|Preferred IUPAC name
3D model (JSmol)
CompTox Dashboard (EPA)
|Molar mass||129.247 g·mol−1|
|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|
|4.01 g/L (at 20 °C)|
|Vapor pressure||4.1 kPa (at 37.70 °C)|
Refractive index (nD)
|GHS Signal word||Danger|
|H225, H301, H314, H412|
|P210, P273, P280, P301+310, P305+351+338, P310|
|Flash point||10 °C (50 °F; 283 K)|
|Lethal dose or concentration (LD, LC):|
LD50 (median dose)
|200–500 mg kg−1 (oral, rat)|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is ?)(|
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-Pr2NEt.
DIPEA consists of a central nitrogen 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, as the two isopropyl groups and the ethyl group occupy much of the space surrounding the nitrogen, only small electrophiles such as protons can react with the nitrogen lone pair.
Occurrence and preparation
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, a combination of properties that makes it a useful organic reagent.
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.
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
Examples of DIPEA used as a substrate
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 are 9.0 and 8.5, respectively.
- Hünig, S.; Kiessel, M. (1958). "Spezifische Protonenacceptoren als Hilfsbasen bei Alkylierungs- und Dehydrohalogenierungsreaktionen". Chemische Berichte. 91 (2): 380–392. doi:10.1002/cber.19580910223.
- Armarego, W. L. F. (2012-10-17). Purification of Laboratory Chemicals. Chai, Christina Li Lin (Seventh ed.). Amsterdam. ISBN 9780123821621. OCLC 820853648.
- Keiper, Sonja; Vyle, Joseph S. (2006-05-12). "Reversible Photocontrol of Deoxyribozyme-Catalyzed RNA Cleavage under Multiple-Turnover Conditions". Angewandte Chemie International Edition. 45 (20): 3306–3309. doi:10.1002/anie.200600164. ISSN 1433-7851. PMID 16619331.
- Sorgi, K. L. (2001). "Diisopropylethylamine". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rd254. ISBN 978-0471936237.
- Dunetz, Joshua R.; Magano, Javier; Weisenburger, Gerald A. (2016-02-05). "Large-Scale Applications of Amide Coupling Reagents for the Synthesis of Pharmaceuticals". Organic Process Research & Development. 20 (2): 140–177. doi:10.1021/op500305s. ISSN 1083-6160.
- Moore, J. L.; Taylor, S. M.; Soloshonok, V. A. (2005). "An efficient and operationally convenient general synthesis of tertiary amines by direct alkylation of secondary amines with alkyl halides in the presence of Huenig's base". Arkivoc. 2005 (part vi): 287–292. EJ-1549C. Archived from the original on 2008-03-04. Retrieved 2006-06-16.
- Chinchilla, Rafael; Nájera, Carmen (2011). "Recent advances in Sonogashira reactions". Chemical Society Reviews. 40 (10): 5084. doi:10.1039/c1cs15071e. ISSN 0306-0012. PMID 21655588.
- Walba, David M.; Thurmes, William N.; Haltiwanger, R. Curtis (1988). "A highly stereocontrolled route to the monensin spiroketal ring system". The Journal of Organic Chemistry. 53 (5): 1046–1056. doi:10.1021/jo00240a022. ISSN 0022-3263.
- Rees, W.; Marcos, C. F.; Polo, C.; Torroba, T.; Rakitin O. A. (1997). "From Hünig's Base to Bis([1,2]dithiolo)-[1,4]thiazines in One Pot: The Fast Route to Highly Sulfurated Heterocycles". Angewandte Chemie International Edition. 36 (3): 281–283. doi:10.1002/anie.199702811.
- Lepore, Salvatore D.; Khoram, Anita; Bromfield, Deborah C.; Cohn, Pamela; Jairaj, Vinod; Silvestri, Maximilian A. (2005). "Studies on the Manganese-Mediated Isomerization of Alkynyl Carbonyls to Allenyl Carbonyls". The Journal of Organic Chemistry. 70 (18): 7443–7446. doi:10.1021/jo051040u. ISSN 0022-3263.