Deamination of Cyclopropylamines
J . Org. Chem., Vol. 64, No. 21, 1999 7761
14. 8 min), and cinnamyl acetate (tR ) 16.8 min). Independent
synthesis19 confirmed the assignments of the NMR spectra.
Dea m in a tion of tr a n s-2-P h en ylcyclop r op yla m in e Hy-
d r och lor id e w ith Ad d ed Sa lts. The procedure was the same
as described above. For each experiment trans-2-phenylcyclo-
propylamine hydrochloride (about 0.25 g), 2 molar equiv of
NaNO2, and a given number of molar equivalents of LiCl were
used. The range of LiCl added was between 0.5 and 2.5 molar
equiv in 0.5 unit steps. LiCl was added to the reaction solution
and completely dissolved before NaNO2 was added. The
product distributions for each reaction was recorded by
analytical GC and plotted as a function of the number of
equivalents of LiCl added.
The reactions in the presence of lithium perchlorate were
carried out in the same fashion. For each experiment a given
number of equivalents of LiClO4 were used. The range of
LiClO4 added was between 0.5 and 2.5 equiv in 0.5 unit steps.
LiClO4 was added to the reaction solution and completely
dissolved before NaNO2 was added. The product distributions
for each reaction was recorded by analytical GC.
a te. N-Nitroso-N-(trans-2-phenylcyclopropyl)urea13 (0.04 g,
2
0.18 mmol) dissolved in 2 mL of H-methanol was added to a
solution of 2H-sodium bicarbonate (1.3 molar equiv, 0.02 g, 0.24
mmol) and 2.5 equiv of sodium azide (0.03 g, 0.45 mmol) in 2
2
mL of H-methanol. The solution was stirred for 1 h during
which time the solution turned from pale yellow to clear. After
1 h, 10 mL of distilled water was added, and the aqueous layer
extracted with three 10 mL portions of dichloromethane. The
organic extract was dried over sodium sulfate and concentrated
in vacuo. The NMR spectrum of the crude product showed that
trans-2-phenylcyclopropyl azide was the only azide formed and
that the peak at 3.1 ppm (CHN3) had decreased in intensity
by 83% compared to the peak at 2.2 ppm (CHC6H5). This
indicated that 83% of the compound underwent an exchange
of protons with deuterium.
Dea m in a t ion of N-Nit r oso-N-(tr a n s-2-m et h ylcyclo-
p r op yl)u r ea in Meth a n ol. In a 10 mL round-bottomed flask
equipped with magnetic stirrer was placed 2 mL of methanol
and 0.3 g of NaHCO3 (3.6 mmol). N-Nitroso-N-(trans-2-
methylcyclopropyl)urea7 (0.06 g, 2.85 mmol) dissolved in 2 mL
of methanol was added, and the solution was stirred for 2 h.
The solution, which initially was colored yellow, turned clear
during this period. The solution was poured into a separatory
funnel, and 20 mL of water was added. The aqueous layer was
extracted with three 10 mL portions of CH2Cl2 and concen-
trated in vacuo. Analysis of the product mixture by analytical
GC (parameter set 1) and comparison of the retention times
with independently synthesized20 or authentic samples identi-
fied the compounds as 3-methoxy-but-1-ene (tR ) 2.8 min,
74.9%) and 1-methoxy-but-2-ene (tR ) 3.4 min, 25.2%).
N-(15N)Nitr oso-N-(tr a n s-2-m eth ylcyclop r op yl)u r ea . To
a cold solution (ice bath) of 1.1 g of trans-2-methylcyclo-
propylurea7 (9.6 mmol) in 17 mL of acetic acid/acetic anhydride
(7:3) was added via syringe pump 15N-sodium nitrite (1 g, 15
mmol containing 98% 15N) in 4 mL of distilled water over a
period of 1 h. After the addition was completed 100 mL of ice
water was added, and the solution was placed in an ice/sodium
chloride bath for an additional 1 h. During this period a light
yellow precipitate formed. The precipitate was collected in a
Buchner funnel by vacuum filtration and washed with ice
water. Drying under vacuum yielded 0.52 g (37%) of N-(15N)-
Nitroso-N-(trans-2-methylcyclopropyl)urea as a yellow powder
(mp ) 91-95 °C (decomp7)). Mass spectroscopic analysis (CI)
of the product showed that it contained 92% 15N label.
Dea m in a tion of tr a n s-2-Meth ylcyclop r op yla m in e Hy-
d r och lor id e. To a 10 mL round-bottomed flask equipped with
a magnetic stirrer was added 0.24 g of trans-2-methylcyclo-
propylamine hydrochloride20 (0.43 mmol) in 2 mL of glacial
acetic acid. To the solution was added 0.29 g of sodium nitrite
(0.85 mmol) in small portions over a period of 1 h. After the
addition was complete the solution was stirred for an ad-
ditional 1 h. Then, 10 mL of water and 10 mL of CH2Cl2 were
added to the solution, followed by extraction with as many 10
mL portions of saturated NaHCO3 as needed to neutralized
the acetic acid. The organic layer was dried over anhydrous
sodium sulfate, and the solvent was removed in vacuo.
Analysis of the product mixture with analytical GC (parameter
set 2) showed a 1.2:1:1 ratio of methylallyl acetate (tR ) 5.1
min), crotyl chloride (tR ) 2.9 min), and crotyl acetate (tR
)
10.0 min). The solution was concentrated to 2 mL by fractional
distillation of the solvent through a 20 cm distillation column
packed with steel wool. The remaining liquid was separated
into its components by preparative GC (column B, Tcol ) 70
°C, Tinj ) 120 °C, Tdet ) 250 °C). The retention times were tR
) 4.3 min for crotyl chloride, tR ) 6.4 min for methylallyl
acetate, and tR ) 8.5 min for crotyl acetate. NMR spectra were
recorded of all compounds and compared to the spectra
obtained from authentic samples21 to confirm the assignments.
Dea m in a tion of tr a n s-2-Meth ylcyclop r op yla m in e Hy-
d r och lor id e w ith Ad d ed Sa lts. The reactions with added
LiCl were carried out as described for the phenyl-substituted
derivatives. Methylallyl chloride was identified through isola-
tion by preparative GC. The NMR of the sample matched the
NMR taken of an authentic sample.22
Dea m in a tion of N-(15N)Nitr oso-N-(tr a n s-2-m eth ylcy-
clop r op yl)u r ea in Meth a n ol w ith Sod iu m Bica r bon a te.
N-(15N)Nitroso-N-(trans-2-methylcyclopropyl)urea (0.2 g, 1.4
mmol) dissolved in 2 mL of methanol was added to a solution
of sodium bicarbonate (1.3 molar equiv, 0.34 g, 4.0 mmol) and
6 equiv of sodium azide (0.52 g, 8.0 mmol) in 2 mL of methanol.
The solution was stirred for 1 h during which time the solution
turned from pale yellow to clear. After 1 h, 10 mL of distilled
water was added, and the aqueous layer was extracted with 3
× 10 mL portions of dichloromethane. GC analysis (parameter
Dea m in a t ion of N-Nit r oso-N-(tr a n s-2-p h en ylcyclo-
p r op yl)u r ea in Meth a n ol. In a 10 mL round-bottomed flask
equipped with magnetic stirrer was placed 2 mL of methanol
and 0.02 g of NaHCO3 (0.24 mmol). N-Nitroso-N-(trans-2-
phenylcyclopropyl)urea7 (0.027 g, 0.19 mmol) dissolved in 2
mL of methanol was added, and the solution was stirred for 2
h. The solution, which initially was colored yellow, turned clear
during this period. The solution was poured into a separatory
funnel, and 20 mL of water was added. The aqueous layer was
extracted with three 10 mL portions of CH2Cl2 and concen-
trated in vacuo. Analysis of the product mixture by analytical
GC (parameter set 1) and separation into its components by
column chromatography (10% ethyl acetate in pentane) yielded
two compounds identified as (1-methoxy-allyl) benzene (77%,
tR ) 10.3 min) and cinnamyl methyl ether (23%, tR ) 14.6
min).13
set 2) showed the presence of crotyl methoxide (20.3%, tR
)
2.6 min), 3-methoxy-but-1-ene (5.6%, tR ) 3.0 min), trans-2-
methylcyclopropyl azide (45%, tR ) 4.3 min), and cis-2-
methylcyclopropyl azide (15%, tR ) 4.8 min), as well as traces
of crotyl azide (6%, tR ) 5.2 min).
Detection of th e 15N Con ten t of th e Dea m in a tion
P r od u cts by GC/MS. The reaction solution was concentrated
to 2 mL by distilling the solvent through a 20 cm steel wool-
packed column. Preparative gas chromatography (column A)
was used to separate the ether components of the reaction
mixture from the azide-substituted products. The azide frac-
tion was collected in a U-shaped collector tube and dissolved
in 0.5 mL of dichloromethane. To determine the 15N content
of the reaction products a gas chromatograph-mass spectrom-
eter combination was used (column of analytical GC, GC
parameters: Tinj ) 150 °C, Tdet ) 70 °C, Tcol ) 30 °C, split
ratio 20/1, ionization current of the MS ) 15 eV). trans-2-
Methylcyclopropyl azide contained 89% of the 15N, cis-2-
methylcyclopropyl azide contained 76% of the 15N label, and
crotyl azide contained no 15N label. When the original 15N
Dea m in a t ion of N-Nit r oso-N-(tr a n s-2-p h en ylcyclo-
p r op yl)u r ea in 2H-Meth a n ol a n d 2H-Sod iu m Bica r bon -
(19) Surzur, J .-M.; Teissier, P. Bull. Soc. Chim. Fr. 1970, 3060.
Buchanan, D. H.; McComas, G. Tetrahedron Lett. 1980, 45, 4317.
(20) Banert, K. Chem. Ber. 1985, 118, 1564.
(21) Beckwith, A. L. J .; Zavitas, A. A. J . Am. Chem. Soc. 1986, 108,
8230. Bergstrom, D. E.; Ruthy, J . L.; Warwick, P. J . Org. Chem. 1981,
46, 1432.
(22) Araki, S.; Ohmori, K.; Butsagan, Y. Synthesis 1984, 841.