An unexpected replacement of a methyl with an amino
in the tetramethylpyrazine system
Received: 27 February 2014 / Accepted: 22 April 2014 / Published online: 11 May 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract A novel and unexpected product, 5-amino-3,6-dimethyl-2-pyr-
azinecarbonitrile (3), was obtained during the attempted to synthesis of 3,5,6-tri-
methyl-2-pyrazinecarbonitrile (2) from its corresponding alcohol (1) by the catalytic
amount of KI or I
in combination with TBHP as an external oxidant. The product
was conﬁrmed by ESI–MS, HRMS,
C-NMR, and 2D-NMR. The
mechanism for the formation of the amino group in the tetramethylpyrazine system
is also proposed.
Keywords Unexpected Á Tetramethylpyrazine Á Methyl Á
Amino group Á Nitrile
Nitrile is widely used in organic and medicinal chemistry because it can be easily
transformed into various functional groups such as ester, amide, carboxylic acid,
amine, aldehyde, ketone, and nitrogen-containing heterocycle, etc. . Furthermore,
over 30 clinical drug and 20 additional compounds in clinical development contain
a nitrile moiety in their chemical structure . Therefore, synthesis of nitriles has
attracted much attention [1, 3–5].
2,3,5,6-tetramethylpyrazine (TMP, Fig. 1) is the main active component of a
well-known traditional Chinese medicine Ligusticum wallichii Franchat (Chuan
Ming Lang, Hui Yao: These authors contributed equally to this work.
Electronic supplementary material The online version of this article (doi:10.1007/s11164-014-1686-
6) contains supplementary material, which is available to authorized users.
M. Lang Á H. Yao Á P. Fu Á W. Cai Á Y. Wang Á P. Yu (&)
Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou 510632, China
Res Chem Intermed (2015) 41:5621–5626