Synthesis of 1,2-diamine ligands based on natural monoterpenoids

Article abstract of DOI:10.1134/S1070428011080021

New nitrogen-containing chiral ligands were synthesized containing terpene fragments of pinane and camphane structure.

Full text of DOI:10.1134/S1070428011080021

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 8, pp. 1130−1138. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © I.A. Dvornikova, E.V. Buravlev, L.L. Frolova, Yu.V. Nelyubina, I.Yu. Chukicheva, A.V. Kuchin, 2011, published in Zhurnal Organicheskoi
Khimii, 2011, Vol. 47, No. 8, pp. 1116−1123.
Synthesis of 1,2-Diamine Ligands Based
on Natural Monoterpenoids
I. A. Dvornikovaa, E. V. Buravleva, L. L. Frolovaa, Yu. V. Nelyubinab,
I. Yu. Chukichevaa, and A. V. Kuchina
aInstitute of Chemistry, Komi Scientific Center, Ural Division, Russian Academy of Sciences, Syktyvkar,167982 Russia
e-mail: dvornikova-ia@chemi.komisc.ru
bNesmeyanov Institute of Organoelemental Compounds, Russian Academy of Sciences, Moscow
Received August 4, 2010
Abstract—New nitrogen-containing chiral ligands were synthesized containing terpene fragments of pinane and
camphane structure.
DOI: 10.1134/S1070428011080021
Enantiomerically pure 1,2-diamines and their
derivatives are widely used as efficient chiral reagents
and ligands in numerous asymmetrical processes [1–3].
The research directed to the creation of new vicinal
diamines in the enantiomerically pure form is topical.
In various enantioselective syntheses available optically
active monoterpernoids are utilized. Today bicyclic
monoterpene derivatives are applied as chiral synthons
in the preparation of ligands for various catalysts. Several
types of ligands, combining 1,2-diamine and terpene
fragments in their molecules found application in the
asymmetrical synthesis, for instance bisamines [4, 5],
bispyridines [6–8], sulfonamides [9, 10], hydroxyamides
[11].
In the 1H NMR spectrum of compound IIb containing a
cyclohexane fragment the signal of protons of the C4H2
appeared as two doublets at 2.53 and 2.71 ppm.
Monoimine (1R,2R,5R)-(IV) was prepared by treating
ketol I with excess ethylenediamine along procedure
[12]. The structure of compound IV was proved by XRD
analysis of the single crystal of (1S,2S,5S)-enantiomer
(see the figure). Geometric parameters of the molecule
fell in the range of values characteristic for this class
compounds [12, 13]. The main distinction consists in
the cisoid position of the NH2 with respect to the N1=C2
We report here on the synthesis of several new
substituted 1,2-diamines containing chiral terpene
fragments of pinane and bornane structures.As the initial
compound of the pinane structure the oxidation product
of (–)-α-pinene, (1R,2R,5R)-2-hydroxy-3-pinanone (I)
was chosen.
Symmetric diiminodiols IIa, IIb were obtained by
the reaction of ketone I with ethylenediamine or (R,R)-
cyclohexane-1,2-diamine at heating in benzene in the
presence of F3B·OEt2 (Scheme 1). In the IR spectra of
imines IIa, IIb a strong band is observed in the region
1643–1653 cm–1 corresponding to the stretching vibrations
of the C=N bond. The 13C and 1H NMR spectra confirm
the structure and the C2-symmetry of compounds IIa, IIb.
General appearance of (1S,2S,5S)-3-[(2-aminoethyl)imino]-
2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol (+)-(IV) with atoms
represented by ellipsoids of thermal oscillations of 50%
probability.
1130

SYNTHESIS OF 1,2-DIAMINE LIGANDS
1131
Crystallographic data and parameters of XRD experiment
for (1S,2S,5S)-3-[(2-aminoethyl)imino]-2,6,6-trimethylbi-
the crystal by weak van der Waals forces (C–H···H–C)
with the formation of a three-dimensional framework.
cyclo[3.1.1]heptan-2-ol (+)-(IV)
In the catalytic asymmetric synthesis chiral nitrogen-
containing ligands based on optically active 1,2-diamines
and substituted salicylaldehydes (diimines and diamines)
are effectively used. These ligands may be symmetric,
containing two identical salicylaldehyde moieties on
the both sides of the diamine, or unsymmetrical. In the
unsymmetrical ligands of this type the second substituent
may be another derivative of the salicylaldehyde, or
a compound of another class. The presence in the ligand
of two substituents with different properties makes it
possible to control simultaneously the electronic and
steric characteristics and may on the whole increase the
catalyst efficiency.
Parameter
Empirical formula
(+)-(IV)
C12H22N2O
M
210.32
Color, crystal habit
Crystal size, mm
T, K
Colorless prisms
0.25 × 0.30 × 0.40
293(2)
Crystal system
Space group
a, Å
Monoclinic
P 21
7.3470(15)
8.0336(16)
10.963(2)
103.95(3)
628.0(2)
2(1)
b, Å
Unsymmetrical diimines Va, Vb were synthesized
by treating amine IV with an appropriate aldehyde in
methanol at 20°C. The NMR spectra of compounds Va,
Vb contain the signals of the terpene and phenol moieties.
In the 1H NMR spectrum the proton signal of azomethine
group characteristic of the salicylaldimines appears as a
singlet in the region of 8.30 ppm, and the singlet of the
phenol hydroxy group, at 13−14 ppm.
c, Å
β, deg
V, Å 3
Z(Z')
F(000)
232
d
c-calc, g·cm–3
1.112
Extinction coefficient μ, cm–1
2θmax, deg
0.71
The stereoselective reduction of the imine bond was
performed with LiAlH4 as reducer. The reduction of
diimines IIa, IIb and Va, Vb gave diamines IIIa, IIIb
and VIa, VIb in 63–77% yields. The amines obtained
were isolated from the reaction mixture as hydrochlorides.
The amine formation was confirmed by the appearance
in the 1H NMR spectrum of the reaction product of the
proton signal of C3HN group in the region of 2.27–
2.90 ppm and by the upfield shift of the C3 signal in the
13C NMR spectrum. The proton signal of the CH2Ar
group in compounds VIa, VIb is observed as a singlet
at 4.00 ppm.
54
Number of measured reflections
1537
Number of independent reflections 1432
Rint
0.0145
Number of reflections with I > 2σ(I) 1281
Number of refined parameters
139
R1
0.0351
0.0779
1.00
wR2
GOF
Residual minimum/maximum e/Å 3 0.113/–0.096
The synthesis of diimine VIII containing two different
terpene fragments was performed by the condensation of
amine IV and optically active aldehyde (+)-(VII) [14]
with an isobornyl substituent (Scheme 2).
1H NMR spectrum of compound VIII contains proton
signals of two different terpene and phenol fragments.
The number, multiplicity, and the integral intensity of the
signals confirm the assumed structure of the compound
obtained. The proton signal of the N=CH group gives
rise to a singlet at 8.30 ppm. The 13C NMR spectrum of
diimine VIII contains 30 signals in agreement with the
assumed structure.
bond; this conformation is stabilized by an intramolecular
hydrogen bond N2–HB···N1 [N···N 2.833(2) Å, NHN
112(1)°]. The main crystallographic data and refining
parameters are presented in the table.
The presence in the molecule of compound (+)-(IV)
two additional proton donors leads to the formation
of endless bands where the molecules are joined by
moderately strong hydrogen bonds N2–HA···O1 [N···O
3.236(2) Å, NHO 144(1)°] and O1–H···N2 [O···N 2.808(2)
Å, OHN 170(1)°]. Supramolecular associates are held in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

DVORNIKOVA et al.
1132
Scheme 1.
R
N
R
R
N
R
10
8
11
OH
OH
HO
OH
HO
O
NH
HN
2
5
1
7
a
b
3
6
9
4
I
IIa, IIb
IIIa, IIIb
a
11 12
OH
OH
OH
N
N
NH
NH2
N
HN
HO
c
b
HO
R
R
R
R
IV
VIa, VIb
Vа, Vb
II, III, R = H (a), R + R = (CH2)4 (b); V, VI, R = H (a), t-Bu (b). a: H2N(CH2)2NH2 [or (R,R)-cyclohexane-1,2-diamine],
PhH, F3B·OEt2, molecular sieves 4Ǻ, 80°C; b: LiAlH4, Et2O; c: salicylaldehyde (or 3,5-di-tert-butyl-2-hydroxybenzalde-
hyde), MeOH, 20°C.
Scheme 2.
10
8
11 12
OH
N
N
2
1
7
3
6 9
4
HO
5
VIII
2'
7'
3'
8'
1'
4'
10'
9'
OH
a
5'
6'
O
b
N
N
(+)-VII
OH HO
3
2
8
4
1
7
10
9
5
6
IX
a: (IV), C6H6, 20°C; b: (R,R)-cyclohexane-1,2-diamine, C6H6, 20°C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

SYNTHESIS OF 1,2-DIAMINE LIGANDS
1133
Scheme 3.
OH
N
N
NH HN
OH HO
O
b
a
OH HO
(_)-VII
X
XI
a: (R,R)-cyclohexane-1,2-diamine, C6H6, 20°C; b: NaBH4, EtOH, boiling.
The symmetric ligands of salenic type IX and X
(R,R)-(–)-Cyclohexane-1,2-diamine, salicylaldehyde,
and 3,5-di-tert-butyl-2-hydroxybenzaldehyde (Alfa
Aesar) were used without additional purification.
Ethylenediamine was boiled and distilled over sodium
metal. Boron trifluoride etherate was distilled at 46°C
(10 mm Hg) over CaH2. All solvents were dried and
purified by standard procedures.
with the isobornyl substituent were obtained by the
condensation of aldehydes (+)-(VII) and (–)-(VII) with
(1R,2R)- cyclohexane-1,2-diamine. Imine X was reduced
into diamine XI by NaBH4 (Scheme 3). The number and
1
integral intensity in the H NMR spectra confirm the
structure and the C2-symmetry of compounds IX–XI.
The proton signal of the azomethine group of diimines
IX, X appears in the region of 8.0 ppm. In the spectrum
of diamine XI the proton signal of the CH2N group is
observed as two doublets at 3.83 and 4.01 ppm.
(1R,2R,5R)-2-Hydroxy-3-pinanone (I), [α]D +39.1°
(C 1.0, CHCl3), was obtained by the oxidation of (1S,2S)-
(–)-α-pinene with potassium permanganate by procedure
[15].
Thus on the basis of available optically active
monoterpene compounds we obtained new symmetric and
unsymmetrical 1,2-diamines promising for the application
as ligands in various asymmetric syntheses.
The synthesis of compounds VIII–XI was carried
out using 2-hydroxy-5-methyl-3-{(1S,2R,4R)-1,7,7-
trimethylbicyclo[2.2.1]hept-exo-2-yl}benzaldehyde
(+)-(VII), [α]D +41.0° (C 0.6, CHCl3) and 2-hydroxy-
5-methyl-3-{(1R,2S,4S)-1,7,7-trimethylbicyclo[2.2.1]-
hept-exo-2-yl}benzaldehyde (–)-(VII), [α]D –40.9°
(C 0.6, CHCl3) obtained by method [14].
EXPERIMENTAL
1H and 13C were registered on a spectrometer Bruker
Avance II (operating frequencies 300 and 75 MHz
respectively) from solutions of compounds in CDCl3.
The assignment of signals was performed using 13C NMR
spectra recorded in the J-modulation mode and the data
of the spectra of 2D heteronuclear correlation 13C–1H
(HETCORR). IR spectra were recorded on a Fourier IR
spectrophotometer Shimadzu IR Prestige 21. Melting
points were measured on a Koeffler heating block. The
specific rotation was measured (22°C) on an automatic
digital polarimeter Kruss P3002RS.
3,3'-(Ethylenediimino)bis{(1R,2R,5R)-2,6,6-tri-
methylbicyclo[3.1.1]heptan-2-ol} (IIa) was obtained by
somewhat modified procedure [12]. A solution of 5.08 g
(30.2 mmol) of (+)-ketol I and 2.72 g (45.3 mmol) of
ethylenediamine in 100 ml of anhydrous benzene was
boiled for 12 h in the presence of 2.57 g (18.1 mmol) of
F3B·OEt2 and 15 g of molecular sieves 4Å. The reaction
mixture was filtered, the molecular sieves were washed
with Et2O. The filtrate was diluted with brine, the product
was extracted with Et2O. The organic extract was washed
with brine and dried with anhydrous K2CO3, the solvent
was removed in a vacuum. To the residue (4.47 g) was
added a little pentane, and 2.29 g of bisimine IIa was
isolated as colorless powder. The mother liquor was
The reaction progress was monitored and the purity of
compounds synthesized was checked by TLC on Sorbfil
plates. The column chromatography was carried out on
silica gel Alfa Aesar 70/230μ.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

DVORNIKOVA et al.
1134
stirred dispersion of 0.58 g (15.39 mmol) of LiAlH4 in
60 ml of anhydrous Et2O. The mixture was boiled for
20 h, cooled to room temperature, and diluted with 30 ml
of water. The reaction products were extracted into Et2O,
organic extracts were dried with K2CO3. On removing the
solvent in a vacuum the residue (1.25 g) was recrystallized
from hexane, and 0.39 g of diamine IIIa was isolated as
colorless crystals. The mother liquor was evaporated, the
residue was dissolved in Et2O, 2 M solution of HCl in
ethanol was added, and dihydrochloride (IIIa)·2HCl was
isolated (0.39 g after recrystallization from EtOH–Et2O).
Overall yield 63%. Colorless crystals, mp 108–110°C
(from hexane), [α]D +49.5° (c 0.5, CHCl3). IR spectrum
(KBr), ν, cm–1: 3332, 2924, 1484, 1388, 1372, 1124, 680.
1H NMR spectrum, δ, ppm: 0.96 s (6H, C9,9'H3), 1.25 s
(12H, C8,8'H3, C10,10'H3), 1.26 d (2H, Hβ7,7', J 8.1 Hz),
1.31 d.d.d (2H, Hβ4,4', J 13.5, 5.9, 2.4 Hz), 1.87 m (2H,
H5,5'), 1.97 t (2H, H1,1', J 5.8 Hz), 2.13 m (2H, Hα7,7'),
2.51 m (2H, Hα4,4'), 2.81 m (4H, C11,11'H2), 2.86 d.d (2H,
Hα3,3', J 9.8, J 5.9 Hz). 13C NMR spectrum, δ, ppm: 24.03
(C9,9'), 27.92 (C8,8'), 28.13 (C7,7'), 28.30 (C10,10'), 38.03
(C4,4'), 38.31 (C6,6'), 40.42 (C5,5'), 49.44 (C11,11'), 54.06
(C1,1'), 57.25 (C3,3'), 71.76 (C2,2'). Found, %: C 72.70;
H 10.90; N 7.70. C22H40N2O2. Calculated, %: C 72.48;
H 11.06; N 7.68.
evaporated, the residue (2.63 g) was separated by column
chromatography on SiO2 (eluent CHCl3–MeOH). We
additionally isolated 1.47 g of symmetric diimine IIa.
Overall yield 3.76 g (69%), colorless crystals (from
hexane), mp 130–132°C, [α]D –6.9° (c 1.2, CHCl3). IR
spectrum (KBr), ν, cm–1: 1653 (C=N). 1H NMR spectrum,
δ, ppm: 0.84 s (6H, C9,9'H3), 1.30 s (6H, C8,8’H3), 1.44 s
(6H, C10,10'H3), 1.55 d (2H, Hβ7,7', J 10.6 Hz), 2.03 m
(4H, H1,1', H5,5'), 2.28–2.35 m (2H, Hα7,7'), 2.57 m (4H,
C4,4'H2), 3.04 br.s (2H, OH), 3.59 m (4H, C11,11'H2). 13C
NMR spectrum, δ, ppm: 22.87 (C9,9’), 27.33 (C8,8'), 28.15
(C7,7'), 28.31 (C10,10'), 33.67 (C4,4'), 38.37 (C5,5'), 38.39
(C6,6'), 50.43 (C1,1'), 51.37 (C11,11'), 76.31 (C2,2'), 176.32
(C3,3').
3,3'-[(1R,2R)-Cyclohexane-1,2-diimino]bis-
{(1R,2R,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan-2-
ol} (IIb). A solution of 1.11 g (6.6 mmol) of (+)-ketol I
and 0.34 g (3.0 mmol) of (1R,2R)-(–)-cyclohexane-1,2-
diamine in 25 ml of anhydrous benzene was boiled for
7 h in the presence of 0.56 g (3.96 mmol) of F3BOEt2
and 3 g of molecular sieves 4Å. The reaction mixture was
filtered, the filtrate was diluted with brine, the product
was extracted with chloroform. The organic extract was
washed with brine and dried with anhydrous K2CO3,
the solvent was removed in a vacuum, the residue was
separated by column chromatography on SiO2 (eluent
hexane–Et2O). Yield 0.52 g (42%). Colorless crystals
(from hexane), mp 113–115°C, [α]D –36.1° (c 0.5,
CHCl3). IR spectrum (KBr), ν, cm–1: 3342 (OH), 1643
(C=N). 1H NMR spectrum, δ, ppm: 0.82 s (6H, C9,9'H3),
1.28 s (6H, C8,8'H3), 1.32 s (6H, C10,10’H3), 1.38 m (4H,
cyclohex.), 1.46 d (2H, Hβ7,7', J 10.5 Hz), 1.53 m (2H,
cyclohex), 1.78 m (2H, cyclohex), 1.98–2.00 m (4H,
3,3'-[(1R,2R)-Cyclohexane-1,2-diamino]bis-
{(1R,2R,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol}
(IIIb). A solution of 2.30 g(13.70 mmol) of (+)-ketol I
and 0.71 g (6.22 mmol) of (1R,2R)-(–)-cyclohexane-1,2-
diamine in 50 ml of anhydrous benzene was boiled for
7 h in the presence of 1.16 g (8.20 mmol) of F3BOEt2
and 6 g of molecular sieves 4Å. The reaction mixture was
filtered, the filtrate was diluted with brine, the product
was extracted with chloroform. The organic extract was
washed with brine and dried with anhydrous K2CO3,
the solvent was removed in a vacuum, the residue was
dissolved in 40 ml of anhydrous Et2O, and it was added
dropwise to a vigorously stirred dispersion of 1.89 g
(49.78 mmol) of LiAlH4 in 120 ml of anhydrous Et2O.
The reaction mixture was stirred at room temperature for
6 h. To the reaction mixture was added dropwise 1.9 ml
of EtOAc, 1.9 ml of 10% water solution of NaOH, 5.7 ml
of water, and the mixture was stirred at room temperature
for 4 h. The precipitate was filtered off, the filtrate was
treated with 10% water solution of HCl. Water solution
was washed with Et2O, 10% solution of NaOH was added,
and the water solution was extracted with Et2O. The ether
solution of amine was dried with K2CO3. On removing the
H1,1', H5,5'), 2.25–2.32 m (2H, Hα7,7'), 2.53 d (2H, H4,4'
,
J 17.9 Hz), 2.53 s (2H, OH), 2.71 d (2H, H4,4', J 17.9 Hz),
3.64 m (2H, =NCH). 13C NMR spectrum, δ, ppm: 23.07
(C9,9'), 24.53 (2CH2- cyclohex), 27.32 (C8,8'), 28.03
(C7,7'), 28.39 (C10,10'), 30.26 (2CH2- cyclohex), 32.73
(C4,4'), 38.14 (C6,6'), 38.44 (C5,5'), 50.15 (C1,1'), 63.68
(C11,11'), 76.09 (C2,2'), 173.62 (C3,3'). Found, %: C 75.60;
H 10.32; N 6.60. C26H42N2O2. Calculated, %: C 75.32;
H 10.21; N 6.76.
3,3'-(Ethylenediamino)bis{(1R,2R,5R)-2,6,6-
trimethylbicyclo[3.1.1]heptan-2-ol} (IIIa) was obtained
by procedure [13]. A solution of 1.11 g (3.08 mmol) of
dihydroxyimine IIa in 25 ml of anhydrous Et2O was
added dropwise under argon atmosphere to a vigorously
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

SYNTHESIS OF 1,2-DIAMINE LIGANDS
1135
solvent in a vacuum the residue (1.19 g) was recrystallized
from hexane. Yield 0.79 g (30% calculated with respect to
the initial ketol). Colorless powder, mp 158–160°C, [α]D
–10.8° (c 0.5, CHCl3). IR spectrum (KBr), ν, cm–1: 3286,
2926, 1496, 1448, 1377, 1114. 1H NMR spectrum, δ, ppm:
0.69 br (2H), 0.94 s (6H, C9,9'H3), 0.96 m (2H, cyclohex),
1.22 s (6H, C8,8'H3), 1.25 s (6H, C10,10'H3), 1.31 d (2H,
Hβ7,7', J 10.4 Hz), 1.17–1.32 m (4H, H4,4', 2H- cyclohex),
1.74 m (2H, cyclohex), 1.82 m (2H, H5,5'), 1.93 t (2H,
H1,1', J 5.8 Hz), 2.05–2.13 m (2H, Hα7,7'), 2.24–2.29 m
(4H, H3,3', 2H- cyclohex), 2.39–2.47 m (2H, H4,4'), 3.05 m
(2H, H11,11'), 5.75 br (2H). 13C NMR spectrum, δ, ppm:
24.12 (C9,9'), 25.04 (2CH2- cyclohex), 27.76 (C7,7'), 27.80
(C8,8'), 31.96 (C10,10'), 32.16 (2CH2- cyclohex), 38.12
(C6,6'), 38.90 (C4,4'), 40.44 (C5,5'), 53.70 (C11,11'), 54.54
(C1,1'), 61.89 (C3,3'), 72.43 (C2,2'). Found, %: C 74.50;
H 11.00; N 6.67. C26H46N2O2. Calculated, %: C 74.59;
H 11.07; N 6.69. The rest of the symmetric diamine was
not isolated from the hexane solution.
H(C) were geometrically calculated and refined in the
isotropic approximation by the rider model with Uiso(H) =
1.2Ueq(Ci), for the methyl groups 1.5Ueq(Cii), where
U(Ci) and U(Cii) are equivalent thermal parameters of
the carbon atoms attached to the corresponding H atoms.
All calculations were done using SHELXTL PLUS 5.0
software [16].
(1R,2R,5R)-3-({2-[(2-Hydroxybenzylidene)-
amino]ethyl}imino)-2,6,6-trimethylbicyclo-[3.1.1]
heptan-2-ol (Va) was obtained from amine (–)-(IV)
and salicylaldehyde by procedure [12]. Yield 82%.
Yellow crystals, mp 97–99°C, [α]D –71.1° (c 0.5, EtOH).
1H NMR spectrum, δ, ppm: 0.65 s (3H, CH3), 1.25 s (3H,
7
CH3), 1.39 s (3H, CH3), 1.43 d (1H, Hβ , J 10.6 Hz),
1.99 m (2H, H1, H5), 2.27 m (1H, Hα ), 2.49 m (2H, C4H2),
7
3.53–3.71 m (2H, C12H2), 3.84–4.03 m (2H, C11H2),
6.84 m (1Harom), 6.91 d (1Harom, J 8.2 Hz), 7.20–7.30 m
(2Harom), 8.33 s (1H, N=CHAr), 13.48 br.s (1H, HOAr).
13C NMR spectrum, δ, ppm: 22.57 (C9), 27.23 (C8), 28.00
(C7), 28.32 (C10), 33.73 (C4), 38.28 (C5, C6), 50.24 (C1),
50.55 (C11), 59.70 (C12), 76.42 (C2), 116.97 (CHarom),
118.43 (CHarom), 118.63 (Carom), 131.18, 132.18 (CHarom),
161.32 (ArOH), 166.05 (N=CHAr), 177.42 (C3).
(1R,2R,5R)-3-[(2-Aminoethyl)imino]-2,6,6-
trimethylbicyclo[3.1.1]heptan-2-ol (IV) was obtained
from (+)-2-hydroxy-3-pinanone I and ethylenediamine
by procedure [12]. Yield 72%. Colorless crystals, mp
62–64°C, [α]D –13.1° (c 0.8, CHCl3). 1H NMR spectrum,
δ, ppm: 0.82 s (3H, CH3), 1.29 s (3H, CH3), 1.44 s (3H,
(1R,2R,5R)-3-({2-[(2-Hydroxy-3,5-di-tert-
butylbenzylidene)amino]ethyl}imino)-2,6,6-
trimethylbicyclo[3.1.1]heptan-2-ol (Vb) was obtained
similarly from amine (–)-(IV) and 3,5-di-tert-butyl-2-
hydroxybenzaldehyde (reaction time 7 h). Yield 96%.
Semicrystalline yellow mass, [α]D –50.4° (c 0.5, EtOH).
IR spectrum (thin film), ν, cm–1: 3421 (OH), 1632 (C=N).
1H NMR spectrum, δ, ppm: 0.67 s (3H, CH3), 1.26 s
(3H, CH3), 1.30 s [9H, C(CH3)3], 1.43 s [12H, C(CH3)3,
CH3), 1.52 d (1H, Hβ , J 10.6 Hz), 1.96–2.05 m (2H, H1,
7
H5), 2.26–2.34 m (1H, Hα ), 2.47 m (2H, C4H2), 2.88–3.02
7
m (2H, C12H2), 3.26 m (2H, C11H2). 13C NMR spectrum,
δ, ppm: 22.82 (C9), 27.29 (C8), 28.11 (C7), 28.27 (C10),
33.69 (C4), 38.30 (C5), 38.41 (C6), 42.60 (C12), 50.31
(C1), 53.38 (C11), 76.21 (C2), 176.76 (C3).
(1S,2S,5S)-3-[(2-Aminoethyl)imino]-2,6,6-
trimethylbicyclo[3.1.1]heptan-2-ol (+)-(IV) was
obtained from (–)-2-hydroxy-3-pinanone [12]. Yield
79%. Colorless crystals, mp 63–65°C (from hexane), [α]D
+13.4° (c 1.0, CHCl3). Crystals suitable for XRD analysis
were obtained by slow evaporation of the solution of
compound (+)-(IV) in hexane. XRD investigation of
compound (+)-(IV) was performed on a four-circle
diffractometer CAD4 Enraf-Nonius (MoKα-radiation,
graphite monochromator, θ/2θ-scanning) at 293 K.
The structure was solved by the direct method and
refined by the least-squares method in the anisotropic
approximation on F2hkl. Hydrogen atoms of NH2 and
OH groups were localized from the difference Fourier
syntheses of the electron density and were refined in
the isotropic approximation. The positions of atoms
CH3], 1.46 d (1H, Hβ , J 10.7 Hz), 1.99 m (2H, H1,
7
H5), 2.24–2.32 m (1H, Hα ), 2.51 m (2H, C4H2), 2.86 s
7
(1H, HOCMe), 3.55–3.73 m (2H, C12H2), 3.84–4.02 m
(2H, C11H2), 7.06 d (1Harom, J 2.4 Hz), 7.36 d (1Harom
,
J 2.4 Hz), 8.35 s (1H, N=CHAr), 13.85 br.s (1H, HOAr).
13C NMR spectrum, δ, ppm: 22.60 (C9), 27.30 (C8), 28.03
(C7), 28.32 (C10), 29.37 [C(CH3)3], 31.47 [C(CH3)3],
33.68 (C4), 34.09 [C(CH3)3], 34.95 [C(CH3)3], 38.32
(C5, C6), 50.26 (C1), 50.84 (C11), 59.61 (C12), 76.45 (C2),
117.71 (Carom), 125.79, 126.77 (CHarom), 136.56, 139.90
(Carom), 158.19 (ArOH), 167.03 (N=CHAr), 177.28
(C3). Found, %: C 76.40; H 10.00; N 6.69. C27H42N2O2.
Calculated, %: C 76.01; H 9.92; N 6.57.
(1R,2R,5R)-3-[2-(2-Hydroxybenzylamino)-
ethylamino]-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

DVORNIKOVA et al.
1136
(VIa). A solution of 4.68 g (14.88 mmol) of diimine Va
in 70 ml of anhydrous Et2O was added dropwise to a
vigorously stirred dispersion of 4.52 g (119.07 mmol) of
LiAlH4 in 280 ml of anhydrous Et2O. The mixture was
stirred at room temperature over 6 h. To the reaction
mixture was added dropwise 4.5 ml of ethyl acetate,
4.5 ml of 10% water solution of NaOH, 13.6 ml of water,
and stirring continued at room temperature for 4 h. The
precipitate was filtered off, the ether solution was dried
with K2CO3. To the ether solution was added 2 M solution
of HCl in ethanol till weakly acidic reaction, and the
solution was stirred at room temperature for 2 h. Yield
of dihydrochloride (VIa)·2HCl 3.51 g (66%). Colorless
powder, mp 218–219°C (from ethanol, decomp.), [α]
D +5.9° (c 1.0, CHCl3). Found, %: C 58.20; H 8.15;
N 7.20. C19H30N2O2·2HCl. Calculated, %: C 58.31;
H 8.24; N 7.16.
1.26 s (6H, 2CH3), 1.29 s [9H, C(CH3)3], 1.29–1.35 m
7
4
(2H, Hβ , Hβ ), 1.43 s [9H, C(CH3)3], 1.90 m (1H,
H5), 1.98 t (1H, H1, J 5.7 Hz), 2.11–2.19 m (1H, Hα ),
7
2.50 m (1H, Hα ), 2.82–2.98 m (5H, C12H2, C11H2, H3),
4
3.99 s (2H, NCH2Ar), 6.88 m (1Harom), 7.24 m (1Harom).
13C NMR spectrum, δ, ppm: 24.00 (C9), 27.93 (C8), 28.16
(C7), 29.62 [C(CH3)3], 31.22 (C10), 31.66 [C(CH3)3],
34.12 [C(CH3)3], 34.87 [C(CH3)3], 37.98 (C4), 38.31 (C6),
40.43 (C5), 48.62, 49.03 (C11, C12), 53.34 (NHCH2Ar),
54.01 (C1), 57.58 (C3), 72.00 (C2), 121.90 (Carom), 123.01,
123.17 (CHarom), 135.91, 140.51 (Carom), 154.53 (ArOH).
(1R,2R,5R)-3-(2-{2-Hydroxy-5-methyl-3-
[(1S,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-
exo-2-yl]benzylideneamino}ethylimino)-2,6,6-
trimethylbicyclo[3.1.1]heptan-2-ol (VIII). A solution
of 0.12 g (0.70 mmol) of amine IV and 0.19 g (0.70 mmol)
of aldehyde (+)-(VII) in 10 ml of anhydrous benzene
was stirred over 10 h at 20°C in the presence of 0.36 g
of molecular sieves 4Å. On completion of the reaction
the solvent was removed under a reduced pressure. The
residue (0.34 g) was subjected to column chromatography
on SiO2 (eluent hexane–Et2O). Yield 0.12 g (36%). Light-
yellow powder, mp 130–132°C (from pentane), [α]D
+3.0° (c 0.4, CHCl3). IR spectrum (KBr), ν, cm–1: 3492
(OH), 1640 (C=N). 1H NMR spectrum, δ, ppm: 0.72 s,
0.75 s, 0.84 s, 0.90 s (12H, C9H3, C8'H3, C9'H3, C10'H3),
1.27 s (3H, C8H3), 1.32–1.39 m (1H, C5'H), 1.43 s (3H,
For isolation of free amine VIa the dihydrochloride
was dissolved in 10% solution of NaOH, the amine was
extracted into dichloromethane, the extract was dried with
K2CO3. On distilling off the solvent thick light-yellow
oily substance was obtained, [α]D +20.0° (c 1.0, CHCl3).
IR spectrum (thin film), ν, cm–1: 3294, 2910, 1610, 1591,
1473, 1373, 1257, 1107, 756. 1H NMR spectrum, δ, ppm:
0.95 s (3H, CH3), 1.24 s, 1.25 s (6H, 2CH3), 1.23–1.33 m
(2H, Hβ , Hβ ), 1.88 m (1H, H5), 1.97 t (1H, H1, J 5.7 Hz),
7
4
7
4
2.10–2.18 m (1H, Hα ), 2.49 m (1H, Hα ), 2.77–2.95 m
(5H, C12H2, C11H2, H3), 4.02 s (2H, NHCH2Ar), 6.78 t
(1Harom, J 7.4 Hz), 6.83 d (1Harom, J 8.0 Hz), 6.99 d
(1Harom, J 7.2 Hz), 7.16 br.t (1Harom). 13C NMR spectrum,
δ, ppm: 23.97 (C9), 27.89 (C8), 28.15 (C7), 31.20 (C10),
37.92 (C4), 38.30 (C6), 40.40 (C5), 48.53, 48.89 (C11,C12),
52.51 (NHCH2Ar), 54.01 (C1), 57.51 (C3), 72.03 (C2),
116.38, 119.04 (CHarom), 122.37 (Carom), 128.33, 128.74
(CHarom), 158.10 (ArOH).
C10H3), 1.46 d (1H, Hβ , J 10.7 Hz), 1.53–1.61 m (3H,
7
C6'H2, C3'H), 1.83 m (2H, C4'H, C5'H), 1.96–2.04 m (2H,
H1, H5), 2.08–2.18 m (1H, C3'H), 2.25–2.32 m (1H, Hα ),
7
2.27 s (3H, CH3Ar), 2.50 m (3H, C4H2, OH), 3.32 br.t
(1H, H2'), 3.53–3.72 m (2H, C11H2), 3.85–3.99 m (2H,
C12H2), 6.85 s (1H, Harom), 7.15 s (1H, Harom), 8.30 s (1H,
N=CHAr), 13.68 br.s (1H, HOAr). 13C NMR spectrum,
δ, ppm: 12.31 (C10'), 20.40 (C9'), 20.79 (CH3Ar), 21.42
(C8'), 22.79 (C9), 27.33 (C8), 27.50 (C5'), 28.09 (C7), 28.37
(C10), 33.67 (C4), 33.99 (C3'), 38.34 (C5), 38.38 (C6),
39.68 (C6'), 44.51 (C2'), 45.73 (C4'), 47.93 (C1'), 49.81
(C7'), 50.26 (C1), 50.84 (C11), 59.65 (C12), 76.47 (C2),
117.45, 126.15 (Carom), 128.62 (CHarom), 131.57 (Carom),
131.75 (CHarom), 158.51 (ArOH), 166.31 (CH=NCH2),
177.33 (C3). Found, %: C 77.50; H 9.48; N 6.00.
C30H44N2O2. Calculated, %: C 77.54; H 9.54; N 6.03.
{4,4'-Dimethyl-6,6'-di[(1S,2R,4R)-1,7,7-
trimethylbicyclo[2.2.1]hept-exo-2-yl]-2,2'-[(1R,2R)-
cyclohexane-1,2-diylbis(iminomethyl)]}diphenol
(IX). A solution of 0.057 g (0.50 mmol) of (1R,2R)-(–)-
(1R, 2R, 5R)-3-[2-(3, 5-Di-tert-butyl-2-
hydroxybenzylamino)ethylamino]-2,6,6-tri-
methylbicyclo[3.1.1]heptan-2-ol (VIb) was obtained
analogously by the reduction of diimine Vb. Yield of
dihydrochloride (VIb)·2HCl after recrystallization
from the mixture EtOH–Et2O 77%. Colorless powder,
mp 231–233°C (decomp.), [α]D +6.0° (c 1.1, EtOH).
Found, %: C 64.30; H 9.51; N 5.45. C27H46N2O2·2HCl.
Calculated, %: C 64.40; H 9.61; N 5.56.
Diamine VIb is a colorless substance, mp 85–87°C,
[α]D +16.2° (c 1.03, CHCl3). IR spectrum (KBr), ν, cm–1:
3437, 3315, 2953, 1602, 1477, 1388, 1360, 1238, 1114,
748. 1H NMR spectrum, δ, ppm: 0.97 s (3H, CH3), 1.25 s,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

SYNTHESIS OF 1,2-DIAMINE LIGANDS
1137
cyclohexane-1,2-diamine and 0.27 g (0.99 mmol) of alde-
hyde (+)-(VII) in 10 ml of anhydrous benzene was stirred
over 12 h at 20°C in the presence of 0.8 g of molecular
sieves 4Å. The reaction mixture was filtered, the solvent
was removed in a vacuum. Yield 0.30 g (96%), yellow
powder, mp 105–107°C, [α]D –412.0° (C 0.5, CHCl3).
washed with brine and dried with K2CO3. The solvent
was removed in a vacuum, the residue was recrystallized
from hexane. Yield 0.012 g (20%), colorless crystals,
1
mp 186–188°C, [α]D –18.1° (C 0.1, CHCl3). H NMR
spectrum, δ, ppm: 0.76 s, 0.82 s, 0.89 s (18H, C8,8'H3,
C9,9'H3, C10,10'H3), 1.10–1.60 m (14H, H3,3', H5,5', C6,6'H2,
1
IR spectrum (KBr), ν, cm-1: 1627 (C=N). H NMR
6H- cyclohex), 1.69 m (2H, cyclohex), 1.79 m (4H, H4,4'
,
spectrum, δ, ppm: 0.72 s, 0.85 s, 0.86 s (18H, C8,8'H3,
H5,5'), 2.10–2.18 m (2H, H3,3'), 2.24 s (6H, CH3Ar), 2.39 m
(2H, 2CH- cyclohex), 3.19 t (2H, H2,2', J 8.9 Hz), 3.83 d,
4.01 d (4H, NCH2Ar, J 13.5 Hz), 6.63 s (2Harom), 7.01 s
(2Harom). 13C NMR spectrum, δ, ppm: 12.34 (C10,10'),
20.44 (C9,9'), 20.92 (CH3Ar), 21.45 (C8,8'), 24.29 (CH2-
cyclohex), 30.94 (CH2- cyclohex), 27.49 (C5,5'), 34.00
(C3,3'), 39.67 (C6,6'), 44.72 (C2,2'), 45.77 (C4,4'), 47.86,
49.72 (C1,1', C7,7'), 50.05 (CH2NH), 59.79 (CH- cyclohex),
121.77, 126.72, 130.80 (Carom), 126.14, 128.02 (CHarom),
154.62 (CaromOH). Found, %: C 80.36; H 10.09; N 4.41.
C42H62N2O2. Calculated, %: C 80.46; H 9.97; N 4.47.
The rest of the diamine was not isolated from the hexane
solution.
C9,9'H3, C10,10'H3), 1.34–2.13 m (22H, C3,3'H2, H4,4'
,
C5,5'H2, C6,6'H2, 4CH2- cyclohex), 2.19 s (6H, CH3Ar),
3.29 m (4H, H2,2', 2CH- cyclohex), 6.68 s (2Harom), 7.09
s (2Harom), 8.14 s (2H, N=CHAr), 13.57 br.s (2H, OH).
13C NMR spectrum, δ, ppm: 12.26 (C10,10'), 20.31 (C9,9'),
20.64 (CH3Ar), 21.44 (C8,8'), 24.31 (2CH2- cyclohex),
32.81 (2CH2- cyclohex), 27.53 (C5,5'), 33.87 (C3,3'),
39.73 (C6,6'), 44.49 (C2,2'), 45.70 (C4,4'), 47.92, 49.81
(C1,1', C7,7'), 72.59 (2CH- cyclohex), 117.33, 126.04,
131.09 (Carom), 128.96, 131.48 (CHarom), 158.10 (ArOH),
165.33 (N=CH–Ar). Found, %: C 81.06; H 9.52; N 4.38.
C42H58N2O2. Calculated, %: C 80.98; H 9.38; N 4.50.
{4,4'-Dimethyl-6,6'-di[(1R,2S,4S)-1,7,7-
trimethylbicyclo[2.2.1]hept-exo-2-yl]-2,2'-[(1R,2R)-
cyclohexane-1,2-diylbis(iminomethyl)]}diphenol
(X) was similarly obtained from aldehyde (–)-(VII).
Yield 96%, yellow powder, mp 115–118°C, [α]D
–386.4° (C 0.5, CHCl3). IR spectrum (KBr), ν, cm–1:
1627 (C=N). 1H NMR spectrum, δ, ppm: 0.79 s, 0.85 s,
0.90 s (18H, C8,8'H3, C9,9'H3, C10,10'H3), 1.28–2.10 m
(22H, C3,3'H2, H4,4', C5,5'H2, C6,6'H2, 4CH2- cyclohex),
2.21 s (6H, CH3Ar), 3.31 m (4H, H2,2', 2CH- cyclohex),
6.74 s (2Harom), 7.11 s (2Harom), 8.18 s (2H, N=CHAr),
13.43 br.s (2H, OH). 13C NMR spectrum, δ, ppm: 12.33
(C10,10'), 20.43 (C9,9'), 20.70 (CH3Ar), 21.42 (C8,8'),
24.28 (2CH2- cyclohex), 33.12 (2CH2- cyclohex), 27.52
(C5,5'), 34.11 (C3,3'), 39.79 (C6,6'), 44.50 (C2,2'), 45.71
(C4,4'), 47.92, 49.74 (C1,1', C7,7'), 72.54 (2CH- cyclohex),
117.42, 126.01, 131.23 (Carom), 128.92, 131.58 (CHarom),
158.14 (ArOH), 165.02 (N=CHAr). Found, %: C 80.76;
H 9.43; N 4.40. C42H58N2O2. Calculated, %: C 80.98;
H 9.38; N 4.50.
ACNOWLEDGMENTS
The study was carried out under a financial support
of the Federal Agency of Science and Innovations (State
contract no. 02.740.11.0081).
REFERENCES
1. Kizirian, J.-C., Chem. Rev., 2008, vol. 108, p. 140.
2. Chelucci, G. and Thummel, R.P., Chem. Rev., 2002,
vol. 102, p. 3129.
3. Fache, F., Schulz, E., Tommasino, M. L., and Lemaire, M.,
Chem. Rev., 2000, vol. 100, p. 2159.
4. Salehi, P., Dabiri, M., Kozehgary, G., andBaghbanzadeh, M.,
Tetra-hedron: Asymmetry., 2009, vol. 20, p. 2609.
5. Yang, K.-S., Lee, W.-D., Pan, J.-F., and Chen, K., J. Org.
Chem., 2003, vol. 68, p. 915.
6. Malkov,A.V., Gordon, M.R., Stončius, S., Hussain, J., and
Kočovský, P., Org. Lett., 2009, vol. 11, p. 5390.
{4,4'-Dimethyl-6,6'-di[(1R,2S,4S)-1,7,7-
trimethylbicyclo[2.2.1]hept-exo-2-yl]-2,2'-[(1R,2R)-
cyclohexane-1,2-diylbis(aminomethyl)]}diphenol (XI).
To a solution of 0.06 g (0.096 mmol) of diimine X in 5 ml
of anhydrous EtOH was added 0.0091 g (0.24 mmol) of
NaBH4. The reaction mixture was heated to boiling and
stirred for 2 h. To the cooled reaction mixture water and
5% solution of NaOH was added. The reaction product
was extracted into dichloromethane, the extract was
7. Chen, Y.-J., Chen, C., Tetrahedron: Asymmetry, 2007,
vol. 18, p. 1313.
8. Malkov,A.V., Pernazza, D., Bell, M., Bella, M., Massa,A.,
Teplý, F., Meghani, P., and Kočovský, P., J. Org. Chem.,
2003, vol. 68, p. 4727.
9. Sun, J., Pan, X., Dai, Z., and Zhu, C., Tetrahedron:
Asymmetry, 2008, vol. 19, p. 2451.
10. Forrat, V.J., Ramun, D.J., and Yus, M., Tetrahedron:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

DVORNIKOVA et al.
1138
Asymmetry, 2007, vol. 18, p. 400.
Verpoort, F. Tetrahedron: Asymmetry, 2006, vol. 17, p. 434.
11. De las Casas, Engel, T., Maroto, B.L., Martnnez, A.G., De
la Moya, and Cerero, S., Tetrahedron: Asymmetry, 2008,
vol. 19, p. 646.
14. Buravlev, E.V., Chukicheva, I.Yu., Dolgushin, F.M., and
Kuchin, A.V., Zh. Org. Khim., 2010, vol. 46, p. 660.
15. Carlson, R.G. and Pierce, J.K., J. Org. Chem., 1971,
12. Dvornikova, I.A., Frolova, L.L., Churakov, A.V., and
vol. 36, p. 2319.
Kuchin, A.V., Izv. Akad. Nauk, Ser. Khim., 2004, p. 1270.
16. Sheldrick, G.M., SHELXTL Program for Solution and
Refinement of Crystal Structure. Version, 5.10, Bruker
AXS Inc., 1998.
13. Markowicz, S.W., Figlus, M., Lejkowski, M., Karolak-
Wojciechowska, J., Dzierzawska-Majewska, A.,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011