A versatile synthesis of new pyrimidinyl nitronyl nitroxides

Article abstract of DOI:10.1039/b309786b

Pyrimidinyl nitronyl nitroxides where the bis-N-oxy fragment is included in a six-membered ring were prepared from diacetonamine by a sequence of reactions including a Grignard reaction, a Ritter reaction and oxidation of the intermediate pyrimidine; the

Full text of DOI:10.1039/b309786b

A versatile synthesis of new pyrimidinyl nitronyl nitroxides†
P. Brough,a R. Chiarelli,b J. Pécaut,a A. Rassat*b and P. Rey*a
a Département de Recherche Fondamentale sur la Matiére Condensée, Service de Chimie Inorganique et
Biologique, (UMR CNRS 5046), 17 Rue des Martyrs F38054, Grenoble Cedex 09, France.
E-mail: rey@drfmc.ceng.cea.fr; Fax: 0033 438 785090; Tel: 0033 438 783568
b Ecole Normale Supérieure, Département de Chimie, (UMR 8640,CNRS-ENS-Université Paris VI ), 24 Rue
Lhomond, F75231, Paris Cedex 05, France. E-mail: andre.rassat@ens.fr; Fax: 0033 144 323325;
Tel: 0033 144 323266
Received (in Cambridge, UK) 14th August 2003, Accepted 17th September 2003
First published as an Advance Article on the web 2nd October 2003
Pyrimidinyl nitronyl nitroxides where the bis-N-oxy frag-
ment is included in a six-membered ring were prepared from
diacetonamine by a sequence of reactions including a
Grignard reaction, a Ritter reaction and oxidation of the
intermediate pyrimidine; the properties of the 2-phenyl-
substituted representative are fully described.
group on the first formed imidosulfate moiety, amino alcohol 6
was expected to yield a tetrahydropyrimidine through a similar
intramolecular reaction.13 However, when reacted with benzo-
nitrile in H2SO4, 6 afforded the corresponding amino-benza-
mide 7a. Attempts to hydrolyze the amide function in strongly
basic medium gave phenyl-substituted 8a (86% yield) and no
traces of 2,4-diamino-2,4-dimethylpentane; alternatively, 7a
could be dehydrated to 8a by azeotropic removal of water in
toluene. 8a was then oxidized with mCPBA as recently
described for related heterocycles14 to give, via the transient
imino nitroxide 9a, the highly stable nitronyl nitroxide 10a in
moderate yield (40%). Following the same synthetic scheme,
10b (R = p-nitrophenyl, 60% yield), 10c (R = p-methox-
yphenyl, 40% yield), 10d (R = 3-pyridyl, 30% yield) and 10e
(R = methyl, 10% yield) were also prepared.‡
The ESR spectra of these nitronyl nitroxides are quite similar
to those of the imidazolinyl analogues.§ In comparison to 1a,
the UV-Visible spectra of 10a in hexane and in ethanol
solutions show a weak hypsochromic shift, an almost 100%
larger absorption coefficient in the visible region and 50%
smaller ones in the UV region.§
In the solid state 10a crystallizes as dark blue needles.¶ The
molecular structure (Fig. 1) exhibits the following structural
features: i) the pyrimidine ring is in a half-chair conformation;
ii) the C6–N1–C2–N3–C4 fragment is nearly planar; bond
lengths are in the range found for five-membered analogs, e.g.
1a,15 and the valence angles are larger than in 1a; iii) the plane
of the phenyl ring makes an angle of 56.4(6)° (in comparison to
24.5 and 29.8 in 1a)15 with the plane of the ONCNO fragment,
so that the molecule is frozen in a chiral conformation; iv) the
shortest intermolecular contacts between neighboring NO
groups are greater than 6.24 Å.
Imidazolidinyl nitronyl nitroxides1 1 have found various
applications, such as trapping reagents for NO,2 spin-labels,3
versatile ligands for magnetic metal–organic complexes,4–6 and
building blocks for purely organic magnetic materials.7 In the
particular field of molecular magnetism structural modifica-
tions of these free radicals have provided a variety of molecular
structures and crystal packings, leading to different inter-
molecular exchange interactions and thus to different magnetic
ground states. However, except for a few examples such as 2,8
these modifications all use Ullmann’s standard synthetic
method,1 and have been mainly restricted to the substituents at
C2.
Although these structural variations, still the object of intense
activity, are potentially infinite, modification of other parts of
the molecule would also provide different possibilities for the
construction of new magnetic materials. In particular, if poly-
functional materials were to be designed, it would be difficult to
obtain diverse properties from a single substituent at C2.
Moreover, Ullmann’s synthesis, based on the radical coupling
of nitro compounds, is lacking in flexibility since it yields only
symmetrical precursors. Other synthetic approaches leading to
stable 3,9 or to unstable 4,10 seem difficult to adapt.
The high-temperature magnetic susceptibility data follow a
Curie–Weiss law (C = 0.378 cm3 K mol21, q = 22.47 K) and
the negative Weiss constant suggests predominant antiferro-
magnetic interactions, as in 1a.7a,b
We report here a versatile stepwise synthesis of new nitronyl
nitroxides 10 (Scheme 1) where the conjugated nitronyl
nitroxide fragment is included in a six-membered ring and for
which varied substitutions may be anticipated. The synthesis of
the phenyl derivative is described as an example.
Freshly prepared diacetonamine 5 was reacted with me-
thylmagnesium iodide to afford 4-amino-2,4-dimethyl-2-penta-
nol, 6.11 Replacement of the hydroxyl group by an amide
function was performed through a Ritter reaction adapted from
the one described for 2,4-dimethyl-2,4-pentanediol,12 in which
the major product of the reaction was a dihydro-oxazine. Since
this indicated a nucleophilic attack of the remaining hydroxyl
† Electronic supplementary information (ESI) available: experimental
procedures for the synthesis of 10a. See http://www.rsc.org/suppdata/cc/b3/
b309786b/
Scheme 1 Synthesis of pyrimidinyl nitronyl nitroxides. a) MeMgI/diethyl
ether; b) RCN/H2SO4; c) Ba(OH)2/H2O, 110 °C; d) mCPBA/THF,
NaIO4.
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This journal is © The Royal Society of Chemistry 2003

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Fig. 1 X-Ray crystal structure of 10a. Relevant structural parameters (Å,
deg.) [and corresponding ones of 1a]. O1–N1 = 1.298(1) [1.266(6)], O2–
N2
= 1.288(1) [1.273(8)], N1–C1 = 1.347(2) [1.351(6)], N2–C1 =
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This synthetic route may easily be extended to prepare
pyrimidinyl nitronyl nitroxides: use of different nitriles allows
substitutions at C2, with the same possibilities as for the
numerous imidazolidinyl nitronyl nitroxides; although re-
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appropriate Grignard reagents and of b-aminoketones may
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substituents at C4, C5 and C6. Furthermore, chiral magnetic
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Notes and references
‡ Melting points (°C) for 10a: 139–140; 10b: 190–192; 10c: 115–117; 10d:
150–151; crystalline 10e spontaneously decomposes at room temperature.
§ Selected data: ESR: aX, (mT) H2O: 9a: aN 0.38 and 1.00; 10a, 10b, 10c
and 10d: aN 0.79; 10e: aN 0.81, aH 0.30. UV-Vis for 10a, lmax/nm (e/mol21
dm3 cm21), n-hexane (c = 4 3 1024 mol L21): 261 (7000), 355 (6900), 626
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24
587 (407), 637 (450)]; EtOH (c = 4.3 10
mol L21): 258 (4500), 326
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b = 21.36(1), c = 9.998(1)Å, b = 96.862(2)°, V = 1323.9(2) Å3, Z = 4,
D (calc.) = 1.241 Mg m23, l(Mo-Ka) = 0.71073 Å, T = 19 °C, 6664
reflections collected, 3093 independent reflections, full-matrix least squares
on F2, 239 parameters, final Rindices [I > 2s(I)]: R1 = 0.0405, wR2
=
0.0879. CCDC 202737. See http://www.rsc.org/suppdata/cc/b3/b309786b/
for crystallographic data in CIF or other electronic format.
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