Mendeleev Commun., 2019, 29, 296–298
R
O(20)
C(19)
R
X
C
X
C(23)
Y
– HX
R
C(20)
C(21)
N
N
R
N
R
Y
C(18)
N(7)
Y
C(17)
N(1)
N(3)
H+
C(22)
C(7A)
C(3A)
N(4)
C(6)
O(2)
N
N
C(5)
O(9)
H
Y
Y
C(8)
C(9)
Scheme 3 General mechanism of vicarious substitution for electron-
deficient azines. Y is an electron-withdrawing group.
C(11)
C(12)
C(13)
C(10)
C(15)
intermediate 5-arylfurazano[3,4-b]pyrazine 4 to yield a key inter-
mediate A, which then eliminates hyponitrous acid producing
compound 3 (Scheme 2).
C(16)
C(14)
O(13)
This suggested mechanism is supported by the following data.
First, the reaction of 4-methoxyphenylglyoxal oxime 2a with
5-(4-methoxyphenyl)furazano[3,4-b]pyrazine 4a prepared before-
hand by the known procedure10 also gave product 3a under
similar conditions, i.e., heating in AcOH–HCl (see Scheme 1).
Second, oximes RCH=NOH, though being weak C-nucleo-
philes, can nevertheless react with electrophiles, as is known for
halogenation11 and Mannich reaction.12 Third, 5-arylfurazano-
[3,4-b]pyrazines 4 as highly electrophilic heterocycles can
undergo the oxidative nucleophilic substitution of hydrogen
(SNH) even with weak C-nucleophiles.13
Figure 1 Molecular structure of compound 3a. The intramolecular N–H···O
hydrogen bond is shown by dashed line. Selected bond lengths (Å): N(1)–O(2)
1.397(3), O(2)–N(3) 1.426(2), N(3)–C(3A) 1.313(3), C(3A)–N(4) 1.358(3),
N(4)–C(5) 1.391(3), C(5)–C(6) 1.499(3), C(6)–N(7) 1.315(3), N(7)–C(7A)
1.386(3), N(1)–C(7A) 1.317(3), C(3A)–C(7A) 1.430(3), C(5)–C(8) 1.370(3),
C(8)–C(9) 1.472(3), O(9)–C(9) 1.262(3). Selected angles (°): O(2)–N(1)–
C(7A) 104.7(2), N(1)–O(2)–N(3) 111.7(2), O(2)–N(3)–C(3A) 103.3(2),
C(3A)–N(4)–C(5) 119.1(2), C(6)–N(7)–C(7A) 114.9(2).
ratio, respectively, i.e. the reaction outcome depended on acidity
of the medium.
The structure of product 3a was determined by X-ray diffrac-
Worthy of particular attention is a similarity of the proposed
mechanism to a known mechanism of vicarious, or eliminative,
nucleophilic substitution of hydrogen in electron-deficient aromatic
carbo- and heterocycles by the action of C-nucleophiles,14 where
the hydrogen atom is eliminated together with a leaving group X,
usually Cl–, attached to the nucleophilic centre (Scheme 3).
Vicarious nucleophilic substitution is known for 5-arylfurazano-
[3,4-b]pyrazines 4 as well.15
The mechanism discussed seems to be a special version of
the vicarious nucleophilic substitution, with the N=O moiety
serving as the leaving group, that differs from the known cases
due to the following features: (1) C-nucleophile is a neutral
molecule rather than carbanion and (2) the reaction proceeds in
acidic medium rather than basic one. The scope of this reaction,
its synthetic value and optimal conditions yet need to be carefully
investigated.
tion (Figure 1).‡
In a similar manner, reaction between 3,4-diaminofurazan
1 and phenylglyoxal oxime 2b afforded compound 3b as a
1
major product (see Scheme 1). H NMR spectra of compounds
3a,b exhibit signals of CH= proton at ca. 6.5 ppm and NH proton
in the low field at ca. 13.5 ppm.
We assume that oxime 2 as a C-nucleophile attacks the
6-position of a highly electrophilic N-protonated form of the
N
Ar
N
Ar
N
N
N
N
2
H+
O
O
4
3
NOH
Ar
NO
Ar
– [HNO]
N
H
N
H
O
O
A
Scheme 2
This study (chemical synthesis) was supported by the Russian
Science Foundation (project no. 18-13-00044). X-ray investiga-
tion was supported by the RUDN University Program ‘5-100.’
Synchrotron radiation-based single-crystal X-ray diffraction
measurements were performed using the Kurchatov Synchrotron
Radiation Source (KSRS) and supported by the Ministry of
Education and Science of the Russian Federation (project code
RFMEFI61917X0007).
‡
Crystal data for 3a. Single crystal (orange plate), C20H16N4O4, M =
= 376.37, monoclinic, space group P21/c, at T = 100 K, a = 19.679(4),
b = 6.7608(14) and c = 13.572(3) Å, b = 102.68(3)°, V = 1761.7(7) Å3,
Z = 4, dcalc = 1.419 g cm–3, F(000) = 784, m = 0.216 mm–1. X-ray diffrac-
tion measurements were carried out using the ‘Belok’ beamline (l =
= 0.96990 Å) of the Kurchatov Synchrotron Radiation Source.5 Total
30968 reflections (3569 unique reflections, Rint = 0.096) were collected
with an oscillation range of 1.0° in the j scanning mode using two
different orientations for the crystal. The semi-empirical correction for
absorption was applied using the SCALA program.6 The data were
indexed and integrated using the iMOSFLM utility from the CCP4
software suite.7,8 The structure was solved by direct methods and refined
by a full-matrix least squares technique on F2 with anisotropic displace-
ment parameters for non-hydrogen atoms. The hydrogen atom of the NH-
group was localized in the difference-Fourier maps and included into the
refinement within the riding model with fixed isotropic displacement
parameters [Uiso(H) = 1.2Ueq(N)]. The other hydrogen atoms were placed
in calculated positions and refined within the riding model with fixed iso-
tropic displacement parameters [Uiso(H) = 1.5Ueq(C) for the Me group
and Uiso(H) = 1.2Ueq(C) for the other groups]. The final divergence
factors were R1 = 0.068 for 2705 independent reflections with I > 2s(I)
and wR2 = 0.160 for all independent reflections, S = 1.028.All calculations
were carried out using the SHELXL program.9
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2019.05.018.
References
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