n-Butyllithium

n-Butyllithium
n-Butyllithium hexamer
IUPAC name butyllithium, tetra-μ3-butyl-tetralithium
Other names NBL, BuLi, 1-lithiobutane
Identifiers
CAS number	109-72-8 Y
PubChem	61028
ChemSpider	10254339 Y
ChEBI	CHEBI:51469 Y
Jmol-3D images	Image 1
SMILES CCCC[Li]
InChI InChI=1S/C4H9.Li/c1-3-4-2;/h1,3-4H2,2H3; Y Key: MZRVEZGGRBJDDB-UHFFFAOYSA-N Y InChI=1/C4H9.Li/c1-3-4-2;/h1,3-4H2,2H3;/rC4H9Li/c1-2-3-4-5/h2-4H2,1H3 Key: MZRVEZGGRBJDDB-NESCHKHYAE
Properties
Molecular formula	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 (<273 K)
Boiling point	decomposes
Solubility in water	reacts violently
Solubility in diethyl ether	soluble
Acidity (pKa)	>35 (need source)
Structure
Molecular shape	tetrameric in solution
Dipole moment	0 D
Hazards
Main hazards	inflames in air, decomposes to corrosive LiOH
Related compounds
Related organolithium reagents	sec-butyllithium tert-butyllithium hexyllithium methyllithium
Related compounds	lithium hydroxide
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Bottles of n-butyllithium in heptane. Note the yellow color and white precipitate.

n-Butyllithium (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 organic synthesis, both industrially and in the laboratory.

Butyllithium is commercially available as solutions (15%, 25%, 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 1800 tonnes.^{[citation needed]}

Although it is a colourless liquid, n-butyllithium is usually encountered as a pale yellow solution in alkanes. Such solutions are stable indefinitely if properly stored,^[1] but in practice, they degrade upon aging. Fine white precipitate (lithium hydride) is deposited and the color changes to orange.

Structure and bonding

Main article: Organolithium reagent

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.^[2] In the case of n-BuLi, the clusters are tetrameric (in ether) or hexameric (in cyclohexane). The cluster is a distorted cubane structure 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-deficient character," n-butyllithium is highly reactive toward Lewis bases.

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⁺.

Preparation

The standard preparation for n-BuLi is reaction of 1-bromobutane or 1-chlorobutane with Li metal:^[1]

2 Li + C₄H₉X → C₄H₉Li + LiX

where X = Cl, Br

The lithium for this reaction contains 1-3% sodium. 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.

Applications

Butyllithium is principally valued as an initiator for the anionic polymerization of dienes, such as butadiene.^[3] The reaction is called "carbolithiation":

C₄H₉Li + CH₂=CH-CH=CH₂ → C₄H₉-CH₂-CH=CH-CH₂Li

Isoprene can be polymerized stereospecifically in this way. Also of commercially importance is the use of butyllithium for the production of styrene-butadiene polymers. Even ethylene will insert into BuLi.^{[citation needed]}

Reactions

Butyllithium is a strong base (pK_a ≈ 50), 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).

Metalation

Main article: Organolithium reagent

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)).^[4] 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 -ates 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.

LiC₄H₉ + R-H → C₄H₁₀ + R-Li

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.

Fe(C₅H₅)₂ + 2 LiC₄H₉ + 2 TMEDA → 2 C₄H₁₀ + Fe(C₅H₄Li)₂(TMEDA)₂

Schlosser's base is a superbase produced by treating butyllithium with potassium tert-butoxide. It is kinetically more reactive than butyllithium and is often used to accomplish difficult metalations. The butoxide anion complexes the lithium and effectively produces butylpotassium, which is more reactive than the corresponding lithium reagent.

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:

n-BuLi + R₂NH + (MeO)₂CO → R₂N-CO₂Me + LiOMe + BuH

Halogen-lithium exchange

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:

C₄H₉Li + RX → C₄H₉X + RLi (X = Br, I)

This reaction is useful for preparation of several types of RLi compounds, particularly aryllithium and some vinyllithium 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:

2 C₄H₉Br + RLi → 2 C₄H₉R + LiBr

2 C₄H₉Li + R'CH=CHBr → 2 C₄H₁₀ + R'C≡CLi + LiBr

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 2 equiv 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).^[1]

Transmetalations

A related family of reactions are the transmetalations, wherein two organometallic compounds exchange their metals. Many examples of such reactions involve Li exchange with Sn:

C₄H₉Li + Me₃SnAr → C₄H₉SnMe₃ + LiAr

where Ar is aryl and Me is methyl

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 metaloids which undergo such exchange reactions are organic compounds of mercury, selenium, and tellurium.

Carbonyl additions

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:

R¹Li + R²CONMe₂ → LiNMe₂ + R²C(O)R¹

Degradation of THF

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 reverse cycloaddition to give enolate of acetaldehyde and ethylene. 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/acetone. Higher temperatures (-25 °C or even -15 °C) are also used.

Thermal decomposition

When heated, n-BuLi, analogously to other alkyllithium reagents with "β-hydrogens", undergoes β-hydride elimination to produce 1-butene and LiH:

C₄H₉Li → LiH + CH₃CH₂CH=CH₂

Safety

Alkyl-lithium compounds are stored under inert gas to prevent loss of activity and for reasons of safety. n-BuLi reacts violently with water:

C₄H₉Li + H₂O → C₄H₁₀ + LiOH

BuLi also reacts with CO₂ to give lithium pentanoate:

C₄H₉Li + CO₂ → C₄H₉CO₂Li

References

1. ^ ^{a b c} Brandsma, L.; Verkraijsse, H. D. (1987). Preparative Polar Organometallic Chemistry I. Berlin: Springer-Verlag. ISBN 3-540-16916-4. .
2. ^ Elschenbroich, C. ”Organometallics” (2006) Wiley-VCH: Weinheim. ISBN 978-3-29390-6.
3. ^ Ulrich Wietelmann and Richard J. Bauer “Lithium and Lithium Compounds” in Ullmann's Encyclopedia of Industrial Chemistry, 2002, Wiley-VCH, Weinheim. doi:10.1002/14356007.a15_393.
4. ^ Sanders, R.; Mueller-Westerhoff, U. T. (1996). "The Lithiation of Ferrocene and Ruthenocene — A Retraction and an Improvement". Journal of Organometallic Chemistry 512 (1-2): 219–224. doi:10.1016/0022-328X(95)05914-B. 

Further reading

• FMC Lithium manufacturer's product sheets
• Environmental Chemistry directory
• Weissenbacher, Anderson, Ishikawa, Organometallics, July 1998, p681.7002, Chemicals Economics Handbook SRI International
• HPV test plan, submitted by FMC Lithium to EPA
• Ovaska, T. V. e-EROS Encyclopedia of Reagents for Organic Synthesis "n-butyllithium." Wiley and sons. 2006. doi:10.1002/047084289X.rb395
• Greenwood, N. N.; Earnshaw, A. Chemistry of the Elements, 2nd ed. 1997: Butterworth-Heinemann, Boston.