Investigation of the Electrophilic Aromatic and Heterocyclic Substitution Reaction

(1)

報名代號：分組編號：(主辦單位填寫)

Investigation of the Electrophilic Aromatic and

Heterocyclic Substitution Reaction

Po-Lin Liu,

1

Yu-Ying Huang,

1

Li-Ya Wang,

2

Chun-Hsi Chang,

1

Fung-Chun Kung,

1

Fung Fuh Wong

＊,1

1

Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91, Hsueh-Shih Rd. Taichung, Taiwan 40402, R.O.C.

2

The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, No. 91, Hsueh-Shih Rd. Taichung, Taiwan 40402, R.O.C.

*Corresponding author. Tel.: +886 4 2205 3366 ext. 5603; Fax: +886 4 2207 8083. E-mail address: ffwong@mail.cmu.edu.tw (F. F. Wong).

Keywords:Pyrimidines, Formamidines, Amidination, Heterocyclization

ABSTRACT: The electrophilic substituted reaction was investigated by using aromatic and heterocyclic substrates, including aminobenzenes, 1-aminonaphthalene, 2-aminopyrazines, 3-aminopyridine, 5-aminoquinoline, and 8-aminoquinoline, with formamide in presence of PBr3. Following the experiments

result, the reactivity of the reaction was found proportional to the electrophilicity of the aromatic or heterocyclic substrate.

Y NH2 O H NH2 N H Z HN Z Y Y N N H2N N N H2N X N NH2 PBr3 Z = C or N > > O H NH2 PBr3 N Z Y N N X Y, Z = C or N Electrophilicity Y Z X = Cl or Br > O H NH2 PBr3 O H NH2 PBr3 Z Y N N NH2 N HN N N + H Y, Z = C or N NH2 Y = H, F, Me, OMe References:

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2. Huuskonen, J.; Salo, M.; Taskinen, J. J. Chem. Inform. Comp. Sci. 1998, 38, 450–456.

3. Aksenov, A. V.; Lyakhovnenko, A. S.; Kugutov, M. M. Chem. Hetero. Comp. 2011, 46, 1262–1265.