6272 J . Org. Chem., Vol. 64, No. 17, 1999
Brown et al.
chemical shifts are in δ relative to BF3‚Et2O. GC analyses were
performed on a chromatograph (catharometer) equipped with
the following columns: a 12 ft × 0.125 in. packed with 10%
SE 30 on Chromosorb W 100-120 mesh; 6 ft × 0.125 in, 15%
Carbowax 20M on Chromosorb W; 9 ft × 0.125 in, 3% OV-17
on Chromosorb-G; SPB-5 (0.25 µm × 30 m) capillary column.
Optical rotations were measured on a polarimeter. Hydride
analysis studies were carried out using the gasimeter. Micro-
analyses were performed at the Microanalytical Laboratory,
Purdue University.
tetrabutylammonium iodide (1.85 g, 5 mmol) was refluxed with
stirring for 30 h. The temperature of the mixture increased
from 53 to 78 °C. Aqueous 5.00 M potassium hydroxide (30
mL, 0.15 mmol) was added, and the mixture was extracted
with n-pentane. Three layers were formed. Adiponitrile (middle
layer) was recovered. The pentane solution was dried over
anhydrous magnesium sulfate, and tert-butylisopropylamine
was isolated by distillation: 8.18 g, (71%), bp 97-99 °C/760
mmHg.
ter t-Bu tyld ieth yla m in e 1b. Diethyl sulfate (33.9 g, 0.22
mol) was slowly added to tert-butylamine (14.62 g, 0.2 mol),
keeping the reaction mixture at reflux, and it was then stirred
for 15 min. Aqueous 8.00 M potassium hydroxide (40 mL, 0.32
mol) was added to the warm mixture. The organic layer was
separated, dried over anhydrous magnesium sulfate, and
treated with diethyl sulfate (33.9 g, 0.22 mol), followed by
heating at 120 °C for 0.5 h. The organic layer, separated after
treatment with potassium hydroxide, was heated at 120 °C
for 0.5 h. Two layers were formed. The upper layer was
separated and dried over anhydrous magnesium sulfate, and
the product was isolated by distillation: 23.0 g, (88%), bp 126-
128 °C (lit.35 chloroplatinate mp 223-225 °C, dec).
Ma ter ia ls. N-tert-Butylmorpholine,27 1a , and diisopropyl
sulfate28 were prepared according to the literature. N-tert-
Butyldiethanolamine (Fluka) and other starting amines (Al-
drich) were commercial products. All solvents were purified
according to literature procedures and stored under nitrogen.
Tetrahydrofuran and dioxane were freshly distilled from
benzophenone ketyl before use. All olefins were distilled from
a small amount of lithium aluminum hydride and stored under
nitrogen. All compounds except amides were commercial
samples and were used as obtained. Amides used in this study
were prepared following literature procedures29 and were fully
analyzed before use.
Bor a n e-Am in e Ad d u cts. Gen er a l P r oced u r e. Diborane
generated as described elsewhere30,31 was passed into a neat
amine (50 mmol) at 0 °C and placed in a bubbler provided with
a sintered glass tip and a magnetic stirring bar. Excess of
diborane not absorbed by the amine was absorbed in a
following bubbler containing tetrahydrofuran (10 mL) over
mercury and cooled in ice-water. A mercury bubbler was
connected to the exit. Diborane was passed into the amine until
the concentration of borane in the THF in the following bubbler
was ∼1.0 M. The borane-amine adduct was stirred overnight
at room temperature prior to disconnecting the bubblers and
then analyzed for active hydride by a standard procedure32
using a 2.00 M hydrochloric acid-glycerol-water (2:1:1)
hydrolysis solution.
ter t-Bu tylisobu tyla m in e 4. A mixture of tert-butylamine
(11.0 g, 0.15 mol), isobutyl bromide (13.7 g, 0.1 mol), adiponi-
trile (10.8 g, 0.1 mol), and tetrabutylammonium iodide (1.85
g, 5 mmol) was refluxed with stirring for 12 h. Aqueous 5.00
M potassium hydroxide (30 mL, 0.15 mmol) was added, and
the mixture was extracted with n-pentane. Three layers were
formed. Adiponitrile (middle layer) was recovered. The pentane
solution was dried over anhydrous magnesium sulfate, and
the product isolated by distillation: 9.56 g, (74%), bp 45-47
°C/40 mmHg.33,34
ter t-Bu tylisop r op yla m in e 5. By Alk yla tion of ter t-
Bu tyla m in e w ith Diisop r op yl Su lfa te. The mixture of tert-
butylamine (14.6 g, 0.2 mol) and diisopropyl sulfate (18.2 g,
0.1 mol) was refluxed for 1 h with stirring. The temperature
increased from 58 to 83 °C. Two phases formed. Aqueous 5.00
M potassium hydroxide (50 mL, 0.25 mol) was added. The
organic layer was separated, and the aqueous layer was
extracted with diethyl ether. The organic solutions were
combined and dried over anhydrous magnesium sulfate, and
the product was isolated by distillation: 9.55 g (83%), bp 98-
100 °C/760 mmHg (lit.8 bp 99-99.5 °C).
ter t-Bu tyld i-n -p r op yla m in e 1c. A mixture of tert-butyl-
amine (29.3 g, 0.4 mol), 1-iodopropane (51.0 g, 0.3 mol), and
glycerol (13.8 g, 0.15 mol) was refluxed for 4 h. Aqueous 8.00
M potassium hydroxide (62.5 mL, 0.5 mol) was added, and the
organic layer was separated and dried over anhydrous mag-
nesium sulfate. tert-Butylamine was removed, and crude tert-
butyl-n-propylamine, 25.1 g, 72% was obtained. It was treated
with 1-iodopropane (25.5 g, 0.15 mol) and glycerol (6.9 g, 75
mmol), and the mixture was refluxed for 6 h. The workup, as
described above, followed by distillation gave 1c: 14.4 g, (61%),
bp 62-63 °C/20 mmHg.
ter t-Bu tylbis(2-m eth oxyeth yl)a m in e 1d . Dimethyl sul-
fate (50.5 g, 0.4 mol) was added dropwise to a vigorously stirred
mixture of N-tert-butyldiethanolamine (16.1 g, 0.1 mol), dichlo-
romethane (100 mL), tetrabutylammonium bromide (3.22 g,
10 mmol), and 50% aqueous sodium hydroxide (80 g, 1 mol),
at 30-40 °C. The stirring was continued for 1 h after the
addition was completed. The organic solution was separated,
and the aqueous layer was extracted with dichloromethane.
The organic solutions were combined. GC analysis showed a
mixture of mono- and diethylated product. The methylation
was repeated using the same amounts of reagents as described
above. The dichloromethane solution after the second workup
was stirred with concentrated aqueous ammonia (50 mL) for
1 h at room temperature, separated, and dried over anhydrous
magnesium sulfate, and the product was isolated by distilla-
tion: 17.0 g, (90%), bp 42-44 °C/0.1 mmHg.
ter t-Bu tyld iisobu tyla m in e 1e. Isobutyryl chloride (10.9
g, 0.1 mol) was added to a solution of tert-butylisobutylamine
(25.9 g, 0.2 mol) in tetrahydrofuran (150 mL) at room tem-
perature and stirred for 1 h. Solids were filtered off and
washed with tetrahydrofuran. N,N-tert-Butylisobutyl-2-meth-
ylpropionamide was isolated by distillation: 18.5 g, 90%, bp
59-60 °C/1.3 mmHg.
A 1.00 M BH3-THF (150 mL, 0.15 mol) was added dropwise
to a solution of the amide (18.0 g, 90 mmol) in tetrahydrofuran
(50 mL) at room temperature, and the mixture was refluxed
for 1 h. Water was added after cooling, followed by slow
addition of 6.00 M hydrochloric acid (60 mL). Tetrahydrofuran
was distilled off, and solid sodium hydroxide (20.0 g, 0.5 mol)
was added. The organic layer was separated, and the aqueous
solution was extracted with n-pentane. The organic solutions
were combined and dried over anhydrous magnesium sulfate,
and the product was isolated by distillation: 14.2 g, (85%), bp
34-35 °C/1.5 mmHg.
By Alk yla tion of ter t-Bu tyla m in e w ith Isop r op yl Br o-
m id e. A mixture of tert-butylamine (11.0 g, 0.15 mol), isopropyl
bromide (12.3 g, 0.1 mol), adiponitrile (10.8 g, 0.1 mol), and
(26) Brown, H. C. Organic Syntheses via Boranes; Wiley-Inter-
science: New York, 1975, p 191. A reprinted edition is currently
available: Organic Syntheses via Boranes; Aldrich Chemical Co.,
Inc.: Milwaukee, WI, 1997; Vol. 1.
(27) Cook, M. J .; Katritzky, A. R.; Moreno Manas, M. J . Chem. Soc.
B 1971, 1330.
(28) Kranzfelder, A. L.; Sowa, F. J . J . Am. Chem. Soc. 1937, 59,
1491.
(29) Vogel, A. I. Practical Organic Chemistry, 5th ed.; Longman:
Essex, 1989.
(30) Reference 8, p 18.
(31) For small-scale generation of diborane, see ref 5a.
(32) Reference 26, p 241.
(33) DeKimpe, N.; Verhe, R.; DeBuyck, L.; Schamp, N. Rec. Trav.
Chim Pays-Bas 1977, 96, 242.
ter t-Bu tylisobu tylm eth yla m in e 2a . A 37% solution of
formaldehyde (6.89 g, 85 mmol) was added dropwise to a
mixture of tert-butylisobutylamine (10.0 g, 77 mmol) and 88%
formic acid (7.85 g, 0.15 mol) at room temperature. The
mixture was heated at 50-55 °C for 5 h. Aqueous 8.00 M
(34) Bu¨ttner, G.; Hu¨nig, S. Ber. 1971, 104, 1088.
(35) Reiber, H. G.; Stewart, T. D. J . Am. Chem. Soc. 1940, 62, 3026.