Jul-Aug 2001
931
Efficient One-Pot Synthesis of Chiral S-Triazole Derivatives
(s, 1H, NH), 7.75-6.97 (m, 5H, PhH), 5.43 (s, 2H, OCH ), 3.34
(s, 1H, SH); ms: (EI) m/z 207 (M , 15.82), 133 (5.28), 131
Anal. Calcd. for C H N OS: C, 60.68; H, 4.31; N, 16.33.
13 11 3
Found: C, 60.59; H, 4.28; N, 16.26.
2
+
(6.67), 114 (25.36), 94 (100), 77 (38.51).
2-α−Naphthyloxymethyl-5-mercapto-1,2,4-triazole (6g).
Anal. Calcd. for C H N OS: C, 52.15; H, 4.38; N, 20.28.
9
9 3
Found: C, 52.26; H, 4.47; N, 20.11.
Compound 6g was obtained as a cream-colored powder in
80.8% yield; mp >220 °C; ir (potassium bromide): ν 3432 (NH),
2-(2-Methyloxyphenyl)oxymethyl-5-mercapto-1,2,4-triazole (6b).
3055 (=C-H), 2912 (CH ), 2550 (SH), 1744, 1587 (C=C, C=N),
2
Compound 6b was obtained as a pale yellow powder in 83.2%
yield; mp 220-222 °C; ir (potassium bromide): ν 3430 (NH), 3028
1
1212, 1080 (C-O-C); H nmr (400 MHz; DMSO-d ): δ 8.15
6
(s, 1H, NH), 7.70-6.73 (m, 7H, α−C H -), 5.47 (s, 2H, OCH ),
10
7
2
(=C-H), 2920 (CH ), 2550 (SH), 1740-1493 (C=C, C=N), 1241,
+
3
4.14 (s, 1H, SH); ms: (EI) m/z 257 (M , 9.25), 144 (100), 127
(18.52), 115 (58.13), 114 (20.38).
-1 1
1150 (C-O-C) cm ; H nmr (400 MHz; DMSO-d ): δ 8.08 (s, 1H,
6
NH), 7.03-6.65 (m, 4H, ArH), 5.22 (s, 2H, OCH ), 2.68 (s, 1H, SH),
2
Anal. Calcd. for C H N OS: C, 60.68; H, 4.31; N, 16.33.
13 11
3
+
2.16 (s, 3H, CH ); ms: (EI) m/z 221 (M , 21.47), 207 (1.61), 147
3
Found: C, 60.61; H, 4.29; N, 16.27.
(5.68), 133 (3.73), 114 (100), 108 (54.28), 91 (11.88), 76 (38.75).
General procedure for Preparing (S)-3-α-phenylethyl-2,4-dihydro-
5-aryloxymethyl-1,2,4-triazolo[3,4-b]-1,3,5-thiadiazines (7a-g).
Anal. Calcd. for C H N OS: C, 54.28; H, 5.01; N, 18.99.
10 11
3
Found: C, 54.36; H, 5.05; N, 18.88.
To a solution of absolute ethanol (5 mL), polyformaldehyde
(6 mmol) and S-(-)-α-phenylethylamine (3 mmol), was added (6)
(3 mmol). The mixture was acidified with hydrochloric acid to
pH 4-5, followed by addition of potassium fluoride (0.1 g). After
the mixture was stirred at 30 °C for 30 minutes, the solution was
heated up to 55 °C for 6-8 hours, and then left to stand overnight.
The solvent was then removed by distillation to leave a solid that
was washed with water and 8% sodium hydroxide, then washed
again with water to neutrality. The solid was recrystallized from
absolute ethanol and purified by column chromatography to
obtain the products 7.
2-(3-Methylphenyl)oxymethyl-5-mercapto-1,2,4-triazole (6c).
Compound 6c was obtained as a pale yellow needle crystals in
85.3% yield; mp 208-210 ºC; ir (potassium bromide): ν 3426
(NH), 3037 (=C-H), 2985 (CH ), 2553 (SH), 1604, 1450 (C=C,
3
-1 1
C=N), 1245, 1042 (C-O-C) cm ; H nmr (400 MHz; DMSO-d ):
6
δ 8.01 (s, 1H, NH), 7.21-6.80 (m, 4H, ArH), 5.26 (s, 2H, OCH ),
2
+
2.69 (s, 1H, SH); 2.10 (s, 3H, CH ); ms: (EI) m/z 221 (M ,
3
26.15), 207 (3.52), 147 (6.88), 133 (5.62), 114 (100), 108 (58.38),
91 (15.23), 76 (35.21).
Anal. Calcd. for C H N OS: C, 54.28; H, 5.01; N, 18.99.
10 11
3
Found: C, 54.22; H, 5.03; N, 18.91.
(S)-3-α-Phenylethyl-2,4-dihydro-5-phenyloxymethyl-1,2,4-tria-
zolo[3,4-b]-1,3,5-thiadiazine (7a).
2-(4-Methylphenyl)oxymethyl-5-mercapto-1,2,4-triazole (6d).
Compound 6d was obtained as a pale yellow powder in 86.5%
yield; mp 205-207 °C; ir (potassium bromide): ν 3384 (NH),
This compound was prepared as a pale yellow powder in
20
-4
75.6% yield, mp 80-82 °C; [α]
-166.6° (c = 1.2 x 10 ,
D
3031 (=C-H), 2921 (CH ), 2550 (SH), 1617, 1514 (C=C, C=N),
3
DMSO); ir (potassium bromide): ν 3029 (=C-H), 2980 (CH -H),
-1 1
2
1236, 1063 (C-O-C) cm ; H nmr (400 MHz; DMSO-d ): δ 8.01
6
1676 (C=N), 1591 (N=C-S), 1275, 1029 (C-O-C) and 688
(s, 1H, NH), 7.01-6.90 (m, 4H, ArH), 5.15 (s, 2H, OCH ), 2.59
(s, 1H, SH), 2.08 (s, 3H, CH ); ms: (EI) m/z 221 (M , 41.26), 147
2
-1
1
(C-S-C) cm ; H nmr (400 MHz; DMSO-d ): δ 7.39-7.28
+
6
3
(m, 10H, Ph-H), 7.11-7.09 (q, 1H, CH, J = 6.73 Hz), 5.45 (s, 1H,
(4.09), 131 (5.58), 114 (19.72), 108 (100), 91 (23.66), 77 (22.40).
N-CH -N), 5.08 (s, 1H, N-CH -N), 4.68 (s, 1H, N-CH -S), 4.40
2
2
2
Anal. Calcd. for C H N OS: C, 54.28; H, 5.01; N, 18.99.
10 11
3
(s, 1H, N-CH -S), 1.46-1.44 (d, 3H, CH , J = 6.48 Hz); ms: (EI)
2
3
Found: C, 54.23; H, 5.10; N, 18.86.
+
m/z 352 (M , 1.13), 260 (0.51), 259 (2.00), 156 (1.65), 147
(1.67), 128 (1.41), 115 (4.03), 107 (2.75), 105 (100), 91 (13.29),
90 (2.20).
2-(2-Chlorophenyl)oxymethyl-5-mercapto-1,2,4-triazole (6e).
Compound 6e was obtained as pale yellow prism crystals in
87.1% yield; mp 153-154 °C; ir (potassium bromide): ν 3383
Anal. Calcd. for C H N OS: C, 64.75; H, 5.72; N, 15.90.
19 20
4
Found: C, 64.39; H, 5.58; N, 15.61.
(NH), 3187 (=C-H), 2980 (CH ), 2553 (SH), 1628, 1488 (C=C,
2
1
C=N), 1239, 1015 (C-O-C), 648 (C-Cl); H nmr (400 MHz;
(S)-3-α-Phenylethyl-2,4-dihydro-5-(2-methyloxyphenyl)-
oxymethyl-1,2,4-triazolo[3,4-b]-1,3,5-thiadiazine (7b).
DMSO-d ): δ 7.41-6.88 (m, 4H, ArH), 5.43 (s, 1H, NH), 5.14
6
(s, 2H, OCH ), 4.20 (s, 1H, SH); ms: (EI) m/z 243 (M+2, 15.47),
2
+
This compound was prepared as a yellow powder in 55.5%
241 (M , 38.93), 206 (0.77), 182 (0.72), 169 (0.87), 167 (1.98),
20
-4
yield, mp 174-176 °C; [α]
–50° (c = 2 x 10 , DMSO); IR
131 (2.91), 130 (32.54), 128 (95.13), 114 (100), 59 (15.54).
D
(potassium bromide) ν 3019 (=C-H), 2931 (CH -H), 1670
(C=N), 1585 (N=C-S), 1234, 1042 (C-O-C) and 696 (C-S-C)
cm ; H NMR (400 MHz; DMSO-d ): δ 7.97-7.27 (m, 9H,
Ar-H), 7.15-7.09 (q, 1H, CH, J = 6.62 Hz), 5.59 (s, 2H, CH -O),
Anal. Calcd. for C H N OClS: C, 44.72; H, 3.34; N, 17.39.
2
9
8 3
Found: C, 44.63; H, 3.31; N, 17.32.
-1
1
6
2-β−Naphthyloxymethyl-5-mercapto-1,2,4-triazole (6f).
2
5.36 (s, 1H, N-CH -N), 4.81 (s, 1H, N-CH -N), 4.69 (s, 1H,
Compound 6f was obtained as a pale yellow powder in 81.2%
yield; mp 216-218 °C; ir (potassium bromide): ν 3428 (NH),
2
2
N-CH -S), 4.59 (s, 1H, N-CH -S), 2.18 (s, 3H, CH -Ph),
2
2
3
1.56-1.54 (d, 3H, CH , J = 6.72 Hz); MS (EI) m/z 259 (7.36), 156
3055 (=C-H), 2980 (CH ), 2553 (SH), 1628, 1513 (C=C, C=N),
3
2
1
(21.83), 147 (10.68), 128 (8.36), 115 (17.46), 114 (100), 108
(67.85), 105 (36.61), 91 (33.92), 90 (11.20).
1212, 1006 (C-O-C); H nmr (400 MHz; DMSO-d ): δ 8.13
6
(s, 1H, NH), 8.05-6.90 (m, 7H, β−C H -), 5.58 (s, 2H, OCH ),
10
7
2
+
4.25 (s, 1H, SH); ms: (EI) m/z 257 (M , 8.37), 144 (100), 130
(1.60), 127 (14.07), 115 (62.87), 114 (17.67).
Anal. Calcd. for C H N OS, C, 65.54; H, 6.05; N, 15.29.
20 22 4
Found: C, 65.36; H, 6.17; N, 15.01.