ORGANOLITHIUM COMPOUNDS

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ORGANOLITHIUM
COMPOUNDS
UMBREEN MIR
CHM 331S
PROF. M. DENK
APRIL 12TH, 2000
HISTORY
Over the years, organolithium compounds have gained an increasing value in chemical
synthesis due to their high reactivity, relatively easy preparation and solubility in inert
solvents.4
The first attempt to synthesize an organolithium compound was with the reaction of
lithium with diethyl mercury.10 Methyl-lithium was first prepared by Schlenk and Holtz
in 1917.16 In 1930, the first successful synthesis of alkyllithiums was obtained from
lithium metal and alkyl halides.10
RX
+
2 Li
RLi + LiX
This fundamental method is still widely employed for the “direct” synthesis of
organolithium compounds. However, this method has not been well understood in the
past. New insights have unfolded over the years on the by-products, such as
hydrocarbons (from coupling), alkanes, and alkenes, corresponding to the alkyl halides,
which suggest that radicals may be involved.10
Figure 1: Mechanism of possible stereochemical pathways.10
Metal-halogen exchange and transmetallation, as well as new procedures have been
introduced to avoid producing racemic species.10
STRUCTURES OF SIMPLE ORGANOLITHIUM COMPOUNDS
Efforts have been made in characterizing the structure of important reagents, both in
solution and in the solid state. Several different forms of these reagents have been
determined, because the degree of association is strongly dependent on the nature of the
solvent used.3
Table 1: Aggregation of Typical Organolithium Compounds 3,7
Compound
Methyl-lithium
Method Used
Solvent
Aggregation
X-ray crystallography
THF, Et2O
Hydrocarbons
TMEDA
Tetrameric
Hexameric
Monomeric
IR and NMR
Hydrocarbons
Ether
Hexameric
Tetrameric
----
----
To date, no crystal
structures have been
determined13
Mass spectroscopy
Hydrocarbons
Predominantly
tetrameric, but some
hexameric particles
present
X-ray powder
diffraction
THF, Et2O
Dimeric
n-butyl-lithium
s-butyl-lithium
t-butyl-lithium
Phenyl-lithium
In 1964, Weiss and Lucken deduced that the structure of methyl-lithium, exists as a
tetramer from its X-ray powder diffraction pattern.16 Today, X-ray crystallographic
methods still confirm methyl-lithium to be a tetramer, but more specifically resembling a
cubane, salt-like structure in the solid state.4, 10
Figure 2: Tetrameric structure of methyl-lithium in the solid state.4, 10
Early infrared studies up until 1957, indicated that methyl-lithium does not exist as a
monomer, even in the gas phase.16 Recently, in 1997, the first unambiguous structural
characterization of monomeric methyl-lithium was discovered. The structure was
determined by millimeter/submillimeter spectroscopy.18
Li
C
H
H
H
Figure 3: Monomeric structure of methyl-lithium18
Ethyl-lithium also exists as tetrameric units of crystals in the solid phase (see Figure 4)
Figure 4: Crystal structure of ethyl-lithium4, 10
Infra-red and Raman spectra suggest that n-butyl-lithium is hexameric in benzene
solution. Figure 5 proposes a structure, which involves carbon bridges, where hydrogen
bridges would be expected.
Figure 5: Suggested structure of n-butyl-lithium hexamer.4, 10
The solid state structure of Lewis-base free phenyl-lithium has recently been confirmed
through synchrotron X-ray powder diffraction.5 Figure 6 illustrates phenyl-lithium as
consisting of dimeric Li2Ph2 molecules. These molecules interact with adjacent Li2Ph2
molecules, forming a polymeric ladder structure.
Figure 6: Dimeric structure of unsolvated, Lewis-base free phenyl-lithium in the solid state.5
PHYSICAL PROPERTIES
Many organolithium compounds are soluble in hydrocarbons, with a few exceptions,
methyl-lithium and phenyl-lithium, which are associated in these solvents.7
Table 2: Comparison of Physical Properties of Typical Organolithium Compounds.4, 6, 7, 10, 14
MW
Compound
n-butyl-lithium
(g/mol
)
64.05
BP (C)
60-80
@760mm
Hg
MP Density
(C)
-95
(g/ml)
0.68
Appearance
Solubility
Soluble in ether,
benzene and
paraffinic
hydrocarbons
Solid/liquid
mixture; clear
yellow
Solid/liquid
mixture; clear light
yellow-yellowish
orange
Colourless,
crystalline
s-butyl-lithium
64.05
-----
-----
0.75
t-butyl-lithium
64.05
36-40
-----
0.66
Methyl-lithium
21.97
34.6
0
0.70
Clear liquid; crystal
salt-like structure in
solid state
Phenyl-lithium
84.04
-----
-----
0.73
Reddish brown
liquid
Soluble in
hydrocarbons
Soluble in
hydrocarbons
Soluble in diethyl
ether; insoluble in
aliphatic
hydrocarbons
Soluble in diethyl
ether; insoluble in
hydrocarbons
SPECTROSCOPIC PROPERTIES
Nuclear magnetic resonance spectroscopy is an extremely useful tool in elucidating the
structures of organolithium compounds in solution.4
Table 3: Comparison of 13C-NMR Spectra of Alkyl-lithium Compounds and the
Corresponding Hydrocarbons 4
Compound
n-C4H9Li
(CH3)3Cli
PhCH2Li
Ph2CLi-n-C5H11
Solvent
Hexane
Cyclohexane
Benzene
Benzene
 (13C) (ppm)
+182
+182
+174.5
+115
J (13C-H) (Hz)
100
--116
---
In Figure 7, 7Li signals for more covalently organolithium compounds appear at the lower
magnetic field and species with a large ionic character are shifted to the higher field.
Figure 7: Li-NMR of organolithium compounds in cyclopentane solution.8
Table 4: IR Spectroscopy of Methyl- and Ethyl-lithium in Benzene Solution 4
Compound
CH3Li (mull)
CHD3Li (mull)
(But 6Li) and (But 7Li)
Ethyl-lithium
a
unaffected by substitution of 6Li for 7Li
b
both in solution and in vapour
Band Frequency (cm-1)
2840-2780a
2150-2027a
2805 and 2725
2940,2840,2760a,b
SYNTHESES OF ORGANOLITHIUM COMPOUNDS
Several organolithium compounds are industrially synthesized, but only some are
produced on a considerable scale. For example, n- and s-butyl-lithium in hydrocarbons
are produced in tonnage quantities.11 The cost is relatively low, and the unlimited storage
period (under room temperature in a well-closed bottle) makes it is desirable to purchase
cylinders of n-butyl-lithium in large quantities (25 litres or more), for laboratory
purposes.2
Some costs of the commercially available organolithium compounds are listed in Table 5.
Table 5: Costs of Commercially Available Organolithium Compounds16
Compound
Butyl-lithium
sec-Butyl-lithium
tert-Butyl-lithium
Iso-butyl-lithium
Methyl-lithium
(Trimethylsilyl)methyl-lithium
Concentration
Size
[M]
(L)
1.6
0.1
8.0
18.0
2.0
0.1
0.8
10.0
0.1
0.8
8.0
1.3
0.1
0.8
1.7
0.1
0.8
8.0
1.6
0.1
1.0
0.1
1.4
0.1
0.8
8.0
1.0
0.1
0.25
Cost
(CDN $)
34.70
505.00
928.60
26.80
129.80
63.80
378.50
1735.40
57.20
101.00
40.40
132.90
939.60
490.30
53.80
37.20
162.70
1235.80
53.60
199.80
The fundamental process of synthesizing an organolithium compound is by lithium metal
and an organic halide. 2, 6, 10, 11
RX
+
2 Li
RLi + LiX
Allyl and benzyl chlorides are avoided because they undergo Wurtz-type reactions. A
more desired method requires the use of lithium halide (bromides and iodides may also
be used). New methods often use organic chlorides, because they are less soluble in ether
and thus produce high yields.11
An inert atmosphere is required in order to perform organolithium procedures. The
cheapest form is “white spot” nitrogen. This technique is sometimes replaced with argon
for preparations with lithium metal, because the metal surface becomes tarnished by a
nitride film in contact with nitrogen.11
For small-scale work, the balloon method is ideal for maintaining an inert atmosphere.
This simple method involves a balloon connected to a syringe needle and inflated by an
inert gas. For larger scale processes, gas bubblers are preferred, as illustrated in Figure 8.
Figure 8: Typical assembly for an organolithium reaction.11
Lithium metal is now commercially available as a wire, shot and as a dispersion in
mineral oil.11 The availablility of dispersions commercially, reduces the hazards involved
in laboratory dispersion methods, in which molten metal is shaken or stirred vigorously in
a high-boiling inert medium.11
SYNTHESES OF TYPICAL ORANOLITHIUM COMPOUNDS
There are several ways in which an organolithium compound can be synthesized. Some
general methods are outlined below.
1. Direct Synthesis: This route involves the reaction between organic halides and lithium
metal.10 The same reaction can be carried out with bromine, but it leads to lower yields.6,7
n-C4H9Cl
+
Li
n-C4H9Li
75-100%
+
C4H9Br
Li
Ether
C4H9Li
+
LiBr
80-90%
2. Metallation: This method involves the interaction of an acid, and the salt of a weaker
acid.10
PhLi(Et2O)
+
3.
C5H5Li
No yield stated
Metal-Halogen Exchange: This reaction was discovered by Gilman and Wittig,10 in
which generalizations were made about this new intriguing method.10
(a) The reaction is reversible
(b) Lithium becomes attached to the organic group, which best stabilizes a negative
charge
(c) The reaction takes place readily with iodides and bromides
(d) The reaction is faster in ethers than in hydrocarbons
This process was introduced to synthesize desired organolithium compounds, which
could not be produced directly from the corresponding alkyl halides and lithium metal.6
C2H5Li
+
CH3I
CH3Li
+
C2H5I
4. Lithium and hydrocarbon acids7
THF
ClCH CH2
+
Li
LiCH CH2
60-65%
SYNTHESES OF POLYORGANOLITHIUM COMPOUNDS
1,1-Diltihio-Organyls
1, 1-dilithio-organyls are obtained from alkynes in a two-step synthesis.17
R C
CH
9-BBN-H
R
CH2
CH
BBN n-BuLi
Li
R
CH2
CH
BBN
Li
Halogen-Metal Exchange Reaction with Lithium Metal.
The direct replacement of halogen in organic compounds with Li metal is limited in the
synthesis of polyorganolithium compounds. After the first step, , , or gamma
elimination of lithium halide is faster than the second halogen-metal exchange. As a
result, only 1,4-dilithiobutane or higher 1,n-dilithioalkanes (n4) can be prepared.16
Br(CH2)nBr
n1
-LiBr
CH2
2 Li
-LiBr
Br(CH2)nLi
n4
n2
-LiBr
CH2=CH2
2 Li
-LiBr
n3
Li(CH2)nLi
-LiBr
There have been many attempts to obtain 1,2- and 1,3-dilithiocompounds from the
preparation of 1,2-dilithioethane from 1,2-dichloro- or 1,2-dibromoethane, and 1,3dilithiopropane from 1,3-dichloropropane with lithium metal. Both of these dilithium
compounds are unstable, and decompose by lithium hydride elimination.16
SAFETY PRECAUTIONS
Great care must be taken when handling, storing or disposing organolithium compounds.
Hazards: In general, organolithium compounds are pyrophoric, corrosive and air and
water sensitive.
Storage: should be kept away from heat, moisture, and any sources of ignition.14 They
are packed under nitrogen in Sure/SealTM bottles15
Disposal: must not be emptied in drains, but disposed in a manner consistent with the
federal, state, and local regulations.
APPLICATIONS
There are several organolithium compounds commercially available. They are normally
sold as solutions in hydrocarbons or ethers. The list of organolithium compounds on sale
as laboratory reagents differs from time to time,11 but some recent compounds are
illustrated in Table 5.
Table 6: Commercially Available Organolithium Compounds15
Compound
Butyl-lithium
Solvent
Hexanes
Cyclohexanes
Pentanes
Toluene
Hexane
Heptane
Cyclohexane
Pentane
15% Heptane
Butyl-lithiumLithium 1butanide complex
s-Butyl-lithium
t-Butyl-lithium
Isobutyl-lithium(Lithium 2-methyl1-propanide
complex)
Diethyl ether
Methyl-lithium(Lithium bromide
complex)
5% Diethyl ether
Methyl-lithium(Lithium
methanide)
(Trimethylsilyl)me Pentane
thyl-lithium
complex
Cyclohexane-ether
Phenyl-lithium
*Concentrations are approximate
(a) Aldrich Chemical Company
(b) Fluka
Concentration
[M]*
1.6, 2.5, 10.0
2.0
2.0
2.5
1.6, 10.0
2.7
1.3
1.5, 1.7
1.6
1.0, 1.5
Supplier
(a)
(b)
(a,b)
(b,a)
(b)
(a,b)
1.4
(a)
1.0
(b)
1.6-1.8
(a,b)
Alkyl-lithiums, in general, span from small-scale synthetic applications to large-scale
industrial processes. They are frequently used for deprotonation2 and catalysts for
polymerization of olefins.6
n-Butyl-lithium is the most industrially important organolithium compound because of its
use as an initiator in polymerization of dienes. It is the basic reagent used for most
reactions proceeding via (polar) organometallic intermediates.2
Methyl-lithium is important in organic synthesis as well as in the preparation of transition
metal complexes.16
COMPUTATIONAL METHODS
Dimers are more common than trimers in the field of organolithium chemistry. However,
6
Li-labeled lithioorganic dimers yield the same 13C-NMR patterns as trimers. Therefore a
simple distinction between the two structures is not possible by the conventional 13CNMR spectroscopy.1 New insights have developed towards the 6Li{13C}-HMQCSY
method, which is now applied to distinguish a cyclic dimer from a cyclic trimer or higher
aggregated species. Calculations confirm that a dimer reveals a pair of cross peaks
located at the chemical shift in the f2 (6Li) domain, whereas the trimer is characterized by
an extra cross peak at the chemical shift of the f1 (6Li) domain. 1 The data obtained by the
2D method reduces misinterpretations as compared to the 1D version, because the main
signal is more sufficiently suppressed through careful pulse calibration and phase
cycling.1
LIBRARY RESOURCES
I initiated my research by consulting the handbook of organometallic chemistry. This
book was particularly useful, since it outlined the basic methods, formulas, and structures
of compounds. Furthermore, the journals available online, such as the Journal of the
American Chemical Society, were excellent resources in researching new developments
in organometallic chemistry. The MSDS databases were also easily accessible since they
were available on the Internet. A large portion of books, which contained information on
my topic, were located at Gerstein downtown. In general, recent articles that could be
retrieved from the Internet were easily accessible, whereas the older literature was
difficult to obtain, since there were a limited amount of copies, which were often
unavailable.
REFERENCES
1. Bauer, W. J. (1996). J. Am. Chem. Soc., 118(23), 5450-5455
2. Brandsma, L. and Verkruijsse, H. (1987). Preparative Polar Organometallic
Chemistry 1. Springer-Verlag, London.
3. Coates, G. E. (1960). Organometallic Compounds. John Wiley and Sons Inc., London
4. Coates, G. E. (1967). Organometallic Compounds Volume 1: The Main Group
Elements. Methuen & Co. Ltd., London
5. Dinnebier, R. E. et al. (1998). J. Am. Chem. Soc., 120(7), 1430-1433
6. Hagihara, N. (1968). Handbook of Organometallic Compounds. W. A. Benjamin Inc.,
New York
7. Komiya, S. (1997). Synthesis of Organometallic Compounds: A Practical Guide.
John Wiley & Sons, New York
8. Salzer, A. and Elschenbroich, C. (1989). Organometallics. VCH Publishers, New
York
9. Stone, F. G. A. and Bruce, M. I. (1969). Organometallic Chemistry. Butterworths,
London
10. Wakefield, B. J. (1974). The Chemistry of Organolithium Compounds. Pergamon
Press, Toronto
11. Wakefield, B. J. (1988). Organolithium Methods. Academic Press, New York
12. Wehmschulte, R. J. and Power, P. (1997) J. Am. Chem. Soc., 119(12), 2847-2852
13. Williard, P. G. and Sun, C. (1997) J. Am. Chem. Soc., 119(48), 11693-11694
14. http://www.msdsonline.com
15. http://www.sigma-aldrich.com
16. Sapse, A., and Schleyer, P. (1995). Lithium Chemistry: A Theoretical and
Experimental Overview. Jon Wiley & Sons, Inc., New York
17. http://mdenk.erin.utoronto.ca (Chapter 1 page 19)
18. Grotjahn, D.B., et al. (1997) J. Am. Chem. Soc., 119(50), 12368-12369
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