Article
J. Agric. Food Chem., Vol. 58, No. 20, 2010 11083
(1:4 v/v). Aspect: highly viscous oil. Yield = 78%. 1H NMR (300.0 MHz,
CDCl3): δ 1.41 (s, 3H, CH3); 1.83-2.13 (m, 2H, CdC-CH2-CH2); 2.15
(s, 3H, CH3); 2.22 (s, 3H, CH3); 2.26 (s, 3H, CH3); 2.70 (t, J = 6.9 Hz, 2H,
CdC-CH2); 4.30 (d, J = 11.4 Hz, 1H, CH2OCO); 4.39 (d, J = 11.4 Hz,
1H, CH2OCO); 4.74 (s, 2H, OCH2Ph); 5.25 (s, 2H, OCH2Ph); 5.27 (s, 2H,
OCH2Ph); 6.98 (d, J = 8.7 Hz, 1H, CHAr); 7.29-7.70 (m, 17H, CHAr). 13
C
Figure 1. Structure of novel antioxidants 1a-1e. For details, see the text.
NMR (75.0 MHz, CDCl3): δ 11.9 (CH3); 12.0 (CH3); 12.9 (CH3); 20.3
(CdC-CH2); 22.4 (CH3); 28.8 (CdC-CH2-CH2); 68.9 (CH2OCO); 70.8
(OCH2Ph); 71.2 (OCH2Ph); 73.8 (OCCH2OCO); 74.8 (OCH2Ph); 113.2
(CAr); 115.5 (CAr); 117.4 (CAr); 123.0 (CAr); 123.2 (CAr); 124.1 (CAr); 126.1
(CAr); 127.1 (CAr); 127.4 (CAr); 127.8 (CAr); 127.9 (CAr); 128.0 (CAr); 128.1
(CAr); 128.3 (CAr); 128.5 (CAr); 128.6 (CAr); 128.7 (CAr); 136.6 (CAr); 136.9
(CAr); 137.9 (CAr); 147.4 (CAr); 148.3 (CAr); 148.6 (CAr); 153.0 (CAr); 166.0
(CdO). MS (m/z): calculated for C42H42O6 = 643.3054; found 643.3087
[M þ H]þ.
56.4 (OCH3); 74.4 (OCH2Ph); 106.9 (CAr); 126.5 (CAr); 128.3 (CAr); 128.5
(CAr); 128.6 (CAr); 138.0 (CAr); 140.6 (CAr); 153.3 (CAr); 167.4 (CdO).
Procedure for the Synthesis of Esters 8a-8e. DCC (3.06 mmol, 2.0
equiv) and DMAP (0.23 mmol, 0.15 equiv) were added under an argon
blanket to an alcoholic solution of compound 7 (1.53 mmol) and the
desired benzoic acid derivative (3.06 mmol, 2.0 equiv) in dry DCM
(40 mL). The mixture was stirred for 15 h at room temperature, and
distilled water (50 mL) was added. The organic layer was removed and
washed once more with distilled water (20 mL), then dried over anhydrous
magnesium sulfate, and concentrated. Finally, the crude product was
purified by flash column chromatography with silica gel, and the solvents
used for elution are described for the particular compounds.
Data for (60-Benzyloxy-20,50,70,80-tetramethylchroman-20-yl) Methyl
4-Benzyloxybenzoate (8a; Scheme 3). Eluent = DCM/hexanes (7:3 v/v).
Aspect: highly viscous oil. Yield = 70%. 1H NMR (300.0 MHz, CDCl3): δ
1.40 (s, 3H, CH3); 1.81-2.10 (m, 2H, CdC-CH2-CH2); 2.11 (s, 3H,
CH3); 2.18 (s, 3H, CH3); 2.22 (s, 3H, CH3); 2.67 (t, J = 6.9 Hz, 2H,
CdC-CH2); 4.29 (d, J = 11.4 Hz, 1H, CH2OCO); 4.38 (d, J = 11.4 Hz,
1H, CH2OCO); 4.69 (s, 2H, OCH2Ph); 5.13 (s, 2H, OCH2Ph); 7.00 (d, J =
8.7 Hz, 1H, CHAr); 7.28-7.53 (m, 10H, CHAr); 8.00 (d, J = 8.7 Hz, 1H,
CHAr). 13C NMR (75.0 MHz, CDCl3): δ 11.9 (CH3); 12.0 (CH3); 12.9
(CH3); 20.3 (CdC-CH2); 22.4 (CH3); 28.8 (CdC-CH2-CH2); 68.9
(CH2OCO); 70.1 (OCH2Ph); 73 0.8 (OCCH2OCO); 74.8 (OCH2Ph);
114.5 (CAr); 117.3 (CAr); 122.8 (CAr); 123.2 (CAr); 126.1 (CAr); 127.5
(CAr); 127.7 (CAr); 127.8 (CAr); 128.2 (CAr); 128.3 (CAr); 128.5 (CAr); 128.7
(CAr); 131.7 (CAr); 136.2 (CAr); 137.9 (CAr); 147.4 (CAr); 148.6 (CAr); 162.6
(CAr); 166.1 (CdO). MS (m/z): calculated for C35H36O5 = 537.2636;
found 537.2637 [M þ H]þ.
Data for (60-Benzyloxy-20,50,70,80-tetramethylchroman-20-yl) Methyl
3,4,5-Tribenzyloxy-benzoate (8e; Scheme 3). Eluent = DCM/hexanes
(4:1 v/v). Aspect: light yellow solids. Yield = 80%. 1H NMR (300.0 MHz,
CDCl3): δ 1.36 (s, 3H, CH3); 1.77-2.06 (m, 2H, CdC-CH2-CH2); 2.12
(s, 3H, CH3); 2.19 (s, 3H, CH3); 2.23 (s, 3H, CH3); 2.66 (t, J = 6.6 Hz, 2H,
CdC-CH2); 4.26 (d, J = 11.4 Hz, 1H, CH2OCO); 4.36 (d, J = 11.4 Hz,
1H, CH2OCO); 4.70 (s, 2H, OCH2Ph); 5.14 (s, 6H, OCH2Ph); 7.22-7.55
(m, 22H, CHAr). 13C NMR (75.0 MHz, CDCl3): δ 11.9 (CH3); 12.1 (CH3);
12.9 (CH3); 20.2 (CdC-CH2); 22.4 (CH3); 28.7 (CdC-CH2-CH2); 69.1
(CH2OCO); 71.2 (OCH2Ph); 73.7 (OCCH2OCO); 74.8 (OCH2Ph); 75.2
(OCH2Ph); 109.1 (CAr); 117.3 (CAr); 123.1 (CAr); 125.1 (CAr); 126.1 (CAr);
127.5 (CAr); 127.6 (CAr); 127.8 (CAr); 127.9 (CAr); 128.0 (CAr); 128.1 (CAr);
128.2 (CAr); 128.4 (CAr); 128.5 (CAr); 128.6 (CAr); 136.7 (CAr); 137.4 (CAr);
137.9 (CAr); 142.5 (CAr); 147.3 (CAr); 148.6 (CAr); 152.5 (CAr); 165.9
(CdO). MS (m/z): calculated for C49H48O7 = 749.3473; found 749.3485
[M þ H]þ.
General Procedure for the Preparation of Antioxidants 1a-1e
(Figure 1). Palladium on charcoal (10% w/w) was added to a solution
of the desired benzylated compound (0.7 mmol in 8 mL of dry THF). The
mixture was stirred at room temperature under an atmosphere of hydro-
gen for 24 h, then filtrated on Celite, and concentrated on a rotary evapo-
rator under reduced pressure. The residue was purified by flash column
chromatography with silica gel, and the solvents used for elution are
described for each individual component below.
Data for (60-Hydroxy-20,50,70,80-tetramethylchroman-20-yl) Methyl
4-Hydroxybenzoate (1a). Eluent = ethyl acetate/hexanes (2:3 v/v). Aspect:
white solids. Yield = 90%. Mp = 139-140 °C. 1H NMR (300.0 MHz,
CDCl3): δ 1.42 (s, 3H, CH3); 1.80-2.09 (m, 2H, CdC-CH2-CH2); 2.10
(s, 3H, CH3); 2.11 (s, 3H, CH3); 2.15 (s, 3H, CH3); 2.67 (t, J = 6.6 Hz, 2H,
CdC-CH2); 4.21 (s, 1H, OH); 4.27 (d, J = 11.4 Hz, 1H, CH2OCO); 4.34
(d, J = 11.4 Hz, 1H, CH2OCO); 5.40 (s, 1H, OH); 6.84 (d, J = 8.7 Hz, 1H,
CHAr); 7.95 (d, J = 8.7 Hz, 1H, CHAr). 13C NMR (75.0 MHz, CDCl3): δ
11.3 (CH3); 11.8 (CH3); 12.2 (CH3); 20.3 (CdC-CH2); 22.2 (CH3); 28.9
(CdC-CH2-CH2); 68.9 (CH2OCO); 73.5 (OCCH2OCO); 115.3 (CAr);
117.1 (CAr); 118.6 (CAr); 121.3 (CAr); 122.5 (CAr); 122.8 (CAr); 132.0
(CAr); 145.0 (CAr); 160.0 (CAr); 166.3 (CdO). MS (m/z): calculated for
C21H24O5 = 357.1697; found 357.1696 [M þ H]þ.
Data for (60-Benzyloxy-20,50,70,80-tetramethylchroman-20-yl) Methyl
3-Methoxy-4-benzyl-oxybenzoate (8b; Scheme 3). Eluent = ethyl acetate/
hexanes (25:75 v/v). Aspect: highly viscous oil. Yield = 75%. 1H NMR
(300.0 MHz, CDCl3): δ 1.39 (s, 3H, CH3); 1.81-2.09 (m, 2H, CdC-
CH2-CH2); 2.11 (s, 3H, CH3); 2.17 (s, 3H, CH3); 2.22 (s, 3H, CH3); 2.67
(t, J = 6.9 Hz, 2H, CdC-CH2); 3.94 (s, 3H, OCH3); 4.26 (d, J = 11.4 Hz,
1H, CH2OCO); 4.39 (d, J = 11.4 Hz, 1H, CH2OCO); 4.69 (s, 2H,
OCH2Ph); 5.23 (s, 2H, OCH2Ph); 6.90 (d, J = 8.10 Hz, 1H, CHAr);
7.27-7.65 (m, 12H, CHAr). 13C NMR (75.0 MHz, CDCl3): δ 11.9 (CH3);
12.0 (CH3); 12.9 (CH3); 20.3 (CdC-CH2); 22.4 (CH3); 28.8 (CdC-
CH2-CH2); 56.1 (OCH3); 68.9 (CH2OCO); 70.8 (OCH2Ph); 73.8
(OCCH2OCO); 74.8 (OCH2Ph); 112.5 (CAr); 112.6 (CAr); 117.4 (CAr);
122.9 (CAr); 123.2 (CAr); 123.5 (CAr); 126.1 (CAr); 127.2 (CAr); 127.8 (CAr);
127.9 (CAr); 128.1 (CAr); 128.3 (CAr); 128.5 (CAr); 128.7 (CAr); 136.4 (CAr);
137.9 (CAr); 147.4 (CAr); 148.6 (CAr); 149.2 (CAr); 152.2 (CAr); 166.2
(CdO). MS (m/z): calculated for C36H38O6 = 567.2741; found 567.2743
[M þ H]þ.
Data for (60-Hydroxy-20,50,70,80-tetramethylchroman-20-yl) Methyl
3-Methoxy-4-hydroxy-benzoate (1b). Eluent = ethyl acetate/hexanes
(1:1 v/v). Aspect: white solids. Yield = 70%. Mp = 171-172 °C. 1H
NMR (300.0 MHz, DMSO-d6): δ 1.03 (s, 3H, CH3); 1.43-1.75 (m, 2H,
CdC-CH2-CH2); 1.75 (s, 3H, CH3); 1.78 (s, 3H, CH3); 1.82 (s, 3H,
CH3); 2.25-2.38 (m, 2H, CdC-CH2); 3.57 (s, 3H, OCH3); 3.90 (d, J =
11.4 Hz, 1H, CH2OCO); 3.99 (d, J = 11.4 Hz, 1H, CH2OCO); 6.17 (s, 1H,
OH); 6.58 (d, J = 8.1 Hz, 1H, CHAr); 7.20 (s, 1H, CHAr); 7.24 (d, J = 8.1
Hz, 2H, CHAr); 8.48 (s, 1H, OH). 13C NMR (75.0 MHz, DMSO-d6): δ 12.1
(CH3); 12.3 (CH3); 13.2 (CH3); 20.2 (CdC-CH2); 22.2 (CH3); 28.8
(CdC-CH2-CH2); 56.0 (OCH3); 68.5 (CH2OCO); 73.7 (OCCH2OCO);
112.9 (CAr); 115.6 (CAr); 117.2 (CAr); 120.8 (CAr); 120.9 (CAr); 121.6 (CAr);
123.2 (CAr); 123.9 (CAr); 144.4 (CAr); 146.0 (CAr); 147.9 (CAr); 152.1 (CAr);
165.8 (CdO). MS: calculated for C22H26O6 = 387.1802; found 387.1781
[M þ H]þ.
Data for (60-Benzyloxy-20,50,70,80-tetramethylchroman-20-yl) Methyl
3,5-Dimethoxy-4-benzyl-oxybenzoate (8c; Scheme 3). Eluent = DCM/
hexanes (4:1 v/v). Aspect: highly viscous oil. Yield = 71%. 1H NMR
(300.0 MHz, CDCl3): δ 1.40 (s, 3H, CH3); 1.84-2.11 (m, 2H, CdC-
CH2-CH2); 2.13 (s, 3H, CH3); 2.18 (s, 3H, CH3); 2.22 (s, 3H, CH3); 2.68
(t, J = 6.9 Hz, 2H, CdC-CH2); 3.87 (s, 6H, OCH3); 4.28 (d, J = 11.4 Hz,
1H, CH2OCO); 4.43 (d, J = 11.4 Hz, 1H, CH2OCO); 4.69 (s, 2H,
OCH2Ph); 5.09 (s, 2H, OCH2Ph); 7.25-7.53 (m, 12H, CHAr). 13C
NMR (75.0 MHz, CDCl3): δ 11.8 (CH3); 12.0 (CH3); 12.9 (CH3); 20.2
(CdC-CH2); 22.3 (CH3); 28.9 (CdC-CH2-CH2); 56.2 (OCH3); 69.2
(CH2OCO); 73.8 (OCCH2OCO); 74.8 (OCH2Ph); 75.0 (OCH2Ph); 106.9
(CAr); 117.3 (CAr); 123.1 (CAr); 125.3 (CAr); 126.1 (CAr); 127.7 (CAr); 127.9
(CAr); 128.0 (CAr); 128.2 (CAr); 128.4 (CAr); 128.5 (CAr); 128.6 (CAr); 137.4
(CAr); 137.9 (CAr); 141.2 (CAr); 147.3 (CAr); 148.7 (CAr); 153.3 (CAr); 166.1
(CdO). MS (m/z): calculated for C37H40O7 = 597.2847; found 597.2831
[M þ H]þ.
Data for (60-Hydroxy-20,50,70,80-tetramethylchroman-20-yl) Methyl 3,5-
Dimethoxy-4-hydroxybenzoate (1c). Eluent = ethyl acetate/hexanes
(2:3 v/v). Aspect: white solids. Yield = 81%. Mp = 144-145 °C. 1H
NMR (300.0 MHz, CDCl3): δ 1.38 (s, 3H, CH3); 1.79-2.06 (m, 2H,
Data for (60-Benzyloxy-20,50,70,80-tetramethylchroman-20-yl) Methyl
3,4-Dibenzyloxy-benzoate (8d; Scheme 3). Eluent = ethyl acetate/hexanes