Diamines having a C2 symmetry. Synthesis and application as ligands in the hydrogenation of prochiral substrates over rhodium complexes

Article abstract of DOI:10.1023/A:1015367111704

Chiral diamines having a C₂ symmetry, (4S,5S)-2,2-dimethyl-4,5-bis(aminomethyl)-1,3-dioxolane and (5S,5′ S)-2,2,2′,2′-tetramethyl-3,3′-diphenyl-5,5′ -bioxazolidine, were synthesized on the basis of (+)-(2R,3R)-tartaric acid. Their structure was proved by X-ray analysis. The products were used as ligands in rhodium catalyst for enantioselective hydrogenation of α -acetamidocinnamic and itaconic acids.

Full text of DOI:10.1023/A:1015367111704

Russian Journal of Organic Chemistry, Vol. 38, No. 1, 2002, pp. 104 110. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 1, 2002,
pp. 112 117.
Original Russian Text Copyright
2002 by Shainyan, Ustinov, Bel’skii, Nindakova.
Dedicated to Full Member of the Russian Academy of Sciences
M.G. Voronkov on the 80th Anniversary of His Birth
Diamines Having a C2 Symmetry.
Synthesis and Application as Ligands in the Hydrogenation
of Prochiral Substrates over Rhodium Complexes*
B. A. Shainyan, M. V. Ustinov, V. K. Bel’skii, and L. O. Nindakova
Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: bagrat@irioch.irk.ru
Received April 18, 2001
Abstract Chiral diamines having a C2 symmetry, (4S,5S)-2,2-dimethyl-4,5-bis(aminomethyl)-1,3-dioxolane
and (5S,5 S)-2,2,2 ,2 -tetramethyl-3,3 -diphenyl-5,5 -bioxazolidine, were synthesized on the basis of
(+)-(2R,3R)-tartaric acid. Their structure was proved by X-ray analysis. The products were used as ligands
in rhodium catalyst for enantioselective hydrogenation of -acetamidocinnamic and itaconic acids.
2,3-O-Isopropylidenedioxy-1,4-bis(diphenylphos-
phino)butane (DIOP, Ia) is widely used as chelating
bis-phosphine ligand in catalysts for asymmetric
hydrogenation [1 6]. Bis-phosphine rhodium(I) com-
plexes are highly efficient stereo- and enantioselective
catalysts for transformations of unsaturated com-
pounds. On the other hand, they are characterized by
increased sensitivity to moisture and oxygen. There-
fore, apart from bis-phosphine ligands, other con-
formationally stable compounds, in particular N,N-bi-
dentate ones which are more resistant to oxidation,
attract researchers’ attention.
which exhibit antitumor activity [8, 9]. We previously
studied hydrogenation with molecular hydrogen of
prochiral unsaturated carboxylic acids over rhodium
catalyst containing ligand Ib; as a result, optical
yields of up to 30% were obtained. We have found
that enhanced stereogeneity of the nitrogen in diamine
ligands is necessary to raise the optical yield of hydro-
genation products [10 12]. In continuation of our
studies on the properties of catalysts for chiral hydro-
genation on the basis of nitrogen analogs of DIOP, we
have synthesized new chelating diamine ligands and
examined the efficiency of some rhodium complexes
derived therefrom in situ in the hydrogenation of
unsaturated prochiral carboxylic acids.
The scheme used previously [13] for preparation of
diamine Ib includes aminolysis of diethyl tartrate and
subsequent cyclization by the action of dimethoxy-
propane and reduction (Scheme 1). However, we
failed to obtain the desired products by this procedure,
X = PPh2 (a), NMe2 (b), NH2 (c), NHPh (d).
Nitrogen analogs of DIOP, namely optically active
diamines like I (X = NH2, NR2), are known as ligands
for chiral catalysts which are used for preparation of
polymers with a high degree of spirality [7], as well
as ligands for synthesis of platinum(II) complexes
____________
Scheme 1.
*
This study was financially supported by the Russian Founda-
tion for Basic Research (project no. 00-03-32578).
R = H (a), Ph (b).
1070-4280/02/3801-0104$27.00 2002 MAIK Nauka/Interperiodica

DIAMINES HAVING A C2 SYMMETRY.
105
presumably because of the poor solubility of amides
IIa and IIb in chloroform.
Table 1. Bond lengths d and bond angles in the mole-
cule of (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dicarbox-
amide (IIIa)
A fairly laborious procedure for preparation of
compound Ic and its analogs with various substituents
in position 2 of the dioxolane ring was described in
[8]. It consists of cyclization of threitol 1,4-bis-
(methanesulfonate) to 1,3-dioxolane-4,5-diyl bis-
(methanesulfonate) (I, X = OSO2CH3), followed by
treatment with sodium azide and reduction of diazide
I (X = N3). We synthesized ligand Ic by a simpler
alternative procedure shown in Scheme 2.
Scheme 2.
Bond
d,
Bond
d,
O1 C3
O1 C1
O2 C1
O2 C2
O3 C6
O4 C7
N1 C6
1.409(3)
1.428(3)
1.428(3)
1.430(3)
1.230(3)
1.230(3)
1.318(3)
N2 C7
C1 C4
C1 C5
C2 C6
C2 C3
C3 C7
1.306(3)
1.499(4)
1.503(5)
1.505(3)
1.535(3)
1.520(3)
The structure of intermediate diamide IIIa was
proved by X-ray analysis. The dioxolane ring in mole-
cule IIIa (Table 1) has a clearly defined envelope
conformation with the O2 atom deviating by 0.51
from the plane formed by the four remaining atoms
(which are coplanar within 0.01 ). Compound IIIa
in crystal gives rise to a three-dimensional network of
intermolecular hydrogen bonds N H O involving
the amide groups (Table 2).
Angle
, deg
Angle
, deg
C3O1C1
C1O2C2
O2C1O1
O2C1C4
O1C1C4
O2C1C5
O1C1C5
C4C1C5
O2C2C6
O2C2C3
109.47(15)
105.83(16)
104.08(17)
109.1(2)
107.5(2)
110.5(3)
111.4(3)
113.9(3)
112.48(17)
102.64(17)
C6C2C3
O1C3C7
O1C3C2
C7C3C2
O3C6N1
O3C6C2
N1C6C2
O4C7N2
O4C7C3
N2C7C3
110.99(18)
110.5(2)
104.69(16)
114.9(2)
123.4(2)
117.96(18)
118.5(2)
124.18(19)
121.1(2)
114.7(2)
Unlike ammonia, the reaction of less basic aniline
with diethyl 2,2-dimethyl-1,3-dioxolane-4,5-dicar-
boxylate (IV) does not give the desired aminolysis
product. When the reaction of diester IV with aniline
was performed under severe conditions (at elevated
temperature in the presence of sodium methoxide),
we obtained an unexpected product, N,N -diphenyl-
1
oxamide, whose structure was confirmed by the H
and 13C NMR spectra and elemental analysis (its
melting point coincided with that reported in the
literature). This product is likely to be formed as
a result of elimination of acetone with opening of
the dioxolane ring, followed by rearrangment and
aminolysis (Scheme 3). The proposed scheme is sup-
ported by identification of volatile products, acetone,
ethanol, and ethyl acetate, which were isolated from
the reaction mixture by distillation and were identified
diethyl tartrate and aniline, and subsequent cyclization
according to Scheme 4 unexpectedly resulted in
formation of (5S,5 S)-2,2,2 ,2 -tetramethyl-3,3 -di-
phenyl-5,5 -bioxazolidine (VII). The structure of
product VII was confirmed by the H and 13C NMR
1
1
spectra. The H NMR spectrum contains signals from
1
by GLC and H NMR spectroscopy.
aromatic protons and CH, CH2, and CH3 groups at
a ratio of 5:1:2:6 rather than 5:1:2:3 as might be
expected for structure Id. Diastereotopic CH3 groups
Our attempt to synthesize diamine Id by reduction
of diamide IIb, which was in turn prepared from
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

106
SHAINYAN et al.
Scheme 3.
appear in the spectrum of VII in CDCl3 as two
singlets, whereas in C6D6 only one singlet is observed.
The structure of compound VII was unambiguously
established by X-ray analysis. The geometric param-
eters of molecule VII are collected in Table 3.
C12, C1 , and C12 atoms deviating from the corre-
sponding planes formed by the other atoms of the
heteroring (which are coplanar within 0.04 ) by
0.50, 0.42, 0.44, and 0.50 , respectively. The angles
between the planes of the phenyl groups and the
neighboring 5-membered rings are as follows: C4 C9
19.7, C15 C20 10.9, C4 C9 5.6, and C15 C20 2.4 ,
i.e., the primed molecule is more planar. The inter-
molecular contacts are consistent with usual van der
Waals interactions.
Scheme 4.
The formation of bioxazolidine VII can be inter-
preted as a cyclization involving two HOCHCH2-
NHPh fragments of molecule VI by the action of
2,2-dimethoxypropane (Scheme 5).
Scheme 5.
A unit cell of compound VII in crystal contains
two symmetry-independent molecules each having its
own C2 pseudosymmetry. The two molecules are
interrelated through a noncrystallographic inversion
center at the point [[1/4,3/4,1/4]]. The conformations
of these molecules differ mainly by the angle formed
by the phenyl group and mean-square plane of the
neighboring heteroring. The tetrahydrooxazole rings
Chiral diamines Ic and VII were tested as ligands
in the catalytic hydrogenation of prochiral substrates,
itaconic acid (VIII) and -acetamidocinnamic acid
(IX), with molecular hydrogen (Table 4). Enantio-
selective hydrogenation of itaconic acid over rhodium
complexes with diamines Ic and VII yields excess
adopt a clearly defined envelope conformation, the C1,
Table 2. Parameters of intermolecular hydrogen bonds in the crystalline structure of compound IIIa
N atom
H atom
O atom
N H,
H
O,
N
O,
NHO, deg
Symmetry transformation
N1
N1
N2
N2
H1N1
H2N1
H1N2
H2N2
O2
O3
O4
O3
0.90
0.88
0.87
0.84
2.28
2.12
2.05
2.01
3.157
2.906
2.907
3.089
166
148
172
155
1
1
x
x, 1/2 + y, 3/2
x, y 1/2, 3/2
1/2, 3/2 y, 1
z
z
z
x
1, y, z
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

DIAMINES HAVING A C2 SYMMETRY.
107
Table. 3. Bond lengths d and bond angles in the molecule of (5S,5 S)-2,2,2 ,2 -tetramethyl-3,3 -diphenyl-5,5 -bioxa-
zolidine (VII)
Bond
d,
Bond
d,
Bond
d,
Bond
d,
O1 C1
O1 C3
O2 C12
O2 C14
N1 C4
N1 C2
N1 C3
N2 C15
N2 C13
N2 C14
C1 C12
C1 C2
C3 C11
C3 C10
C4 C9
1.420(3)
1.430(3)
1.417(3)
1.424(3)
1.381(3)
1.430(3)
1.467(4)
1.368(3)
1.426(3)
1.473(3)
1.499(4)
1.516(4)
1.495(5)
1.505(5)
1.397(4)
O1 C3
O1 C1
O2 C14
O2 C12
N1 C4
N1 C2
N1 C3
N2 C15
N2 C13
N2 C14
C1 C12
C1 C2
C3 C10
C3 C11
C4 C5
1.417(3)
1.426(3)
1.424(3)
1.426(3)
1.385(3)
1.433(3)
1.468(3)
1.374(3)
1.436(3)
1.475(3)
1.484(3)
1.498(4)
1.490(5)
1.510(5)
1.392(4)
C4 C5
1.398(4)
1.382(4)
1.359(5)
1.365(5)
1.377(4)
1.512(3)
1.492(4)
1.507(4)
1.395(4)
1.396(4)
1.376(4)
1.365(5)
1.365(4)
1.373(4)
C4 C9
1.396(4)
1.371(4)
1.369(5)
1.370(4)
1.372(4)
1.506(3)
1.494(4)
1.508(4)
1.390(4)
1.399(4)
1.378(4)
1.359(4)
1.374(4)
1.374(4)
C5 C6
C5 C6
C6 C7
C6 C7
C7 C8
C7 C8
C8 C9
C8 C9
C13 C13
C14 C21
C14 C22
C15 C16
C15 C20
C16 C17
C17 C18
C18 C19
C19 C20
C12 C13
C14 C21
C14 C22
C15 C20
C15 C16
C16 C17
C17 C18
C18 C19
C19 C20
Angle
, deg
Angle
, deg
Angle
, deg
Angle
, deg
C1O1C3
107.7(2)
C3 O1 C1
110.63(19)
108.72(18)
121.5(2)
126.3(2)
109.8(2)
122.3(2)
127.0(2)
110.67(19)
110.4(2)
103.8(2)
114.7(2)
102.3(2)
103.7(2)
107.8(3)
112.8(3)
106.1(2)
113.6(3)
C11C3C10
N1C4C9
112.5(3)
120.0(3)
122.3(3)
117.7(3)
120.1(3)
121.5(3)
119.1(3)
121.2(3)
120.5(3)
110.6(2)
C10 C3 C11
N1 C4 C5
N1 C4 C9
C5 C4 C9
C6 C5 C4
C7 C6 C5
C6 C7 C8
C7 C8 C9
C8 C9 C4
O2 C12 C1
112.2(3)
123.0(3)
119.8(2)
117.2(3)
120.7(3)
121.7(3)
118.3(3)
121.2(3)
120.9(3)
110.1(2)
103.5(2)
114.6(2)
102.3(2)
102.94(19)
108.4(2)
113.0(2)
105.6(2)
C12O2C14
C4N1C2
108.97(17) C14 O2 C12
120.6(2)
126.9(2)
111.0(2)
121.4(2)
127.3(2)
111.0(2)
110.8(2)
C4 N1 C2
N1C4C5
C4N1C3
C4 N1 C3
C9C4C5
C2N1C3
C2 N1 C3
C6C5C4
C15N2C13
C15N2C14
C13N2C14
O1C1C12
O1C1C2
C15 N2 C13
C15 N2 C14
C13 N2 C14
O1 C1 C12
C7C6C5
C6C7C8
C7C8C9
C8C9C4
103.78(18) O1 C1 C2
O2C12C1
O2C12C13
C1C12C13
N2C13C12
O2C14N2
O2C14C21
N2C14C21
O2C14C22
C12C1C2
N1C2C1
112.6(2)
102.1(2)
103.0(2)
104.9(3)
114.8(3)
109.7(2)
111.1(3)
C12 C1 C2
N1 C2 C1
O1 C3 N1
O1 C3 C10
N1 C3 C10
O1 C3 C11
N1 C3 C11
104.68(18) O2 C12 C13
112.1(2)
103.2(2)
103.3(2)
104.3(2)
115.2(2)
110.3(2)
C1 C12 C13
N2 C13 C12
O2 C14 N2
O2 C14 C21
N2 C14 C21
O2 C14 C22
O1C3N1
O1C3C11
N1C3C11
O1C3C10
N1C3C10
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108
SHAINYAN et al.
Table 3. (Contd.)
Angle
, deg
Angle
, deg
Angle
, deg
Angle
, deg
N2C14C22
C21C14C22
N2C15C16
N2C15C20
C16C15C20
110.8(2)
112.2(3)
120.0(2)
123.3(2)
116.7(2)
N2 C14 C22
C21 C14 C22
N2 C15 C20
N2 C15 C16
C20 C15 C16
113.0(2)
113.1(3)
123.0(2)
120.0(2)
116.9(2)
C17C16C15
C18C17C16
C17C18C19
C18C19C20
C19C20C15
121.4(3)
120.6(3)
119.1(3)
121.2(3)
121.0(3)
C17 C16 C15
C18 C17 C16
C17 C18 C19
C20 C19 C18
C19 C20 C15
120.8(3)
121.7(3)
118.0(3)
121.8(3)
120.8(3)
( )-(S)-methylsuccinic acid; however, the optical yield
of the product is greater when primary diamine was
used as ligand. From -acetamidocinnamic acid,
excess ( )-(R)-N-acetylphenylalanine was obtained in
both cases with moderate optical yields. The low
optical yields of the hydrogenation products over
rhodium complex with ligand VII can be explained
by steric factor: because of its large size diamine
VII is incapable of competing with olefins for
coordination site at the transition metal, so that the
hydrogenation occurs mainly over achiral rhodium(I)
complexes.
evacuation. ( )-(R,R)-DIOP [14] and (Z)- -acetamido-
cinnamic acid and its methyl ester [15] were prepared
by known methods.
(4S,5S)-4,5-Bis(aminomethyl)-2,2-dimethyl-1,3-
dioxolane (Ic). A suspension of 7.72 g (0.2 mol) of
LiAlH4 in 170 ml of anhydrous dioxane was refluxed
for 30 min, and 14.2 g (0.075 mol) of compound IIIc
was added in small portions while stirring. When the
reaction was complete, the mixture was cooled and
filtered, the precipitate was treated with hot dioxane
(3 150 ml), the extract was combined with the fil-
trate and evaporated on a rotary evaporator, and the
residue was distilled under reduced pressure. Yield 9 g
(75%), bp 73 75 C (3 mm), [ ]D = 8.17 (c = 8.7,
benzene). Mass spectrum, m/z (Irel, %): 114 (71)
[M NH2 CH2NH2]+, 72 (100) [M CH2NH2
EXPERIMENTAL
The NMR spectra were recorded on a Bruker DPX-
400 spectrometer at 400 (1H) and 100 MHz (13C)
using HMDS as internal reference; the chemical shifts
are given relative to TMS. The mass spectra (70 eV)
were obtained on an LKB 2091 instrument. GLC
analysis was performed on an LKhM-80 chromato-
graph, equipped with a thermal conductivity detector;
2000 3-mm column packed with 5% of SE-30 on
Chromaton N-AW-HMDS; carrier gas helium. The
optical rotations were measured on a Polamat A spec-
tropolarimeter at = 546 nm and were recalculated to
= 589 with a factor of 1.17543. The X-ray diffrac-
tion data were obtained on a Syntex P1 diffractometer
(CuK irradiation, -filter, /2 scanning). Arrays
of experimental reflections were treated with account
taken of the Lorentz and polarization factors, with
no regard to X-ray irradiation of the sample. The
structures were solved by the direct method and were
refined using the full-matrix least-squares procedure
in anisotropic approximation for non-hydrogen atoms
and isotropic approximation for hydrogen atoms
(which were localized experimentally from the dif-
ference Fourier syntheses).
Me2CO]+, 44 (74) [C2H4NH2]+, 30 (54) [CH2NH2]+.
1H NMR spectrum (CDCl3), , ppm: 1.40 s (6H,
Me2C), 1.55 br.s (2H, NH2), 2.82 d.m (2H, HA in
2
2
CH2, J = 13.3 Hz), 2.89 d.m (2H, HB in CH2, J =
13.3 Hz), 3.77 m (2H, CH). 13C NMR spectrum
(CDCl3), C, ppm: 27.43 (CH3), 44.32 (CH2),
80.34 (CH).
(4R,5R)-2,3-Dihydroxy-N,N -diphenylsuccin-
amide (IIb). A mixture of 26 g (0.126 mol) of diethyl
tartrate, 46 ml (0.5 mol) of aniline, and 20 ml of
1,3,5-trimethylbenzene was heated at 170 175 C with
simultaneous distillation of liberated ethanol (for 6
10 h, until 1,3,5-trimethylbenzene began to distil
over). After cooling, the colorless crystals were fil-
tered off, washed with chloroform, and dried. Yield
24 g (64%), mp 180 C (decomp.), [ ]D = +87.7
(c = 0.35, acetone). Mass spectrum, m/z (Irel, %): 253
(35) [M H2O CHO]+, 180 (7) [M PhNHCO]+, 120
(14) [PhNHCO]+, 92 (100) [PhNH]+, 77 (20) [Ph]+.
1H NMR spectrum (DMSO-d6), , ppm: 4.50 d (2H,
3
3
CH, J = 6.5 Hz), 6.02 d (2H, OH, J = 6.5 Hz),
Thoroughly purified and degassed solvents were
used in the hydrogenation. The catalytic mixtures
were prepared under argon using a system which
ensured supply of purified gas and the possibility for
3
3
7.07 t (2H, p-H, J = 7.4 Hz), 7.31 t (4H, m-H, J =
7.9 Hz), 7.74 d (4H, o-H, J = 7.2 Hz), 9.59 s (2H,
NH). 13C NMR spectrum (DMSO-d6), C, ppm: 73.86
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

DIAMINES HAVING A C2 SYMMETRY.
109
(CH), 120.18 (Co), 124.19 (Cp), 129.25 (Cm), 139.01
(Ci), 171.41 (C O).
Table 4. Hydrogenation of itaconic (VIII) and -acet-
amidocinnamic (IX) acids over [Rh(COD)2]+ CF3SO3 in
the presence of diamines Ic and VII (cRh = 2 10 M;
3
(4R,5R)-2,2-Dimethyl-1,3-dioxolane-4,5-dicar-
boxamide (IIIa). A 100-ml high-pressure reactor
was charged with 20 g (0.081 mol) of diethyl (4R,5R)-
2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate prepared
by cyclization of diethyl tartrate under the action of
2,2-dimethoxypropane. The reactor was cooled to
40 C, 50 70 ml of liquid ammonia was added, and
the reactor was closed, kept for 6 8 h at 50 C, cooled
to 10 C, opened, and allowed to warm up to room
temperature. Excess ammonia was evaporated on
a water bath (50 60 C), the released ethanol was
removed on heating to 60 C under reduced pressure,
and the colorless crystals were dried in a vacuum.
Yield 15 g (99%), mp 158 60 C, [ ]D = 12.9 (c =
1.66, EtOH). Mass spectrum, m/z (Irel, %): 173 (16)
[M CH3]+, 145 (35) [M CONH]+, 130 (22) [M
(CH3)2CO]+, 86 (100) [130 CONH2]+, 44 (52)
[CONH2]+, 43 (51) [CONH]+. 1H NMR spectrum
(DMSO-d6), , ppm: 1.39 s (6H, CH3), 4.43 s (2H,
CH), 7.40 s (2H, NHA), 7.47 s (2H, NHB). 13C NMR
spectrum (DMSO-d6), C, ppm: 26.20 (CH3), 77.36
(CH), 111.53 (C), 171.34 (C O). X-Ray diffraction
data: C7H12N2O4; colorless prism 0.45 0.35
0.30 mm. Unit cell parameters (rhombic): a =
5.3769(6), b = 7.7750(9), c = 22.092(2) ; V =
923.56(17) 3; Z = 4, d = 1.353 g/cm3; space group
MeOH benzene ratio 2: 1, diamine Rh ratio 2: 1; 25 C)
Substrate pH , Chemical Optical yield,
2
Ligand
(S/Rh)
atm
yield, %
% (isomer)
Ic
Ic
VIII
IX
1
1
0
0
Ic
Ic
VII
VII
IX (25)
VIII (50)
IX (25)
VIII (50)
35
35
35
35
20
100
45
2.6 (R)
25.4 (S)
11.1 (R)
7.8 (S)
100
(2S,3S)-2,3-Dihydroxy-1,4-bis(phenylamino-
methyl)butane (VI). Compound IIb, 21 g (0.07 mol),
was added in small portions while stirring to a sus-
pension of 7 g (0.184 mol) of LiAlH4 in 200 ml of
boiling anhydrous dioxane. When the reaction was
complete, the mixture was cooled, and the precipitate
was filtered off and treated with boiling dioxane
(3 150 ml). The extract was combined with the fil-
trate and evaporated on a rotary evaporator, and the
residue was recrystallized from chloroform. Yield
11 g (58%), mp 112 115 C, [ ]D = +87.7 (c = 0.35,
acetone). Mass spectrum, m/z (Irel, %): 148 (39) [M
H2O PhNHCH2]+, 107 (57) [PhNHCH3]+, 106 (100)
P212121. Final divergence factors R = 0.026, Rw
0.072 [from 762 reflections with I > 2 (I)].
=
1
[PhNHCH2]+, 92 (20) [PhNH]+, 77 (14) [Ph]+. H
N,N -Diphenyloxamide (V). A mixture of 5 g
(0.02 mol) of diethyl 2,2-dimethyl-1,3-dioxolane-
4,5-dicarboxylate and 2.2 g (0.04 mol) of sodium
methoxide in 20 ml of aniline was heated at the
boiling point in a flask equipped with a high Vigreaux
column, a volatile fraction (bp 62 70 C) being dis-
tilled off. The boiling point of the mixture rose from
110 to 188 C. The mixture was boiled until volatile
products no longer distilled off and was cooled, and
the crystals were filtered off, washed with water to
neutral reaction, and dried. Yield 4 g (85%),
mp 238 C. Mass spectrum, m/z (Irel, %): 240 (100)
M+, 121 (43) [M PhNCO]+, 120 (39) [PhNHCO]+,
NMR spectrum (DMSO-d6), , ppm: 2.99 d.d.d (2H,
2
3
HA in CH2, J = 12.6, J = 7.2, 4.8 Hz), 3.22 d.d.d
3
(2H, HB in CH2, 2J = 12.6, J = 6.7, 4.7 Hz), 3.68 m
3
(2H, CH), 4.68 d (2H, OH, J = 5.9 Hz), 5.35 d.d
3
3
(2H, NH, J = 4.7, 4.8 Hz), 6.50 t (2H, p-H, J =
3
7.3 Hz), 6.58 d (4H, o-H, J = 7.7 Hz), 7.05 t (4H,
m-H, J = 7.7 Hz). 13C NMR spectrum (DMSO-d6),
3
C, ppm: 45.79 (CH2), 70.04 (CH), 112.11 (Co),
115.51 (Cp), 128.81 (Cm), 148.99 (Ci). Found, %:
C 70.01; H 7.38; N 10.15. C16H20N2O2. Calculated,
%: C 70.56; H 7.40; N 10.29.
(5S,5 S)-2,2,2 ,2 -Tetramethyl-3,3 -diphenyl-5,5 -
bioxazolidine (VII). A Soxhlet apparatus was charged
with 2 g (7.35 mmol) of compound VI, 20 ml of
chloroform, 2.5 ml (0.02 mol) of 2,2-dimethoxy-
propane, 10 mg of p-toluenesulfonic acid, and 10 g
of 4- molecular sieves. The mixture was heated for
7 8 h under reflux and cooled, 20 mg of K2CO3 was
added, the mixture was filtered and evaporated to
dryness, the residue was dissolved in 150 ml of
hexane, and the solution was filtered and evaporated
to obtain product VII as colorless crystals with
mp 109 110 C. [ ]D = +35 (c = 3.48, benzene).
1
92 (91) [PhNH]+, 77 (48) [Ph]+. H NMR spectrum
3
(DMSO-d6), , ppm: 7.16 t (2H, p-H, J = 6.7 Hz),
3
7.38 m (4H, m-H), 7.87 d (4H, o-H, J = 7.5 Hz),
10.81 s (2H, NH). 13C NMR spectrum (DMSO-d6),
C, ppm: 120.55 (Co), 124.73 (Cp), 128.84 (Cm),
137.72 (Ci), 158.70 (C O). Found, %: C 68.88;
H 5.00; N 11.48. C14H12N2O2. Calculated, %:
1
C 69.99; H 5.03; N 11.66. According to the H NMR
data and GLC (using authentic samples), the volatile
fraction contained methanol, acetone, ethanol, and
ethyl acetate.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

110
SHAINYAN et al.
1H NMR spectrum, , ppm: in CDCl3: 1.58 s and
1.62 s (6H, CH3), 3.35 m (1H, HA in CH2), 3.47 m
(1H, HB in CH2), 4.39 m (1H, CH), 6.74 m (6H, m-H,
p-H), 7.18 m (4H, o-H); in C6D6: 1.42 s (6H, CH3),
3.03 d.d (1H, HA in CH2, J = 8.6, J = 6.1 Hz),
3.13 m (1H, HB in CH2), 4.09 m (1H, CH), 6.62 d.d
(2H, m-H), 6.76 t (1H, p-H), 7.14 d.d (2H, o-H).
5. Reiss, J. and Hetfleis, Collect. Czech. Chem. Com-
mun., 1986, vol. 51, nos. 1 2, pp. 340 346.
6. Nindakova, L.O., Shainyan, B.A., Albanov, A.I.,
and Ustinov, M.V., Russ. J. Org. Chem., 2000,
vol. 36, no. 11, pp. 1612 1617.
2
3
7. Okamoto, Y., Shohi, H., and Yuki, H., J. Polymer
Sci., Polymer Lett., 1983, vol. 21, no. 8, pp. 601 607.
13C NMR spectrum (C6D6), C, ppm: 26.19, 26.28
(CH3), 49.31 (CH2), 74.72 (CH), 95.18 (C), 115.17
(Co), 118.21 (Cp), 129.31 (Cm), 145.02 (Ci). Found,
%: C 74.61; H 8.08; N 8.10. C22H28N2O2. Calculated,
%: C 74.97; H 8.01; N 7.95. X-Ray diffraction data:
C22H28N2O2; colorless prism (rhombic), 0.45 0.28
0.25 mm. Unit cell parameters: a = 10.915(1), b =
17.407(2), c = 20.485(3) ; V = 3892.1(8) 3; Z = 8,
d = 1.203 g/cm3. Space group P212121. Final diverg-
ence factors R = 0.029, Rw = 0.073 [from 2959 reflec-
tions with I > 2 (I].
8. US Patent no. 5395947, 1993; Chem. Abstr., 1993,
vol. 118, no. 224389b.
9. Kim, D.K., Kim, G., Gam, J., Cho, Y.B., Kim, H.T.,
Tai, J.H., Kim, K.H., Hong, W.-S., and Park, J.G.,
J. Med. Chem., 1994, vol. 37, no. 10, pp. 1471 1485.
10. Gamez, P., Fache, F., and Lemaire, M., Tetrahedron:
Asymmetry, 1995, vol. 6, no. 3, pp. 705 718.
11. Touchard, F., Bernard, M., Fache, F., Delbecq, F.,
Guiral, V., Sautet, P., and Lemaire, M., J. Organo-
met. Chem., 1998, vol. 567, nos. 1 2, pp. 133 136.
12. Robert, F. and Sinou, D., J. Organomet. Chem.,
2000, vol. 604, no. 1, pp. 99 102.
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