V. Alcolea et al. / European Journal of Medicinal Chemistry 123 (2016) 407e418
415
4.1.14. 4-Chloropyrimidin-2-yl thiocyanate (2e)
vacuum by rotatory evaporation. The residue was washed with
water and recrystallized from isopropanol. A green powder was
obtained. Yield: 7%; mp: 169e171 ꢀC. 1H NMR (400 MHz, DMSO-
From 2,4-dichloropyrimidine. Conditions: 24 h at reflux in
acetone. The product was isolated by extraction with dichloro-
methane (50 mL ꢃ 2) after pouring the reaction into water (25 mL)
and was recrystallized from isopropanol. A yellow powder was
obtained. Yield: 6%; mp: 118e119 ꢀC. 1H NMR (400 MHz, DMSO-d6):
d6):
NMR (100 MHz, DMSO-d6):
d C
4.88 (s, 2H, eCH2e), 7.86e7.88 ppm (m, 4H, H of phenyl). 13
d
44.6 (eCH2e), 124.3 (C4 þ C7), 132.2
(C3a þ C7a), 135.7 (C5 þ C6), 167.6 ppm (C1 þ C3). IR (KBr):
n
d
7.93 (d, 1H, J ¼ 5.4 Hz, H5), 8.77 ppm (d, 1H, J ¼ 5.4 Hz, H6). 13
C
1772 þ 1718 cmꢁ1 (s; C]O). MS [m/z (% abundance)]: 160 (100), 133
(18), 104 (24), 76 (36), 50 (17). Elemental Analysis calculated (%) for
C9H7NO2S: C: 55.94, H: 3.65, N: 7.25; found: C: 55.79, H: 3.57, N:
7.26.
NMR (100 MHz, DMSO-d6):
d 108.0 (eSCN), 119.8 (C5), 122.2 (C6),
161.6 (C2),164.5 ppm (C4). IR (KBr): n
2167 (w; C^N),1542 cmꢁ1 (s;
C]N). MS [m/z (% abundance)]: 173 (28), 171 (100; Mþꢂ) 136 (10),
113 (100). Elemental Analysis calculated (%) for C5H2N3ClS: C:
35.00, H: 1.16, N: 24.50; found: C: 35.50, H: 1.34, N: 24.71.
4.1.19. 2-(Selanylmethyl)-1H-isoindole-1,3(2H)-dione (4b)
From 4f. Conditions: 2 h at r.t. in dry THF with LiAlH4 and
20 min at 0 ꢀC with succinic acid. The product was extracted with
dichloromethane and recrystallized from ethanol. A green powder
was obtained. Yield: 4%; mp: 151e152 ꢀC. 1H NMR (400 MHz,
4.1.15. Quinoline-2-thiol (3a)
From 2-chloroquinoline. Conditions: 4 h at reflux in ethanol
absolute. Solvent was removed under vacuum by rotatory evapo-
ration. Purified by column chromatography on silica gel using
toluene/dioxane (6:4; v:v) as mobile phase. A yellow powder was
obtained. Yield: 11%; mp: 174e176 ꢀC. 1H NMR (400 MHz, DMSO-
DMSO-d6):
phenil). 13C NMR (100 MHz, DMSO-d6):
(C4 þ C7), 132.0 (C3a þ C7a), 132.2 (C5 þ C6), 168.2 ppm (C1 þ C3).
d
5.06 (s, 2H, eCH2e), 7.85e7.86 ppm (m, 4H, H of
d
42.3 (eCH2e), 123.7
d6):
(m, 2H, H6 þ H7), 7.78 (d, 1H, J ¼ 7.8 Hz, H5), 7.84 (d, 1H, J ¼ 9.1 Hz,
H4), 13.70 ppm (s, 1H, SH). 13C NMR (100 MHz, DMSO-d6):
117.0
(C3), 123.1 (C4a), 125.0 (C6), 128.8 (C5), 132.1 (C8), 132.3 (C7), 135.7
d
7.26 (dd, 1H, J ¼ 1.7, 9.1 Hz, H3), 7.32e7.36 (m, 1H, H8), 7.60
IR (KBr):
n
3366 (w; SeeH), 3058 (w; CeHarom),
1772 þ 1715 cmꢁ1 (s; C]O). MS [m/z (% abundance)]: 160 (100), 133
(15), 104 (19), 76 (26). Elemental Analysis calculated (%) for
C9H7NO2Se: C: 45.02, H: 2.94, N: 5.83; found: C: 44.95, H: 3.03, N:
5.82.
d
(C4), 140.0 (C8a), 182.1 ppm (C2). IR (KBr):
n 3008 (w; CeHarom),
1620 cmꢁ1 (s; C]N). MS [m/z (% abundance)]: 161 (100; Mþꢂ), 128
(75), 117 (22). Elemental Analysis calculated (%) for C9H7NS: C:
67.05, H: 4.38, N: 8.69; found: C: 67.05, H: 4.67, N: 8.73.
4.1.20. (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl
thiocyanate (4e)
From
2-(bromomethyl)isoindoline-1,3-dione.
Conditions:
4.1.16. 2-(Methylsulfanyl)quinoline (3c)
2.5 h at reflux in acetone. The reaction mixture was poured into
water (50 mL) and the precipitate was filtered and washed with
water and ether (25 mL of each). A white powder was obtained.
From 3a. Conditions: 4 h at r.t. in DMSO. Recrystallized from
hexane. A white powder was obtained. Yield: 18%; mp: 54e55 ꢀC.
1H NMR (400 MHz, CDCl3):
d
2.75 (s, 3H, eCH3), 7.27 (d, 1H,
Yield: 54%; mp: 133e134 ꢀC. 1H NMR (400 MHz, DMSO-d6):
d 5.32
J ¼ 8.7 Hz, H3), 7.46 (t, 1H, J ¼ 7.5 Hz, H6), 7.68 (t, 1H, J ¼ 7.7 Hz, H7),
(s, 2H, eCH2e), 7.91e7.93 (m, 2H, H4 þ H7), 7.98e8.00 ppm (m, 2H,
7.75 (dd,1H, J ¼ 1.1, 8.1 Hz, H8), 7.93 (d,1H, J ¼ 8.7 Hz, H4), 8.03 ppm
H5 þ H6). 13C NMR (100 MHz, DMSO-d6):
d 47.7 (eCH2e), 112.6
(d, 1H, J ¼ 8.4 Hz, H5). 13C NMR (100 MHz, DMSO-d6):
d
13.24
(eSCN), 124.6 (C4 þ C7), 132.1 (C3a þ C7a), 136.2 (C5 þ C6),
(eCH3), 121.4 (C3), 126.2 (C6), 126.5 (C4a), 128.2 (C5), 128.9 (C8),
166.9 ppm (C1 þ C3). IR (KBr):
n 3012 (m; CeHarom), 2158 (m;
130.8 (C7), 136.7 (C4), 148.5 (C8a), 160.3 ppm (C2). IR (KBr):
n
3052
C^N), 1720 cmꢁ1 (s; C]O). MS [m/z (% abundance)]: 191 (2), 160
(w; CeHarom), 2923 (w; CeHaliph), 1612 cmꢁ1 (s; C]N). MS [m/z (%
abundance)]: 175(37; Mþꢂ), 147(86), 129(83), 104(74), 76(100),
50(45). Elemental Analysis calculated (%) for C10H9NS: C: 68.53, H:
5.18, N: 7.99; found: C: 68.49, H: 5.46, N: 8.01.
(100), 133 (21), 58 (7). Elemental Analysis calculated (%) for
C10H6N2O2S: C: 55.04, H: 2.77, N: 12.84; found: C: 54.45, H: 2.64, N:
12.65.
4.1.21. (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl
selenocyanate (4f)
4.1.17. 2-(Methylselanyl)quinoline (3d)
From 2-chloroquinoline. Conditions: 1.1 mmol of NaBH4 solved
in absolute ethanol were added to a solution of 0.5 mmol of
dimethyldiselenide in absolute ethanol (15 mL) under N2 atmo-
sphere. After 30 min stirring in dark at r.t., 1 mmol of 2-
chloroquinoline was added. The mixture was stirred at reflux for
5 h and then poured into water. The product was extracted with
water and purified by flash chromatography eluting with hexane/
acetate (95:5; v:v). Colorless oil was obtained. Yield: 7%. 1H NMR
Full description of this compound can be found in a previous
work [52] (compound 1o).
4.1.22. (6-Bromobenzo[d] [1,3]dioxol-5-yl)methanethiol (5a)
From 5-bromo-6-(bromomethyl)benzo[d] [1,3]dioxole. Condi-
tions: 1.7 mmol of 5-bromo-6-(bromomethyl)benzo[d] [1,3]dioxole
were added to a solution of 1.7 mmol of KSAc in dry N,N-dime-
thylformamide (10 mL). The mixture was stirred in dark at r.t. for
16 h. Then, 25 mL of water were added and a white precipitate
appeared. The precipitate was solved in 10 mL of methanol and
mixed with 10 mL of aqueous solution of NaOH 3 M. After 4 h at r.t.,
the precipitate was filtered and recrystallized from a mixture of
ethanol/dichloromethane (3:1; v:v). Crystals were solved in
dichloromethane and after filtering the solvent was removed under
vacuum by rotatory evaporation. A white powder was obtained.
(400 MHz, DMSO-d6):
d
2.65 (s, 3H, eCH3), 7.38 (d, 1H, J ¼ 8.6 Hz,
H3), 7.49 (t,1H, J ¼ 7.4 Hz, H6), 7.69 (t,1H, J ¼ 7.7 Hz, H7), 7.76 (d,1H,
J ¼ 7.2 Hz, H8), 7.90 (d, 1H, J ¼ 8.5 Hz, H4), 8.05 ppm (d, 1H,
J ¼ 7.3 Hz, H5). 13C NMR (100 MHz, DMSO-d6):
d 10.4 (eCH3), 121.0
(C3), 127.0 (C6), 127.5 (C4a), 128.3 (C5), 128.9 (C8), 129.9 (C7), 136.4
(C4), 146.7 (C8a), 156.3 ppm (C2). IR (NaCl):
n 3056 (m; CeHarom),
2927 (m; CeHaliph), 1613 cmꢁ1 (s; C]N). MS [m/z (% abundance)]:
223(30), 143(100), 128(36), 101(26). Elemental Analysis calculated
(%) for C10H9NSe: C: 54.07, H: 4.08, N: 6.31; found: C: 54.39, H: 4.42,
N: 6.32.
Yield: 5%; mp: 146e147 ꢀC. 1H NMR (400 MHz, DMSO-d6):
1H, SH), 3.84 (s, 2H, eCH2eS), 6.06 (s, 2H, OeCH2eO), 6.94 (s, 1H,
H4), 7.21 ppm (s, 1H, H7). 13C NMR (100 MHz, DMSO-d6):
36.0
(eCH2eSe), 102.9 (C2), 111.4 (C4), 112.9 (C6), 113.4 (C7), 131.0 (C5),
d 3.66 (s,
d
4.1.18. 2-(Sulfanylmethyl)-1H-isoindole-1,3(2H)-dione (4a)
From 4e. Conditions: 3 h at r.t. in dry THF with LiAlH4 and
30 min at r.t. with succinic acid. Solvent was removed under
148.0 (C7a), 148.3 ppm (C3a). IR (KBr): n 3437 (w; SeH), 2911 (m;
CeHaliph), 1684 cmꢁ1 (s; C]C). MS [m/z (% abundance)]: 247 (4;
Mþꢂ), 230 (11), 213 (100), 166(21), 75(12). Elemental Analysis