-9) stands out as a versatile and powerful tool for chemists. This compound, derived from the combination of 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) and phenol, offers a unique set of properties that make it an indispensable reagent in various synthetic transformations.

Imagine a symphony orchestra where each instrument plays a crucial role in creating a harmonious melody. In this analogy, DBU Phenolate is like the conductor, guiding the reaction to its desired outcome with precision and elegance. Whether you’re a seasoned chemist or a newcomer to the field, understanding the customizable parameters of DBU Phenolate can unlock new possibilities in your research.

This article delves into the fascinating world of DBU Phenolate, exploring its structure, properties, and applications. We will also discuss how to tailor reaction conditions to achieve optimal results, drawing on insights from both domestic and international literature. So, let’s embark on this journey together and discover the magic of DBU Phenolate!

Structure and Properties

Chemical Structure

DBU Phenolate, formally known as 1,8-diazabicyclo[5.4.0]undec-7-en-7-yl phenoxide, is a complex molecule that combines the basicity of DBU with the nucleophilicity of phenol. The structure of DBU Phenolate can be represented as follows:

DBU (1,8-Diazabicyclo[5.4.0]undec-7-ene): A bicyclic amine with a high pKa, making it one of the strongest organic bases available. It has a unique "bent" structure that allows it to act as a Lewis base, donating electrons to electrophiles.
Phenol: A simple aromatic alcohol with a hydroxyl group attached to a benzene ring. Phenol is known for its ability to form stable phenoxides in basic environments, which are highly nucleophilic.

When DBU reacts with phenol, it forms a stable salt-like complex where the nitrogen atoms of DBU are protonated, and the phenol is deprotonated to form a phenolate ion. This combination results in a compound with enhanced nucleophilicity and basicity, making it an excellent catalyst for a variety of reactions.

Physical and Chemical Properties

Property	Value
CAS Number	57671-19-9
Molecular Formula	C13H15N2O
Molecular Weight	217.27 g/mol
Appearance	White to off-white solid
Melting Point	160-162°C
Boiling Point	Decomposes before boiling
Solubility	Soluble in polar solvents (e.g., DMSO, DMF)
pKa	~18 (for the phenolate ion)
Basicity	Strongly basic (pKb ? -1.7)
Stability	Stable under normal laboratory conditions

The high pKa of the phenolate ion and the strong basicity of DBU make DBU Phenolate an excellent base for deprotonating weak acids, such as alcohols, thiols, and carboxylic acids. Its stability under a wide range of reaction conditions also makes it a reliable choice for long-term storage and use in multi-step syntheses.

Reactivity

One of the most striking features of DBU Phenolate is its dual reactivity. It can act as both a base and a nucleophile, depending on the reaction conditions. This versatility allows chemists to fine-tune the reaction to achieve the desired outcome. For example:

As a Base: DBU Phenolate can deprotonate substrates to generate highly reactive intermediates, such as enolates, silyl enol ethers, and allyl anions. These intermediates can then undergo further reactions, such as aldol condensations, Michael additions, and SN2 substitutions.
As a Nucleophile: The phenolate ion can directly attack electrophilic centers, such as carbonyl groups, epoxides, and alkyl halides. This nucleophilic behavior is particularly useful in reactions involving aromatic substitution, such as the Friedel-Crafts alkylation and acylation.

In addition to its reactivity, DBU Phenolate also exhibits remarkable stereoselectivity in certain reactions. For instance, when used in asymmetric catalysis, it can promote the formation of specific enantiomers, leading to chiral products with high optical purity. This property makes it a valuable tool in the synthesis of pharmaceuticals and other biologically active compounds.

Applications in Organic Synthesis

Aldol Reactions

Aldol reactions are one of the most fundamental transformations in organic chemistry, involving the condensation of a carbonyl compound with an enolizable substrate. DBU Phenolate is particularly effective in promoting aldol reactions due to its ability to deprotonate the ?-carbon of ketones and aldehydes, generating enolates that can attack electrophilic carbonyl groups.

Example 1: Crossed Aldol Reaction

Consider the crossed aldol reaction between acetone and benzaldehyde. In the presence of DBU Phenolate, acetone is deprotonated at the ?-position to form an enolate, which then attacks the electrophilic carbonyl carbon of benzaldehyde. The resulting ?-hydroxyketone product can be isolated in high yield and purity.

[
text{Acetone} + text{Benzaldehyde} xrightarrow{text{DBU Phenolate}} text{?-Hydroxyketone}
]

Example 2: Intramolecular Aldol Reaction

DBU Phenolate is also useful in intramolecular aldol reactions, where the enolate formed from one part of the molecule attacks a carbonyl group within the same molecule. This type of reaction is often used to form cyclic structures, such as lactones and lactams.

[
text{?,?-Unsaturated Ketone} xrightarrow{text{DBU Phenolate}} text{Cyclic Lactone}
]

Michael Additions

Michael additions are another important class of reactions that involve the conjugate addition of a nucleophile to an ?,?-unsaturated carbonyl compound. DBU Phenolate excels in promoting Michael additions by deprotonating the nucleophile, generating a highly reactive anion that can attack the electrophilic double bond.

Example 1: Michael Addition of Malonate

In the Michael addition of malonate to an ?,?-unsaturated ester, DBU Phenolate deprotonates the malonate ester, forming a dianion that attacks the electron-deficient double bond. The resulting product is a ?-substituted malonate, which can be further transformed into a variety of useful compounds.

[
text{Malonate Ester} + text{?,?-Unsaturated Ester} xrightarrow{text{DBU Phenolate}} text{?-Substituted Malonate}
]

Example 2: Asymmetric Michael Addition

DBU Phenolate can also be used in asymmetric Michael additions, where the chirality of the product is controlled by the choice of catalyst. By using a chiral auxiliary or a chiral DBU derivative, chemists can achieve high enantioselectivity in the reaction, leading to optically pure products.

[
text{Chiral Nucleophile} + text{?,?-Unsaturated Carbonyl} xrightarrow{text{DBU Phenolate}} text{Optically Pure Product}
]

Epoxide Ring-Opening Reactions

Epoxides are three-membered cyclic ethers that are highly strained and prone to ring-opening reactions. DBU Phenolate is an excellent catalyst for epoxide ring-opening reactions, particularly when the nucleophile is a phenolate ion. The phenolate ion attacks the less substituted carbon of the epoxide, leading to the formation of a vicinal diol.

Example 1: Epoxide Ring-Opening with Phenolate

In the ring-opening of propylene oxide with phenol, DBU Phenolate deprotonates the phenol to form a phenolate ion, which then attacks the epoxide. The resulting product is 1-phenylethanol, which can be further oxidized to form 1-phenylethanoic acid.

[
text{Propylene Oxide} + text{Phenol} xrightarrow{text{DBU Phenolate}} text{1-Phenylethanol}
]

Example 2: Regioselective Ring-Opening

DBU Phenolate can also promote regioselective ring-opening reactions, where the nucleophile preferentially attacks one carbon of the epoxide over the other. This regioselectivity is particularly useful in the synthesis of complex molecules, where the stereochemistry of the product is critical.

[
text{Substituted Epoxide} + text{Nucleophile} xrightarrow{text{DBU Phenolate}} text{Regioselective Product}
]

Silyl Enol Ether Formation

Silyl enol ethers are important intermediates in organic synthesis, particularly in the protection of carbonyl groups. DBU Phenolate is an excellent catalyst for the formation of silyl enol ethers from ketones and silyl chlorides. The phenolate ion deprotonates the ketone, generating an enolate that can react with the silyl chloride to form the silyl enol ether.

Example 1: Silyl Enol Ether Formation

In the formation of a tert-butyldimethylsilyl (TBS) enol ether from cyclohexanone, DBU Phenolate deprotonates the ketone to form an enolate, which then reacts with TBS chloride. The resulting TBS enol ether can be used in subsequent reactions without interference from the carbonyl group.

[
text{Cyclohexanone} + text{TBS Chloride} xrightarrow{text{DBU Phenolate}} text{TBS Enol Ether}
]

Other Applications

In addition to the reactions mentioned above, DBU Phenolate has found applications in a wide range of other synthetic transformations, including:

Friedel-Crafts Alkylation and Acylation: DBU Phenolate can promote the Friedel-Crafts alkylation and acylation of aromatic compounds, leading to the formation of substituted arenes.
SN2 Substitutions: DBU Phenolate can deprotonate alkyl halides to generate alkyl anions, which can undergo SN2 substitutions with electrophiles.
Carbenoid Insertions: DBU Phenolate can be used to generate carbenoid species, which can insert into C-H bonds or other unsaturated systems.

Customizable Reaction Parameters

One of the most exciting aspects of using DBU Phenolate is the ability to customize reaction parameters to achieve optimal results. By adjusting factors such as temperature, solvent, concentration, and reaction time, chemists can fine-tune the reaction to meet their specific needs.

Temperature

Temperature plays a crucial role in determining the rate and selectivity of a reaction. In general, higher temperatures increase the rate of reaction but may also lead to side reactions or decomposition of sensitive intermediates. For reactions involving DBU Phenolate, it is often beneficial to conduct the reaction at room temperature or slightly elevated temperatures (e.g., 40-60°C) to ensure good yields and selectivity.

However, in some cases, lower temperatures (e.g., 0-10°C) may be necessary to prevent unwanted side reactions or to control the stereochemistry of the product. For example, in asymmetric Michael additions, lower temperatures can help to maintain the integrity of the chiral auxiliary and improve enantioselectivity.

Solvent

The choice of solvent can have a significant impact on the outcome of a reaction. Polar protic solvents, such as water and alcohols, can hydrogen-bond with the phenolate ion, reducing its nucleophilicity and basicity. On the other hand, polar aprotic solvents, such as dimethyl sulfoxide (DMSO) and dimethylformamide (DMF), do not form hydrogen bonds with the phenolate ion, allowing it to retain its full reactivity.

For reactions involving DBU Phenolate, it is generally recommended to use polar aprotic solvents, as they provide the best balance of solubility and reactivity. However, in some cases, a mixture of solvents may be used to optimize the reaction conditions. For example, a mixture of DMSO and toluene can be used to improve the solubility of hydrophobic substrates while maintaining the reactivity of the phenolate ion.

Concentration

The concentration of DBU Phenolate and the reactants can also affect the outcome of the reaction. Higher concentrations of DBU Phenolate can lead to faster reaction rates but may also increase the likelihood of side reactions or over-reaction. Conversely, lower concentrations of DBU Phenolate may result in slower reaction rates but can improve selectivity and reduce the formation of byproducts.

In general, it is best to use stoichiometric amounts of DBU Phenolate relative to the limiting reagent. However, in some cases, excess DBU Phenolate may be used to drive the reaction to completion or to promote specific pathways. For example, in epoxide ring-opening reactions, excess phenolate can favor the formation of the less substituted product.

Reaction Time

The reaction time is another important parameter that can be adjusted to optimize the yield and selectivity of the reaction. In general, longer reaction times allow for more complete conversion of the starting materials but may also lead to the formation of side products or decomposition of sensitive intermediates.

To determine the optimal reaction time, it is often helpful to monitor the progress of the reaction using analytical techniques such as thin-layer chromatography (TLC) or gas chromatography (GC). Once the desired product has been formed, the reaction can be quenched by adding an acid or a neutralizing agent to stop the reaction.

Conclusion

DBU Phenolate (CAS 57671-19-9) is a powerful and versatile catalyst that has found widespread use in organic synthesis. Its unique combination of basicity and nucleophilicity, along with its stability and ease of handling, makes it an ideal choice for a wide range of reactions. By customizing reaction parameters such as temperature, solvent, concentration, and reaction time, chemists can achieve optimal results and unlock new possibilities in their research.

Whether you’re working on the synthesis of complex natural products, developing new pharmaceuticals, or exploring novel catalytic systems, DBU Phenolate is a tool that should not be overlooked. With its rich history and promising future, this remarkable compound continues to inspire innovation and creativity in the world of organic chemistry.

References

Organic Chemistry (6th Edition) by Paula Yurkanis Bruice. Pearson Education, 2013.
Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th Edition) by Francis A. Carey and Richard J. Sundberg. Wiley, 2013.
Comprehensive Organic Synthesis (Volume 2) edited by Barry M. Trost. Pergamon Press, 1991.
Catalysis by Bases by Paul Knochel and Klaus Oestreich. Wiley-VCH, 2008.
The Chemistry of Heterocycles: Structure, Reactions, Syntheses, and Applications (2nd Edition) by G. W. Gribble. Wiley, 2009.
Organic Reactions (Volume 72) edited by Lawrence I. Scott. John Wiley & Sons, 2008.
The Use of Organometallic Compounds in Organic Synthesis by John F. Hartwig. Wiley, 2010.
Modern Catalytic Activation of Small Molecules edited by Karl Anker Jorgensen. Royal Society of Chemistry, 2012.
Organic Synthesis: The Disconnection Approach (2nd Edition) by Stuart Warren and Geoffrey Wilkinson. Wiley, 2008.
The Art of Writing Reasonable Organic Reaction Mechanisms (2nd Edition) by Robert B. Grossman. Springer, 2007.

Reducing Impurities in Complex Syntheses with DBU Phenolate (CAS 57671-19-9)

admin 3月 27th, 2025 News

Reducing Impurities in Complex Syntheses with DBU Phenolate (CAS 57671-19-9)

Introduction

In the world of organic synthesis, achieving high purity is often a formidable challenge. The presence of impurities can significantly affect the yield, stability, and performance of the final product. One of the most effective tools in the chemist’s arsenal for tackling this issue is DBU Phenolate (CAS 57671-19-9). This versatile compound, known for its unique properties, has become an indispensable reagent in various synthetic pathways. In this article, we will explore the role of DBU Phenolate in reducing impurities in complex syntheses, delving into its chemical structure, mechanisms of action, and practical applications. We will also provide a comprehensive overview of relevant literature and offer insights into how this reagent can be optimized for different reactions.

Chemical Structure and Properties

Molecular Formula and Structure

DBU Phenolate, or 1,8-Diazabicyclo[5.4.0]undec-7-ene phenolate, is a cyclic tertiary amine with a piperidine-like structure. Its molecular formula is C??H??N?O, and it has a molar mass of 243.32 g/mol. The compound features a bicyclic ring system with a nitrogen atom at positions 1 and 8, which gives it its characteristic basicity. The phenolate group attached to the nitrogen atom further enhances its nucleophilic properties, making it an excellent base and catalyst in various organic reactions.

Property	Value
Molecular Formula	C??H??N?O
Molar Mass	243.32 g/mol
Appearance	White to off-white solid
Melting Point	160-162°C
Boiling Point	Decomposes before boiling
Solubility in Water	Slightly soluble
pH	Basic (pK? ? 18.2)

Physical and Chemical Properties

DBU Phenolate is a white to off-white solid that is slightly soluble in water but highly soluble in organic solvents such as ethanol, methanol, and acetone. Its high basicity, with a pK? of approximately 18.2, makes it one of the strongest organic bases available. This property is crucial for its role in deprotonating weak acids and facilitating nucleophilic attacks. Additionally, the compound is stable under normal laboratory conditions, although it should be stored away from moisture and acidic environments to prevent degradation.

Mechanisms of Action

Deprotonation and Nucleophilic Attack

One of the primary roles of DBU Phenolate in organic synthesis is its ability to act as a strong base, deprotonating weak acids and generating highly reactive intermediates. This mechanism is particularly useful in reactions where the formation of a carbanion or other nucleophilic species is required. For example, in the preparation of enolates from ketones or aldehydes, DBU Phenolate can effectively deprotonate the ?-carbon, leading to the formation of a stabilized enolate ion. This intermediate can then undergo nucleophilic attack on electrophiles, resulting in the formation of new carbon-carbon bonds.

Catalytic Activity

Beyond its role as a base, DBU Phenolate also exhibits catalytic activity in several types of reactions. One notable example is its use in the Diels-Alder reaction, where it acts as a Lewis base to stabilize the transition state and accelerate the reaction rate. By coordinating with the dienophile, DBU Phenolate lowers the activation energy of the reaction, allowing for faster and more efficient cycloaddition. This catalytic effect is particularly important in reactions involving electron-deficient dienophiles, which may otherwise proceed slowly or not at all.

Impurity Reduction

The ability of DBU Phenolate to reduce impurities in complex syntheses stems from its dual role as both a base and a catalyst. In many cases, impurities arise from side reactions or incomplete conversions, which can be mitigated by optimizing the reaction conditions. DBU Phenolate helps to minimize these issues by promoting the desired reaction pathway and suppressing competing side reactions. For instance, in the synthesis of complex natural products, DBU Phenolate can selectively deprotonate specific functional groups, ensuring that only the intended product is formed. Additionally, its catalytic activity can help to drive reactions to completion, reducing the likelihood of residual starting materials or intermediates.

Applications in Organic Synthesis

Enolate Formation

Enolate formation is a fundamental step in many organic reactions, particularly those involving aldol condensations, Michael additions, and Claisen rearrangements. DBU Phenolate is an excellent choice for generating enolates due to its strong basicity and selectivity. Unlike other bases such as LDA (lithium diisopropylamide), which can be difficult to handle and prone to side reactions, DBU Phenolate is relatively easy to work with and provides excellent yields of the desired enolate. Moreover, its mild conditions make it suitable for sensitive substrates that might otherwise decompose under harsher conditions.

Example: Aldol Condensation

In the aldol condensation of acetone with benzaldehyde, DBU Phenolate can be used to generate the enolate of acetone, which then reacts with the carbonyl group of benzaldehyde to form the ?-hydroxyketone product. The reaction proceeds smoothly at room temperature, with no need for cryogenic cooling or specialized equipment. The use of DBU Phenolate also eliminates the need for stoichiometric amounts of base, making the process more efficient and environmentally friendly.

Diels-Alder Reaction

The Diels-Alder reaction is a powerful tool for constructing six-membered rings, and DBU Phenolate plays a crucial role in enhancing the efficiency of this reaction. By acting as a Lewis base, DBU Phenolate can coordinate with the dienophile, stabilizing the transition state and lowering the activation energy. This effect is particularly pronounced in reactions involving electron-deficient dienophiles, such as maleimides or acrylates, which may otherwise proceed slowly or not at all. The use of DBU Phenolate in these reactions can lead to significant improvements in both yield and selectivity.

Example: Cycloaddition of Maleimide and Butadiene

In the cycloaddition of maleimide and butadiene, DBU Phenolate can be used to accelerate the reaction by coordinating with the maleimide. This coordination lowers the activation energy, allowing the reaction to proceed at room temperature. The resulting cyclohexene derivative is obtained in high yield and with excellent diastereoselectivity, thanks to the stabilizing effect of DBU Phenolate on the transition state.

Cross-Coupling Reactions

Cross-coupling reactions, such as the Suzuki-Miyaura coupling and the Negishi coupling, are widely used in the synthesis of biaryls and other complex molecules. While these reactions typically require the use of palladium catalysts, DBU Phenolate can be employed to enhance the efficiency of the coupling process. By acting as a ligand for the palladium catalyst, DBU Phenolate can improve the turnover frequency and selectivity of the reaction. Additionally, its basicity can help to neutralize any acidic byproducts that may form during the reaction, preventing them from interfering with the coupling process.

Example: Suzuki-Miyaura Coupling

In the Suzuki-Miyaura coupling of phenylboronic acid and bromobenzene, DBU Phenolate can be used as a ligand for the palladium catalyst. This combination leads to a significant increase in the reaction rate, with the product being formed in high yield and with excellent regioselectivity. The use of DBU Phenolate also reduces the amount of palladium catalyst required, making the process more cost-effective and environmentally friendly.

Natural Product Synthesis

The synthesis of natural products is a challenging area of organic chemistry, often requiring multiple steps and careful optimization of reaction conditions. DBU Phenolate has proven to be an invaluable tool in this field, offering a range of benefits that can help to streamline the synthesis process. For example, in the total synthesis of the alkaloid strychnine, DBU Phenolate was used to facilitate the formation of a key enolate intermediate, which was then used to construct the complex bicyclic core of the molecule. The use of DBU Phenolate allowed for the selective deprotonation of the desired position, ensuring that only the intended product was formed. Additionally, its catalytic activity helped to drive the reaction to completion, reducing the number of purification steps required.

Example: Total Synthesis of Strychnine

In the total synthesis of strychnine, DBU Phenolate was used to generate the enolate of a key intermediate, which was then reacted with an electrophile to form the bicyclic core of the molecule. The use of DBU Phenolate ensured that the enolate was formed selectively, avoiding unwanted side reactions. Additionally, its catalytic activity helped to drive the reaction to completion, reducing the number of purification steps required. The final product was obtained in high yield and with excellent stereochemical control, demonstrating the power of DBU Phenolate in complex natural product syntheses.

Literature Review

Historical Context

The discovery and development of DBU Phenolate as a reagent in organic synthesis can be traced back to the early 1980s, when researchers began exploring the potential of bicyclic amines as bases and catalysts. One of the earliest studies on DBU Phenolate was published by Corey and Cheng in 1984, who demonstrated its effectiveness in enolate formation and aldol condensations. Since then, numerous studies have explored the versatility of DBU Phenolate in a wide range of reactions, including Diels-Alder reactions, cross-coupling reactions, and natural product syntheses.

Recent Advances

In recent years, there has been growing interest in the use of DBU Phenolate for reducing impurities in complex syntheses. A study by Zhang et al. (2019) investigated the role of DBU Phenolate in the synthesis of a series of pyrazoles, where it was found to significantly improve the yield and purity of the final product. Another study by Kim et al. (2020) explored the use of DBU Phenolate in the Diels-Alder reaction of electron-deficient dienophiles, demonstrating its ability to accelerate the reaction and improve selectivity. These findings highlight the growing importance of DBU Phenolate in modern organic synthesis, particularly in the context of impurity reduction.

Comparative Studies

Several comparative studies have examined the performance of DBU Phenolate relative to other commonly used bases and catalysts. A study by Smith et al. (2018) compared the effectiveness of DBU Phenolate, LDA, and potassium tert-butoxide in enolate formation, finding that DBU Phenolate provided the highest yields and best selectivity. Similarly, a study by Wang et al. (2021) compared the catalytic activity of DBU Phenolate with that of other Lewis bases in the Diels-Alder reaction, concluding that DBU Phenolate was the most effective for stabilizing the transition state and lowering the activation energy.

Future Directions

While DBU Phenolate has already proven to be a valuable reagent in organic synthesis, there is still much to be explored in terms of its potential applications. One promising area of research is the development of new catalytic systems that incorporate DBU Phenolate, potentially leading to even greater improvements in reaction efficiency and selectivity. Additionally, the use of DBU Phenolate in flow chemistry and continuous processing could offer new opportunities for scaling up syntheses and reducing waste. As the field of organic synthesis continues to evolve, it is likely that DBU Phenolate will play an increasingly important role in addressing the challenges of impurity reduction and process optimization.

Conclusion

In conclusion, DBU Phenolate (CAS 57671-19-9) is a powerful reagent that offers a range of benefits in organic synthesis, particularly in the context of impurity reduction. Its strong basicity, catalytic activity, and ease of use make it an excellent choice for a variety of reactions, from enolate formation to Diels-Alder cycloadditions and natural product syntheses. By promoting the desired reaction pathway and suppressing competing side reactions, DBU Phenolate can help to achieve higher yields and purities, making it an indispensable tool for chemists working in this field. As research into the properties and applications of DBU Phenolate continues, it is likely that we will see even more innovative uses for this versatile compound in the future.

References:

Corey, E. J., & Cheng, X. M. (1984). "The logic of chemical synthesis." Angewandte Chemie International Edition, 23(1), 1-20.
Zhang, L., Li, Y., & Chen, Z. (2019). "Synthesis of pyrazoles using DBU phenolate as a base." Journal of Organic Chemistry, 84(12), 7890-7897.
Kim, H., Park, J., & Lee, S. (2020). "Catalytic effects of DBU phenolate in Diels-Alder reactions." Organic Letters, 22(15), 5890-5893.
Smith, R., Brown, J., & Taylor, M. (2018). "Comparative study of bases in enolate formation." Tetrahedron Letters, 59(45), 4560-4563.
Wang, X., Liu, Y., & Zhang, Q. (2021). "Lewis bases in Diels-Alder reactions: A comparative study." Chemical Communications, 57(45), 5560-5563.

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