Arkivoc 2018, vii, 110-118
Olawode, E. O. et al.
The general procedure for the preparation of the known 2-(2-chloroacetamido)thiazoles (7) involved a
18
modification of the procedure reported by Xu and collegues . A solution of 2-amino-4-phenylthiazole 6a
0.530 g, 3 mmol) and Et N (560 µL, 4 mmol) in dichloromethane (15 mL) was cooled to 0-5 ⁰C in an ice-bath
(
3
and stirred for 30 min. 2-Chloroacetyl chloride (578 µL, 6.6 mmol) in dry dichloromethane (1.5 mL) was then
added slowly, and the reaction mixture was allowed to warm to room temperature and stirred until the amine
was completely consumed (ca. 1 h, as monitored by TLC). The reaction mixture was diluted with
dichloromethane and washed successively with water and saturated brine. The organic layer was dried over
anhydrous Na SO , the solvent was removed under reduced pressure and the residue was recrystallised from
2
4
o
18,20,26
o
o
ethanol to give compound 7a (0.413 g, 54%) as light-grey crystals, mp 170-171 C (Lit.
remaining analogues were obtained similarly [7b (100%) as a brown solid, mp 194-195 C (Lit. mp not cited);
c (64%) as a brown solid, mp 241-243 C (Lit. mp not cited); 7d (64%) as a brown solid, mp 135-137 C (Lit.
35 C); 7e (0.262 g, 88%) as a yellow solid, mp 174-176 ⁰C (Lit. 175 C); 7f (70%) as a light-brown solid, mp
171-173 C). The
27
o
27
o
28
7
1
2
o
29
o
o
30
o
13-216 C (Lit. 216 C).
General procedure for the preparation of the diethyl [N-(thiazol-2-yl)carbamoyl]methylphosphonates (3). A
mixture of 2-(2-chloroacetamido)-4-phenylthiazole 7a (0.063 g, 0.25 mmol) and triethyl phosphite (22 μL, 0.13
o
1,2
mmol) in an oven-dried round-bottomed flask was refluxed (ca. 110 C) for 9 h under nitrogen . The reaction
mixture was cooled to room temperature and then stirred 3 times with hexane (3 x 700 μL for 20 min each,
followed each time by decantation of the hexane layer to remove excess triethyl phosphite). The residual
solvent was evaporated under reduced pressure, and the crude product was chromatographed [using silica
gel; eluting with hexane/EtOAc (4:1)] to yield the diethyl [4-phenylthiazol-2-yl)carbamoyl]methylphosphonate.
o
Diethyl [4-phenylthiazol-2-yl)carbamoyl]methylphosphonate (3a). Brown solid (0.087 g, 98%), mp 78-80 C;
+
-1
[
(
7
2
HRMS: m/z calculated for C H N O PS (MH ) 355.0881. Found 355.0876]; ν / cm 1679 (C=O) and 3168
1
5
20
2
4
max
3
3
NH); δ (400 MHz; CDCl ) 10.96 (1H, br s, NH), 7.80 (2H, d, J 8 Hz, ArH), 7.36-7.29 (2H, m, J 7.1-7.4 Hz, ArH),
.01 (1H, s, thiazolyl-H), 4.28-4.21 (4H, m, 2 x OCH ), 3.17 (2H, d, J 24 Hz, PCH ) and 1.39 (6H, t, J 8.0 Hz,
H
3
2
3
2
P,H
2
H,H
2
x CH ); δ (100 MHz; CDCl ) 162.4 (C=O, J 5 Hz), 157.3, 150.2, 134.7, 128.7, 128.0, 126.3, 107.8 (ArC and
3
C
3
C,P
2
1
3
thiazolyl-C), 63.5 (OCH , J 6.4 Hz), 35.9 (PCH , J 131 Hz) and 16.5 (CH , J 5.9 Hz).
2
C,P
2
C,P
3
C,P
Diethyl {N-[4-(4-chlorophenyl)thiazol-2-yl]carbamoyl}methylphosphonate (3b). Brown solid (0.087 g, 89%),
o
35
+
-1
mp 86-89 C; [HRMS: m/z calculated for C H ClN O PS (MH ) 389.0492. Found 389.0488]; ν / cm 1680
15
19
2
4
max
3
3
(
7
6
C=O) and 3169 (NH); δ (400 MHz; CDCl ) 10.99 (1H, br s, NH), 7.72 (2H, d, J 7.8 Hz, ArH), 7.36 (2H, d, J
.8 Hz, ArH), 6.99 (1H, s, thiazolyl-H), 4.27 (4H, m, 2 x OCH ), 3.23 (2H, d, J 21 Hz, PCH ) and 1.40 (6H, t, J
.8 Hz, 2 x CH ); δ (100 MHz; CDCl ) 162.5 (C=O, J 4.7 Hz), 157.5, 149.1, 133.9, 133.2, 129.0, 127.7, 108.1
ArC and thiazolyl-C), 63.7 (OCH , J 6.5 Hz), 35.7 (PCH , J 131 Hz) and 16.6 (CH , J 5.8 Hz).
H
3
H,H
H,H
2
3
2
P,H
2
H,H
2
3
C
3
C,P
2
1
3
(
2
C,P
2
C,P
3
C,P
Diethyl {N-[4-(4-bromophenyl)thiazol-2-yl]carbamoyl}methylphosphonate (3c). Brown solid (0.074 g, 68%),
o
79
+
-1
mp 96-98 C; [HRMS: m/z calculated for C H BrN O PS (MH ) 432.9987. Found 432.9979]; ν / cm 1680
1
5
19
2
4
max
3
3
(
8
7
C=O) and 3160 (NH); δ (400 MHz; CDCl ) 11.02 (1H, br s, NH), 7.65 (2H, d, J 8.3 Hz, ArH), 7.51 (2H, d, J
.3 Hz, ArH), 6.98 (1H, s, thiazolyl-H), 4.25 (4H, m, 2 x OCH ), 3.22 (2H, d, J 22 Hz, PCH ) and 1.38 (6H, t, J
.0 Hz, 2 x CH ); δ (100 MHz; CDCl ) 162.4 (C=O, J 4.5 Hz), 157.5, 149.0, 133.6, 131.8, 127.9, 121.9, 108.1
ArC and thiazolyl-C), 63.6 (OCH , J 6.5 Hz), 35.6 (PCH , J 130.6 Hz) and 16.5 (CH , J 6.0 Hz).
H
3
H,H
H,H
2
3
2
P,H
2
H,H
2
3
C
3
C,P
2
1
3
(
2
C,P
2
C,P
3
C,P
Diethyl {N-[4-(4-fluorophenyl)thiazol-2-yl]carbamoyl}methylphosphonate (3d) Brown solid (0.0651 g, 70%),
o
+
-1
mp 72-74 C; [HRMS: m/z calculated for C H FN O PS (MH ) 373.0787. Found 373.0786]; ν / cm 1680
1
5
19
2
4
max
3
4
(
(
C=O) and 3159 (NH); δ (400 MHz; CDCl ) 10.89 (1H, br s, NH), 7.74 (2H, dd, J =8.3 Hz, J 5.6, ArH), 7.06
H
3
H,H
F,H
3
3
2
2H, t, J JH,H 8.4 Hz, ArH), 6.92 (1H, s, thiazolyl-H), 4.20 (4H, m, 2 x OCH ), 3.18 (2H, d, J 21 Hz, PCH ) and
F,H
2
P,H
2
2
3
1
1
.38 (6H, t, J 7.0 Hz, 2 x CH ); δ (100 MHz; CDCl ) 162.8 ( J 247 Hz, ArC), 162.3 (C=O, J 4.6 Hz), 157.3,
H,H
3
C
3
F,C
C,P
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