Synthesis of new enantiomeric 1,2-diamines containing a myrtenyl fragment

Article abstract of DOI:10.1134/S1070428007030037

Some new bi -and tridentate nitrogen-containing chiral ligands were synthesized on the basis of natural monoterpenoids, (+)-and (-)-myrtenals and (+)-myrtenol. A procedure was proposed for the synthesis of unsymmetrical ligands containing terpenoid and o-hydroxyphenyl fragments. Nauka/Interperiodica 2007.

Full text of DOI:10.1134/S1070428007030037

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 3, pp. 352–358. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © I.A. Dvornikova, L.L. Frolova, A.V. Kuchin, I.P.Beletskaya, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 3,
pp. 357–362.
Synthesis of New Enantiomeric 1,2-Diamines
Containing a Myrtenyl Fragment
I. A. Dvornikovaa, L. L. Frolovaa, A. V. Kuchina, and I. P. Beletskayab
a Institute of Chemistry, Komi Research Center, Ural Division, Russian Academy of Sciences,
ul. Pervomaiskaya 48, Syktyvkar, 167982 Russia
e-mail: dvornikova-ia@chemi.komisc.ru
b Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
Received May 10, 2006
Abstract—Some new bi- and tridentate nitrogen-containing chiral ligands were synthesized on the basis of
natural monoterpenoids, (+)- and (–)-myrtenals and (+)-myrtenol. A procedure was proposed for the synthesis
of unsymmetrical ligands containing terpenoid and o-hydroxyphenyl fragments.
DOI: 10.1134/S1070428007030037
In the recent time, nitrogen-containing ligands have
been widely used in organic synthesis, especially in
catalytic asymmetric syntheses [1]. Chiral nonracemic
1,2-diamines and their derivatives, such as 1,2-di-
imines and 1,2-diamides, are used in the alkylation of
aldehydes [2, 3], reduction of prochiral ketones [4, 5],
oxidation [6, 7], cyclopropanation [8, 9], epoxidation
[10, 11], and other reactions. In addition, vicinal di-
amines are intermediate products in the preparation of
heteroelement-containing ring systems [12] and chiral
auxiliaries in diastereoselective syntheses [13]. Sym-
metric 1,2-diamines are used for optical resolution of
racemic compounds [14, 15] and determination of
enantiomeric purity of chiral compounds by NMR
spectroscopy [15, 16]. Despite numerous known
1,2-diamines, new enantiomerically pure ligands are
extensively designed. Monoterpenoids, in particular
α-pinene and its derivatives, were reported [17–20] as
chiral reagents in asymmetric syntheses. Accessibility
of both enantiomers of these compounds with an ac-
ceptable optical purity makes it possible to obtain
promising chiral ligands on their base.
The present article reports on the synthesis of sym-
metric and several unsymmetrical diamines containing
a chiral terpene fragment. As initial terpene com-
pounds we used products of oxidation of α-pinene,
myrtenal and myrtenol. The structure of the newly
synthesized compounds was determined by 1H and 13C
NMR spectroscopy.
Diamine IV with a C2 symmetry was synthesized in
two steps. In the first step, (+)-myrtenal (II) reacted
with 0.5 equiv of ethylenediamine in benzene in the
presence of anhydrous Na2SO4 to give diimine (+)-III,
Scheme 1.
CHO
N
N
N
NH2
H2NCH2CH2NH2
PhH, Na2SO4
SeO2
+
I
II
III
11 12
10
8
NH HN
NH
NH2
1
2
NaBH4, EtOH
+
7
6
3
9
5
4
IV
V
352

SYNTHESIS OF NEW ENANTIOMERIC 1,2-DIAMINES
353
Scheme 2.
OH
Cl
NH
NH2
H2NCH2CH2NH2
MeOH
SeO2, EtOH
Ph3P, CCl4
I
VI
VII
V
(1) 2-HOC6H4CHO
(2) NaBH4, EtOH
13
NH HN
HO
14
15
VIII
and reduction of the latter with NaBH4 in ethanol
afforded 69% of diamine (1S,5R)-IV (Scheme 1). The
reaction with equimolar amounts of compound II and
ethylenediamine, apart from the major product (IV),
gave a small amount of amine V which was identified
in the reaction mixture by TLC. Dihydrochlorides of
IV and V are characterized by different solubilities, so
that they can readily be separated. Diamine (+)-IV
isolated from the corresponding dihydrochloride con-
tained no impurity of V. In the 13C NMR spectrum
of IV we observed 11 signals; this suggests that the
reaction is stereoselective (only one stereoisomer is
formed). Likewise, from (–)-myrtenal we obtained the
corresponding (1R,5S)-diamine.
Diamine (+)-V was synthesized by reaction of (+)-VII
with 20 equiv of ethylenediamine in methanol at 60°C.
After purification by column chromatography, the
yield of (+)-V was 77%.
Compound V can be used as chiral intermediate for
the design of unsymmetrical ligands having different
substituents on the nitrogen atoms. The possibility for
varying electronic and steric properties of these sub-
stituents gives rise to extended scope of application
and enhanced efficiency of catalysts derived from the
ligands thus obtained. The second substituent can be
introduced using, e.g., salicylaldehyde. By condensa-
tion of compound V with salicylaldehyde, followed by
reduction with sodium tetrahydridoborate, we obtained
tridentate ligand VIII containing phenol and terpene
fragments (Scheme 2).
We previously [21] described an analogous reaction
with a terpene ketone, 2-hydroxypinan-3-one. Insofar
as ketones react with 1,2-diamines much more dif-
ficultly, the major product in the reaction with a large
excess of ethylenediamine was the corresponding
monoimine. In the reaction with aldehydes, initially
formed monoimine reacts with the second aldehyde
molecule at a considerably higher rate than does the
initial diamine. In this case, an appreciable amount of
the corresponding diimine may be formed. In fact, the
reaction of myrtenal with ethylenediamine even at
a ratio of 1:20 gave (after chromatographic separation)
29% of monosubstituted amine V and 43% of disub-
stituted amine IV.
We have synthesized compound X as an analog of
the known inhibitor of multidrug-resistant tumor cells,
SDB-Ethylenediamine [23, 24], in which the open-
chain isoprenoid component is replaced by a bicyclic
isoprenoid residue. As starting compound we used
myrtenyl chloride prepared from α-pinene with an op-
tical purity of ~40%. Analogous N,N'-disubstituted di-
amines are also used in asymmetric catalysis [25–27];
therefore, enantiomerically pure unsymmetrical di-
amine X attracts interest as ligand for metal-complex
catalysts.
With a view to obtain mainly monoalkylated deriv-
ative X, the reaction was performed with 4 equiv of
N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine. After
separation by column chromatography, the yield of
unsymmetrical diamine X was 60% (Scheme 3). The
13C NMR spectrum of X contained 30 signals, for
carbon atoms in the two aromatic fragments are non-
Unsymmetrical diamine V was synthesized by
alkylation of ethylenediamine with the corresponding
halogen derivative. The starting compound was
(+)-myrtenol (VI) which was obtained by oxidation of
(+)-α-pinene (I) with selenium(IV) oxide. (+)-Myr-
tenyl chloride (VII) was prepared by treatment of VI
with triphenylphosphine in carbon tetrachloride fol-
lowing a procedure analogous to that described in [22].
1
equivalent. In the H NMR spectrum of X, signals
belonging to protons in the aromatic and terpene
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 3 2007

DVORNIKOVA et al.
354
Scheme 3.
8
3
4
7
9
2
10
12 11
5
Cl
6
13
14
NH HN
NH
N
13'
14'
1
19'
19
15
18'
17'
18
15'
16'
17
16
MeO
OMe
MeO
OMe
MeO
OMe
MeO
OMe
IX
X
N
N
+
MeO
OMe
MeO
OMe
NH
N
HCl
X
·2HCl
MeO
OMe
MeO
OMe
XI
The purity of initial compounds was checked by GLC
on a Ktistall-2000M chromatograph equipped with
an HP-5MS quartz capillary column, 60000×0.25 mm,
and a flame ionization detector; carrier gas helium.
The progress of reactions and the purity of products
were monitored by TLC on Silufol and Sorbfil plates
using hexane–diethyl ether (0 to 50% of the latter) and
chloroform–methanol–concentrated aqueous ammonia
(100:10:1) as eluents; spots were visualized by treat-
ment with a solution of vanillin or ninhydrin, followed
by heating to 100–120°C, and with a solution of
Bromocresol Purple.
moieties were present. The signal intensity ratio for the
aromatic and methyl protons confirmed the structure of
X as monoalkylated product. The NH signal appeared
as a broadened singlet at δ 1.76 ppm.
Preliminary tests showed that the newly synthe-
sized ligands are capable of forming complexes with
various metal ions; therefore, they can be used as
chiral ligands in asymmetric syntheses. Compound V
is promising from the viewpoint of obtaining unsym-
metrical ligands via reactions with various electro-
philic reagents.
(1S,5R)-(+)-Myrtenal (II), [α]D = +13.3° (neat), and
(1R,5S)-(–)-myrtenal, [α]D = –10.7° (neat), were pre-
pared by oxidation of (1R,5R)-(+)-α-pinene (I), [α]D =
+42° (neat), and (1S,5S)-(–)-α-pinene, [α]D = –42°
(neat), respectively, with an equimolar amount of sele-
nium dioxide. Ethylenediamine was boiled and then
distilled over metallic sodium.
EXPERIMENTAL
The H and 13C NMR spectra were recorded on
1
a Bruker AM spectrometer at 400.13 and 100.61 MHz,
respectively, using CDCl3 as solvent; the chemical
shifts were measured relative to the solvent signals
(δ 7.24 ppm, δC 77.00 ppm). Signals were assigned on
the basis of the J-modulation 13C NMR spectra and
13C–1H heteronuclear correlation spectra (HETCOR).
The IR spectra were obtained on a Specord M-80
spectrometer. The melting points were determined on
a Kofler hot stage. The specific rotations were
measured at 22°C using a circular CM-3 polarimeter.
N,N'-Bis{[(1S,5R)-6,6-dimethylbicyclo[3.1.1]-
hept-2-en-2-yl]methylidene}ethane-1,2-diamine
(III). A solution of 1.46 g (9.72 mmol) of (1S,5R)-(+)-
myrtenal (II) and 0.29 g (4.86 mmol) of ethylenedi-
amine in 15 ml of anhydrous benzene was stirred for
9 h at room temperature in the presence of 9 g of
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SYNTHESIS OF NEW ENANTIOMERIC 1,2-DIAMINES
355
anhydrous sodium sulfate. The mixture was filtered,
the precipitate was washed with benzene, and the
solvent was removed from the filtrate under reduced
pressure to isolate 1.53 g (97%) of diimine III. Yellow
semicrystalline material, [α]D = –13.7° (c = 6.3,
CHCl3). IR spectrum (film), ν, cm–1: 1638 (C=N),
for compound IV. Yield 72%, [α]D = –34.5° (c = 1.6,
EtOH); dihydrochloride: colorless crystals, mp 221°C
(from EtOH; decomp.), [α]D = –33.5° (c = 1.2, H2O).
b. Compounds IV and V (reaction with excess
ethylenediamine). A solution of 3.11 g (20.7 mmol) of
(+)-myrtenal (II) and 24.9 g (414.1 mmol) of
ethylenediamine in 30 ml of anhydrous benzene was
stirred for 9 h at room temperature in the presence of
anhydrous sodium sulfate. The inorganic salt was
filtered off and washed with benzene, and the solvent
and excess ethylenediamine were removed from the
filtrate under reduced pressure. The residue, 3.69 g of
a mixture of imines, was dissolved in 50 ml of ethanol,
the solution was added dropwise to a solution of 0.73 g
of NaBH4 in 30 ml of ethanol, and the mixture was
stirred for 1 h on heating. The mixture was cooled,
diluted with water, treated with a 5% solution of
NaOH, and extracted with chloroform. The extract was
washed with a saturated aqueous solution of sodium
chloride and dried over K2CO3, the solvent was re-
moved under reduced pressure, and the residue, 3.65 g
of mixture IV/V, was separated by column chromatog-
raphy on silica gel (100–250 μm; gradient elution with
chloroform–methanol, 1 to 30% of the latter) to isolate
1.57 g (43%) of compound IV and 1.06 g (29%) of V.
1
1620 (C=C). H NMR spectrum, δ, ppm: 0.74 s (6H,
CH3), 1.05 d (2H, 7-Hβ, J = 8.89 Hz), 1.30 s (6H,
CH3), 2.12 m (2H, 5-H), 2.36–2.45 m (6H, 4-H, 7-Hα),
2.89 m (2H, 1-H), 3.70 s (4H, 11-H), 5.92 m (2H,
13
3-H), 7.65 s (2H, 10-H). C NMR spectrum, δC, ppm:
20.84 (C9), 25.80 (C8), 31.13 (C4), 32.21 (C7), 37.49
(C6), 39.83 (C5), 40.78 (C1), 60.94 (C11), 134.31
(C3), 147.85 (C2), 163.91 (C10). Found, %: C 81.29;
H 10.30; N 8.59. C22H32N2. Calculated, %: C 81.43;
H 9.94; N 8.63.
N,N'-Bis{[(1S,5R)-6,6-dimethylbicyclo[3.1.1]-
hept-2-en-2-yl]methyl}ethane-1,2-diamine (IV).
a. A solution of 1.53 g (4.71 mmol) of diimine III in
22 ml of ethanol was added under stirring to a solution
of 0.36 g (9.43 mmol) of NaBH4 in 16 ml of anhydrous
ethanol. The mixture was stirred for 0.5 h on heating,
cooled, diluted with 20 ml of water, treated with a 5%
solution of sodium hydroxide, and extracted with
chloroform. The extract was washed with a saturated
aqueous solution of NaCl and dried over K2CO3, and
the solvent was removed under reduced pressure. The
residue, 1.54 g, was dissolved in diethyl ether, and
a 2 M solution of hydrogen chloride in alcohol was ad-
ded to obtain dihydrochloride IV·2HCl. Yield 1.46 g
(78%), colorless crystals, mp 220°C (from ethanol;
decomp.), [α]D = +28.3° (c = 1.0, EtOH). Found, %:
C 65.50; H 9.33; N 6.98. C22H36N2·2HCl. Calculated,
%: C 65.82; H 9.54; N 6.98.
(1S,5R)-(6,6-Dimethylbicyclo[3.1.1]hept-2-en-3-
yl)methanol [VI, (+)-myrtenol]. A solution of 33 g
(0.3 mol) of selenium dioxide in 50 ml of ethanol was
added over a period of 1 h under stirring to 68 g
(0.5 mol) of (+)-α-pinene (I) heated to 70–75°C, and
the mixture was then stirred for 2 h at that temperature.
The mixture was cooled, the precipitate of selenium
was filtered off, and the filtrate was subjected to steam
distillation to remove volatile products. The organic
phase was separated and dried over anhydrous MgSO4.
We thus obtained 44.2 g (65%) of a mixture containing
(according to the GLC data), 16% of unreacted
α-pinene (I), 29% of myrtenol (VI), and 35% of
myrtenal (II). This mixture was added under stirring to
a solution of 1.9 g (0.05 mol) of NaBH4 in 100 ml of
ethanol, and the mixture was stirred until compound II
disappeared (TLC). Dilute hydrochloric acid was
added to the mixture to decompose excess NaBH4, and
the mixture was diluted with water and extracted with
diethyl ether. The extract was washed with water, dried
over MgSO4, and the residue, 38.5 g (87%) of a mix-
ture containing 63% of pyrtenol (GLC), was separated
by fractional distillation under reduced pressure. Yield
of (+)-myrtenol (VI) 21.8 g (32%, calculated on the
Diamine IV (base). Slightly yellowish viscous
material, yield 1.11 g (69%, calculated on the initial
aldehyde), [α]D = +34.6° (c = 3.8, EtOH). IR spectrum
1
(film), ν, cm–1: 3320 (N–H), 1665 (C=C). H NMR
spectrum, δ, ppm: 0.84 s (6H, CH3), 1.17 d (2H, 7-Hβ,
J = 8.5 Hz), 1.28 s (6H, CH3), 1.42 br.s (2H, NH),
2.09 m (4H, 1-H, 5-H), 2.18–2.31 m (4H, 4-H),
2.38 d.t (2H, 7-Hα, J = 8.5, J = 5.6 Hz), 2.69 m (4H,
11-H), 3.11 m (4H, 10-H), 5.36 m (2H, 3-H). 13C NMR
spectrum, δC, ppm: 21.06 (C9), 26.24 (C8), 31.19 (C4),
31.62 (C7), 38.00 (C6), 40.99 (C5), 44.42 (C1), 48.82
(C11), 54.73 (C10), 117.31 (C3), 146.81 (C2).
N,N'-Bis{[(1R,5S)-6,6-dimethylbicyclo[3.1.1]-
hept-2-en-2-yl]methyl}ethane-1,2-diamine was syn-
thesized from (1R,5S)-(–)-myrtenal as described above
initial α-pinene), bp 103–105°C (13 mm); nD20
=
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 3 2007

DVORNIKOVA et al.
356
1.4960, [α]D = +48.5° (c = 14.8, EtOH); published data
[28]: [α]D = +44.3° (c = 3.21, CHCl3). IR spectrum
IR spectrum (film), ν, cm–1: 3300 br (N–H), 1665
(C=C). H NMR spectrum, δ, ppm: 0.84 s (3H, CH3),
1
1
(film), ν, cm–1: 3350 (O–H), 1660 (C=C). H NMR
1.17 d (1H, 7-Hβ, J = 8.5 Hz), 1.28 s (3H, CH3),
1.59 br.s (3H, NH, NH2), 2.09 m (2H, 1-H, 5-H), 2.17–
2.32 m (2H, 4-H), 2.38 d.t (1H, 7-Hα, J = 8.5, J =
5.6 Hz), 2.63–2.66 m (2H, 11-H), 2.78–2.81 m (2H,
12-H), 3.12 m (2H, 10-H), 5.37 m (1H, 3-H).
13C NMR spectrum, δC, ppm: 21.01 (C9), 22.60 (C8),
31.13 (C4), 31.56 (C7), 37.96 (C6), 40.92 (C5), 41.68
(C12), 44.38 (C1), 51.87 (C11), 54.60 (C10), 117.40 (C3),
146.65 (C2). Dihydrochloride V·2HCl, mp 200–202°C
(from propan-2-ol; decomp.), [α]D = +18.6° (c = 1.8,
ethanol). Found, %: C 53.68; H 8.94; N 10.34.
C12H22N2 ·2HCl. Calculated, %: C 53.93; H 9.05;
N 10.48.
spectrum, δ, ppm: 0.82 s (3H, CH3), 1.17 d (1H, 7-Hβ,
J = 8.7 Hz), 1.28 s (3H, CH3), 1.84 br.s (1H), 2.11 d.d
(2H, J = 1.1, J = 5.6 Hz), 2.26 m (2H), 2.39 m (1H),
3.96 m (2H, 10-H), 5.45 t (1H, 3-H, J = 1.2 Hz).
13C NMR spectrum, δC, ppm: 21.1 (C9), 26.2 (C8), 31.1
(C7), 31.6 (C4), 37.9 (C6), 41.0 (C5), 43.4 (C1), 65.9
(C10), 117.7 (C3), 147.9 (C2).
(1S,5R)-2-(Chloromethyl)-6,6-dimethylbicyclo-
[3.1.1]hept-2-ene [VII, (+)-myrtenyl chloride].
A solution of 2.28 g (14.98 mmol) of (+)-myrtenol
(VI) and 4.32 g (16.47 mmol) of triphenylphosphine in
16 ml of carbon tetrachloride was heated for 6 h under
reflux. The mixture was cooled to room temperature,
the precipitate of triphenylphosphine oxide was filtered
off and washed with hexane, the solvent was removed
from the filtrate under reduced pressure, hexane was
added to the residue, and the precipitate of Ph3PO was
filtered off again. The filtrate was partially evaporated,
and the residue was passed through a thin layer of
silica gel. Removal of the solvent gave 2.15 g (84%) of
compound VII as a colorless oily liquid, nD20 = 1.4952,
[α]D = +37.9° (c = 3.1, EtOH; published data [29]:
nD20 = 1.4954. IR spectrum (film), ν, cm–1: 1665 (C=C),
(1S,5R)-2-{2-(6,6-Dimethylbicyclo[3.1.1]hept-2-
en-2-ylmethylamino)ethylaminomethyl}phenol
(VIII). A solution of 0.3 g (1.54 mmol) of diamine V
and 0.19 g (1.54 mmol) of salicylaldehyde in 5 ml of
anhydrous methanol was stirred for 6 h at ~20°C. The
solvent was removed under reduced pressure, the
residue, 0.46 g, was dissolved in 10 ml of ethanol, the
resulting solution was added dropwise to a solution of
0.12 g of NaBH4 in 5 ml of ethanol, and the mixture
was stirred for 1 h on heating. The mixture was cooled,
diluted with water, treated with a 5% solution of
sodium hydroxide, and extracted with chloroform. The
organic extract was washed with a saturated aqueous
solution of sodium chloride and dried over K2CO3, the
solvent was removed under reduced pressure, the
residue was treated with diethyl ether, and the colorless
precipitate was filtered off. Yield 0.27 g (59%),
mp 107–109°C, [α]D = +14.4° (c = 0.4, CHCl3). IR
spectrum (KBr), ν, cm–1: 3430, 3300, 2917,1665, 1582,
1
705 (C–Cl). H NMR spectrum, δ, ppm: 0.83 s (3H,
CH3), 1.17 d (1H, 7-Hβ, J = 8.0 Hz), 1.30 s (3H, CH3),
2.07–2.55 m (5H), 3.96 m (2H, 10-H), 5.59 m (1H,
3-H). 13C NMR spectrum, δC, ppm: 21.42 (C9), 26.42
(C8), 31.54 (C4), 31.84 (C7), 38.34 (C6), 40.95 (C5),
44.76 (C1), 48.16 (C10), 122.22 (C3), 144.67 (C2).
N-{[(1S,5R)-6,6-Dimethylbicyclo[3.1.1]hept-2-en-
2-yl]methyl}ethane-1,2-diamine (V). A solution of
1.51 g (8.85 mmol) of compound VII and 10.63 g
(176.93 mmol) of ethylenediamine in 30 ml of metha-
nol was stirred for 3 h at 55–60°C. The solvent and
most part of excess ethylenediamine were removed
under reduced pressure, the residue was treated with
2 M hydrochloric acid, the resulting solution was
washed with diethyl ether, and the organic extracts
were discarded. The aqueous phase was treated with
a 5% solution of sodium hydroxide and extracted with
diethyl ether. The extract was washed with a saturated
aqueous solution of sodium chloride and dried over
K2CO3, the solvent was removed under reduced pres-
sure, and the residue was subjected to chromatography
on silica gel (gradient elution with chloroform–
methanol, 1 to 30% of the latter). Yield 1.32 g (77%),
yellowish oily liquid, [α]D = +23.9° (c = 5.3, EtOH).
1
1489, 1420, 1264, 758. H NMR spectrum, δ, ppm:
0.83 s (3H, CH3), 1.15 d (1H, 7-Hβ, J = 8.6 Hz), 1.28 s
(3H, CH3), 2.07–2.09 m (2H, 1-H, 5-H), 2.19–2.31 m
(2H, 4-H), 2.38 d.t (1H, 7-Hα, J = 8.5, J = 5.6 Hz),
2.71–2.78 m (4H, 11-H, 12-H), 3.10 m (2H, 10-H),
4.00 s (2H, 13-H), 5.35 m (1H, 3-H), 6.76 t.d (1H,
H
arom, J = 7.6, J = 1.2 Hz), 6.82 d (1H, Harom, J =
8.0 Hz), 6.98 d (1H, Harom, J = 6.8 Hz), 7.14 t.d (1H,
Harom, J = 7.8, J = 2.0 Hz). 13C NMR spectrum, δC,
ppm: 21.09 (C9), 26.23 (C8), 31.21 (C4), 31.64 (C7),
38.04 (C6), 40.95 (C5), 44.35 (C1), 47.88 (C12), 48.13
(C11), 52.53 (C13), 54.58 (C10), 116.35 (CHarom), 117.91
(C3), 118.86 (CHarom), 122.59 (C14), 128.26 (CHarom),
128.60 (CHarom), 146.48 (C2), 158.35 (C15). Found, %:
C 73.20; H 9.00; N 9.00. C19H28N2O. Calculated, %:
C 75.96; H 9.39; N 9.32.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 3 2007

SYNTHESIS OF NEW ENANTIOMERIC 1,2-DIAMINES
357
XI in diethyl ether. Yield 1.03 g (72%), colorless
amorphous substance. Found, %: C 63.10; H 7.47;
N 4.76. C30H42N2O4·2HCl. Calculated, %: C 63.48;
H 7.81; N 4.94.
N,N'-Bis(3,4-dimethoxybenzyl)ethane-1,2-di-
amine (IX) was synthesized from 3,4-dimethoxybenz-
aldehyde and ethylenediamine in the presence of
NaBH4 according to the known procedure [30]. After
recrystallization from diethyl ether, yield 72%. 1H NMR
spectrum, δ, ppm: 1.65 br.s (2H, NH), 2.76 s (4H,
CH2), 3.72 s (4H, CH2), 3.86 s and 3.87 s (6H each,
OCH3), 6.79–6.87 m (6H, Harom). 13C NMR spectrum,
δC, ppm: 48.72, 53.66, 55.74, 55.84, 110.92, 111.27,
120.07, 133.08, 147.90, 148.87.
This study was performed under financial support
by the INTAS International Research Center (grant
no. 99-1541) and by the Russian Foundation for Basic
Research (project no. 00-03-40139)
REFERENCES
N,N'-Bis(3,4-dimethoxybenzyl)-N-(6,6-dimethyl-
bicyclo[3.1.1]hept-2-en-2-ylmethyl)ethane-1,2-di-
amine (X). A solution of 0.72 g (4.2 mmol) of com-
pound VII in 30 ml of methanol was added dropwise
over a period of 2.5 h to a solution of 6.08 g
(16.9 mmol) of diamine IX in 30 ml of methanol under
stirring at room temperature. The mixture was heated
to 60°C and stirred for 4 h at that temperature. The sol-
vent was removed under reduced pressure, the residue
was dissolved in chloroform, and the solution was
treated with a saturated aqueous solution of K2CO3.
The aqueous phase was extracted with chloroform, the
organic extracts were dried over K2CO3 and evaporat-
ed under reduced pressure, the residue was treated with
hexane, and (after a time) the precipitate of unreacted
diamine IX was filtered off. The hexane solution was
evaporated, and the residue, 1.96 g, containing reaction
products and a small amount of the initial diamine was
subjected to column chromatography on silica gel
using chloroform and chloroform–methanol (100:1) as
eluents. Yield 1.33 g (68%). Colorless oily substance.
IR spectrum (film), ν, cm–1: 3320, 2944, 2840, 1660,
1612, 1596, 1520, 1468, 1422, 1368, 1266, 1238, 1158,
1112, 1032, 810, 758, 668. 1H NMR spectrum, δ, ppm:
0.82 s (3H, CH3), 1.17 d (1H, 7-Hβ, J = 8.5 Hz), 1.27 s
(3H, CH3), 1.79 br.s (1H, NH), 2.10 m (1H), 2.20–
2.31 m (3H), 2.35–2.40 m (1H), 2.46–2.52 m (1H),
2.59–2.73 m (3H), 2.86–2.96 m (2H), 3.35 d (1H, J =
13.6 Hz), 3.55–3.60 m (3H), 3.76 s (3H, OCH3), 3.85 s
(3H, OCH3), 3.86 s (3H, OCH3), 3.87 s (3H, OCH3),
5.42 br.s (1H, =CH–CH2), 6.75–6.84 m (6H, Harom).
13C NMR spectrum, δC, ppm: 21.16 (CH3); 26.38
(CH3); 31.39 (C4); 31.82 (C7); 37.97 (C6); 40.91 (C5);
44.48 (C1); 46.87 (C12); 53.23, 53.79 (C13, C13'); 55.62,
55.85, 55.91, 55.95 (OCH3); 58.14, 60.24 (C11, C10);
110.82, 111.01 (C15, C15'); 111.41, 111.77 (C18, C18');
119.97, 120.07, 120.72 (C19, C19', C3); 132.66, 133.27
(C14, C14'); 146.37 (C2); 147.87, 147.96 (C17, C17');
148.86, 148.95 (C16, C16'). Dihydrochloride XI·2HCl
was obtained by adding a 2 N solution of hydrogen
chloride in alcohol to a solution of 1.25 g of diamine
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