A new method for the reduction of nitronyl nitroxides

Article abstract of DOI:10.1016/S0040-4039(03)01621-6

Reduction of nitronyl nitroxides using hexamethylenetetramine is a very convenient method for preparing the corresponding imino nitroxides and 2-imidazoline N-oxides.

Full text of DOI:10.1016/S0040-4039(03)01621-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6397–6399
A new method for the reduction of nitronyl nitroxides
Elena Yu. Fursova, Victor I. Ovcharenko,* Galina V. Romanenko and Eugene V. Tretyakov
International Tomography Center, Siberian Branch of Russian Academy of Sciences, Institutskaya 3a, Novosibirsk 630090,
Russia
Received 4 May 2003; revised 16 June 2003; accepted 27 June 2003
Abstract—Reduction of nitronyl nitroxides using hexamethylenetetramine is a very convenient method for preparing the
corresponding imino nitroxides and 2-imidazoline N-oxides.
© 2003 Elsevier Ltd. All rights reserved.
The reaction of nitronyl nitroxide 1a with
Cu(NO3)2·3H2O gave [Cu(1a)2](NO3)2(H2O)2, in which
Cu2+ is square planar (Fig. 1).1,2
a HMTA proved to be a convenient method for the
preparation of both 2a and 3a (Scheme 1).1,2
Taking [Cu(1a)2]2+ as a building block we attempted the
preparation of a highly dimensional heterospin struc-
ture using hexamethylenetetramine (HMTA) as a
bridge capable of forming two-dimensional (5,3 )-nets
by reaction with Cu2+ square matrices.3 However,4unex-
pectedly, the reaction of 1a with HMTA produced
[Cu(3a)2](NO3)2, whose coordination sites are occupied
by two 2-imidazoline N-oxide molecules 3a (Fig. 2).1,2
Figure 1. Structure of [Cu(1a)2]2+. Selected metrical parame-
ters: CuꢀO 1.990(2), CuꢀN 1.959(3), CuꢀONO2 2.539(3),
,
NꢀOCu 1.305(3), NꢀO 1.272(3) A; OCuN 91.03(9), NOCu
122.8(2)°.
Significantly, in the absence of HMTA, the reaction of
1a with Cu(NO3)2·3H2O did not lead to reduction of 1a.
Therefore, the presence of HMTA in the reaction mix-
ture is essential for the reduction of 1a. Methods of
transforming nitronyl nitroxides into imino nitroxides or
further reduction products, 2-imidazoline N-oxides, are
scarce,4 which prompted us to investigate the possibility
of reducing nitronyl nitroxides using HMTA.
Figure 2. Structure of [Cu(3a)2]2+. Selected metrical parame-
,
ters: CuꢀO 1.931(2), CuꢀN 1.933(3), NꢀOꢀCu 1.349(4) A;
OCuN 92.9(1), NOCu 125.2(2)°.
Indeed, when reacting with HMTA in CH3OH, 1a is
gradually reduced to 2a, as indicated by the color change
of the solution (from dark blue to red). After a day, the
solution contained a significant amount of 3a along with
2a. No other products of transformation of 1a by
HMTA were observed. The ratio of 2a to 3a in the
reaction mixture depends on the reaction time; the longer
the reaction time, the larger the amount of 3a accumu-
lated in the reaction mixture. Thus, treatment of 1a with
Keywords: imino nitroxide; nitronyl nitroxide; reduction.
* Corresponding author. Tel.: +7-3832-331945; fax: +7-3832-331399;
e-mail: ovchar@tomo.nsc.ru
Scheme 1. The reduction of nitronyl nitroxides to imino
nitroxides and 2-imidazoline N-oxides.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01621-6

6398
E. Yu. Furso6a et al. / Tetrahedron Letters 44 (2003) 6397–6399
As in the case of 1a, the reaction of nitronyl nitroxide
1b with HMTA gave, depending on the reaction time,
imino nitroxide 2b or 2-imidazoline N-oxide 3b
(Scheme 1), whose physicochemical characteristics were
identical to those of the authentic samples described
elsewhere.5
Note that the reduction of nitronyl nitroxides to imino
nitroxides using HMTA may also be used in those cases
where known procedures are inapplicable. Thus, for
some time we were unable to obtain nitroxide 2c.
However, heating 2-(1H-tetrazol-5-yl)-4,4,5,5-tetra-
methyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl sodium
salt6 (1c) with NaNO2 in water in the presence of
AcOH or in DMF5 led to a change of color from
deep-blue to orange, indicating that compound 2c had
been formed. However, we were unable to isolate 2c.
Boiling 1c with PPh3 in MeOH5 for two days did not
give 2c according to TLC data. Previously, 1c had been
synthesized by the reaction of NaN3 with 1d. Attempts
to apply the same approach to the synthesis of 2c failed
because on heating with NaN3, compound 2d decom-
posed before 2c started to form. Compound 2c could
only be synthesized when HMTA was employed as a
reducing agent.1,2
Figure 4. Stereoview of the frame structure of 3a. Selected
,
metrical parameters: OꢀN 1.346(2) A, NꢀH···O% 0.89(3),
,
2.21(3), 2.966(2) A, 142(2), NꢀH···O¦ 0.93(2), 1.69(3), 2.614(2)
,
A, 174(2).
1EZ, UK (fax: +44(0)-1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk).
Also note the following peculiarities of the structures of
2c and 3a. In solid 2c, each sodium atom is bonded to
three imino nitroxide molecules, forming polymer lay-
ers (Fig. 3).
Acknowledgements
The work was supported by RFBR (03-03-32518),
Minobr (E02-5.0-188), BRHE (REC-008) grants and
‘Integration’ programs of SB RAS.
The presence of two NꢀH groups and two groups
capable of forming stable H-bonds in molecule 3a
proved to be favorable for framework construction
(Fig. 4).
References
Crystallographic data (excluding structure factors) for
the structures in this paper, have been deposited with
the Cambridge Crystallographic Data Centre as supple-
mentary publication numbers CCDC 209718-209723.
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2
1. 2-(Imidazol-4-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imi-
dazol 3-oxide 1-oxyl (1a) was synthesized according to the
standard procedure,7 by the reaction of 2,3-bis(hydroxyl-
amino)-2,3-dimethylbutane8 with 4(5)-imidazole carbalde-
hyde with further oxidation by PbO2. Summary yield 85%;
mp 184–185°C; veff/i=1.73 (295 K); aN=7.70 G. Anal.
found: C, 54.0; H, 6.9; N, 24.8. Calcd for C10H15N4O2: C,
53.8; H, 6.8; N, 25.0%.
[Cu(1a)2](NO3)2. A solution of Cu(NO3)2 (27 mg, 0.112
mmol) in water (1.5 ml) was added to a solution of 1a (50
mg, 0.195 mmol) in water (4 ml). The dark blue crystals
that precipitated 6 h later were filtered off and washed
with acetone (2–3 ml). Yield 65%; temp. of decomp.
>203°C. Anal. found: C, 38.0; H, 4.9; N, 22.1. Calcd for
CuC20H30N10O10: C, 37.9; H, 4.8; N, 22.1.
[Cu(3a)2](NO3)2. A solution of Cu(NO3)2 (27 mg, 0.112
mmol) in water (1.5 ml) was added to a solution of 1a (50
mg, 0.195 mmol) in water (4 ml), then a solution of
HMTA (7 mg, 0.05 mmol) in water (1 ml) was added.
After a day, brown crystals were filtered off and washed
with cold water. Yield 55%; temp. of decop. >270°C. Anal.
found: C, 40.0; H, 5.4; N, 23.5. Calcd for C20H32CuN10O8:
C, 39.8; H, 5.3; N, 23.2.
Figure 3. Structure of a layer in 2c. Selected metrical parame-
ters: NaꢀO 2.346(5), NaꢀN 2.439(5)–2.522(5), OꢀN 1.278(5)
2-(1H-Tetrazol-5-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-
imidazol-1-oxyl sodium salt (2c). Typical procedure. A
,
A, NONa 126.6(3)°.

E. Yu. Furso6a et al. / Tetrahedron Letters 44 (2003) 6397–6399
6399
solution of 1c (1.12 g, 3.96 mmol) and HMTA (137 mg,
0.98 mmol) in MeOH (10 ml) was stirred for 10 h at room
temperature. Then, PbO2 (2.0 g, 8.4 mmol) was added and
the reaction mixture was stirred for 1 h. The precipitate
was filtered off and washed with EtOH. The solvent was
distilled from the filtrate in vacuo, and the residue was
quenched with acetone (5 ml) and filtered off. The product
was crystallized from a mixture of MeOH with AcOEt.
The initial colorless crystalline precipitate was removed by
filtration and the filtrate was kept in a refrigerator for a
few days. The resulting orange crystals were filtered off.
Yield 520 mg (57%); temp. of decomp. 285°C. Anal.
found: C, 41.4; H, 5.2. Calcd for C8H12N6NaO: C, 41.6;
H, 5.2%. veff/i=1.73 (295 K), aN1=9.39 G, aN2=4.54 G.
2-(Imidazol-4-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imi-
dazol 1-oxyl (2a). Yield 57%; mp 174–175°C; veff/i=1.74
(295 K), aN1=9.35 G, aN2=4.30 G. Anal. found: C, 57.7;
H, 7.5. Calcd for C10H15N4O: C, 57.9; H, 7.3.
R1=0.0514, wR2=0.1141 for all data. CCDC reference
number 209722. For [Cu(3a)2](NO3)2: C20H32CuN10O8,
Mw=604.10, monoclinic, space group P21/n, (No. 14),
,
a=7.301(1), b=23.701(4), c=8.002(1) A, i=105.295(3)°,
3
V=1335.7(3) A , Z=2, Dcalcd=1.502 g cm−3, v=0.881
,
mm−1, 5676 reflections measured, 1920 unique (Rint
=
0.1116), 1920 observed (I>2|(I)), 243 parameters, Goof=
0.827, R1=0.0462, wR2=0.1167 (I>2|(I)), R1=0.0636,
wR2=0.1324 for all data. CCDC reference number
209718. For 2c: C8H12N6NaO, Mw=231.23, monoclinic,
space group P21/c, a=10.354(2), b=8.962(1), c=12.915(2)
3
,
,
A, i=113.630(1)°, V=1097.9(3) A , Z=4, Dcalcd=1.399 g
cm−3, v=0.133 mm−1, reflections collected/unique=3059/
1564 (Rint=0.1199), 194 parameters, Goof=0.870, R1=
0.0619, wR2=0.1114 (I>2|(I)), R1=0.1155, wR2=0.1287
for all data. CCDC reference number 209720. For 3a:
C10H16N4O, Mw=208.27, orthorhombic, space group
,
P212121, a=7.5254(9), b=12.096(2), c=12.488(2) A, V=
4,4,5,5-Tetramethyl-4,5-dihydro-1H,3%H-[2,4%]biimidazolyl
3-oxide (3a). The reaction time was 3 days. Yield 55%; mp
216–220°C. Anal. found: C, 57.5; H, 8.0; N, 26.9. Calcd
for C10H16N4O: C, 57.6; H, 7.7; N, 26.9.
3
1136.7(2) A , Z=4, Dcalcd=1.217 g cm−3, v=0.083 mm−1
,
,
reflections collected/unique=4924/1638 (Rint=0.1301), 201
parameters, Goof=1.009, R1=0.0391, wR2=0.0989 (I>
2|(I)), R1=0.0404, wR2=0.1002 for all data. CCDC refer-
ence number 209721. The reflection data were collected on
a Smart Apex Bruker AXS, Mo-Ka radiation (u=0.71073
2. Cystal data for 1a·CH3OH: C11H19N4O3, Mw=255.30,
monoclinic, space group P21/n, a=10.081(1), b=
,
12.260(2), c=11.614(2) A, i=110.884(2)°, V=1341.0(3)
,
,
A), all structures were solved using standard direct method
3
A , Z=4, Dcalcd=1.265 g cm−3, v=0.094 mm−1, reflections
techniques, and refined using full-matrix least-squares
based on F2. Hydrogen atoms were localized in Dz synthe-
sis and refined isotropically with anisotropic non-hydrogen
atoms.
collected/unique=5700/1929 (Rint=0.2027), 231 parame-
ters, Goof=0.932, R1=0.0640, wR2=0.1393 (I>2|(I)),
R1=0.0909, wR2=0.1525 for all data. CCDC reference
number 209723. For 2a: C10H15N4O, Mw=255.30, tri-
3. Moulton, B.; Lu, J.; Zaworotko, M. J. J. Am. Chem. Soc.
2001, 123, 9224.
4. Volodarsky, L. B.; Reznikov, V. A.; Ovcharenko, V. I.
Synthetic Chemistry of Stable Nitroxides; CRC Press Inc:
Boca Raton, 1994; p. 221.
(
clinic, space group P1, a=13.972(3), b=14.044(3), c=
,
14.484(3) A, h=111.036(5), i=95.644(5), k=113.217(5)°,
V=2340.7(9) A , Z=8, Dcalcd=1.176 g cm−3, v=0.080
3
,
mm−1
,
reflections collected/unique=9993/6626 (Rint
=
0.0851), 752 parameters, Goof=0.763, R1=0.0642, wR2=
0.1039 (I>2|(I)), R1=0.2088, wR2=0.1447 for all data.
5. Ullman, E. F.; Call, L.; Osiecki, J. H. J. Org. Chem. 1970,
35, 3623.
CCDC
reference
number
209719.
For
6. Tretyakov, E. V.; Fokin, S. V.; Romanenko, G. V.;
Ovcharenko, V. I. Polyhedron 2003, 22, 1965.
7. Ullman, E. F.; Osiecki, J. H.; Boocock, D. G. B.; Darcy,
R. J. Am. Chem. Soc. 1972, 94, 7049.
[Cu(1a)2](NO3)2·3H2O: C20H36CuN10O13, Mw=688.13,
orthorhombic, space group Pccn, a=13.353(3), b=
3
,
,
25.864(6), c=8.675(2) A, V=2996.3(12) A , Z=4, Dcalcd
=
1.525
g
cm−3
,
v=0.808
mm−1
,
reflections
8. Ovcharenko, V.; Fokin, S.; Rey, P. Mol. Cryst. Liq. Cryst.
1999, 334, 109.
collected/unique=11733/2149 (Rint=0.0758), 274 parame-
ters, Goof=0.761, R1=0.0394, wR2=0.1048 (I>2|(I)),