Amine and Ethylenediamine Li Reductions
J . Org. Chem., Vol. 65, No. 21, 2000 7103
mmol) in t-butylamine (8 mL) and ethylenediamine (0.72 g,
12 mmol) was cooled to -18 °C, and lithium (0.084 g, 12 mmol),
in small pieces, was added rapidly. After 2 h the reaction
mixture was allowed to warm to room temperature. After 5 h,
an aliquot of the reaction mixture showed 75% of N-methyl-
decanoic acid amide 6 and 17% of N-(2-aminoethyl)deca-
noic acid amide 10.
t-Bu tyla m in e a n d N,N′-d im eth yleth ylen ed ia m in e So-
lu tion . A solution of N-benzyl-N-methyldecanoic acid amide
4 (2.75 g, 10 mmol) in t-butylamine (30 mL) and N,N′-
dimethylethylenediamine (5.3 g, 60 mmol) was cooled in an
ice bath. Lithium (0.42 g, 0.06 g-atoms) in small pieces was
added at once. After 11 h, the reaction mixture was poured
into a mixture of 1 M hydrochloric acid (100 mL) and ice (50
g). The crystalline product was collected by filtration and
washed with water. The crude N-methyldecanoic acid amide
6 (1.3 g, 70%) was 91% pure by glpc. The material was stirred
with 0.5 M hydrochloric acid (20 mL), filtered, and dried to
give 1.14 g (61%) of product which was 96.4% pure by glpc.
The crude amide was recrystallized from 7 mL of hexane and
cooled to freezer temperature, to give 1.07 g (58%) of N-
methyldecanoic acid amide 6 which was more than 99% pure
by glpc.
n -P r op yla m in e Solu tion w ith t-Bu ta n ol. A solution of
N-benzyl-N-methyldecanoic acid amide 6 (10 g, 0.036 mol) in
n-propylamine (100 mL), ethylenediamine (13 g, 0.216 mol),
and t-butanol (16 g, 0.216 mol) was cooled to -18 °C, and
lithium (1.77 g, 0.252 mol), in small pieces was added rapidly.
After 15 min, the temperature raised to 12 °C and then
lowered. After another 45 min, the reaction turned blue and
after another 30 min a yellow solution was obtained. The
reaction mixture was poured over 75 g of crushed ice and water
(75 mL). The mixture was extracted with ether, and the
combined ether extracts were washed with brine. The ether
was evaporated, and the residue was dissolved in THF (50 mL)
and 3 N hydrochloric acid (15 mL). The solution was heated
under reflux for 2 h and then cooled and diluted with brine
(50 mL). The mixture was extracted with ether, and the
combined ether extracts were washed with brine and filtered
through 1PS filter paper. The ether was evaporated, and the
residue was distilled to give 2.0 g (36%) of n-decanal 8, bp 100-
105 °C (15 mm).
Red u ction of Th ioa n isole 11. Thioanisole 11 (1.24 g, 0.01
mol) in n-propylamine (10 mL) and ethylenediamine (1.8 g,
0.03 mol) at 0 °C was treated with lithium (0.21 g, 0.03 gram-
atom). The reaction mixture turned dark blue. After 1 h the
ice bath was removed, and the reaction was continued for 3 h
at room temperature. The reaction mixture was then poured
onto concentrated hydrochloric acid (25 mL) and ice (25 g).
The mixture was extracted with ether. The ether solution was
dried over sodium sulfate and evaporated to give 0.9 g (82%)
of thiophenol 12 which was 91% pure by glpc (6% thioanisole
11).
n-propylamine (50 mL) and ethylenediamine (6 g, 0.10 mol)
in a three-neck flask equipped with a mechanical stirrer,
condenser, and a thermometer. Approximately half of the
lithium was added at once. The remainder of the lithium was
added after most of the first portion had dissolved. After 2 h,
the lithium had all reacted and the reaction mixture was
poured onto ice and extracted with ether. The ether was
evaporated to give 1.9 g of crude 1-adamantanemethanol 17
which was sublimed under vacuum to give l.5 g (75%) of
slightly yellow 1-adamantanemethanol 17. This sample showed
the same NMR spectrum as authentic material.
Red u ction of 1-Ad a m a n ta n em eth yl Meth a n esu lfon a te
16. Reduction of a sample of 1-adamantanemethyl methane-
sulfonate24 by the procedure described above gave a 70% yield
of 1-adamantanemethanol 17.
Red u ction of Mor p h olin e p-Tolu en esu lfon a m id e 18.
Lithium (3.9 g, 0.56 gram-atom) was added in two portions to
a solution of morpholine p-toluenesulfonamide25 18 (15 g, 0.062
mol) in n-propylamine (250 mL), ethylenediamine (37 g, 0.62
mol) and t-butanol (9.2 g, 0.12 mol) at room temperature. One-
half of the lithium was added, and after an hour most of it
had dissolved and the second portion was added. The reaction
was continued to another 3.5 h and then cooled in an ice bath
and treated with methanol (30 mL). Water (120 mL) was
added, and the reaction mixture was evaporated under reduced
pressure. Water (100 mL) was added, and the reaction mixture
was concentrated under reduced pressure, cooled, and acidified
with concentrated hydrochloric acid. The mixture was ex-
tracted with ether, and the combined ether extracts were
washed with brine. The ether was filtered and distilled at
atmospheric pressure. The residue was distilled through a
short path still at 12 mm to give 2.9 g (38%) of p-toluenethiol
19 which was 95% pure by glpc.
Red u ction of 4-Meth ylcycloh exa n on e Oxim e 20. In a
three-neck flask fitted with a condenser, mechanical stirrer,
and a thermometer was placed a solution of 4-methylcyclo-
hexanone oxime26 20 (12.7 g, 0.1 mol) in 100 mL of n-
propylamine and ethylenediamine (30 g, 0.50 mol). Lithium
(3.5 g, 0.5 gram-atom) in small pieces was added all at once.
After about 25 min, the temperature rose to 55 °C and the
mixture refluxed briskly. After 1 h, the reaction was blue-green
and all of the lithium had reacted. The reaction mixture was
mixed with 200 g of ice and extracted with ether. The ether
solution was washed with 15% sodium hydroxide and brine
and then dried over magnesium sulfate. The ether was
evaporated, and the residue was distilled to give 7.9 g (70%)
of 4-methylcyclohexylamine 21, bp 148-150 °C (atm), which
was 93.5% trans and 6.5% cis by glpc on a J &W column,
CDXB, 30 M × 0.25 mm. at 100 °C.
Red u ction of 4-Meth ylcycloh exa n on e O-Meth yloxim e
22. A solution of 4-methylcyclohexanone O-methyloxime27
(21.15 g, 0.15 mol) in n-propylamine (150 mL), ethylenedi-
amine (72 g, 1.2 mol), and t-butanol (89 g, 1.2 mol) was treated
with lithium (8.4 g, 1.2 gram-atoms) added in two portions.
Addition of half of the lithium caused a temperature rise to
62 °C and vigorous reflux. After the reaction subsided and the
reaction cooled to 50 °C, the remaining lithium was added
which caused another exotherm and vigorous reflux. After the
blue color dissipated, the reaction mixture was poured onto
100 g of ice. The mixture was extracted with hexane; the
combined hexane extracts were washed with brine and filtered
through 1PS filter paper. After distillation of the hexane at
atmospheric pressure, 4-methylcyclohexylamine 21 (12.6 g,
72%), bp 148-150 °C (atm), was obtained after distillation
through a short Vigreux column.
Clea va ge of 1-Ad a m a n ta n a m in e p-Tolu en esu lfon a -
m id e 13. 1-Adamantanamine p-toluenesulfonamide22 13 (4 g,
0.13 mmol), n-propylamine (50 mL), and ethylenediamine (6.3
g, 0.11 mol) were placed in a three-neck round-bottomed flask
equipped with a mechanical stirrer, condenser, and thermom-
eter. Lithium wire (0.64 g, 0.091 gram-atom) was added in two
portions. Addition of one-half of the lithium gave a dark color
and the temperature rose to 42 °C. After an hour the temper-
ature began to fall and the remainder of the lithium was
added. The blue color dissipated over 45 min, the reaction
mixture was poured onto ice, and the resulting mixture was
extracted with ether. The ether was washed with brine and
distilled at atmospheric pressure. The residue was sublimed
at 90 °C (12 mm) to give 1.79 (91%) of 1-adamantanamine 14.
Redu ction of 1-Adam an tan em eth yl p-Tolu en esu lfon ate
15. Lithium (0.61 g, 0.087 gram-atom) was added to 1-ada-
mantanemethyl p-toluenesulfonate23 15 (4.0 g, 0.012 mol) in
Red u ction of n -Hep ta n a l Oxim e 23. In a 1 L three-neck
round-bottomed flask fitted with a condenser and a thermom-
(24) Dubowchik, G. M.; Padilla, L.; Edinger, K.; Firestone, R. A. J .
Org. Chem. 1996, 61, 4676-4684.
(25) Klamann, D.; Bertsch, H. Chem. Ber. 1956, 89, 2007-12.
(26) Ungnade, H. E.; McLared, A. D. J . Org. Chem. 1945, 10, 29-
33.
(27) Dong, Y.; Vennerstrom, J . L. J . Org. Chem. 1998, 63, 8582-
8585.
(22) Stetter, H.; Meyer, J .; Schwarz, M.; Wulff, K. Chem. Ber. 1960,
93, 226-230.
(23) Stetter, H.; Schwarz, M.; Hirschorn, A. Chem. Ber. 1959, 71,
429-430.