Non-nucleophilic base

As the name suggests, a non-nucleophilic base is a sterically hindered organic base that is a poor nucleophile. 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 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 around 10-13)

N,N-Diisopropylethylamine (DIPEA, also called Hünig's Base[1]), pK_a = 10.75
1,8-Diazabicycloundec-7-ene (DBU) - useful for E2 elimination reactions, 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[2] pK_a = 3.58
Phosphazene bases, such as t-Bu-P₄[3]

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 (LDA), pK_a = 36
Silicon-based amides, such as sodium and potassium bis(trimethylsilyl)amide (NaHMDS and KHMDS, respectively)
Lithium tetramethylpiperidide (LiTMP or harpoon base)

Other strong non-nucleophilic bases are sodium hydride and potassium hydride. 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, is used to deprotonate an ester to give the enolate in the Claisen ester condensation, instead of undergoing a nucleophilic substitution.

This reaction (deprotonation with LDA) is commonly used to generate enolates.

gollark: "Dear apioform,Yes, this time works for me.Yours sincerely, wico979"

gollark: ↓ gollark

gollark: ↓ palaiologos

gollark: It's perfectly consistent. You're just bad.

gollark: We use Wireguard.

References

K. L. Sorgi, "Diisopropylethylamine," Encyclopedia of Reagents for Organic Synthesis, 2001. doi:10.1002/047084289X.rd254
Rafael R. Kostikov, Sánchez-Sancho Francisco, María Garranzo and M. Carmen Murcia "2,6-Di-t-butylpyridine" Encyclopedia of Reagents for Organic Synthesis 2010. doi:10.1002/047084289X.rd068.pub2
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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[1] K. L. Sorgi, "Diisopropylethylamine," Encyclopedia of Reagents for Organic Synthesis, 2001. doi:10.1002/047084289X.rd254

[2] Rafael R. Kostikov, Sánchez-Sancho Francisco, María Garranzo and M. Carmen Murcia "2,6-Di-t-butylpyridine" Encyclopedia of Reagents for Organic Synthesis 2010. doi:10.1002/047084289X.rd068.pub2

[3] 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