Oxidative Nꢀnitration of secondary amines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
2045
(5.5 g, 58%) was obtained as a light yellow oil, b.p. 78—80 °C
(0.5 Torr) (b.p. 95—100 °C (1.5 Torr)18) and m.p. 7—8 °C.
1H NMR spectrum (CDCl3, δ): 1.49 (br.s., 1 H, NH); 2.42
(t, 4 H, CH2—CO, J = 6.6 Hz); 2.81 (t, 4 H, CH2—N, J = 6.6 Hz);
3.59 (s, 6 H, OMe).
The mechanism of formation of Nꢀnitrosoamines 4 in
the oxidative nitration reaction remains unclear. Accuꢀ
mulation of AcOH in the presence of NaNO2 and secondꢀ
ary amine (see Scheme 2) is not the reason for formation of
Nꢀnitrosoamines 4, since the addition of 2 equiv. of Et3N
or NaOH to the reaction mixture has virtually no effect on
the products ratio. The substitution of PhIO for PhI(OAc)2
in the reaction with amine 1d in MeOH virtually does not
change the ratio of the nitration (3d) and nitrosation (4d)
products, although it results in a fivefold decrease in the
total yield of the products.
It can be suggested that both Nꢀnitroamines 3 and
Nꢀnitrosoamines 4 are the decomposition products of the
same intermediate complex B and are formed upon cleavꢀ
age of the I—O or N—O bonds, respectively. In the case of
intramolecular nitration reaction, the process is analoꢀ
gous to the presumed mechanism of oxidative Cꢀnitration
(see Scheme 1). However, this process can be intermolecꢀ
ular as well.
Reaction of 1d with MNO2 (M = Na, K, Li, Ag) and PhI(OAc)2
(general procedure). Solutions (each component in 1.0 mL solꢀ
vent) of MNO2 (0.33 mmol), 1d (0.30 mmol), and PhI(OAc)2
(0.33 mmol) were mixed in the mentioned order at 0—5 °C and
stirred under these conditions for 30 min. The solvent was evapꢀ
orated at 25—30 °C, the residue was extracted with CDCl3
(0.8 mL). 1H NMR spectrum of the sample obtained was recordꢀ
ed. The yields and the products ratios are given in Table 1.
Reactions of secondary amines 1a—e with sodium nitrite in
the presence of PhI(OAc)2 (general procedure). A solution of
PhI(OAc)2 (1.65 g, 5 mmol) in MeOH (15 mL) was added over
5 min to a solution of secondary amine 1a—e (5 mmol) and
NaNO2 (0.35 g, 5 mmol) in MeOH (15 mL) under cooling with
ice water and stirring. After 30 min, the reaction mixture was
concentrated in vacuo. The residue was mixed with water
(10 mL), extracted with CH2Cl2 (3×20 mL), the extracts were
dried (Na2SO4) and concentrated in vacuo. The products were
isolated by preparative chromatography (ethyl acetate). The
yields and the products ratio are given in Table 2.
Scheme 4
NꢀNitrobis(2ꢀmethoxycarbonylethyl)amine (3c). 1H NMR
spectrum (CDCl3, δ, J/Hz): 2.77 (t, 4 H, CH2—N, J = 6.5); 3.70
(s, 6 H, OMe), 4.05 (t, 4 H, CH2—CO, J = 6.5). M.p. 57—58 °C
(MeOH) (m.p. 60—61 °C (MeOH)).19
1H NMR spectra of Nꢀbenzylidenebenzylamine (5),10 Nꢀnitroꢀ
diethylamine (3а),20 Nꢀnitrosodiethylamine (4а),21 Nꢀnitromorꢀ
pholine (3е),20 and Nꢀnitrosomorpholine (4е)22 are identical to
those of authentic samples obtained according to the procedures
described in literature. 1H NMR spectra of Nꢀnitrobis(2ꢀcyanoꢀ
ethyl)amine (3d), Nꢀnitrosobis(2ꢀmethoxycarbonylethyl)amine
(4c), and Nꢀnitrosobis(2ꢀcyanoethyl)amine (4d) are given below.
NꢀNitrosobis(2ꢀmethoxycarbonylethyl)amine (4c). A solution
of NaNO2 (0.42 g, 6 mmol) in water (1 mL) was added to
a solution of 1c (0.94 g, 5 mmol) in AcOH (1 mL) and water
(4 mL) under cooling with ice water and stirring. The reaction
mixture was stirred under the same conditions for 1 h, then
extracted with CH2Cl2 (3×20 mL). The extract was washed with
water, dried (Na2SO4), and concentrated in vacuo. NꢀNitrosoꢀ
bis(2ꢀmethoxycarbonylethyl)amine (4с) (0.83 g, 77%) was obꢀ
tained as a light yellow oil. Found (%): C, 44.20; H, 6.74;
N, 12.15. C8H14N2O5. Calculated (%): C 44.04; H, 6.42;
N, 12.80. 1H NMR spectrum (CDCl3, δ, J/Hz): 2.53 (t, 2 H,
cisꢀCH2—N, J = 6.5); 2.85 (t, 2 H, cisꢀCH2—CO, J = 6.5); 3.66
(s, 3 H, cisꢀOMe), 3.68 (s, 3 H, transꢀOMe), 3.78 (t, 2 H,
transꢀCH2—CO, J = 7.0); 4.43 (t, 2 H, transꢀCH2—N, J = 7.0).
13C NMR spectrum (СDCl3, δ): 30.5 (cisꢀCH2—N), 33.4
(transꢀCH2—N), 40,8 (cisꢀCH2—CO), 48.7 (transꢀCH2—CO),
51.8 (cisꢀOCH3), 51.9 (transꢀOCH3), 171.0 (cisꢀCO), 171.5
(transꢀCO). Mass spectrum, m/z: 218 [M+].
Experimental
1
H, 13C, and 14N NMR spectra were recorded on a Bruker
AMꢀ300 spectrometer with operating frequencies 300.13, 75.5,
and 21.5 MHz, respectively. Chemical shifts are given relative to
SiMe4 (1H and 13C) or PhNO2 14N, external standard). Mass
(
spectra were registered on a Kratos MSꢀ30 instrument (EI,
70 eV). The reaction course was monitored by TLC (Merck 60
F254), silica gel (Chemapol Silica gel L 100/160) was used for
preparative thinꢀlayer chromatography. PhI(OAc)2 (98%, Aldꢀ
rich) was used as purchased. NꢀNitrobis(2ꢀcyanoethyl)amine
(3d),13 bis(2ꢀcyanoethyl)amine (1d),14 tetraethylammonium niꢀ
trite,15 and iodosobenzene16 were obtained according to known
procedures.
Compounds 3d, 4c, and 4d, whose 1H NMR spectra have
not been described in the literature, were synthesized by indeꢀ
pendent methods and used as standards for a comparison of
1H NMR spectra in the identification of the analogous products.
Dimethyl iminodipropionate (1c). A solution of K2CO3 (3.50 g,
0.025 mol) in water (10 mL) was added to a solution of dimethyl
iminodipropionate hydrochloride17 (11.27 g, 0.05 mol) in water
(20 mL). The mixture was extracted with CH2Cl2 (3×20 mL),
the extracts were dried (Na2SO4) and concentrated in vacuo at
35—40 °C. The residue was distilled in vacuo. Compound 1с
NꢀNitrobis(2ꢀcyanoethyl)amine (3d). Obtained according to
the known procedure.13 M.p. 53—54 °C (54—55 °C13). 1H NMR
spectrum (CDCl3, δ): 2.89 (t, 4 H, CH2—N, J = 7.9 Hz); 4.14
(t, 4 H, CH2—СN, J = 7.9 Hz).
NꢀNitrosobis(2ꢀcyanoethyl)amine (4d). A solution of NaNO2
(0.83 g, 12 mmol) in water (2 mL) was added to a solution of
bis(2ꢀcyanoethyl)amine (1d)14 (1.23 g, 10 mmol) in AcOH
(2 mL) and water (8 mL) under cooling with ice water and stirꢀ