Synthesis, characterization and crystal structure of 4,7-dioxo-7- phenylheptanoic acid

Article abstract of DOI:10.14233/ajchem.2014.17199

4,7-Dioxo-7-phenylheptanoic acid was synthesized from acetophenone and furfural. Firstly, acetophenone reacted with furfural in the presence of sodium hydroxide at room temperature, then the product of the first step was transformed into 4,7-dioxo-7-phenylheptanoic by the process of hydrolyzation by using acetic acid and hydrochloric acid. The product was characterized by 1H NMR and LC-MS. The crystal structure of compound 1 was investigated using X-ray diffraction and SHELXTL-97 software and it was first reported here. The result indicated that compound 1 crystallized in the monoclinic system, space group P2(1)/c with a = 5.3007 (14), b = 28.405 (8), c = 7.679(2) ?, V = 1130.4 (5) ?³; Z 4.

Full text of DOI:10.14233/ajchem.2014.17199

Asian Journal of Chemistry; Vol. 26, No. 10 (2014), 3116-3118
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.17199
Synthesis, Characterization and Crystal Structure of 4,7-Dioxo-7-phenylheptanoic Acid
1,2
1,2
2
2,*
WEI ZHUANG , CHAO-FAN JU , XIU-QIN ZHANG , JIAN XIAO1,2 and KAI WANG
1School of Petrochemical Engineering, Changzhou University, Changzhou 213164, Jiangsu Province, P.R. China
2High Technology Research Institute of Nanjing University, Changzhou 213162, Jiangsu Province, P.R. China
*Corresponding author: E-mail: wkcoool@163.com
Received: 11 February 2014;
Accepted: 14 April 2014;
Published online: 10 May 2014;
AJC-15192
4,7-Dioxo-7-phenylheptanoic acid was synthesized from acetophenone and furfural. Firstly, acetophenone reacted with furfural in the
presence of sodium hydroxide at room temperature, then the product of the first step was transformed into 4,7-dioxo-7-phenylheptanoic
by the process of hydrolyzation by using acetic acid and hydrochloric acid. The product was characterized by 1H NMR and LC-MS. The
crystal structure of compound 1 was investigated using X-ray diffraction and SHELXTL-97 software and it was first reported here. The
result indicated that compound 1 crystallized in the monoclinic system, space group P2(1)/c with a = 5.3007 (14), b = 28.405 (8), c =
7.679(2) Å, V = 1130.4 (5) Å3; Z 4.
Keywords: 4,7-Dioxo-7-phenylheptanoic, Synthesis, Characterization, Crystal structure.
O
O
O
INTRODUCTION
NaOH
r.t.
O
O
The photochromism is an interesting phenomenon that
has been attracted attention for several decades.Various photo-
chromic compounds were synthesized and used in ophthalmic
lenses1, information storage2 and smart windows3. Compared
to other photochromic families, the naphthopyran compounds
have the advantages of the low initial color, low solvachro-
mism, high color density and large color gamut provided by
the ring open form when substituted with various electron
donating and withdrawing groups4,5. Furthermore, many
naphthopyran derivatives have good biological activities and
pharmacological activities6, such as dysplasia resistance7,
tracheitis resisitance8, antibacterial property and anticancer.
Naphthol derivatives are widely concerned as the most
important intermediates to synthesize naphthopyran comp-
ounds9,10. 4,7-Dioxo-7-phenylheptanoic acid (1) can be utilized
to synthesize the compound 5-hydroxy-1H-cyclopenta[a]-
naphthalen-3(2H)-one through a two-step reaction. Herein, we
introduce a new synthetic method of compound 1 from aceto-
phenone (1) and furfural (2) with an overall yield of about
52.9 %. Meanwhile, the crystal structure of 1 was also investi-
gated. The synthetic route of compound I was presented as
Scheme-I.
H
1
2
3
O
CH3COOH,HCl,H2O
C6H12,reflux
COOH
O
I
Scheme-I: Route for the synthesis of compound 1
99 % determined by GC. Acetophenone was purchased from
Sinopharm Chemical Reagent Co. Ltd of China. All other
chemicals were of reagent grade and used without purification
as received.
1H NMR spectrum was obtained with Bruker AV-500
spectrometer at 500.13 MHz and measured in CDCl3 solution
at 30 0.5 °C. The sample was dissolved in a 5 mm diameter
tube at a concentration of 20 mg/mL. X-ray diffraction was
performed on a Bruker APEXII CCD diffractometer. Mass
spectrum of 1 was analyzed using Trace DSQ LC/MS (Thermo
Electron Co., USA).
Synthesis of compound 1: A 250-mL, round-bottomed
flask with a stirring bar and a pressure-equalizing addition
funnel was charged with 1 (4 g, 0.0333 mol), 2 (3.36 g, 0.0350
mol) and ethanol (40 mL). Sodium hydroxide (0.667 g, 0.0166
mol) in water (20 mL) was added through the dropping funnel
EXPERIMENTAL
Furfural was supplied byWell Chemical Co. Ltd of Jiangsu
(Yancheng, People's Republic of China), its mass content is

Vol. 26, No. 10 (2014)
Synthesis, Characterization and Crystal Structure of 4,7-Dioxo-7-phenylheptanoic Acid 3117
to the solution. The reaction mixture was stirred magnetically
for 4 h at room temperature. After the reaction was completed,
the solvents were removed on a rotary evaporator. The resulting
dark brown residue was dissolved in ethyl acetate. The organic
layer was washed with 5 % sodium hydrogen sulfite solution
(3 × 40 mL) and saturated sodium chloride solution (3 × 40
mL) and dried over anhydrous sodium sulfate. Filtration and
removal of the solvent gave the product as a dark brown viscous
liquid. The crude product was subjected to silica gel column
chromatography, using a gradient elution with petroleum ether-
ethyl acetate to obtain 3 (6.27 g, 0.0316 mol).
Fig. 1. General appearance of compound 1 with the atoms represented by
thermal vibration ellipsoids of 50 % probability
Compound 3 (6.27 g, 0.0316 mol) was dissolved in cyclo-
hexane (75 mL) and was added to a mixture of acetic acid (30
mL), hydrochloric acid (22 mL), ethanol (22 mL) and water
(30 mL). The reaction mixture was heated on an oil bath under
reflux, while stirring mechanically for 24 h.After the reaction
was completed, the solvent and acids were removed under
reduced pressure. The resultant dark brown product was treated
with saturated aqueous sodium hydrogen carbonate until there
was no further evolution of carbon dioxide and then extracted
with diethyl ether to remove the unreacted compound 3. The
aqueous layer was acidified with 20 % sulphuric acid and
extracted into ethyl acetate. The ethyl acetate extract was dried
over anhydrous sodium sulphate and concentrated under
reduced pressure. By that means, 4.13 g (52.9 %, m.p. 117-
118 °C) of the compound (1) can be obtained in the form of a
brown grainy crystal.
Fig. 2. Packing diagram for compound 1
TABLE-1
Crystals of 1 that suitable for X-ray diffraction were
obtained by slow evaporation of dichloromethane solution
of 1.
CRYSTALLOGRAPHIC DATA FOR COMPOUND 1
Properties
Data
Molecular formula
Molecular weight
Temperature (K)
C13H14O4
234.24
293 (2)
X-ray crystallography:A colorless block-like crystal of
compound 1 grown in dichloromethane with dimensions of
1.00 mm × 0.50 mm × 0.15 mm was used for structural determi-
nation. Diffraction data were collected on a Bruker APEXII
CCD diffractometer by using graphite monochromated MoKα
radiation (λ = 0.71073 Å). The structure was solved by direct
methods with SHELXS-97 and refined on the F2 by full-matrix
least-squares method with SHELXL-97. All non-hydrogen
atoms were refined anisotropically.
Wavelength (Å)
0.71073
Crystal system
Space group
a (Å )
b (Å )
Monoclinic
P2(1)/c
5.3007 (14)
28.405 (8)
7.679 (2)
1130.4 (5)
c (Å )
Volume (Å3)
Z
4
Calculated density (g/cm3)
Absorption coefficient (mm-1)
F (000)
1.376
0.10
496.0
RESULTS AND DISCUSSION
In the 1H NMR of compound 1, the peak at 3.30-3.32 ppm
was ascribed to the proton of methylene which was substituted
by benzoyl group. The other data was described as below, 1H
NMR (CDCl3): δ 2.68-2.70 (2H, t), 2.86-2.91 (4H, m), 3.30-
3.32 (2H, t), 7.44-7.49 (2H, m), 7.54-7.57 (1H, m), 7.96-7.99
(2H, m).
In the LC spectrum peak at 2.626 minute ascribed to the
compound 1. In the MS spectrum, the existence of the peaks
at right end showed the compound 1, m/z 234.90 was ascribed
to molecular ion peak (M+), m/z 256.85 was ascribed to M + Na
peak.
The crystal configuration of compound 1 was confirmed
by X-ray structural analysis. Experimental details for X-ray
data collection were presented in Table-1 and the geometric
parameters for compound 1 were listed in Table-2. Molecular
structure and packing plot of compound 1 were showed in
Figs. 1 and 2, respectively.
Crystal size (mm)
Theta range for data collection (º)
Reflections collected/unique
Completeness to theta = 25.38 (%)
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I>2σ (I)]
R indices (all data)
Largest diff. peak and hole (e. Å-3)
1.00 × 0.50 × 0.15
1.4 to 26.0
2226/1971 [R(int) = 0.044]
99.7
0.905 and 0.985
Full-matrix least-squares on F2
2226/15/155
1.081
R1 = 0.0564, wR2 = 0.1269
R1 = 0.0486, wR2 = 0.1228
0.29 and -0.48
According to the data from X-ray crystallographic analysis,
compound 1 crystallized in a P2(1)/c space group of the
triclinic system. All H atoms were positioned geometrically
and constrained to ride on their parent atoms, with C-H = 0.93
Å for aromatic H. Other H atoms were positioned geometrically
and refined using a riding model, with C-H = 0.96 Å for alkyl
H, with Uiso(H) =1.2 Ueq(C) for aromatic H and Uiso(H)

3118 Zhuang et al.
Asian J. Chem.
TABLE-2
GEOMETRIC PARAMETERS FOR COMPOUND 1
TABLE-3
HYDROGEN-BOND GEOMETRY FOR COMPOUND 1
Bond Dist. (Å) Bond
C1—C2 1.382(3)
Dist. (Å)
D–H···A
O4–H4A···O4
C1–H1···O2
C5–H5···O1
C12–H12A···O4
D–H
H···A
D···A
D–H···A
C8—H8B
C9—C10
C9—H9A
C9—H9B
C10—O2
0.9700
1.498(2)
0.9700
0.9700
1.205(2)
1.504(2)
1.514(2)
0.9700
0.9700
1.490(2)
0.9700
0.9700
1.255(2)
1.260(2)
0.8501
–
0.85 Å
0.93Å
0.93Å
0.97Å
2.31 Å
2.56Å
2.46Å
2.58Å
2.647 (2) Å
3.289 (3) Å
3.324 (3) Å
3.394 (3) Å
104?
136?
155?
140?
C1—C6
C1—H1
C2—C3
C2—H2
C3—C4
C3—H3
C4—C5
C4—H4
C5—C6
C5—H5
C6—C7
C7—O1
C7—C8
C8—C9
C8—H8A
1.390(3)
0.9300
1.371(3)
0.9300
1.373(3)
0.9300
1.384(3)
0.9300
C10—C11
C11—C12
C11—H11A
C11—H11B
C12—C13
C12—H12A
C12—H12B
C13—O3
C13—O4
O4—H4A
–
= 1.5 Ueq(C) for other H. There are no intramolecular
hydrogen bonds in the structure. There are 4 intermolecular
hydrogen bonds in the structure and the hydrogen-bond
geometry for compound 1 was listed in Table-3. Unit cell
parameters: a = 5.3007 (14), b = 28.405 (8), c = 7.679 (2) Å,
V = 1130.4 (5) Å3; Z = 4.
1.383(3)
0.9300
1.492(3)
1.207(2)
1.507(2)
1.513(2)
0.9700
ACKNOWLEDGEMENTS
Angle
Data (º)
Angle
Data (º)
C2—C1—C6
C2—C1—H1
C6—C1—H1
C3—C2—C1
C3—C2—H2
C1—C2—H2
C2—C3—C4
C2—C3—H3
C4—C3—H3
C3—C4—C5
C3—C4—H4
C5—C4—H4
C6—C5—C4
C6—C5—H5
C4—C5—H5
C5—C6—C1
C5—C6—C7
C1—C6—C7
O1—C7—C6
O1—C7—C8
C6—C7—C8
C7—C8—C9
C7—C8—H8A
C9—C8—H8A
C7—C8—H8B
C9—C8—H8B
120.22(18)
119.9
119.9
120.17(18)
119.9
119.9
119.96(19)
120.0
120.0
120.54(19)
119.7
H8A—C8—H8B
C10—C9—C8
C10—C9—H9A
C8—C9—H9A
C10—C9—H9B
C8—C9—H9B
H9A—C9—H9B
O2—C10—C9
108.0
115.67(15)
108.4
108.4
108.4
The authors are gratefully acknowledged the support of
Nanjing University and Changzhou University in analysis.
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108.4
107.4
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123.54(16)
121.31(16)
115.14(15)
113.52(15)
108.9
108.9
108.9
108.9
107.7
115.92(15)
108.3
108.3
108.3
108.3
O2—C10—C11
C9—C10—C11
C10—C11—C12
C10—C11—H11A
C12—C11—H11A
C10—C11—H11B
C12—C11—H11B
H11A—C11—H11B
C13—C12—C11
C13—C12—H12A
C11—C12—H12A
C13—C12—H12B
C11—C12—H12B
H12A—C12—H12B
O3—C13—O4
119.7
119.88(18)
120.1
120.1
119.22(17)
122.82(16)
117.96(16)
119.68(17)
120.57(17)
119.76(15)
111.20(15)
109.4
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107.4
120.48(17)
119.13(17)
120.33(17)
109.1
173.66(17)
10.4 (3)
-169.45(16)
179.36(15)
8.6 (3)
109.4
109.4
109.4
O3—C13—C12
O4—C13—C12
C13—O4—H4A
C1—C6—C7—C8
O1—C7—C8—C9
C6—C7—C8—C9
C7—C8—C9—C10
C8—C9—C10—O2
C8—C9—C10—C11
O2—C10—C11—C12 -13.0 (2)
167.92(15)
C10—C11—C12—C13 71.2 (2)
C11—C12—C13—O3 29.3 (3)
C11—C12—C13—O4 -153.45(18)
C6—C1—C2—C3 -0.1(3)
C1—C2—C3—C4 -0.6(3)
C2—C3—C4—C5 0.7(3)
C3—C4—C5—C6 -0.1(3)
C4—C5—C6—C1 -0.7(3)
C4—C5—C6—C7 178.25(18)
C2—C1—C6—C5 0.8(3)
-172.37(16)
C2—C1—C6—C7 -178.20(17) C9—C10—C11—C12
C5—C6—C7—O1 174.9(2)
C1—C6—C7—O1 -6.2(3)
C5—C6—C7—C8 -5.3(3)
Symmetry code: (i) x, y ,z (ii)-x, 1/2 + y, 1/2-z.