As the name suggests, a non-nucleophilic base is a
sterically hindered
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
organic
Organic may refer to:
* Organic, of or relating to an organism, a living entity
* Organic, of or relating to an anatomical organ
Chemistry
* Organic matter, matter that has come from a once-living organism, is capable of decay or is the product ...
base that is a poor
nucleophile
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they ar ...
. Normal bases are also nucleophiles, but often chemists seek the proton-removing ability of a base without any other functions. Typical non-nucleophilic bases are bulky, such that protons can attach to the basic center but
alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...
and complexation is inhibited.
Non-nucleophilic bases
A variety of amines and nitrogen heterocycles are useful bases of moderate strength (pK
a of conjugate acid
*
''N'',''N''-Diisopropylethylamine (DIPEA, also called Hünig's Base), p
*
1,8-Diazabicycloundec-7-ene (DBU) - useful for E2
elimination reaction
An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one- or two-step mechanism. The one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as the E1 r ...
s, pK
a = 13.5
*
1,5-Diazabicyclo(4.3.0)non-5-ene (DBN) - comparable to DBU
*
2,6-Di-tert-butylpyridine, a weak non-nucleophilic base pK
a = 3.58
*
Phosphazene bases, such as t-Bu-P
4[''Activation in anionic polymerization: Why phosphazene bases are very exciting promoters'' S. Boileau, N. Illy Prog. Polym. Sci., 2011, 36, 1132-1151, {{doi, 10.1016/j.progpolymsci.2011.05.005]
Non-nucleophilic bases of high strength are usually anions. For these species, the pK
as of the conjugate acids are around 35–40.
*
Lithium diisopropylamide
Lithium diisopropylamide (commonly abbreviated LDA) is a chemical compound with the molecular formula . 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 ...
(LDA), pK
a = 36
* Silicon-based amides, such as
sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...
and
potassium bis(trimethylsilyl)amide (NaHMDS and KHMDS, respectively)
*
Lithium tetramethylpiperidide
Lithium tetramethylpiperidide (often abbreviated LiTMP or LTMP) is a chemical compound with the molecular formula . It is used as a non-nucleophilic base, being comparable to LiHMDS in terms of steric hindrance.
Synthesis
It is synthesised by the ...
(LiTMP or harpoon base)
Other strong non-nucleophilic bases are
sodium hydride
Sodium hydride is the chemical compound with the empirical formula Na H. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na+ and H− ions, in ...
and
potassium hydride
Potassium hydride, KH, is the inorganic compound of potassium and hydrogen. It is an alkali metal hydride. It is a white solid, although commercial samples appear gray. It is a powerful superbase that is useful in organic synthesis. It is sold ...
. These compounds are dense, salt-like materials that are insoluble and operate by surface reactions.
Some reagents are of high basicity (pK
a of conjugate acid around 17) but of modest but not negligible nucleophilicity. Examples include
sodium ''tert''-butoxide and
potassium ''tert''-butoxide.
Example
The following diagram shows how the hindered base,
lithium diisopropylamide
Lithium diisopropylamide (commonly abbreviated LDA) is a chemical compound with the molecular formula . 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 ...
, is used to
deprotonate an
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
to give the
enol
In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). T ...
ate in the
Claisen ester condensation, instead of undergoing a nucleophilic substitution.
:
This reaction (deprotonation with LDA) is commonly used to generate enolates.
References