English

• 1. INTRODUCTION

  1,5-Diketones are a class of important structural motifs found in many natural products and pharmaceutical compounds, which are associated with a broad spectrum of biological activities, such as antitumor activity^[1], antidiabetic activity^[2], anti-inflammation^[3] and anti-infection^[4]. They can also serve as versatile building blocks converting to many useful heterocyclic compounds^{[5, 6]}. Consequently, many methods have been reported for the synthesis of 1,5-diketones skeleton^[7-12]. Among them, Michael addition of α,β-unsaturated carbonyl compounds with ketones^{[7, 8]}, dimerization of the condensation products between aryl methyl ketones and aldehydes^[9], and ozonolysis of cyclopentene are notable examples^[10]. Despite the significant progress made in this field, some of these protocols often suffered from certain limitations (e.g., the usage of expensive metal catalysts, harsh reaction conditions, and low yields, etc.), which greatly hindered their application. Thus, the development of a facile and atom-economic method to construct polysubstituted 1,5-diketones is highly attractive.

  Transition-metal-free multicomponent reactions play an important role in organic synthesis and medicinal chemistry because they are inexpensive and environmental friendly and can avoid potential transition metal contamination in the products^[13-17]. However, controlling chemoselectivity and regioselectivity are the major issues in developing novel organic synthesis reaction under transition-metal-free conditions owing to the intrinsic mechanistic limitation^[18]. To the best of our knowledge, the antioxidant activities of 1,5-diketone derivatives have not been reported. As a part of our continuing interest in the transition-metal-free reactions^{[19, 20]}, we report herein a simple and efficient method for the synthesis of 1,5-diketones from phenols, α-bromoketones and alkenes using K₂CO₃ as catalyst, and the 1,5-diketone derivatives showed promising antioxidant potency through free radical scavenging activity test.

  2. EXPERIMENTAL

  2.1 Instruments and reagents

  Unless stated otherwise, commercial reagents were used without further purification. All reagents were weighed and handled in air at room temperature. NMR spectra were obtained using a Bruker Avance 400 spectrometer (¹H at 400 MHz, and ¹³ C at 101 MHz). Chemical shifts for the ¹H NMR and ¹³C NMR spectra were reported in parts per million (ppm) from tetramethylsilane with the solvent resonance (CDCl₃: δ 7.26 ppm) and solvent (CDCl₃: δ 77.0 ppm) as the internal standards, respectively. HRMS was obtained using a LCMS-IT-TOF mass spectrometer. Melting points were obtained using an electrothermal PIF YRT-3 apparatus without correction. Crystal structure was determined using an AtlasS2 diffractometer. GC-MS analysis was performed using an Agilent 6890GC/5973 mass spectrometer.

  2.2 Synthesis and structure characterization

  A mixture of phenol 1 (0.5 mmol), α-bromoketone 2 (0.6 mmol), alkene 3 (0.5 mmol) and K₂CO₃ (3.0 equiv.) was added to 2 mL DMSO. The mixture was stirred at 85 ℃ for 4 h, and monitored periodically by TLC. Upon completion, the reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with water and brine, dried over Na₂SO₄ and filtered. The solvent was removed under vacuum. The residue was purified by flash column chromatography to afford 1,5-diketone 4 (Scheme 1).

  Scheme 1

  

  Scheme 1.  Procedure of preparing the title compounds

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  Table 1

  

  Table 1.  Preparation of 1,5-Diketone Derivatives 4a~4h

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  Methyl 5-oxo-4-phenoxy-5-phenylpentanoate (4a)  Purification via flash column chromatography with 40% ethyl acetate/petroleum ether gave the yield of 81% as a yellow oil (purity > 99%). ¹H NMR (400 MHz, CDCl₃) δ 8.19~8.13 (m, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.25~7.17 (m, 2H), 6.92 (t, J = 7.4 Hz, 1H), 6.84 (d, J = 7.9 Hz, 2H), 5.55 (dd, J = 9.2, 3.8 Hz, 1H), 3.69 (s, 3H), 2.74 (ddd, J = 17.0, 8.3, 6.9 Hz, 1H), 2.62 (dt, J = 17.2, 6.2 Hz, 1H), 2.41 (dddd, J = 10.6, 8.4, 6.8, 3.8 Hz, 1H), 2.31~2.19 (m, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 197.9, 173.4, 157.5, 134.2, 133.9, 129.6, 128.9, 128.8, 121.6, 115.2, 78.7, 51.8, 29.5, 28.1. HRMS (ESI) m/z: calcd for C₁₈H₁₈O₄Na [M + Na]⁺ 321.1090; found 321.1086.

  Methyl 5-(4-methoxyphenyl)-4-(naphthalen-1-yloxy)-5-oxopentanoate (4b)  Purification via flash column chromatography with 40% ethyl acetate/petroleum ether yielded 80% as a yellow solid (purity > 99%); m.p: 133~135 ℃. ¹H NMR (400 MHz, CDCl₃) δ 8.38 (dd, J = 6.0, 3.1 Hz, 1H), 8.20 (t, J = 5.8 Hz, 2H), 7.76 (dd, J = 6.1, 3.2 Hz, 1H), 7.58~7.44 (m, 2H), 7.38 (d, J = 8.3 Hz, 1H), 7.22 (dd, J = 15.6, 7.7 Hz, 1H), 6.92 (d, J = 8.9 Hz, 2H), 6.59 (d, J = 7.7 Hz, 1H), 5.61 (dd, J = 7.2, 5.9 Hz, 1H), 3.82 (s, 3H), 3.67 (s, 3H), 2.83~2.64 (m, 2H), 2.58~2.39 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 196.4, 173.5, 164.1, 153.2, 134.6, 131.3, 127.5, 127.1, 126.6, 125.7, 125.6, 125.3, 122.1, 121.0, 114.1, 105.6, 79.5, 55.5, 51.8, 29.9, 28.4. HRMS (ESI) m/z: calcd. for C₂₃H₂₃O₅ [M + H]⁺ 379.1536; found 379.1533.

  Methyl 4-(2-iodophenoxy)-5-oxo-5-phenylpentanoate (4c)  Purification via flash column chromatography with 40% ethyl acetate/petroleum ether afforded 84% yield as a white solid (purity > 99%); m.p: 68~70 ℃. ¹H NMR (400 MHz, CDCl₃) δ 8.21~8.14 (m, 2H), 7.75 (dd, J = 7.8, 1.5 Hz, 1H), 7.63~7.57 (m, 1H), 7.49 (dd, J = 10.6, 4.7 Hz, 2H), 7.13 (td, J = 8.3, 1.6 Hz, 1H), 6.66 (td, J = 7.6, 1.2 Hz, 1H), 6.53 (dd, J = 8.3, 1.1 Hz, 1H), 5.53 (dd, J = 9.1, 4.1 Hz, 1H), 3.69 (s, 3H), 2.93~2.80 (m, 1H), 2.71 (ddd, J = 17.4, 6.8, 5.8 Hz, 1H), 2.53~2.28 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 197.2, 173.3, 155.8, 139.7, 133.9, 133.7, 129.3, 128.9, 128.8, 123.1, 112.4, 86.4, 80.1, 51.7, 29.5, 28.1. HRMS (ESI) m/z: calcd. for C₁₈H₁₈IO₄ [M + H]⁺ 425.0238; found 425.0233.

  Ethyl 4-(2-iodophenoxy)-5-(4-methoxyphenyl)-5-oxo-pentanoate(4d)  Purification via flash column chromatography with 40% ethyl acetate/petroleum ether provided 88% yield as a white solid (purity > 99%); m.p: 72~74 ℃. ¹H NMR (400 MHz, CDCl₃) δ 8.16 (t, J = 5.8 Hz, 2H), 7.71 (dd, J = 7.8, 1.5 Hz, 1H), 7.15~7.03 (m, 1H), 6.92 (d, J = 8.9 Hz, 2H), 6.65~6.56 (m, 1H), 6.55~6.48 (m, 1H), 5.44 (dd, J = 9.0, 4.2 Hz, 1H), 4.12 (qd, J = 7.1, 1.8 Hz, 2H), 3.81 (s, 3H), 2.81 (dt, J = 17.0, 7.7 Hz, 1H), 2.67 (dt, J = 17.2, 6.3 Hz, 1H), 2.43~2.30 (m, 2H), 1.21 (t, J = 7.2 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 195.8, 173.0, 164.2, 156.0, 139.7, 131.4, 129.4, 126.8, 123.1, 114.1, 112.6, 86.4, 80.4, 60.7, 55.6, 29.9, 28.5, 14.3. HRMS (ESI) m/z: calcd. for C₂₀H₂₁IO₅Na [M + Na]⁺ 491.0324; found 491.0323.

  Methyl 4-(2-iodophenoxy)-5-(4-methoxyphenyl)-5-oxopentanoate (4e)  Purificaton via flash column chromatography with 40% ethyl acetate/petroleum ether gave the yield of 85% as a yellow oil (purity > 99%). ¹H NMR (400 MHz, CDCl₃) δ 8.18 (d, J = 8.9 Hz, 2H), 7.73 (dd, J = 7.8, 1.3 Hz, 1H), 7.16~7.05 (m, 1H), 6.95 (d, J = 8.9 Hz, 2H), 6.64 (t, J = 7.4 Hz, 1H), 6.53 (d, J = 8.4 Hz, 1H), 5.42 (dd, J = 8.8, 4.3 Hz, 1H), 3.85 (s, 3H), 3.68 (s, 3H), 2.88~2.77 (m, 1H), 2.70 (dt, J = 17.3, 6.3 Hz, 1H), 2.42~2.33 (m, 2H). ¹³C NMR (101 MHz, CDCl₃) δ 195.8, 173.5, 164.2, 156.0, 139.7, 131.5, 129.4, 126.8, 123.1, 114.1, 112.5, 86.4, 80.4, 55.6, 51.8, 29.7, 28.5. HRMS (ESI) m/z: calcd. for C₁₉H₂₀IO₅ [M + H]⁺ 455.0347; found 455.0345.

  Methyl 4-(2-iodophenoxy)-5-oxo-5-(p-tolyl)pentanoate (4f)  Purificaton via flash column chromatography with 40% ethyl acetate/petroleum ether yielded 83% as a white solid (purity > 99%); m.p: 114~116 ℃. ¹H NMR (400 MHz, CDCl₃) δ 8.08 (d, J = 8.2 Hz, 2H), 7.72 (dd, J = 7.8, 1.3 Hz, 1H), 7.27 (d, J = 8.1 Hz, 2H), 7.13~7.05 (m, 1H), 6.63 (t, J = 7.6 Hz, 1H), 6.52 (d, J = 8.2 Hz, 1H), 5.50 (dd, J = 8.9, 4.1 Hz, 1H), 3.67 (s, 3H), 2.89~2.78 (m, 1H), 2.69 (dt, J = 17.3, 6.3 Hz, 1H), 2.47~2.31 (m, 5H); ¹³C NMR (101 MHz, CDCl₃) δ 196.9, 173.4, 156.0, 145.1, 139.7, 131.4, 129.7, 129.5, 129.1, 123.1, 112.6, 86.5, 80.2, 51.8, 29.7, 28.4, 21.8. HRMS (ESI) m/z: calcd. for C₁₉H₂₀IO₄ [M + H]⁺ 439.0396; found 439.0392.

  Ethyl 4-(2-iodophenoxy)-5-oxo-5-(p-tolyl)pentanoate (4g)  Purificaton via flash column chromatography with 40% ethyl acetate/petroleum ether provided the yield of 88% as a yellow oil (purity > 99%). ¹H NMR (400 MHz, CDCl₃) δ 8.08 (d, J = 8.3 Hz, 2H), 7.75 (dd, J = 7.8, 1.6 Hz, 1H), 7.29 (d, J = 8.1 Hz, 2H), 7.12 (td, J = 8.3, 1.6 Hz, 1H), 6.65 (td, J = 7.6, 1.2 Hz, 1H), 6.53 (dd, J = 8.3, 1.1 Hz, 1H), 5.49 (dd, J = 9.0, 4.2 Hz, 1H), 4.23~4.04 (m, 2H), 2.83 (dt, J = 17.2, 7.7 Hz, 1H), 2.68 (ddd, J = 17.2, 6.9, 5.8 Hz, 1H), 2.48~2.33 (m, 5H), 1.24 (t, J = 7.1 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 196.9, 173.0, 156.0, 1451, 139.7, 131.4, 129.6, 129.4, 129.1, 123.1, 112.5, 86.5, 80.3, 60.7, 29.9, 28.4, 21.8, 14.2. HRMS (ESI) m/z: calcd. for C₁₉H₂₀IO₄ [M + H]⁺ 453.0552; found 453.0548.

  Methyl 4-(4-ethoxyphenoxy)-5-(4-methoxyphenyl)-5-oxopentanoate(4h)  Purificaton via flash column chromatography with 40% ethyl acetate/petroleum ether gave the yield of 82% as a yellow oil (purity > 99%). ¹H NMR (400 MHz, CDCl₃) δ 8.20~8.07 (m, 2H), 6.98~6.90 (m, 2H), 6.78~6.71 (m, 4H), 5.34 (dd, J = 9.2, 3.9 Hz, 1H), 3.91 (q, J = 7.0 Hz, 2H), 3.86 (s, 3H), 3.69 (s, 3H), 2.76~2.54 (m, 2H), 2.41~2.15 (m, 2H), 1.37~1.26 (m, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 196.9, 173.6, 164.1, 153.7, 151.8, 131.3, 127.2, 116.3, 115.4, 114.1, 79.8, 63.9, 55.5, 51.8, 29.6, 28.4, 14.9. HRMS (ESI) m/z: calcd. for C₂₁H₂₅O₆ [M + H]⁺ 373.1640; found 373.1636.

  2.3 Crystal data and structure determination

  The crystal of compound 4f was cultivated from ethanol, and the colorless prism with dimensions of 0.13mm × 0.12mm × 0.11mm was selected for X-ray analysis. The diffraction data were collected at 100 (10) K byusing a Super-Nova (Dual, Cu source at zero) four-circle diffractometer with graphite-monochromated Mo-Kα radiation (λ = 0.71073 Å) at a multi-scan mode. In the range of 2.404≤θ ≤24.997° (–8≤h≤10, –7≤k≤10, –14≤l≤13), a total of 5855 reflections were collected and 3152 were independent with R_int = 0.0326, of which 2931 were observed (I > 2σ(I)). The crystal structure was solved by direct methods using the SHELXS-97 program and expanded by Fourier technique^[21]. All non-hydrogen atoms were refined anisotropically, and the hydrogen atoms were located according to the theoretical model. The final refinement converged at R = 0.0342, wR = 0.0691, S = 1.045, (Δ/σ)_max = 0.001, (Δρ)_max = 0.76 and (Δρ)_min = –1.00 e/ų.

  2.4 Antioxidant activity evaluation

  The evaluation protocol for antioxidant capacity of 1,5-diketone derivatives has been adopted according to the reported standard procedure^[22]. Approximately 7 mmol/L ABTS was mixed with 2.45 mmol/L potassium persulfate in the dark at room temperature for 24 h as ABTS⁺ solution. The ABTS⁺ solution was diluted with ethanol to the absorbance of 0.700 ± 0.002 at 734 nm. Approximately 1 mL of different concentrations of the sample was added to 1 mL of ABTS⁺ solution and kept in the dark for 30 min, and the absorbance was tested at 734 nm. The ABTS⁺ scavenging activity of the samples was calculated using the following formula:

  $ {\text{ABT}}{{\text{S}}^{\text{ + }}}{\text{ scavenging activity }} (\% ) = \frac{{{A_0} - {A_1}}}{{{A_0}}} \times 100\% $

  where A₀ is the absorbance of the control and A₁ represents the absorbance with the test sample. Butylated hydroxytoluene (BHA) and vitamin C (VC) were used as reference for comparison. The result was expressed as IC₅₀ (mg/mL, μg/mL).

  3. RESULTS AND DISCUSSION

  3.1 Structure description of compound 4f

  The structure of compound 4f was testified by HRMS, ¹H NMR, ¹³C NMR and single-crystal X-ray analysis. The selected bond lengths and bond angles for compound 4f are described in Table 2, and its molecular structure and packing diagram are shown in Figs. 1 and 2, respectively.

  Table 2

  

  Table 2.  Selected Bond Lengths (Å) and Bond Angles (°) of Compound 4f

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  Bond	Dist.		Bond	Dist.		Bond	Dist.
  I(1)–C(6)	2.094(3)		C(1)–C(2)	1.393(4)		C(9)–C(14)	1.396(4)
  O(1)–C(1)	1.366(4)		C(17)–C(16)	1.534(4)		C(3)–C(4)	1.387(5)
  O(1)–C(7)	1.432(4)		C(17)–C(18)	1.499(4)		C(10)–C(11)	1.381(5)
  O(4)–C(18)	1.341(4)		C(16)–C(7)	1.520(4)		C(13)–C(14)	1.386(4)
  O(4)–C(19)	1.445(4)		C(7)–C(8)	1.539(4)		C(13)–C(12)	1.397(5)
  O(3)–C(18)	1.209(4)		C(8)–C(9)	1.487(4)		C(11)–C(12)	1.393(4)
  O(2)–C(8)	1.223(4)		C(2)–C(3)	1.388(5)		C(12)–C(15)	1.511(5)
  C(6)–C(1)	1.408(4)		C(5)–C(4)	1.389(5)
  C(6)–C(5)	1.383(5)		C(9)–C(10)	1.401(4)
  Angle	(°)		Angle	(°)		Angle	(°)
  C(1)–O(1)–C(7)	117.6(2)		O(3)–C(18)–C(17)	126.1(3)		C(4)–C(3)–C(2)	120.9(3)
  C(18)–O(4)–C(19)	115.6(2)		O(1)–C(7)–C(16)	106.8(2)		C(3)–C(4)–C(5)	119.2(3)
  C(1)–C(6)–I(1)	119.5(2)		O(1)–C(7)–C(8)	110.7(2)		C(11)–C(10)–C(9)	120.3(3)
  C(5)–C(6)–I(1)	120.4(2)		O(3)–C(18)–O(4)	123.7(3)		C(14)–C(13)–C(12)	120.8(3)
  C(5)–C(6)–C(1)	120.1(3)		O(2)–C(8)–C(7)	118.6(3)		C(13)–C(14)–C(9)	120.6(3)
  O(1)–C(1)–C(6)	116.4(3)		O(2)–C(8)–C(9)	122.3(3)		C(10)–C(11)–C(12)	121.3(3)
  O(1)–C(1)–C(2)	124.6(3)		C(9)–C(8)–C(7)	119.0(2)		C(13)–C(12)–C(15)	121.1(3)
  C(2)–C(1)–C(6)	119.0(3)		C(3)–C(2)–C(1)	120.1(3)		C(11)–C(12)–C(13)	118.2(3)
  C(18)–C(17)–C(16)	112.7(3)		C(6)–C(5)–C(4)	120.7(3)		C(11)–C(12)–C(15)	120.6(3)
  C(7)–C(16)–C(17)	112.9(3)		C(10)–C(9)–C(8)	117.7(3)		C(14)–C(9)–C(10)	118.6(3)
  O(4)–C(18)–C(17)	110.2(3)		C(14)–C(9)–C(8)	123.7(3)		C(16)–C(7)–C(8)	109.3(3)

  Figure 1

  

  Figure 1.  Crystal structure of compound 4f

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  Figure 2

  

  Figure 2.  Fragment of the crystal packing of compound 4f

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  The crystal structure of compound 4f contained two benzene rings, benzene ring A built by the C(1), C(2), C(3), C(4), C(5) and C(6) atoms and benzene ring B made up of atoms C(9), C(10), C(11), C(12), C(13), and C(14). The average bond lengths and bond angles of phenyl rings were in normal ranges. The bond lengths for the carbonyl groups of O(2)~C(8) and O(3)~C(18) are 1.223(4) and 1.209(4) Å. respectively. The O(1)~C(7) and O(4)~C(19) exhibit typical single bonds in 1.432(4) and 1.445(4) Å. The bond distances of O(1)~C(1) (1.366(4) Å) and O(4)~C(18) (1.341(4) Å) were slightly shorter than the standard single C–O bond (1.43 Å)^[23] due to the existence of sp² hybridization of the corresponding O atom with the phenyl ring or carbonyl. The torsion angles of C(16)–C(7)–C(8)–C(9) and C(16)–C(17)–C(18)–O(4) are –81.9(3)° and –174.2(3)°, which indicated the two carbonyl groups are not opposite. The angle between the two benzene rings is 84.37°.

  3.2 Antioxidant activity

  The antioxidant activities of the title 1,5-diketone derivatives were evaluated using the ABTS⁺ radical cation decolorization assay. As shown in Table 3, these results suggested that antioxidant capacity decreased in the order of 4a > 4h > 4d > 4b > 4e > 4g > 4f > 4c. Especially, compound 4a exhibited better antioxidant performance than BHA (butylated hydroxytoluene) and VC (vitamin C).

  Table 3

  

  Table 3.  Antioxidative Capacities of 1,5-Diketones, VC and BHT

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  Samples	ABTS+ (IC50)
  4a (μg/mL)	0.15 ± 0.001
  4b (mg/mL)	1.71 ± 0.004
  4c (mg/mL)	2.50 ± 0.007
  4d (mg/mL)	0.92 ± 0.001
  4e (mg/mL)	1.94 ± 0.003
  4f (mg/mL)	2.03 ± 0.003
  4g (mg/mL)	1.96 ± 0.006
  4h (mg/mL)	0.11 ± 0.001
  VC (μg/mL)	2.34 ± 0.002
  BHT (μg/mL)	1.80 ± 0.003

  3.3 Reaction process research

  A series of control experiments was subsequently carried out to develop a deeper understanding of the reaction process (Scheme 2). Initially, the reaction of phenol (1a) with 2-bromo-1-phenylethan-1-one (2a) was performed under the optimal conditions, and 5a was detected in 96% yield (Scheme 2a). When the reaction of 5a and 3a was conducted under the standard conditions, the target product methyl 5-oxo-4-phenoxy-5-phenylpentanoate (4a) was obtained in 84% yield (Scheme 2b), suggesting that 5a might be an intermediate in this reaction. In addition, kinetic studies further confirmed that this reaction could undergo a sequential three-component tandem process (Fig. 3).

  Scheme 2

  

  Scheme 2.  Control experiments

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  Figure 3

  

  Figure 3.  Kinetics of reaction monitored by GC-MS

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  4. CONCLUSION

  In summary, we have successfully established a transition-metal-free catalytic route for the construction of 1,5-diketone derivatives from easily available starting materials. The target compound 4f was investigated through X-ray crystallography. In addition, compound 4a showed promising antioxidant potency through ABTS⁺ radical cation decolorization assay. The current study provides a clue for further development of new types of antioxidant agents.

  
  
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  Scheme 1  Procedure of preparing the title compounds

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  Figure 1  Crystal structure of compound 4f

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  Figure 2  Fragment of the crystal packing of compound 4f

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  Scheme 2  Control experiments

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  Figure 3  Kinetics of reaction monitored by GC-MS

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  Table 1.  Preparation of 1,5-Diketone Derivatives 4a~4h

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  Table 2.  Selected Bond Lengths (Å) and Bond Angles (°) of Compound 4f

  Bond	Dist.		Bond	Dist.		Bond	Dist.
  I(1)–C(6)	2.094(3)		C(1)–C(2)	1.393(4)		C(9)–C(14)	1.396(4)
  O(1)–C(1)	1.366(4)		C(17)–C(16)	1.534(4)		C(3)–C(4)	1.387(5)
  O(1)–C(7)	1.432(4)		C(17)–C(18)	1.499(4)		C(10)–C(11)	1.381(5)
  O(4)–C(18)	1.341(4)		C(16)–C(7)	1.520(4)		C(13)–C(14)	1.386(4)
  O(4)–C(19)	1.445(4)		C(7)–C(8)	1.539(4)		C(13)–C(12)	1.397(5)
  O(3)–C(18)	1.209(4)		C(8)–C(9)	1.487(4)		C(11)–C(12)	1.393(4)
  O(2)–C(8)	1.223(4)		C(2)–C(3)	1.388(5)		C(12)–C(15)	1.511(5)
  C(6)–C(1)	1.408(4)		C(5)–C(4)	1.389(5)
  C(6)–C(5)	1.383(5)		C(9)–C(10)	1.401(4)
  Angle	(°)		Angle	(°)		Angle	(°)
  C(1)–O(1)–C(7)	117.6(2)		O(3)–C(18)–C(17)	126.1(3)		C(4)–C(3)–C(2)	120.9(3)
  C(18)–O(4)–C(19)	115.6(2)		O(1)–C(7)–C(16)	106.8(2)		C(3)–C(4)–C(5)	119.2(3)
  C(1)–C(6)–I(1)	119.5(2)		O(1)–C(7)–C(8)	110.7(2)		C(11)–C(10)–C(9)	120.3(3)
  C(5)–C(6)–I(1)	120.4(2)		O(3)–C(18)–O(4)	123.7(3)		C(14)–C(13)–C(12)	120.8(3)
  C(5)–C(6)–C(1)	120.1(3)		O(2)–C(8)–C(7)	118.6(3)		C(13)–C(14)–C(9)	120.6(3)
  O(1)–C(1)–C(6)	116.4(3)		O(2)–C(8)–C(9)	122.3(3)		C(10)–C(11)–C(12)	121.3(3)
  O(1)–C(1)–C(2)	124.6(3)		C(9)–C(8)–C(7)	119.0(2)		C(13)–C(12)–C(15)	121.1(3)
  C(2)–C(1)–C(6)	119.0(3)		C(3)–C(2)–C(1)	120.1(3)		C(11)–C(12)–C(13)	118.2(3)
  C(18)–C(17)–C(16)	112.7(3)		C(6)–C(5)–C(4)	120.7(3)		C(11)–C(12)–C(15)	120.6(3)
  C(7)–C(16)–C(17)	112.9(3)		C(10)–C(9)–C(8)	117.7(3)		C(14)–C(9)–C(10)	118.6(3)
  O(4)–C(18)–C(17)	110.2(3)		C(14)–C(9)–C(8)	123.7(3)		C(16)–C(7)–C(8)	109.3(3)

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  Table 3.  Antioxidative Capacities of 1,5-Diketones, VC and BHT

  Samples	ABTS+ (IC50)
  4a (μg/mL)	0.15 ± 0.001
  4b (mg/mL)	1.71 ± 0.004
  4c (mg/mL)	2.50 ± 0.007
  4d (mg/mL)	0.92 ± 0.001
  4e (mg/mL)	1.94 ± 0.003
  4f (mg/mL)	2.03 ± 0.003
  4g (mg/mL)	1.96 ± 0.006
  4h (mg/mL)	0.11 ± 0.001
  VC (μg/mL)	2.34 ± 0.002
  BHT (μg/mL)	1.80 ± 0.003

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