4-Dimethylaminopyridine

From Wikipedia, the free encyclopedia
  (Redirected from 4-dimethylaminopyridine)
Jump to: navigation, search
For the cyanide antidote, see 4-Dimethylaminophenol.
4-Dimethylaminopyridine
4-Dimethylaminopyridine chemical structure.png
Names
IUPAC name
4-dimethylaminopyridine
Systematic IUPAC name
4-(dimethylamino)azine
N,N-dimethyl-4-aminoazine
4-(dimethylamino)azabenzene
N,N-dimethyl-4-aminoazabenzene
Other names
4-(dimethylamino)pyridine
N,N-dimethyl-4-aminopyridine
DMAP
Identifiers
1122-58-3 YesY
ChemSpider 13646 YesY
Jmol-3D images Image
PubChem 14284
Properties
C7H10N2
Molar mass 122.17 g/mol
Melting point 110 to 113 °C (230 to 235 °F; 383 to 386 K)
Boiling point 162 °C (324 °F; 435 K) at 50 mmHg
Acidity (pKa) 17.95[1] (pKa of conjugate acid in acetonitrile)
Hazards
SDS External MSDS
EU classification Toxic T Corrosive C
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY verify (what isYesY/N?)
Infobox references

4-Dimethylaminopyridine (DMAP) is a derivative of pyridine with the chemical formula (CH3)2NC5H4N. This colourless solid is a useful nucleophilic catalyst for a variety of reactions such as esterifications with anhydrides, the Baylis-Hillman reaction, hydrosilylations, tritylation, the Steglich rearrangement, Staudinger synthesis of β-lactams and many more. Chiral DMAP analogues are used in kinetic resolution experiments of mainly secondary alcohols and Evans auxiliary type amides.[2][3][4]

Preparation[edit]

DMAP can be prepared in a two-step procedure from pyridine, which is first oxidized to 4-pyridylpyridinium cation. This cation then reacts with dimethylamine:[5]

Preparation of DMAP.png

Esterification catalyst[edit]

In the case of esterification with acetic anhydrides the currently accepted mechanism involves three steps. First, DMAP and acetic anhydride react in a pre-equilibrium reaction to form an ion pair of acetate and the acetylpyridinium ion. In the second step the alcohol attacks the acetyl group of the acetylpyridinium ion to form an ester. In this step the acetate counterion acts as a base to remove the proton from the alcohol while the alcohol acts as a nucleophile and forms a covalent bond with the acetyl group. The bond from the acetyl group to the catalyst gets cleaved to generate the catalyst and the ester. The described bond formation and breaking process runs synchronous concerted without the appearance of a tetrahedral intermediate. The acetic acid formed will then protonate the DMAP. In the last step of the catalytic cycle the auxiliary base (usually triethylamine or pyridine) deprotonates the protonated DMAP, reforming the catalyst. The reaction runs through the described nucleophilic reaction pathway irrespective of the anhydride used, but the mechanism changes with the pKa value of the alcohol used. For example, the reaction runs through a base-catalyzed reaction pathway in the case of a phenol. In this case, DMAP acts as a base and deprotonates the phenol, and the resulting phenolate ion adds to the anhydride.[6]

Safety[edit]

DMAP has a relatively high toxicity and is particularly dangerous because of its ability to be absorbed through the skin. It is also corrosive.[7]

References[edit]

  1. ^ Kaljurand, I., Kütt, A., Sooväli, L., Rodima, T., Mäemets, V., Leito, I., Koppel, I. A. (2005). "Extension of the Self-Consistent Spectrophotometric Basicity Scale in Acetonitrile to a Full Span of 28 pKa Units:  Unification of Different Basicity Scales". J. Org. Chem. 70: 1019–1028. doi:10.1021/jo048252w. PMID 15675863. 
  2. ^ Donald J Berry, Charles V Digiovanna, Stephanie S Metrick and Ramiah Murugan (2001). "Catalysis by 4-dialkylaminopyridines". Arkivoc: 201–226. 
  3. ^ Höfle, G., Steglich, W., Vorbrüggen, H. (1978). "4-Dialkylaminopyridines as Highly Active Acylation Catalysts". Angew. Chem. Int. Ed. Engl. 17 (8): 569–583. doi:10.1002/anie.197805691. 
  4. ^ Ryan P. Wurz (2007). "Chiral Dialkylamine Catalysts in Asymmetric Synthesis". Chem. Rev. 107 (12): 5570–5595. doi:10.1021/cr068370e. PMID 18072804. 
  5. ^ Shinkichi Shimizu, Nanao Watanabe, Toshiaki Kataoka, Takayuki Shoji, Nobuyuki Abe, Sinji Morishita, Hisao Ichimura "Pyridine and Pyridine Derivatives" in "Ullmann's Encyclopedia of Industrial Chemistry" 2007; Wiley-VCH, Weinheim. doi:10.1002/14356007.a22_399
  6. ^ S. Xu, I. Held, B. Kempf, H. Mayr, Wolfgang Steglich, H. Zipse (2005). "The DMAP-Catalyzed Acetylation of Alcohols - A Mechanistic Study (DMAP = 4-(dimethylamino)-pyridine)". Chem. Eur. J. 11 (16): 4751–4757. doi:10.1002/chem.200500398. PMID 15924289. 
  7. ^ DMAP MSDS - Fischer Science

Further reading[edit]