for the synthesis of methylenebisamides and other applications … · 2015-11-18 · 1 ammonium...
TRANSCRIPT
1
Ammonium persulfate activated DMSO as the one-carbon synthon for the synthesis of methylenebisamides and other applications
Pankaj S. Mahajan, Subhash D. Tanpure, Namita A. More, Jayant M. Gajbhiye, and
Santosh B. Mhaske*
CSIR-National Chemical Laboratory, Division of Organic Chemistry, Pune 411 008, India
Email: [email protected]
Table of Contents:
Pages
1. General Information and general procedure…………………………….2
2. Experimental procedures and characterization data……………………..3-10
3. References…………………………………………………………….....11
4. Copies of 1H, 13C, DEPT, HRMS Spectra ………………………………12-78
Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2015
2
General information
All reagents and solvents were used as received from commercial sources unless otherwise
noted. All amides were procured from commercial sources and used as it is. All experiments
were carried out under air atmosphere. Pre-coated plates (silica gel 60 PF254, 0.25 mm or 0.5
mm) were utilized for thin layer chromatography (TLC). Column chromatographic purifications
were carried out on flash silica-gel (240–400 mesh) using petroleum ether and ethyl acetate as
eluents. The 1H, 13C NMR spectra were recorded on 200/400/500 MHz, and 50/100/125 MHz
NMR spectrometers, respectively in CDCl3/DMSO-d6. Chemical shifts were reported as δ values
from standard peaks. Melting points are uncorrected. Mass spectra were taken on LC-MS (ESI)
mass or GC-MS mass spectrometer. HRMS were scanned on Quadrupole-Orbitrap Mass
Spectrometer available at our institutional facility.
General procedure for the synthesis of methylenebisamides
A solution of amide (50 mg, 1 equiv), ammonium persulfate [(NH4)2S2O8] (2 equiv) and DMSO
(6 equiv) in 1,4-dioxane (2 mL) was heated at 100 oC in a round bottom flask, equipped with a
stirring bar and water condenser, until the reaction was complete as indicated by thin layer
chromatography. After completion, the reaction mixture was filtered through a cotton plug and
1,4-dioxane was removed under vacuum. The residue was then dissolved in ethyl acetate (10
mL) and washed with warm water (4 mL) and brine (3 mL x 2). The organic layer was dried over
anhydrous sodium sulfate and the crude product was purified by flash column chromatography to
furnish corresponding methylenebisamides in good to excellent yields.
N,N’-methylenedibenzamide (2).1 Reaction time: 6 h; Rf: 0.5 (1:1, EtOAc:Pet. Ether);
White solid; mp 210-212 oC; 51 mg, 98%; 1H NMR (400 MHz, CDCl3) δ 7.80-7.70 (m, 6H),
3
7.43 (t, J = 5.9 Hz, 2H), 7.40-7.30 (m, 4H), 5.00 (t, J = 5.9 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 168.6, 133.4, 132.0, 128.6, 127.3, 45.7; HRMS-ESI (m/z) calcd [(C15H14O2N2)+Na]+:
277.0947, found: 277.0946.
N,N’-methylenebis(2-(trifluoromethyl)benzamide) (3). Reaction time: 18 h; Rf = 0.6
(EtOAc:Pet. Ether, 1:1). White solid; 36 mg, 70%, mp 213-215 oC; 1H NMR (400 MHz, DMSO-
d6): δ 9.26 (t, J = 5.6, 2H), 7.78 (d, J = 7.8, 2H), 7.74 (t, J = 7.6, 2H), 7.65 (t, J = 7.6, 2H),
7.51(d, J = 7.3, 2H), 4.69 (t, J = 5.6, 2H); 13C NMR (100 MHz, DMSO-d6): δ 167.6, 132.5,
130.0, 128.8, 125.3-126.4 (m, CF3), 126.0, 122.6, 44.4; HRMS-ESI (m/z) calcd
[C17H12O2N2F6+Na]+: 413.0695, found 413.0687.
N,N’-methylenebis(2-bromobenzamide) (4). Reaction time: 30 h; Rf: 0.5 (1:1, EtOAc:Pet.
Ether); White solid; mp 213-215 oC; 37 mg, 72%; 1H NMR (400 MHz, DMSO-d6) δ 9.13 (t, J =
5.6 Hz, 2H), 7.65 (d, J = 7.3 Hz, 2H), 7.46-7.34 (m, 6H), 4.71 (t, J = 5.6 Hz, 2H); 13C NMR (100
MHz, DMSO-d6) δ 167.7, 138.7, 132.9, 131.2, 129.2, 127.7, 119.1, 44.5; HRMS-ESI (m/z) calcd
[(C15H12O2N279Br2)+H]+: 410.9338, found: 410.9345.
N,N’-methylenebis(2-iodobenzamide) (5). Reaction time: 16 h; Rf: 0.5 (3:2, EtOAc:Pet.
Ether); White solid; mp 231-233 oC; 35 mg, 68%; 1H NMR (500 MHz, DMSO-d6) δ 9.07 (t, J =
5.5 Hz, 2H), 7.88 (d, J = 8.0 Hz, 2H), 7.47-7.43 (m, 2H), 7.40-7.35 (m, 2H), 7.20-7.14 (m, 2H),
4.70 (t, J = 5.5 Hz, 2H); 13C NMR (125 MHz, DMSO-d6) δ 169.2, 142.4, 139.3, 131.1, 128.5,
128.1, 93.6, 44.7; HRMS-ESI (m/z) calcd [(C15H12O2N2I2)+H]+: 506.9061, found: 506.9056.
N,N’-methylenebis(2-methyl-3-nitrobenzamide) (6). Reaction time: 30 h; Rf: 0.5 (9:1,
EtOAc:Pet. Ether); White solid; mp 277-279 oC; 34 mg, 65%; 1H NMR (400 MHz, DMSO-d6) δ
9.28 (t, 5.5 Hz, 2H), 7.94 (d, J = 7.8 Hz, 2H), 7.61 (d, J = 7.8 Hz, 2H), 7.51 (t, J = 7.8 Hz, 2H),
4
4.77 (t, J = 5.5 Hz, 2H), 2.40 (s, 6H); 13C NMR (100 MHz, DMSO-d6) δ 168.1, 150.7, 140.0,
131.5, 129.1, 127.4, 124.9, 44.6, 15.6; HRMS-ESI (m/z) calcd [(C17H16O6N4)+Na]+: 395.0962,
found: 395.0960.
N,N’-methylenebis(4-methylbenzamide) (7). 1 Reaction time: 5 h; Rf = 0.5 (EtOAc:Pet.
Ether, 2:3). White solid; 39 mg, 74%, mp 205-207 oC; 1H NMR (500 MHz, DMSO-d6): δ 8.93 (t,
J = 5.5 Hz, 2H), 7.81(d, J = 7.9 Hz, 4H), 7.26 (d, J = 7.9 Hz, 4H), 4.84 (t, J = 5.5 Hz, 2H), 2.34
(s, 6H); 13C NMR (125 MHz, DMSO-d6): δ 166.5, 141.4, 131.4, 128.9, 127.6, 45.3, 21.1; ESI-
MS (m/z): 305 (M+Na).
N,N’-methylenebis(4-isopropylbenzamide) (8).2 Reaction time: 7 h; Rf = 0.3 (EtOAc:Pet.
Ether, 1:1). White solid; 49 mg, 94%, mp 181-183 oC; 1H NMR (400 MHz, DMSO-d6): δ 8.96 (t,
J = 5.6 Hz, 2H), 7.83 (d, J = 8.3 Hz, 4H), 7.32 (d, J = 8.3 Hz, 4H), 4.84 (t, J = 5.6 Hz, 2H), 2.98-
2.87 (m, 2H), 1.20 (d, J = 6.8 Hz, 12H); 13C NMR (100 MHz, DMSO-d6): δ 166.6, 152.2, 131.8,
127.8, 126.4, 45.2, 33.5, 23.8; HRMS-ESI (m/z) calcd [C21H26O2N2+Na]+: 361.1886, found
361.1881.
N,N’-methylenebis(4-methoxybenzamide) (9).1 Reaction time: 4 h; Rf: 0.5 (13:7,
EtOAc:Pet. Ether); White solid; mp 199-201 oC; 48 mg, 93%; 1H NMR (400 MHz, DMSO-d6): δ
8.88 (t, J = 5.6 Hz, 2H), 7.89 (d, J = 8.8 Hz, 4H), 6.98 (d, J = 8.8 Hz, 4H), 4.82 (t, J = 5.6 Hz,
2H), 3.80 (s, 6H); 13C NMR (100 MHz, DMSO-d6): δ 166.1, 161.9, 129.5, 126.4, 113.6, 55.5,
45.3; HRMS-ESI (m/z) calcd [(C17H18N2O4)+Na]+: 337.1159, found: 337.1156.
N,N’-methylenebis(4-nitrobenzamide) (10).1 Reaction time: 18 h; Rf: 0.5 (7:3, EtOAc:Pet.
Ether); White solid; mp 247-249 oC; 37 mg, 71%; 1H NMR (500 MHz, DMSO-d6) : δ 9.5 (bs,
2H), 8.33-8.31 (m, 4H), 8.14-8.12 (m, 4H), 4.9 (s, 2H); 13C NMR (125 MHz, DMSO-d6) : δ
5
165.2, 149.3, 139.7, 129.2, 123.7, 45.5; HRMS-ESI (m/z) calcd [(C15H12O6N4)+Na]+: 367.0649,
found: 367.0647.
N,N’-methylenebis(4-chlorobenzamide) (11).1 Reaction time: 9 h; Rf: 0.5 (9:11,
EtOAc:Pet. Ether); White solid; mp 248-250 oC; 44 mg, 84%; 1H NMR (400 MHz, DMSO-d6): δ
9.18 (t, 5.5 Hz, 2H), 7.92 (d, J = 8.6 Hz, 4H), 7.54 (d, J = 8.6 Hz, 4H), 4.84 (t, 5.5 Hz, 2H); 13C
NMR (100 MHz, DMSO-d6): δ 165.7, 136.5, 132.9, 129.6, 128.6, 45.4; HRMS-ESI (m/z) calcd
[(C15H12O2N235Cl2)+Na]+: 345.0168, found: 345.0166.
N,N’-methylenebis(2-naphthamide) (12).2 Reaction time: 24 h; Rf: 0.5 (1:1, EtOAc:Pet.
Ether); White solid; mp 235-237 oC; 38 mg, 73%; 1H NMR (400 MHz, DMSO-d6): δ 9.27 (t, J =
5.4 Hz, 2H), 8.55 (s, 2H), 8.04-7.95 (m, 8H), 7.65-7.57 (m, 4H), 4.99 (t, J = 5.4 Hz, 2H); 13C
NMR (100 MHz, DMSO-d6): δ 166.8, 134.4, 132.3, 131.5, 129.1, 128.1, 128.0, 127.9, 127.8,
126.9, 124.5, 45.5; HRMS-ESI (m/z) calcd [(C23H18N2O2)+Na]+: 377.1260, found: 377.1266.
N,N’-methylenebis(thiophene-2-carboxamide) (19).3 Reaction time: 6 h; Rf: 0.6
(EtOAc:Pet. Ether, 1:1). White solid; 48 mg, 91%, mp 224-226 oC; 1H NMR (400 MHz, DMSO-
d6): δ 9.16 (t, J = 5.6 Hz, 2H), 7.88 (d, J = 3.7 Hz, 2H), 7.77 (d, J = 4.9 Hz, 2H), 7.14 (t, J = 4.9
Hz, 2H), 4.78 (t, J = 5.6 Hz, 2H); 13C NMR (100 MHz, DMSO-d6): δ 161.7, 139.7, 131.5, 128.9,
128.3, 44.7; HRMS-ESI (m/z) calcd [C11H10O2N2S2+Na]+: 289.0076, found 289.0072.
(2E,2’E)-N,N’-methylenebis(3-phenylacrylamide) (21). 1 Reaction time: 5 h; Rf: 0.5 (3:2,
EtOAc:Pet. Ether); White solid; mp 256-258 oC; 38 mg, 74%; 1H NMR (400 MHz, DMSO-d6): δ
8.81 (t, J = 6.1 Hz, 2H), 7.58-7.53 (m, 4H), 7.48 (d, J = 15.6 Hz, 2H), 7.45-7.36 (m, 6H), 6.69
(d, J = 15.6 Hz, 2H), 4.64 (t, J = 6.1 Hz, 2H); 13C NMR (100 MHz, DMSO-d6): δ 165.6, 139.7,
6
135.0, 129.9, 129.2, 127.8, 122.0, 43.8; HRMS-ESI (m/z) calcd [(C19H18N2O2)+Na]+: 329.1260,
found: 329.1259.
N,N’-methylenebis(2-phenylacetamide) (22).1 Reaction time: 11 h; Rf: 0.5 (1:1,
EtOAc:Pet. Ether); White solid; mp 213-215 oC; 40 mg, 77%; 1H NMR (400 MHz, DMSO-d6): δ
8.73 (t, J = 5.9 Hz, 2H), 7.30-7.19 (m, 10H), 4.38 (t, J = 5.9 Hz, 2H), 3.41 (s, 4H); 13C NMR
(100 MHz, DMSO-d6): δ 170.9, 136.4, 129.2, 128.4, 126.6, 43.6, 42.2; HRMS-ESI (m/z) calcd
[(C17H18O2N2)+Na]+; 305.1260, found: 305.1259.
N,N’-methylenebis(2-(2,6-difluorophenyl)acetamide) (23). Reaction time: 24 h; Rf: 0.5
(2:3, EtOAc:Pet. Ether); White solid; mp 281-283 oC; 31 mg, 60%; 1H NMR (400 MHz, DMSO-
d6): δ 8.80 (t, J = 5.9 Hz, 2H), 7.43-7.28 (m, 2H ), 7.15-6.98 (m, 4H), 4.42 (t, J = 5.9 Hz, 2H),
3.52 (s, 4H); 13C NMR (100 MHz, DMSO-d6): δ 168.8, 161.4 (dd, JCF = 245.8, 8.5 Hz), 129.2 (t,
JCF = 10.0 Hz), 112.0 (t, JCF = 20.0 Hz), 111.4 (dd, JCF = 19.3, 6.9 Hz), 43.8, 28.8; HRMS-ESI
(m/z) calcd [(C17H14N2O2F4)+H]+: 355.1064, found: 355.1061.
N,N’-methylenebis(2-(XXXaphthalene-1-yl)acetamide) (24). Reaction time: 30 h; Rf: 0.5
(7:3, EtOAc:Pet. Ether); White solid; mp 279-281oC; 22 mg, 40%; 1H NMR (400 MHz, DMSO-
d6): δ 8.87 (t, J = 6.1 Hz, 2H), 8.06 (d, J = 8.8 Hz, 2H), 7.92 (d, J = 9.0 Hz, 2H), 7.82 (d, J = 9.0
Hz, 2H), 7.59 – 7.39 (m, 8H), 4.44 (t, J = 6.1 Hz, 2H), 3.90 (s, 4H); 13C NMR (100 MHz,
DMSO-d6): δ 170.9, 133.6, 132.8, 132.2, 128.6, 127.9, 127.3, 126.2, 125.9, 125.8, 124.6, 43.7,
39.65; HRMS-ESI (m/z) calcd [(C25H22O2N2)+H]+: 383.1754, found: 383.1750.
N,N’-(methylene-d2)dibenzamide (2a). DMSO-d6 was used instead of DMSO. Reaction
time: 6 h; Rf: 0.5 (1:1, EtOAc:Pet. Ether); White solid; mp 224-226 oC; 50 mg, 94%; 1H NMR
7
(400 MHz, CDCl3): δ 7.74 (d, J = 7.3 Hz, 4H), 7.61 (bs, 2H), 7.44 (t, J = 7.2 Hz, 2H), 7.34 (t, 7.5
Hz, 4H); HRMS-ESI (m/z) calcd [(C15H122H2O2N2)+Na]+: 279.1073, found: 279.1078.
Procedure for the synthesis of pthalimide (16). The solution of amide 15 (50 mg, 1
equiv, 0.30 mmol), ammonium persulfate [(NH4)2S2O8] (138 mg, 2 equiv, 0.60 mmol) and
DMSO (130 µL, 6 equiv, 1.82 mmol) in 1,4-dioxane (2 mL) was heated at 100 oC in a round
bottom flask, equipped with a stirring bar and water condenser, until the reaction was complete
(3 h) as indicated by thin layer chromatography. After completion, the reaction mixture was
filtered through a cotton plug and 1,4-dioxane was removed under vacuum. The residue was then
dissolved in ethyl acetate (10 mL) and washed with warm water (4 mL) and brine (3 mL x 2).
The organic layer was dried over anhydrous sodium sulfate and the crude product was purified
by flash column chromatography to furnish pthalimide (16) in 98% yield (44 mg).
Isoindoline-1,3-dione (16).4 Reaction time: 3 h; Rf: 0.5 (1:4, EtOAc:Pet. Ether); White
solid; mp 237-239 oC; 44 mg, 98%; 1H NMR (400 MHz, DMSO-d6): δ 11.33 (s, 1H), 7.82 (s,
4H); 13C NMR (100 MHz, DMSO-d6): δ 169.5, 134.5, 132.8, 123.2; GC-MS (M+) : 147.0
Procedure for the synthesis of diphenylthiadiazole (18). The solution of thiamide 17
(50 mg, 1 equiv, 0.36 mmol), ammonium persulfate [(NH4)2S2O8] (166 mg, 2 equiv, 0.72 mmol)
and DMSO (154 µL, 6 equiv, 2.16 mmol) in 1,4-dioxane (2 mL) was heated at 100 oC for 5
minutes in a round bottom flask, equipped with a stirring bar and water condenser. The reaction
mixture was filtered through a cotton plug and 1,4-dioxane was removed under vacuum. The
residue was then dissolved in ethyl acetate (10 mL) and washed with warm water (4 mL) and
brine (3 mL x 2). The organic layer was dried over anhydrous sodium sulfate and the crude
8
product was purified by flash column chromatography to furnish 3,5-diphenyl-1,2,4-thiadiazole
(18) in 92% yield (40 mg).
3,5-diphenyl-1,2,4-thiadiazole (18).5 Reaction time: 5 min; Rf: 0.5 (1:19, EtOAc:Pet.
Ether); White solid; mp 95-97 oC; 40 mg, 92%; 1H NMR (400 MHz, CDCl3): δ 8.32 (dd, J = 7.6,
1.9 Hz, 2H), 7.98 (dd, J = 7.4, 2.1 Hz, 2H), 7.50-7.42 (m, 6H); 13C NMR (100 MHz, CDCl3): δ
188.1, 173.8, 132.8, 131.9, 130.7, 130.4, 129.3, 128.7, 128.3, 127.5; HRMS-ESI (m/z) calcd
[(C14H10N2S)+H]+: 239.0637, found: 239.0636.
Procedure for the synthesis of 2-(3-oxo-3-phenylpropyl)benzo[d]isothiazol-3(2H)-
one 1,1-dioxide (30). The solution of acetophenone (29, 50 mg, 1 equiv, 0.42 mmol), saccharine
(28, 152 mg, 2 equiv, 0.83 mmol), ammonium persulfate [(NH4)2S2O8] (190 mg, 2 equiv, 0.83
mmol) and DMSO (177 µL, 6 equiv, 2.46 mmol) in 1,4-dioxane (2 mL) was heated for 20 h at
120 oC in a Schlenk tube equipped with a stirring bar. The reaction mixture was filtered through
a cotton plug and 1,4-dioxane was removed under vacuum. The residue was then dissolved in
ethyl acetate (10 mL) and washed with warm water (4 mL) and brine (3 mL x 2). The organic
layer was dried over anhydrous sodium sulfate and the crude product was purified by flash
column chromatography to furnish 2-(3-oxo-3-phenylpropyl)benzo[d]isothiazol-3(2H)-one 1,1-
dioxide (30) in 52% yield (68 mg).
2-(3-oxo-3-phenylpropyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide (30).6 Reaction time:
20 h; Rf: 0.5 (3:7, EtOAc:Pet. Ether); White solid; mp 137-139 oC; 68 mg, 52%; 1H NMR (400
MHz, CDCl3) δ 8.02 – 7.98 (m, 1H), 7.92 – 7.74 (m, 5H), 7.51 (t, J = 7.7 Hz, 1H), 7.39 (t, 7.7
Hz, 2H), 4.19 (t, 7.8 Hz, 2H), 3.50 (t, 7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 196.8, 158.8,
9
137.7, 136.2, 134.8, 134.4, 133.5, 128.7, 128.0, 127.3, 125.2, 120.9, 36.8, 34.4; HRMS-ESI
(m/z) calcd [(C16H13O4NS)+Na]+: 338.0457, found: 338.0452.
Mechanistic aspect study:
Procedure for Radical trapping experiment. The solution of amide 1 (50 mg, 1 equiv,
0.41 mmol), ammonium persulfate [(NH4)2S2O8] (188 mg, 2 equiv, 0.82 mmol), TEMPO (128
mg, 2 equiv, 0.82 mmol) and DMSO (175 µL, 6 equiv, 2.46 mmol) in 1,4-dioxane (2 mL) was
heated for 24 h at 100 oC in a round bottom flask, equipped with a stirring bar and water
condenser. Only a trace amount of product was seen on TLC. Repetition of the same reaction
using BHT (145 mg, 4 equiv, 0.66 mmol) as a radical scavenger showed the same result.
Procedure using DMS instead of DMSO. The solution of amide 1 (50 mg, 1 equiv, 0.41
mmol), ammonium persulfate [(NH4)2S2O8] (188 mg, 2 equiv, 0.82 mmol), and DMS (232 mg, 6
equiv, 2.47 mmol) in 1,4-dioxane (2 mL) was heated for 6 h at 100 oC in a round bottom flask,
equipped with a stirring bar and water condenser. Usual work-up followed by column
chromatographic (2:3, ethyl acetate: petroleum ether) purification furnished 23 mg, 44% of 2.
Procedure using NH4I instead of (NH4)2S2O8. The solution of amide 1 (50 mg, 1 equiv,
0.41 mmol), ammonium iodide [NH4I] (119 mg, 2 equiv, 0.82 mmol) and DMSO (175 µL, 6
equiv, 2.46 mmol) in 1,4-dioxane (2 mL) was heated at 100 oC in a round bottom flask,
equipped with a stirring bar and water condenser. Even after heating for 24 h there was no
reaction and the starting material was recovered unchanged.
10
Procedure for trapping the formaldehyde equivalent intermediate to furnish
compound 32. To the solution of compound 31 ( 250 mg, 1.48 mmol, 1 eq) in 2 mL 1,4-dioxane
added sequentially APS (628 mg, 2.97 mmol, 2 eq) and DMSO (0.64 mL, 8.91 mmol, 6 eq) and
heated at 100 oC for 5 h then solvents were evaporated under vacuum and added 10 mL ethyl
acetate and washing of brine was given (5 mL X 2). Organic layer was separated dried over
sodium sulfate and column chromatography was done with 3:7 (ethyl acetate: petroleum ether) to
give 104 mg, 40% of 32.
Bis(2,4,6-trimethoxyphenyl)methane (32).7 Rf: 0.5 (1:5, EtOAc:Pet. Ether); White solid;
mp 110-112 oC; 1H NMR (400 MHz, CDCl3) δ 6.10 (s, 4H), 3.85 (s, 2H), 3.78 (s, 6H), 3.71 (s,
12H); 13C NMR (100 MHz, CDCl3) δ 159.2, 158.6, 111.9, 91.1, 56.0, 55.2, 16.6; HRMS-ESI
(m/z) calcd[(C19H25O6)+H]+; 349.1646, found: 349.1646.
Compound 34 as a plausible intermediate. The compound 33 was prepared as per the
literature procedure.8 To the solution of compound 33 (80 mg, 0.44 mmol, 1 eq) in 2 mL 1,4-
dioxane added sequencially 4-methoxy benzamide (66 mg, 0.44 mmol, 1 eq), APS (50 mg, 0.22
mmol, 0.5 eq) and heated at 50 oC for 5 h then reaction mixture was directly loaded on column
and purification done with 1:1 (ethylacetate: petroleum ether) to give 63 mg, 50% of 35 and 10
mg, 18% of benzamide 1 (based on 1H NMR) and 10 mg, 15% of compound 9 (corresponding to
4-methoxy benzamide).
N-((methylthio)methyl)benzamide(33).8 Rf: 0.3 (1:5, EtOAc:Pet. Ether); White Solid; mp
105-107 oC; 1H NMR (200 MHz, CDCl3): δ 7.84-7.78 (m, 2H), 7.58-7.41 (m, 3H), 6.49 (bs, 1H),
4.60 (d, J = 6.3 Hz, 2H), 2.22 (S, 3H).
N-(benzamidomethyl)-4-methoxybenzamide (35). Rf: 0.3 (1:1, EtOAc:Pet. Ether); White
Solid; 1H NMR (500 MHz, CDCl3) δ 7.82 (d, J = 7.3 Hz, 2H), 7.79 (d, J = 8.9 Hz, 2H), 7.74 (t, J
= 6.1 Hz, 1H), 7.64 (t, J = 6.1 Hz, 1H), 7.46 (t, J = 7.3 Hz, 1H), 7.42 (t, J =7.3 Hz, 2H), 6.90 (d,
J = 8.9 Hz, 2H), 5.04 (t, J = 6.1 Hz, 2H), 3.84 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 168.5,
168.0, 162.6, 133.5, 132.0, 129.1, 128.6, 127.2, 125.7, 113.8, 55.4, 45.6; HRMS-ESI (m/z)
calcd[(C16H16N2O3)+Na]+; 307.1053, found: 307.1046.
11
References
(1) Q. Wang, L. Sun, Y. Jiang, C. Li, Beil. J. Org. Chem., 2008, 4, 51.
(2) J. Mao, Faming Zhuanli Shenqing CN 104447391 A 20150325, 2015.
(3) N. Mameda, M. R. Marri, S. Peraka, A. K. Macharla, S. Kodumuri, D. Chevella, G. Naresh,
N. Nama, Catal. Commun., 2015, 61, 41.
(4) M. A. Ali, S. M. A. H. Siddiki, K. Kon, J. Hasegawa, K. Shimizu, Chem. Eur. J., 2014, 20,
14256.
(5) K. Yajima, K. Yamaguchi, N. Mizuno, Chem. Commun., 2014, 50, 6748.
(6) K. Sun, X. Wang, Y. Jiang, Y. Lv, L. Zhang, B. Xiao, D. Li, Z. Zhu, L. Liu, Chem. Asian J.,
2015, 10, 536.
(7) J. Tummatorn, C. Thongsornkleeb, S. Ruchirawat, Tetrahedron, 2012, 68, 4732.
(8) L. Bernardi, R. DeCastiglione, U. Scarponl, J. C. S. Chem. Commun., 1975, 320.
12
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
6.01 4.00 2.00
TMSCDCL3
0.00
4.98
5.00
5.01
7.19
7.32
7.33
7.35
7.42
7.43
7.45
7.74
7.76
7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2
6.01 4.002.00
CDCL3
7.197.
327.
337.
357.
427.43
7.45
7.747.
76
O
NH
NH
O
2
1H NMR, 400 MHz
13
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
Chloroform-d
45.7
1
77.0
0
127.
2612
8.60
132.
0313
3.37
168.
57
13C NMR, 100 MHz
O
NH
NH
O
2
14
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
45.7
1
127.
2612
8.60
132.
03
DEPT NMR, 100 MHz
O
NH
NH
O
2
15
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
4.02 2.01 2.002.00
DMSO-d6H2O
2.50
3.33
4.67
4.69
4.70
7.50
7.52
7.63
7.65
7.67
7.72
7.74
7.76
7.77
7.79
9.25
9.26
9.28
7.9 7.8 7.7 7.6 7.5
4.02 2.03 2.01
7.507.
52
7.63
7.65
7.677.72
7.74
7.76
7.77
7.79
NH
O
NH
O
CF3 F3C3
1H NMR, 400 MHz
16
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
0
44.4
2
122.
5712
5.29
126.
0012
6.38
128.
7813
0.03
132.
5113
6.10
167.
63
135 130 125
125.
2912
6.00
126.
3212
6.38
126.
42
128.
78
130.
03
132.
51
136.
10
13C NMR, 100 MHz
NH
O
NH
O
CF3 F3C3
17
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
44.4
2
126.
3912
8.78
130.
0313
2.52
DEPT NMR, 100 MHz
NH
O
NH
O
CF3 F3C3
18
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
6.112.07 2.001.96
TMSDMSO-d6H2O
0.00
2.50
3.34
4.69
4.71
4.72
7.34
7.36
7.38
7.39
7.41
7.42
7.44
7.46
7.64
7.66
9.12
9.13
9.15
7.7 7.6 7.5 7.4 7.3
6.112.07
7.347.
367.36
7.387.
387.
397.39
7.41
7.41
7.427.42
7.44
7.46
7.64
7.66
1H NMR, 400 MHz
NH
O
NH
O
Br Br4
19
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
0
44.5
0
119.
12
127.
6812
9.17
131.
1913
2.91
138.
66
167.
65
13C NMR, 100 MHz
NH
O
NH
O
Br Br4
20
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO d6
39.9
6
44.5
0
127.
6812
9.18
131.
1913
2.92
DEPT NMR, 100 MHz
NH
O
NH
O
Br Br4
21
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
2.13 2.032.022.01 2.00
DMSO-d6H2O
2.50
3.33
4.69
4.70
4.71
7.16
7.17
7.18
7.19
7.36
7.38
7.43
7.44
7.46
7.87
7.89
9.06
9.07
9.08
8.0 7.5
2.132.02 2.001.96
7.157.16
7.177.17
7.18
7.197.36
7.38
7.43
7.44
7.46
7.87
7.89
O
NH
NH
O
I I5
1H NMR, 500 MHz
22
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
0
44.7
0
93.6
0
128.
0912
8.53
131.
06
139.
3314
2.37
169.
19
140 135 130
128.
0912
8.53
131.
06
139.
33
142.
37
13C NMR, 125 MHz
O
NH
NH
O
I I5
23
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
44.7
0
128.
1112
8.54
131.
08
139.
33
DEPT NMR, 125 MHz
O
NH
NH
O
I I5
24
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
6.002.042.01 2.00 2.00
DMSO-d6H2O
2.40
2.50
3.44
4.76
4.77
4.79
7.49
7.51
7.53
7.60
7.62
7.93
7.95
9.27
9.28
9.30
9.0 8.5 8.0 7.5
2.042.01 2.00
7.51
7.537.60
7.627.93
7.95
9.279.28
9.30
1H NMR, 400 MHz
NO2
NH
O
NH
O
NO26
25
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
15.6
2
39.7
0
44.5
9
124.
9312
7.40
129.
1413
1.54
140.
04
150.
67
168.
08
13C NMR, 100 MHz
NO2
NH
O
NH
O
NO26
26
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
15.6
2
44.5
8
124.
9312
7.40
131.
54
DEPT NMR, 100 MHz
NO2
NH
O
NH
O
NO26
27
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
6.064.01 4.012.00 2.00
DMSO-d6
2.34
2.50
4.83
4.84
4.85
7.25
7.26
7.80
7.81
8.92
8.93
8.94
NH
O
NH
O
7
1H NMR, 500 MHz
28
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
21.1
1
39.7
0
45.2
7
127.
6112
8.94
131.
36
141.
44
166.
51
13C NMR, 125 MHz
NH
O
NH
O
7
29
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
21.1
1
45.2
6
127.
6112
8.94
DEPT NMR, 125 MHz
NH
O
NH
O
7
30
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
12.574.044.01 2.072.01 2.00
DMSO-d6H2O
1.19
1.21
2.50
2.89
2.91
2.93
2.94
2.96
3.34
4.83
4.84
4.85
7.31
7.33
7.82
7.84
8.94
8.96
8.97
NH
O
NH
O
8
1H NMR, 400 MHz
31
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
23.8
3
33.5
3
39.7
0
45.2
2
126.
3512
7.75
131.
82
152.
18
166.
55
13C NMR, 100 MHz
NH
O
NH
O
8
32
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
23.8
3
33.5
3
45.2
2
126.
3512
7.75
DEPT NMR, 100 MHz
NH
O
NH
O
8
33
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
6.094.014.00 2.002.00
DMSO-d6H2O
2.50
2.50
3.34
3.80
4.81
4.82
4.83
6.97
6.99
7.88
7.90
8.87
8.88
8.90
8 .9 8.8 8.7 8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9
4.002.00
7.88
7.90
8.87
8.88
8.90
O
NH
O
NH
O
O9
1H NMR, 400 MHz
34
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
0
45.2
5
55.5
3
113.
63
126.
3612
9.49
161.
87
166.
10
13C NMR, 100 MHz
O
NH
O
NH
O
O9
35
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
39.9
6
45.2
5
55.5
3
113.
64
129.
50
DEPT NMR, 100 MHz
O
NH
O
NH
O
O9
36
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
4.06 2.052.02
DMSO-d6H2O
2.50
3.34
4.90
8.12
8.14
8.31
8.31
8.33
9.49
8.40 8.35 8.30 8.25 8.20 8.15 8.10 8.05
4.064.00
8.128.
128.
148.
148.318.
318.
338.
33
O
NH
NH
O
O2N NO210
1H NMR, 500 MHz
37
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
0
45.4
8
123.
70
129.
16
139.
68
149.
34
165.
16
13C NMR, 125 MHz
O
NH
NH
O
O2N NO210
38
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
45.4
8
123.
71
129.
17
DEPT NMR, 125 MHz
O
NH
NH
O
O2N NO210
39
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
4.024.00 2.001.98
DMSO-d6H2O
2.50
3.34
4.83
4.84
4.86
7.53
7.55
7.91
7.93
9.17
9.18
9.19
9.0 8.5 8.0 7.5
4.024.001.98
7.537.
55
7.91
7.93
9.17
9.18
9.19
O
NH
NH
O
Cl Cl11
1H NMR, 400 MHz
40
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
0
45.3
6
128.
5612
9.59
132.
85
136.
47
165.
66
13C NMR, 100 MHz
O
NH
NH
O
Cl Cl11
41
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
45.3
6
128.
5712
9.59
13DEPT NMR, 100 MHz
O
NH
NH
O
Cl Cl11
42
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
8.03 4.012.00 2.002.00
DMSO-d6H2O
2.50
3.36
4.97
4.99
5.00
7.57
7.59
7.60
7.62
7.64
7.97
7.99
8.00
8.03
8.55
9.26
9.27
9.29
9 .0 8.5 8.0
8.03 4.012.002.00
7.59
7.60
7.62
7.64
7.97
7.99
8.00
8.03
8.55
9.26
9.27
9.29
NH
O
NH
O
12
1H NMR, 400 MHz
43
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
0
45.5
1
124.
4812
6.94
127.
8212
8.06
129.
1013
1.47
132.
3113
4.44
166.
77
134 133 132 131 130 129 128 127 126 125 124
124.
48
126.
9412
7.82
127.
9112
8.03
128.
06
129.
10
131.
47
132.
31
134.
44
13C NMR, 100 MHz
NH
O
NH
O
12
44
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
45.5
1
124.
4712
6.95
127.
8112
7.91
128.
0412
9.10
129 128 127 126 125 124
124.
47
126.
95
127.
8112
7.91
128.
0412
8.05
129.
10
DEPT NMR, 100 MHz
NH
O
NH
O
12
45
12.5 12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
4.211.00
DMSO-d6H2O
2.50
3.36
7.82
11.3
3
NH
O
O16
1H NMR, 400 MHz
46
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
0
123.
15
132.
8113
4.54
169.
46
13C NMR, 100 MHz
NH
O
O16
47
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
123.
15
134.
54
DEPT NMR, 100 MHz
NH
O
O16
48
8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
6.162.002.00
TMSCDCl3
0.00
7.18
7.39
7.41
7.42
7.44
7.45
7.46
7.48
7.49
7.97
7.99
8.31
8.32
8.33
8.33
8.4 8.3 8.2 8.1 8.0
2.002.00
7.97
7.977.
997.
99
8.318.
328.
33
1H NMR, 400 MHz
N
SN
18
49
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
Chloroform-d
77.0
0
127.
4712
8.32
128.
6812
9.25
130.
3513
0.67
131.
9113
2.84
173.
77
188.
10
134 133 132 131 130 129 128 127
127.
47
128.
3212
8.68
129.
25
130.
3513
0.67
131.
91
132.
84
13C NMR, 100 MHz
N
SN
18
50
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
127.
4712
8.32
128.
6912
9.26
130.
3613
1.92
DEPT NMR, 100 MHz
N
SN
18
51
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
2.032.02 2.01 2.00
DMSO-D6H2O in DMSO-d6
2.50
3.39
4.77
4.78
4.80
7.13
7.14
7.15
7.76
7.78
7.87
7.88
9.14
9.16
9.17
4.80 4.75
2.00
4.774.
78
4.80
7.15 7.10
2.01
7.137.14
7.15
7.90 7.85 7.80 7.75 7.70
2.03 1.98
7.76
7.787.87
7.88
9.20 9.15 9.10
2.02
9.149.
16
9.17
SO
NH
NH
SO
19
1H NMR, 400 MHz
52
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
0
44.7
2
128.
2512
8.95
131.
52
139.
72
161.
69
13C NMR, 100 MHz
SO
NH
NH
SO
19
53
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
44.6
8
128.
2412
8.94
131.
52
DEPT NMR, 100 MHz
SO
NH
NH
SO
19
54
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
6.43 2.002.00 2.00
DMSO-d6H2O
2.50
3.39
4.63
4.64
4.66
6.67
6.71
7.37
7.39
7.40
7.42
7.47
7.50
7.55
7.57
8.79
8.81
8.82
8 .5 8.0 7.5 7.0
6.434.03 2.002.00
6.67
6.71
7.37
7.39
7.40
7.42
7.43
7.44
7.47
7.50
7.55
7.57
8.79
8.81
8.82
O
NH
NH
O
21
1H NMR, 400 MHz
55
160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
0
43.8
1
122.
00
127.
8312
9.21
129.
86
135.
00
139.
69
165.
61
13C NMR, 100 MHz
O
NH
NH
O
21
56
160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
43.8
1
122.
01
127.
8412
9.22
129.
88
139.
70
DEPT NMR, 100 MHz
O
NH
NH
O
21
57
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
10.19 4.052.06 2.00
DMSO-d6H2o
2.50
3.37
3.41
4.36
4.38
4.39
7.19
7.21
7.22
7.24
7.26
7.28
7.30
8.72
8.73
8.74
HN
O
HN
O22
1H NMR, 400 MHz
58
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.7
042
.19
43.5
6
126.
5512
8.38
129.
21
136.
38
170.
87
13C NMR, 100 MHz
HN
O
HN
O22
59
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
42.1
943
.56
126.
5512
8.38
129.
22
DEPT NMR, 100 MHz
HN
O
HN
O22
60
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
4.00 4.002.00 2.002.00
DMSO-d6H2O
2.50
3.37
3.52
4.41
4.42
4.44
7.03
7.04
7.05
7.06
7.08
7.09
7.31
7.33
7.35
7.37
7.39
8.78
8.80
8.81
8 .5 8.0 7.5 7.0
4.002.002.00
7.04
7.05
7.06
7.08
7.09
7.31
7.33
7.33
7.35
7.37
7.37
7.39
8.78
8.80
8.81
F
FNH
O
NH
OF
F23
1H NMR, 400 MHz
61
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
28.7
6
39.7
0
43.8
0
111.
2511
1.50
111.
8111
2.02
112.
21
129.
2512
9.35
160.
0716
0.16
162.
5216
2.60
168.
77
163.0162.5 162.0 161.5 161.0 160.5 160.0
160.
0716
0.16
162.
5216
2.60
129.5 129.0
129.
1512
9.25
129.
35
112.5 112.0 111.5 111.0
111.
2511
1.31
111.
4311
1.50
111.
81
112.
02
112.
21
13C NMR, 100 MHz
F
FNH
O
NH
OF
F23
62
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
28.7
6
43.7
9
111.
2611
1.50
129.
1512
9.26
111.5 111.0
111.
2611
1.32
111.
4411
1.50
129.5 129.0
129.
15
129.
26
129.
36
DEPT NMR, 100 MHz
F
FNH
O
NH
OF
F23
63
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
8.15 4.002.092.03 2.02
DMSO-d6H2O
2.50
3.40
3.90
4.42
4.44
4.45
7.41
7.42
7.49
7.50
7.50
7.52
7.81
7.83
7.91
7.93
8.05
8.07
8.86
8.87
8.89
9.0 8.5 8.0 7.5
8.152.092.03 2.03 2.03
7.42
7.507.50
7.51
7.52
7.537.81
7.837.91
7.93
8.05
8.07
8.868.87
8.89
NH
O
NH
O
24
1H NMR, 400 MHz
64
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
DMSO-d6
39.6
539
.70
43.7
4
124.
5512
5.75
126.
1912
7.30
127.
9712
8.59
132.
2213
2.83
133.
56
170.
91
130 125
124.
55
125.
7512
5.88
126.
1912
7.30
127.
9712
8.59
132.
2213
2.83
133.
56
13C NMR, 100 MHz
NH
O
NH
O
24
65
150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
39.6
5
43.7
6
124.
5612
5.76
125.
8912
6.21
127.
3112
7.97
128.
60
130 129 128 127 126 125 124
124.
56
125.
7612
5.89
126.
21
127.
31
127.
97
128.
60
DEPT NMR, 100 MHz
NH
O
NH
O
24
66
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
5.03 2.02 2.01 2.01
TMSCDCl3
0.00
3.48
3.50
3.52
4.17
4.19
4.21
7.19
7.39
7.41
7.51
7.77
7.79
7.81
7.85
7.88
7.88
7.90
7.99
8.00
8.0 7.5
5.03 2.021.000.98
7.37
7.39
7.41
7.497.
517.
52
7.75
7.75
7.777.
797.79
7.81
7.817.
857.
887.88
7.90
7.99
8.00
8.01
4.0 3.5
2.01 2.01
3.483.
503.
524.174.
194.
21
O
NS
O
O O30
1H NMR, 400 MHz
67
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
Chloroform-d
34.4
336
.79
77.0
0
120.
9512
5.17
127.
3112
8.02
128.
6813
3.51
134.
3813
4.79
136.
1613
7.69
158.
77
196.
78
135 130 125
120.
95
125.
17
127.
3112
8.02
128.
68
133.
5113
4.38
134.
79
136.
16
137.
69
13C NMR, 100 MHz
O
NS
O
O O30
68
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
34.4
336
.79
120.
9512
5.18
128.
0212
8.68
133.
5213
4.38
134.
80
DEPT NMR, 100 MHz
O
NS
O
O O30
69
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
4.04 4.03
TMSH2OCDCl3
0.00
1.74
7.19
7.32
7.34
7.36
7.42
7.44
7.46
7.61
7.73
7.75
7.8 7.7 7.6 7.5 7.4 7.3
4.04 4.032.012.00
7.32
7.34
7.36
7.427.
447.
46
7.61
7.73
7.75
NH
O
NH
OD D
2a
1H NMR, 400 MHz
70
HRMS-ESI
NH
O
NH
OD D
2a
71
HRMS-ESI
O
NH
NH
O
2
72
8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
12.034.00
Chloroform-d
3.71
3.78
3.85
6.10
7.27
3.90 3.85 3.80 3.75 3.70 3.65 3.60 3.55 3.50
12.036.002.00
3.71
3.78
3.85
OMe
MeO OMe
MeO
OMe
OMe32
1H NMR, 400 MHz
73
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
Chloroform-d
16.6
1
55.1
556
.02
76.6
877
.00
77.3
1
91.0
6
111.
89
158.
6115
9.20
13C NMR, 100 MHz
OMe
MeO OMe
MeO
OMe
OMe32
74
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
16.6
1
55.1
656
.03
91.0
6
DEPT NMR, 100 MHz
OMe
MeO OMe
MeO
OMe
OMe32
75
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
3.02 3.002.00 1.980.92
Chloroform-d
2.22
4.58
4.61
6.49
7.27
7.45
7.46
7.48
7.49
7.51
7.52
7.78
7.78
7.81
7.82
7.82
NH
O
S
33
1H NMR, 200 MHz
76
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
3.002.51 2.032.001.991.00
Chloroform-d
3.84
5.03
5.04
5.05
6.89
6.91
7.27
7.40
7.42
7.43
7.46
7.48
7.64
7.78
7.80
7.81
7.82
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8
2.51 2.001.991.01 1.00
Chloroform-d
6.89
6.91
7.27
7.40
7.42
7.43
7.45
7.46
7.48
7.62
7.64
7.65
7.72
7.74
7.75
7.78
7.80
7.81
7.82
NH
O
NH
O
OMe35
1H NMR, 500 MHz
77
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
Chloroform-d
45.6
4
55.4
0
77.0
0
113.
80
125.
7412
7.21
128.
5812
9.11
131.
9513
3.54
162.
62
168.
0216
8.46
130 125
125.
74
127.
21
128.
5812
9.11
131.
95
133.
54
13C NMR, 125 MHz
NH
O
NH
O
OMe35
78
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
45.6
4
55.4
1
113.
80
127.
2212
8.59
129.
1213
1.96
DEPT NMR, 125 MHz
NH
O
NH
O
OMe35