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DABCO

1,4-Diazabicyclo[2.2.2]octane (DABCO), also known as triethylenediamine (TEDA), is a bicyclic with the molecular formula C₆H₁₂N₂ and a molecular weight of 112.17 g/mol. It features a bridged structure with two unhindered tertiary nitrogen atoms positioned at the bridgeheads, conferring exceptional nucleophilicity and basicity, with pKₐ values of 3.0 and 8.7 for its conjugate acids. DABCO manifests as hygroscopic white crystals with an ammonia-like odor, a of 158 °C, a of 174 °C, and high in (450 g/L) and organic solvents such as and . First synthesized in 1943 through the cyclization of salts, DABCO is now commercially produced via the catalytic thermolysis of or , yielding a product known for over a century under earlier names like quinolidine. Its strong basic and nucleophilic character enables it to form adducts with compounds like and , while its ease of handling and eco-friendliness make it a preferred in synthetic chemistry. DABCO serves primarily as an efficient catalyst in the production of polyurethane foams, where it promotes the urethane formation reaction, and in organic transformations such as Baylis-Hillman reactions, Morita-Baylis-Hillman reactions, [4+2] annulations, and cycloadditions, often achieving yields exceeding 80–90%. Beyond , it finds applications in pharmaceutical , pesticide production, , and as an anti-fade reagent in , as well as a radiation-protective agent in biological contexts. Despite its utility, DABCO is flammable and corrosive, necessitating careful handling to avoid skin and eye irritation.

Structure and properties

Molecular structure

DABCO has the molecular formula C₆H₁₂N₂ and the systematic IUPAC name 1,4-diazabicyclo[2.2.2]octane. This compound exhibits a bridged bicyclic architecture consisting of two nitrogen atoms positioned at the bridgehead sites, interconnected by three ethylene (-CH₂-CH₂-) bridges, forming a symmetric cage-like framework. As a ditertiary amine, both nitrogen atoms lack attached hydrogen atoms, with their lone pairs readily available and unhindered by the rigid structure, contributing to its high nucleophilicity. X-ray crystallographic studies reveal typical C-N bond lengths ranging from 1.456 to 1.472 and C-C bond lengths around 1.54 for DABCO in crystalline forms. The adopts a twisted chair-like conformation in its three six-membered rings, with N-C-C-N torsion angles typically between -21° and 16°, emphasizing the overall rigidity and symmetry of the [2.2.2]octane scaffold. This conformation can be visualized through Newman projections along the C-N bonds, showing eclipsed or staggered bridges that maintain the compact, three-dimensional without significant distortion.

Physical properties

DABCO is a colorless, hygroscopic crystalline solid with a characteristic ammonia-like odor. It possesses a molecular weight of 112.17 g/mol. Under standard conditions, DABCO exhibits a melting point of 158–160 °C and a boiling point of 174 °C at 760 mmHg. Its density is 1.14 g/cm³ at 20 °C. The rigidity of its bicyclic structure contributes to this relatively high melting point. DABCO displays high solubility in water, reaching approximately 45 g/100 mL at 25 °C, as well as in alcohols such as ethanol (77 g/100 g at 25 °C) and chloroform; it is less soluble in nonpolar solvents like hexane. Key spectroscopic data for DABCO include a ¹H NMR spectrum (300 MHz, CDCl₃) showing a singlet at 2.79 ppm for the 12 methylene protons; ¹³C NMR reveals a signal at approximately 52.5 ppm for the CH₂ carbons. The IR spectrum lacks N–H stretching bands characteristic of primary or secondary amines, featuring instead C–N stretching vibrations around 1100–1400 cm⁻¹.

Chemical properties

DABCO displays strong basicity attributable to its two unhindered tertiary amine groups, with the pKa values of its conjugate acids being 3.0 and 8.7 in . This basicity arises from the of the bicyclic framework, which positions the lone pairs for effective proton acceptance without significant steric hindrance. The unhindered nitrogens also contribute to its high nucleophilicity in non-reactive contexts. The compound exhibits thermal stability up to approximately 230 °C, beyond which decomposition initiates, as evidenced by safety data showing decomposition above 234 °C under standard conditions. DABCO demonstrates hydrolytic stability under neutral aqueous conditions, remaining intact without degradation, but undergoes protonation in acidic media to form the corresponding ammonium salts. It shows resistance to oxidation under ambient conditions, with no significant reactivity toward atmospheric oxygen or typical environmental oxidants at room temperature. Stable salts, such as the hydrochloride [DABCOH]⁺Cl⁻, are readily formed with strong acids and exhibit good solubility and crystallinity. DABCO has notable due to its functionalities, which facilitate intermolecular interactions like bonding and van der Waals forces in solutions or solids. The are governed by stepwise processes: the primary equilibrium is DABCO + H⁺ ⇌ [DABCOH]⁺, with an association constant K₁ ≈ 10⁹ M⁻¹ derived from the of 8.7; the secondary [DABCOH]⁺ + H⁺ ⇌ [DABCOH₂]²⁺ has a much lower constant K₂ ≈ 10³ M⁻¹, reflecting electrostatic repulsion in the dication. These equilibria underscore DABCO's preference for monoprotonation under mildly acidic conditions.

Synthesis and production

Laboratory synthesis

The original laboratory synthesis of DABCO was reported in 1943 by Otto Hromatka and Eva Engel at the . This method involves the cyclization of the dihydrobromide salt of 1-(2-bromoethyl) under basic conditions to form the bicyclic structure. An alternative preparative route utilizes double alkylation of with to generate a bis(haloethyl) intermediate, followed by intramolecular cyclization to yield DABCO. The precursor salt is treated with in refluxing to promote the intramolecular nucleophilic , affording DABCO after . The product is purified by at 50 °C and 0.3 mmHg pressure to obtain a white crystalline solid. DABCO can also be converted in the laboratory to its bis(sulfur dioxide) , known as DABSO, which serves as a stable solid intermediate for SO2 delivery in synthetic transformations. This is formed by reacting DABCO with gaseous SO2 at : \text{DABCO} + 2 \ \text{SO}_2 \rightarrow \text{DABCO} \cdot (\text{SO}_2)_2 The reaction is typically conducted by bubbling SO2 into a suspension of solid DABCO until absorption ceases, yielding a colorless crystalline solid that can be stored indefinitely under ambient conditions.

Industrial production

The primary industrial production of DABCO (1,4-diazabicyclo[2.2.2]octane), also known as triethylenediamine (TEDA), involves the catalytic thermolysis of ethylenediamine in a vapor-phase reaction. This process trimerizes ethylenediamine to form the bicyclic structure, as represented by the simplified equation: $3 \ce{H2NCH2CH2NH2} \rightarrow \ce{C6H12N2} + 4 \ce{NH3} The reaction typically occurs at temperatures of 250–500 °C, with optimal ranges around 310–390 °C, under pressures of 0.01–40 , often using a weight hourly space velocity (WHSV) of 0.05–6 h⁻¹. Catalysts employed include zeolites, particularly pentasil-type structures with high SiO₂/M₂O₃ ratios (e.g., >1400:1 for Al-based), which enhance selectivity and conversion. Earlier methods utilized metal oxide catalysts such as or supported on alumina, operating in the 200–300 °C range to promote and cyclization while minimizing side reactions. An alternative industrial route starts from or in the presence of , using zeolite catalysts like or titanium silicalite-1 (TS-1). This vapor-phase process runs at approximately 400 °C, achieving yields exceeding 90% for TEDA based on converted feed, with high EDA conversion rates up to 99%. These zeolite-based systems offer improved efficiency and reduced byproduct formation compared to traditional metal oxides. In both methods, the reaction proceeds in a fixed-bed , where the vaporized feed is passed over the catalyst bed, followed by of the effluent gas stream at 20–100 °C to condense products. The crude mixture undergoes to isolate pure TEDA (boiling point ~174 °C), with recycled as overhead vapor. Side products, notably , are separated and recycled back to the to boost overall and economic viability, minimizing in continuous operations. Global production of DABCO supports the industry and is classified as a high-production-volume chemical, with major manufacturers including (holder of the DABCO trademark), and Chemicals, , Dow, , Huntsman, , and . Annual capacity is estimated in the range of several thousand metric tons, driven by demand for catalysts in manufacturing.

Chemical reactivity

As a nucleophilic catalyst

DABCO serves as a nucleophilic in the Morita-Baylis-Hillman (MBH) reaction, where it initiates the process by adding to the β-carbon of an activated alkene, such as an (CH₂=CH-EWG, where EWG is an like CO₂R), forming a zwitterionic intermediate. This enolate-like species then attacks the carbonyl carbon of an (RCHO), followed by proton transfer and elimination of DABCO to yield the MBH . The overall transformation is represented by the equation: \ce{CH2=CH-EWG + RCHO ->[DABCO] R-CH(OH)-C(=CH2)-EWG} This reaction, first reported using DABCO as the catalyst, enables the stereoselective formation of densely functionalized allylic alcohols under mild conditions. In aza-Michael additions, DABCO functions primarily through its basicity to deprotonate nucleophiles, generating the corresponding species that adds to the β-carbon of α,β-unsaturated carbonyl compounds, such as acrylates or enones. The resulting β-amino carbonyl product is formed via proton transfer, with DABCO facilitating the activation without direct covalent involvement in the key bond-forming step. This catalysis is particularly effective for primary and secondary , proceeding in high yields under solvent-free or mild conditions. DABCO also accelerates acylation reactions, such as formation from acid chlorides and , by acting as a catalyst. It forms an acylammonium intermediate upon attack on the acid chloride, which is then displaced by the , regenerating DABCO and enhancing the reaction rate compared to uncatalyzed processes. This mechanism is analogous to the role of tertiary in Schotten-Baumann esterifications, providing clean and efficient synthesis of . Asymmetric variants of these reactions employ chiral DABCO derivatives, such as C₂-symmetric 2,3-disubstituted analogs, to induce in the MBH reaction, achieving enantiomeric excesses up to 90% for certain substrates like aryl aldehydes with . These modified catalysts influence the conformation of the zwitterionic intermediate, directing the facial selectivity of the aldehyde addition. Similar chiral DABCOs have been applied to asymmetric aza-Michael additions, though with varying degrees of enantiocontrol depending on the and acceptor.00153-G) DABCO catalysis provides significant rate enhancements in these nucleophilic processes, with accelerations up to 10⁴-fold observed for additions to certain acceptors like modified acrylates, attributed to the stabilization of the zwitterionic intermediates and lowered barriers.

As a Lewis base

DABCO, as a tertiary with two accessible lone pairs, acts as a base by donating electrons to various Lewis acids, forming stable coordination . Notable examples include its coordination to metal ions such as silver(I), where it forms the [Ag(DABCO)2]+ , characterized by a linear N-Ag-N geometry within three-dimensional coordination polymers featuring exceptional microporosity when paired with tetrahedral anions like BF4- or ReO4-. Similarly, DABCO coordinates to boron-based Lewis acids, as exemplified by the formation of the DABCO·BF3 via the reaction: \text{DABCO} + \text{BF}_3 \rightarrow \text{DABCO} \cdot \text{BF}_3 This adduct has been detected in solution through 11B and 19F NMR spectroscopy, confirming the dative bond from the nitrogen lone pair to the empty p-orbital of boron. Binding constants for such interactions vary depending on the Lewis acid; for instance, DABCO exhibits strong affinity toward soft metal centers like Ag(I), with stability enhanced by its bicyclic rigidity that minimizes steric distortion in the complexes. Beyond classical coordination, DABCO participates in charge-transfer complexes with electron-deficient species, facilitating reactions like sulfonylation. In this context, DABCO forms a colored with arene sulfonyl chlorides, such as p-toluenesulfonyl chloride (TsCl), through π-interactions and partial electron donation from its to the electrophilic center. This interaction triggers C-N bond cleavage in DABCO, enabling the synthesis of N-alkylated derivatives under mild conditions, as supported by UV-vis showing characteristic charge-transfer bands. DABCO also engages in hydrogen bonding as a base, serving as both an acceptor and donor in solid-state structures. In the bis(perhydrate) salt DABCO·2H2O2, the neutral DABCO molecules are incorporated into a hydrogen-bonded framework where the atoms accept protons from the H2O2 moieties, forming infinite chains along the lattice with O-H···N distances around 2.8 . This arrangement stabilizes the perhydrate, highlighting DABCO's role in through lone pair-mediated hydrogen bonds. Spectroscopic evidence for DABCO's lone pair donation is evident in NMR studies of its adducts. For example, in the DABCO·BF3 complex, the 19F NMR signal shifts downfield due to the deshielding effect from electron withdrawal by the coordinated , while 11B NMR shows a characteristic resonance indicative of tetrahedral coordination. These shifts directly reflect the donation of from the , altering the electronic environment around both the base and acid components.

As a singlet oxygen quencher

DABCO acts as a physical quencher of (¹O₂), deactivating the to ground-state (³O₂) via , without significant or consumption of DABCO. The involves formation of a or direct to form an of DABCO, represented by the equation: \text{DABCO} + {}^1\text{O}_2 \rightarrow \text{DABCO}^* + {}^3\text{O}_2 where DABCO* denotes the of DABCO. This process is facilitated by the tertiary structure of DABCO, which allows for effective interaction with ¹O₂ through . The rate constant for physical quenching (k_q) by DABCO is on the order of 10^8 M⁻¹ s⁻¹ in common solvents such as , , and , with values ranging from 8 × 10^6 to 3.4 × 10^8 M⁻¹ s⁻¹ depending on the solvent polarity and experimental conditions. The quenching efficiency is such that concentrations around 40 μM can quench approximately 50% of generated ¹O₂, as evidenced by halved decay rates of chemical traps like 9,10-dimethylanthracene in sensitized systems. The reactive quenching component (k_r) is minimal compared to the physical pathway, making DABCO suitable for protective applications where preservation of the quencher is desired. In photochemical applications, DABCO is commonly added to reaction mixtures sensitized by or to suppress unwanted photooxidation of substrates, thereby enhancing reaction selectivity and yield. For instance, in -catalyzed cross-dehydrogenative couplings, inclusion of DABCO significantly reduces side products from ¹O₂-mediated oxidation, confirming its role in deactivating the reactive species. Similarly, DABCO protects organic dyes and biomolecules from photooxidative damage; it improves the photostability of sensitizers in optical sensing materials by quenching ¹O₂ before it can react with vulnerable chromophores or amino acid residues like and . Compared to natural quenchers like , which exhibits a much higher quenching rate constant of approximately 10^{10} M⁻¹ s⁻¹, DABCO is less potent on a per-molecule basis but offers advantages in , non-volatility, and compatibility with aqueous or polar media for synthetic and analytical uses. Experimental determination of the quenching rate typically involves time-resolved , monitoring the decay lifetime (τ) of ¹O₂ emission at 1270 nm in the presence of varying DABCO concentrations, where 1/τ = 1/τ_0 + k_q [DABCO], with τ_0 being the lifetime in the absence of quencher.

Applications

In organic synthesis

DABCO serves as a versatile organocatalyst in the Morita–Baylis–Hillman (MBH) reaction, enabling the synthesis of densely functionalized allylic alcohols from aldehydes and activated alkenes such as acrylates. Typical conditions involve 5–20 mol% DABCO at , often in polar solvents, affording yields of 70–95% for a range of substrates including aromatic and aliphatic aldehydes. This nucleophilic facilitates carbon-carbon bond formation without metal additives, making it valuable for constructing complex scaffolds in synthesis. In the preparation of derivatives, DABCO promotes C–N bond cleavage and cyclization reactions, yielding biologically active compounds relevant to pharmaceuticals. For instance, DABCO-mediated reactions of N-substituted precursors under mild heating (50–80°C) generate substituted in 60–90% yields, with applications in synthesizing antiviral and anticancer agents. These transformations leverage DABCO's bicyclic structure for selective activation, avoiding harsh reagents and enabling scalable routes to [piperazine-based drug](/page/Piperazine /page/Drug) intermediates. DABCO also plays a key role in multi-component reactions, such as one-pot aza-Henry and Knoevenagel–Michael sequences, streamlining the assembly of heterocycles and β-nitro carbonyls. In the aza-Henry reaction, 10–20 mol% DABCO catalyzes nitroalkane additions to imines at ambient conditions, yielding 80–95% of nitroamines, often integrated into tandem processes for derivatives. Similarly, Knoevenagel–Michael cascades with 1,3-dicarbonyls and aldehydes proceed efficiently (yields >85%) under DABCO promotion, forming bis-enols or chromenes in aqueous media. From a perspective, DABCO-derived ionic liquids enhance by acting as recyclable catalysts, minimizing waste in transformations. These solvents, such as [C4dabco][BF4], can be recovered up to six cycles with <5% activity loss in additions, reducing solvent use by over 90% compared to traditional methods. This recyclability supports eco-friendly protocols for large-scale synthesis, aligning with principles of and reduced environmental impact. A notable industrial application involves DABCO-catalyzed steps in the production of precursors, a broad-spectrum . Using 1 mol% DABCO in solvents at 40–100 °C (typically 60–85 °C), the process achieves high-purity intermediates in 85–95% yields, enabling efficient manufacturing without metal contaminants.

In polymer chemistry

DABCO, or 1,4-diazabicyclo[2.2.2]octane, was first adopted in the as a catalyst for rigid foams, marking a significant advancement in the commercialization of materials during that era. Its introduction facilitated efficient foam production by accelerating key reactions, laying the foundation for widespread use of tertiary amine catalysts in the industry. In polyurethane foam manufacturing, DABCO serves as a dual catalyst, promoting both the gelling —where isocyanates react with polyols to form urethane linkages—and the blowing , in which isocyanates react with to produce amines and gas for foam . The blowing proceeds as RNCO + H₂O → RNH₂ + CO₂, with DABCO enhancing the rate through its strong nucleophilic properties. Typical loadings range from 0.1 to 0.5 parts per hundred (phr) in formulations containing polyols and isocyanates, allowing precise control over gel and blow times to achieve balanced foam rise and curing. This balance is critical for preventing issues like foam collapse or uneven . DABCO also functions as a co-catalyst in resin curing, often paired with primary or secondary amines to accelerate the and improve cure rates. In foams, its catalytic action influences final material properties, such as cell structure and ; for instance, optimized DABCO use contributes to uniform open-cell morphologies in flexible foams with densities of 20–40 kg/m³.

Other uses

DABCO, also known as triethylenediamine (TEDA), is impregnated into as part of ASZM-TEDA formulations to enhance its protective capabilities in respiratory equipment against agents. This impregnation facilitates the and neutralization of toxic gases, including nerve agents, through base-catalyzed in synergy with metal impregnants like and silver, promoting the decomposition of organophosphorus compounds like or . Such treated carbons are standard in military-grade filters for broad-spectrum defense. Beyond applications, DABCO serves as an effective quencher in photostable formulations for fluorescent dyes, improving the longevity of agents in and systems by preventing oxidative . DABCO is also used in baths as a brightener and stabilizer, enhancing the quality of metal deposits in processes such as silver or . Additionally, DABCO acts as a radiation-protective agent in biological contexts, protecting purified transforming DNA from inactivation by near-ultraviolet light through quenching of singlet oxygen. In emerging materials science, DABCO functions as a structure-directing agent in the solvothermal synthesis of metal-organic frameworks (MOFs), where it acts as a ditopic pillar ligand to assemble three-dimensional porous structures with metals like zinc, nickel, or copper and dicarboxylate linkers such as 1,4-benzenedicarboxylate (BDC). For instance, in the synthesis of [Zn₂(BDC)₂(DABCO)], DABCO bridges adjacent layers to form a robust framework with high surface area, suitable for gas storage and catalysis. Similar roles are observed in [Ni₂(BDC)₂(DABCO)] and related polymorphs, where solvothermal conditions (typically 100–150°C in DMF or ethanol) enable precise control over pore size and topology. These DABCO-pillared MOFs exhibit tunable flexibility and enhanced CO₂ adsorption compared to non-pillared analogs.