Report No xxxx - Instytut Fizyki JÄ drowej PAN

1 H NMR DETECTION OF σ-ADDUCTS IN S N H REACTIONS
OF 3-NITRO-1,5-NAPHTHYRIDINES WITH CHLOROMETHYL
PHENYL SULFONE
Maria Grzegożek, Barbara Szpakiewicz
Instytute of Organic Chemistry and Technology,
Cracow University of Technology, PL 31155 Kraków, Poland
3-Nitro-1,5-naphthyridines 1a-e undergo vicarious nucleophilic substitution (VNS) of
the aromatic hydrogen when reacting with chloromethyl phenyl sulfone in basic solution.
These S N H reactions occur very selectively, giving product of substitution of hydrogen at
position ortho to the nitro group in nitronaphthyridines [1]. The reaction process take place
between 3-nitro-1,5-naphthyridines and carboanion such as carboanion chloromethyl phenyl
sulfone. In the first step addition of the carboanion to the 1 results in the formation of σ-
adduct 2, which undergoes base induced β-elimination of HCl form carboanion which is
subsequently protonated during the workup procedure giving product 3 [2] (Scheme).
N
N
SO 2 Ph
H CHCl
CH 2 SO 2 Ph
NO 2
N
NO 2
N
NO 2
ClCH 2 SO 2 Ph
1 ) - HCl
−
NaOH / DMSO
R
2 ) + H 3 O +
N R
N R
1 2 σ-adduct 3
. R = H, Cl, OC 2 H 5 , NHCH 3 , OH
In order to confirm the intermediates in the above-mentioned reactions are detectable
anionic σ-adducts like 2, we have measured the 1 H NMR spectra of 3-nitro-1,5-
naphthyridines 1a-e in solution of NaOD in DMSO containing 1.1 equivalents of
chloromethyl phenyl sulfone. It was observed that in the spectra nearly all signals are shifted
upfield, particularly considerably the signals of the protons at the carbon atoms which form σ-
adducts. Addition of carboanion of chloromethyl phenyl sulfone to the sp 2 carbon atom of 3-
nitro-1,5-naphthyridines induces the change of its hybridization from sp 2 to sp 3 (tetrahedral
centre of σ-adduct) which is reflected in a considerable upfield shift signal of the hydrogen
atom attached to the particular carbon atom. This rehybridization sp 2 to sp 3 is due to the σ-
adduct formation. The corresponding 1 H NMR data of 3-nitro-1,5-naphthyridines 1a-e and
their (phenylsulfonyl) chloromethyl-σ-adducts 2a-e are compiled in Table. The upfield shift
∆δ of the signals of the C-4 hydrogen atom at the tetrahedral centre of 4-(phenylsulfonyl)-
chloromethyl-σ-adducts 2a-e lie between 2.56 - 3.51 ppm and are in the same range as those
found for amino-σ-adducts of some 3-nitro-1,5-naphthyridines ∆δ 2.55 -3.81 [3] and for σ-
adducts of nitroquinolines with chloromethyl phenyl sulfone ∆δ 2.90 - 4.11 [4].
Summing up, 1 H NMR spectroscopy is a very good method to detection of intermediary
covalent σ-adducts, like 2 and the determination of their structures plays an important role in
the interpretation of the mechanism of VNS reaction.
The 1 H NMR spectra were recorded on Mercury 300 „varian”(300 MHz) spectrometer.
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