Hypervalent iodine in synthesis 53: Synthesis of 2,4-disubstituted and 2,4,5-trisubstituted 1,3-selenazoles

Article abstract of DOI:10.1055/s-2000-6407

α-Tosyloxylation of ketones with [hydroxy(tosyloxy)iodo]benzene, followed by treatment with primary selenoamides provides a convenient method of synthesis of selenazoles without the use of lachrymatory and toxic α-haloketones. The synthetic method is simple, mild and the yields are higher.

Full text of DOI:10.1055/s-2000-6407

PAPER
1219
Hypervalent Iodine in Synthesis 53: Synthesis of 2,4-Disubstituted and 2,4,5-
Trisubstituted 1,3-Selenazoles
Peng-Fei Zhang, Zhen-Chu Chen*
Department of Chemistry, Zhejiang University (XiXi Campus), Hangzhou, Zhejiang 310028, P. R. China
E-mail: zhenchuc@mail.HZ.Zj.CN
Received 3 February 2000; revised 27 March 2000
Abstract: a-Tosyloxylation of ketones with [hydroxy(tosyloxy)io-
do]benzene, followed by treatment with primary selenoamides pro-
vides a convenient method of synthesis of selenazoles without the
use of lachrymatory and toxic a-haloketones. The synthetic method
is simple, mild and the yields are higher.
Key words: a-tosyloxylation, selenium, primary selenoamides,
[hydroxy(tosyloxy)iodo]benzene (HTIB), cyclization, 2,4-disubsti-
tuted and 2,4,5-trisubstituted 1,3-selenazoles, heterocycles
Scheme
1
The products are characterized by microanalyses, H
NMR, IR and mass spectral data. The microanalyses and
1H NMR spectra are consistent with the proposed struc-
tures. In the infrared there are two characteristic intense
absorption centered in n = 1530-1460cm-1 and 1410-
1360 cm-1 regions due to the selenazole ring. All mass
spectra show the correct molecular ions peaks and ion
clusters. The reaction is found to be general and applica-
ble to aliphatic ketones or aromatic ketones with electron-
donating or electron-withdrawing groups. Additionally,
the reaction can be carried out readily with several sele-
noamides containing various substitutes, such as N,N-
dimethylamino, methoxy, methyl, chloro and nitro
groups.
The selenazole derivatives are of marked interest because
of their antitumor, antibacterial and other notable activi-
ties.1 However, since the first preparation of selenazoles
appeared in 1889,2a for decades after this no further details
were found in the literature. Only after 1940 was a some-
what more intensive study of the selenazoles began.
The number of the selenazole derivatives hithero is few.
There are probably two reasons for the small number of
selenazole derivatives to be found in the literature. One of
these is that there is practically only one useful method for
preparing selenazoles, in contrast to the many methods
available for oxazoles and thiazoles. Corresponding to the
Hantzch thiazole synthesis, this consists of the condensa-
tion of a-haloketones with selenoamides.2 On the other
hand, the essential selenium containing starting materials
are less readily available than the sulfur analog intermedi-
ates.
In conclusion, the present study provides a one-pot proce-
dure for the synthesis of selenazoles which has some ad-
vantages, such as avoiding the use of lachrymatory and
toxic a-haloketones, simplicity of the procedure and high-
er yields.
There is considerable current interest and research activity
in hypervalent iodine compounds.3 It has been demon-
strated that the [hydroxy(tosyloxy)iodo]benzene (HTIB)
is a versatile reagent in organic synthesis and especially
useful is the reaction of HTIB with ketones leading to
a-tosyloxylketones. This reaction followed by treatment
with the appropriate nucleophilies in situ offers a variety
of valuable synthetic methods. In addition, we have re-
cently developed a simple method for synthesis of sele-
noamides.4 On the basis of these facts, we were prompted
to examine the a-tosyloxylation of ketones with HTIB fol-
lowed by treatment with selenoamides. Such reaction
would provide a new route to selenazoles without use of
lachrymatory and toxic a-haloketones.5
Selenoamides were prepared according to the literature.4a MeOH
was distilled from Na prior to use. Melting points were determined
on a X4-Data microscopic melting point apparatus and were uncor-
1
rected. Microanalyses were obtained using Carlo-Erba 1106. H
NMR spectra were obtained at 500MHz or 60MHz (AVANCE
DMX500 or JEOL PMX60SI) in DMSO-d6 or CDCl3 using TMS as
an interal standard. IR spectra were recorded on a Perkin Elmer 683
spectrometer at r.t. Mass spectra were obtained by electron impact
at 70ev (HP5989B).
2,4-Diphenylselenazole (3a); Typical Procedure
To a solution of acetophenone (0.24 g, 2 mmol) in MeCN (15 mL)
was added HTIB (0.79 g, 2 mmol) and the mixture was refluxed for
45 min, and then the solvent was evaporated in vacuo. Then MeOH
(10 mL) and a solution of selenobenzamide (0.14 g, 1 mmol) in
MeOH (10 mL) was added under N2. After the addition was com-
plete, refluxing was continued for 30 min. The mixture was then
concentrated under reduced pressure and the residue was chromato-
graphed on a silica gel plate using mixtures of cyclohexane/EtOAc
(8:2) as eluent to afford 3a; yield: 0.22 g (78%); mp 97-99 °C
(Lit.2d mp 99 °C).
Herein we report our result, a new effective method for the
synthesis of selenazoles by cyclocondensation of a-tosy-
loxylketones with selenoamides. We have found that the
a-tosyloxylation of ketones with HTIB, followed by treat-
ment with selenoamides gave selenazoles in one-pot
(Scheme). The results are summarized in the Table.
Synthesis 2000, No. 9, 1219–1222 ISSN 0039-7881 © Thieme Stuttgart · New York

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P.-F. Zhang, Z.-C. Chen
PAPER
Table Synthesis of Selenazoles 3a–3t
a The yields based on selenoamides as limiting reagents
IR (KBr): n = 3100(m), 1500(s), 1380(s) cm-1.
1H NMR (DMSO-d6): d = 8.687 (s 1 H), 8.008-8.064 (m, 5 H),
7.352-7.528 (m, 5 H).
13C NMR (DMSO-d6): d = 120.024, 125.602, 125.965, 127.155,
128.038, 128.545, 129.775, 134.123, 134.959, 154.844, 172.511.
MS: m/z = 288 (M+, 5), 286 (M+, 17), 284 (M+, 9), 185 (18), 183
1H NMR (DMSO-d6): d = 8.828 (s,1 H), 7.802-8.005 (m, 5 H),
7.127-7.553 (m, 4 H).
MS: m/z = 305 (M+, 28), 303 (M+, 100), 301 (M+, 49), 202 (24), 200
(84), 198 (40), 120 (92).
Anal. calcd for C15H10FNSe: C, 59.62; H, 3.34; N, 4.63. Found: C,
59.67; H, 3.29; N, 4.65.
(100), 181 (52), 103 (10), 77 (5), 76 (27), 51 (10).
4-(4-Bromophenyl)-2-phenylselenazole (3c)
Mp 76-77 °C.
IR (KBr): n = 3090(m), 1495(s), 1370(s) cm-1.
4-(4 -Flurophenyl)-2-phenylselenazole (3b)
Mp 112-114 °C.
IR (KBr): n = 3125(m), 1480(s), 1390 (s) cm-1.
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Synthesis of 2,4-Disubstituted and 2,4,5-Trisubstituted 1,3-Selenazoles
1221
1H NMR (CDCl3): d = 8.70 (s, 1 H), 7.73-8.03 (m, 5 H), 7.10-7.31
(m, 4 H).
MS: m/z = 253 (M+, 33), 251 (M+, 100), 249 (M+, 49), 150 (19), 148
(58), 146 (30), 68 (29), 53 (33).
MS: m/z = 365 (M+, 99), 363 (M+, 100), 361 (M+, 48), 262 (70), 260
(71), 258 (35), 182 (80), 180 (84).
Anal. calcd for C12H13NSe: C, 57.60; H, 5.24; N, 5.60. Found: C,
57.81; H, 5.16; N, 5.63.
Anal. calcd for C15H10BrNSe: C, 49.62; H, 2.78; N, 3.86. Found: C,
49.93; H, 2.54; N, 3.99.
5-Acetyl-4-methyl-2-phenylselenazole (3j)
Mp 71-73 °C.
4-(4-Chlorophenyl)-2-phenylselenazole (3d)
Mp 136-138 °C.
IR (KBr): n = 3110(m), 1490(s), 1385(s) cm-1.
IR (KBr): n = 2920(m), 1650(s), 1485(s), 1350(s) cm-1.
1H NMR (CDCl3): d = 7.20-7.90 (m, 5 H), 2.60 (s, 3 H), 2.40 (s, 3
H).
1H NMR (CDCl3): d = 8.75 (s, 1 H), 7.70-8.05 (m, 5 H), 7.11-7.52
(m, 4 H).
MS: m/z = 267 (M+, 31), 265 (M+, 100), 263 (M+, 49), 164 (20), 162
(60), 160 (29), 119 (34), 104 (33).
MS: m/z = 321 (M+, 17), 319 (M+, 35), 317 (M+, 17), 218 (45), 216
(100), 214 (32), 138 (25), 136 (75), 101 (9).
Anal. calcd for C12H11NOSe: C, 54.56; H, 4.20; N, 5.30. Found: C,
54.62; H, 3.97; N, 5.26.
Anal. calcd for C15H10ClNSe: C, 56.53; H, 3.16; N, 4.39. Found: C,
56.65; H, 3.09; N, 4.51.
5-Acetyl-2-(2,4-dichlorophenyl)-4-methylselenazole (3k)
Mp 91-93 °C.
4-(4-Methylphenyl)-2-phenylselenazole (3e)
IR (KBr): n = 2980, 2960(s), 1645(s), 1470(s), 1375(s) cm-1.
Mp 117-119 °C.
IR (KBr): n = 3120(m), 2940(s), 1495(s), 1320 (s) cm-1.
1H NMR (CDCl3): d = 7.30-7.50 (m, 3 H), 2.71 (s, 3 H), 2.50 (s, 3
H).
1H NMR (CDCl3): d = 8.46 (s,1 H), 7.73-8.01 (m, 5 H), 7.02-7.55
(m, 4 H), 2.35 (s, 3 H).
MS: m/z = 335 (M+, 17), 333 (M+, 36), 331 (M+, 19), 164 (17), 162
(52), 160 (25), 119 (31), 82 (3), 76 (9), 43 (100).
MS: m/z = 301 (M+, 31), 299 (M+, 100), 297 (M+, 48), 198 (25), 196
(77), 194 (39), 116 (84), 101 (11).
Anal. calcd for C12H9Cl2NOSe: C, 43.26; H, 2.27; N, 4.20. Found:
C, 43.23; H, 2.96; N, 4.25.
Anal. calcd for C16H13NSe: C, 64.43; H, 4.39; N, 4.70. Found: C,
64.52; H, 4.31; N, 4.76.
2-(2,4-Dichlorophenyl)-4-phenylselenazole (3l)
Mp 103-105 °C.
4-(3-Nitrophenyl)-2-phenylselenazole (3f)
Mp 67-69 °C.
IR (KBr): n = 3080(m), 1460(s), 1380(s), 1360 (s) cm-1.
IR (KBr): n = 3120(m), 1515(s), 1385(s) cm-1.
1H NMR (CDCl3): d = 8.42 (s, 1 H), 7.79-7.90 (m, 3 H), 7.30-7.50
(m, 5 H).
1H NMR (CDCl3): d = 8.93 (s,1 H), 7.91-8.03 (m, 5 H), 7.33-7.61
(m, 4 H).
MS: m/z = 355 (M+, 15), 353 (M+, 25), 351 (M+, 12), 184 (6), 182
(19), 180 (9), 102 (18), 77 (31), 76 (26), 51 (14).
MS: m/z = 332 (M+, 34), 330 (M+, 100), 328 (M+, 49), 229 (23), 227
(68), 225 (33), 147 (81), 122 (7).
Anal. calcd for C15H9Cl2NSe: C, 51.01; H, 2.57; N, 3.92. Found: C,
51.61; H, 2.52; N, 4.01.
Anal. calcd for C15H10N2O2Se: C, 54.72; H, 3.06; N, 8.51. Found:
C, 54.83; H, 2.98; N, 8.89.
5-Benzoyl-2-(4-N,N-dimethylaminophenyl)-4-methylselena-
zole (3m)
Mp 64-66 °C.
IR (KBr): n = 2940(s), 1650(s), 1495(s), 1400(s) cm-1.
5-Benzoyl-4-methyl-2-phenylselenazole (3g)
Mp 88-90 °C.
IR (KBr): n = 2950(m), 1638(s), 1500(s), 1410(s) cm-1.
1H NMR(CDCl3): d = 7.65-8.05 (m, 5 H), 7.25-7.50 (m, 5 H), 2.50
(s, 3 H).
1H NMR (CDCl3): d = 7.70-7.90 (m, 2 H), 7.21-7.35 (m, 5 H),
6.62-6.79 (m, 2 H), 2.95 (s, 6 H), 2.40 (s, 3 H).
MS: m/z = 372 (M+, 19), 370 (M+, 60), 368 (M+, 29), 226 (3), 224
(10), 222 (5), 144 (9), 105 (100), 77 (63).
MS: m/z = 329 (M+, 22), 327 (M+, 67), 325 (M+, 33), 226 (1), 224
(3), 222 (2), 182 (9), 144 (10), 119 (9), 105 (100), 77 (64).
Anal. calcd for C19H18N2OSe: C, 61.79; H, 4.91; N, 7.59. Found: C,
61.83; H, 4.89; N, 7.61.
Anal. calcd for C17H13NOSe: C, 62.58; H, 4.02; N, 4.29. Found: C,
62.61; H, 3.99; N, 4.26.
2-(4-N,N-Dimethylaminophenyl)-4-phenylselenazole (3n)
Mp 94-96 °C.
IR (KBr): n = 3100(m), 2960(s), 1460(s), 1360(s), 860(s) cm-1.
2-Phenyl-4,5,6,7-tetrahydrobenzoselenazole (3h)
Bp 67-69 °C/5 Torr.
IR (neat): n = 2880-2860(m), 1480(s), 1285(s) cm-1.
1H NMR (CDCl3): d = 7.10-7.90 (m, 5 H), 2.75 (t, 4 H, J = 2 Hz),
1.75 (m, 4 H).
1H NMR (CDCl3): d = 8.71 (s, 1 H), 7.72-7.86 (m, 4 H), 7.25-7.48
(m, 5 H ), 2.93 (s, 6 H).
MS: m/z = 330 (M+, 32), 328 (M+, 100), 326 (M+, 48), 184 (28), 182
(83), 180 (41), 102 (88), 77 (32), 76 (13).
MS: m/z = 265 (M+, 31), 263 (M+, 100), 261 (M+, 49), 162 (27), 160
(82), 158 (40), 80 (11).
Anal. calcd for C17H16N2Se: C, 62.39; H, 4.93; N, 8.56. Found: C,
62.53; H, 4.66; N, 8.61.
Anal. calcd for C13H13NSe: C, 59.57; H, 4.99; N, 5.34. Found: C,
59.61; H, 4.96; N, 5.22.
2-(4-Nitrophenyl)-4-phenylselenazole (3o)
Mp 69-71 °C.
IR (KBr): n = 3100(m), 1505(s), 1455(s) cm-1.
4-Ethyl-5-methyl-2-phenylselenazole (3i)
Bp 96-98 °C/5 Torr.
IR (neat): n = 2960, 2930(s), 1510(s), 1295(s) cm-1.
1H NMR (CDCl3): d = 7.60-7.80 (m, 2 H), 7.20-7.30 (m, 3 H),
2.36-2.75 (q, 2 H), 2.35 (s, 1 H), 1.05-1.30 (t, 3 H).
1H NMR(CDCl3): d = 8.82 (s, 1 H), 7.60-7.85 (m, 2 H), 7.45-
7.54(m, 5 H), 7.20-7.30 (m, 2 H).
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P.-F. Zhang, Z.-C. Chen
PAPER
MS: m/z = 332 (M+, 7), 330 (M+, 21), 328 (M+, 10), 184 (30), 182
MS: m/z = 297 (M+, 19), 295 (M+, 57), 293 (M+, 28), 164 (17), 162
(100), 180 (49), 102 (68), 77 (23), 76 (11).
(53), 160 (26), 119 (35), 104 (30), 82 (7), 43 (100).
Anal. calcd for C15H10N2O2Se: C, 54.73; H, 3.06; N, 8.51. Found:
C, 55.03; H, 2.99; N, 8.60.
Anal. calcd for C13H13NO2Se: C, 53.07; H, 4.45; N, 4.76. Found: C,
53.61; H, 4.38; N, 4.79.
2-(4-Chlorophenyl)-4-phenylselenazole (3p)
Mp 106-108 °C (Lit.2d mp108 °C).
IR (KBr): n = 3090(m), 1465(s), 1375(s), 870 (vs) cm-1.
References
(1) (a) Shafiee, A.; Mazloumi, A.; Cohen, V. I. J. Heterocycl.
Chem. 1979, 16, 1563.
1H NMR(CDCl3): d = 8.75 (s, 1 H), 8.10-8.20 (m, 4 H), 7.45-7.60
(m, 5 H).
(b) Shafiee, A. ; Shafaati, A.; Khamench, B. H. J. Heterocycl.
Chem. 1989, 26, 709.
(c) Shafiee, A.; Khashayarmanesh, Z.; Kamal, F. J. Sci.
Islamic Repub. Iran. 1990, 1, 111; Chem. Abstr. 1991, 115,
49544.
2-(4-Methoxyphenyl)-4-phenylselenazole (3q)
Mp 103-105 °C (Lit.2d mp 105 °C).
IR (KBr): n = 3092(m), 2980(s), 1505(s), 1365(s) cm-1.
1H NMR (CDCl3): d = 8.48 (s,1 H), 7.83-7.92 (m, 2 H), 7.00-7.42
(m, 2 H), 6.96-7.03 (m, 5 H), 3.80 (s, 3 H).
(2) (a) Hofmann, G. Liebigs Ann. Chem. 1889, 250, 294.
(b) French Patent 757767 (1934), Kodak-pathe; Chem.
Abstr.1934, 28, 3246.
2-(4-Methylphenyl)-4-phenylselenazole (3r)
Mp 134-136 °C (Lit.2d mp 136 °C).
(c) Brooker, L. G. S.; White, F. L. US Patent 2005411 (1935);
Chem.Abstr..1935, 29, 5282.
(d) Cohen, V. I. Synthesis 1979, 66.
IR (KBr): n = 3105(m), 2990, 2940(s), 1505(s), 1400(s) cm-1.
1H NMR (CDCl3): d = 8.60 (s, 1 H), 7.91-8.00 (m, 4 H), 7.21-7.39
(m, 5 H), 2.35 (s, 3 H).
(3) For reviews see:
(a) Stang, P. J. Angew. Chem. Int. Ed. Engl. 1992, 31, 274.
(b) Prakash, O.; Saini, N.; Sharma, P. K. Heterocycles 1994,
38, 409.
5-Benzoyl-2-(4-methylphenyl)-4-methylselenazole (3s)
Mp 89-91 °C.
IR (KBr): n = 2970, 2940(s), 1635(s), 1500(s), 1405(s) cm-1.
1H NMR (CDCl3): d = 7.68-8.00 (m, 4 H), 7.10-7.60 (m, 5 H), 2.44
(s, 3 H), 2.38 (s, 3 H).
MS: m/z = 343 (M+, 20), 341 (M+, 60), 339 (M+, 30), 226 (2), 224
(5), 222 (3), 181 (18), 144 (2), 105 (100).
(c) Prakash, O.; Saini, N.; Sharma, P. K. Synlett 1994, 221.
(d) Wipf, P.; Venkatraman, S. J. Org. Chem. 1996, 61, 8004.
(e) Zhdankin, V. V.; Stang, P. J. Tetrahedron 1998, 54, 10927.
(4) (a) Zhao, H.-R.; Ruan, M.-D.; Fan, W.-Q.; Zhou, X.-J Synth.
Commun. 1994, 24, 1761.
(b) Ruan, M.-D.; Zhang, P.-F.; Tao, Y.; Fan, W.-Q. Synth.
Commun. 1996, 26, 2617.
(5) Moriarty et al. reported a similar synthesis of 2-amino-
substituted 1,3-selenazoles from selenoureas.
Moriarty, R. M.; Vaid, B. K.; Duncan, M. P.; Levy, S. G.;
Prakash, O.; Goyal, S. Synthesis 1992, 845
Anal. calcd for C18H15NOSe: C, 63.54; H, 4.44; N, 4.12. Found: C,
63.71; H, 4.39; N, 4.27.
5-Acetyl-2-(4-methoxyphenyl)-4-methylselenazole (3t)
Mp 68-70 °C.
IR (KBr): n = 2995-2920(s), 1665(s), 1490(s), 1390(s) cm-1.
1H NMR (CDCl3): d = 7.85-7.96 (m, 2 H), 7.31-7.50 (m, 2 H), 3.84
(s, 3 H), 2.55 (s, 3 H), 2.38 (s, 3 H).
Article Identifier:
1437-210X,E;2000,0,09,1219,1222,ftx,en;F01100SS.pdf
Synthesis 2000, No. 9, 1219–1222 ISSN 0039-7881 © Thieme Stuttgart · New York