7
34
H. K. GEN C¸ ER ET AL.
0
.61 mL) in ethyl acetate (20 mL) was added dropwise. After com- d ¼ 7.31 (2H, d, J ¼ 8.2 Hz, 1,4-disubs. benzene –CH–), 7.19 (2 H, d,
pletion of dropping the reaction mixture was stirred at room tem- J ¼ 8.1 Hz, 1,4-disubs. benzene –CH–), 4.45 (2 H, s, –CH –), 3.77
perature for 2 h. The solvent was evaporated and precipitated (3 H, s, –CH
2
), 3.61 (1 H, q, J ¼ 7.1 Hz, –CH–), 1.28 (3 H, d, J ¼ 7.1 Hz,
3
1
3
product was washed with water, dried and then recrystallized –CH
3
.
C-NMR (75 MHz, DMSO-d
6
): d ¼ 175.7, 153.6, 141.2, 135.4,
þ
from ethanol to afford 2-(4-(bromomethyl)phenyl) propionic acid 129.5, 128.0, 44.8, 34.0 and 18.8. HRMS (m/z): [M þ H] calcd for
4
5
(
5). Yield; 79% .
C
12
H
14
4
N O
2
S: 279.0910; found 279.0912.
2
.1.6.6.
2-(4-((Benzo[d]thiazol-2-ylthio)methyl)phenyl)propanoic
2
.1.6. General procedure for the synthesis of 2-(4-substitutedme-
thylphenyl)propionic acid (6a–6n)
-(4-Bromo-methylphenyl) propionic acid (0.001 mol, 0.243 g) and
ꢂ1
ꢁ
acid (6f). Yield: 80%, M.P.¼128.2–130.8 C. FTIR (ATR, cm ): 3120
1
(
O–H), 1734 (C¼O), 1067, 854, 742. H-NMR (300 MHz, DMSO-d
6
):
2
d ¼ 13.87 (1 H, s, –COOH), 7.62–7.67 (2 H, m, BT –CH–), 7.45 (2 H, d,
appropriate (benz)azolylthiol derivative (0.001 mol) were dissolved
in acetone. The solution was refluxed at 40 C for 12 h. Acetone
was evaporated, residue was washed with water, filtered, dried
and recrystallized from ethanol to obtain final products (6a–6n) .
J ¼ 8.1 Hz, 1,4-disubs. benzene –CH–), 7.34–7.32 (2 H, m, BT –CH–),
ꢁ
7
.25 (2 H, d, J ¼ 8.1 Hz, 1,4-disubs. benzene –CH–), 4.67 (2 H, s,
–
CH
2
–), 3.67 (1 H, q, J ¼ 7.4 Hz, –CH–),1.34 (3 H, d, J ¼ 7.4 Hz, –CH
3
).
4
6
13
C-NMR (75 MHz, DMSO-d ): d ¼ 175.7, 164.3, 151.7, 141.2, 135.5,
6
131.2, 129.9, 129.6, 128.1, 125.1, 118.8, 110.7, 44.8, 35.7 and 18.9.
þ
2
.1.6.1. 2-(4-(((4,5-Dihydrothiazol-2-yl)thio)methyl)phenyl)propanoic
HRMS (m/z): [M þ H] calcd for C17
3
H15NO S: 330.0617; found
ꢁ
ꢂ1
acid (6a). Yield: 77%, M.P.¼154.2–156.3 C, FTIR (ATR, cm ): 3410 330.0617.
1
(
O–H), 1701 (C¼O), 1047, 845, 777. H-NMR (300 MHz, DMSO-d
6
):
d ¼ 7.36 (2 H, d, J ¼ 8.2 Hz, 1,4-disubs. benzene–CH–), 7.25 (2 H, d,
2.1.6.7. 2-(4-(((5-Chlorobenzo[d]thiazol-2-yl)thio)methyl)phenyl)pro-
J ¼ 8.2 Hz, 1,4-disubs. benzene–CH–), 4.46 (2 H, s, –CH –), 4.21 (1 H,
ꢁ
2
panoic acid (6g). Yield: 85%, M.P.¼162.3–164.7 C, FTIR (ATR,
t, J ¼ 8.2 Hz, –CH
2
), 3.64 (1 H, q, J ¼ 7.1 Hz, –CH–), 3.59 (1 H, t,
ꢂ1
1
cm ): 3030 (O–H), 1715 (C¼O), 1063, 860, 799. H-NMR (500 MHz,
1
3
J ¼ 8.2 Hz, –CH
2
–), 1.33 (3 H, d, J ¼ 7.1 Hz, –CH
3
). C-NMR (75 MHz,
DMSO-d ): d ¼ 8.06 (1 H, d, J ¼ 8.6 Hz, benzothiazole –CH–), 7.98
6
DMSO-d
6
): d ¼ 175.7, 156.1, 141.3, 134.9, 129.6, 128.2, 60.4, 44.8,
(
1 H, d, J ¼ 2.0 Hz, benzothiazole –CH–), 7.47 (2 H, d, J ¼ 8.2 Hz, 1,4-
þ
3
2
7.2, 35.1 and 18.9. HRMS (m/z): [M þ H] calcd for C H NO S :
1
3
15
2 2
disubs. benzene –CH–), 7.43 (1 H, dd, J ¼ 8.6–2.0 Hz, benzothiazole
CH–), 7.27 (2 H, d, J ¼ 8.2 Hz, 1,4-disubs. benzene –CH–), 4.64 (2 H,
s, –CH
82.0617; found 282.0603.
–
2
1
–), 3.67 (1 H, q, J ¼ 7.2 Hz, –CH–), 1.35 (3 H, d, J ¼ 7.2 Hz,
3
2
.1.6.2. 2-(4-(((1-Methyl-1H-imidazol-2-yl)thio)methyl)phenyl)propa- –CH3). C-NMR (125 MHz, DMSO-d ): d ¼ 175.7, 169.5, 154.0, 141.2,
6
ꢂ1
noic acid (6b). Yield: 76%, M.P.¼liquid, FTIR (ATR, cm ): 3391 135.3, 133.9, 131.7, 129.7, 128.2, 125.0, 123.7, 121.1, 44.8, 36.8 and
1
þ
(O–H), 1717 (C¼O), 1038, 860, 698. H-NMR (300 MHz, DMSO-d
6
): 18.9. HRMS (m/z): [M þ H] calcd for C H NO S Cl: 364.0227;
1
7
14
2 2
d ¼ 7.82 (1 H, d, J ¼ 2.0 Hz, imidazole –CH–), 7.78 (1 H, d, J ¼ 2.0 Hz, found 364.0218.
imidazole –CH–), 7.19 (2 H, d, J ¼ 8.3 Hz, 1,4-disubs. benzene –CH–),
7
.14 (2 H, d, J ¼ 8.3 Hz, 1,4-disubs. benzene –CH–), 4.41 (2 H, s,
2.1.6.8. 2-(4-(((5-Methoxybenzo[d]thiazol-2-yl)thio)methyl)phenyl)-
–CH
2
–), 3.64 (1 H, q, J ¼ 7.1 Hz, –CH–), 3.54 (3 H, s, –CH
3
), 1.34 (3 H,
ꢁ
propanoic acid (6 h). Yield: 77%, M.P.¼166.5–168.2 C, FTIR (ATR,
1
3
d, J ¼ 7.1 Hz, –CH ). C-NMR (75 MHz, DMSO-d ): d ¼ 175.6, 141.6,
ꢂ1
1
3
6
cm ): 3071 (O–H), 1724 (C¼O), 1082, 835, 694. H-NMR (500 MHz,
1
(
39.2, 135.1, 129.3, 128.2, 125.9, 121.6, 44.8, 35.3 and 18.9. HRMS
DMSO-d ): d ¼ 7.87 (1 H, d, J ¼ 8.8 Hz, benzothiazole –CH–),
6
m/z): [M þ H]þ calcd for C14
16 2 2
H N O S: 277.1005; found 277.1000.
7
7
.46–7.45 (3 H, m, 1,4-disubs. benzene –CH–, benzothiazole –CH–),
.27 (2 H, d, J ¼ 8.1 Hz, 1,4-disubs. benzene –CH–), 7.01 (1 H, dd,
2
.1.6.3. 2-(4-(((1H-1,2,4-Triazol-3-yl)thio)methyl)phenyl)propanoic J ¼ 8.0–2.5 Hz, benzothiazole –CH–), 4.62 (2 H, s, –CH –), 3.84 (3 H,
2
ꢂ1
acid (6c). Yield: 85%, M.P.¼liquid, FTIR (ATR, cm ): 3393 (O–H), s, –OCH ), 3.67 (1 H, q, J ¼ 7.1 Hz, –CH–), 1.35 (3 H, d, J ¼ 7.1 Hz,
3
1
13
1
717 (C¼O), 1022, 858. H-NMR (300 MHz, DMSO-d
6
): d ¼ 9.02 (1 H, –CH ). C-NMR (125 MHz, DMSO-d ): d ¼ 175.6, 158.0, 148.5, 141.6,
3
6
d, J ¼ 8.2 Hz, triazole –CH–), 7.18 (2 H, d, J ¼ 8.2 Hz, 1,4-disubs. ben- 134.6, 134.5, 129.5, 128.4, 128.0, 115.1, 114.7, 96.6, 56.4, 44.8, 37.0
þ
zene –CH–), 7.15 (2 H, d, J ¼ 8.3 Hz, 1,4-disubs. benzene –CH–), 4.41 and 18.9. HRMS (m/z): [M þ H] calcd for C H NO S : 360.0723;
1
8
17
3 2
(2 H, s, –CH
2
), 3.64 (1 H, q, J ¼ 7.1 Hz, –CH–), 1.29 (3 H, d, J ¼ 7.1 Hz, found 360.0724.
1
3
–CH
3
). C-NMR (75 MHz, DMSO-d
6
): d ¼ 175.7, 153.6, 141.2, 135.4,
þ
1
C
29.5, 127.7, 44.8, 35.5 and 19.0. HRMS (m/z): [M þ H] calcd for
2.1.6.9. 2-(4-(((1H-benzo[d]imidazol-2-yl)thio)methyl)phenyl)propa-
H
12 13
N
3
O
2
S: 264.0801; found 264.0789.
ꢁ
ꢂ1
noic acid (6i). Yield: 78%, M.P.¼208.7–210.9 C, FTIR (ATR, cm ):
1
3
142 (O–H), 1699 (C¼O), 1072, 851, 735. H-NMR (500 MHz, DMSO-
2
.1.6.4. 2-(4-(((4-Methyl-4 H-1,2,4-triazol-3-yl)thio)methyl)phenyl)- d ): d ¼ 7.69–7.66 (2 H, m, benzimidazole –CH–), 7.44–7.41 (4 H, m,
6
ꢂ1
propanoic acid (6d). Yield: 81%, M.P.¼liquid, FTIR (ATR, cm ): 1,4-disubs. benzene –CH–, benzimidazole –CH–), 7.27 (2 H, d,
1
3
d
420 (O–H), 1721 (C¼O), 1024, 822, 760. H-NMR (300 MHz, DMSO- J ¼ 8.0 Hz, 1,4-disubs. benzene –CH–), 4.72 (2 H, s, –CH –), 3.66
2
1
3
6
): d ¼ 8.28 (1 H, s, triazole –CH–), 7.19 (2 H, d, J ¼ 8.3 Hz, 1,4-dis- (1 H, q, J ¼ 7.1 Hz, –CH–). C-NMR (125 MHz, DMSO-d ): d ¼ 175.6,
6
ubs. benzene –CH–), 7.14 (2 H, d, J ¼ 8.3 Hz, 1,4-disubs. benzene 150.2, 141.6, 134.7, 134.6, 129.5, 128.4, 125.0, 113.9, 44.8, 35.2 and
þ
–CH–), 4.41 (2 H, s, –CH
2
–), 3.64 (1 H, q, J ¼ 7.1 Hz, –CH–), 3.55 (3 H, 18.9. HRMS (m/z): [M þ H] calcd for C H N O S: 313.1005; found
1
7 16 2 2
1
3
s, –CH
d
3
), 1.29 (3 H, d, J ¼ 7.1 Hz, –CH
3
). C-NMR (75 MHz, DMSO- 313.1009.
6
): d ¼ 175.6, 156.8, 143.2, 140.7, 136.8, 130.0, 127.6, 44.7, 35.3,
þ
2
2
7.03 and 18.9. HRMS (m/z): [M þ H] calcd for C H N O S:
1
3
15
3
2
2.1.6.10.
2-(4-(((5-Methyl-1H-benzo[d]imidazol-2-yl)thio)methyl)-
78.0958; found 278.0952.
ꢁ
1
phenyl)propanoic acid (6j). Yield: 80%, M.P.¼209.1–211.6 C, FTIR
ꢂ1
(
ATR, cm ): 3051 (O–H), 1701 (C¼O), 1070, 856, 799. H-NMR
2
.1.6.5. 2-(4-(((1-Methyl-1 H-tetrazol-5-yl)thio)methyl)phenyl)propa- (500 MHz, DMSO-d ): d ¼ 7.58 (1 H, d, J ¼ 8.4 Hz, benzimidazole
6
ꢂ1
noic acid (6e). Yield: 82%, M.P.¼liquid, FTIR (ATR, cm ): 3374 –CH–), 7.49 (1 H, s, benzimidazole –CH–), 7.40 (2 H, d, J ¼ 7.9 Hz,
1
(O–H), 1717 (C¼O), 1038, 860, 698. H-NMR (300 MHz, DMSO-d
6
): 1,4-disubs. benzene –CH–), 7.30–7.26 (3 H, m, 1,4-disubs. benzene