T. Rosenau et al. / Tetrahedron 58 2ꢀ00ꢀ) 3073±3078
3077
7
.08 )s, 3H, CH ꢀ, 2.17 )s, 3H, CH ꢀ, 2.41 )s, 3H,
a
8b
2
N±CH ꢀ, 2.43 )m, 2H, N±CH ꢀ, 2.62 )t, 2H, CH ꢀ, 3.55
)
N-methylmorpholine, 13, 14, and morpholine )0.96 g, 11%
rel. to NMMOꢀ, residual NMMO is retained on the column.
While the secondary amine morpholine was cleanly sepa-
rated, separation of 13 and 14 from the excess N-methyl-
morpholine was incomplete, so that the fractions containing
the coupling products with N-methylmorpholine impurities
were again chromatographed under identical conditions,
giving the products N-methylmorpholine )1.07 g, approx.
11% rel. to NMMOꢀ, 13 )0.141 g, 0.7% rel. to NMMOꢀ,
14 )0.071 g, 0.035% rel. to NMMOꢀ.
3
3
4
3
2
2
m, 2H, N±CH ±CH ±Oꢀ, 3.61 )dd, 1H, N±CH±CH ±Oꢀ,
2 2 2
3
.67 )dd, 1H, N±CH±CH ±Oꢀ, 4.03 )dd, 1H, N±CHꢀ, 4.85
2
1
3
7a
8b
4
)
s, b, 1H, OHꢀ; C NMR: d 12.5 ) Cꢀ, 12.7 ) Cꢀ, 20.1 ) Cꢀ,
3
3
1.5 ) Cꢀ, 43.1 )N±CH ꢀ, 53.9 )N±CH ꢀ, 56.4 )N±CHꢀ, 64.4
3 2
2
4a
)
CH ±Oꢀ, 72.9 )CH±CH ±Oꢀ, 74.5 ) Cꢀ, 115.3 ) Cꢀ; 116.6
2 2
7
8
5
6
8a
) Cꢀ, 123.8 ) Cꢀ, 125.6 ) Cꢀ, 144.8 ) Cꢀ, 146.3 ) Cꢀ. Anal.
calcd. for C H NO )515.8ꢀ: C, 76.84; H, 11.14; N, 2.72;
found: C, 76.62; H, 11.40; N, 2.54.
3
3
57
3
1
4.4.1. 4-ꢀ2-Morpholinoethyl)morpholine, 13. H NMR: d
4
.3. Isolation of trapping product 10
2
.42 )m, 8H, N±CH ±CH ±Oꢀ, 2.44 )s, 4H, N±CH ±CH ±
2 2 2 2
1
3
A solution of NMMO )1, 100 mmol, 11.9 gꢀ and g-toco-
pherol )6, 20 mmol, 8.33 gꢀ in chloroform )500 mLꢀ was
cooled to 2788C under inert atmosphere. Finely powdered
ferrous chloride )100 mmol, 12.70 gꢀ and tetrabutylammo-
nium tetra¯uoroborate )20 mmol, 6.60 gꢀ were added at
once, and the mixture was stirred for 2 h. n-Hexane
Nꢀ, 3.64 )m, 8H, N±CH
50.9 )N±CH ±CH ±Nꢀ, 53.5 )N±CH
)N±CH ±CH ±Oꢀ. Anal. calcd. for C10
2
±CH
2
±Oꢀ;
C NMR: d
±CH ±Oꢀ, 64.7
)200.28ꢀ:
2
2
2
2
H
N
2
O
2
2
20
2
C, 59.97; H, 10.06; N, 13.99; found: C, 60.05; H, 10.12; N,
13.72.
)
200 mLꢀ was added, and the mixture was stirred for an
4.4.2. 4-Methyl-3-ꢀmorpholinomethyl)morpholine, 14.
1
additional hour. The mixture was warmed to room tempera-
ture, concentrated to a volume of about 200 mL at a
temperature below 208C, and again cooled to 08C. Solids
were removed by ®ltration, the ®ltrate was discarded. The
residue was triturated with 50 mL of chloroform, then
n-hexane was added )100 mLꢀ and the mixture was left
standing for 12 h at 08C. The resulting precipitate was
removed by ®ltration, washed with 10 mL of cold n-hexane,
dried under reduced pressure and suspended in aqueous
ethanol )v/v1:1ꢀ. The undissolved residue was removed
by ®ltration and dried under reduced pressure, providing
H NMR: d 2.22 )m, 1H, N±CH
±N±CH ±CH ±Oꢀ, 2.38 )m, 1H, CH±
ꢀ, 2.46 )m, 3H, CH±N±CH , N±CH, N±CH
CHꢀ, 3.38 )m, 1H, CH ±N±CH ±CH ±Oꢀ, 3.45 )m, 1H,
CH ±N±CH ±CH ±Oꢀ, 3.53 )m, 2H, CH ±N±CH ±CH
Oꢀ, 3.62 )m, 2H, CH ±N±CH ±CH ±Oꢀ, 3.71 )m, 1H,
CH ±N±CH±CH ±Oꢀ, 3.82 )m, 1H, CH
2
±CHꢀ, 2.31 )N±CH ꢀ,
3
2.32 )m, 4H, CH
N±CH
2
2
2
±
2
2
2
3
2
2
±
2
3
2
2
2
2
2
2
2
±N±CH±CH ±
2
3
2
3
1
3
Oꢀ; C NMR: d 47.2 )N±CH
53.9 )N±CHꢀ, 53.5 )CH ±N±CH
±N±CH ±CH
ꢀ, 52.9 )±N±CH
±CHꢀ,
3
2
ꢀ, 54.3 )CH±CH
±Oꢀ, 68.2 )CH
±N±
±N±
3
2
2
2
CH
, d.i.ꢀ, 65.4 )CH
2
3
2
2
CH
±CH
±O, d.i.ꢀ, 70.1 )N±CH±CH ±Oꢀ. Anal. calcd.
2
2
2
10 as a white, waxy solid )0.012 g, 0.11% rel. to 6, 0.02%
rel. to 1ꢀ, mp53±57 8C.
for C10
H
20
N
2
O
2
)200.28ꢀ: C, 59.97; H, 10.06; N, 13.99;
found: C, 60.11; H, 9.89; N, 13.76.
4
.3.1. 4-[6-Hydroxy-2,7,8-trimethyl-2-ꢀ4,8,12-trimethyl-
tridecyl)-chroman-5-yl]-4-methyl-morpholinium tetra-
4.5. Isolation of intermediate 15
1
7a
¯
3
uoroborate, 10. H NMR: d 1.99 )s, 3H, CH ꢀ, 2.11 )s,
3
8b 4
H, CH ꢀ, 2.93 )t, 2H, CH ꢀ, 3.55 )s, 3H, N±CH ꢀ, 3.58
All preparation steps were carried out quickly under a ¯ow
of N to minimize contact with air moisture. A solution of
3
2
3
)
2
1
)
m, 4H, N±CH ±CH ±Oꢀ, 4.14 )m, 2H, N±CH ꢀ, 4.23 )dt,
2
2
2
2
1
H, N±CH ꢀ, 5.9 )s, b, 1H, OHꢀ; C NMR: d 12.2 ) Cꢀ,
3
7a
NMMO )1, 10 mmol, 1.19 gꢀ in chloroform )100 mLꢀ was
cooled to 2788C under inert atmosphere. Finely powdered
ferrous chloride )10 mmol, 1.27 gꢀ was added at once, and
the mixture was stirred for 30 min. After warming to
room temperature, solids were removed by ®ltration and
washed with 10 mL of chloroform. The combined ®ltrates
were again cooled to 2788C, and 20 mL of chloroform
containing one dropof concentrated sulfuric acid were
added. The mixture became immediately cloudy. After
stirring for 2 h, the precipitate was removed, washed with
2
8
2.5 ) Cꢀ, 20.1 ) Cꢀ, 30.3 ) Cꢀ, 54.9 )N±CH ꢀ, 55.6
b
4
3
3
2
4
N±CH , d.i.ꢀ, 67.4 )O±CH , d.i.ꢀ, 74.5 ) Cꢀ, 115.6 ) Cꢀ,
2 2
7
20.1 ) Cꢀ, 124.1 ) Cꢀ, 127.9 ) Cꢀ, 142.5 ) Cꢀ, 147.4 ) Cꢀ.
8
5
6
8a
1
Anal. calcd. for the hydrogensulfate salt C H NO S
)
3
3
59
7
613.90ꢀ: C 64.57, H 9.69, N 2.28; found: C 64.42, H
.90, N 2.14.
9
4
.4. Isolation of coupling products 13 and 14
A solution of NMMO )1, 100 mmol, 11.9 gꢀ in chloroform
500 mLꢀ was cooled to 2788C under inert atmosphere.
dry Et O )10 mLꢀ and dried in vacuo to provide 15 as
2
)
sulfate salt containing minor amounts ),2%ꢀ of 13, 14,
N-methylmorpholine and morpholine as the respective
sulfates.
Finely powdered ferrous chloride )100 mmol, 12.70 gꢀ
was added at once, and the mixture was stirred for 5 h.
Solids were removed by ®ltration and washed with 50 mL
of chloroform. The combined ®ltrates were warmed to room
temperature, concentrated to a volume of about 200 mL, and
4.5.1.
sulfate, 15. H NMR: d 2.84 )m, 2H, N±CH
2.92 )m, 2H, N±CH ±CH ±Oꢀ, 3.21 )m, 2H, N ±CH
4-Methyl-4-ꢀmorpholinomethyl)morpholinium
1
±CH ±Oꢀ,
2
2
1
thoroughly extracted with saturated NaHCO )®ve times
3
2
2
2
2
2
±
±
±
1
1
1
Na SO . The aqueous extracts were discarded. The organic
00 mL, not less!ꢀ and brine )50 mLꢀ, and dried over
CH
CH
2
2
±Oꢀ, 3.24 )s, 3H, N ±CH
±O, N±CH ±CH ±Oꢀ, 3.77 )m, 4H, N ±CH ±CH
2
3
ꢀ, 3.28 )m, 6H, N ±CH
1
2
4
2
2
1
3
phase was concentrated to a volume of about 10 mL and was
chromatographed on acidic aluminium oxide )Brockmann
grade Iꢀ. Elution with methylene chloride/absolute ethanol
Oꢀ, 4.12 )dd, 2H, N
)N±CH ꢀ, 62.4 )CH
)CH ±N±CH ±CH ±O, d.i.ꢀ, 66.5 )CH
d.i.ꢀ, 69.1 )CH ±N±CH ±CH ±O, d.i.ꢀ, 79.3 )N±CH
2
1
±CH
2
±Nꢀ; C NMR: d 56.5
±CH ±O, d.i.ꢀ, 64.0
±N±CH ±CH ±O,
±Nꢀ.
±N±CH
3
2
2
2
3
2
2
2
2
2
)
v/v4:1ꢀ afforded the product amines in the order
3
2
2