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Close-up of the delocalized bonds between butyl and lithium | |||
Names | |||
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IUPAC name butyllithium, tetra-μ3-butyl-tetralithium | |||
Other names NBL, BuLi, 1-lithiobutane | |||
Identifiers | |||
3D model (JSmol) | |||
ChEBI | |||
ChemSpider | |||
ECHA InfoCard | 100.003.363 | ||
PubChem CID | |||
UNII | |||
CompTox Dashboard (EPA) | |||
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Properties | |||
C4H9Li | |||
Molar mass | 64.06 g·mol−1 | ||
Appearance | colorless liquid unstable usually obtained as solution | ||
Density | 0.68 g/cm3, solvent defined | ||
Melting point | −76 °C (−105 °F; 197 K) (<273 K) | ||
Boiling point | 80 C | ||
Exothermic decomposition | |||
Solubility | Ethers such as THF, hydrocarbons | ||
Acidity (pKa) | 50 (of the conjugate acid) [1] | ||
Structure | |||
tetrameric in solution | |||
0 D | |||
Hazards | |||
Occupational safety and health (OHS/OSH): | |||
Main hazards | Pyrophoric (spontaneously combusts in air), decomposes to corrosive LiOH | ||
NFPA 704 (fire diamond) | |||
Related compounds | |||
Related organolithium reagents | sec-butyllithium tert-butyllithium hexyllithium methyllithium | ||
Related compounds | lithium hydroxide | ||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
n-Butyllithium C4H9Li (abbreviated n-BuLi) is an organolithium reagent. It is widely used as a polymerization initiator in the production of elastomers such as polybutadiene or styrene-butadiene-styrene (SBS). Also, it is broadly employed as a strong base (superbase) in the synthesis of organic compounds as in the pharmaceutical industry.
Butyllithium is commercially available as solutions (15%, 25%, 1.5 M, 2 M, 2.5 M, 10 M, etc.) in alkanes such as pentane, hexanes, and heptanes. Solutions in diethyl ether and THF can be prepared, but are not stable enough for storage. Annual worldwide production and consumption of butyllithium and other organolithium compounds is estimated at 2000 to 3000 tonnes. [2]
Although butyllithium is colorless, n-butyllithium is usually encountered as a pale yellow solution in alkanes. Such solutions are stable indefinitely if properly stored, [3] but in practice, they degrade upon aging. Fine white precipitate (lithium hydride) is deposited and the color changes to orange. [3] [4]
n-BuLi exists as a cluster both in the solid state and in a solution. The tendency to aggregate is common for organolithium compounds. The aggregates are held together by delocalized covalent bonds between lithium and the terminal carbon of the butyl chain. [5] In the case of n-BuLi, the clusters are tetrameric (in ether) or hexameric (in cyclohexane). The cluster is a distorted cubane-type cluster with Li and CH2R groups at alternating vertices. An equivalent description describes the tetramer as a Li4 tetrahedron interpenetrated with a tetrahedron [CH2R]4. Bonding within the cluster is related to that used to describe diborane, but more complex since eight atoms are involved. Reflecting its electron-rich character, n-butyllithium is highly reactive toward Lewis acids.
Due to the large difference between the electronegativities of carbon (2.55) and lithium (0.98), the C−Li bond is highly polarized. The charge separation has been estimated to be 55–95%. For practical purposes, n-BuLi can often be considered to react as the butyl anion, n-Bu−, and a lithium cation, Li+.
The standard preparation for n-BuLi is reaction of 1-bromobutane or 1-chlorobutane with Li metal: [3]
If the lithium used for this reaction contains 1–3% sodium, the reaction proceeds more quickly than if pure lithium is used. Solvents used for this preparation include benzene, cyclohexane, and diethyl ether. When BuBr is the precursor, the product is a homogeneous solution, consisting of a mixed cluster containing both LiBr and BuLi, together with a small amount of octane. BuLi forms a weaker complex with LiCl, so that the reaction of BuCl with Li produces a precipitate of LiCl.
Solutions of butyllithium, which are susceptible to degradation by air, are standardized by titration. A popular weak acid is biphenyl-4-methanol, which gives a deeply colored dilithio derivative at the end point. [6]
Butyllithium is principally valued as an initiator for the anionic polymerization of dienes, such as butadiene. [7] The reaction is called "carbolithiation":
Isoprene can be polymerized stereospecifically in this way. Also of commercial importance is the use of butyllithium for the production of styrene-butadiene polymers. Even ethylene will insert into BuLi. [8]
Butyllithium is a strong base (pKb ≈ -36), but it is also a powerful nucleophile and reductant, depending on the other reactants. Furthermore, in addition to being a strong nucleophile, n-BuLi binds to aprotic Lewis bases, such as ethers and tertiary amines, which partially disaggregate the clusters by binding to the lithium centers. Its use as a strong base is referred to as metalation. Reactions are typically conducted in tetrahydrofuran and diethyl ether, which are good solvents for the resulting organolithium derivatives (see below).
One of the most useful chemical properties of n-BuLi is its ability to deprotonate a wide range of weak Brønsted acids. t-Butyllithium and s-butyllithium are more basic. n-BuLi can deprotonate (that is, metalate) many types of C−H bonds, especially where the conjugate base is stabilized by electron delocalization or one or more heteroatoms (non-carbon atoms). Examples include acetylenes (H−CC−R), methyl sulfides (H−CH2SR), thioacetals (H−CH(SR)2, e.g. dithiane), methylphosphines (H−CH2PR2), furans, thiophenes and ferrocene (Fe(H−C5H4)(C5H5)). [9] In addition to these, it will also deprotonate all more acidic compounds such as alcohols, amines, enolizable carbonyl compounds, and any overtly acidic compounds, to produce alkoxides, amides, enolates and other salts of lithium, respectively. The stability and volatility of the butane resulting from such deprotonation reactions is convenient, but can also be a problem for large-scale reactions because of the volume of a flammable gas produced.
The kinetic basicity of n-BuLi is affected by the solvent or cosolvent. Ligands that complex Li+ such as tetrahydrofuran (THF), tetramethylethylenediamine (TMEDA), hexamethylphosphoramide (HMPA), and 1,4-diazabicyclo[2.2.2]octane (DABCO) further polarize the Li−C bond and accelerate the metalation. Such additives can also aid in the isolation of the lithiated product, a famous example of which is dilithioferrocene.
Schlosser's base is a superbase produced by treating butyllithium with potassium t-butoxide. It is kinetically more reactive than butyllithium and is often used to accomplish difficult metalations. While some n-butylpotassium is present and is a stronger base than n-BuLi, the reactivity of the mixture is not exactly the same as isolated n-butylpotassium. [10]
An example of the use of n-butyllithium as a base is the addition of an amine to methyl carbonate to form a methyl carbamate, where n-butyllithium serves to deprotonate the amine:
Butyllithium reacts with some organic bromides and iodides in an exchange reaction to form the corresponding organolithium derivative. The reaction usually fails with organic chlorides and fluorides:
This lithium–halogen exchange reaction is useful for preparation of several types of RLi compounds, particularly aryl lithium and some vinyl lithium reagents. The utility of this method is significantly limited, however, by the presence in the reaction mixture of n-BuBr or n-BuI, which can react with the RLi reagent formed, and by competing dehydrohalogenation reactions, in which n-BuLi serves as a base:
These side reaction are significantly less important for RI than for RBr, since the iodine–lithium exchange is several orders of magnitude faster than the bromine–lithium exchange. For these reasons, aryl, vinyl and primary alkyl iodides are the preferred substrates, and t-BuLi rather than n-BuLi is usually used, since the formed t-BuI is immediately destroyed by the t-BuLi in a dehydrohalogenation reaction (thus requiring two equivalents of t-BuLi). Alternatively, vinyl lithium reagents can be generated by direct reaction of the vinyl halide (e.g. cyclohexenyl chloride) with lithium or by tin–lithium exchange (see next section). [3]
A related family of reactions are the transmetalations, wherein two organometallic compounds exchange their metals. Many examples of such reactions involve lithium exchange with tin:
The tin–lithium exchange reactions have one major advantage over the halogen–lithium exchanges for the preparation of organolithium reagents, in that the product tin compounds (C4H9SnMe3 in the example above) are much less reactive towards lithium reagents than are the halide products of the corresponding halogen–lithium exchanges (C4H9Br or C4H9Cl). Other metals and metalloids which undergo such exchange reactions are organic compounds of mercury, selenium, and tellurium.
Organolithium reagents, including n-BuLi are used in synthesis of specific aldehydes and ketones. One such synthetic pathway is the reaction of an organolithium reagent with disubstituted amides:
THF is deprotonated by butyllithium, especially in the presence of TMEDA, by loss of one of four protons adjacent to oxygen. This process, which consumes butyllithium to generate butane, induces a ring opening to give enolate of acetaldehyde and ethylene. [11] Therefore, reactions of BuLi in THF are typically conducted at low temperatures, such as –78 °C, as is conveniently produced by a freezing bath of dry ice and acetone. Higher temperatures (−25 °C or even −15 °C) are also used.
When heated, n-BuLi, analogously to other alkyllithium reagents with "β-hydrogens", undergoes β-hydride elimination to produce 1-butene and lithium hydride (LiH):
Alkyl-lithium compounds are stored under inert gas to prevent loss of activity and for reasons of safety. n-BuLi reacts violently with water:
This is an exergonic and highly exothermic reaction. If oxygen is present the butane produced may ignite.
BuLi also reacts with CO2 to give lithium pentanoate:
In organometallic chemistry, organolithium reagents are chemical compounds that contain carbon–lithium (C–Li) bonds. These reagents are important in organic synthesis, and are frequently used to transfer the organic group or the lithium atom to the substrates in synthetic steps, through nucleophilic addition or simple deprotonation. Organolithium reagents are used in industry as an initiator for anionic polymerization, which leads to the production of various elastomers. They have also been applied in asymmetric synthesis in the pharmaceutical industry. Due to the large difference in electronegativity between the carbon atom and the lithium atom, the C−Li bond is highly ionic. Owing to the polar nature of the C−Li bond, organolithium reagents are good nucleophiles and strong bases. For laboratory organic synthesis, many organolithium reagents are commercially available in solution form. These reagents are highly reactive, and are sometimes pyrophoric.
In organometallic chemistry, acetylide refers to chemical compounds with the chemical formulas MC≡CH and MC≡CM, where M is a metal. The term is used loosely and can refer to substituted acetylides having the general structure RC≡CM. Acetylides are reagents in organic synthesis. The calcium acetylide commonly called calcium carbide is a major compound of commerce.
Lithium diisopropylamide is a chemical compound with the molecular formula LiN(CH 2)2. It is used as a strong base and has been widely utilized due to its good solubility in non-polar organic solvents and non-nucleophilic nature. It is a colorless solid, but is usually generated and observed only in solution. It was first prepared by Hamell and Levine in 1950 along with several other hindered lithium diorganylamides to effect the deprotonation of esters at the α position without attack of the carbonyl group.
1-Bromobutane is the organobromine compound with the formula CH3(CH2)3Br. It is a colorless liquid, although impure samples appear yellowish. It is insoluble in water, but soluble in organic solvents. It is primarily used as a source of the butyl group in organic synthesis. It is one of several isomers of butyl bromide.
Phenyllithium is an organometallic agent with the empirical formula C6H5Li. It is most commonly used as a metalating agent in organic syntheses and a substitute for Grignard reagents for introducing phenyl groups in organic syntheses. Crystalline phenyllithium is colorless; however, solutions of phenyllithium are various shades of brown or red depending on the solvent used and the impurities present in the solute.
tert-Butyllithium is a chemical compound with the formula (CH3)3CLi. As an organolithium compound, it has applications in organic synthesis since it is a strong base, capable of deprotonating many carbon molecules, including benzene. tert-Butyllithium is available commercially as hydrocarbon solutions; it is not usually prepared in the laboratory.
Grignard reagents or Grignard compounds are chemical compounds with the general formula R−Mg−X, where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride Cl−Mg−CH3 and phenylmagnesium bromide (C6H5)−Mg−Br. They are a subclass of the organomagnesium compounds.
Methyllithium is the simplest organolithium reagent, with the empirical formula CH3Li. This s-block organometallic compound adopts an oligomeric structure both in solution and in the solid state. This highly reactive compound, invariably used in solution with an ether as the solvent, is a reagent in organic synthesis as well as organometallic chemistry. Operations involving methyllithium require anhydrous conditions, because the compound is highly reactive toward water. Oxygen and carbon dioxide are also incompatible with MeLi. Methyllithium is usually not prepared, but purchased as a solution in various ethers.
sec-Butyllithium is an organometallic compound with the formula CH3CHLiCH2CH3, abbreviated sec-BuLi or s-BuLi. This chiral organolithium reagent is used as a source of sec-butyl carbanion in organic synthesis.
Lithium bis(trimethylsilyl)amide is a lithiated organosilicon compound with the formula LiN(Si(CH3)3)2. It is commonly abbreviated as LiHMDS or Li(HMDS) (lithium hexamethyldisilazide - a reference to its conjugate acid HMDS) and is primarily used as a strong non-nucleophilic base and as a ligand. Like many lithium reagents, it has a tendency to aggregate and will form a cyclic trimer in the absence of coordinating species.
PMDTA (N,N,N′,N′′,N′′-pentamethyldiethylenetriamine) is an organic compound with the formula [(CH3)2NCH2CH2]2NCH3. PMDTA is a basic, bulky, and flexible, tridentate ligand that is a used in organolithium chemistry. It is a colorless liquid, although impure samples appear yellowish.
Organomanganese chemistry is the chemistry of organometallic compounds containing a carbon to manganese chemical bond. In a 2009 review, Cahiez et al. argued that as manganese is cheap and benign, organomanganese compounds have potential as chemical reagents, although currently they are not widely used as such despite extensive research.
Organosodium chemistry is the chemistry of organometallic compounds containing a carbon to sodium chemical bond. The application of organosodium compounds in chemistry is limited in part due to competition from organolithium compounds, which are commercially available and exhibit more convenient reactivity.
Organocerium chemistry is the science of organometallic compounds that contain one or more chemical bond between carbon and cerium. These compounds comprise a subset of the organolanthanides. Most organocerium compounds feature Ce(III) but some Ce(IV) derivatives are known.
Vinyllithium is an organolithium compound with the formula LiC2H3. A colorless or white solid, it is encountered mainly as a solution in tetrahydrofuran (THF). It is a reagent in synthesis of organic compounds, especially for vinylations.
ortho-Carborane is the organoboron compound with the formula C2B10H12. The prefix ortho is derived from ortho. It is the most prominent carborane. This derivative has been considered for a wide range of applications from heat-resistant polymers to medical applications. It is a colorless solid that melts, without decomposition, at 320 °C.
Lithium cyclopentadienide is an organolithium compound with the formula C5H5Li. The compound is often abbreviated as LiCp, where Cp− is the cyclopentadienide anion. Lithium cyclopentadienide is a colorless solid, although samples often are pink owing to traces of oxidized impurities.
In organometallic chemistry, metal–halogen exchange is a fundamental reaction that converts an organic halide into an organometallic product. The reaction commonly involves the use of electropositive metals and organochlorides, bromides, and iodides. Particularly well-developed is the use of metal–halogen exchange for the preparation of organolithium compounds.
In organic chemistry, Wittig reagents are organophosphorus compounds of the formula R3P=CHR', where R is usually phenyl. They are used to convert ketones and aldehydes to alkenes:
(Trimethylsilyl)methyllithium is classified both as an organolithium compound and an organosilicon compound. It has the empirical formula LiCH2Si(CH3)3, often abbreviated LiCH2tms. It crystallizes as the hexagonal prismatic hexamer [LiCH2tms]6, akin to some polymorphs of methyllithium. Many adducts have been characterized including the diethyl ether complexed cubane [Li4(μ3-CH2tms)4(Et2O)2] and [Li2(μ-CH2tms)2(tmeda)2].