4-Dimethylaminopyridine

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For the cyanide antidote, see 4-Dimethylaminophenol.
4-Dimethylaminopyridine
IUPAC name

4-dimethylaminopyridine

Systematic 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
CAS number 1122-58-3 YesY
PubChem 14284
ChemSpider 13646 YesY
Jmol-3D images Image 1
Properties
Molecular formula C7H10N2
Molar mass 122.17 g/mol
Melting point 110-113 °C
Boiling point 162 °C at 50 mmHg
Hazards
MSDS External MSDS
EU classification T C
 YesY (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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.[1][2][3]

Preparation

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:[4]

Esterification catalyst

Main article: Steglich esterification

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.[5]

Safety

DMAP has a relatively high toxicity and is particularly dangerous because of its ability to be absorbed through the skin. It is also corrosive.[6]

References

  1. ↑ Donald J Berry, Charles V Digiovanna, Stephanie S Metrick and Ramiah Murugan (2001). "Catalysis by 4-dialkylaminopyridines". Arkivoc: 201–226. 
  2. ↑ 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. 
  3. ↑ Ryan P. Wurz (2007). "Chiral Dialkylamine Catalysts in Asymmetric Synthesis". Chem. Rev. 107 (12): 5570–5595. doi:10.1021/cr068370e. PMID 18072804. 
  4. ↑ 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
  5. ↑ 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. 
  6. ↑ DMAP MSDS - Fischer Science

Further reading

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