In the introduction of this thesis the reactions of pteridines and pyrido[2,3- b
]-pyrazines with nucleophiles are reviewed. In the following chapters the results of an NMR investigation on the formation of σ-adducts between these azaaromatic ring systems and nitrogen nucleophiles, especially KNH 2
, are described. In order to establish the structures of these - not isolable - σ-adducts, the 1
H and 13
C NMR spectra of pteridine, pyrido[2,3- b
]pyrazine and a number of derivatives of both these heterocyclic systems, containing one or more OCH 3
, SCH 3
, CH 3
, t-C 4
, OH, NH 2
, NHNH 2
, F, Cl, Br and C 6
substituents, were extensively analyzed. All resonance signals in the NMR spectra were unequivocally assigned.
By means of 1
H and 13
C NMR, pteridines are shown to form in principle two different σ-adducts with NH 3
: at -60°C one molecule of NH 3
adds to C-4, yielding 4-amino-3,4-dihydro-2-R-pteridines (R=H, Cl), or alternatively, at temperatures up to +25°C, the addition of two molecules of NH 3
to C-7 and C-6 takes place, causing the formation of 6,7-diamino-4-R-2-X-5,6,7,8-tetrahydropteridines (R=X=H, R=H, X=Cl, OCH 3
, SCH 3
, C 6
, R=CH 3
, X=Cl. R=C 6
, X=Cl,H). This detailed NMR spectral information allowed straightforward interpretation of the 13
C NMR spectra of the covalent hydrates 3,4-dihydro-4-hydroxypteridine, 6,7-dihydroxy-5,6,7,8-tetrahydroxypteridine and their cationic species.
Due to the rapid decomposition of pteridine in KNH 2
, no σ-adduct could ever be detected. In sharp contrast, three σ-adducts between KNH 2
and pyrido[2,3- b
]-pyrazines are described i.e.
the 3-amino-3,4-dihydropyrido[2,3- b
]pyrazinide ion, the 3-amino-2-t-butyl-3,4-dihydro-6-chloropyrido[2,3- b
]pyrazinide ion and the 2-amino-1,2-dihydro-3-phenylpyrido[2,3- b
The results are subsequently presented concerning the investigation of the reaction of KNH 2
with 2-X-4,6,7-triphenylpteridines (X=SCH 3
, Cl, F, H). Two reactions are found to take place : aminolysis at C-2, yielding 2-amino-4,6,7-triphenylpteridine (X=SCH 3
, Cl, F) and ring contraction, giving rise to the formation of 2-X-6,8-diphenylpurines (X=SCH 3
, H). By studying the aminolysis with both 15
N labelled pteridines and with K 15
it is proved that the displacement at C-2 in the case of X=SCH 3
, occurs via a ring-opening and ring closing sequence [S N
(ANRORC)]mechanism to the extent of 50-85% (depending on [KNH 2
]); in the case of X=F this amounts to 40% and in the case of X=Cl to 100%.
It is further proved that in the ring contraction of 2-methylthio-4,6,7-triphenylpteridine 85% of C-7 is expelled and 10% of C-6, both processes being preceded by addition of amide ion to C-7 and C-6 respectively.
The possible elimination of C-7 and
C-6 is clearly demonstrated by the fact that both
4,7-diphenyl-2-methylthiopteridines undergo ring contraction to the same product i.e.
6,8-diphenyl-2-methylthiopurine. As a consequence in the former isomer only C-7 is eliminated, while in the latter exclusively C-6 is expelled.
In the next chapter the reactions of 6-chloro-2-R 1
, 3-R 2
]pyrazines [R 1
=H, R 2
, R= t
, R 2
=H, R 1
=H, CH 3
, C 6
, phenanthro(9,10)] with KNH 2
These compounds undergo ring contraction into 2-R-1H-imidazo[4,5- b
]pyridines (R=H, C 6
), besides reductive dechlorination. It is found that ring contraction of 2,3-diphenyl-6-X-pyrido[2,3- b
]pyrazines takes place exclusively if X=Cl; in the case of X=F only aminolysis is found, and in the case of X=Br reductive debromination occurs exclusively.
The investigation on the mechanism of the ring contraction of 6-chloropyrido-[2,3- b
]pyrazine into 1H-imidazo[4,5- b
]pyridine is performed by using both is 15
N-4 and 13
C-2 labelled compounds and K 15
. The results can be explained by the initial formation of a σ-adduct of amide ion at C-2 - unfortunately not detectable by spectroscopic methods - in which σ-adduct, by an intramolecular rearrangement, the chlorine atom and C-2 are expelled simultaneously.