Synthesis of 1,3-selenazoles and bis(selenazoles) from primary selenocarboxylic amides and selenourea

Article abstract of DOI:10.1055/s-2004-822312

The reaction of nitriles with P₂Se₅ in the presence of EtOH-H₂O afforded primary selenocarboxylic amides. The cyclization of these compounds with α-halo ketones afforded a variety of functionalized 1,3-selenazoles. The use of P₂Se₅ also allowed the convenient synthesis of selenocarboxylic diamides which were transformed into bis(selenazol-2-yl)alkanes ('bis-selenazoles'). A practical method for the synthesis of selenourea was developed. This useful small building block was successfully applied to the synthesis of primary 2-amino-1,3- selenazoles.

Full text of DOI:10.1055/s-2004-822312

PAPER
875
Synthesis of 1,3-Selenazoles and Bis(selenazoles) from Primary Selenocar-
boxylic Amides and Selenourea
1
, 3-Selenazoles an
a
d Bis(selen
r
a
zoles)
f
l
rom Se
h
lenocarboxy
e
lic Amides
i
a
nd Se
n
lenourea z Geisler,* Wolf-Diethard Pfeiffer, Andreas Künzler, Harald Below, Ehrenfried Bulka, Peter Langer*
Institut für Chemie und Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Soldmannstr. 16, 17487 Greifswald, Germany
Fax +49(3834)864346; E-mail: peter.langer@uni-greifswald.de
Received 13 October 2003
more readily available in pure form and less prone to hy-
drolysis than Al2Se3.13 Herein, we report the application of
our methodology to the synthesis of a variety of 1,3-sel-
enazoles, bis(selenazol-2-yl)alkanes (‘bis-selenazoles’)
Abstract: The reaction of nitriles with P2Se5 in the presence of
EtOH–H2O afforded primary selenocarboxylic amides. The cy-
clization of these compounds with a-halo ketones afforded a variety
of functionalized 1,3-selenazoles. The use of P2Se5 also allowed the
convenient synthesis of selenocarboxylic diamides which were and 2-amino-1,3-selenazoles.14,15
transformed into bis(selenazol-2-yl)alkanes (‘bis-selenazoles’). A
practical method for the synthesis of selenourea was developed.
This useful small building block was successfully applied to the
synthesis of primary 2-amino-1,3-selenazoles.
Selenocarboxylic Amides and 1,3-Selenazoles
Key words: cyclizations, heterocycles, nitriles, selenium, amides
In our preliminary communication, we showed that pri-
mary selenocarboxylic amides can be prepared in good
yields by reaction of nitriles with P2Se5.11 Slow addition
of water to the reaction mixture resulted in formation of
small amounts of hydrogen selenide in situ which subse-
quently added to the nitrile (Scheme 1). The reaction of
Selenium represents an essential element for higher or-
ganisms.1 In this context, the selenium containing en-
zymes glutathioneperoxidase and 5¢-deiodase type 1 play
an important role. In fact, a number of diseases can result
from selenium deficiency.2,3 Therefore, selenium contain-
ing molecules are of considerable biochemical and phar-
macological relevance. A prominent example is the
antitumor and antiviral active C-glycosyl selenazole sel-
enazofurin.4 Unfortunately, selenium compounds are in
most cases less stable than the corresponding sulfur ana-
logues. In addition, the methods and conditions available
for the synthesis of sulfur compounds can often not be ap-
plied to selenium. Therefore, the development of new
methods for the synthesis of small selenium-containing
building blocks is of considerable current interest.
benzonitrile,
cyclohexylacetonitrile,
2-tolylnitrile,
MeCN, diphenylacetonitrile, and 1-naphthylacetonitrile
with P2Se5 afforded the selenocarboxylic amides 2a–f
(Scheme 1, Table 1) in good yields.
P2Se5
- P2O5
+ H2O
H2Se (in situ)
Se
R1
C
N
R1
NH2
2a-f
EtOH
1a-f
Scheme 1 Synthesis of selenocarboxylic amides by reaction of ni-
triles with P2Se5
In contrast to 1,3-thiazoles, there exist only limited meth-
ods for the synthesis of 1,3-selenazoles.5 Many syntheses
rely on the cyclization of primary selenoureas and seleno-
carboxylic amides. Selenocarboxylic amides have been
prepared by the use of H2Se, NaSeH6 (generated from
NaBH4–Se),6,7 tris(trimethylsilyl)monoselenophosphate8
or Al2Se3.9,10 However, there are a number of drawbacks
associated with these methods.11 Primary selenocarboxyl-
ic amides are not available to date by reaction of amides
with Woollins reagent.12
The cyclization of selenobenzoic amides 2a–f with phen-
acyl bromides 3a–e afforded the 1,3-selenazoles 4a–p in
34–98% yield (Scheme 2, Table 1). The regioselectivity
of cyclization is supported by analysis of the 2J (SeH) cou-
pling constants for the hydrogen atoms 5-H and by com-
parison with known selenazole syntheses.5,6 The yields
are generally lower for cyclizations of aliphatic than for
aromatic substrates.
We have recently reported a new and convenient method
for the synthesis of primary selenocarboxylic amides by
reaction of nitriles with P2Se5 in the presence of EtOH–
H2O.11 From a preparative viewpoint, the use of P2Se5 is
more convenient and reliable than the use of Al2Se3 and is
less toxic than CO, NaSeH or H2Se. In addition, P2Se5 is
O
Br
R2
R3
R3
Se
Se
3a-e
R2
R1
R1
2a-f
NH2
N
EtOH, reflux
4a-p
SYNTHESIS 2004, No. 6, pp 0875–0884
Advanced online publication: 15.03.2004
x
x
.
x
x
.2
0
0
4
Scheme 2 Synthesis of 1,3-selenazoles 4a–p
DOI: 10.1055/s-2004-822312; Art ID: T10803SS.pdf
© Georg Thieme Verlag Stuttgart · New York

876
K. Geisler et al.
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Table 1 Yields of 1,3-Selenazoles 4a–p
2
a
4
a
b
c
d
e
f
R1
R2
R3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
H
Mp (°C)
99–100
122–123
134–135
135–136
36–37
Yield 4 (%)a
Ph
Ph
8716
86
Ph
4-MeC6H4
4-BrC6H4
4-(O2N)C6H4
Ph
Ph
9816
9816
44
Ph
b
c-Hex
c-Hex
c-Hex
c-Hex
Me
4-MeC6H4
4-BrC6H4
4-(O2N)C6H4
4-MeC6H4
4-(O2N)C6H4
4-BrC6H4
Et
53–54
49
g
h
i
77–78
54
86–88
45
c
d
e
92–95
42
j
Me
136–137
95–96
45
k
l
2-MeC6H4
2-MeC6H4
Ph2CH
Ph2CH
Ph2CH
2-Naphthyl
95
125/0.02 Torrb
148–149
187–188
106–107
117–120
34
m
n
o
p
Ph
96
4-(O2N)C6H4
Ph
98
7217
73
f
4-BrC6H4
a Isolated yields.
b Boiling point.
(Scheme 4). The reaction of P2Se5 with 1,2-dicyanoethane
Bis-selenazoles
(8b) and 1,4-dicyanobutane (8c) gave selenosuccinic di-
The reaction of a-cyanoacetic amide (5) with P2Se5 (1 amide (9b) and selenoadipic diamide (9c), respectively.
equiv) afforded the novel monoselenomalonic diamide 6 The cyclization of 9b and 9c with phenacyl bromide af-
(Scheme 3). The nitrile was chemoselectively attacked in forded the bis-selenazoles 10b and 10c, respectively.
the presence of the amide moiety. The reaction of 6 with
Se Se
P2Se5
phenacyl bromide (2 equiv) resulted in formation of prod-
uct 7 containing an oxazole and a selenazole moiety.
NC
CN
n
H2N
NH2
EtOH, H2O
n
8a-c
9a-c
O
O
O
Se
P2Se5
CN
O
H2N
H2N
NH2
EtOH, H2O
Br
6
Ph
5
Se
Se
EtOH, reflux
(13 - 57%)
Ph
Ph
N
N
n
Br
(n = 1, 2, 4)
10a-c
Ph
Se
O
EtOH, reflux
Scheme 4 Synthesis of bis(selenazol-2-yl)alkanes 10
Ph
N
Ph
N
7 (48%)
2-Aminoselenazoles
Scheme 3 Synthesis of 1,3-selenazole 7
The synthesis of primary 2-aminoselenazoles from sele-
nourea (12) was studied next (Scheme 5). Known meth-
ods for the synthesis of 12 require the generation and
handling of the highly toxic gaseous hydrogen selenide
(H2Se).18 Therefore, our first goal was the development of
a more convenient approach to this useful small molecule.
The reaction of P2Se5 with cyanamide afforded, after op-
The synthesis of non-annulated bis(selenazol-2-yl)al-
kanes (‘bis-selenazoles’) has, to the best of our know-
ledge, not yet been reported. The reaction of malonic
dinitrile (8a) with P2Se5 (2 equiv) afforded the novel sele-
nomalonic diamide (9a). The double cyclization of 9a
with phenacyl bromide gave the bis-selenazole 10a
Synthesis 2004, No. 6, 875–884 © Thieme Stuttgart · New York

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1,3-Selenazoles and Bis(selenazoles) from Selenocarboxylic Amides and Selenourea
877
timization of the conditions (see experimental section), Product 16 resides in the form of the iminoselenazolidine
the desired unstable product in acceptable yield. The cy- rather than the aminoselenazole tautomer (Scheme 6).
clization of 12 with a-bromo ketones 3 afforded the de- However, both tautomers A and B are possible for the imi-
sired primary 2-aminoselenazoles 13 in 68–94% yield noselenazolidine. The tautomerism of the corresponding
(Method A, Table 2). A second strategy for the synthesis sulfur analog was studied in detail by Hartmann.21
of 2-aminoselenazoles has been previously reported by
Heimgartner and others.19 We have adopted this ap-
Se
NH
HCl
proach, which does not require the use of 12, to the syn-
thesis of 2-aminoselenazoles 13 (Method B). The stable
benzoylselenourea (14) was prepared according to
Douglass20 by reaction of an acetone solution of potassi-
um selenocyanate with benzoyl chloride and subsequent
addition of ammonia.19 The cyclization of 14 with 3 af-
forded the protected 2-aminoselenazoles 15 which were
subsequently deprotected by treatment with phosphoric or
sulfuric acid. The two-step transformations of 14 into 13
were carried out in very good overall yields (except for the
synthesis of 13b).
H2N
N
.
.
A
Cl
CN
Se
Se
H2N
NH2
EtOH, reflux
NH2
HCl
HN
N
12
B
16
Scheme 6 Cyclization of selenourea with chloroacetonitrile
The cyclization of selenosemicarbazide (17)22 with desyl
bromide afforded the novel 2-hydrazinoselenazole 18
(Scheme 7). This compound represents a useful building
block for the synthesis of other selenazoles, such as pyra-
zole-substituted 1,3-selenazoles. The formation of a
1,2,4-selenadiazine isomer was excluded by comparison
of 18 with an authentic sample of the latter.
The reaction of selenourea with chloroacetonitrile afford-
ed the selenazolidine 16. The latter was formed by attack
of the selenium atom onto the chloride and subsequent cy-
clization by attack of the nitrogen atom onto the nitrile.
Se
P2Se5
H2N CN
H2N
NH2
O
EtOH, H2O
Method A
11
Br
12 (37%)
Ph
Ph
Se
NH2
Se
O
Ph
H2N
H2N
R2
Ph
N
N
R1
H
EtOH
Reflux
N
H
EtOH, reflux
Br
17
18
3
R2
R1
Scheme 7 Cyclization of selenosemicarbazide with desyl bromide
Se
O
H2N
N
Ph
Cl
CAUTION: Toxic hydrogen selenide is generated in small quanti-
ties during the reaction of P2Se5 with nitriles and water or during the
hydrolysis of P2Se5 in air.
13a-e
KSeCN
NH3
acid
P2Se5
Method B
R2
A mixture of red phosphorus (20 mmol) and grey selenium powder
(50 mmol) was heated in a tube with a small Bunsen burner flame
until the reaction was complete. The reaction mixture was ground
and powdered to give P2Se5 as a grey solid. The reagent was stored
under inert atmosphere and was prepared freshly for all applica-
tions. The product is slowly hydrolyzed, if exposed to the air.
O
O
Se
NH2
3
Se
Ph
R1
Ph
N
H
N
N
EtOH
Reflux
H
14
15a-e
Scheme 5 Synthesis of 2-aminoselenazoles 13
Table 2 Yields of 2-Aminoselenazoles 13
Selenobenzoic Amide (2a)
To a refluxing EtOH solution (30 mL) of benzonitrile (5.15 g, 50.0
mmol) and freshly prepared P2Se5 (9.12 g, 20.0 mmol) was added
dropwise H2O (6 mL) over 2 h. After cooling, the solution was fil-
tered and H2O was added to the filtrate, which resulted in formation
of a precipitate. The latter was filtered off and recrystallized (C6H6–
petroleum ether) to give 2a.
13 R1
R2
Mp (°C)
Yield (%) Yield (%)
(A)a
(B)b
a
b
c
Ph
H
H
H
H
Ph
131–132
168
87
99 + 84 (83)
88 + 51 (45)
96 + 91 (87)
88 + 99 (87)
90 + 95 (86)
4-MeC6H4
4-BrC6H4
4-(O2N)C6H4
Ph
84
Yield: 7.73 g (84%); golden needles; mp 125.5–126 °C.
IR (KBr): 667 (m), 687 (m) 835 (m), 1260 (m), 1309 (m), 1320 (w),
1415 (m), 1628 (s) cm–1.
175
94
d
e
250
91
Anal. Calcd for C7H7NSe (184.10): C, 45.67; H, 3.83; N, 7.60.
Found: C, 45.80; H, 3.82; N, 7.50.
199–201
68
a Yields for method A.
Cyclohexaneselenocarboxylic Amide (2b)
Cyclohexanecarbonitrile (5.45 g, 50.0 mmol) was dissolved in a
mixture of EtOH (20 mL) and H2O (3 mL). To the refluxing solu-
b Yields for method B: yield of 15 + 13 (in brackets: yields over two
steps, 14 → 13).
Synthesis 2004, No. 6, 875–884 © Thieme Stuttgart · New York

878
K. Geisler et al.
PAPER
tion was added freshly prepared P2Se5 (9.12 g, 20.0 mmol) in small
portions over 2 h. The solution was cooled and filtered. H2O (20
mL) was added to the filtrate, which resulted in formation of a pre-
cipitate. The mixture was extracted with benzene. The combined or-
ganic layers were dried (Na2SO4), filtered and concentrated.
Addition of petroleum ether resulted in crystallization of the prod-
uct. The crude product was dried (desiccator, P2O5) and recrystal-
lized (C6H6–petroleum ether) to give 2b.
H2O (3 mL) was added dropwise to the refluxing solution within 3.5
h. The solution was concentrated in vacuo. After cooling to 20 °C,
a crystalline precipitate formed which was filtered off and recrystal-
lized (EtOH) to give 2f.
Yield: 2.66 g (35%); as yellow prisms; mp 130–132 °C.
IR (KBr): 791 (s), 891 (m), 1065 (w), 1265 (m) 1304 (m), 1355 (m),
1401 (m), 1445 (s), 1635 (s), 3116 (m) cm–1.
Anal. Calcd for C11H9NSe (234.16): C, 56.42; H, 3.87; N, 5.98.
Found: C, 56.40; H, 3.90; N, 5.80.
Yield: 2.50 g (26%); colorless needles; mp 130–133 °C.
IR (KBr): 780 (m), 900 (w), 965 (s), 1150 (w), 1235 (w), 1291 (s),
1365 (m), 1415 (m), 1475 (s), 1650 (s), 2940 s) cm–1.
2,5-Diphenyl-1,3-selenazole (4a)
Anal. Calcd for C7H13NSe (190.15): C, 44.22; H, 6.89; N, 7.37.
Found: C, 44.14; H, 6.74; N, 7.67.
An EtOH solution (20 mL) of selenobenzoic amide (1.84 g, 10.0
mmol) and phenacyl bromide (1.99 g, 10.0 mmol) was stirred for 10
min, which resulted in an increase of the temperature. After cooling,
the mixture was poured into H2O (20 mL), which resulted in the for-
mation of a precipitate. This was filtered off and recrystallized
(EtOH) to give 4a.
2-Methylselenobenzoic Amide (2c)
This compound was obtained by reaction of 2-methylbenzonitrile
(11.8 g, 100.0 mmol) with freshly prepared P2Se5 (9.12 g, 20.0
mmol) as described for 2a.
Yield: 2.47 g (87%); colorless lamella; mp 99 °C.
Yield: 5.94 g (30%); yellow needles (C6H6–petroleum ether); mp
109–111 °C.
IR (KBr): 686 (m) 730 (s), 758 (s), 835 (w), 868 (w), 919 (w), 952
(s), 999 (w), 1027 (m), 1043 (s), 1071 (m), 1152 (m), 1279 (m),
1442 (s), 1481 (s), 1509 (w), 1579 (w), 1598 (w), 3114 (m) cm–1.
IR (KBr): 660 (m), 728 (m), 855 (m), 1045 (w), 1130 (w), 1155 (w),
1230 (w), 1265 (w), 1290 (m), 1420 (s), 1620 (s) cm–1.
1H NMR (C6D6, 300 MHz): d = 2.15 (s, 3 H, CH3), 5.90 (br, 1 H,
NH), 6.78–7.22 (m, 4 H, Ar), 8.20 (br, 1 H, NH).
13C NMR (C6D6, 75 MHz): d = 19.67 (CH3), 125.67, 125.68,
126.22, 126.24, 128.99, 130.70 (Ar), 210.46 (C=Se).
1H NMR (CDCl3, 300 MHz): d = 7.38–8.01 (m, 10 H, ArH), 8.06
[s, 1 H, Hetar, 2J (SeH) = 58.3 Hz].
13C NMR (CDCl3, 75 MHz): d = 118.26 (C-5), 126.72 (Ar), 127.08
(Ar), 127.91 (Ar), 128.70 (Ar), 128.97 (Ar), 130.21 (Ar), 135.42
(Ar), 136.41 (Ar), 156.93 (C-4), 173.87 (C-2).
MS (EI, 70 eV): m/z (%) = 199 (100, M+).
77Se NMR (CDCl3, Me2Se): d = 712.69.
Anal. Calcd for C8H9NSe (198.13): C, 48.50; H, 4.58; N, 7.07, Se,
38.86. Found: C, 48.50; H, 4.30; N, 7.10; Se, 39.50.
MS (70 eV): m/z (%) = 285 (M+, 59), 182 (100), 103 (16), 102 (86),
89 (8), 77 (13), 51 (8), 28 (16).
Anal. Calcd for C15H11NSe (284.22): C, 63.39; H, 3.90; N, 4.93.
Found: C, 63.45; H, 3.92; N, 4.91.
Selenoacetic Amide (2d)
To freshly prepared P2Se5 (36.48 g, 80.0 mmol) was added dropwise
MeCN (8.20 g, 200.0 mmol). Subsequently, H2O (10 mL) was add-
ed dropwise over 5 h at 80 °C. After cooling, the solution was fil-
tered and H2O (20 mL) was added to the filtrate. The aq layer was
extracted with benzene. The combined organic layers were dried
(Na2SO4), filtered and concentrated. The product crystallized upon
cooling (ice) to give 2d.
2-Phenyl-4-tolyl-1,3-selenazole (4b)
This compound was obtained by reaction of selenobenzoic amide
(1.84 g, 10.0 mmol) with 4-methylphenacyl bromide (2.13 g, 10.0
mmol) in EtOH (20 mL) following the procedure as described for
4a.
Yield: 2.56 g (86%); colorless needles (EtOH); mp 122–123 °C.
Yield: 12.15 g (50%); colorless prisms (C6H6); mp 125–126 °C.
IR (KBr): 691 (s), 742 (s), 822 (s), 952 (s), 1040 (s), 1226 (m), 1272
(w), 1294 (w), 1441 (m), 1480 (s), 1511 (m), 3106 (m) cm–1.
IR (KBr): 640 (s), 730 (w), 770 (m), 1040 (m), 1290 (s), 1365 (m),
1415 (s), 1485 (s), 1660 (s) cm–1.
1H NMR (CDCl3, 300 MHz): d = 2.38 (s, 3 H, Me), 7.22–7.99 (m,
Anal. Calcd for C2H5NSe (122.03): C, 19.69; H, 4.13; N, 11.48.
Found: C, 19.50; H, 4.20; N, 11.40.
9 H, ArH), 8.02 [s, 1 H, Hetar, 2J (SeH) = 48.60 Hz].
13C NMR (CDCl3, 75 MHz): d = 21.27 (Me), 117.42 (C-5), 126.59
(Ar), 127.05 (Ar), 128.93 (Ar), 129.36 (Ar), 130.11 (Ar), 132.73
(Ar), 136.46 (Ar), 137.66 (Ar), 156.97 (C-4), 173.67 {C-2, 1J [(C-
2)Se] = 130.3 Hz}.
77Se NMR (CDCl3, Me2Se): d = 709.64.
MS (70 eV): m/z (%) = 299 (M+, 79), 297 (40), 196 (100), 194 (56),
Diphenylselenoacetamide (2e)
Diphenylacetonitrile (4.83 g, 25.0 mmol) was dissolved in EtOH
(80 mL). To the refluxing solution was added freshly prepared
P2Se5 (13.7 g, 30.0 mmol) and H2O (4.5 mL) in small portions over
24 h. The solution was cooled, filtered and H2O was added to the fil-
trate. The mixture was extracted with Et2O. The combined organic
layers were dried (Na2SO4), filtered and the filtrate was concentrat-
ed. The product crystallized to give 2e.
116 (44), 115 (90), 89 (13), 78 (13), 77 (12), 51 (9), 28 (6).
Anal. Calcd for C16H13NSe (298.25): C, 64.44; H, 4.39; N, 4.70.
Found: C, 64.41; H, 4.31; N, 4.69.
Yield: 5.50 g (81%); yellow prisms (C6H6–petroleum ether); mp
148.5–150 °C.
2-Phenyl-4-(4-bromophenyl)-1,3-selenazole (4c)
This compound was obtained by reaction of selenobenzoic amide
(1.84 g, 10.0 mmol) with 4-bromophenacyl bromide (2.76 g, 10.0
mmol) in EtOH (20 mL) following the procedure as described for
4a.
IR (KBr): 612 (m), 700 (s), 835 (m), 1180 (m), 1200 (m), 1295 (s),
1420 (m), 1450 (m), 1620 (s) cm–1.
Anal. Calcd for C14H13NSe (274.23): C, 61.32; H, 4.78; N, 5.11.
Found: C, 61.30; H, 4.90; N, 5.05.
Yield: 3.56 g (98%); colorless needles (EtOH); mp 134–135 °C.
Naphth-1-yl-selenocarboxylic Amide (2f)
An EtOH solution (50 mL) of 1-naphthylacetonitrile (5.0 g, 13.0
mmol) and freshly prepared P2Se5 (5.96 g, 13.0 mmol) was refluxed.
IR (KBr): 667 (m), 765 (s), 833 (m), 1006 (m), 1037 (w), 1071 (w),
1224 (w), 1478 (s), 1506 (m), 1634 (m), 3050 (m), 3108 (m) cm–1.
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1,3-Selenazoles and Bis(selenazoles) from Selenocarboxylic Amides and Selenourea
879
1H NMR (CDCl3, 300 MHz): d = 7.87–8.01 (m, 9 H, ArH), 8.05 [s,
1 H, Hetar, 2J (SeH) = 48.5 Hz].
MS (EI, 70 eV): m/z (%) = 362/364 (M+, 40), 314/316 (48), 301/303
(100), 260/262 (44), 207 (8), 180/182 (48), 101 (40), 89 (30), 55
(14), 41 (18).
IR (KBr): 820 (s), 870 (w), 895 (s), 990 (m), 1030 (w), 1120 (w),
1160 (m), 1180 (w), 1300 (m), 1370 (w), 1445 (m), 1515 (s), 2940
(m), 3030 (w), 3120 (w) cm–1.
1H NMR (CDCl3, 200 MHz): d = 1.23–2.28 (m, 8 H, CH2-cyclohex-
yl), 2.34 (s, 3 H Me), 2.93 (m, 1 H, CH-cyclohexyl), 3.41–3.49 (m,
1 H, CH-cyclohexyl), 7.13–7.76 (m, 4 H, ArH), 7.89 (s, 1 H, 5-H-
Hetar).
13C NMR (CDCl3, 50 MHz): d = 21.24 (Me), 25.85 (CH2-cyclohex-
yl), 115.99 (C-5), 126.50 (CH, Ar), 129.29 (CH, Ar), 133.0 (Ar),
137.32 (Ar), 155 (C-4), 184.04 (C-2).
Anal. Calcd for C15H10NBrSe (363.12): C, 49.62; H, 2.78; N, 3.85.
Found: C, 49.10; H, 2.90; N, 3.79.
2-Phenyl-4-(4-nitrophenyl)-1,3-selenazole (4d)
This compound was obtained by reaction of selenobenzoic amide
(1.84 g, 10.0 mmol) with 4-nitrophenacyl bromide (2.44 g, 10.0
mmol) in EtOH (20 mL) following the procedure as described for
4a.
MS (EI, 70 eV): m/z (%) = 305 (M+, 60), 250 (54), 237 (94), 196
(64), 114 (100), 91 (15), 55 (20), 41 (23), 28 (15).
Anal. Calcd for C16H19NSe (304.29): C, 63.15; H, 6.29; N, 4.60.
Found: C, 63.20; H, 6.30; N, 4.34.
Yield: 3.24 g (98%); yellow prisms (EtOH); mp 135.5–136.5 °C.
IR (KBr): 735 (m), 757 (s), 766 (m), 847 (s), 860 (m), 956 (m), 1046
(m), 1243 (m), 1284 (m), 1336 (s), 1445 (m), 1480 (s), 1519 (s),
1592 (s), 1502 (s), 3107 (m) cm–1.
2-Cyclohexyl-4-(4¢-bromophenyl)-1,3-selenazole (4g)
This compound was obtained by reaction of cyclohexaneselenocar-
boxylic amide (1.90 g, 10.0 mmol) and 4-bromophenacyl bromide
(2.76 g, 10.0 mmol) in EtOH (150 mL) following the procedure as
described for 4e.
1H NMR (CDCl3, 300 MHz): d = 7.43–8.30 (m, 9 H, ArH), 8.32 [s,
1 H, 5-H, 2J (SeH) = 43.1 Hz].
13C NMR (CDCl3, 75 MHz): d = 122.06 (C-2), 124.18 (CH, Ar),
127.16 (CH, Ar), 127.21 (CH, Ar), 129.14 (CH, Ar), 130.74 (CH,
Ar), 135.87 (Ar), 141.13 (Ar), 147.06 (Ar), 154.58 (C-4), 174.87
(C-2).
77Se NMR (CDCl3, Me2Se): d = 730.16.
MS (EI, 70 eV): m/z (%) = 329 (M+, 100), 328 (48), 300 (2), 257 (2),
227 (80), 197 (30), 181 (32), 169 (17), 117 (16), 103 (12), 89 (95),
77 (26).
Yield: 1.99 g (54%); colorless needles (EtOH); mp 77–78 °C.
IR (KBr): 850 (m), 895 (w), 1010 (w), 1045 (w), 1080 (w), 1170
(w), 1190 (w), 1300 (w), 1401 (w), 1470 (m), 1515 (m), 2380 (m),
2960 (m) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.22–1.55 (m, 4 H, CH2-cyclohex-
yl), 1.84–2.20 (m, 4 H, CH2-cyclohexyl), 2.97–3.05 (m, 1 H, CH-
cyclohexyl), 3.68–3.75 (m, 1 H, CH-cyclohexyl), 7.48–7.79 (m, 4
H, ArH), 7.97 [s, 1 H, 5-H, 2J (SeH) = 47.10 Hz].
13C NMR (CDCl3, 75 MHz): d = 18.44 (CH2), 25.84 (CH2), 26.9
(CH2), 34.48 (CH2), 45.85 (CH), 117.37 (C-5), 121.58 (CH, Ar),
128.20 (CH, Ar), 131.72 (CH, Ar), 134.64 (Ar), 154.01 (C-4),
184.58 (C-2).
Anal. Calcd for C15H10N2O2Se (329.15): C, 54.73; H, 3.06; N, 8.51.
Found: C, 54.40; H, 3.20; N, 8.49.
2-Cyclohexyl-4-phenyl-1,3-selenazole (4e)
A mixture of cyclohexaneselenocarboxylic amide (1.90 g, 10.0
mmol) and phenacyl bromide (1.99 g, 10.0 mmol) in EtOH (28 mL)
was stirred for 10 min and subsequently briefly refluxed. After cool-
ing to 20 °C, selenium was filtered off. The mixture was poured into
H2O (50 mL). The precipitated product was filtered off and recrys-
tallized from EtOH to give 4e.
77Se NMR (CDCl3, Me2Se): d = 719.88.
MS (70 eV): m/z (%) = 369 (M+, 46), 316 (39), 303 (80), 301 (100),
299 (43), 262 (35), 260 (44), 182 (41), 101 (32), 55 (31), 41 (39), 28
(13).
Anal. Calcd for C15H16NBrSe (369.16): C, 48.80; H, 4.37; N, 3.79.
Found: C, 48.62; H, 4.41; N, 3.74.
Yield: 1.28 g (44%); colorless prisms; mp 36–37 °C.
IR (KBr): 820 (s), 870 (w), 900 (m), 1030 (m), 1350 (m), 1515 (s),
2945 (m), 3030 (w), 3120 (w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.31–3.07 (m, 10 H, cyclohexyl),
2.97 (s, 1 H, CH-cyclohexyl), 7.36–7.89 (m, 5 H, ArH), 7.96 [s, 1
H, 5-H, 2J (SeH) = 51.70 Hz].
13C NMR (CDCl3, 75 MHz): d = 25.85 (CH2-cyclohexyl), 26.00
(CH2-cyclohexyl), 34.49 (CH2-cyclohexyl), 45.85 (CH-cyclohex-
yl), 116.85 (C-5), 126.63 (Ar), 127.58 (Ar), 128.62 (Ar), 135.71
(Ar), 155.15 (C-4), 184.21 (C-2).
77Se NMR (CDCl3, MeSe): d = 713.5.
MS (70 eV): m/z (%) = 291 (M+, 71), 290 (37), 262 (12), 237 (81),
223 (100), 221 (74), 102 (97), 90 (10), 77 (10), 55 (10), 51 (8), 41
(17), 28 (12).
2-Cyclohexyl-4-(4¢-nitrophenyl)-1,3-selenazole (4h)
This compound was obtained by reaction of cyclohexaneselenocar-
boxylic amide (1.90 g, 10.0 mmol) and 4-nitrophenacyl bromide
(2.44 g, 10.0 mmol) in EtOH (125 mL) following the procedure as
described for 4e.
Yield: 1.58 g (45%); orange needles (EtOH); mp 86–88 °C.
IR (KBr): 870 (m), 897 (w), 1001 (w), 1030 (w), 1115 (m), 1160
(w), 1200 (w), 1345 (s), 1470 (s), 1515 (s), 1608 (s), 2870 (m), 2945
(m), 3120 (w) cm–1.
1H NMR (DMSO-d6, 300 MHz): d = 1.16–2.26 (m, 9 H, CH2-cyclo-
hexyl), 2.98 (m, 1 H, CH-cyclohexyl), 7.54–7.86 (m, 4 H, ArH),
8.54 (s, 1 H, 5-H).
MS (EI, 70 eV): m/z (%) = 336 (M+, 50), 734 (16), 285 (76), 273
(100), 231 (23), 181 (20), 169 (8), 89 (43), 41 (20), 28 (5).
Anal. Calcd for C15H18NBrSe (290.27): C, 48.51; H, 4.82; N, 4.82.
Found: C, 48.62; H, 4.71; N, 4.49.
Anal. Calcd for C15H16N2O2Se (335.25): C, 53.74; H, 4.81; N, 8.36.
Found: C, 54.08; H, 4.81; N, 8.66.
2-Cyclohexyl-4-tolyl-1,3-selenazole (4f)
This compound was obtained by reaction of cyclohexaneselenocar-
boxylic amide (1.90 g, 10.0 mmol) with 4-methylphenacyl bromide
(2.13 g, 10.0 mmol) in EtOH (50 mL) following the procedure as
described for 4e.
2-Methyl-4-(4¢-tolyl)-1,3-selenazole (4i)
A mixture of selenoacetic amide (1.22 g, 10.0 mmol) and 4-meth-
ylphenacyl bromide (2.13 g, 10.0 mmol) in EtOH (30 mL) and py-
ridine (0.79 g, 10.0 mmol) was stirred at 20 °C for 10 min. A
colorless precipitate of pyridine hydrobromide was filtered off and
Yield: 1.49 g (49%); colorless needles (EtOH–H2O); mp 53–54 °C.
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K. Geisler et al.
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Yield: 3.60 g (96%); yellow rods (EtOH); mp 148–149 °C.
the filtrate was concentrated. After cooling (0 °C), a crystalline pre-
cipitate was formed. Recrystallization (EtOH) of which gave 4i.
1H NMR (CDCl3, 100 MHz): d = 4.57 (s, 1 H, CH), 7.08–7.99 (m,
15 H, Ar, 5-H).
Yield: 0.99 g (42%); colorless prisms; mp 92–95 °C.
1H NMR (CDCl3, 100 MHz): d = 2.35 (s, 3 H, Me-Tol), 2.77 (s, 3
MS (EI, 70 eV): m/z (%) = 374 (M+, 100).
H, 2-Me), 7.08–7.80 (m, 5 H, Ar, 5-H).
Anal. Calcd for C22H17NSe (374.35): C, 70.58; H, 4.58; N, 3.74.
Found: C, 70.0; H, 4.40; N, 3.67.
MS (EI, 70 eV): m/z (%) = 236 (M+, 100).
Anal. Calcd for C11H11NSe (236.18): C, 55.94; N, 4.69; N, 5.93.
Found: C, 55.98; H, 4.81; N, 5.86.
2-Benzhydryl-4-(4¢-nitrophenyl)-1,3-selenazole (4n)
This compound was obtained by reaction of diphenylselenoacetic
amide (2.74 g, 10.0 mmol) and 4-nitrophenacyl bromide (2.44 g,
10.0 mmol) in EtOH (30 mL) following the procedure as described
for 4a.
2-Methyl-4-(4¢-nitrophenyl)-1,3-selenazole (4j)
This compound was obtained by reaction of selenoacetic amide
(1.22 g, 10.0 mmol) with 4-nitrophenacyl bromide (2.44 g, 10.0
mmol) in EtOH (20 mL) following the procedure as described for
4a.
Yield: 4.10 g (98%); light yellow prisms (EtOH–DMF, 2:1); mp
187–188 °C.
Yield: 1.20 g (45%); yellow needles (EtOH); mp 136–137 °C.
1H NMR (CDCl3, 100 MHz): d = 5.82 (s, 1 H, CH), 7.10–8.38 (m,
14 H, ArH), 8.39 (s, 1 H, 5-H, Hetar).
IR (KBr): 741 (s), 851 (s), 1108 (s), 1319 (m), 1339 (s), 1503 (s),
1529 (m), 3115 (m) cm–1.
MS (EI, 70 eV): m/z (%) = 420 (M+, 100).
1H NMR (CDCl3, 300 MHz): d = 2.83 (s, 3 H, Me), 8.03–8.28 (m,
Anal. Calcd for C22H16N2Se (419.35): C, 63.02; H, 3.85; N, 6.68.
Found: C, 63.04; H, 4.00; N, 6.64.
4 H, ArH) 8.21 [s, 1 H, 5-H, 2J (SeH) = 45.90 Hz].
13C NMR (CDCl3, 75 MHz): d = 23.32 (Me), 122.32 (C-5), 124.19
(CH, Ar), 127.12 (CH, Ar), 141.16 (Ar), 146.96 (Ar), 153.21 (C-4),
172.82 (C-2).
77Se NMR (CDCl3, Me2Se): d = 767.07.
2-Benzhydryl-4,5-diphenyl-1,3-selenazole (4o)
This compound was obtained by reaction of diphenylselenoacetic
amide (2.74 g, 10.0 mmol) with desyl bromide (2.75 g, 10.0 mmol)
in EtOH (30 mL) following the procedure as described for 4a.
MS (EI, 70 eV): m/z (%) = 268 (M+, 100), 266 (49), 227 (80), 197
(30), 181 (34), 169 (18), 101 (14), 89 (96), 76 (28), 64 (17), 51 (15),
28 (7).
Yield: 3.24 g (72%); colorless needles (EtOH–DMF, 2:1); mp
106.5–107 °C.
1H NMR (CDCl3, 100 MHz): d = 5.77 (s, 1 H, CH), 7.12–7.54 (m,
20 H, ArH).
Anal. Calcd for C10H8N2O2Se (267.15): C, 44.96; H, 3.02; N, 10.49.
Found: C, 44.79; H, 3.08; N, 10.51.
MS (EI, 70 eV): m/z (%) = 450 (M+, 100).
2-(2¢-Methylpheny)-4-(4¢-bromophenyl)-1,3-selenazole (4k)
This compound was obtained by reaction of 2-methylselenobenzoic
amide (1.98 g, 10.0 mmol) and 4-bromophenacyl bromide (2.76 g,
10.0 mmol) in EtOH (50 mL) following the procedure as described
for 4a.
Anal. Calcd for C28H21NSe (450.45): C, 74.66; H, 4.70; N, 3.11.
Found: C, 74.74; H, 4.80; N, 3.03.
2-(Naphth-1¢-yl)-4-(4¢-bromophenyl-1,3-selenazole (4p)
This compound was obtained by reaction of 1-naphthylselenocar-
boxylic amide (0.234 g, 1.0 mmol) and 4-bromophenacyl bromide
(0.27 g, 1.0 mmol) in EtOH (20 mL) as described for 4a.
Yield: 3.60 g (95%); colorless prisms (EtOH–H2O); mp 95–96 °C.
1H NMR (CDCl3, 100 MHz): d = 2.64 (s, 3 H, Me), 6.96–8.18 (m,
8 H, ArH), 8.19 (s, 1 H, 5-H, Hetar).
Yield: 0.30 g (73%); colorless prisms (EtOH); mp 117–120 °C.
IR (KBr): 791 (s), 811 (m), 912 (s), 1005 (m), 1090 (s),1192 (m),
1235 (s) 1354 (w), 1415 (m), 1525 (s), 1615 (s), 3116 (m) cm–1.
MS (EI, 70 eV): m/z (%) = 378 (M+, 100).
Anal. Calcd for C16H12NBrSe (377.15): C, 50.96; H, 3.21; N, 3.71.
Found: C, 50.90; H, 3.40; N, 3.39.
1H NMR (CDCl3, 200 MHz): d = 2.38 (s, 3 H, Me), 7.51–8.05 (m,
11 H, Ar) 8.22 [s, 1 H, Hetar, 2J (SeH) = 48.0 Hz].
2-(2¢-Methylphenyl)-4-ethyl-1,3-selenazole (4l)
13C NMR (CDCl3, 50 MHz): d = 120.03 (C-5), 121.85 (Ar), 125.08
(CH-Ar), 125.90 (CH-Ar), 126.46 (CH-Ar) 127.46 (CH-Ar),
128.28 (CH-Ar), 129.07 (CH-Ar), 129.74 (Ar), 130.59 CH-(Ar),
131.85 (CH-Ar), 133.28 (Ar), 134.09 (Ar), 134.35 (Ar), 155.63 (C-
4, Hetar), 173.68 (C-2, Hetar).
This compound was obtained by reaction of 2-methylselenobenzoic
amide (2.97 g, 15.0 mmol) and 1-chlorobutan-2-one (1.60 g, 15.0
mmol) in EtOH (20 mL) following the procedure as described for
4a. The product was dissolved in H2O and filtered. Addition of NH3
resulted in separation of a yellow oil which was distilled in vacuo
(124–125 °C/0.02 torr).
Anal. Calcd for C16H13NSe (413.18): C, 55.23; H, 2.93; N, 3.39.
Found: C, 55.40; H, 3.09; N, 3.36.
Yield: 1.27 g (34%).
Monoselenomalonic Amide (6)
1H NMR (CDCl3, 100 MHz): d = 1.22 (t, 3 H, Me), 2.59 (s, 3 H, Me-
To an EtOH solution (15 mL) of cyanoacetic amide (4.20 g, 50.0
mmol) was added NH3 until pH 8 was attained. To the solution was
added freshly prepared P2Se5 (9.12 g, 20.0 mmol). Subsequently,
H2O (3 mL) was added dropwise to the refluxing solution over 2 h.
The solution was cooled and filtered. H2O was added to the filtrate,
which resulted in precipitation of 6.
Tol), 3.01–3.32 (q, 2 H, CH2), 7.22–7.46 (m, 5 H, Ar, 5-H).
MS (EI, 70 eV): m/z (%) = 250 (M+, 100).
Anal. Calcd for C12H13NSe (250.21): C, 57.61; H, 5.24; N, 5.60.
Found: C, 57.80; H, 5.30; N, 5.39.
2-Benzhydryl-4-phenyl-1,3-selenazole (4m)
This compound was obtained by reaction of diphenylselenoacetic
amide (2.74 g, 10.0 mmol) and phenacyl bromide (1.99 g, 10.0
mmol) in EtOH (30 mL) following the procedure as described for
4a.
Yield: 3.88 g (47%); brown needles (EtOH); mp 119.5–121 °C.
IR (KBr): 705 (m), 852 (m), 920 (m), 1098 (m), 1301 (s), 1399 (m),
1652 (s), 1995 (s), 3121 (m).
MS (EI, 70 eV): m/z (%) = 165 (M+, 100).
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1,3-Selenazoles and Bis(selenazoles) from Selenocarboxylic Amides and Selenourea
881
Anal. Calcd for C3H6N2OSe (165.05): C, 21.83; H, 3.66; N, 16.97.
Found: C, 21.81; H, 3.52; N, 21.97.
Yield: 0.488 g (57%); yellow needles (EtOH); mp 107 °C.
IR (KBr): 725 (s), 770 (s), 795 (m), 815 (s), 1021 (m), 1071 (m),
1121 (m), 1305 (w), 1401 (w), 1431 (m), 1511 (s) cm–1.
1H NMR (CDCl3, 100 MHz): d = 4.99 (s, 2 H, CH2), 7.00–8.25 (m,
12 H, Ar, 5-H).
(4¢-Phenyloxazolyl-2¢-yl)-4-phenylselenazolyl-2-methane (7)
A mixture of monoselenomalonic amide (0.33 g, 2.0 mmol) and
phenacyl bromide (0.8 g, 4.0 mmol) in EtOH (15 mL) was stirred
for 20 min with evolution of heat. After cooling with ice, a crystal-
line product formed, which was was filtered off and recrystallized
(EtOH) to give 7.
1,2-Bis(4-phenylselenazol-2-yl)ethane (10b)
This compound was obtained by reaction of diselenosuccinic amide
(0.24 g, 1.0 mmol) and phenacyl bromide (0.40 g, 2.0 mmol) in
EtOH (10 mL) as described for 7.
Yield: 0.35 g (48%); colorless lamella; mp 197 °C.
IR (KBr): 699 (m), 725 (m), 776 (m), 901 (w), 1027 (m), 1124 (m),
1310 (w), 1426 (m), 1506 (m), 3196 (m) cm–1.
1H NMR (DMSO-d6, 200 MHz): d = 4.34 (s, 2 H, CH2), 7.27–7.70
(m, 12 H, Ar, 2 × 5-H, Hetar).
MS (EI, 70 eV): m/z (%) = 366 (M+, 100).
Yield: 0.06 g (13%); colorless needles (EtOH); mp 130.5–132 °C.
IR (KBr): 935 (w), 1030 (m), 1191 (m), 1290 (m), 1445 (m), 3080
(w), 3120 (w) cm–1.
1H NMR (CDCl3, 100 MHz): d = 3.62–3.65 (m, 4 H, CH2), 7.29–
7.86 (m, 12 H, ArH and 5-H).
Anal. Calcd for C19H14N2OSe: (365.29): C, 62.47; H, 3.86; N, 7.67.
Found: C, 62.41; H, 3.91; N, 7.71.
MS (EI, 70 eV): m/z (%) = 442 (M+, 55).
Anal. Calcd for C20H16N2Se2 (442.28): C, 54.31; H, 3.64; N, 6.33.
Found: C, 54.22; H, 3.74; N, 5.95.
Diselenomalonic Amide (9a)
Malonic dinitrile (2.20 g, 33.0 mmol) was dissolved in pyridine (35
mL). To the solution was added freshly prepared P2Se5 (36.4 g, 80.0
mmol) and H2O (12 mL) in a Soxhelet tube. The mixture was shak-
en for 3 h. H2O was added to the solution which resulted in precip-
itation of a yellow solid. The crude product was dried (desiccator,
P2O5) and was recrystallized from EtOH to give 9a.
1,4-Bis(4-phenylselenazol-2-yl)butane (10c)
This compound was obtained by reaction of diselenoadipic amide
(0.27 g, 1.0 mmol) and phenacyl bromide (0.40 g, 2.0 mmol) in
EtOH (20 mL) as described for 7.
Yield: 0.10 g (21%); light brown needles (EtOH); mp 108–110 °C.
Yield: 3.93 g (52%); yellow prisms; mp 97 °C (decomp.).
IR (KBr): 835 (s), 920 (w), 1036 (m), 1080 (w), 1101 (w), 1190 (w),
1285 (w), 1325 (w), 1445 (m), 1525 (s), 3030 (w), 3081 (w), 3118
(w) cm–1.
1H NMR (DMSO-d6, 100 MHz): d = 1.92 (m, 4 H, 2 CH2), 3.13 (m,
4 H, 2 CH2), 7.38–7.94 (m, 10 H, Ar), 8.50 (s, 2 H, 5-H).
MS (EI, 70 eV): m/z = 470 (M+, 42), 392 (21), 250 (91), 236 (77),
234 (44), 224 (28), 182 (68), 102 (100), 77 (9), 28 (3).
IR (KBr): 630 (m), 890 (m), 965 (s), 995 (m), 291 (s) 1365 (m),
1456 (s), 1650 (s) cm–1.
MS (CI): m/z (%) = 229 (M+, 100).
Anal. Calcd for C3H6N2Se2 (228.01): C, 15.80; H, 2.65; N, 12.28.
Found: C, 15.75; H, 2.60; N, 12.44.
Diselenosuccinic Amide (9b)
Anal. Calcd for C22H20N2Se2 (470.33): C, 56.18; H, 4.29; N, 5.96.
Found: C, 56.25; H, 4.31; N, 6.10.
Succinic dinitrile (3.20 g, 40.0 mmol) was dissolved in EtOH (10
mL). To the solution was added freshly prepared P2Se5 (9.12 g, 20.0
mmol). H2O (5 mL) was added dropwise to the refluxing solution
over 2.5 h. The hot solution was filtered. After cooling, the solution
was again filtered and H2O was added to the filtrate, which resulted
in precipitation of 9b. The product was dried (desiccator, P2O5).
Selenourea (12)18
Cyanamide (4.10 g, 100.0 mmol) was dissolved in H2O (20 mL). To
the refluxing solution was added freshly prepared P2Se5 (9.12 g,
20.0 mmol) in small portions over 3 h. The solution was subse-
quently refluxed for 1 h. The solution was cooled to give a precipi-
tate. The precipitate was filtered off, recrystallized from H2O and
dried (desiccator, P4O10) to give 12.
Yield: 1.20 g (12%); yellow prisms; the product decomposed during
recrystallization from EtOH, so therefore the mp is not reported.
IR (KBr): 1165 (m), 1475 (s), 1620 (s) cm–1.
Yield: 4.50 g (37%); colorless needles; mp 204–206 °C.
IR (KBr): 1110 (w), 1415 (w), 1495 (s), 1630 (s) cm–1.
MS (CI): m/z (%) = 243 (M+, 100).
Anal. Calcd for C4H8N2Se2 (242.04): C, 19.85; H, 3.33; N, 11.57.
Found: C, 19.90; H, 3.42; N, 11.65.
Anal. Calcd for CH4N2Se (123.02): C, 9.76; H, 3.28; N, 22.77.
Found: C, 9.81; H, 3.32; N, 22.67.
Diselenoadipic Amide (9c)
2-Amino-5-phenyl-1,3-selenazole (13a)
Method A
This compound was obtained by reaction of adipic dinitrile (4.30 g,
40.0 mmol) with freshly prepared P2Se5 (9.12 g, 20.0 mmol) as de-
scribed for 9a.
An EtOH solution (30 mL) of selenourea (1.23 g, 10.0 mmol) and
phenacyl bromide (1.99 g, 10.0 mmol) was briefly refluxed and the
hot solution was filtered. After cooling of the filtrate to 20 °C, aq
NH3 (2 mL, concd) and, subsequently, H2O (20 mL) were added. A
precipitate formed, which was recrystallized from EtOH–H2O to
give 13a.
Yield: 1.60 g (16%); yellow prisms; the product decomposed during
recrystallization from EtOH, so therefore the mp is not reported.
IR (KBr): 1135 (m), 1355 (m) 1475 (s), 1655 (s) cm–1.
MS (CI): m/z (%) = 268 (M+, 100).
Yield: 1.94 g (87%); colorless needles; mp 131–132 °C.
Anal. Calcd for C6H12N2Se2 (270.09): C, 26.68; H, 4.48; N, 10.37.
Found: C, 26.50; H, 4.50; N, 10.10.
IR (KBr): 825 (s), 900 (m), 1198 (m), 1325 (s), 1571 (s), 1608 (s),
1665 (s), 3130 (m), 3376 (m), 3478 (m) cm–1.
Bis(4-phenylselenazol-2-yl)methane (10a)
1H NMR (DMSO-d6, 300 MHz): d = 7.41–7.69 (m, 6 H, Ar, 1 H, 5-
H), 9.00 (s, br, 2 H, NH2).
This compound was obtained by reaction of diselenomalonic amide
(0.45 g, 2.0 mmol) and phenacyl bromide (0.80 g, 4.0 mmol) in
EtOH (20 mL) as described for 7.
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13C NMR (DMSO-d6, 75 MHz): d = 126.02, 129.13, 129.27,
UV (EtOH): lmax (log e) = 300 (3.92), 345 nm (4.39).
130.12, 139.29, 174.22, 201.14.
Anal. Calcd for C9H7N2BrSe (302.03): C, 35.79; H, 2.34; N, 9.28.
Found: C, 35.88; H, 2.31; N, 9.29.
77Se NMR (DMSO-d6, 60% Me2Se in CDCl3): d = 556.40.
MS (70 eV): m/z (%) = 224 (M+, 86), 182 (82), 102 (100), 80 (19),
77 (14), 51 (13), 28 (26).
Method B
A mixture of 2-benzoylamino-4-(4¢-bromophenyl)-1,3-selenazole
15c (4.06 g, 10.0 mmol) was refluxed in aq H2SO4 (68%, 60 mL) for
1.5 h. The work up was carried out as described for 13a (Method B).
UV (EtOH): lmax (log e) = 235 (4.36), 289 nm (3.82).
Anal. Calcd for C9H8N2Se (223.14): C, 48.45; H, 3.61; N, 12.55.
Found: C, 48.51; H, 3.72; N, 12.62.
Yield: 2.77 g (91%); colorless needles; mp 175 °C.
Method B
2-Amino-4-(4-nitrophenyl)-1,3-selenazole (13d)
Method A
This compound was obtained by reaction of selenourea (1.23 g, 10.0
mmol) with 4-nitrophenacyl bromide (2.44 g, 10.0 mmol) in EtOH
(60 mL) following the procedure as described for 13a.
2-Benzoylamino-4-phenyl-1,3-selenazole 15a (3.27 g, 10.0 mmol)
was refluxed in aq H2SO4 (68%, 60 mL) for 30 min. The benzoic
acid was removed by steam distillation. After cooling, the solution
was poured into H2O (200 mL) and was neutralized by addition of
aq NaOH (10%). The precipitated product was filtered off and re-
crystallized from C6H6 to give 13a.
Yield: 2.44 g (91%); brown rods (HOAc); mp 250 °C.
IR (KBr): 729 (m), 1300 (s),1550 (s), 1650 (s) cm–1.
Yield: 1.83 g (84%); colorless needles; mp 132 °C.
1H NMR (CDCl3, 300 MHz): d = 5.31 (br s, 2 H, NH2), 7.15–7.77
2-Amino-4-tolyl-1,3-selenazole (13b
(m, 4 H, ArH), 7.21 [s, 1 H, 5-H, 2J (SeH) = 48.60 Hz].
Method A
13C NMR (DMSO-d6, 75 MHz): d = 111.37 (C-5), 124.09 (CH, Ar),
126.86 (CH, Ar), 136.08 (Ar), 139.02 (Ar), 146.82 (C-4), 173.00
(C-2).
MS (70 eV): m/z (%) = 269 (M+, 100), 239 (7), 226 (26), 197 (14),
181 (12), 142 (5), 117 (4), 101 (6), 89 (54), 77 (6), 75 (10), 51 (6).
A mixture of selenourea (1.23 g, 10.0 mmol) and 4-methylphenacyl
bromide (2.13 g, 10.0 mmol) in EtOH (50 mL) was refluxed for 5
min. The hot solution was filtered. After cooling, a solution of NH3
(5 mL, concd) was added to the filtrate to give a crystalline precip-
itate. The precipitate was filtered, washed with H2O and recrystal-
lized (EtOH) to give 13b.
UV (EtOH): lmax (log e) = 266 (4.04), 361 nm (4.02).
Yield: 1.99 g (84%); colorless needles (EtOH); mp 168 °C.
Anal. Calcd for C9H7N3O2Se (268.13): C, 40.32; H, 2.63; N, 15.67.
Found: C, 40.38; H, 2.61; N, 15.74.
IR (KBr): 688 (m), 726 (s), 823 (s), 1028 (s), 1185 (m), 1285 (m),
1300 (s), 1321 (s), 1494 (m), 1521 (s), 1522 (s), 1556 (s), 1599 (s),
1646 (m), 3029 (m), 3108 (m) cm–1.
Method B
A mixture of 2-benzoylamino-4-(4¢-nitrophenyl)-1,3-selenazole
15d (3.72 g, 10.0 mmol) was refluxed in aq H2SO4 (70%, 75 mL)
for 2 h. The work up was carried out as described for 13a (Method
B). The crude product was treated with hot EtOH and was recrystal-
lized (HOAc) to give 13d.
1H NMR (CDCl3, 300 MHz): d = 2.35 (s, 3 H, Me), 5.49 (br s, 2 H,
NH2), 7.15–7.67 (m, 4 H, Ar), 7.21 [s, 1 H, 5-H, 2J (SeH) = 50.30
Hz].
13C NMR (CDCl3, 75 MHz): d = 20.71 (Me), 107.23 {C-5, 1J [(C-
5)Se] = 97.11 Hz}, 126.24 (Ar), 129.25 (Ar), 132.85 (Ar), 137.30
(Ar), 152.08 (C-4), 168.89 {C-2, 1J [(C-2)Se] = 126.70 Hz}.
Yield: 2.66 g (99%); brown rods; mp 250 °C.
77Se (CDCl3, Me2Se): d = 591.28.
MS (EI, 70 eV): m/z (%) = 238 (M+, 100), 236 (44), 196 (71), 194
2-Amino-4,5-diphenyl-1,3-selenazole (13e)
Method A
A mixture of selenourea (1.23 g, 10.0 mmol) and desyl bromide
(2.75 g, 10.0 mmol) in EtOH (50 mL) was refluxed for 30 min. Af-
ter cooling with ice, a crystalline precipitate was formed. The pre-
cipitate was filtered off and washed with Et2O. The free base of 13e
was obtained by addition of aq NH3 (concd) to an ethanolic solution
of the hydrobromide.
(37), 116 (46), 114 (91), 91 (15), 77 (3), 64 (12), 51 (6), 28 (36).
UV (EtOH): lmax (log e) = 238 (4.38), 289 nm (3.90).
Anal. Calcd for C10H10N2Se: (237.16): C, 50.64; H, 4.25; N, 11.81.
Found: C, 50.68; H, 4.31; N, 11.76.
Method B
Yield: 2.02 g (68%); colorless needles (EtOH); mp 199–201 °C.
1H NMR (DMSO-d6, 200 MHz): d = 7.12–7.38 (m, 10 H, Ar).
13C NMR (DMSO-d6, 50 MHz): d = 124.28 (C-5), 126.65 (CH, Ar),
127.05 (CH, Ar), 127.90 (CH, Ar), 128.57 CH, Ar), 128.85 (CH,
Ar), 129.22 (CH, Ar), 135.08 (Ar), 136.08 (Ar), 145.70 (C-4),
167.13 (C-2).
2-Benzoylamino-4-tolyl-1,3-selenazole 15b (3.77 g, 10.0 mmol)
was refluxed in aq H3PO4 (85%, 60 mL) for 2 h. The work up was
carried out as described for 13a (Method B).
Yield: 1.21 g (51%); colorless needles (EtOH); mp 168 °C.
2-Amino-4¢-bromophenyl-1,3-selenazole (13c)
Method A
MS (EI, 70 eV): m/z (%) = 300 (M+, 100), 258 (22), 220 (8), 193 (6),
A mixture of selenourea (1.23 g, 10.0 mmol) and 4-bromophenacyl
bromide (2.76 g, 10.0 mmol) in EtOH (60 mL) was refluxed for 10
min. After cooling, aq NH3 (5 mL, concd) and H2O (20 mL) were
added. The precipitated product was filtered off and recrystallized
from C6H5 to give 13c.
178 (78), 152 (7), 128 (4), 110 (3), 89 (6), 51 (2).
UV (EtOH): lmax (log e) = 241 (4.29), 329 nm (3.91).
Anal. Calcd for C15H12N2Se (299.23): C, 60.21; H, 4.04; N, 9.36.
Found: C, 60.21; H, 4.31; N, 9.46.
Yield: 2.84 g (94%); colorless needles; mp 175 °C.
Method B
1H NMR (CDCl3, 300 MHz): d = 5.40 (br s, 2 H, NH2), 7.30–7.87
A mixture of 2-benzoylamino-4,5-diphenyl-1,3-selenazole 15e
(3.72 g, 10.0 mmol) was refluxed in aq H2SO4 (68%, 60 mL) for 2
h. The work up was carried out as described for 13a (Method B).
(m, 4 H, ArH), 7.21 [s, 1 H, 5-H, 2J (SeH) 48.30 Hz].
MS (EI, 70 eV): m/z (%) = 302/304 (M+, 100), 260/262 (40), 180/
182 (24), 111 (9), 101 (20), 89 (12), 78/80 (12), 51 (6).
Yield: 2.84 g (95%); colorless rods (EtOH); mp 199–201 °C.
Synthesis 2004, No. 6, 875–884 © Thieme Stuttgart · New York

PAPER
1,3-Selenazoles and Bis(selenazoles) from Selenocarboxylic Amides and Selenourea
883
2-Benzoylamino-4-phenyl-1,3-selenazole (15a)
2-Benzoylamino-4,5-diphenyl-1,3-selenazole (15e)
A mixture of benzoylselenourea (2.30 g, 10.0 mmol) and phenacyl
bromide (1.99 g, 10.0 mmol) in acetone (20 mL) was refluxed for
20 min. After cooling to 20 °C, aq NH3 (4 mL, concd) was added to
give a crystalline precipitate. The precipitate was recrystallized
from EtOH to give 15a.
A mixture of benzoylselenourea (2.30 g, 10.0 mmol) and desyl bro-
mide (2.75 g, 10.0 mmol) in acetone (20 mL) was refluxed for 20
min. The work-up was carried out as described for 15a.
Yield: 3.63 g (90%); colorless prisms (EtOH); mp 170 °C.
Anal. Calcd for C22H16N2OSe (403.34): C, 65.51; H, 4.00; N, 6.95.
Found: C, 65.61; H, 3.99; N, 6.92.
Yield: 3.23 g (99%); colorless needles; mp 165.5 °C.
IR (KBr): 901 (w), 1030 (w), 1066 (w), 1089 (w), 1198 (w), 1305
(s), 1575 (s), 1685 (s), 3080 (w) cm–1.
2-Amino-4-imino-4,5-dihydro-1,3-selenazole Hydrochloride
(16)
1H NMR (CDCl3, 200 MHz): d = 2.17 (s, 1 H, NH), 7.31–7.78 (m,
Selenourea (0.98 g, 8.0 mmol) was dissolved in hot EtOH (30 mL).
An EtOH solution of chloroacetonitrile (0.60 g, 8.0 mol) was neu-
tralized with pyridine and the solution was added dropwise, and the
mixture was refluxed for 5 min. After cooling, a colorless precipi-
tate formed which was filtered off to give 16.
10 H, Ar), 7.82 [s, 1 H, 5-H, 2J(SeH) = 47 Hz].
13C NMR (CDCl3, 50 MHz): d = 113.26 (5-C, Hetar), 126.22 (CH,
Ar), 127.30 (CH, Ar), 127.71 (CH, Ar), 128.58 (CH, Ar), 128.73
(CH, Ar), 131.78, 132.72, 135.23, 150.61, 160.75 (C), 165.41
(C=O).
MS (EI, 70 eV): m/z (%) = 328 (M+, 34), 326 (17), 182 (6), 105
(100), 77 (75), 51 (16), 28 (2).
Yield: 0.90 g (56%); colorless prisms (EtOH–Et2O); mp 198.5 °C.
1H NMR (DMSO-d6, 200 MHz): d = 4.57 (s, 2 H, 5-CH2), 9.90 (s,
+
2 H, NH2), 10.44 (br s, 2 H, =NH2 ).
UV (EtOH): lmax (log e) = 241 (4.43), 276 (4.23), 317 nm (3.92).
13C NMR (DMSO-d6, 50 MHz): d = 35.13 (CH2), 183.92 (C-4),
184.54 (C-2).
MS (EI, 70 eV): m/z (%) = 162 (M+, 38).
Anal. Calcd for C16H12N2OSe (327.23): C, 58.73; H, 3.70; N, 8.56.
Found: C, 58.81; H, 3.82; N, 8.72.
2-Benzoylamino-4-tolyl-1,3-selenazole (15b)
Anal. Calcd for C3H6N3ClSe (198.51): C, 18.15; H, 3.04; N, 21.17.
Found: C, 18.21; H, 3.01; N, 20.91.
A mixture of benzoylselenourea (2.30 g, 10.0 mmol) and 4-meth-
ylphenacyl bromide (2.13 g, 10.0 mmol) in acetone (20 mL) was re-
fluxed for 20 min. The work-up was carried out following the
procedure as given for 15a.
2-Hydrazino-4,5-diphenyl-1,3-selenazole (18)
To a solution of selenosemicarbazide (1.38 g, 10.0 mmol) was add-
ed EtONa [prepared from sodium (0.46 g) and EtOH (20 mL). A so-
lution of desyl bromide (2.75 g, 10.0 mmol) in anhyd EtOH (20 mL)
was added dropwise within 30 min at 20 °C with stirring. The solu-
tion was subsequently allowed to stand at 20 °C for 1 h. The precip-
itated product was filtered off and recrystallized (EtOH) to give 18.
Yield: 3.00 g (88%); colorless lamella (EtOH); mp 186–187 °C.
IR (KBr): 721 (s), 1300 (s), 1563 (s), 1617 (w) cm–1.
MS (EI, 70 eV): m/z (%) = 342 (M+, 100).
UV (EtOH, nm): lmax (log e) = 244 (4.39), 273 (4.25), 322 nm
(3.85).
Yield: 2.20 g (70%); colorless needles (EtOH); mp 199–200 °C.
1H NMR (CDCl3, 300 MHz): d = 7.05–7.48 (m, 10 H, Ar).
MS (EI, 70 eV): m/z (%) = 315 (M+, 25), 298 (8), 282 (4), 258 (8),
218 (14), 206 (8), 190 (4), 178 (100), 152 (10), 126 (3), 105 (6), 86
(24), 63 (9), 51 (19).
Anal. Calcd for C17H14N2OSe (341.27): C, 59.83; H, 4.13; N, 8.21.
Found: C, 58.81; H, 4.22; N, 8.22.
2-Benzoylamino-4-(4¢-bromophenyl)-1,3-selenazole (15c)
A mixture of benzoylselenourea (2.30 g, 10.0 mmol) and of 4-bro-
mophenacyl bromide (2.78 g, 10.0 mmol) in acetone (20 mL) was
refluxed for 20 min. The work-up was carried out following the pro-
cedure as described for 15a.
Anal. Calcd for C15H13N3Se (314.25): C, 57.33; H, 4.17; N, 13.37.
Found: C, 57.21; H, 4.31; N, 13.36.
Yield: 3.89 g (96%); colorless lamella (BuOH); mp 231 °C.
MS (EI, 70 eV): m/z (%) = 406 (M+, 100).
Acknowledgement
Financial support from the Deutsche Forschungsgemeinschaft
(Heisenberg-scholarship for P. L.) is gratefully acknowledged.
UV (EtOH, nm): lmax (log e) = 246 (4.42), 283 (4.34), 320 nm
(3.87).
Anal. Calcd for C16H11N2BrOSe (406.14): C, 47.32; H, 2.73; N,
6.90. Found: C, 47.31; H, 2.72; N, 6.92.
References
(1) Schwar, K.; Foltz, C. M. J. Am. Chem. Soc. 1957, 79, 3292.
(2) Mills, G. C. J. Biol. Chem. 1957, 229, 189.
2-Benzoylamino-4-(4¢-nitrophenyl)-1,3-selenazole (15d)
A mixture of benzoylselenourea (2.30 g, 10.0 mmol) and 4-nitro-
phenacyl bromide (2.44 g, 10.0 mmol) in acetone (20 mL) was re-
fluxed for 20 min. The work-up was carried out following the
procedure as described for 15a.
(3) Rotruck, J. T.; Pope, A. E.; Ganther, H. E.; Swanson, A. B.;
Hafemann, D. G.; Hoekstra, W. G. Science 1973, 179, 588.
(4) Goldstein, B. M.; Kennedy, S. D.; Hennen, W. J. J. Am.
Chem. Soc. 1990, 112, 8265; and references cited therein.
(5) (a) Larsen, R. 1,3-Selenazoles, In Comprehensive
Heterocyclic Chemistry II, Vol. 3; Katritzky, A.; Rees, C.
W.; Scriven, E. F. V., Eds.; Eds. Elsevier Science: Oxford,
1996, Chap. 8. (b) Wirth, T. Organoselenium Chemistry.
Modern Developments in Organic Synthesis; Springer:
Berlin, 2000. (c) Koketsu, M.; Nada, F.; Ishihara, H.
Synthesis 2002, 195; and references cited therein.
Yield: 3.27 g (88%); colorless lamella (BuOH); mp 239 °C.
IR (KBr): 721 (s), 1313 (s), 1516 (s), 1605 (s), 1671 (s) cm–1.
MS (EI, 70 eV): m/z (%) = 372 (M+, 100).
UV (EtOH): lmax (log e) = 233 (4.39), 260 (4.14), 330 nm (3.62).
Anal. Calcd for C16H11N3O3Se (372.24): C, 51.63; H, 2.98; N,
11.29. Found: C, 51.61; H, 2.92; N, 11.22.
(d) Geisler, K.; Pfeiffer, W.-D.; Müller, C.; Nobst, E.; Bulka,
E.; Langer, P. Synthesis 2003, 1215.
Synthesis 2004, No. 6, 875–884 © Thieme Stuttgart · New York

884
K. Geisler et al.
PAPER
(15) For the synthesis of N,N-disubstituted selenocarboxylic
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Synthesis 2004, No. 6, 875–884 © Thieme Stuttgart · New York