Lecture Manuscript
By Iain Watson No. 961681970
Lecture of Tuesday January 11, 2000
Factors that Influence the Polarity of Metal Carbon Bonds
The degree of ionicity of organometallic compounds depends on how well the carbon atom can stabilize a negative
charge. The stabilization of negative charge is difficult to assess directly. The acidity of the compounds is taken instead.
Instead of comparing the relative stabilities of different carbanions R-, it is often much easier and chemically more
sensible to compare the pKa values of the of the corresponding acid R-H. As a general rule, highly stabilized carbanions
R-correspond to acidic hydrocarbons R-H. The acidity of hydrocarbons cover a vast range of > 50 orders of magnitude:
Compound
CH4, alkanes
Ph-H
PhCH2-H
Ph3C-H
HCC-H, alkynes
Fluorene
H2O
cyclopentadiene
pKa
50
37
35
30
25
21
15.7
15
Compound
NO2CH2-H
NC-H
MeCO2H
1,3-Cyclopentanedione
O3Cl-OH
(NO2)3C-H
H2SO4
(NC)3C-H
pKa
10
9.4
4.7
4.5
0
0
-2
-5
The pKa values helps to understand why polar organometallic compounds are generally very water sensitive. Water is a
stronger acid than most hydrocarbons and immediately protonates carbanions R- to the hydrocarbons R-H. Anions
derived from hydrocarbons with pKa < 15.7. will be unstable in water. In addition, pKa tables can be used to determine
which hydrocarbon will be preferentially deprotonated in a given mixture. Sometimes pK a values can seem unusually
high, or low. For example 1,3-cyclopentanedione, which has a pKa of 4.5 due to the forced conjugation of the anion.
O
O
H
Conjugations vs. Hybridization (p vs. s)
Even in the absence of activating substituents, hydrocarbons can show a wide variation of different C-H acidities. The
following diagram by Schlosser illustrates that hybridization ("geometry") and conjugation have a powerful influence on
the acidity of hydrocarbons:
Note the particularly strong effect of aromatic conjugation (cyclopentadiene, pK = 15). As hybridization increases so
does the ‘s’ character in the molecule.1
For a good discussion on hybridization see Carey, F.A. and Sundberg, R.J. “Advanced Organic Chemistry, Part A:
Structure and Mechanisms,” 3rd Edition. Plenum Press, New York, 1990, p.2-11.
1
Solvents
The appropriate choice of a solvent is often a key factor for the successful synthesis and use of an organometallic
compound. Protic solvents, those containing readily mobile protons, such as those bound to oxygen, nitrogen and sulfur,
are rarely compatible with organometallic reactions. Examples of Protic solvents include water (pK a = 15.7), alcohols
ROH (pKa ~ 18) and amines R2NH (pKa ~ 22). With aprotic solvents all hydrogen is bound to carbon. Hydrocarbon
solvents like pentane, hexane, benzene and toluene are attacked only by the most reactive organometallic compounds.
The dielectric constant of a solvent is a function of the permanent dipole of the respective solvent molecule and its
polarizability. Polarizability is the ease of distortion of a molecules electron density. The dielectric constant of a solvent
is a good indicator of the ability of that solvent to accommodate separation of charge. However, the dielectric constant
does not indicate the ability of the solvent molecules to interact with the solute at close range. Direct solute-solvent
interactions will depend on the specific structures of the molecules. 2 Below is a table of the dielectric constants of some
common solvents.3
Nonpolar
Hexane
Carbon tetrachloride
Dioxane
Benzene
Diethyl ether
Chloroform
Tetrahydrofuran
Aprotic Solvents
Polar
1.9
Pyridine
2.2
Acetone
2.2
Hexamethylphosphoramide
2.3
Nitromethane
4.3
Dimethylformamide
4.8
Acetonitrile
7.6
Dimethyl sulfoxide
Protic Solvents
12
21
30
36
37
38
47
Acetic acid
Trifluoroacetic acid
tert-Butyl alcohol
Ammonia
Ethanol
Methanol
Water
6.1
8.6
12.5
(22)
24.5
32.7
78
Ethers are decomposed by a number of organo alkali compounds and are rapidly decomposed by strong bases,
halogenating agents or Lewis acids. The choice of solvent in any organometallic reaction is crucial to it’s success or
failure. It should also be noted that because of the quantities and frequencies of their use solvents are one of the most
common causes of accidents in the laboratory. Especially be aware of the flammability of the hydrocarbons and ethers,
the toxisity of benzene, chloroform and carbon tetrachloride and the possibility of peroxide contamination with ethereal
solvents.
Purification of Solvents
Organometallic compounds, especially basic compounds such as Grignard reagents, metal hydrides and organolithiums
require the use of carefully dried solvents. There are two steps in the drying of any solvent, pre-drying followed by
rigorous drying. The reagents used for rigorous drying are very reactive and must be treated with care, it is also
important to avoid dangerous reactions between certain solvents and drying reagents. A great deal of work on the
purification of solvents was carried out by D.R. Burfield and R.H. Smithers et al. who ran quantitative studies on the
efficiency drying agents in the late 1970s and early 1980s. Below are some comments on important drying agents: 4
Calcium chloride, CaCl2: Effective for pre-drying hydrocarbons and ethers by reversible hydrate formation. Will react
with acids, alcohols, amines and some carbonyl compounds.
Calcium hydride, CaH2: Dries by irreversible formation of H2 and calcium hydroxide upon contact with water. Will
rigorously dry amines, pyridines and HMPA, but is also effective for hydrocarbons, and DMF. Residues should be
disposed by slow and careful addition of water.
Lithium aluminium hydride, LiAlH4: May be used for drying ethers, but is less effective then sodium-benzophenone.
Due to the fact that it may explosively decompose over 100oC most discourage its use.
Molecular sieves: Sodium and calcium aluminosilicates with cage-like crystal lattice structures containing pores of
various sizes, but most commonly 3Å and 4Å. After activation at 250 oC, under vacuum, for 24 h, molecular sieves are an
extremely powerful desiccant. They can be stored in an oven over 100 oC for only a few weeks since they are rapidly
hydrolysed in air.
Carey, F.A. and Sundberg, R.J. “Advanced Organic Chemistry, Part A: Structure and Mechanisms,” 3 rd Edition. Plenum
Press, New York, 1990, p.232-233.
3
Riddick, J.A. and Bunger, W.B. (eds.), Organic Solvents, Vol. II of Techniques of Organic Chemistry, 3rd Edition,
Wiley-Interscience, New York, 1970.
4
Casey, M., Lygo, J.L.B., Procter, G. “Advanced Practical Organic Chemistry.” Chapman & Hall, New York, 1990, pp.
28-33
2
Phosphorus pentoxide, P2O5: A rapid and efficient that is limited by high reactivity. Most commonly used for
desiccators, but may also be used to dry acetonitrile and hydrocarbons. Phosphorus pentoxide reacts with alcohols,
amines, acids and carbonyl compounds and causes the decomposition of HMPA, DMSO and acetone. It is best
destroyed by careful addition to ice water followed by neutralisation with base. Never add water to P 2O5, the reaction is
very exothermic.
Sodium, Na: Sodium is used to dry hydrocarbons and ethers. Its chief disadvantage is that the metal surface rapidly
becomes coated with an inert material, therefore, it should not be used unless the solvent is pre-dried. Sodium reacts
with benzophenone to give a dark blue colour caused by the ketyl radical. Sodium residues are destroyed by the slow,
careful addition of ethanol, stirred well until no lumps of sodium remain. After carefully adding methanol the mixture is
allowed to sit for several hours and is then added to a large excess of water. Never use sodium to dry chlorinated
solvents, an explosive reaction can occur.
Ethereal Solvents
Ethereal solvents (Et2O, THF, DME and dioxan) can contain substantial amounts of peroxides formed from exposure to
the air. Peroxides can cause serious explosions and must be removed before distillation.
Test for peroxides:5 add 1 mL the solvent to 1 mL of a 10% solution of sodium iodide in acetic acid. A yellow colour
indicates the presence of low concentrations of peroxides while a brown colour indicates high concentrations.
Low concentrations of peroxides can be removed be a variety of methods.6 A common method is to shake the solvent
with concentrated aqueous ferrous sulfate. Ethers are usually pre-dried over calcium chloride or sodium wire, and
rigorously dried over sodium-benzophenone. Careful preliminary drying is important because ethereal solvents can all
dissolve substantial quantities of water.
Solvent
Diethyl Ether
Et2O
Tetrahydrofuran
THF
1,4-Dioxane
Formula
C4H10O
bp
34oC
mp
-116oC
C4H8O
66oC
-108oC
C4H8O2
101oC
12oC
1,2-Dimethoxyethane
DME, glyme
2-Methoxyethylether
diglyme
1,2-bis(2-Methoxyethoxy)
ethane, triglyme
C4H10O2
85oC
-58oC
C6H14O3
162oC
-64oC
C8H18O4
216oC
-45oC
Cost
98+% ACS reagent
4L $77.70
99+% ACS reagent
4L $97.40
99+% ACS reagent
4L $141.50
99+%
4L $220.40
99%
4L $162.40
99%
3 kg $173.60
Toxicity
low
high,
carcinogen
high,
carcinogen
high
high
high
The boiling point of the ethers is particularly important. To prevent decomposition of the often thermolabile
organometallic compound, the preferred way of isolation is to evaporate the solvent at room temperature under vacuum.
The solvent is collected in a trap cooled with liquid nitrogen, a procedure called cryogenic distillation. Diethylether,
Dioxane, THF and Et3N are easily evaporated in vacuum most frequently used. The other solvents have high boiling
points (difficult to remove) and are also quite expensive. They cannot be distilled over LiAlH 4, because their boiling
points exceeds the decomposition temperature of LiAlH 4. As a result, these solvents are only use if high boiling points
are desirable (reflux temperature) or if their solubilizing power is needed (glyme & derivatives). Ethers can coordinate to
organometallic compounds (oxygen lone pairs). This helps to accelerate many organometallic reactions. For the
formation of Grignard reagents RMgHal, the choice of ethers is essential.
Decomposition of Ethers: Halogenation
Although ethers are chemically fairly robust, they can be decomposed by a small number of reagents:
 Bases
 Lewis acids
 Halogenation agents
Chlorine and bromine reacts with ethers to form the highly carcinogenic alpha-halo-ethers:
5
6
Casey, M., Lygo, J.L.B., Procter, G. “Advanced Practical Organic Chemistry.” Chapman & Hall, New York, 1990, p.36
Burfield, D.R. J. Org. Chem., 1982, 47, 3821.
The following transition metal chlorides are strongly oxidizing and can lead to the chlorination of ethers:
V
VCl4
(NbCl5)2
VI
VII
MoCl5
WCl6 > WCl5
ReCl5
Amine Solvents
The importance of these solvents has decreased since the 1940s. Many of these solvents, such as TEA, py and liquid
ammonia, are bases, which can be important in applications. The use of liquid ammonia as a solvent has gradually been
replaced, however there are still some important uses such as reactions involving lithium amide or sodium amide as bases
and dissolving metal type reductions (the Birch reaction) 7
CO2-
CO2-
Li, NH3
EtOH
Birch Reduction with an electron withrawing group gives the 1,4-dihydro derivative
OMe
OMe
Li, NH3
H+
EtOH
H2O
O
Synthesis of cyclohexenones via reduction of methoxybenzenes followed by hydrolysis
Pyridine and triethylamine can both be dried by distilling from CaH2 into 4 A molecular sieves.
Solvent
Triethylamine
TEA, Et3N
Pyridine
py
Liquid ammonia
NH3
Formula
C6H15N
bp
89oC
mp
-115oC
C5H5N
115oC
-42oC
NH3
-33oC
-78oC
Cost
99.5%
2 L $77.00
99+% ACS reagent
4L $192.70
99.99+% in lecture bottle
170g $373.40
Toxicity
high
high,
carcinogen
Ammonia gas is condensed directly into a reaction vessel via a dry-ice condenser (shown below)
Carey, F.A. and Sundberg, R.J. “Advanced Organic Chemistry, Part B: Reactions and Synthesis,” 3 rd Edition. Plenum
Press, New York, 1990, p.256-257.
7
First ammonia is allowed to flush the system before an acetone/CO2 bath is added into the condenser. The ammonia will
condense and when the reaction vessel has the required amount the flow is shut off. Ammonia can be dried by placing
sodium pieces in the flask until the dark blue colour persists, followed by distillation of the ammonia into a reaction
vessel.
Hydrocarbon Solvents
Hydrocarbon solvents such as hexanes, pentane, benzene and toluene are very non-polar solvents which are regularly
used in organometallic chemistry. Due to their non-polar nature these solvents are relatively easy to dry.
Hexanes is a mixture of hexane isomers and usually also contains some methylcyclopentane. Hexanes and pentane can be
dried by simply distilling into 4 A molecular sieves. Benzene and toluene are first pre-dried with CaH2 (3% w/v for 6 h)
then distilled into 4 A molecular sieves. This should reduce the water content to < 1ppm.
Solvent
Hexanes
Benzene
Toluene
PhMe
Pentane
Formula
mixture of hexane
isomers plus
methylcyclopentane
C6H6
bp
68-70oC
mp
-
Cost
98.5+% ACS reagent
4L $96.40
Toxicity
high
80oC
5.5oC
C7H9
110.6oC
-93oC
high,
carcinogen
high
C5H12
35-36oC
-130oC
99% ACS reagent
4L $96.40
99.5+% ACS reagent
4L $60.70
98%
4 L $67.20
high