3612
K. Grela, L. Konopski / Tetrahedron 66 (2010) 3608–3613
71–72 ꢀC/2 Torr). FTIR (film): 2971 (C–H), 1605 (C]N), 1236 (N–O);
1H NMR: 1.40 (s, 6H, 2CH3), 2.00 (t, 2H, J 7.5 Hz, C–CH2CH2), 2.03 (s,
3H, COCH3), 2.59 (t, 2H, J 7.5 Hz, C-CH2CH2); MS, m/z (int.%): 127
After 30 min, the reaction mixture was washed with hexane
(10 mLꢃ6), the combined organic layers dried over anhydrous
magnesium sulfate and filtered, affording a blue solution of
nitroso nitrile monomers. In case of all other compounds, the
white solid precipitate of the oxidation product (nitroso nitrile
dimer) was filtered off after 1 h (except compounds 2e and
3edafter 2 h), washed with water (5 mLꢃ3) and dried in vac-
uum. The resulting grayish precipitate, containing some in-
organic salts was washed with hot chloroform (50 ꢀC, 5 mLꢃ3)
and filtered. The blue solution containing the appropriate nitroso
nitrile monomer was filtered through a layer of silica gel for
chromatography, and the solvent was removed in vacuum at rt,
affording a deep blue oil of the nitroso compound monomer, that
solidified quickly into the colourless dimer.
ꢂ
(78, Mþ ), 112 (35, [MꢁCH3]þ), 95 (25), 69 (23), 55 (46), 41 (100).
4.2.6. 5,5-Dimethyl-1-oxy-4,5-dihydro-3H-pyrrol-2-ylamine
(3d)
(starting from compound 1d10 according to the general procedure). A
solution of 4-methyl-4-nitropentanenitrile (1d, 710 mg, 5 mmol) in
diethyl ether (5 mL) was added dropwise with stirring to a flask
containing Al(Hg) freshly prepared from aluminium foil and mer-
cury (II) chloride, following the general procedure. Yield of the title
compound 3d 544 mg (85%). A colourless, viscous oil of 2d solidified
into white crystals of 3d. Mp 218–220 ꢀC (dec), white plates, lit.10
238 ꢀC (dec). FTIR (KBr pellet): 3200 (N–H), 2970 (C–H), 1690
(C]N),1200 (N–O); 1H NMR (CD3OD): 1.31 (s, 6H, 2CH3),1.98 (t, 2H,
J 7.5 Hz, C–CH2CH2), 2.65 (t. 2H, J 7.5 Hz, C–CH2CH2); MS, m/z
4.3.1. 3-Methyl-3-nitrosobutanenitrile dimer (4b) (starting from hy-
droxylamine 2b according to the general procedure). A solution of 3-
methyl-3-hydroxylaminobuta-nenitrile 2b (222 mg, 1.95 mmol)
and sodium hydrogen carbonate (0.25 g, 2.97 mmol) in water
(7.5 mL) was treated with a solution of sodium periodate (0.59 g,
2.75 mmol) in water (10 mL). Yield 46 mg (21%), blue oil solidifying
after recrystallization (10% chloroform/hexane), mp 59–62 ꢀC
(white plates). FTIR (KBr pellet): 2998 (C–H), 2250 (C^N), 1262
(N2O2, nitroso dimer); 1H NMR: 1.47 (s, 6H, 2CH3, monomer), 1.56
(s, 6H, 2CH3, dimer), 2.65 (s, 2H, CH2); 14N NMR:12b ꢁ576.95 (NO),
ꢂ
(int.%): 128 (100, Mþ ), 113 (43, [MꢁCH3]þ), 111 (24), 96 (58), 82 (9),
69 (20).
4.2.7. 5-(2-Cyanoethyl)-2,2-dimethyl-5-hydroxylamine-1,3-dioxane
(2e) and 2-amino-8,8-dimethyl-1-oxy-1-aza-7,9-dioxaspiro[4.5]dec-
2-ene (3e). A solution of the nitrile 1e (0.783 g, 3.66 mmol) in
tetrahydrofuran/ether (15 mL, 2:1 v/v) was added to Al(Hg) pre-
pared from aluminium foil (0.187 g, 7 mmol) and mercury (II)
chloride (0.05 g) in THF (11 mL) containing water (0.1 mL)
according to the general procedure. A colourless solid, mp 170–
174 ꢀC dec, (33% chloroform/hexane), containing the hydroxyl-
amine 2e (70%) and the spirocyclic nitrone 3e (30%). FTIR (film):
3443 (N–H, O–H), 2994 (C–H), 2257 (C^N), 1692 (C]N), 1198 (N–
O), 1087 (C–O); 1H NMR (CD3OD): 2e 70%: 1.36, 1.43 (2s, 6H, hy-
droxylamine (CH3)2), 1.75 (t, 2H, J 8 Hz, CH2CH2CN), 2.53 (t, 2H, J
8 Hz, CH2CH2CN), 3.75 (s, 4H, hydroxylamine 2OCH2); 3e
(30%):1.34, 1.52 (2s, 6H, nitrone (CH3)2), 2.23 (t, 2H, J 8 Hz, nitrone
C–CH2CH2), 2.70 (t, 2H, J 8 Hz, nitrone C–CH2CH2), 3.52 (d, 2H, J
11.5 Hz, nitrone O–CH2–C–CH2–O), 4.38 (d, 2H, J 11.5 Hz, nitrone
O–CH2–C–CH2–O); MS, m/z (int.%): 2e 167 (34), 149 (100), 132 (2),
113 (7), 57 (19); 3e 184 (2), 169 (6), 153 (1), 112 (25), 96 (100), 69
(23); elemental analysis: found C 54.10, H 7.93, N 13.96, C9H16N2O3
requires C 53.99, H 8.08, N 13.99%.
ꢂ
127.45 (CN); EIMS:12a m/z (int.%): 113 (0.2, MHþ), 112 (0.3, Mþ ), 82
(61, [MꢁNO]þ), 72 (22), 55 (100), 54 (38), 53 (11), 42 (13), 41 (40),
39 (36); elemental analysis: found C 53.48, H 7.39, N 25.15, calcu-
lated for C10H16N4O2, C 53.56, H 7.19, N 24.98%.
4.3.2. 4-Methyl-4-nitrosopentanenitrile dimer (4d) (starting from
nitrone 3d according to the general procedure). A solution of 5,5-
dimethyl-1-oxy-4,5-dihydro-3H-pyrrol-2-ylamine 3d (250 mg,
1.95 mmol) and sodium hydrogen carbonate (0.25 g, 2.97 mmol)
in water (7.5 mL) was treated with a solution of sodium periodate
(0.59 g, 2.75 mmol) in water (10 mL). Yield 86 mg (35%), grayish
solid, mp 61–62 ꢀC (white plates, 20% chloroform/hexane). FTIR
(KBr pellet): 2990 (C–H), 2240 (C^N), 1280 (N2O2, nitroso di-
mer); 1H NMR: 1.47 (s, 6H, CH3, monomer), 1.62 (s, 6H, CH3,
dimer), 2.23–2.47 (m, 4H, CH2CH2); 14N NMR:12b ꢁ598.58 (NO),
ꢂ
4.2.8. 2-Hydroxylamino-2-methylpropanenitrile (2a). Compound
2a via the Miller method.24 Hydrocyanic acid (4 g, 4.4 mL,
0.148 mol) was cooled to 0 ꢀC in a round bottom flask. (CAUTION!
The reagent is extremely toxic and volatile (bp 26 ꢀC), work only in
an efficient fume hood). Water (1.2 mL) was added dropwise
resulting 77% hydrocyanic acid and acetone oxime (6 g, 0.082 mol)
was rapidly added with stirring. The reaction mixture was kept for
five days at 6 ꢀC and the HCN was carefully evaporated at rt under
a mild nitrogen stream in a fume hood. The resulting semisolid was
washed with pentane (2ꢃ10 mL) to remove unreacted acetone
oxime and the residue was crystallized from 33% pentane/diethyl
ether affording white needles, yield 2.25 g (27%). Mp 90–92 ꢀC
(lit.24 98–99 ꢀC). FTIR and MSdsee Section 4.2.1.
131.45 (C^N); EIMS, m/z (int.%):12a 127 (0.5, MHþ ), 126 (0.1,
ꢂ
M
þ ), 96 (53, [MꢁNO]þ), 69 (34), 68 (14), 57 (41), 56 (11), 55
(100), 54 (9), 53 (15), 42 (23), 41 (57), 39 (16); FIB-MS: 275 (27,
[2MþNa]þ), 253 (67, [2MþH]þ); elemental analysis: found C
56.64, H 7.79, N 21.86, calculated for C12H20N4O2, C 57.12, H 7.99,
N 22.20%.
4.3.3. 5-(2-Cyanoethyl)-2,2-dimethyl-5-nitroso-1,3-dioxane dimer
(4e) (starting from mixture of hydroxylamine 2e and amino nitrone
3e according to the general procedure). A solution obtained in the
procedure 4.2.5 mixture of 5-(2-cyano-ethyl)-2,2-dimethyl-5-hy-
droxylamine-1,3-dioxane (2e) and 2-amino-8,8-dimethyl-1-oxy-1-
aza-7,9-dioxaspiro[4.5]dec-2-ene (3e) (390 mg, 1.95 mmol) and
sodium hydrogen carbonate (0.25 g, 2.97 mmol) in water (7.5 mL)
4.3. General procedure for oxidation of nitrones or
hydroxylamines 2b, 2d, 3d, 2e and 3e to nitroso compounds
4b, 4d, 4e with sodium periodate (according to5 with some
modifications)
was treated with a solution of sodium periodate (0.59 g,
2.75 mmol) in water (10 mL). Yield 297 mg (77%), greyish solid, mp
56–58 ꢀC (white plates, 33% chloroform/hexane). FTIR (KBr pellet):
2990 (C–H), 2247 (C^N),1278 (N2O2, nitroso dimer); 1H NMR: 1.32,
1.43 (2s, 6H, 2CH3, monomer), 1.39, 1.40 (s, 6H, 2CH3, dimer), 2.11–
2.29 (m, 4H, CH2CH2CN monomer), 2.35–2.58 (m, 4H, CH2CH2CN
dimer), 3.87 (d, 2H, J 12.6 Hz, O–CH2–C–CH2–O monomer), 3.96 (d,
2H, J 12.9 Hz, O–CH2–C–CH2–O dimer), 4.55 (d, 2H, J 12.9 Hz, O–
CH2–C–CH2–O dimer), 4.58 (d, 2H, J 12.6 Hz, O–CH2–C–CH2–O
monomer); 14N NMR:12b ꢁ595.78 (NO), 130.25 (C^N); EIMS:12a
m/z (int.%): 168 (8, [MꢁNO]þ), 153 (7), 111 (18), 110 (17), 82 (43),
80 (12), 59 (100), 55 (24), 54 (20), 53 (25), 43 (30), 41 (9); elemental
A
solution of appropriate hydroxylamine or nitrone
(1.95 mmol) and sodium hydrogen carbonate (0.25 g, 2.97 mmol)
in water (7.5 mL) was placed in a flask protected against light
with aluminium foil. Then, a solution of sodium periodate
(0.59 g, 2.75 mmol) in water (10 mL) was slowly added with
stirring at rt. In the case of
b-hydroxylamino nitrile 2b, the oxi-
dation product was a blue oil (nitroso compound monomer).