Synthesis in water and antimicrobial activity of 5-trichloromethyl-4,5- dihydroisoxazoles

Article abstract of DOI:10.1080/00397911.2012.706349

Two series of 5-trichloromethylisoxazoles were synthesized from the cyclocondensation of 1,1,1-trichloro-4-methoxy-3-alken-2-ones [Cl ₃CC(O)C(R²) = C(R¹)O Me, where R¹ = H, Me, Et, Pr, iso-Pr, cyclo-Pr, Bu, terc

Full text of DOI:10.1080/00397911.2012.706349

1
Synthesis in water and antimicrobial activity of 5-trichloromethyl-
4,5-dihydroisoxazoles
Alex F. C. Floresa, Luciana A. Piovesana, Alynne A. Soutoa, Marano A. Pereirab, Marcos A. P.
Martinsa, Tatiane L. Ballianob, Givanildo S. da Silvab
aNUQUIMHE - Departamento de Química, Universidade Federal de Santa Maria
97105 900, Santa Maria, RS, Brazil
bLabCriMM Instituto de Química e Biotecnologia - Universidade Federal de Alagoas
57072-970, Maceió, AL, Brazil
Supplementary Information
1H and 13C NMR data and spectra for 5-trichloromethyl-5-hydroxy-4,5-dihydroisoxazoles (2)
1
and 1H and 13C NMR data 5-trichloromethylisoxazoles (3) are presented. The H and 13C
spectra were recorded at 298 K on a Bruker DPX 400 spectrometer (1H at 400.13 MHz, 13C at
100.63 MHz) with a digital resolution of  0.01 ppm. All chemical shifts are expressed in
1
ppm, and H and 13C are reported with respect to internal TMS. 0.1 M CDCl3 solutions were
used. Also show the X-ray diffraction data for 5-trichloromethyl-5-hydroxy-3-propyl-4,5-
dihydroisoxazole
(2d)
and
5-trichloromethyl-5-hydroxy-3,4-hexamethylene-4,5-
dihydroisoxazole (2o). Biological assays were used to screen 5-trichloromethyl-5-hydroxy-
4,5-dihydroisoxazole (2) for the antibacterial activity.
Data for 2a: Yield 85%, m.p.: 141–142°C/ Lit. 143–144°C [1]; 1H NMR (200 MHz, DMSO-
d6): 3.29 (dd, 1H, J 18.5 Hz, J 1.6 Hz, H4), 3.74 (dd, 1H, J 18.5 Hz, J 1.6 Hz, H4’), 7.11 (br,
1H, OH), 7.48 (t, 1H, J 1.6 Hz, H3); 13C NMR (50 MHz, DMSO-d6): 148.8 (C3), 46.3 (C4),
110.5 (C5), 102.3 (CCl3); MS (70 eV): m/z 204 (M+, 25), 187 (40), 117 (20), 86 (100); Anal.
Calcd. for C4H4Cl3NO2: C, 23.5; H, 2.0; N, 6.9; found C, 23.7; H, 2.1; N, 7.0.
1
2b: Yield 89%, m.p.: 127–128°C/ Lit. 127°C [2]; H NMR (200 MHz, DMSO-d6): 2.04 (s,
3H,Me), 3.23 (d, 1H, J 18.8 Hz, H4), 3.76 (d, 1H, J 18.8 Hz, H4’), 6.98 (s, 1H, OH); 13C
NMR (50 MHz, DMSO-d6): 156.7 (C3), 47.9 (C4), 111.1 (C5), 101.9 (CCl3), 12.3 (Me); MS

2
(70 eV): m/z 218 (M+, 40), 201 (60), 117 (14), 101 (58), 58 (100); Anal. Calcd. for
C5H6Cl3NO2: C, 27.5; H, 2.8; N, 6.4; found C, 27.7; H, 2.9; N, 6.4.
1
2c: Yield 96%, m.p.: 121–122°C/ Lit 121–122°C [2]; H NMR (200 MHz, DMSO-d6): 1.16
(t, 3H, J 7.4 Hz, Me), 2.41 (q, 2H, J 7.4 Hz, -CH2-), 3.23 (d, 1H, J 18.6 Hz, H4), 3.71 (d, 1H,
J 18.6 Hz, H4’); 13C NMR (50 MHz, DMSO-d6): δ 161.7 (C3), 47.1 (C4), 111.7 (C5), 102.7
(CCl3), 21.6 (-CH2-), 10.9 (Me); MS (70 eV): m/z 232 (M+, 25), 215 (27), 117 (100), 71 (61);
Anal. Calcd. for C6H8Cl3NO2: C, 31.0; H, 3.5; N, 6.0; found C, 31.2; H, 3.6; N, 6.0.
2d: Yield 93%, m.p.: 140–141°C/ Lit. 140°C27; 1H NMR (200 MHz, DMSO-d6): 0.96 (t, 3H,
J 7.6 Me), 1.65 (sx, 2H, J 7.2 Hz, -CH2-), 2.4 (t, 2H, J 7.2, -CH2-), 3.24 (dt, 1H, J 18 Hz, J 0.8
Hz, H4), 3.69 (dt, 1H, J 18 Hz, J 0.8 Hz, H4’); 13C NMR (50 MHz, DMSO-d6): δ 160.5 (C3),
47.2 (C4), 111.5 (C5), 102.7 (CCl3), 29.8 (-CH2-), 20 (-CH2-), 13.7 (Me); MS (70 eV): m/z
246 (M+, 20), 229 (23), 117 (72), 85 (100); Anal. Calcd. for C7H10Cl3NO2: C, 34.1; H, 4.1; N,
5.7; found C, 34.3; H, 4.2; N, 5.7.
1
2e: Yield 91%, m.p.: 139–140°C/ Lit. 139–140°C [3]; H NMR (200 MHz, DMSO-d6): 1.2
(d, 6H, J 6.8 Me), 2.75 (sp, 1H, J 6.8 Hz, CH), 3.28 (dd, 1H, J 18.6 Hz, J 0.8 Hz, H4), 3.69
13
(dt, 1H, J 18.6 Hz, J 0.8 Hz, H4’); C NMR (50 MHz, DMSO-d6): 164.9 (C3), 45.3 (C4),
111.6 (C5), 102.8 (CCl3), 29.8 (CH), 20.1 (Me); MS (70 eV): m/z 246 (M+, 10), 229 (13),
117 (100), 85 (40); Anal. Calcd. for C7H10Cl3NO2: C, 34.1; H, 4.1; N, 5.7; found C, 34.3; H,
4.2; N, 5.7.
1
2f: Yield 89%, m.p.: 165°C/ Lit. 164–165°C [3]; H NMR (200 MHz, DMSO-d6): 0.82 (m,
2H, cis to CH), 0.91 (dm, 2H, trans to CH), 1.78 (m, 1H, CH), 3.07 (d, 1H, J 18.5 Hz, H4),
13
3.55 (d, 1H, J 18.5 Hz, H4’); C NMR (50 MHz, DMSO-d6): 162.5 (C3), 45.3 (C4), 111.6
(C5), 102.6 (CCl3), 9.45 (CH), 6.4, 6.1 (-CH2-); MS (70 eV): m/z 244 (M+, 50), 227 (18),
117 (72), 83 (68); Anal. Calcd. for C7H8Cl3NO2: C, 34.4; H, 3.3; N, 5.7; found C, 34.5; H,
3.4; N, 5.7.
1
2g: Yield 96%, m.p.: 156°C/ Lit. 152–154°C [3]; H NMR (200 MHz, DMSO-d6): 0.97 (d,
6H, J 6.6, Me), 2.05 (m, 1H, CH), 2.27 (d, 2H, J 7.0, CH2), 3.22 (d, 1H, J 18.5 Hz, H4), 3.69

3
1
13
(d, H, J 18.5 Hz, H4’); C NMR (50 MHz, DMSO-d6): δ 160 (C3), 47.5 (C4), 111.6 (C5),
102.8 (CCl3), 36.8 (CH2), 26.7 (CH), 22.5, 22.6 (Me); MS (70 eV): m/z 260 (M+, 30), 243
(35), 143 (72), 117 (16), 100 (31), 57 (100); Anal. Calcd. for C8H12Cl3NO2: C, 36.9; H, 4.6;
N, 5.4; found C, 37.0; H, 4.6; N, 5.4.
1
2h: Yield 91%, m.p.: 169°C/ Lit. 170–171°C [3]; H NMR (200 MHz, DMSO-d6): 1.22 (s,
9H, Me), 3.30 (d, 1H, J 18.5 Hz, H4), 3.73 (d, 1H, J 18.5 Hz, H4’); 13C NMR (50 MHz,
DMSO-d6): 166.9 (C3), 44.4 (C4), 111.6 (C5), 102.4 (CCl3), 33.6 (Cq), 26.7 (Me); MS (70
eV): m/z 259 (M+, 10), 243 (11), 143 (15), 117 (10), 57 (100); Anal. Calcd. for C8H12Cl3NO2:
C, 36.9; H, 4.6; N, 5.4; found C, 37.0; H, 4.6; N, 5.4.
1
2i: Yield 87%, m.p.: 90–91°C/ Lit. 88–92°C [4]; H NMR (200 MHz, DMSO-d6): 3.41 (d,
13
1H, J 18.9 Hz, H4), 3.86 (d, 1H, J 18.9 Hz, H4’), 4.5 (s, 2H, -CH2-); C NMR (50 MHz,
DMSO-d6): δ 157.3 (C3), 44.7 (C4), 112.9 (C5), 102.0 (CCl3), 37.9 (-CH2-); MS (70 eV):
m/z 297 (M+, 10), 280 (10), 233 (25), 177 (100), 117 (43); Anal. Calcd. for C5H5BrCl3NO2:
C, 20.2; H, 1.7; N, 4.7; found C, 20.5; H, 1.9; N, 4.7.
1
2j: Yield 90%, m.p.: 84–85°C/ Lit. 85–86°C [4]; H NMR (200 MHz, DMSO-d6): 3.60 (d,
1H, J 18.9 Hz, H4), 4.05 (d, 1H, J 18.9 Hz, H4’), 6.9 (s, 1H, CH); 13C NMR (50 MHz,
DMSO-d6): δ 158.6 (C3), 42.6 (C4), 113.7 (C5), 101.4 (CCl3), 30.8 (CH); MS (70 eV): m/z
373 (M+, 5), 356 (8), 256 (17), 211 (100), 173 (23), 117 (53); Anal. Calcd. for
C5H4Br2Cl3NO2: C, 20.2; H, 1.7; N, 4.7; found C, 20.5; H, 1.9; N, 4.7.
1
2m: Yield 95%, m.p.: 106–107°C; H NMR (200 MHz, DMSO-d6): 1.35 (d, 3H, J 7.5 Hz,
Me), 3.9 (qd, 1H, J 7.5 Hz, 1,2 Hz, H4), 7.38 (d, 1H, J 1.2 Hz, H3); 13C NMR (50 MHz,
DMSO-d6): δ 152.8 (C3), 48.8 (C4), 109.1 (C5), 102,7 (CCl3), 11.2 (Me); MS (70 eV): m/z
219 (M+, 19), 201 (17), 117 (100), 55 (90); Anal. Calcd. for C5H6Cl3NO2: C, 27.5; H, 2.8; N,
6.4; found C, 27.7; H, 2.9; N, 6.4.
2n: Yield 95%; m.p.: 148–150°C/ Lit. 150°C [5]; 1H NMR (200 MHz, CDCl3) 1.22–2.61 (m,
8H, -CH2-), 3.51 (dd, J 12 Hz, 6 Hz, H4); 13C NMR (50 MHz, CDCl3) 161.6 (C3), 53.4 (C4),
110.2 (C5), 103.5 (CCl3), 27.6, 25.8, 25.7, 24 (-CH2-). MS (EI, 70 eV): m/z (%): 259 (M+,

4
29), 242 (100), 224 (44), 189 (37), 117 (39), 95 (61). Anal. Calcd. for C8H10Cl3NO2: C, 37.17;
H, 3.90, N, 5.42; found: C, 37.20; H, 3.90; N, 5.50.
1
2o: Yield 90%; m.p.: 121°C/ Lit. 118–120°C [5]; H NMR (200 MHz, CDCl3)  1.58–1.67
(m, 5H, -CH2-), 1.77–1.82 (m, 3H, -CH2-), 1.9–1.97 (m, 1H, -CH2-), 2.1–2.15 (m, 1H, -CH2-),
2.44–2.5 (m, 1H, -CH2-), 2.67–2.72 (m, 1H, -CH2-), 3.7 (dd, J 7.2 Hz, 4.0 Hz, H4); 13C NMR
(50 MHz, CDCl3)  164.2 (C3), 54.1 (C4), 110.2 (C5), 102.6 (CCl3), 26.3, 26.0, 25.8, 25.6,
25.3, 24.7 (-CH2-). MS (EI, 70 eV): m/z (%): 273 (M+, 29), 256 (35), 238 (49), 203 (45), 117
(57), 107 (35), 95 (100). Anal. Calcd. for C10H14Cl3NO2: C, 41.49; H, 4.92, N, 4.89; found: C,
41.5; H, 5.1; N, 4.60.
1
2p: Yield 87%; m.p.: 141–142°C/ Lit. 140–142°C [5]; H NMR (400 MHz, CDCl3) 1.14 (t,
3H, J 7.4 Hz, Me), 1.31 (d, 3H, J 7.4 Hz, Me), 2.30 (m, 2H, -CH2-), 3.72 (q, 1H, J 7.4 Hz,
13
H4); C NMR (50 MHz, CDCl3) 165.0 (C3), 49.9 (C4), 110.9 (C5), 103.8 (CCl3), 20.4 (-
CH2-), 12.0 (Me-4), 10.5 (Me). MS (EI, 70 eV): m/z (%): 247 (M+, 29), 230 (60), 212 (59),
176 (64), 130 (100), 117 (39), 72 (41). Anal. Calcd. for C7H10Cl3NO2: C, 34.11; H, 4.09, N,
5.68; found: C, 34.0; H, 4.0; N, 5.70.
2q: Yield 97%; m.p.: 156°C/ Lit. 155–158°C [5]; 1H NMR (200 MHz, CDCl3) 1.30 (d, 3H, J
13
7.4 Hz, Me), 4.10 (q, 1H, J 7.4 Hz, H4), 7.30 (m, 3H, Ph), 7.51 (m, 2H, Ph); C NMR (50
MHz, CDCl3) 162.0 (C3), 47.3 (C4), 110.8 (C5), 102.2 (CCl3), 127, 127.8, 128.8, 130.2 (Ph).
MS (EI, 70 eV): m/z (%): 281 (M+, 29), 263 (100), 246 (29), 211 (54), 120 (37), 117 (39), 76
(41). Anal. Calcd. for C10H8Cl3NO2: C, 44.85; H, 3.42, N, 4.76; found: C, 45.0; H, 3.5; N,
4.70.
Data for 3a: Yield 93%, yellow oil/ Lit. 24–26°C [1]; 1H NMR (200 MHz, CDCl3): δ 6.98 (d,
1H, J 2.0 Hz, H4), 8.61 (d, 1H, J 2.0 Hz, H3); 13C NMR (50 MHz, CDCl3): δ 152 (C3), 104.6
(C4), 168.5 (C5), 85.2 (CCl3); MS (70 eV): m/z 187 (M+, 100), 152 (46), 117 (65), 40 (79);
Anal. Calcd. for C4H2Cl3NO: C, 25.8; H, 1.08; N, 7.5; found C, 26.0; H, 1.0; N, 7.5.

5
1
3b: Yield 92%, m.p.: yellow oil/ Lit. oil [5]; H NMR (200 MHz, CDCl3): 2.78 (s, 3H,Me),
13
7.25 (s, 1H, H4); C NMR (50 MHz, CDCl3): δ 161.4 (C3), 105.7 (C4), 168.7 (C5), 85.5
(CCl3), 11.4 (Me); MS (70 eV): m/z 201 (M+, 100), 166 (30), 131 (45), 117 (30), 56 (70);
Anal. Calcd. for C5H4Cl3NO: C, 29.92; H, 2.0; N, 6.99; found C, 30.0; H, 2.0; N, 7.0.
3c: Yield 95%, yellow oil; 1H NMR (200 MHz, CDCl3): 1.28 (t, 3H, J 7.6 Hz, Me), 2.73 (q,
2H, J 7.6 Hz, -CH2-), 6.87 (s, 1H, H4); 13C NMR (50 MHz, DMSO-D6): δ 166.5 (C3), 104.5
(C4), 168.7 (C5), 85.6 (CCl3), 20.1 (-CH2-), 12.7 (Me); MS (70 eV): m/z 214 (M+, 95), 179
(77), 143 (100), 117 (45), 71 (80); Anal. Calcd. for C6H6Cl3NO: C, 33.6; H, 2.82; N, 6.53;
found C, 33.5; H, 3.0; N, 6.5.
3e: Yield 92%, yellow oil; 1H NMR (200 MHz, CDCl3): 1.31 (d, 6H, J 7.2 Hz, Me), 3.08 (sp,
13
1H, J 7.2 Hz, CH), 6.93 (s, H, H4); C NMR (50 MHz, CDCl3): δ 170.5 (C3), 103.5 (C4),
168.7 (C5), 85.6 (CCl3), 27.3 (CH), 21.5 (Me); MS (70 eV): m/z 229 (M+, 100), 194 (70),
158 (85), 117 (40), 75 (78); Anal. Calcd. for C7H8Cl3NO: C, 36.79; H, 3.53; N, 6.13; found C,
36.5; H, 3.4; N, 6.1.
3f: Yield 95%, yellow oil; 1H NMR (200 MHz, CDCl3): 0.89–0.94 (m, 2H, -CH2-), 1.05–1.13
(m, 2H, -CH2-), 2.06 (m, 1H, CH), 6.72 (d, 1H, J 1.2 Hz, H4); 13C NMR (50 MHz, CDCl3): δ
167.8 (C3), 102.6 (C4), 168.6 (C5), 85.5 (CCl3), 8.5 (-CH2-), 7.8 (CH); MS (70 eV): m/z 226
(M+, 95), 191 (27), 156 (40), 117 (55), 81 (54), 41 (100); Anal. Calcd. for C7H6Cl3NO: C,
37.1; H, 2.67; N, 6.18; found C, 36.8; H, 2.5; N, 6.2.
3g: Yield 95%, yellow oil; 1H NMR (200 MHz, CDCl3): 1,01 (d, 6H, J 7.5 Me), 2.08 (m, 1H,
13
J 7.5 Hz, CH), 2.64 (d, 2H, J 7.5, -CH¬2-), 6.88 (s, 1H, H4); C NMR (50 MHz, CDCl3):
164.4 (C3), 105 (C4), 168.6 (C5), 85.5 (CCl3), 35.2 (-CH2-), 28.2 (CH), 22.4 (Me); MS (70
eV): m/z 242 (M+, 90), 207 (43), 172 (72), 125 (25), 117 (40), 87 (100); Anal. Calcd. for
C8H10Cl3NO: C, 39.6; H, 4.16; N, 5.78; found C, 39.8; H, 4.2; N, 5.9.
1
3h: Yield 88%, yellow oil; H NMR (200 MHz, CDCl3): 1.35 (s, 9H,Me), 6.98 (s, 1H, H4);
13C NMR (50 MHz, CDCl3): δ 173.1 (C3), 103.2 (C4), 168.6 (C5), 85.5 (CCl3), 33.0 (Cq),
29.3 (Me); MS (70 eV): m/z 242 (M+, 80), 207 (10), 185 (25), 172 (41), 125 (30), 117 (100),

6
57 (79); Anal. Calcd. for C8H10Cl3NO: C, 39.6; H, 4.16; N, 5.79; found C, 39.8; H, 4.3; N,
5.5.
1
3i: Yield 89%, red oil/ B. p. Lit. 94–96°C/4 mBar [5]; H NMR (200 MHz, CDCl3): 4.94 (s,
2H, -CH2Br), 7.22 (s, 1H, H4); 13C NMR (50 MHz, CDCl3): δ 162.4 (C3), 104.3 (C4), 169.4
(C5), 85.1 (CCl3), 35.6 (CH2Br); (Me); MS (70 eV): m/z 280 (M+, 95), 245 (17), 210 (50),
200 (100), 186 (35), 165 (60), 117 (25), 95 (67); Anal. Calcd. for C5H3BrCl3NO: C, 21.5; H,
1.08; N, 5.01; found C, 21.8; H, 1.0; N, 5.3.
1
3j: Yield 90%, m.p. 71°C/ Lit. 68–70°C [5]; H NMR (400 MHz, CDCl3): 7.23 (s, 1H, H4),
7.36 (s, 1H, CHBr2); 13C NMR (100 MHz, CDCl3): δ 165.9 (C3), 104.3 (C4), 170.4 (C5), 84.6
(CCl3), 27.0 (CHBr2); MS (70 eV) m/z 359 (M+, >5), 289 (75), 242 (30), 175 (56), 117 (100),
68 (72); Anal. Calcd. for C5H2Br2Cl3NO: C, 16.76; H, 0.56; N, 3.91; found C, 16.8; H, 0.6; N,
4.0.

7
Figure S1: 1H NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-propyl-4,5-dihydroisoxazole (2d), CDCl3.

8
Figure S2: 1H NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-propyl-4,5-dihydroisoxazole (2d), CDCl3.

9
Figure S3: 13C NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-propyl-4,5-dihydroisoxazole (2d), CDCl3.

10
Figure S4: 1H NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-cyclopropyl-4,5-dihydroisoxazole (2f), CDCl3.

11
Figure S5: 1H NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-cyclopropyl-4,5-dihydroisoxazole (2f), CDCl3.

12
Figure S6: 13C NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-cyclopropyl-4,5-dihydroisoxazole (2f), CDCl3.

13
Figure S7: DEPT 135 13C NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-cyclopropyl-4,5-dihydroisoxazole (2f), CDCl3.

14
Figure S8: DEPT 135 13C NMR spectrum of the 3-bromomethyl-5-trichloromethyl-5-hydroxy-4,5-dihydroisoxazole (2i), CDCl3.

15
Figure S9: 13C[H] NMR spectrum of the 3-bromomethyl-5-trichloromethyl-5-hydroxy-4,5-dihydroisoxazole (2i), CDCl3.

16
Figure S10: 1H NMR spectrum of the 5-trichloromethyl-3,4-hexamethylene-5-hydroxy-4,5-dihydroisoxazole (2o), CDCl3.

17
Figure S11: 1H NMR spectrum of the 5-trichloromethyl-3,4-hexamethylene-5-hydroxy-4,5-dihydroisoxazole (2o), CDCl3.

18
Figure S12: 13C[H] NMR spectrum of the 5-trichloromethyl-3,4-hexamethylene-5-hydroxy-4,5-dihydroisoxazole (2o), CDCl3.

19
Cl3C
HO
N
O
Figure S13: 1H NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-(2-phenylethyl)-4,5-dihydroisoxazole (2k), CDCl3.

20
CH2
Ph
3
4
CH2Ph
Cl3C
HO
4
N
O
4
5
Figure S14: 1H NMR spectrum of 2k in CDCl3, expanded between 2.5–7.6 ppm.

21
3
4
Cl3C
HO
N
O
5
Ph
CH
2 CH2
4
5
3
Cl3C
Figure S15: 13C NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-(2-phenylethyl)-4,5-dihydroisoxazole (2k), CDCl3.

22
MeS
Cl3C
HO
N
O
Figure S16: 1H NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-(1-thiomethylethyl)-4,5-dihydroisoxazole (2l), CDCl3.

23
SMe
MeS
6
Me
4
5
3
Cl3C
HO
N
O
1
4
CH
HO
CH
4
Figure S17: 13C NMR spectrum of 2h in CDCl3, expanded between 1.2–4.2 ppm.

24
4
SMe Me
MeS
CH
6
4
5
3
Cl3C
HO
N
O
1
5
3
Cl3C
Figure S18: 13C NMR spectrum of the 5-trichloromethyl-5-hydroxy-3-(1-thiomethylethyl)-4,5-dihydroisoxazole (2l), CDCl3.

25
MeS
6
4
5
3
4
CH
SMe
Cl3C
HO
Me
N
O
1
Figure S19: 13C NMR spectrum of 2l in CDCl3, expanded between 0–55 ppm.

26
3
MeS
6
4
5
3
Cl3C
HO
N
O
1
5
Cl3C
Figure S20: 13C NMR spectrum of 2l in CDCl3, expanded between 95–164 ppm.

27
Table S1. Crystal data and structure refinement 2d.
Identification code
Empirical formula
Formula weight
Temperature
2d
C7 H10 Cl3 N O2
246.51
293(2) K
Wavelength
0.71073 Å
Crystal system
Space group
Monoclinic
P21/c
Unit cell dimensions
a = 10.304(2) Å α=90.000°
b = 5.7322(1) Å β= 104.346(1)°
c = 18.2694(3) Å γ= 90.000°
1045.44(3) Å3
Volume
Z
4
Density (calculated)
Absorption coefficient
F(000)
1.566 mg/m3
0.844 mm-1
504
Crystal size
0.12 × 0.26 × 0.28 mm3
3.43 to 27.87°.
Theta range for data collection
Index ranges
-13≤ h ≤13, -7 ≤ k ≤7, -22 ≤ l ≤23
12664
Reflections collected
Independent reflections
Completeness to theta = 27.86°
Refinement method
Computing
2363 [R(int) = 0.0630]
98.8%
Full-matrix least-squares on F2
COLLECT[6], HKL Denzo and Scalepack
[7], SHELXS-97[8], SHELXL-97[8]
0.8493 and 0.8493
Full-matrix least-squares on F2
2363 / 0 / 118
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
1.085
Final R indices [I>2sigma(I)]
R1 = 0.0442, wR2 = 0.1080

28
Table S2. Atomic coordinates (x104) and equivalent isotropic displacement parameters
(Å2x103). U(eq) is defined as one-third of the trace of the orthogonalized Uij tensor 2d.
Atom
Cl1
Cl2
Cl3
O1
O2
N1
C1
x
y
z
U(eq)
0.04414(5)
0.09915(5)
0.18575(6)
0.38606(3)
0.34366(3)
0.43514(5)
0.16277(7)
0.29751(6)
0.38492(7)
0.29040(18)
0.4218(2)
0.3015(3)
0.2258(3)
0.20679(0)
-0.14027(0)
-0.21529(0)
-0.0626(3)
0.2081(3)
-0.0040(3)
-0.0020(3)
0.1203(3)
0.1880(3)
0.2928(3)
0.2948(5)
0.3419(5)
0.1275(7)
0.11113(3)
0.22805(3)
0.09190(3)
0.23161(7)
0.13461(7)
0.30946(9)
0.15721(0)
0.19352(9)
0.32348(0)
0.25629(0)
0.40034(1)
0.43243(3)
0.44338(6)
0.0494(2)
0.0471(2)
0.0523(2)
0.0390(4)
0.0381(4)
0.0382(5)
0.0323(5)
0.0290(5)
0.0333(5)
0.0316(5)
0.0488(7)
0.0580(9)
0.0854(3)
C2
C3
C4
C5
C6
C7
Table S3. Bond lengths (Å) for 2d.
Atom 1
Cl1
C5
Atom 2
C1
Bond (Å)
1.7673(8)
1.521(4)
1.7774(9)
1.495(5)
1.7644(8)
0.9700
C6
Cl2
C6
C1
C7
Cl3
C4
C1
H4A
N1
O1
1.427(2)
0.9700
C4
H4B
C2
O1
1.450(2)
0.9700
C5
H5A
C2
O2
1.375(2)

29
C5
O2
C6
N1
C6
C1
C7
C2
C7
C3
C7
C3
H5B
H2O2
H6A
C3
0.9700
0.8500
0.9700
1.268(2)
0.9700
H6B
C2
1.550(2)
0.9600
H7A
C4
1.528(2)
0.9600
H7B
C4
1.491(3)
0.9600
H7C
C5
1.492(3)
Table S4. Bond angles [°] for 2d.
Atom 1
N1
Atom 2
Atom 3
C2
Angle (°)
O1
C4
O2
C4
N1
C4
C1
C4
C1
C4
C1
C5
C1
C5
C1
C5
109.50(14)
111.00
C2
H4A
H2O2
H4B
C3
C2
105.00
C2
111.00
O1
110.14(5)
111.00
C3
H4A
Cl3
Cl1
C3
110.05(0)
111.00
H4B
C2
Cl1
H4A
Cl1
C3
109.85(2)
109.00
H4B
Cl2
108.31(0)
109.00
H5A
C2
Cl2
C3
110.05(2)
109.00
H5B
C2
Cl3
C6
110.40(2)
109.00
H5A

30
Cl2
C6
C1
C5
C2
C5
C2
C6
C2
C6
C2
C6
C2
C6
C2
C6
C3
C7
C3
C7
C3
C7
C4
C7
C5
C7
C6
C7
Cl3
H5B
O2
108.64(9)
109.00
O1
110.09(4)
108.00
H5A
O1
H5B
C1
105.71(4)
109.00
C5
H6A
C1
O2
106.14(3)
109.00
C5
H6B
C4
O2
116.16(5)
109.00
C7
H6A
C4
O1
104.54(3)
109.00
C7
H6B
C4
C1
114.34(4)
108.00
H6A
N1
H6B
C5
121.63(8)
110.00
C6
H7A
C5
C4
124.98(7)
109.00
C6
H7B
C4
N1
113.68(6)
109.00
C6
H7C
C3
C2
102.45(4)
109.00
H7A
C3
H7B
C6
113.25(8)
109.00
H7A
C5
H7C
C7
114.1(2)
109.00
H7B
H7C