A new nitroxide radical derived from 2,2,4,6,6-pentamethyl-1,2,5,6-tetrahydro-pyrimidine and its conversion to 2,2,4, 6,6-pentamethyl-1,2,5,6-tetrahydro-pyrimidine-1-oxyl

Article abstract of DOI:10.1016/S0040-4039(00)01557-4

The new oxaziridine nitroxide, 2,2,4,4,6-pentamethyl-7-oxa-1,3-diaza-bicyclo[4.1.0]heptan-3-oxyl, has been obtained in 90% yield by oxidation of 2,2,4,6,6-pentamethyl-1,2,5,6-tetrahydro-pyrimidine with MCPBA in ether. This nitroxide is stable in the solid state or in non-protic solvents. It was converted to the known 2,2,4,6,6-pentamethyl-1,2,5,6-tetrahydro-pyrimidine-1-oxyl by successive reduction with LiAlH₄ and oxidation with Ag₂O, with a reproducible yield of 16% from the starting tetra-hydropyrimidine. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01557-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8787–8789
A new nitroxide radical derived from
2
,2,4,6,6-pentamethyl-1,2,5,6-tetrahydro-pyrimidine and its
conversion to
2
,2,4,6,6-pentamethyl-1,2,5,6-tetrahydro-pyrimidine-1-oxyl
Wen-li Huang, Robert Chiarelli and Andr e´ Rassat*
Ecole Normale Sup e´ rieure and CNRS, 24 rue Lhomond, F75231 Paris Cedex 05, France
Received 24 July 2000; accepted 12 September 2000
Abstract
The new oxaziridine nitroxide, 2,2,4,4,6-pentamethyl-7-oxa-1,3-diaza-bicyclo[4.1.0]heptan-3-oxyl, has
been obtained in 90% yield by oxidation of 2,2,4,6,6-pentamethyl-1,2,5,6-tetrahydro-pyrimidine with
MCPBA in ether. This nitroxide is stable in the solid state or in non-protic solvents. It was converted to
the known 2,2,4,6,6-pentamethyl-1,2,5,6-tetrahydro-pyrimidine-1-oxyl by successive reduction with
LiAlH4 and oxidation with Ag O, with a reproducible yield of 16% from the starting tetra-
2
hydropyrimidine. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: hydroxylamine; nitroxides; oxaziridines; polymerization; pyrimidines.
1
Recently, Volodarsky and Kosover reported the preparation of 2,2,4,6,6-pentamethyl-1,2,5,6-
tetrahydro-pyrimidine-1-oxyl 1 with yield varying from 24 to 50%, by direct oxidation of
2
,2,4,6,6-pentamethyl-1,2,5,6-tetrahydro-pyrimidine 2 with hydrogen peroxide in the presence of
sodium tungstate. This radical was found to decompose slowly in solution or in the pure state,
but after conversion in 50% yield to the stable hydroxylamine 3 by hydrazine, it could be
quantitatively recovered through a new oxidation by MnO (Scheme 1).
2
2
Because of a reported application of 1 in living radical polymerization, we investigated
another preparation: when 2 (14 g) was treated with MCPBA (42 g) in ethyl ether (450 mL), 1
3
was not obtained, but the new oxaziridine nitroxide 4 was isolated in 90% yield, no trace of 1
1
,4
or the isomeric nitroneꢀnitroxide 5 were detected. 1,2-Diphenylhydrazine selectively reduced
5
the aminoxyl group to afford the new oxaziridine–hydroxylamine 6 in 70% yield, while LiAlH
4
6
reduced both the aminoxyl and oxaziridine groups to 3 in 36% yield. This hydroxylamine was
then oxidized to 1 by Ag O in 50% yield.
2
*
Corresponding author. Tel: +33 (0)144323266; fax: +33 (0)144323325; e-mail: andre.rassat@ens.fr
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01557-4

8788
Scheme 1. (i) MCPBA (90%); (ii) LiAlH (36%); (iii) 1,2-Diphenylhydrazine (72%); (iv) Ag O (50%)
4
2
4
Although 4 and 5 have similar ESR spectra and close mp, they differ by the presence of two
asymmetric carbon atoms in 4. This structure was confirmed by partial resolution through
7
8
complexation with b-cyclodextrin and partial separation on chiral HPLC columns. Similarly,
1
3
5
the C NMR spectrum of 6 displays four non-equivalent methyl groups, thus excluding the
isomeric hydroxynitrone structure.
1
,4
Crystalline 4 may be kept unchanged at room temperature. Its solutions in ethyl ether,
petroleum ether, benzene, chloroform or cyclohexane did not show any decay of their ESR
signals after a month at room temperature, but in water, methanol or ethanol, these signals
9
disappeared within few days, probably because of hydrolysis of the oxaziridine ring.
10
Although the conversion of oxaziridines to nitrones is well documented, we could not
transform 4 into 5 by thermal isomerization or by elution on silica gel.
Like other nitroxide radicals, 4 may be used in living radical polymerization; this is now being
studied.
References
1
2
3
. Volodarsky, L.; Kosover, V. Tetrahedron Lett. 2000, 41, 179–181.
. Volodarsky, L.; Kosover, V. US Patent 5 847 035; Dec. 8, 1998.
. 2,2,4,4,6-Pentamethyl-7-oxa-1,3-diaza-bicyclo[4.1.0]heptan-3-oxyl, 4: Mp=52–53°C (heptane); IR: absence of
−
1
w
CꢁN
at 1670 cm ; anal. calcd for C H N 0 (185.24): C, 58.35; H, 9.25; N, 15.12; O, 17.27. Found: C, 58.60;
9 l7 2 2
−
1
H, 9.36; N, 15.24; O, 17.54; esr (H O, LiCl): a =15.8 G (DH =1.8 G); UV: (ethanol) 410 nm (m=10 mol
2
N
pp
−
1
−1
−1
cm ), 235 nm (m=3490 mol cm ). In ethanol solution, both the esr signal and the UV absorption at 410 nm
decay with a half life of ca. 17 h at room temperature.
4
5
. Volodarsky, L. B.; Tikhonov, A. Y. Izvest. Akad. Nauk SSSR, Ser. Khim 1977, 11, 2619–2622.
1
. 2,2,4,4,6-Pentamethyl-7-oxa-1,3-diaza-bicyclo[4.1.0]heptan-3-ol, 6: Mp=98.5–99°C; H NMR (250 MHz, CDCl )
3
13
l 1.16 (s, 3H), 1.25 (s, 3H), 1.41 (s, 3H), 1.53 (s, 6H), 2.06–2.28 (d, J=16 Hz, 1H); C NMR (250 MHz, CDC13)
l: 24.5, 24.9, 25.26, 27.4, 29.2, 40.6, 54.9, 77.4, 80.2.
1
6
. Compound 3 (660 mg) was obtained from 2 (2 g) with LiAlH (750 mg) in ethyl ether (20 mL): Mp=156°C (lit.
4
−
l
1
−1
1
1
6
42–144°C, ethyl acetate); IR: 1670 cm , (lit. 1620 cm ); H NMR (250 MHz, CDC1 ) l 1.16 (s, 6H), 1.42 (s,
3
13
H), 1.94 (s, 3H), 2.23 (s, 2H). C NMR (250 MHz, CDCl ) l 25.6, 27.0, 27.45, 45.6, 54.8, 77.17, 161.6; anal.
3
calcd for C H N O (170.25): C, 63.49; H, 10.66; N, 16.45; O, 9.40. Found: C, 63.45; H, 10.87; N, 16.29; O, 9.44.
9
18
2

8789
7
. 1.6 g of 4 were added to a solution of 10 g of b-cyclodextrin in 200 mL of water. After 3 hours a precipitate
appeared. The filtrate was extracted with ethyl ether, dried on sodium sulfate and evaporated, 700 mg of 4 was
recovered. They were treated again with a solution of 4 g of cyclodextrin in 200 ml of water. After extraction,
2
10 mg of enantiomerically enriched nitroxide 4 was obtained. A solution (41 mg/mL) of this radical in
−
1
−1
cyclohexane (1 cm cell) shows Dm=0.038 mol cm at 456 nm. Determination of the e.e. was not possible:
attempted resolution by HPLC on chiral columns (tris(phenylcarbamoyl)cellulose/SiO , triacetylcellulose, or
2
tribenzoylcellulose) gave a clear indication of the chirality of 4, but with only a weak separation of the
enantiomers.
8
9
. We thank Professor Mannschreck (University of Regensburg) for this analysis.
. Milliet, P.; Lusinchi, X. Tetrahedron 1974, 30, 2825–2832.
10. D o¨ pp, D.; D o¨ pp, H. In Nitronen; Klamann, D.; Hagemann, H., Eds. Methoden der Organischen Chemie
(Houben-Weyl), Band E14b, Teil 2, Georg Thieme Verlag: Stuttgart, 1990; pp. 1490–1494. See also Bohe, L.;
Lusinchi, M.; Lusinchi, X. Tetrahedron 1999, 55, 155–166 and references cited therein.
.