Hypervalent iodine in synthesis 50: A novel method of synthesis of selenazoles by cyclocondensation of selenoamides and alkynyl(phenyl)iodonium salts

Article abstract of DOI:10.1002/jhet.5570380233

A novel method for the synthesis of selenazoles by cyclocondensation of primary selenoamides and alkynyl(phenyl)iodomium salts and the reaction mechanism are reported. The synthetic method is simple, mild and the yields are high.

Full text of DOI:10.1002/jhet.5570380233

Mar-Apr 2001
Hypervalent Iodine in Synthesis 50: A Novel Method of Synthesis
of Selenazoles by Cyclocondensation of Selenoamides
and Alkynyl(Phenyl)Iodonium Salts
503
Peng-Fei Zhang and Zhen-Chu Chen*
Department of Chemistry, Zhejiang University (XiXi Campus) , Hangzhou, Zhejiang 310028, China
Received July 3, 2000
A novel method for the synthesis of selenazoles by cyclocondensation of primary selenoamides and
alkynyl(phenyl)iodomium salts and the reaction mechanism are reported. The synthetic method is simple,
mild and the yields are high.
J. Heterocyclic Chem., 38, 503 (2001).
Introduction.
Although the first reported preparations of selenazoles
go back to the year 1889, for decades after this no further
details were found in the literature. Only after 1940 was a
somewhat more intensive study of the selenazoles begun.
Selenazole derivatives possess antitumor activity, antibac-
terial activity and other notable activities [1].
There are probably two reasons for the small number of
investigations be found in the area of selenazole chemistry.
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 Hantzsch thiazole synthesis, this
consists of the condensation of α-haloketones with
selenoamides [2]. Also, the essential selenium containing
starting materials are not as readily available as those of
the sulfur analogue intermediates.
spectra show the correct molecular ions peaks, ion clus-
ters and fragmentation patterns shown in Scheme 2.
In our earlier reports dealing with hypervalent iodine in
organic synthesis, it has been observed that alkyny-
l(phenyl)iodonium salts are highly reactive toward many
nucleophilic heteroatoms [3]. In addition, we have recently
developed a simple method for the synthesis of
selenoamides [4]. These facts prompted us to examine the
reaction of alkynyl(phenyl)iodonium salts with
selenoamides, Such a reaction would provide a new route
to selenazoles.
The reaction was found to be general and applicable to
alkylethynyl(phenyl)iodonium salts or phenylethnyl-
(phenyl)iodonium salt. Several arylselenoamides con-
taining various substituents, such as chloro, methyl,
methoxy and dimethylamino groups, were successfully
reacted.
A plausible mechanism for the formation of selenazoles
(3) is analogous to the synthesis of thiazoles from
alkynyliodonium salts and thioamides [5] and is shown in
Scheme 3. It involves the selenophilic attack of the iodo-
nium atom of alkynyl(phenyl)iodonium salts (1) on the
selenoamides (2) to form primary addition products (4)
followed by an unusual room temperature polyhetero-
Claisen rearrangement [6] and 1,1-elimination of iodoben-
zene to generate carbene (7), final cycloaromatization of
the resulting carbene to give selenazoles (3).
Herein we report our result, a new effective method for
the synthesis of selenazoles by cyclocondensation of
alkynyl(phenyl)iodonium salts with selenoamides. Under
reflux condition, simple stirring of the mixture of
alkynyl(phenyl)iodonium salts (1) with selenoamides (2)
in methanol under an atmosphere of dry nitrogen in the
presence of triethyl amine (Et N) gave, after workup and
3
isolation, the desired products, selenazoles (3) in good
yields as shown in Table I.
The products are characterized by microanalyses, H
1
NMR, IR and Mass-spectral data. The microanalyses and
proton NMR spectra are consistent with the proposed
structures. In the infrared there are two characteristic
In summary, a novel method for the synthesis of sele-
nazoles based on the cyclocondensation of alkynyl-
(phenyl)iodnium salts and selenoamides has been devel-
oped. The synthetic method is simple, mild and the
yields are high. Furthermore, the method now described
-1
intense absorptions centered around 1530-1460 cm and
-1
1410-1380 cm due to the selenazole ring. All mass

504
P.-F. Zhang and Z.-C. Chen
Vol. 38
uncorrected. Microanalyses were obtained using Carlo-Erba
1
1106. H Nmr spectra were obtained at 500MHz or 60MHz
(AVANCE DMX500 or JEOL PMX60 ) in dimethyl-d sulfox-
SI
6
ide (DMSO-d ) or deuteriochloroform (CDCl ) using TMS as
6
3
an interal standard. Ir spectra were recorded on a Perkin Elmer
683 spectrometer at room temperature. Mass spectra were
acquired under electron impact conditions with 70 eV ionizing
potential (HP5989B).
2,4-Diphenylselenazole (3a).
To a solution of Selenobenzamide (0.28 g, 2 mmol) in dry
methanol (5 ml) was added a solution of phenylethynyliodonium salt
(0.95 g, 2 mmol) and 1 ml Et N in dry methanol (5 ml) under a nitro-
3
gen atmosphere. The mixture was refluxed for 30 minutes and then
concentrated under reduced pressure. The residue was recrystallized
with ethanol (EtOH) to give pure 3a, 0.47 g (82% yield); white
can give a contribution to the growing applications of
selenazoles.
1
lamelae crystals, mp 97-99 (lit. [2d] 99 °C); H NMR (DMSO-d ): δ
6
13
8.69(s, 1H), 8.06-8.01(m, 5H), 7.53-7.35(m, 5H); C NMR
(DMSO-d ): δ 120.02, 125.60, 125.97, 127.16, 128.04, 128.55,
EXPERIMENTAL
General Procedures.
6
129.78, 134.12, 134.96, 154.84, 172.51; IR (KBr): ν 3100 (m) 1500
-1
+
(s) and 1380 (s) cm ; MS: 288(M , 5), 286(17), 284(9), 185(18),
183(100), 181(52), 103(70), 77(5), 76(27), 51(10). Compounds 3b-
3j were prepared following the same procedure as 3a.
All experiments were carried out under dry nitrogen using
standard Schlenk techniques. selenoamides were prepared
according to the literature [4a]. Methanol was distilled from
sodium metal (Na) prior to use. Melting points were determined
2-(2,4-Dichlorophenyl)-4-phenylselenazole (3b).
Compound 3b has mp. 103-105 °C; IR (KBr): ν 3120 (m), 1515
-1
1
(s), 1385 (s) cm ; H NMR (CDCl ): δ 8.42 (s, 1H), 7.79-7.90
on a X -Data microscopic melting point apparatus and are
3
4

Mar-Apr 2001
Hypervalent Iodine in Synthesis 50: A Novel Method of Synthesis of Selenazole
505
+
4-Methoxymethyl-2-(4-methylphenyl)selenazole (3i).
(m, 3H), 7.30-7.50 (m, 5H); MS: 355(M ,15), 353(25), 351(12),
184(6), 182(19), 180(9), 102(18), 77(31), 76(26), 51(14).
Anal. Calcd for C H Cl NSe: C, 51.01; H, 2.57; N, 3.92.
Compound 3i has mp 116-117 °C; IR (KBr): ν 3105 (m), 1570
-1
1
15
9
2
(s), 1460 (s) cm ; H NMR (CDCl ): δ 8.03 (s, 1H), 7.60-7.90
3
Found: C, 51.37; H, 2.89; N, 4.31.
(m, 2H), 7.20-7.40 (m, 2H), 4.25 (s, 2H), 3.40 (s, 3H), 2.40 (s,
+
3H); MS: 269(M ,15), 267(42), 265(22), 166(29), 164(100),
2-(p-N,N-Dimethylaminophenyl)-4-phenylselenazole (3c).
Compound 3c has mp. 94-96 °C; IR (KBr): ν 3100 (m), 2960
162(49), 84(43).
Anal. Calcd for C
H NOSe: C, 54.14; H, 4.92; N, 5.26.
12 13
-1
1
(s), 1460 (s), 1360 (s), 860 (s) cm ; H NMR (CDCl ): δ
3
Found: C, 54.51; H, 4.55; N, 4.61.
8.71(s,1H), 7.72-7.86 (m, 4H), 7.25-7.48 (m, 5H), 2.93 (s, 6H);
+
4-(n-Hexyl)-2-phenylselenazole (3j).
MS: 330(M ,32), 328(100), 326(48), 184(28), 182(83), 180(41),
102(88), 77(32), 76(13).
Compound 3j was obtained as a yellow Oil; IR: ν 3090 (m),
Anal. Calcd for C
H N Se: C, 62.39; H, 4.93; N, 8.56.
-1
1
17 16 2
1565 (s), 1405 (s) cm ; H NMR (CDCl ): δ 8.05 (s, 1H), 7.05-
3
Found: C, 62.78; H, 4.53; N, 8.92.
7.50 (m, 5H), 3.64 (t, 2H, J = 7.6 Hz), 2.44 (m, 2H), 1.10-1.32
+
(m, 6H), 0.90 (t, 3H, J = 8.0Hz); MS: 295(M ,4), 293(13),
2-(4-Chlorophenyl)-4-phenylselenazole (3d).
291(6), 192(33), 190(100), 188(52), 110(17), 39(41).
Compound 3d has mp. 106-108 °C (lit. [2d] 108 °C); IR (KBr):
ν 3090 (m), 1465 (s), 1375 (s), 870 (vs) cm ; H NMR (CDCl ):
δ 8.75 (s, 1H), 8.10-8.20 (m, 4H), 7.45-7.60 (m, 5H).
Anal. Calcd for C
H NSe: C, 61.64; H, 6.55; N, 4.79.
15 19
-1
1
3
Found: C, 62.02; H, 6.23; N, 4.43.
2-(4-Methylphenyl)-4-phenylselenazole (3e).
REFERENCES AND NOTES
Compound 3e has mp 134-136 °C (lit. [2d] 136 °C); IR (KBr):
-1
1
ν 3105 (m), 2990, 2940 (s), 1505 (s), 1400 (s) cm ; H NMR
[1a] A. Shafiee, A. Mazloumi and V. I. Cohen, J. Heterocyclic.
Chem., 16, 1563 (1979); [b] A. Shafiee, A. Shafaati and B. H.
Khamench, J. Heterocyclic Chem., 26, 709 (1989); [c] A. Shafiee, Z.
Khashayarmanesh and F. Kamal, J. Sci., Islamic Repub. Iran., 1, 111
(1990); [d] H. Maeda, N. Kambe, N. Sonoda, S. Fujiwara and T.
Shin-ike, Tetrahedron, 53,13667(1997).
[2a] G. Hofmann, Justus Liebigs Ann. Chem., 250, 294 (1889);
[b] French Patent 757767 (1934), Kodak-pathe; Chem. Abstr., 28,
3246 (1934); [c] Leslie G. S. Brooker and Frank L. White U.S. Patent
2005,411(1935); Chem. Abstr., 29, 5282 (1935); [d] V. I. Cohen,
Synthesis, 66 (1979); [e] R. M. Moriarty, B. K. Vaid, M. P. Duncan,
S. G. Levy, O. Prakash and S. Goyal, Synthesis, 845(1992).
[3a] Z.-D. Liu and Z.-C. Chen, Synth. Commun., 22, 1997
(1992); [b] Z.-D. Liu and Z.-C. Chen, J. Org. Chem., 58, 1924
(1993); [c] J.-L. Zhang, Z.-C. Chen, Synth. Commun., 27, 3881
(1997); [d] J.-L. Zhang and Z.-C. Chen, Synth. Commun., 27, 3757
(1997); [e] J.-L. Zhang, Z.-C. Chen, Synth. Commun., 28, 175
(1998).
(CDCl ): δ 8.60 (s, 1H), 7.91-8.00 (m, 4H), 7.21-7.39 (m, 5H),
3
2.35 (s, 3H).
2-(4-Methoxyphenyl)-4-phenylselenazole (3f).
Compound 3f has mp 103-105 °C (lit. [2d] 105 °C); IR (KBr):
-1
1
ν 3092 (m), 2980 (s), 1505 (s), 1365 (s) cm ; H NMR (CDCl ):
3
δ 8.48 (s, 1H), 7.83-7.92 (m, 2H), 7.00-7.42 (m, 2H), 6.96-7.03
(m, 5H), 3.80 (s, 3H).
4-Methoxymethyl-2-phenylselenazole (3g).
Compound 3g has mp 59-60 °C; IR (KBr): ν 3100 (m), 1585
-1
1
(s), 1460 (s) cm ; H NMR (CDCl ): δ 8.39 (s, 1H), 7.30-7.52
3
+
(m, 5H), 4.83 (s, 2H), 3.70 (s, 3H); MS: 255(M ,11), 253(33),
251(17), 152(30), 150(100), 148(51), 70(41).
Anal. Calcd for C
H NOSe: C, 52.39; H, 4.40; N, 5.55.
11 11
Found: C, 52.71; H, 4.69; N, 5.02.
2-(4-Chlorophenyl)-4-methoxymethylselenazole (3h).
Compound 3h has mp 79-80 °C; IR (KBr): ν 3100 (m), 1580 (s),
[4a] H.-R. Zhao, M.-D. Ruan, W.-Q. Fan and X.-J. Zhou.,
Synth. Commun., 24, 1761 (1994); [b] M.-D. Ruan, P.-F. Zhang, Y.
Tao and W.-Q. Fan, Synth. Commun., 26, 2617(1996).
-1
1
1450 (s) cm ; H NMR (CDCl ): δ 8.30 (s, 1H), 7.70-7.90 (m,
3
+
2H), 7.33-7.55 (m, 2H), 4.96 (s, 2H), 3.78 (s, 3H); MS: 289(M ,8),
[5] P. Wipf and S.Venkatraman, J. Org. Chem., 61, 8004
(1996).
287(26), 285(13), 152(30), 150(100), 148(49), 70(48).
Anal. Calcd for C H ClNOSe: C, 46.09; H, 3.52; N, 4.89.
11 10
[6] S. Blechert, Synthesis, 71 (1989).
Found: C, 46.43 H, 3.82; N, 4.53.