Lanthanide triflates
Encyclopedia
Lanthanide triflates are triflate salts of the lanthanide
family with many uses in organic chemistry
as Lewis acid
catalysts. The catalysts act similarly to aluminium chloride
or ferric chloride, but are stable in water, which makes it possible to use water as a solvent instead of organic solvents.
metal ion and three triflate ions. The lanthanides, or rare earth metals, are the elements from Lanthanum
to Lutetium in the periodic table
. Triflate is a contraction of trifluoromethanesulfonate; its molecular formula is CF3SO3, and is commonly designated ‘OTf’. Triflic acid is a ‘superacid
’ so its conjugate base ions are very stable. The metal triflate complex is strongly electrophilic, thus acts as a strong Lewis acid
.
Common Lewis acids include aluminium chloride
, ferric chloride and boron trifluoride
. These reactions are usually carried out in organic solvents; AlCl3, for example, reacts violently with water. Typical solvents are dichloromethane
and benzene
.
acylations and alkylations, which are one of few ways to add C-C bonds to aromatics. The synthesized products are used in many products including pharmaceuticals and agrochemicals.
These reactions are usually carried out with AlCl3 as the catalyst, in an organic solvent. In the acylation reaction, AlCl3 complexes with the product. It must be added in large excess and is destroyed during product recovery, so atom efficiency is poor. The reaction is quenched with water, creating large volumes of corrosive aluminous, acidic waste- 3 mol HCl per mol AlCl3. In one example, Clark et al. estimate 0.9 kg of AlCl3 is wasted per kilogram of dimethyl acetophenone produced. Product separation can also be difficult.
Lanthanide triflates can dramatically cut the impact of these syntheses. They are able to achieve high conversion using small quantities. These catalysts are stable in water, so avoid the need for organic solvents; some reaction rates are even enhanced by aqueous systems. They don’t complex with products, so separation is simple, and the catalyst is easily recovered- in many cases the solution is simply reused.
La(OTf)3 catalysts can also reduce the number of processing steps and use greener reagents; Walker et al. reported successful acylation
yields using carboxylic acid
directly, rather than acyl chloride. Their process generates only a small volume of aqueous sodium bicarbonate
waste. Similar results have been cited for the direct acetylation of alcohol
s.
forming reactions, such as Diels-Alder, aldol
, and allyl
ation reactions. Some reactions require a mixed solvent, such as aqueous formaldehyde
, although Kobayashi et al. have developed alternative surfactant-water systems.
Michael additions are another very important industrial method for creating new carbon-carbon bonds, often with particular functional groups attached. Addition reactions are inherently atom efficient, so are preferred synthesis pathways. La(OTf)3 catalysts not only enable these reactions to be carried out in water, but can also achieve asymmetric catalysis, yielding a desired enantio-specific or diastereo-specific product.
. Pyridine
compounds are common in biology
and have many applications. Normally, pyridine is synthesized from acetaldehyde
, formaldehyde
and ammonia
under high temperatures and pressures. Lanthanide triflates can be used to synthesize pyridine by catalysing either the condensation of aldehydes and amines, or the aza Diels-Alder reaction
catalytic synthesis. Again, water can be used as a solvent, and high yields can be achieved under mild conditions.
Nitro compounds are common in pharmaceuticals, explosives, dye
s, and plastics. As for carbon compounds, catalysed Michael additions and aldol reaction
s can be used. For aromatic nitro compounds, synthesis is via a substitution reaction
. The standard synthesis is carried out in a solution of nitric acid
, mixed with excess sulfuric acid
to create nitronium ions. These are then substituted on to the aromatic species. Often, the para-isomer is the desired product, but standard systems have poor selectivity. As for acylation, the reaction is normally quenched with water, and creates copious acidic waste. Using a La(OTf)3 catalyst in place of sulfuric acid reduces this waste considerably. Clark et al. report 90% conversion using just 1 mol% of ytterbium triflate in weak nitric acid, generating only a small volume of acidic waste.
La(OTf)3 catalysts have also been used for cyanations, and three-component reactions of aldehydes, amines & nucleophiles.
Generally, the benefits of these catalysts include:
catalysts. Unlike most conventional catalysts, these compounds are stable in water, so avoid the need for organic solvents, and can be recovered for reuse. Since leading researcher Kobayashi’s 1991 paper on their catalytic effect in water, the range of researched applications for La(OTf)3 catalysts has exploded. The commercialisation of these techniques has the potential to significantly reduce the environmental impact of the chemical industries.
One vendor MSDS lists safety considerations including dermal/eye/respiratory/GI burns on contact. It also lists possible hazardous decomposition products including CO, CO2, HF and SOx. The compounds are hygroscopic, so care is required for storage and handling. However, these considerations also apply to the more common catalysts.
These possible disadvantages are difficult to quantify, as essentially all public domain publications on their use are by research chemists, and do not include Life Cycle Analysis or budgetary considerations. Future work in these areas would greatly encourage their uptake by industry.
synthesis. It has also been trialled in green solvents other than water, such as ionic liquid
s and supercritical carbon dioxide
. To enhance recovery, researchers have developed La(OTf)3 catalysts stabilised by ion exchange resin
or polymer backbones, which can be separated by ultrafiltration
. Solvent-free systems are also possible with solid-supported catalysts.
Lanthanide
The lanthanide or lanthanoid series comprises the fifteen metallic chemical elements with atomic numbers 57 through 71, from lanthanum through lutetium...
family with many uses in organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
as Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
catalysts. The catalysts act similarly to aluminium chloride
Aluminium chloride
Aluminium chloride is the main compound of aluminium and chlorine. It is white, but samples are often contaminated with iron trichloride, giving it a yellow colour. The solid has a low melting and boiling point. It is mainly produced and consumed in the production of aluminium metal, but large...
or ferric chloride, but are stable in water, which makes it possible to use water as a solvent instead of organic solvents.
Molecular structure
Lanthanide triflates consist of a lanthanideLanthanide
The lanthanide or lanthanoid series comprises the fifteen metallic chemical elements with atomic numbers 57 through 71, from lanthanum through lutetium...
metal ion and three triflate ions. The lanthanides, or rare earth metals, are the elements from Lanthanum
Lanthanum
Lanthanum is a chemical element with the symbol La and atomic number 57.Lanthanum is a silvery white metallic element that belongs to group 3 of the periodic table and is the first element of the lanthanide series. It is found in some rare-earth minerals, usually in combination with cerium and...
to Lutetium in the periodic table
Periodic table
The periodic table of the chemical elements is a tabular display of the 118 known chemical elements organized by selected properties of their atomic structures. Elements are presented by increasing atomic number, the number of protons in an atom's atomic nucleus...
. Triflate is a contraction of trifluoromethanesulfonate; its molecular formula is CF3SO3, and is commonly designated ‘OTf’. Triflic acid is a ‘superacid
Superacid
According to the classical definition superacid is an acid with an acidity greater than that of 100% pure sulfuric acid, which has a Hammett acidity function of −12. According to the modern definition, superacid is a medium, in which the chemical potential of the proton is higher than in pure...
’ so its conjugate base ions are very stable. The metal triflate complex is strongly electrophilic, thus acts as a strong Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
.
Lewis acid catalysis
Lewis acids are used to catalyse a wide variety of reactions. The mechanism steps are:- Lewis acid forms a polar coordinate with a basic site on the reactant (such as an O or N)
- Its electrons are drawn towards the catalyst, thus activating the reactant
- The reactant is then able to be transformed by a substitution reactionSubstitution reactionIn a substitution reaction, a functional group in a particular chemical compound is replaced by another group. In organic chemistry, the electrophilic and nucleophilic substitution reactions are of prime importance...
or addition reactionAddition reactionAn addition reaction, in organic chemistry, is in its simplest terms an organic reaction where two or more molecules combine to form a larger one.... - The product dissociates and catalyst is regenerated
Common Lewis acids include aluminium chloride
Aluminium chloride
Aluminium chloride is the main compound of aluminium and chlorine. It is white, but samples are often contaminated with iron trichloride, giving it a yellow colour. The solid has a low melting and boiling point. It is mainly produced and consumed in the production of aluminium metal, but large...
, ferric chloride and boron trifluoride
Boron trifluoride
Boron trifluoride is the chemical compound with the formula BF3. This pungent colourless toxic gas forms white fumes in moist air. It is a useful Lewis acid and a versatile building block for other boron compounds.-Structure and bonding:...
. These reactions are usually carried out in organic solvents; AlCl3, for example, reacts violently with water. Typical solvents are dichloromethane
Dichloromethane
Dichloromethane is an organic compound with the formula CH2Cl2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. Although it is not miscible with water, it is miscible with many organic solvents...
and benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
.
Friedel-Crafts Reactions
Lanthanide triflates can replace conventional Lewis acids in various types of reactions. One important class is Friedel-CraftsFriedel-Crafts reaction
The Friedel–Crafts reactions are a set of reactions developed by Charles Friedel and James Crafts in 1877. There are two main types of Friedel–Crafts reactions: alkylation reactions and acylation reactions. This reaction type is a form of electrophilic aromatic substitution...
acylations and alkylations, which are one of few ways to add C-C bonds to aromatics. The synthesized products are used in many products including pharmaceuticals and agrochemicals.
These reactions are usually carried out with AlCl3 as the catalyst, in an organic solvent. In the acylation reaction, AlCl3 complexes with the product. It must be added in large excess and is destroyed during product recovery, so atom efficiency is poor. The reaction is quenched with water, creating large volumes of corrosive aluminous, acidic waste- 3 mol HCl per mol AlCl3. In one example, Clark et al. estimate 0.9 kg of AlCl3 is wasted per kilogram of dimethyl acetophenone produced. Product separation can also be difficult.
Lanthanide triflates can dramatically cut the impact of these syntheses. They are able to achieve high conversion using small quantities. These catalysts are stable in water, so avoid the need for organic solvents; some reaction rates are even enhanced by aqueous systems. They don’t complex with products, so separation is simple, and the catalyst is easily recovered- in many cases the solution is simply reused.
La(OTf)3 catalysts can also reduce the number of processing steps and use greener reagents; Walker et al. reported successful acylation
Acylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....
yields using carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
directly, rather than acyl chloride. Their process generates only a small volume of aqueous sodium bicarbonate
Sodium bicarbonate
Sodium bicarbonate or sodium hydrogen carbonate is the chemical compound with the formula Na HCO3. Sodium bicarbonate is a white solid that is crystalline but often appears as a fine powder. It has a slightly salty, alkaline taste resembling that of washing soda . The natural mineral form is...
waste. Similar results have been cited for the direct acetylation of alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s.
Other C-C bond-forming reactions
La(OTf)3 catalysts have been used for many other carbon-carbon bondCarbon-carbon bond
A carbon–carbon bond is a covalent bond between two carbon atoms. The most common form is the single bond: a bond composed of two electrons, one from each of the two atoms. The carbon–carbon single bond is a sigma bond and is said to be formed between one hybridized orbital from each...
forming reactions, such as Diels-Alder, aldol
Aldol
An aldol or aldol adduct is a beta-hydroxy ketone or aldehyde, and is the product of aldol addition ....
, and allyl
Allyl
An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl...
ation reactions. Some reactions require a mixed solvent, such as aqueous formaldehyde
Formaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...
, although Kobayashi et al. have developed alternative surfactant-water systems.
Michael additions are another very important industrial method for creating new carbon-carbon bonds, often with particular functional groups attached. Addition reactions are inherently atom efficient, so are preferred synthesis pathways. La(OTf)3 catalysts not only enable these reactions to be carried out in water, but can also achieve asymmetric catalysis, yielding a desired enantio-specific or diastereo-specific product.
C-N bond-forming reactions
Lewis acids are also used to catalyse many C-N bond-forming reactionsCarbon-nitrogen bond
A carbon–nitrogen bond is a covalent bond between carbon and nitrogen and is one of the most abundant bonds in organic chemistry and biochemistry....
. Pyridine
Pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
compounds are common in biology
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...
and have many applications. Normally, pyridine is synthesized from acetaldehyde
Acetaldehyde
Acetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part...
, formaldehyde
Formaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...
and ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
under high temperatures and pressures. Lanthanide triflates can be used to synthesize pyridine by catalysing either the condensation of aldehydes and amines, or the aza Diels-Alder reaction
Aza Diels-Alder reaction
The Aza Diels-Alder reaction converts imines and dienes to tetrahydropyridines. This organic reaction is a modification of the Diels-Alder reaction. The nitrogen atom can be part of the diene or the dienophile....
catalytic synthesis. Again, water can be used as a solvent, and high yields can be achieved under mild conditions.
Nitro compounds are common in pharmaceuticals, explosives, dye
Dye
A dye is a colored substance that has an affinity to the substrate to which it is being applied. The dye is generally applied in an aqueous solution, and requires a mordant to improve the fastness of the dye on the fiber....
s, and plastics. As for carbon compounds, catalysed Michael additions and aldol reaction
Aldol reaction
The aldol reaction is a powerful means of forming carbon–carbon bonds in organic chemistry.Discovered independently by Charles-Adolphe Wurtz and Alexander Porfyrevich Borodin in 1872, the reaction combines two carbonyl compounds to form a new β-hydroxy carbonyl compound...
s can be used. For aromatic nitro compounds, synthesis is via a substitution reaction
Substitution reaction
In a substitution reaction, a functional group in a particular chemical compound is replaced by another group. In organic chemistry, the electrophilic and nucleophilic substitution reactions are of prime importance...
. The standard synthesis is carried out in a solution of nitric acid
Nitric acid
Nitric acid , also known as aqua fortis and spirit of nitre, is a highly corrosive and toxic strong acid.Colorless when pure, older samples tend to acquire a yellow cast due to the accumulation of oxides of nitrogen. If the solution contains more than 86% nitric acid, it is referred to as fuming...
, mixed with excess sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
to create nitronium ions. These are then substituted on to the aromatic species. Often, the para-isomer is the desired product, but standard systems have poor selectivity. As for acylation, the reaction is normally quenched with water, and creates copious acidic waste. Using a La(OTf)3 catalyst in place of sulfuric acid reduces this waste considerably. Clark et al. report 90% conversion using just 1 mol% of ytterbium triflate in weak nitric acid, generating only a small volume of acidic waste.
La(OTf)3 catalysts have also been used for cyanations, and three-component reactions of aldehydes, amines & nucleophiles.
Advantages
The substitution of organic solvents by water reduces the amount of waste and the metals are recoverable and hence reusable.Generally, the benefits of these catalysts include:
- Selective, often producing fewer by-products than standard methods
- Asymmetric catalysts: chiral forms can be highly diastereo- and enantio-selective
- Some reactions can use greener non-chlorinated reagents, and reduce the number of synthesis steps
- Less toxic and not corrosive, so safer and easier to handle
- Mild reaction conditions are safer and reduce energy consumption.
Green catalysts
Lanthanide triflates are one of the most promising green chemistryGreen chemistry
Green chemistry, also called sustainable chemistry, is a philosophy of chemical research and engineering that encourages the design of products and processes that minimize the use and generation of hazardous substances...
catalysts. Unlike most conventional catalysts, these compounds are stable in water, so avoid the need for organic solvents, and can be recovered for reuse. Since leading researcher Kobayashi’s 1991 paper on their catalytic effect in water, the range of researched applications for La(OTf)3 catalysts has exploded. The commercialisation of these techniques has the potential to significantly reduce the environmental impact of the chemical industries.
Disadvantages
The main disadvantages of these new catalysts compared with conventional ones are less industrial experience, reduced availability and increased purchase cost. As they contain rare metals and sulfonate ions, the production of these catalysts may itself be a polluting or hazardous process. For example, metal extraction usually requires large quantities of sulfuric acid. Since the catalyst is recoverable, these disadvantages would be less over time, and the cost savings from reduced waste treatment and better product separation may be substantially greater.One vendor MSDS lists safety considerations including dermal/eye/respiratory/GI burns on contact. It also lists possible hazardous decomposition products including CO, CO2, HF and SOx. The compounds are hygroscopic, so care is required for storage and handling. However, these considerations also apply to the more common catalysts.
These possible disadvantages are difficult to quantify, as essentially all public domain publications on their use are by research chemists, and do not include Life Cycle Analysis or budgetary considerations. Future work in these areas would greatly encourage their uptake by industry.
Recent developments
Researchers are continually finding new applications where it can replace other less efficient, more toxic Lewis acids. Recently it has been tested in curing epoxies and other polymerisation reactions, and in polysaccharidePolysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
synthesis. It has also been trialled in green solvents other than water, such as ionic liquid
Ionic liquid
An ionic liquid is a salt in the liquid state. In some contexts, the term has been restricted to salts whose melting point is below some arbitrary temperature, such as . While ordinary liquids such as water and gasoline are predominantly made of electrically neutral molecules, ILs are largely made...
s and supercritical carbon dioxide
Supercritical carbon dioxide
Supercritical carbon dioxide is a fluid state of carbon dioxide where it is held at or above its critical temperature and critical pressure.Carbon dioxide usually behaves as a gas in air at STP or as a solid called dry ice when frozen...
. To enhance recovery, researchers have developed La(OTf)3 catalysts stabilised by ion exchange resin
Ion exchange resin
An ion-exchange resin or ion-exchange polymer is an insoluble matrix normally in the form of small beads, usually white or yellowish, fabricated from an organic polymer substrate. The material has highly developed structure of pores on the surface of which are sites with easily trapped and...
or polymer backbones, which can be separated by ultrafiltration
Ultrafiltration
Ultrafiltration is a variety of membrane filtration in which hydrostatic pressure forces a liquid against a semipermeable membrane. Suspended solids and solutes of high molecular weight are retained, while water and low molecular weight solutes pass through the membrane...
. Solvent-free systems are also possible with solid-supported catalysts.