Hypervalent iodine in synthesis 81: A one-pot procedure for the synthesis of 1H-imidazole derivatives by cyclocondensation of ketones with [Hydroxy(tosyloxy)iodo]benzene and amidines

Article abstract of DOI:10.1055/s-2001-18059

Tosyloxylation of ketones with [hydroxy(tosyloxy)iodo]benzene (HTIB), followed by treatment with amidines provides a one-pot procedure for the synthesis of 1H-imidazole derivatives with good yields.

Full text of DOI:10.1055/s-2001-18059

SHORT PAPER
2075
Hypervalent Iodine in Synthesis 81: A One-Pot Procedure for the Synthesis of
H-Imidazole Derivatives by Cyclocondensation of Ketones with
Hydroxy(tosyloxy)iodo]benzene and Amidines
1
[
H
P
ypervalent Io
e
dine in Syn
n
thesis 81:
A
g
O
ne Pot Sy
-
o
F
f
1
H
-Imidazol
e
Derivativ
i
Department of Chemistry, Zhejiang University (Xi-Xi Campus), Hangzhou, 310028, P. R. China
E-mail: zhenchuc@mail.HZ.Zj.CN
Received 12 March 2001; revised 23 April 2001
+
H
.
+
Abstract: -Tosyloxylation of ketones with [hydroxy(tosyloxy)io-
do]benzene (HTIB), followed by treatment with amidines provides
a one-pot procedure for the synthesis of 1H-imidazole derivatives
with good yields.
Ph
.
H
.
NH
Ph
-PhCN
+
- CH
PhCNH
Ph
N
N
H
Key words: -tosyloxylation, [hydroxy(tosyloxy)iodo]benzene
Scheme 2
(
HTIB), amidines, 1H-Imidazole
peaks. Compound 3a is taken as an example to describe
the proposed general fragmentation mechanism of the im-
idazole ring (Scheme 2).
The imidazole nucleus is found in a variety of natural
1
products such as vitamin B and its derivatives, histidine
1
2
2
3
derivatives, imidazole nucleosides and nucleotides.
A plausible mechanism for the formation of imidazole 3
is shown in Scheme 3. It involves the nucleophilic attack
of the amidine 2 to the carbon atom of α-tosyloxylketone
to form substituted product 5 followed by an usual eno-
Therefore, its synthesis has become increasingly impor-
tant, and several syntheses of imidazole derivatives were
4
reported in literature. As part of our programme directed
towards the use of hypervalent iodine reagents in organic
5
lization of ketone and elimination of H O to give imida-
2
synthesis, we have recently reported a convenient synthe-
zole 3.
sis of selenazoles by cyclocondensation of ketones with
[
hydroxy(tosyloxy)iodo]benzene and selenoamides.6 In conclusion, the present study provides a one-pot proce-
Herein, we would like to report a one-pot procedure for dure for the synthesis of 1H-imidazole derivatives, which
the synthesis of imidazoles, which includes α-tosyloxyla- have the advantages of avoiding the use of lachrymatory
tion of ketones with [hydroxy(tosyloxy)iodo]benzene in
acetonitrile, followed by treatment with amidines in chlor-
oform. The overall yields of imidazoles are 42–67% with-
out isolation of any intermediates (Scheme 1).
Table One-Pot Synthesis of 1H-Imidazole Derivatives
Products R1
R2
R3
Reaction Yield (%)a
time (h)
R2
a. PhI(OH)OTs/CH CN
O
3
NH
3
a
Ph
H
H
H
H
H
H
H
H
Ph
3.0
2.5
2.5
2.5
3.5
3.5
3.0
3.0
3.5
3.5
4.0
3.5
63
67
62
65
53
49
53
42
61
66
57
51
R CCH R
1 2 2
NH
R1
R3
3b
p-FC H
Ph
b. R CNH /CHCl , reflux
6
4
3
2
3
N
3
3
3
3
3
3
3
c
d
e
f
p-ClC H
4
Ph
(1)
(2)
(3)
6
p-BrC H
Ph
Scheme 1
6
4
p-MeC H
Ph
6
4
Ph
CH3
CH3
CH3
Ph
The reaction was found to be general and applicable to ac-
etophenones, aliphatic ketones or -diketones. Several sub-
stituted acetophenones such as fluoro, bromo, chloro and
methyl successfully reacted. The results are summarized
in the Table. The products were characterized by melting
g
h
i
p-FC H
6
4
p-ClC H
6
4
Ph
CH CO
3
1
13
point, microanalysis, H and C NMR, IR and MS data.
+
3j
Ph
CH3
Ph
The mass spectra showed the correct M and fragment
3
k
CH3
Ph
CH CO
Ph
3
Synthesis 2001, No. 14, 26 10 2001. Article Identifier:
3
l
CH3
CH3
1
©
437-210X,E;2001,0,14,2075,2077,ftx,en;F02401SS.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
aThe yields based on ketones as limiting reagents.

2
076
P.-F. Zhang, Z.-C. Chen
SHORT PAPER
1
3
C NMR (CDCl ): δ = 115.75, 125.38, 126.25, 128.86, 128.98,
3
R
3
NH
3
R C=NH
2
129.04, 129.78, 131.55, 132.65, 134.46, 147.23.
HN
(2)
O
PhI(OH)OTs
O
ONH
CCHR
IR (KBr): 2750–3428 (br), 1600 (m), 1551 (m), 1483 (s), 1453 (s),
1408 (s), 1089 (s), 1010 (s), 941 (s), 849 (s), 827 (vs) cm .
R
1
CCH
2
R
2
[
R
1
CCHR
2
]
R
1
2
–1
-
HOTs
OTs
(5)
(
1)
(4)
+
+
MS: m/z (%) =256 (M , 35), 254 (M , 100), 153 (2), 151 (4), 117
19), 116 (14), 104 (4), 89 (38), 77 (5).
R
2
R
3
(
H-N
HO
-H O
2
NH
NH
C=CR
R
1
Anal. Calcd for C H ClN : C, 70.73; H, 4.35; N, 11.00. Found: C,
15 11 2
71.11; H, 4.74; N, 11.32.
R
3
R
1
2
N
(
3)
(
6)
4
(5)-(4-Bromophenyl)-2-phenylimidazole (3d)
7
Mp 180–182 °C (Lit. mp 178 °C).
Scheme 3
1
H NMR (CDCl ): δ = 7.39–7.88 (m, 9H), 7.31 (s, 1H).
3
and toxic α-halogenoketones, simplicity of the procedure IR (KBr): 2870–3425 (br), 1607 (s), 1581 (s), 1550 (s), 1488 (s),
–
1
1
460 (s), 1315 (s), 1177 (s), 1070 (s), 692 (vs) cm .
and higher yields.
+
+
MS: m/z (%) = 300 (M , 98), 298 (M , 100), 197 (5), 195 (5), 117
18), 104 (4), 89 (41), 77 (5).
(
Mps (uncorrected) were determined on a X -Data microscopic
4
melting point apparatus. Microanalyses were obtained using EA-
4
(5)-(4-methylphenyl)-2-phenylimidazole (3e)
1
13
1
110 (Carlo-Erba). H and C NMR spectra were obtained at 400
4a
Mp 177–179 °C (Lit. mp 183 °C).
MHz (AVANCE DMX400, Bruker) in CDCl using TMS as an in-
3
1
H NMR (CDCl ): δ = 7.35–7.89 (m, 9H), 7.34 (s, 1H), 2.35 (s, 3H).
ternal standard. IR spectra were recorded on a VECTOR 22 (Bruk-
er) spectrometer at r.t. Mass spectra were obtained by electron
impact at 70 eV (HP5989B).
3
IR (KBr): 2500–3432 (br), 2921 (s), 1682 (s), 1608 (s), 1458 (s),
1
–1
440 (s), 1236 (s), 1101 (s), 974 (s), 813 (s) cm .
+
MS: m/z (%) = 234 (M , 100), 130 (37), 119 (67), 117 (26), 104
1
H-Imidazoles 3a–3l; General Procedure
(20), 103 (27), 91 (45), 89 (19), 77 (40).
To a solution of ketone 1 (1 mmol) in MeCN (10 mL) was added
solid [hydroxy(tosyloxy)iodo]benzene (0.392 g, 1 mmol) and the
mixture was refluxed for 45 min; the suspended solution became
2
-Methyl-4(5)-phenylimidazole (3f)
4
d
Mp 161–162 °C (Lit. mp 161 °C).
clear. A solution of amidine (1.2 mmol) in CHCl (20 mL) was add-
3
1
ed and refluxing was continued for a period of time (Table). The
solvent was removed under reduced pressure and the residue was
subjected to chromatography (silica gel; cyclohexane–EtOAc, 4:1)
to give pure product.
H NMR (CDCl ): δ = 11.53 (br, 1H), 7.23–7.81 (m, 6H), 2.43 (s,
3
3H).
IR (KBr): 2700–3470 (br), 2960 (s), 1615 (s), 1597 (s), 1445 (s),
–1
1
374 (s), 1190 (s), 1177 (s), 1140 (s), 1090 (s), 955 (s), 945 (s) cm .
+
MS: m/z (%) = 158 (M , 100), 117 (43), 104 (18), 90 (41), 89 (76),
77 (20).
2
,4(5)-Diphenylimidazole (3a)
4
b
Mp 166–168 °C (Lit. mp 168 °C).
1
H NMR (CDCl ): δ = 10.80 (br, 1H), 7.19–7.88 (m, 10H), 7.25 (s,
3
4
(5)-(4-Fluorophenyl)-2-methylimidazole (3g)
1
H).
Mp 130–132 °C.
IR (KBr): 2500–3405 (br), 1700 (m), 1606 (m), 1489 (m), 1459 (s),
1
H NMR (CDCl ): δ = 7.86 (s, 1H), 7.44–7.79 (m, 2H), 6.74–7.12
m, 2H), 2.46 (s, 3H).
–
1
3
1
040 (m), 1000 (m) cm .
(
13
+
MS: m/z (%) = 220 (M , 100), 117 (35), 104 (14), 90 (52), 89 (61),
C NMR (CDCl ): δ = 15.01, 115.81, 125.34, 126.61, 129.07,
3
7
7 (19).
1
31.55, 151.15, 162.04 (d, J = 243.8 Hz).
IR (KBr): 2650–3510 (br), 2965 (s), 1599 (s), 1507 (s), 1382 (s),
4
(5)-(4-Fluorophenyl)-2-phenylimidazole (3b)
–1
1
236 (s), 1189 (s), 1177 (s), 1084 (s), 912 (s), 815 (s) cm .
Mp 167 –168 °C.
+
1
MS: m/z (%) = 176 (M , 100), 135 (7), 117 (17), 108 (22), 107 (20),
H NMR (CDCl ): δ = 7.85 (s, 1H), 7.77–7.84 (m, 2H), 7.28–7.70
3
9
0 (3), 89 (9), 77 (7).
(
m, 5H), 7.04–7.08 (m, 2H).
1
3
Anal. Calcd for C H FN : C, 68.18; H, 5.15; N, 15.90. Found: C,
C NMR (CDCl ): δ = 115.51, 115.73, 125.38, 126.65, 126.73,
10
9
2
3
6
8.39; H, 5.47; N, 15.51.
1
28.94, 129.26, 129.35, 129.89, 147.15, 162.08 (d, J = 244.4 Hz).
IR (KBr): 2500–3340 (br), 1601 (s), 1571 (s), 1542 (s), 1496 (s),
4
(5)-(4-Chlorophenyl)-2-methylimidazole (3h)
–1
1
458 (s), 1399 (s), 1085 (s), 964 (s), 840 (vs), 814 (s) cm .
Mp 124–125 °C.
+
MS: m/z (%) = 238 (M , 100), 135 (10), 117 (19), 108 (20), 107
1
H NMR (CDCl ): δ = 7.35–7.80 (m, 4H), 7.31 (s, 1H), 2.43 (s, 3H).
3
(
12), 90 (4), 89 (9), 77 (6).
1
3
C NMR (CDCl ): δ = 15.11, 115.93, 125.47, 128.83, 129.79,
3
Anal. Calcd for C H FN : C, 75.62; H, 4.65; N, 11.76. Found: C,
1
5
11
2
1
32.71, 134.49, 151.43.
7
5.99; H, 4.96; N, 12.16.
IR (KBr): 2700–3500 (br), 2962 (s), 1600 (s), 1555 (s), 1490 (s),
1
–
1
410 (s), 1385 (s), 1250 (s), 1150 (s), 1065 (s), 936 (s), 827 (s) cm .
4
(5)-(4-Chlorophenyl)-2-phenylimidazole (3c)
+
+
Mp 159–161 °C.
MS: m/z (%) = 194 (M , 34), 192 (M , 100), 153 (2), 151 (8), 117
(12), 116 (13), 104 (6), 89 (31), 77 (6).
1
H NMR (CDCl ): δ = 7.70–7.87 (m, 4H), 7.34–7.41 (m, 5H), 7.33
3
(
s, 1H).
Anal. Calcd for C H ClN : C, 62.35; H, 4.71; N, 14.54. Found: C,
1
0
9
2
6
2.70; H, 4.34; N, 14.88.
Synthesis 2001, No. 14, 2075–2077 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Hypervalent lodine in Synthesis 81: A One Pot Synthesis of 1H-Imidazole Derivatives
2077
5
(4)-Acetyl-2,4(5)-diphenylimidazole (3i)
IR (KBr): 2980–3585 (br), 2986 (m), 2922 (m), 1638 (s), 1595 (s),
1446 (s), 1375 (s), 1210 (s), 1176 (s), 1067 (s), 908 (s) cm .
–
1
Mp 68–70 °C.
1
+
H NMR (CDCl ): δ = 7.29–8.18 (m, 10H), 2.21 (s, 3H).
MS: m/z (%) =172 (M , 100), 131 (21), 116 (10), 104 (58), 77 (12).
3
IR (KBr): 3100–3469 (br), 2985 (s), 1730 (s), 1695 (s), 1598 (s),
–
1
1
450 (s), 1372 (s), 1152 (s), 1017 (s), 915 (s) cm .
References
+
MS: m/z (%) = 262 (M , 100), 153 (39), 105 (38), 77 (16).
(
1) Grimmet, M. R. Comprehensive Organic Chemistry, Vol. 4;
Anal. Calcd for C H N O: C, 77.84; H, 5.38; N, 10.68. Found: C,
7.47; H, 5.76; N, 10.31.
17
14
2
Barton, D.; Ollis, W. B., Eds.; Pergammon Press: New York,
7
1979.
(
(
(
2) Fox, S. W. Chem. Rev. 1943, 32, 47.
5
(4)-Methyl-2,4(5)-diphenylimidazole (3j)
3) Townsend, L. B. Chem. Rev. 1967, 67, 533.
4) (a) Vorlaufige, M. Chem. Ber. 1901, 34, 637. (b) Burtles,
R.; Pyman, F. L. J. Chem. Soc. 1923, 123, 361.
(c) Weidenhagen, R.; Herrmann, R. Chem. Ber. 1935, 68,
4
b
Mp 211–213 °C (Lit. mp 215 °C).
1
H NMR (CDCl ): δ = 8.51 (s, 1H), 7.18–7.78 (m, 10H), 2.37 (s,
3
3
H).
1
8
2
953. (d) Bredereck, H.; Theilig, G. Chem. Ber. 1953, 86,
8. (e) Novelli, A.; Santis, A. D. Tetrahedron Lett. 1967,
65. (f) Kornis, R. M.; Nyitrai, J.; Lempert, K. Chem. Ber.
IR (KBr): 3050–3410 (br), 2922 (s), 1645 (s), 1600 (s), 1565 (s),
–
1
1
487 (s), 1410 (s), 1145 (s), 1087 (s) cm .
+
MS: m/z (%) = 234 (M , 100), 131 (28), 116 (6), 77 (12).
1971, 104, 3080. (g) Scheinbaum, M. L.; Dines, M. B.
Tetrahedron Lett. 1971, 2205. (h) Nakanishi, S.; Nantaku,
J.; Otsuji, Y. Chem. Lett. 1983, 341. (i) Inoue, M.;
Matsumoto, K.; Ohta, A. J. Heterocycl. Chem. 1983, 20,
1277. (j) Singh, B. Heterocycles 1992, 34, 2373.
5
(4)-Acetyl-4(5)-methyl-2-phenylimidazole (3k)
Mp 54–56 °C.
1
H NMR (CDCl ): δ = 7.38–8.03 (m, 5H), 2.54 (s, 3H), 2.25 (s, 3H).
3
(
5) (a) Stang, P. J.; Surber, B. W.; Chen, Z. C.; Roberts, K. A.;
Anderson, A. G. J. Am. Chem. Soc. 1987, 109, 228.
IR (KBr): 3015–3506 (br), 2980 (s), 2926 (s), 1685 (s), 1597 (s),
1
8
492 (s), 1449 (s), 1385 (s), 1344 (s), 1266 (s), 1134 (s), 1006 (s),
83 (s) cm .
(b) Chen, Z. C.; Jin, Y. Y.; Stang, P. J. J. Org. Chem. 1987,
–
1
52, 4117. (c) Chen, Z. C.; Stang, P. J.; Jin, Y. Y. J. Org.
+
MS: m/z (%) = 200 (M , 100), 97 (39), 77 (10), 43 (31).
Chem. 1987, 52, 4115. (d) Yan, J.; Zhong, L. R.; Chen, Z. C.
J. Org. Chem. 1991, 56, 459. (e) Liu, Z. D.; Chen, Z. C. J.
Org. Chem. 1993, 58, 1924. (f) Chen, D. W.; Chen, Z. C.
Tetrahedron Lett. 1994, 35, 7637. (g) Yan, J.; Chen, Z. C.
Tetrahedron Lett. 1999, 40, 5757.
Anal. Calcd for C H N O: C, 71.98; H, 6.04; N, 13.99. Found: C,
12
12
2
7
1.62; H, 5.68; N, 13.63.
2
,5(4)-Dimethyl-4(5)-phenylimidazole (3l)
(
(
6) Zhang, P. F.; Chen, Z. C. Synthesis 2000, 1219.
7) Kempter, G.; Spindler, J.; Fiebig, H. J.; Sarodnick, G. J.
Prakt. Chem. 1971, 313, 977.
4e
Mp 230 °C (Lit. mp 230 °C).
1
H NMR (CDCl ): δ = 8.49 (s, 1H), 6.95–7.67 (m, 5H), 2.48 (s, 3H),
3
2
.36 (s, 3H).
Synthesis 2001, No. 14, 2075–2077 ISSN 0039-7881 © Thieme Stuttgart · New York