Supramolecular interactions in sodium N-(ethoxythioxomethyl)-β- alaninate-water (4/6) crystal and its application in synthesis of L-carnosine

Article abstract of DOI:10.1007/s10870-012-0374-x

Compound sodium N-(ethoxythioxomethyl)-β-alaninate (sodium 3-(ethoxycarbonothioyl)propanoate) was synthesized and characterized by IR, ¹HNMR, ESI-HRMS and single crystalX-ray diffraction. Single crystalX-ray diffraction analysis showed that the title compound crystallized in the triclinic space group P-1 with cell parameters a = 10.142 (2) A, b = 13.738 (3) A, c = 15.751 (3) A, α= 72.937 (2)°, β = 78.694 (2)°, γ = 89.999 (2)°, V = 2053.4 (7) A³, D_c = 1.464 g cm-3, Z = 2. In the extended structure of sodium N-(ethoxythioxomethyl)-β-alaninate-water (4/6), (NaL)₄· 6H₂O [L = CH₃CH₂OC(S)NHCH₂CH ₂COO], ligands (Ls) are stabilized by intermolecular O-H···O, N-H···O, C- H···O and weak O-H···S and C-H···S linkages, which further consolidate the crystal packing, making the ligand chains stacked along [0-1 1], and intramolecular O-H···S hydrogen bond is also observed. Each Na atom is surrounded with six O atoms, forming an octahedron and mutually bonded as tetramers. These tetramers are linked through O atom bridges from water molecules, extending as layers in the ab plane. In addition, synthesis of β-alanyl dipeptides was developed with particular focus on the preparation of L-carnosine. Springer Science+Business Media New York 2012.

Full text of DOI:10.1007/s10870-012-0374-x

J Chem Crystallogr (2012) 42:1182–1189
DOI 10.1007/s10870-012-0374-x
ORIGINAL PAPER
Supramolecular Interactions in Sodium N-(Ethoxythioxomethyl)-
b-Alaninate–Water (4/6) Crystal and Its Application in Synthesis
of L-Carnosine
•
•
•
Shi-Jie Zhang Feng Xu Wei-Ji Yang
Wei-Xiao Hu
Received: 12 April 2012 / Accepted: 20 September 2012 / Published online: 4 October 2012
Ó Springer Science+Business Media New York 2012
Abstract Compound sodium N-(ethoxythioxomethyl)-
b-alaninate (sodium 3-(ethoxycarbonothioyl)propanoate) was
synthesized and characterized by IR, 1H NMR, ESI-HRMS and
single crystal X-ray diffraction. Single crystal X-ray diffraction
analysis showed that the title compound crystallized in the
triclinic space group P-1 with cell parameters a = 10.142 (2)
synthesis of b-alanyl dipeptides was developed with particular
focus on the preparation of L-carnosine.
Keywords Sodium N-(ethoxythioxomethyl)-b-alaninate ꢀ
Synthesis ꢀ Crystal structure ꢀ Supramolecular interaction ꢀ
Carnosine
˚
˚
˚
A, b = 13.738 (3) A, c = 15.751 (3) A, a = 72.937 (2)°, b =
3
˚
78.694 (2)°, c = 89.999 (2)°, V = 2053.4 (7) A , Dc = 1.464
Introduction
g cm-3, Z = 2. In the extended structure of sodium N-(eth-
oxythioxomethyl)-b-alaninate–water (4/6), (NaL)4ꢀ6H2O
[L = CH3CH2OC(S)NHCH2CH2COO], ligands (Ls) are sta-
bilized by intermolecular O–HꢀꢀꢀO, N–HꢀꢀꢀO, C–HꢀꢀꢀO and
weak O–HꢀꢀꢀS and C–HꢀꢀꢀS linkages, which further consolidate
the crystal packing, making the ligand chains stacked along
[0–1 1], and intramolecular O–HꢀꢀꢀS hydrogen bond is also
observed. Each Na atom is surrounded with six O atoms,
forming an octahedron and mutually bonded as tetramers.
These tetramers are linked through O atom bridges from water
molecules, extending as layers in the ab plane. In addition,
1,3-Thiazinane-2,6-dione 5 was a versatile building block in
the synthesis of b-alanyl dipeptides [1], especially in the
synthesis of L-carnosine [2], which is a naturally-occurring
dipeptide widely and abundantly distributed in high con-
centrations in mammalian tissue and skeletal muscle cells,
responsible for a variety of activities, in particular, antioxi-
dant activity[3, 4]. A modified preparationof 1,3-thiazinane-
2,6-dione 5 was reported by our group starting from ethanol
by tandem reactions with aqueous sodium hydroxide and
carbon disulfide, bromoethane and b-alanine with triethyl
benzyl ammonium chloride as phase transfer catalyst to yield
sodium N-(ethoxythioxomethyl)-b-alaninate 3a, which was
neutralized by hydrochloric acid and cyclized with an overall
yield of 72 % (based on b-alanine) [5].
However, O,S-diethyl carbonodithioate 2 reacted with
b-alanine was prone to obtaining sodium N-(ethoxythioxom-
ethyl)-b-alaninate 3a and sodium N-[(ethylthio)thioxometh-
yl]-b-alaninate 3b, due to the cleavage of C–S or C–O bond of
compound 2 (Scheme 1). From the 1H NMR spectrum of the
hydrolyzed product (Fig. 1), it indicated that compounds 4a
and 4b coexisted with a ratio of approximately 3:2, which
varied slightly from batch-to-batch, and cyclization of both
compounds 4a and 4b led to solely 1,3-thiazinane-2,6-dione 5
in ethyl acetate. L-Carnosine 6 was obtained from L-histidine
and compound 5, and this method was also feasible to prepare
b-alanyl dipeptides with moderate to good yields.
S.-J. Zhang ꢀ W.-J. Yang
Graduate School, Zhejiang Chinese Medical University,
Hangzhou 310053, People’s Republic of China
e-mail: medchem@zcmu.edu.cn
F. Xu
Department of Biological and Chemical Engineering, Taizhou
Vocational and Technical College, Taizhou 318000, Zhejiang,
People’s Republic of China
W.-X. Hu (&)
College of Pharmaceutical Science, Zhejiang University of
Technology, Hangzhou 310032, People’s Republic of China
e-mail: huyang@mail.hz.zj.cn
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1183
Scheme 1 Synthetic route of
L-carnosine
Fig. 1 1H NMR spectrum of mixture 4a and 4b
Synthesis of Sodium N-(Ethoxythioxomethyl)-b-Alaninate
3a and Sodium N-[(Ethylthio)thioxomethyl]-b-Alaninate
3b
In order to study these intermediates, we tried to grow
single crystals of the mixed product 4a or 4b in various
conditions, and finally the single crystals of 3a were
obtained as the sodium salt.
To a solution of sodium hydroxide (24.0 g, 600 mmol) in
water (29.5 mL) was added ethanol (35.5 mL, 610 mmol)
at 20–25 °C. Carbon disulfide (48.6 g, 640 mmol) was then
added dropwise in 40–60 min and white solid precipitated.
The mixture was further stirred for 1 h until homogenous.
Methanol (60 mL), benzyl triethyl ammonium bromide
(TEBA) (4.0 g, 20 mmol) were added, and then ethyl
bromide (65.4 g, 600 mmol) was added dropwise in
40–60 min. The mixture was stirred for 6 h and the filtrate
was a solution of O,S-diethyl carbonodithioate 2.
Experimental
General Information on Reagents and Techniques
Melting points were determined using an X-4 apparatus
and are uncorrected. Infrared (IR) spectra were recorded on
a Thermo Nicolet Avatar 370 FT-IR spectrometer. 1H
NMR spectra were recorded on a Brucker AVANCE III
(500 MHz) spectrometer with TMS as an internal standard.
Mass spectra were recorded on a Waters GCT Premier
instrument with EI source or on an Agilent 6210 TOF LC/
MS instrument with ESI source. High resolution mass
spectrum (HRMS) was measured on an Agilent 6210 TOF
LC/MS instrument with ESI source. Optical rotation was
determined in a 1 cm cell with a path length of 1 dm using
a Rudolph autopol IV automatic polarimeter (NaD line).
To a stirred mixture of b-alanine (40.0 g, 450 mmol)
suspended in methanol (50 mL) was added 45 % aqueous
sodium hydroxide (28.5 mL). Then the prepared filtrate
O,S-diethyl carbonodithioate 2 in methanol was added
dropwise in 40–60 min and the temperature was allowed to
45 °C with evolution of ethanethiol gas. After about 1 h,
the solution was concentrated under vacuum and left pale
yellow solid, which was a mixture of 3a and 3b.
123

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J Chem Crystallogr (2012) 42:1182–1189
Caution: Ethanethiol has a strongly disagreeable odor and
the reaction mixture became clear and was further stirred for
30 min at 10 °C. Formic acid (ca. 2 mL) was added to pH 4.2
with evolution of gas, and then 25 % TEAH was added with
care to pH 8.2. The solvent was removed under vacuum left
colorless oily liquid, to which anhydrous ethanol (300 mL)
was added to precipitate white solid. After filtration the
solid was washed by 95 % ethanol, dichloromethane and
ethyl ether to give white powders 6: 3.4 g (75.6 %), mp:
is toxic. Operations concerning ethanethiol must be carried
out in a well-ventilated hood and the released ethanethiol gas
should be absorbed by aqueous sodium hydroxide or potas-
sium permanganate.
Suitable crystals of 3a for the X-ray crystal structure
determination were grown from water by slow evaporation
of the solvent.
25
249–250 °C; ½aꢁD = 20.5° (c = 2, H2O); IR (KBr, cm-1):
Characterization for 3a: white solid, mp: 166–169 °C; IR
(KBr, cm-1): 3,239, 2,984, 1,645, 1,609, 1,556, 1,427, 1,402,
1,191; 1H NMR (500 MHz, D2O, d ppm): 4.38–4.33 (m, 2H,
CH3CH2–), 3.62–3.58 (m, 2H, –NH–CH2–), 2.44–2.39 (m,
2H, –CH2CO–), 1.23–1.19 (m, 3H, CH3CH2–); ESI-HRMS:
[M ? H] 200.0341 for C6H10NNaO3S ? H (Calcd. 200.
0357).
3,241, 3,060, 2,623, 2,025, 1,645, 1,584; 1H NMR(500
MHz, D2O, d ppm): 2.56 (tt, J = 6.5 Hz, 2H, NH2–CH2–),
2.89 (s, J = 5.5 Hz, 1H, –CHH–CH–), 3.03 (s, J = 5.0 Hz,
1H, –CHH–CH–), 3.12 (tt, J = 5.5 Hz, 2H, –CH2–CO), 4.37
(t, J = 5.0 Hz, 1H, –CH–COOH), 6.85 (s, 1H, –N–CH–NH–
), 7.61 (t, 1H, –NH–CH–CH2); ESI–MS (m/z, %): 225 ([M–
H]?,100), 216 (11), 182 (10), 114 (11).
Synthesis of 1,3-Thiazinane-2,6-Dione 5
The mixture 3a and 3b was dissolved in water (75 mL),
and washed with ethyl acetate (250 mL). The aqueous
layer was acidified by 6 N hydrochloric acid (ca. 100 mL)
to pH 2, and extracted by ethyl acetate (3 9 150 mL). The
organic ethyl acetate layer was washed by brine
(2 9 100 mL) and dried over anhydrous magnesium sul-
fate. After concentration, the residue was washed with
petroleum ether and yielded pale yellow solid of 4a and 4b,
which was used directly without further purification.
To a solution of prepared mixture of 4a and 4b (5.51 g,
ca. 30 mmoL) in ethyl acetate (25.5 mL) at 10–15 °C was
added dropwise a solution of phosphorus tribromide
(8.93 g, 33 mmol) in ethyl acetate (10 mL) in 20 min to
precipitate white solid. The mixture was further stirred
for 40 min at 25 °C, monitored by TLC (ethyl acetate:
n-hexane = 3:7). After completion, 5 % sodium bicar-
bonate (35 mL) was added, and extracted with ethyl ace-
tate (3 9 25 mL), washed by brine and dried over
anhydrous magnesium sulfate. Concentration of the solvent
left sticky residue (ca. 3.8 g), which was stirred with ethyl
acetate (2.5 mL) and cooled to precipitate white powders
5: 3.30 g (84.0 %), mp: 89–92 °C; IR (KBr, cm-1): 3,311,
3,212, 1,730, 1,636, 1,052, 1,032; 1H NMR (500 MHz,
CDCl3, d ppm): 7.35 (br, 1H, NH), 3.60 (q, J = 5.0 Hz,
2H, –CH2–CO), 2.85 (t, J = 6.0 Hz, 2H, –CH2–NH);
EI-MS (m/z, %): 131 (M?, 98), 103 (22), 98 (100).
Crystal Structure Determination and Refinement for 3a
A colorless tabular single crystal of 3a with approximate
dimensions of 0.30 9 0.25 9 0.25 mm was mounted on the
top of a glass fiber in a random orientation. The data col-
lection was performed on a Brucker SMART APEX CCD
area detector diffractometer equipped with a graphite-
˚
monochromatic MoKa (k = 0.71073 A) radiation using the
SMART program [6]. The collected data were reduced by
using the program SAINT and empirical absorption correc-
tion was made by using the SADABS program. Out of
the total 11,083 reflections collected in the range of 2.2° B
h B 25.5° (–12 B h B 11, -16 B k B 16, -19 B l B 14)
at 293 (2) K, 7,659 were independent with Rint = 0.022 and
5,528 were observed (I [ 2r(I)). The structure was solved
by direct methods and refined on F2 by full-matrix least-
squares techniques with SHELXS97 and SHELXL97 [7]. All
of the non-hydrogen atoms were refined anisotropically, and
the hydrogen atoms were located by geometry calculation
and riding on the related parent atoms and refined isotropi-
˚
cally. The C–H distances were within the range 0.96–0.97 A
and Uiso(H) values were set at 1.2 or 1.5 times Ueq(C). Other
H atoms were fixed geometrically and treated as riding on the
parent N or O atoms by a mixture of independent and con-
strained refinement. Atoms C22, C23, C32, C33 from the
ligand possessed relatively high parameters from thermal
motion. This situation itself was very characteristic for long
chain fragments, and was not possible to resolve this disor-
der. Thus, these atoms were refined with similar Uij (SIMU)
restraints for atomic thermal parameters and this afforded
well-refinable model. A full-matrix least-squares refinement
gave the final R = 0.081, wR = 0.172 (w = 1/[r2(Fo2) ?
(0.0736P)2 ? 0.5088P], where P = (Fo2 ? 2F2c)/3), S = 1.27,
Synthesis of L-Carnosine 6
To a solution of L-histidine (3.1 g, 20 mmol) in water
(30 mL) cooled to 10 °C was added 25 % aqueous tetraethyl
ammonium hydroxide (TEAH) adjusting the pH to 9.2. 1,3-
Thiazinane-2,6-dione 5 (3.9 g, 30 mmol) was added to the
mixture in portions in 30 min and maintaining the pH
between 8.2 and 9.2 by adding 25 % TEAH. After addition,
-3
.
˚
(D/r)max = 0.001, (Dq)max = 0.71 and (Dq)min = -0.80 eA
Crystallographic details for 3a are given in Table 1.
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J Chem Crystallogr (2012) 42:1182–1189
1185
b-alanyl-glycine (b-Ala-Gly), b-alanyl-b-alanine (b-Ala-b-
Ala), b-alanyl-DL-methionine (b-Ala-DL-Met) with the
corresponding amino acids, respectively, with moderate to
good yields. And it should be noted that the proper pH
values were quite important to precipitate the desired
b-alanyl dipeptides.
Table 1 Crystal data and structure refinement of 3a
Compound no
3a
Compound
C24H52N4Na4O18S4
Colorless
904.94
Color
Formula weight
Temperature (K)
Crystal system
Space group
293(2)
N-(Ethoxythioxomethyl)-b-alanine (LH) 4a is an inter-
mediate in the synthesis of L-carnosine [1]. The crystal
structure of (NaL)4ꢀ6H2O 3a is described in the space group
P-1 with all atoms located in general positions. Compound
3a comprises four NaL and six water molecules in the
asymmetric unit (Fig. 2), and selected bond lengths Na–O
and bond angles O–Na–O or Na–O–Na are listed in Table 2.
The hydrogen bonds in crystal 3a are shown in Fig. 3 and
listed in Table 3. It is noteworthy that the carboxylate O(4)vii
[symmetry code: (vii) x - 1, y, z] is intermolecularly bonded
as C–HꢀꢀꢀO and N–HꢀꢀꢀO linkages, and involved as bifurcated
hydrogen bonds with two H atoms, H(22B) and H(2X),
riding on C(22) and N(2) atoms, respectively. Similar
bifurcated hydrogen bonds were found with O(10)vi [sym-
metry code: (vi) -x ? 1, -y, -z] as C(32)–H(32A)ꢀꢀꢀO(10)vi
and N(3)–H(3X)ꢀꢀꢀO(10)vi. By extending the molecules down
b axis, another carboxylate O(11)ii is found to be intermo-
lecularly bonded as bifurcated hydrogen bonds with H(1X)
and H(4X)v riding on O(1) and N(4)v atoms from two distinct
molecules. Atom S(4)v is bonded with H(1Y), thus forming a
R23ð8Þ motif, which consists of three molecules at different
symmetry positions [symmetry codes: (ii) x, y ? 1, z; (v) -x,
-y ? 1, -z]. On the whole, there exist four O–HꢀꢀꢀOi, ii, iii, iv
[symmetrycodes:(i)-x ? 1, -y ? 1,-z; (ii)x, y ? 1, z; (iii)
-x, -y, -z; (iv) x, y - 1, z], three N–HꢀꢀꢀOiii, vi, vii [symmetry
codes:(iii) -x, -y, -z; (vi) -x ? 1, -y, -z; (vii) x - 1, y, z],
twoC–HꢀꢀꢀOvi, vii [symmetrycodes:(vi)-x ? 1, -y, -z; (vii)
Triclinic
P-1
Unit-cell dimensions
˚
a (A)
10.142(2)
13.738(3)
15.751(3)
72.937(2)
78.694(2)
89.999(2)
2053.4(7)
2
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
3
˚
Volume A
Z
Dcacl (g cm-3
)
1.464
F(000)
952
Index ranges
-12 B h B 11
-16 B k B 16
-19 B l B 14
0.347
Absorption coefficient (mm-1
)
˚
Radiation/k ( A)
0.71073
hmin, hmax (°)
2.2, 25.5
Reflections measured
11,083
Independent/observed reflections
Data/restraints/parameters
Goodness-of-fit on F2
Shift/su_max
7,659/5,528
7,659/36/491
1.272
0.001
Final R indices
R1 = 0.0604
wR2 = 0.1582
R1 = 0.0808
wR2 = 0.1719
0.71 and -0.80
R indices [I [ 2r(I)]
-3
)
˚
Largest diff. Peak and hole ( eA
Results and Discussion
Numerous methods for the preparation of L-carnosine have
been reported from chemo-synthsis to bio-synthesis [8–11].
1,3-Thiazinane-2,6-dione 5 was a key intermediate in the
expedient and scalable synthesis of L-carnosine. The most
critical point was to strictly control the pH in reaction
between 8.5 and 9.2 by the speed of adding TEAH and 1,3-
thiazinane-2,6-dione 5 to aqueous L-histidine. The reaction
could not proceed in acidic or weak basic conditions, as
compound 5 favored to reacting with hydroxyl ion rather
than with L-histidine.
The reaction scope was preliminarily extended with
different amino acids. The reactions went smoothly to yield
Fig. 2 A view of molecule 3a, showing the atom-numbering scheme.
Displacement ellipsoids are drawn at the 30 % probability level
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J Chem Crystallogr (2012) 42:1182–1189
˚
Table 2 Selected bond lengths (A) and bond angles (°) of 3a
˚
(A)
Bond length
Na(1)–O(3)
2.328(3)
2.407(3)
2.441(3)
2.471(3)
2.473(3)
2.487(3)
2.339(3)
2.414(3)
2.434(3)
2.446(3)
2.459(3)
2.576(3)
(°)
Na(3)–O(9)
2.325(3)
2.414(3)
2.439(3)
2.457(3)
2.477(3)
2.496(3)
2.338(3)
2.427(3)
2.432(3)
2.448(3)
2.452(3)
2.568(3)
Na(1)–O(1)
Na(3)–O(8)
Na(1)–O(2)
Na(1)–O(6)i
Na(1)–O(14)ii
Na(3)–O(12)iii
Na(3)–O(13)iii
Na(3)–O(7)
Na(1)–O(4)i
Na(3)–O(10)
Na(4)–O(11)
Na(4)–O(13)
Na(4)–O(10)
Na(4)–O(12)iii
Na(4)–O(14)
Na(4)–O(12)
Na(2)–O(5)
Na(2)–O(6)
Na(2)–O(4)i
Na(2)–O(2)
Na(2)–O(7)
Na(2)–O(2)i
Bond angle
O(3)–Na(1)–O(1)
O(1)–Na(1)–O(6)i
O(2)–Na(1)–O(14)ii
O(3)–Na(1)–O(4)i
O(6)i–Na(1)O(4)i
O(5)–Na(2)–O(6)
O(5)–Na(2)–O(4)i
O(2)–Na(2)–O(7)
O(6)–Na(2)–O(2)i
O(4)i–Na(2)–O(2)i
Na(2)–O(7)–Na(3)
103.3(1)
84.5(1)
174.7(1)
96.1(1)
77.97(9)
109.8(1)
106.2(1)
159.3(1)
91.89(9)
52.53(8)
111.2(1)
O(9)–Na(3)–O(8)
102.8(1)
84.4(1)
O(8)–Na(3)–O(13)iii
O(12)iii–Na(3)–O(7)
O(9)–Na(3)–O(10)
O(13)iii–Na(3)–O(10)
O(11)–Na(4)–O(13)
O(11)–Na(4)–O(10)
O(12)iii–Na(4)–O(14)
O(13)–Na(4)–O(12)
O(10)–Na(4)–O(12)
Na(4)–O(14)–Na(1)iv
173.7(1)
96.3(1)
78.39(9)
110.0(1)
106.4(1)
159.7(1)
91.52(9)
52.52(8)
111.4(1)
Symmetry codes: (i) -x ? 1, -y ? 1, -z; (ii) x, y ? 1, z; (iii) -x, -y, -z; (iv) x, y - 1, z
x - 1, y, z] intermolecular hydrogen bonds that further con-
solidate the crystal packing. Sulfur atoms are not that good
acceptors of hydrogen bonds such as O–HꢀꢀꢀS, N–HꢀꢀꢀS, and
C–HꢀꢀꢀS as are the oxygen or nitrogen atoms, and these bon-
dings are generally weak [12, 13]. In the crystal, three weak
intermolecular O–HꢀꢀꢀSiii, v, vi [symmetry codes: (iii) -x, -y,
-z; (v) -x, -y ? 1, -z; (vi) -x ? 1, -y, -z], two inter-
molecular C–HꢀꢀꢀSiii, v [symmetry codes: (iii) -x, -y, -z;
(v) -x, -y ? 1, -z] interactions and intramolecular O–HꢀꢀꢀS
contact are observed.
showing different Na–O bonding geometry. Atoms
Na(n) (n = 1 or 3) bond to six O atoms, half from car-
boxylate groups of three ligands and three from water
molecules. However, atoms Na(n) (n = 2 or 4) bond to six
O atoms, one-third of which are from two carboxylate O
atoms of one ligand, and one-third from the rest two
ligands whose carboxylate groups offer one O atom each,
and last two O atoms are from two water molecules.
Likewise, on the other aspect, the ligands also exhibit two
different coordination modes. The ligands L(n) (n = 2 or
4) participate in two Na–O bonds, and the ligands
L(n) (n = 1 or 3) take part in five Na–O bonds. For
example, in L(1), atom O(2) chelates to three atoms Na(1),
Na(2) and Na(2)i, and atom O(4) merely shares between
atoms Na(1)i and Na(2)i [symmetry code: (i) -x ? 1,
-y ? 1, -z]. Generally, atom Na(1) shares octahedral O
atom edges with atoms Na(2), Na(2)i and Na(4)ii, and atom
Na(2) shares octahedral edges with atoms Na(1), Na(3),
Na(1)i, Na(2)i, and atom Na(3) shares with atoms Na(2),
Na(4), Na(4)iii, and atom Na(4) shares with atoms Na(3)iii,
Na(4)iii, Na(3) [symmetry codes: (i) -x ? 1, -y ? 1, -z;
In an extended network, every Na atom exquisitely
coordinates to six O atoms, and the lengths of Na–O bonds
˚
are within the range 2.325 (3) -2.576 (3) A, which are in
good agreement with the values found in other related
structures with Na–O bonds [14–17]. Octahedra centred on
Na are built, but with different coordination modes
(Fig. 4). As for Na(1), the O(14)ii–Na(1)–O(2) axis
(angle = 174.7 (1)°) penetrates the O(1)/O(6)i/O(4)i/O(3)
˚
coordination plane with the mean deviation of 0.2164 A,
˚
and the distance of atom Na(1) from this plane is 0.0196 A.
Atoms Na(n) (n = 1–4) bond to three distinct L ligands,
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J Chem Crystallogr (2012) 42:1182–1189
1187
Fig. 3 Hydrogen-bonded molecule 3a. For the sake of clarity, displacement ellipsoids are drawn at the 10 % probability level and only atoms
related are labelled. Dashed lines indicate hydrogen bonds. [Symmetry codes: (i) -x ? 1, -y ? 1,-z; (ii) x, y ? 1, z; (iii) -x, -y,-z; (iv) x,
y - 1, z; (v) -x, -y ? 1, -z; (vi) -x ? 1, -y, -z; (vii) x - 1, y, z]
˚
Table 3 Hydrogen-bonding geometry of 3a (A, °)
D–HꢀꢀꢀA
D–H
HꢀꢀꢀA
DꢀꢀꢀA
D–HꢀꢀꢀA
O(1)–H(1X)ꢀꢀꢀO(11)ii
0.76
0.78
0.90
0.89
0.89
0.85
0.85
0.85
0.85
1.00
0.74
0.97
0.97
0.97
0.97
2.00
2.68
1.96
1.97
2.10
2.58
2.06
2.66
1.91
2.36
2.17
2.87
2.55
2.55
2.82
2.730(4)
3.453(3)
2.838(4)
2.846(4)
2.959(4)
3.301(3)
2.876(4)
3.437(3)
2.755(4)
3.299(3)
2.885(4)
3.644(4)
3.384(5)
3.383(6)
3.582(4)
162
170
167
167
163
143
162
152
171
157
163
138
144
144
136
O(1)–H(1Y)ꢀꢀꢀS(4)v
N(2)–H(2X)ꢀꢀꢀO(4)vii
N(3)–H(3X)ꢀꢀꢀO(10)vi
N(4)–H(4X)ꢀꢀꢀO(11)iii
O(7)–H(7A)ꢀꢀꢀS(3)vi
O(7)–H(7B)ꢀꢀꢀO(1)i
O(8)–H(8B)ꢀꢀꢀS(1)
O(13)–H(13X)ꢀꢀꢀO(3)iv
O(14)–H(14X)ꢀꢀꢀS(2)iii
O(14)–H(14Y)ꢀꢀꢀO(8)iii
C(13)–H(13A)ꢀꢀꢀS(4)v
C(22)–H(22B)ꢀꢀꢀO(4)vii
C(32)–H(32A)ꢀꢀꢀO(10)vi
C(43)–H(43A)ꢀꢀꢀS(1)iii
Symmetry codes: (i) -x ? 1, -y ? 1, -z; (ii) x, y ? 1, z; (iii) -x, -y, -z; (iv) x, y - 1, z; (v) -x, -y ? 1, -z; (vi) -x ? 1, -y, -z; (vii) x -
1, y, z
(ii) x, y ? 1, z; (iii) -x, -y, -z]. The resulting arrange-
ment constitutes cage-like tetramers, exhibiting a crystal-
lographic inversion centre in the centre. These tetramers
are l4-bridging to each other by water O(7) and O(14)
atoms, extending in ab plane.
From the overall crystal packing diagram (Fig. 5), the
chains of Ls are stacked along [0–1 1], and all Na atoms lie
almost in the ab plane [the maximum deviation from the
˚
plane is 0.01787 A], where the molecules propagate as
layers to give a multi-bonded supramolecular network.
123

1188
J Chem Crystallogr (2012) 42:1182–1189
Fig. 4 Part of the infinite framework of linked NaO6 octahedra, showing the arrangement of Na–O bonding. Displacement ellipsoids are drawn
at the 10 % probability level and branched chains not involved in the motif shown have been omitted for clarity [Symmetry codes: (i) -x ? 1,
-y ? 1, -z; (ii) x, y ? 1, z; (iii) -x, -y, -z; (vi) -x ? 1, -y, -z]
Fig. 5 Crystal packing diagram of molecule 3a?, as viewed down the a axis. Displacement ellipsoids are drawn at the 10 % probability level
and hydrogen atoms are omitted
Supplementary Material
The Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK; Fax: ?44-1223-336033.
CCDC-873587 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge at www.ccdc.cam.ac.uk/conts/retrieving.html, by
e-mailing data_request@ccdc.cam.ac.uk, or by contacting
Acknowledgments The authors would like to thank Min-Qin Chen
and Jing-Mei Wang (Fudan University) for the help in resolving the
X-ray crystallographic data. This work was carried out with the
financial assistance from Science and Technology Department of
123

J Chem Crystallogr (2012) 42:1182–1189
1189
Zhejiang Province (No. 2007C21156), China and S.-J. Zhang thanks
Research Fund from Zhejiang Chinese Medical University
(2011ZY26).
7. Sheldrick GM (2008) Acta Crystallogr A 64:112–122
8. Inaba C, Higuchi S, Morisaka H, Kuroda K, Ueda M (2010) Appl
Microbiol Biotechnol 86:1895–1902
9. Heyland J, Antweiler N, Lutz J, Heck T, Geueke B, Kohler HPE,
Blank LM, Schmid A (2010) Microb Biotechnol 3:74–83
10. D’Arrigo P, Kanerva LT, Li XG, Saraceno C, Servi S, Tessaro D
(2009) Tetrahedron Asymmetry 20:1641–1645
References
11. Cherevin MS, Zubreichuk ZP, Popova LA, Gulevich TG,
Knizhnikov VA (2007) Russ J Gen Chem 77:1576–1579
12. Tan KW, Ng CH, Maah MJ, Ng SW (2008) Acta Crystallogr E
64:o1344
13. Tabatabaee M, Saheli S (2011) J Chem Crystallogr 41:670–673
14. Muir KW, MacDonald A, MacDonald A (2004) Acta Crystallogr
C 60:m645–m647
¨
15. Damian E, Eriksson L, Sandstrom M (2006) Acta Crystallogr C
62:m419–m420
16. Forsyth CM, Dean PM, MacFarlane DR (2007) Acta Crystallogr
C 63:m169–m170
17. Wang QY, Zhang ZT (2011) J Chem Crystallogr 41:1467–1471
1. Dewey RS, Schoenewaldt EF, Joshua H, Paleveda WJ, Schwam
H, Barkemeyer H, Arison BH, Veber DF, Strachan RG,
Milkowski J, Denkewalter RG, Hirschmann R (1971) J Org
Chem 36:49–59
2. Vinick FJ, Jung S (1983) J Org Chem 48:392–393
3. Guiotto A, Calderan A, Ruzza P, Borin G (2005) Curr Med Chem
12:2293–2315
4. Bellia F, Vecchio G, Rizzarelli
43:153–163
E (2012) Amino Acids
5. Zhu P, Xuan RC, Hu WX (2008) Chin J Pharm 39:647–649
6. Bruker (2000) SMART, SAINT and SADABS. Bruker AXS Inc.,
Madison
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