N,N-diisopropylethylamine on:
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''N'',''N''-Diisopropylethylamine, or Hünig's base, is an
organic compound
Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...
that is a tertiary amine
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
. It is named after the German chemist . It is used in organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...
as a 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. Typic ...
. It is commonly abbreviated as DIPEA, DIEA, or ''i''-Pr2NEt.
Structure
DIPEA consists of a centralnitrogen
Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...
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
The International Union of Pure and Applied ...
and two isopropyl
In organic chemistry, a propyl group is a three-carbon alkyl substituent with chemical formula for the linear form. This substituent form is obtained by removing one hydrogen atom attached to the terminal carbon of propane. A propyl substituent ...
groups. A lone pair of electrons resides on the nitrogen atom, which can react with electrophiles. However, the three alkyl group
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl group is derived from a cy ...
s on the nitrogen atom create steric hindrance
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is generally a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivi ...
, so only small electrophile
In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively Electric charge, charged, have an ...
s such as protons
A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' ( elementary charge). Its mass is slightly less than the mass of a neutron and approximately times the mass of an electron (the pro ...
can react with the nitrogen lone pair.
Occurrence and preparation
DIPEA is commercially available. It is traditionally prepared by thealkylation Alkylation is a chemical reaction that entails transfer of an alkyl group. 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 effecting al ...
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
Diethyl sulfate (DES) is an organosulfur compound with the formula (C2H5)2SO4. It occurs as a colorless, oily liquid with a faint peppermint odor. It is toxic, combustible, and likely carcinogenic chemical compound. Diethyl sulfate is used as an ...
.
Pure DIPEA exists as a colorless liquid, although commercial samples can be slightly yellow. If necessary, the compound can be purified by distillation
Distillation, also classical distillation, is the process of separating the component substances of a liquid mixture of two or more chemically discrete substances; the separation process is realized by way of the selective boiling of the mixt ...
from potassium hydroxide
Potassium hydroxide is an inorganic compound with the formula K OH, and is commonly called caustic potash.
Along with sodium hydroxide (NaOH), KOH is a prototypical strong base. It has many industrial and niche applications, most of which utili ...
or calcium hydride
Calcium hydride is the chemical compound with the formula , an alkaline earth hydride. This grey powder (white if pure, which is rare) reacts vigorously with water, liberating hydrogen gas. is thus used as a drying agent, i.e. a desiccant.
is ...
.
Uses and reactions
DIPEA is a sterically hindered organic base that is commonly employed as a proton scavenger. Thus, like2,2,6,6-tetramethylpiperidine
2,2,6,6-Tetramethylpiperidine, abbreviated TMP, HTMP, or TMPH, is an organic compound of the amine class. In appearance, it is a colorless liquid and has a "fishy", amine-like odor. This amine is used in chemistry as a hindered base ( hindered am ...
and triethylamine
Triethylamine is the chemical compound with the formula N(CH2CH3)3, commonly abbreviated Et3N. Like triethanolamine and the tetraethylammonium ion, it is often abbreviated TEA. It is a colourless volatile liquid with a strong fishy odor remini ...
, 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 thealkylation Alkylation is a chemical reaction that entails transfer of an alkyl group. 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 effecting al ...
of secondary amine
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
s to tertiary amine
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
s by alkyl halide
The haloalkanes (also known as halogenoalkanes or alkyl halides) are alkanes containing one or more halogen substituents of hydrogen atom. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalka ...
s. This is often hampered by an unwanted Menshutkin reaction
In organic chemistry, the Menshutkin reaction converts a tertiary amine into a quaternary ammonium salt by reaction with an alkyl halide. Similar reactions occur when tertiary phosphines are treated with alkyl halides.
The reaction is the m ...
forming a quaternary ammonium salt
In organic chemistry, quaternary ammonium cations, also known as quats, are positively-charged polyatomic ions of the structure , where R is an alkyl group, an aryl group or organyl group. Unlike the ammonium ion () and the primary, secondary, ...
, but is absent when DIPEA is present.
:
Transition metal catalyzed cross-coupling reactions
DIPEA can be used as a base in a number oftransition metal
In chemistry, a transition metal (or transition element) is a chemical element in the d-block of the periodic table (groups 3 to 12), though the elements of group 12 (and less often group 3) are sometimes excluded. The lanthanide and actinid ...
catalyzed
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
cross-coupling reactions, such as the Heck coupling and the Sonogashira coupling
The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon–carbon bonds. It employs a palladium catalyst as well as copper co-catalyst to form a carbon–carbon bond between a terminal alkyne and an aryl or vi ...
(as illustrated below).
:
Swern oxidation
Although triethylamine is traditionally employed as the hindered base inSwern oxidation
In organic chemistry, the Swern oxidation also known as Moffatt-Swern, named after Daniel Swern, is a chemical reaction whereby a primary or secondary Alcohol (chemistry), alcohol () is redox, oxidized to an aldehyde () or ketone () using oxalyl ...
s, the structurally similar DIPEA can be used instead, as exemplified below.
:
Examples of DIPEA used as a substrate
DIPEA forms a complexheterocyclic
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...
compound called scorpionine (bis( ,2ithiolo)- ,4hiazine) upon reaction with disulfur dichloride
Disulfur dichloride (or disulphur dichloride by the British English spelling) is the inorganic compound of sulfur and chlorine with the Chemical formula, formula . It is an amber oily liquid.
Sometimes, this compound is incorrectly named ''sulfur ...
that is catalyzed by DABCO
DABCO (1,4-diazabicyclo .2.2ctane), also known as triethylenediamine or TEDA, is a bicyclic organic compound with the formula N2(C2H4)3. This colorless solid is a highly nucleophilic tertiary amine base, which is used as a catalyst and reagent in ...
in a one-pot synthesis
In chemistry a one-pot synthesis is a strategy to improve the efficiency of a chemical reaction in which a reactant is subjected to successive chemical reactions in just one reactor. This is much desired by chemists because avoiding a lengthy ...
.
:
Comparison with triethylamine
DIPEA andtriethylamine
Triethylamine is the chemical compound with the formula N(CH2CH3)3, commonly abbreviated Et3N. Like triethanolamine and the tetraethylammonium ion, it is often abbreviated TEA. It is a colourless volatile liquid with a strong fishy odor remini ...
are structurally very similar, with both compounds considered hindered organic bases. Due to their structural similarity, DIPEA and triethylamine
Triethylamine is the chemical compound with the formula N(CH2CH3)3, commonly abbreviated Et3N. Like triethanolamine and the tetraethylammonium ion, it is often abbreviated TEA. It is a colourless volatile liquid with a strong fishy odor remini ...
can be used interchangeably in most applications. The nitrogen atom in DIPEA is more hindered than the nitrogen atom in triethylamine. However, triethylamine is a slightly stronger base than DIPEA; the p''K''a values of the respective conjugate acid
A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid gives a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as it loses a hydrogen ion in the rever ...
s in dimethyl sulfoxide
Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula . This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is ...
are 9.0 and 8.5, respectively.
References
{{DEFAULTSORT:Diisopropylethylamine, N,N- Alkylamines Non-nucleophilic bases Diisopropylamino compounds Tertiary amines