Research on the aromaticity and stability of pyrimidine, pyrazine,
pyridazine
1. Introduction
Diazabenzenes are important biological active compounds, they can be used to synthesize many
chemical compounds, such as pharmaceutical products.1 Many efficient methods have been
reported, especially derivatives of pyrimidine2, pyrazine3, reports of synthesis of pyridazine
derivatives4 is less than other two compounds. Maybe the reason is that pyridazine derivatives
are less stable experimently and theoretically, and they haven’t been found in nature.
Experimental chemists can’t explain the different aromaticity and stability of these three
compounds, it must be explicated theoretically.
Contrastingly, much less researches on the aromaticity5 and stability5d, 6 of diazabenzenes
have been reported. Though chemists tried many different methods to explore aromaticity and
stability of pyrimidine, pyrazine, pyridazine, there are no consistent conclusions. Also no
statistical correlations among different aromaticity indices have been obtained.5a, 7
Mosquera5d thought stability of a series of position isomers could not be judged by their
aromaticity, other structural factors also had influences on their stability.(2006) Schleyer8
ascribed their different stability to germinal N lone pair-NN σ bond repulsion.(2010) However,
another report said that it is the different bonds, two C-N bonds or C-C and N-N bond, leading to
different stability between 1,3-isomers and 1,2-isomers.6a(2011) For substituted π-electron
systems, steric effect can also influence their aromaticity.9(1993)
Energetic, magnetic and geometric criteria fail to quantify aromaticity of pyrimidines, pyrazines,
pyridazines, but they can distinguish whether they are aromatic or antiaromatic. As isomerization
stabilization energy (ISE) is a more accurate method than aromatic stabilization energy (ASE),10
nucleus independent chemical shift (NICS)11 is the most popular magnetic criterion, consequently
we use them to evaluate aromaticity of pyrimidine, pyrazine and pyridazine. Shishkin12 found that
aromaticity had a negative correlation with ring flexibility, then we suppose inner angles of a
aromatic ring may be served as a criterion to evaluate its aromaticity.
2. Method of calculation
Verevkin6b used different theoretical methods to calculate thermochemical properties, they
suggested G3 was the best method to calculate thermochemical properties of these three
compouds. (2012 y) Here we use G3 to optimize all compounds. All calculations are carried out by
Gaussian 09 package of program. All the variance of inner angles and NICS values are calculated
according to the structures optimized by G3 method, NICS values are calculated at
B3LYP/6-311++G** level, ISE values are calculated with G3(0K) values. The amino substituted
structures are almost planar with torsion angles less than 1°, other structures are all planar.
1.
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