N,N-Diisopropylethylamine

N,N-Diisopropylethylamine

Skeletal formula of N,N-diisopropylethylamine Skeletal formula of N,N-diisopropylethylamine File:N,N-Diisopropylethylamine-3D-balls-by-AHRLS-2012.png
File:N,N-Diisopropylethylamine-3D-vdW-by-AHRLS-2012.png File:N,N-Diisopropylethylamine-3D-sticks-by-AHRLS-2012.png
Names
Preferred IUPAC name N-Ethyl-N-(propan-2-yl)propan-2-amine
Other names Ethyldi(propan-2-yl)amine N-ethyl-N-isopropylpropan-2-amine Ethyldi(isopropyl)amine Hünig's base DIPEA
Identifiers
CAS Number	7087-68-5 checkY
3D model (JSmol)	Interactive image
ChemSpider	73565 checkY
ECHA InfoCard
EC Number	230-392-0
E number
MeSH	N,N-diisopropylethylamine
PubChem CID	81531
UNII	5SIQ15721L checkY
UN number	2733
CompTox Dashboard (EPA)	{{#property:P3117}}
InChI InChI=1S/C8H19N/c1-6-9(7(2)3)8(4)5/h7-8H,6H2,1-5H3 checkY Key: JGFZNNIVVJXRND-UHFFFAOYSA-N checkY
SMILES CCN(C(C)C)C(C)C
Properties
Chemical formula	C8H19N
Molar mass	129.247 g·mol−1
Appearance	Colorless liquid
Odor	Fishy, ammoniacal
Density	0.742 g mL−1
Melting point	−50 to −46 °C (−58 to −51 °F; 223 to 227 K)
Boiling point	126.6 °C; 259.8 °F; 399.7 K
Solubility in water	4.01 g/L (at 20 °C)
Vapor pressure	4.1 kPa (at 37.70 °C)
Refractive index (nD)	1.414
Hazards
GHS labelling:
Pictograms	GHS02: Flammable GHS05: Corrosive GHS06: Toxic
Signal word	Danger
Hazard statements	H225, H301, H314, H412
Precautionary statements	P210, P273, P280, P301+P310, P305+P351+P338, P310
Flash point	10 °C (50 °F; 283 K)
Explosive limits	0.7–6.3%
Lethal dose or concentration (LD, LC):
LD50 (median dose)	200–500 mg kg−1 (oral, rat)
Related compounds
Related amines	Triethylamine 2,6-Di-tert-butylpyridine 1,5-Diazabicyclo(4.3.0)non-5-ene 1,8-Diazabicycloundec-7-ene
Related compounds	Triisopropylamine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). ☒N verify (what is checkY☒N ?) Infobox references

N,N-Diisopropylethylamine, or Hünig's base, is an organic compound that is a tertiary amine. It is named after the German chemist Siegfried Hünig. It is used in organic chemistry as a non-nucleophilic base. It is commonly abbreviated as DIPEA, DIEA, or i-Pr₂NEt.

Structure

DIPEA consists of a central nitrogen atom that is bonded to an ethyl group and two isopropyl groups. A lone pair of electrons resides on the nitrogen atom, which can react with electrophiles. However, the three alkyl groups on the nitrogen atom create steric hindrance, so 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 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, 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.

File:Use of DIPEA in amide coupling between acid chloride and amine.png

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.

The use of Hünig's base for alkylating secondary amines

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 coupling and the Sonogashira coupling (as illustrated below).

File:Generic Sonogashira coupling with DIPEA as base.png

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.

File:Swern oxidation with DIPEA.png

Examples of DIPEA used as a substrate

DIPEA forms a complex heterocyclic compound called scorpionine (bis([1,2]dithiolo)-[1,4]thiazine) upon reaction with disulfur dichloride that is catalyzed by DABCO in a one-pot synthesis.

Hünig's base in the synthesis of scorpionine

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 hindered than the nitrogen atom in triethylamine. However, triethylamine is a slightly stronger base than DIPEA; the pK_a values of the respective conjugate acids in dimethyl sulfoxide are 9.0 and 8.5, respectively.