Synthesis and crystal structure analysis of methyl 2-hydroxyimino-3-phenyl- propionate

Article abstract of DOI:10.1007/s10870-009-9581-5

As precursors of α-amino acids, methyl 2-hydroxyimino-3-phenyl- propionate (F.W. 193.20) was synthesized, characterized by ¹H NMR, IR, element analysis and confirmed by X-ray crystal structure analysis. This compound crystallizes in monoclinic

Full text of DOI:10.1007/s10870-009-9581-5

J Chem Crystallogr (2009) 39:870–873
DOI 10.1007/s10870-009-9581-5
ORIGINAL PAPER
Synthesis and Crystal Structure Analysis of Methyl
2-Hydroxyimino-3-phenyl-propionate
Xiao-liu Li Æ Xiao-li Zhen Æ Jian-rong Han Æ
Shouxin Liu
Received: 7 September 2008 / Accepted: 4 June 2009 / Published online: 18 June 2009
Ó Springer Science+Business Media, LLC 2009
Abstract As precursors of a-amino acids, methyl
-hydroxyimino-3-phenyl-propionate (F.W. 193.20) was
a-Oximino acidic esters are particularly useful precursors of
2
a-amino acids. The catalytic hydrogenation of a-oximino
acids or esters affords a convenient method for the synthesis
of a-amino acids. Miller et al. [1] reported synthesis of a-
amino acids by reduction of a-oximino acidic esters with
titanium(III) chloride and sodium borohydride. a-Oximino
acidic esters as precursors of a-amino acid are readily
available either by reaction of hydroxylamines with a-keto
acid derivatives or by nitrosation of diethyl malonate [2]. In
addition, a-oximino acidic esters have been utilized in
various ways for the preparation of nitro compounds [3] and
chloro nitroso compounds [4]. Thus, study on synthetic
methods of a-oximino acidic esters is very important.
Generally, a-oximino acids or esters [5] may be prepared
from (a) a-keto acids or esters [6]; (b) a-halogen acids or
esters [7, 8]; (c) substituted acetoacetic [9] or malonic esters
[10] and (d) substituted malonic acids [11]. In the present
work, we wish to report the synthesis of methyl 2-hydro-
xyimino-3-phenyl-propionate by nitrosation oximation of
substituted malonic esters (Scheme 1). It is characterized by
1
synthesized, characterized by H NMR, IR, element anal-
ysis and confirmed by X-ray crystal structure analysis. This
compound crystallizes in monoclinic class under the space
˚
group P2 /c with cell parameters, a = 8.6435(17) A,
1
˚
˚
b = 5.4957(11) A, c = 21.146(4) A; b = 97.12(3)°, and
Z = 4. The structure exhibits inter-molecular hydrogen
bonds of the type O–HꢀꢀꢀN, O–HꢀꢀꢀO, C–HꢀꢀꢀO.
Keywords a-Oximino ester ꢀ Nitrosation ꢀ Oximation ꢀ
Synthesis ꢀ Crystal structure ꢀ Hydrogen bond
Introduction
Natural amino acids and peptides are particularly interest-
ing natural leads due to their potent biological activities.
However, unnatural a-amino acids have also acquired great
importance in medicinal chemistry, therefore the synthesis
of unnatural a-amino acids have attracted intense interest.
1
H NMR, IR and element analysis, and the ester’s crystal
structure was determined by X-ray diffraction analyses.
X. Li (&) ꢀ X. Zhen
College of Chemistry and Environmental Science,
Hebei University, 071002 Baoding, People’s Republic of China
e-mail: lixl@hbu.edu.cn
Experimental
General. Meltingpoints, measuredwithanXt-4apparatus,are
1
uncorrected. H NMR spectra were recorded on a Bruker
X. Zhen ꢀ J. Han
College of Sciences, Hebei University of Science and
Technology, 050018 Shijiazhuang,
People’s Republic of China
AVANCE II500 instrument in CDCl solution, using tetra-
3
methylsilane as an internal reference. Elemental analyses
were performed on a Perkin-Elmer 2400C instrument. Infra-
red spectra were recorded on PE-1730 instruments.
S. Liu (&)
College of Chemical and Pharmaceutical Engineering,
Hebei University of Science and Technology,
050018 Shijiazhuang, People’s Republic of China
e-mail: chlsx@263.net
Starting material benzyl chloride 1 was commercially
available and used without further purification. All chem-
icals were reagent grade and were used without further
1
23

J Chem Crystallogr (2009) 39:870–873
871
COOCH
CH
3
3
NaOCH3
CH
2
Cl
COOCH3
(500 MHz, CDCl , ppm) d 3.83(s,3H), 3.99(s,2H),7.20–
3
+
2
CH2 CH
COOCH
3
7.32 (m,5H), 9.64 (s,1H); IR (KBr) m 3,227, 1,742, 1,650,
COOCH
-
1
1
2
1,600, 1,495 cm ; Anal. Calcd. for C H NO : C, 62.17;
10 11 3
H, 5.74; N, 7.25. Found: C, 62.29; H, 5.65; N, 7.33.
CH
3
ONO
CH
C
N
COOCH
3
2
NaOCH
3
HO
3
X-Ray Crystallography
Scheme 1 Route of synthesis of 3
Crystals of the Oximino Ester suitable for X-ray diffraction
analysis were obtained by slow evaporation from ethyl
acetate after 7 days at room temperature. The data were
purification, unless noted otherwise. The solvent ethanol
was refluxed over sodium turnings and then distilled
fractionally.
collected with graphite-monochromated MoKa radiation
˚
(
k = 0.71073 A). The structure was solved using direct
methods and refined by full-matrix least-squares tech-
niques. All non-hydrogen atoms were assigned anisotropic
displacement parameters in the refinement. All hydrogen
atoms were added at calculated positions and refined using
The Preparation of Substituted Dimethyl Malonate 2
Metal sodium (4.6 g, 0.2 mol) were added to a 250 ml
reaction flask, which was fitted with magnetic stirrer, reflux
condenser, thermometer and dropping funnel. Then anhy-
drous ethanol (100 ml) was slowly added dropwise under
magnetic stirrer until metal sodium was entirely dissolved.
After cooling the solution to 50 °C, dimethyl malonate
2
a riding model. The structures were refined on F using
SHELXTL-97 [12]. The crystals used for the diffraction
study showed no decomposition during data collection. The
2
final R values (on F ) were 0.0404 of the title compound.
The crystal data and some details of the structure deter-
mination are summarized in Table 1. The selected bond
lengths and bond angles are given in Table 2.
(
0.2 mol) was added dropwise to above solution at 50 °C.
The mixture was stirred magnetically for 10 min, then
benzyl chloride 1 (0.205 mmol) was added to the reaction
solution, and the mixture was heated to reflux for 4 h. The
solvent was removed in vacuo. The residue obtained was
added to equal volume mixture of water and ice, and the
organic layer was separated. Water layer was extracted
with ethyl acetate (4 9 30 ml) and united with organic
Table 1 Crystallographic data and structure refinement for complex 3
Empirical formula
Formula weight
Temperature (K)
10 3
C H11NO
193.20
113(2)
0.71073
layer and dried over MgSO . The solution was condensed
4
˚
Wavelength (A)
under reduced pressure to obtain the crude product 2,
which could be used directly next reaction without
purification.
Crystal system, space group
Unit cell dimensions
Monoclinic, P2(1)/n
˚
a = 8.6435(17) A,
˚
b = 5.4957(11) A,
˚
c = 21.146(4) A;
b = 97.12(3)°
996.7(3)
Synthesis of Methyl 2-Hydroxyimino-3-Phenyl-
Propionate
3
˚
Volume (A )
-
3
)
Z, calculated density (g cm
4, 1.287
2
(0.1 mol) were added to a 250 ml reaction flask, which
-
1
)
Absorption coefficient (mm
0.096
was fitted with mechanical stirrer, refluxing condenser
having a drying tube and dropping funnel. After cooling to
F
(000)
408
-3
)
Crystal size (mm
0.18 9 0.16 9 0.12
1.94–25.02°
-9 B h B 10, -6 B k B 6,
-
20 °C with liquid nitrogen, methyl nitrite (0.105 mol)
Range for data collection
Limiting indices
was added. Then CH ONa solution (0.1 mol) was slowly
3
added dropwise under mechanical stirrer. The mixture
was placed in refrigeratory for 12 h. The solvents were
removed in vacuo, the residue obtained was added to equal
volume mixture of water. The mixture was controlled
pH = 6 with dilution hydrochloric acid, which extracted
with ethyl acetate (4 9 50 ml) and combined organic layer
and dried over anhydrous Na SO . The solution was con-
-
25 B l B 25
Reflections collected/unique
Completeness to H = 25.01
Refinement method
6,972/1,763 [Rint = 0.0357]
99.7%
2
Full-matrix least-squares on F
2
Goodness-of-fit on F
1.068
Final R indices [I [ 2r(I)]
R indices (all data)
R
R
1
1
= 0.0404, wR
2
2
= 0.1005
= 0.1075
2
4
= 0.0503, wR
densed under reduced pressure, followed by column chro-
matography over silica gel (AcOEt/hexane, 1:1) gave
Extinction coefficient
0.051(7)
0.163 and -0.194 e A
-3
˚
1
Largest diff. peak and hole
colorless solid 3 in 92% yield. m.p. 74–76 °C H NMR
123

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72
J Chem Crystallogr (2009) 39:870–873
˚
Table 2 Selected bond lengths (A) and angles (°) for 3
Results and Discussion
0
O(1)–C(9)
1.220 (2)
1.494 (6)
1.321 (2)
1.450 (2)
1.3956 (16)
0.8200
C(9)–O(1)–C(10 )
C(8)–N(1)–O(3)
N(1)–C(8)–C(7)
N(1)–C(8)–C(9)
C(7)–C(8)–C(9)
O(1)–C(9)–O(2)
O(1)–C(9)–C(8)
O(2)–C(9)–C(8)
110.6 (4)
The crystal structure of 3 is illustrated in Fig. 1. It is
composed of a phenyl ring moiety, a oxime group and a
ester group, eight atoms O1, O2, O3, N1, C7, C8, C9, C10
display an almost coplanar configuration and with a mean
0
O(1)–C(10 )
O(2)–C(9)
O(2)–C(10)
O(3)–N(1)
O(3)–H(3)
N(1)–C(8)
113.65 (13)
126.75 (15)
114.51 (15)
118.72 (15)
124.39 (16)
121.29 (16)
114.33 (16)
˚
deviation to the least square plane 0.0166 A, and it is
almost vertical with aromatic ring C1–C6, their dihedral
angle is 84.4(6)°.
1.285 (2)
Intermolecular hydrogen bond of the type O–HꢀꢀꢀN O–
HꢀꢀꢀO, and C–HꢀꢀꢀO are found in the crystal structure of 3
(
seen in Table 3). Atom N1, O2, O3 acts as a hydrogen-
bond donor respectively, via atom H3–O3 to generate
the supramolecular structures. They are O3–H3ꢀꢀꢀN1
˚
(
2.769 A, 136.2°), O3–H3ꢀꢀꢀO2 (3.356, 158°), O3–
H3ꢀꢀꢀO3 (3.359, 111°) with symmetry code 1 - x, -y,
-
z. Furthermore, the structures of a-oximino acidic esters
are linked layer by layer, in which up and down are
connect by bifurcated hydrogen bonds of C5–H5ꢀꢀꢀO1
(
symmetry code: x, -1 ? y, z), C7–H7ꢀꢀꢀO3 (symmetry
code: x, 1 ? y, z) and C10–H10ꢀꢀꢀO1 (symmetry code:
1 ? x, y, z). The hydrogen bonds make the molecules
-
form a column along a-axis, When viewed along the
a-axis, the molecules are interlinked by hydrogen bonds
as shown in Fig. 2.
Fig. 1 The molecular structures of 3, showing the atom-labelling
scheme. Displacement ellipsoids are drawn at the 30% probability
level
Supplementary Material
Table 3 Hydrogen bonded geometry, distances and angles are given
˚
in (A) and (°)
Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supple-
mentary publication no. CCDC-696915. Copies of available
material can be obtained, free of charge, on application to
the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK (fax: ?44-1223-336033 or e-mail:deposit@ccdc.cam.
ac.uk).
No. D–HꢀꢀꢀA
Hd ( )D – d(HꢀꢀꢀA) d(DꢀꢀꢀA) h(D–
HꢀꢀꢀA)
Symmetry
code
1
2
3
O3–
H3ꢀꢀꢀN1
O3–
H3ꢀꢀꢀO2
O3–
H3ꢀꢀꢀO3
0.820 2.118
0.820 2.582
0.820 2.98
2.769
3.356
3.359
136.2
158.0
111.0
1-x,
-y,-z
1-x,
-y,-z
1-x,
-y,-z
D donor, A acceptor
Fig. 2 The hydrogen bond
system between molecular 3,
The dashed lines represent the
intermolecular hydrogen bonds
(H-bonds are drawn between
donor and acceptor atoms)
1
23

J Chem Crystallogr (2009) 39:870–873
873
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