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Phase-transfer catalyst
Phase-transfer catalyst
Phase-transfer catalyst
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In chemistry, a phase-transfer catalyst or PTC is a catalyst that facilitates the transition of a reactant from one phase into another phase where reaction occurs. Phase-transfer catalysis is a special form of catalysis and can act through homogeneous catalysis or heterogeneous catalysis methods depending on the catalyst used. Ionic reactants are often soluble in an aqueous phase but insoluble in an organic phase in the absence of the phase-transfer catalyst. The catalyst functions like a detergent for solubilizing the salts into the organic phase. Phase-transfer catalysis refers to the acceleration of the reaction upon the addition of the phase-transfer catalyst. PTC is widely exploited industrially.[1] Polyesters for example are prepared from acyl chlorides and bisphenol-A. Phosphothioate-based pesticides are generated by PTC-catalyzed alkylation of phosphothioates.

Liquid-liquid-liquid triphase transfer catalysis, Molecular Catalysis 466 (2019) 112–121

In ideal cases, PTC can be fast and efficient, minimizing the need for expensive or dangerous solvents and simplifying purification[2] Phase-transfer catalysts are "green"—by allowing the use of water, the need for organic solvents is lowered.[3][4]


Types

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Tris(2-(2-methoxyethoxy)ethyl)amine is a typical industrial phase transfer catalyst.

Phase-transfer catalysts for anionic reactants are often quaternary ammonium salts. Commercially important catalysts include benzyltriethylammonium chloride, methyltricaprylammonium chloride and methyltributylammonium chloride. Organic phosphonium salts are also used, e.g., hexadecyltributylphosphonium bromide. The phosphonium salts tolerate higher temperatures.

An alternative to the use of "quat salts" is to convert alkali metal cations into hydrophobic cations. Crown ethers are used for this purpose on the laboratory scale. Polyethylene glycols and their amine derivatives are common in practical applications. One such catalyst is tris(2-(2-methoxyethoxy)ethyl)amine. These ligands encapsulate alkali metal cations (typically Na+ and K+), affording lipophilic cations. Polyethers have a hydrophilic "interiors" containing the ion and a hydrophobic exterior.

Chiral phase-transfer catalysts have also been demonstrated.[5] Asymmetric alkylations are catalyzed by chiral quaternary ammonium salts derived from cinchona alkaloids.[6]

A variety of functionalized catalysts have been evaluated for PTC. One example is the Janus interphase catalyst, applicable to organic reactions on the interface of two phases via the formation of Pickering emulsion.[7]

Limitations

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Quaternary ammonium cations degrade by Hofmann degradation to amines, especially at higher temperatures preferred by process chemists. The resulting amines can be difficult to remove from the product. Phosphonium salt are unstable toward base, degrading to phosphine oxide.[1]

Laboratory examples

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For example, the nucleophilic substitution reaction of an aqueous sodium cyanide solution with an ethereal solution of 1-bromooctane does not readily occur. The 1-bromooctane is poorly soluble in the aqueous cyanide solution, and the sodium cyanide does not dissolve well in the ether. Upon the addition of small amounts of hexadecyltributylphosphonium bromide, a rapid reaction ensues to give nonyl nitrile:

By the quaternary phosphonium cation, cyanide ions are "ferried" from the aqueous phase into the organic phase.[8]

Subsequent work demonstrated that many such reactions can be performed rapidly at around room temperature using catalysts such as tetra-n-butylammonium bromide and methyltrioctylammonium chloride in benzene/water systems.[9]

Phase-boundary catalysis

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Phase-boundary catalysis (PBC) is a type of PTC wherein catalysis occurs at a phase boundary. Some zeolites can be modified to operate by PBC: they are hydrophobic on the inside and hydrophilic on the outside.[10] In some sense, PBC resemble enzymes. The major difference between this system and enzyme is lattice flexibility. The lattice of zeolite is rigid, whereas the enzyme is flexible. Phase-boundary catalytic (PBC) systems can be contrasted with conventional catalytic systems. PBC is primarily applicable to reactions at the interface of an aqueous phase and organic phase. In these cases, an approach such as PBC is needed due to the immiscibility of aqueous phases with most organic substrate. In PBC, the catalyst acts at the interface between the aqueous and organic phases. The reaction medium of phase boundary catalysis systems for the catalytic reaction of immiscible aqueous and organic phases consists of three phases; an organic liquid phase, containing most of the substrate, an aqueous liquid phase containing most of the substrate in aqueous phase and the solid catalyst.

Design of phase-boundary catalyst

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Schematic representation of the advantage of phase-boundary catalysis in comparison with conventional catalytic system.

A zeolite is treated with alkylsilane to render its surface hydrophobic.[10] For examplex n-octadecyltrichlorosilane (OTS) has been used to modify W-Ti-NaY materials Due to the hydrophilicity of the w-Ti-NaY surface.

Phase transfer agents (PTAs)

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Not all phase transfer processes involve catalysis. A distinction can be made between phase-transfer catalysts (PTCs), which facilitate catalytic turnover between immiscible phases, and phase transfer agents (PTAs), which operate in stoichiometric or excess amounts to assist the movement of solutes between phases without participating in a catalytic cycle.

Phase transfer agents are typically surfactant-like molecules or ligands that aid in the extraction, stabilisation, or dispersion of compounds—particularly nanoparticles, ions, or polymers—between immiscible media such as water and organic solvents. Unlike PTCs, these agents are not regenerated and are often retained in the final product or dispersion medium.

Examples of PTAs include:

  • Cetyltrimethylammonium bromide (CTAB) – often used to transfer metal nanoparticles from aqueous to organic media via bilayer or micellar encapsulation.
  • Oleylamine (OAm) and octadecylamine (ODA) – long-chain primary amines used in nanochemistry for transferring and stabilising hydrophilic nanoparticles in nonpolar organic solvents.[11]
  • Crown ethers and polyethylenglycol (PEG) derivatives – in specific stoichiometric applications, these compounds can also act as phase transfer agents, especially in inorganic or polymer-related systems.

Phase transfer agents play a crucial role in the synthesis and processing of colloidal nanomaterials, hybrid polymers, and functional coatings. They are especially relevant in materials science contexts such as electrospinning, thin-film fabrication, and surface functionalisation, where precise control over dispersion and compatibility between components is essential.

See also

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References

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

Phase-transfer catalyst

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from Grokipedia
A phase-transfer catalyst (PTC) is a substance that facilitates the transfer of a reactant, typically an anion, from one immiscible phase—such as an aqueous phase—to another, like an organic phase, where the reaction takes place, thereby enabling efficient interactions between reagents that would otherwise be separated by phase boundaries. Phase-transfer catalysis typically involves or salts, or ethers, which form lipophilic pairs that solubilize inorganic anions in nonpolar solvents, accelerating reaction rates by orders of magnitude compared to uncatalyzed systems. The mechanism often proceeds via an extraction , where the catalyst extracts the anion from the aqueous phase into the organic phase (Starks mechanism), or through interfacial reactions where occurs at the phase boundary (Makosza mechanism), with the catalyst regenerating after each cycle. This approach is particularly effective for nucleophilic substitutions, alkylations, oxidations, and carbonylations, allowing the use of inexpensive, concentrated bases like aqueous NaOH or KOH without the need for phase-soluble equivalents. The concept emerged in the late 1960s, with foundational work by researchers like Mieczysław Makosza in 1969, who hypothesized the mechanistic role of phase transfer, and Charles M. Starks in 1971, who formalized the term and extraction mechanism. Early commercial applications date back to 1946 for specific processes, but widespread adoption followed in the 1970s, leading to over 500 industrial uses by the 1990s, generating billions in annual economic value. Key advantages of PTC include simplified procedures, reduced energy and solvent consumption, high yields and selectivity, and through minimized waste, making it scalable for both laboratory synthesis and large-scale . Recent advancements incorporate chiral catalysts for asymmetric synthesis, expanding its utility in pharmaceutical production.

Fundamentals

Definition and Basic Principles

Phase-transfer catalysis (PTC) is a synthetic that facilitates reactions between reagents dissolved in immiscible phases, such as an aqueous phase and an organic solvent, by employing a phase-transfer agent to shuttle reactive across the phase boundary. This approach addresses the inherent inefficiency of biphasic systems, where direct contact between reactants is limited due to poor of ionic or polar in nonpolar media. By enabling the transfer of anions or cations, PTC allows reactions to occur under mild conditions, often at ambient temperature and , without requiring exotic solvents or elevated temperatures. The core principle of PTC relies on the use of a lipophilic phase-transfer agent, typically a quaternary or cation (denoted as Q⁺), which forms a neutral, extractable ion pair with an ionic reactant from the aqueous phase. This ion pair partitions into the organic phase, where the transferred species exhibits enhanced reactivity due to reduced and increased nucleophilicity compared to its hydrated form in . The catalyst is regenerated after the reaction, allowing it to cycle back to the aqueous phase for further transfers, thus requiring only catalytic amounts. In a standard PTC setup, the reaction occurs in a vigorously stirred of two immiscible phases: an aqueous phase containing the ionic reactant (e.g., a or anion) and a base, and an organic phase housing the nonpolar substrate. The phase-transfer agent, initially dissolved in the organic phase as Q⁺X⁻, equilibrates at the interface to extract the desired anion Y⁻, forming Q⁺Y⁻ in the organic phase for reaction. This process is illustrated by the key equilibrium for ion pair formation and extraction: \ceQ+X−(org)+Y−(aq)⇌Q+Y−(org)+X−(aq)\ce{Q+ X- (org) + Y- (aq) ⇌ Q+ Y- (org) + X- (aq)} where Q⁺ is the lipophilic cation, X⁻ the counteranion, and Y⁻ the reactive anion being transferred.

Historical Development

The origins of phase-transfer catalysis trace back to the early 1950s, when researchers observed enhanced reaction rates in biphasic systems through the use of quaternary ammonium salts as emulsifiers or phase mediators. In 1951, Jarrouse reported the first deliberate application of such salts to facilitate the alkylation of phenylacetonitrile with dimethyl sulfate in a two-phase aqueous-organic medium, noting significant rate improvements without fully understanding the mechanism. During the 1950s and 1960s, scattered observations accumulated, including the use of these salts in emulsion polymerizations and halide displacements, where they unexpectedly promoted ion transfer across immiscible phases, though the phenomenon was not yet systematized. The field coalesced in the late and early through pioneering work by Makosza, who in 1969 demonstrated efficient of nitroalkanes under biphasic conditions using quaternary ammonium salts, attributing the effect to anion extraction into the organic phase. Charles M. Starks formalized the concept in 1971, coining the term "phase-transfer " in a seminal paper that described the catalytic role of onium salts in facilitating reactions between aqueous anions and organic substrates. Starks' 1978 book, co-authored with Liotta, established the foundational principles, mechanisms, and applications, becoming a cornerstone reference. Concurrently, Dehmlow's monograph provided early comprehensive reviews of synthetic applications, while Soviet researcher V. S. Gol'dberg contributed mechanistic insights and practical examples in the and ; Steven L. Regen introduced polymer-supported variants (triphase catalysis) in 1979, enabling catalyst recovery. Industrial adoption accelerated in the 1970s, with the first commercial processes emerging in , such as the esterification of penicillin derivatives, leveraging PTC to reduce solvent use and improve yields under mild conditions. The 1980s saw expansion into asymmetric PTC, pioneered by researchers like O'Donnell, Dolling, and Wynberg, who developed chiral quaternary ammonium salts for enantioselective alkylations, achieving modest but promising selectivities. In the 1990s and 2000s, PTC integrated with principles, emphasizing solvent minimization and recyclability; polymer-supported catalysts, building on Regen's work, gained traction for heterogeneous systems, while Gol'dberg's 1992 book highlighted specialized applications. By the 2020s, refinements included incorporation into continuous flow processes for scalable alkylations and biphasic biocatalytic cascades, enhancing and enzyme stability in aqueous-organic systems. More recent developments in the 2020s include combined asymmetric catalysis using transition metals and PTC, as well as applications in fuel desulfurization.

Mechanisms

Extraction Mechanism

The extraction mechanism, also known as the Starks mechanism, describes how a phase-transfer catalyst (PTC), typically a lipophilic or salt such as Q⁺Cl⁻, facilitates the transfer of an anionic reactant from an aqueous phase to an organic phase through ion-pair formation and equilibration at the liquid-liquid interface. In this process, the PTC cation Q⁺, which is soluble in the organic phase, pairs with the target anion Y⁻ from the aqueous phase to form a lipophilic ion pair Q⁺Y⁻ that migrates into the organic phase, where it can react with an organic substrate; the original anion (e.g., Cl⁻) is released back into the aqueous phase, allowing the PTC to be regenerated and recycled. This shuttling enhances the effective concentration of the reactive anion in the organic medium, often increasing its nucleophilicity by reducing effects. The mechanism proceeds through three primary steps. First, ion exchange occurs at the phase interface: Q⁺X⁻ (organic) + Y⁻ (aqueous) ⇌ Q⁺Y⁻ (organic) + X⁻ (aqueous), governed by the relative lipophilicities of the anions involved. Second, the extracted ion pair Q⁺Y⁻ reacts with the organic substrate in the bulk organic phase, such as in a nucleophilic substitution: Q⁺Y⁻ + R-Z → R-Y + Q⁺Z⁻ (organic). Third, the regenerated Q⁺Z⁻ returns to the interface, where Z⁻ exchanges back into the aqueous phase, completing the catalytic cycle. This contrasts with interfacial mechanisms, where reactions occur primarily at the phase boundary without significant bulk-phase transfer of ions. This mechanism is particularly applicable to reactions where the anion's reactivity in the organic phase is crucial, such as nucleophilic substitutions (e.g., alkylations with CN⁻ or OH⁻), and requires a sufficiently lipophilic PTC to ensure favorable partitioning of the ion pair into the organic . Efficiency is influenced by several factors, including the partition coefficients of the PTC-anion pairs (which determine extraction yields), (affecting anion and availability), and (impacting equilibration rates and ). The overall often follows pseudo-first-order kinetics with respect to PTC concentration under conditions where anion transfer is rate-limiting.

Interfacial Mechanism

The interfacial mechanism in phase-transfer catalysis (PTC) operates primarily at the boundary between immiscible phases, where the phase-transfer catalyst (PTC) concentrates reactive species to facilitate reactions without substantial bulk-phase transfer. This process is common in systems exhibiting high interfacial tension, such as those involving concentrated aqueous bases like NaOH or KOH and nonpolar organic solvents, and it predominates when using less lipophilic PTCs that preferentially adsorb at the interface rather than dissolve significantly in the organic phase. Pioneered by Mieczysław Mąkosza in the late , this mechanism enhances reaction rates by localizing anions and organic substrates at the phase boundary, where reduced leads to higher nucleophilicity. The key steps begin with the adsorption of the PTC, typically an onium salt, and inorganic anions (e.g., OH⁻) onto the liquid-liquid interface from the aqueous phase. This is followed by the reaction of the interfacial anion with an organic substrate that diffuses to the boundary, forming products that subsequently desorb into the respective phases. Unlike the extraction mechanism, which relies on ion-pair in the bulk organic phase for reaction, the interfacial pathway features negligible transfer of lipophilic ion pairs into the organic bulk, keeping the process confined to the surface. This mechanism is particularly suited for rapid interfacial reactions, such as hydrolyses of alkyl halides or oxidations involving inorganic anions, where the short lifetime of reactive intermediates favors boundary-localized chemistry. It contrasts with the extraction mechanism's emphasis on bulk-organic reactions by prioritizing surface adsorption over phase solubility. Several factors influence the efficiency of the interfacial mechanism, including the stirring rate, which modulates the interfacial area available for adsorption and reaction; additives, which can alter and anion partitioning; and the overall interfacial area, often enhanced in setups. The reaction rate depends on the interfacial concentration of the reactive anion, generally following a form such as r=k[anion]interfacer = k [\text{anion}]_{\text{interface}}, where kk incorporates substrate concentration at the boundary. Kinetic evidence supporting the interfacial mechanism includes studies demonstrating zero-order dependence on organic-phase stirring rates, indicating that mass transfer in the bulk organic phase is not rate-limiting and that reactions proceed dominantly at the interface. Such observations have been reported in base-catalyzed isomerizations and carbanion reactions using polyethylene glycol catalysts.

Phase-Transfer Agents

Onium Salts

Onium salts, particularly quaternary ammonium and phosphonium salts, serve as the most common phase-transfer agents due to their lipophilic cations paired with various anions, enabling the transport of inorganic anions into organic phases. These cations, often denoted as Q⁺, feature a central nitrogen or phosphorus atom bonded to four alkyl groups, such as in tetraalkylammonium (e.g., Bu₄N⁺) or tetraalkylphosphonium ions. The general structure follows the formula NR₄⁺ or PR₄⁺, where R represents alkyl substituents, and increases with the length of these chains, with optimal performance typically observed for C8–C18 alkyl groups that balance in organic solvents and ion-pairing efficiency. These salts are prepared via quaternization reactions, involving the of tertiary amines or phosphines with alkyl halides, yielding stable ion pairs like Q⁺X⁻. Common examples include (TBAB) and benzyltriethylammonium chloride (BTEAC), which are widely employed for their and catalytic efficacy in biphasic systems. Key properties of onium salts include high thermal stability relative to other agents, allowing operation up to approximately 150°C before significant decomposition via pathways like Hofmann elimination, though phosphonium variants often exhibit superior resistance to heat and base. They demonstrate good recyclability in multiple reaction cycles and selectivity toward soft, lipophilic anions, facilitating ion exchange as represented by the process Q⁺X⁻ → Q⁺Y⁻, where Y⁻ is the transferred anion. These attributes make onium salts inexpensive and versatile for classical phase-transfer catalysis, though their decomposition at elevated temperatures limits use in demanding conditions.

Macrocyclic and Polymeric Agents

Macrocyclic phase-transfer agents, such as crown ethers and cryptands, represent a class of ligands that facilitate the transport of inorganic anions across immiscible phase boundaries through selective cation complexation. Unlike salts that rely on electrostatic ion pairing, these agents form host-guest inclusion complexes with metal cations, enabling anion activation in organic media. Crown ethers are cyclic polyethers characterized by repeating (-CH₂CH₂O-) units forming a ring structure that provides a cavity for cation binding. The nomenclature, such as 18-crown-6, indicates 18 atoms in the ring with 6 oxygen donors, which preferentially complexes potassium ions (K⁺) due to optimal cavity size matching the ionic radius. Smaller variants like 12-crown-4 exhibit size-selective complexation for lithium ions (Li⁺), allowing tailored selectivity in phase-transfer reactions. The complexation can be represented as: M++Crown⇌[M⋅Crown]+\text{M}^{+} + \text{Crown} \rightleftharpoons [\text{M} \cdot \text{Crown}]^{+} This equilibrium enhances the solubility and reactivity of the associated anion in nonpolar solvents. Cryptands extend the macrocyclic concept to three-dimensional structures, featuring bridged polyether chains that encapsulate cations more securely than planar crown ethers. The [2.2.2]-cryptand, with three ethylene bridges connecting nitrogen atoms, forms inclusion complexes with alkali metals, exhibiting higher stability constants due to the cage-like topology that minimizes ligand exchange. For instance, lipophilic derivatives of [2.2.2]-cryptand activate anions like azide (N₃⁻) in aqueous-organic two-phase systems, outperforming crown ethers in nucleophilic substitutions by reducing cation-anion interactions. Polymeric phase-transfer agents incorporate macrocyclic or polyether units into solid supports or soluble chains for improved practicality. Crown ethers and cryptands can be covalently bound to resins via long alkyl spacers, enabling with facile separation by . Poly(ethylene glycol) (PEG), particularly PEG-400, serves as a non-ionic, soluble alternative, mimicking functionality through its flexible oxyethylene backbone that solvates cations without forming rigid cavities. These polymeric variants allow recycling—up to multiple cycles in substitution reactions—while maintaining activity, offering economic and environmental benefits over homogeneous catalysts. The specificity of macrocyclic and polymeric agents for particular cations enables milder reaction conditions, such as lower temperatures or reduced base concentrations, compared to non-selective onium salts. Chiral crown ethers, incorporating asymmetric substituents on the polyether ring, have been employed in asymmetric phase-transfer catalysis to achieve high enantioselectivity in reactions like α-alkylation of enolates, with enantiomeric excesses often exceeding 90%.

Types

Classical Phase-Transfer Catalysis

Classical phase-transfer catalysis employs a biphasic system consisting of an aqueous phase containing a base, such as (NaOH), and an organic phase with a water-immiscible solvent like (DCM) or , where the organic substrate resides. A phase-transfer catalyst, typically a quaternary salt like (TBAB), is added to facilitate the transfer of the anionic from the aqueous to the organic phase. This setup enables reactions between reagents insoluble in each other's phases by generating a lipophilic pair, such as Q⁺OH⁻, that migrates to the organic phase. Typical reactions catalyzed under these conditions include nucleophilic substitutions, such as the of , where phenol (ArOH) reacts with an alkyl (RX) to form the corresponding aryl alkyl ether (ArOR). For instance, in the O-alkylation of phenol with butyl using 50% aqueous NaOH, as solvent, and TBAB as catalyst, high yields are obtained at . Other examples encompass the Darzens condensation, involving α-halo esters and aldehydes to produce epoxy esters, often achieving 80-90% yields with triethylbenzylammonium chloride in 50% NaOH. Additionally, of epoxides proceeds efficiently, opening the ring with aqueous base under PTC to yield diols. These reactions are generally conducted at and , with PTC loadings of 1-10 mol% to optimize catalyst efficiency. Vigorous stirring enhances the interfacial area, promoting anion transfer. Kinetically, classical PTC is often mass-transfer limited in the organic phase, particularly for where anion transfer is rate-determining, leading to dependencies on agitation speed and catalyst . A key benefit is the avoidance of dipolar aprotic solvents like (DMF), which are typically required for homogeneous anionic activations but pose environmental and handling challenges. The general scheme for anionic activation in such systems can be represented as: ArOH+RX→Q+Br−,NaOH (aq),organic solventArOR+HX\text{ArOH} + \text{RX} \xrightarrow{\text{Q}^+\text{Br}^-, \text{NaOH (aq)}, \text{organic solvent}} \text{ArOR} + \text{HX}
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