''N'',''N''-Diisopropylethylamine, or Hünig's base, is an
organic compound and an
amine. It is named after the German chemist Siegfried Hünig. It is used in
organic chemistry as a
base. It is commonly abbreviated as DIPEA, DIEA, or ''i''-Pr
2NEt.
Structure
DIPEA consists of a central
nitrogen atom that is bonded to an
ethyl group
In organic chemistry, an ethyl group (abbr. Et) is an alkyl substituent with the formula , derived from ethane (). ''Ethyl'' is used in the International Union of Pure and Applied Chemistry's nomenclature of organic chemistry for a saturated ...
and two
isopropyl groups. A lone pair of electrons resides on the nitrogen atom, which can react with electrophiles. However, as the two isopropyl groups and the ethyl group occupy much of the space surrounding the N atom, only small
electrophiles such as
protons can react with the nitrogen lone pair.
Occurrence and preparation
DIPEA is commercially available. It is traditionally prepared by the
alkylation of
diisopropylamine
Diisopropylamine is a secondary amine with the chemical formula (Me2CH)2NH (Me = methyl). Diisopropylamine is a colorless liquid with an ammonia-like odor. Its lithium derivative, lithium diisopropylamide, known as LDA is a widely used reagent.
...
with
diethyl sulfate.
Pure DIPEA exists as a colorless liquid, although commercial samples can be slightly yellow. If necessary, the compound can be purified by
distillation from
potassium hydroxide or
calcium hydride.
Uses and reactions
DIPEA is a sterically hindered organic base that is commonly employed as a proton scavenger. Thus, like
2,2,6,6-tetramethylpiperidine and
triethylamine, DIPEA is a good base but 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 are ...
, DIPEA has low solubility in water, which makes it very easily recovered in commercial processes, a combination of properties that makes it a useful organic reagent.
Amide coupling
It is commonly used as the hindered base in amide coupling reactions between a carboxylic acid (typically activated, for example, as an acid chloride, as illustrated below) and a nucleophilic amine. As DIPEA is hindered and poorly nucleophilic, it does not compete with the nucleophilic amine in the coupling reaction.
:
Alkylations
DIPEA has been investigated for its use as a selective reagent in the
alkylation of
secondary amines to
tertiary amines by
alkyl halides. This is often hampered by an unwanted
Menshutkin reaction forming a
quaternary ammonium salt, but is absent when DIPEA is present.
:
Transition metal catalyzed cross-coupling reactions
DIPEA can be used as a base in a number of
transition metal catalyzed cross-coupling reactions, such as the
Heck Heck may refer to:
* HECK (band), a British rock band
* Heck (surname)
* Heck, Dumfries and Galloway, Scotland
* Heck, North Yorkshire, England
* Heck cattle
* Heck horse
* Heck reaction, a chemical reaction that forms a substituted alkene
* ...
coupling and the
Sonogashira coupling (as illustrated below).
:
Swern oxidation
Although triethylamine is traditionally employed as the hindered base in
Swern oxidations, the structurally similar DIPEA can be used instead, as exemplified below.
:
Examples of DIPEA used as a substrate
DIPEA forms a complex
heterocyclic compound called scorpionine (bis(
,2ithiolo)-
,4hiazine) upon reaction with
disulfur dichloride
Disulfur dichloride is the inorganic compound of sulfur and chlorine with the Chemical formula, formula S2Cl2.
Some alternative names for this compound are ''sulfur monochloride'' (the name implied by its empirical formula, SCl), ''disulphur dich ...
that is catalyzed by
DABCO in a
one-pot synthesis.
:
Comparison with triethylamine
DIPEA and
triethylamine are structurally very similar, with both compounds considered hindered organic bases. Due to their structural similarity, DIPEA and
triethylamine can be used interchangeably in most applications. The nitrogen atom in DIPEA is more shielded than the nitrogen atom in triethylamine. However, triethylamine is a slightly stronger base than DIPEA; the
pKas of the respective
conjugate acids in
dimethyl sulfoxide
Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds a ...
are 9.0 and 8.5, respectively.
References
{{reflist
Alkylamines
Non-nucleophilic bases
Diisopropylamino compounds
Tertiary amines