The reactions of 2-(chloroseleno)benzoyl chloride with nucleophiles

Article abstract of DOI:10.1016/S0040-4020(02)00789-5

The reactions of 2-(chloroseleno)benzoyl chloride with N, O and S nucleophiles such as alkanols, aminoalkanols, phenols, thiols, aminothiols and thiophenols have been investigated. It was found that the most reactive was a primary amino group which simult

Full text of DOI:10.1016/S0040-4020(02)00789-5

Tetrahedron 58 (2002) 7531–7537
The reactions of 2-(chloroseleno)benzoyl chloride
with nucleophiles
*
Mariusz Osajda and Jacek Młochowski
´
Institute of Organic Chemistry, Biochemistry and Biotechnology, Wrocław University of Technology, Wyb. Wyspianskigo 27,
50-375 Wrocław, Poland
Received 4 December 2001; revised 17 June 2002; accepted 4 July 2002
Abstract—The reactions of 2-(chloroseleno)benzoyl chloride with N, O and S nucleophiles such as alkanols, aminoalkanols, phenols, thiols,
aminothiols and thiophenols have been investigated. It was found that the most reactive was a primary amino group which simultaneously
underwent selenenylation–acylation. Less reactive hydroxy and thiol groups were selenenylated and/or acylated depending on the structure
of the substrate and reaction conditions. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
inchided aminocarboxylic acids,9 aminoalkylphospho-
nates,17 carboxyamides and sulfonamides,18 pyrrolidine
N-oxide substituted with a phenylamino group,19 or
compounds with active methylene groups (ketones and
other C–H acids).20,21 Acylation of methanol with
2-(chloroseleno)benzoyl chloride was mentioned by Lesser
et al.22,23 but in these old papers no structural evidence was
provided. Most recently, the reaction of two long-chain
alkanols was reported but diselenides were found as the final
products.24
Organoselenium compounds have been extensively applied
in organic synthesis, materials synthesis, ligand chemistry
and biologically relevant processes.1,2 Among them benz-
isoselenazol-3(2H )-ones (particularly ebselen) play an
important role in biology and medicine as biological
response modifiers, mainly antiinflammatory agents.3,4 In
our previous work, some of these compounds were synthe-
sized and reported as immunostimulants and virucides.
They exhibited modest activity as inducers of different
cytokines, such as interferons (mainly IFN-g), tumor
necrosis factor (IFN-a), interleukines (IL-2, IL-6), and
other factors in human peripheral blood leukocyte cul-
tures.5–9 Moreover, some of them were active as inhibitors
of endothelial nitric oxide synthase (ce NOS).9–11 Although
some methods for their synthesis are known most of them
were synthesized starting from 2-(chloroseleno)benzoyl
chloride (1), a well known and easy to obtain reagent.6,9,12–14
To the best of our knowledge, no information concerning
the reactions of 2-(chloroseleno)benzoyl chloride with a
broad spectrum of different mono and bisnucleophiles
such as phenols, diols aromatic alcohols, aminoalkanols,
hydroxylamine, aminophenols, thiols, dithiols and amino-
thiols has been published. The main goal of the work
presented here was to generalize the competition of both
electrophilic centers of 2-(chloroseleno)benzoyl chloride
toward N, O and S nucleophiles particularly to these having
two nucleophilic centers in the molecule.
This particular compound has two different electrophilic
centers. One of them (hard electrophilic center) is localized
on the carbonyl carbon atom and the second one (soft
electrophilic center) is the selenium atom. Both of these
centers may compete toward nucleophiles such as amine
nitrogen, thiol sulfur and hydroxide oxygen atoms.
Although many reactions of 2-(chloroseleno)benzoyl
chloride with nucleophiles have been studied, the majority
of the reactants were primary aromatic, aliphatic and
heteroaromatic amines6,12– 16 or compounds having a
primary amino group and other functional groups com-
pletely inactive toward acylation or selenylation. They
2. Results and discussion
The first group of nucleophiles used in this work were
hydroxy compounds—some alkanols, diols and hydroxy-
arenes (phenol and catechol) (Scheme 1). The reagent (1)
was added stepwise to the nucleophile in the ratio 1:1 or 1:3
(sometimes the nucleophile was used in a larger excess).
The alkanols (ethanol and 1-dodecanol), 1,4-butanediol and
benzyl alcohol reacted with the hard electrophilic center
of chloride (1) localized on the carbonyl carbon atom.
O-Acylation proceeded faster than O-selenenylation and
stable 2-(chloroseleno)benzoates (2a–2d) were formed,
even when the alcohol was used in a large excess. Acid
Keywords: nucleophiles; acylation; selenium halogen compounds;
selenium heterocycles.
*
Corresponding author. Tel.: þ48-71-3202419; fax: þ48-71-3284064;
e-mail: mlochowski@kchf.ch.pwr.wroc.pl
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00789-5

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M. Osajda, J. Młochowski / Tetrahedron 58 (2002) 7531–7537
Scheme 1.
hydrolysis of these esters gave 2,20-diselenobisbenzoates
(3a–3d) (Scheme 1). This provides the evidence that the
chloroseleno (and not the chlorocarbonyl group) was
present in the starting 2. Otherwise 2,20-dielenobisbenzoic
acid (7) should have formed.
of (9) resulted in 2,20-diselenobis(benzoic acid) (7) and
confirmed proposed structure.
Aminoalkanols reacted with chloride (1) only at the amino
group since its reactivity toward acylation and selenenyl-
ation was substantially higher than reactivity of the hydroxy
group, and 2-(hydroxyalkyl)benzisoselenazol-3(2H )-ones
(8a–8c) were produced (Scheme 2). Reaction of ortho and
meta aminophenols with 2-(chloroseleno)benzoyl chloride
(1) gave only tarry mixtures of unidentified products but
when an electron-withdrawing moiety such as a carboxylic
acid group or pyridine nitrogen atom was present in the
aromatic ring, the corresponding 2-substituted bensiso-
selenazol-3(2H )-ones (10, 11) were produced in high
Phenol reacted differently. C-Selenenylation of the aromatic
ring, in the para position, instead of O-selenenylation
of the hydroxy group, took place, and selenide (5) was
produced. Catechol and ethylene glycol also reacted with
2-(chloroseleno)benzoyl chloride 1 in a different way to
alkanols, 1,4-butanediol and benzyl alcohol. In this case,
O-selenenylation proceeded faster than O-acylation and
2-(ethoxyseleno)benzoyl chlorides (6, 4) were formed. Acid
hydrolysis of the products (6, 4) to known 2,20-diseleno-
bis(benzoic acid) (7)25 (Scheme 1) confirmed the proposed
structure.
1
yields. The IR and H NMR spectra of compounds (8, 10,
11) are characteristic for 2-substitued benzisoselenazol-
3(2H )-ones and similar to these reported earlier for other
compounds of this class.6,9,14
It has been known that when diamines are treated with
chloride (1) both amino groups react and bisbenzisoselena-
zol-3(2H )-ones are produced.14 We expected that in the
case of compounds having amino and hydroxy groups
both of them would react with the electrophilic centers
of chloride (1). When chloride (1) was treated with
hydroxylamine, the reaction proceeded in this way and
cyclic diselenide (9) was produced, but it was an exception.
In the IR spectrum of diselenide (9) two nCvO absorption
bands at 1654 and 1705 cm21 for OvC–N and OvC–O
groups, respectively, were observed.26 The acid hydrolysis
The third group of reactants investigated were S-nucleo-
philes—thiols, dithiols, and thiophenol (Scheme 3).
Generally, thiols reacted differently to O-nucleophiles and
selenenylation of the sulfur atom was preferred. When
the chloride (1) was treated with equimolar amount of
1-propanethiol only S-selenenylation, took place and
selenosulfide (13) was formed. When the same thiol was
used in a large excess, both S-selenenylation and S-acylation
proceeded giving selenosulfide (16). 2-Mercaptoethanol and
thiophenol reacted in a similar way producing the

M. Osajda, J. Młochowski / Tetrahedron 58 (2002) 7531–7537
7533
Scheme 2.
corresponding selenosulfides (12) and (14) while 1,2-etha-
nethiol gave cyclic product 0(15). Acid hydrolysis of the
selenosulfides (12–14) to 2,2 -diselenobis(benzoic acid) (7)
is a proof that in all of these compounds the chlorocarbonyl
group is present and confirmed the proposed structures. The
broad absorption bands nCO, in the IR spectra of
the compounds (14–16) (1661–1745 cm21) are similar to
these nCO values observed for compounds which have
OvC–S group such as 3-chloropropylthioacetate
(nCO¼1680 cm21).26
Scheme 3.

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M. Osajda, J. Młochowski / Tetrahedron 58 (2002) 7531–7537
Scheme 4.
Aminothiols reacted in a similar way to aminoalkanols
(Scheme 4). Since reactivity of the amino group toward
selenenylation–acylation was substantially higher than
reactivity of the thiol group, the nitrogen atom of
the amino group was incorporated into the heterocyclic
ring and 2-thioalkyl or thioarylbenzisoselenazol-3(2H )-
ones (17–19) were formed. Similarly, their IR and 1H
NMR spectra compared to these of other 2-substitued
benzisoselenazol-3(2H )-ones6,9,14 confirmed proposed
structures.
4. Experimental
All reagents and solvents were purchased from Aldrich or
Fluka. 2-(Chloro-seleno)benzoyl chloride (1) was prepared
according to the literature.4 Melting points were determined
with a Digital Melting Point Apparatus Electrothermal IA
9100. H NMR and 13C NMR spectra were recorded in
1
DMSO-d6 on a Bruker DRX 300 spectrometer 300 MHz.
Chemical shifts d are reported in ppm relative to TMS. For
compounds 2a, 10, 13, 19, selected as representatives of
each class of compounds, 13C NMR spectra were recorded.
IR spectra were measured on a Perkin–Elmer 2000 FT
spectrometer.
3. Conclusions
4.1. Reaction of chloride (1) with alkanols, diols and
phenols
It has been found that 2-(chloroseleno)benzoyl chloride
reacts with N, O and S nucleophiles as selenenylating,
acylating or as a tandem selenenylating–acylating bis-
electrophile. The results of the reactions depend on the
nucleophile and the molar ratio of the reagents. Selenenyl-
ation of thiols, catechol and ethylene glycol proceeded
faster than acylation. For alkanols, 1,4-butanediol and
benzyl alcohol different process was observed (O-acylation
proceeded faster than O-selenenylation). In the case of
phenol, selenylation took place on the carbon atom of the
aromatic ring activated by the para hydroxy group. These
results can be explained in terms of the hard and soft acid
and base theory (HSAB principle).27 The sulfur atom in
thiols, being a soft nucleophilic center, is selenylated
preferentially, and subsequent acylation takes place when
the thiol is used in excess. The oxygen atoms in catechol,
ethylene glycol or the 4-carbon atom in an aromatic ring
being softer nucleophilic centers than oxygen atoms in
alkanols, benzyl alcohol or 1,4-butanediol are selenylated
while the later are acylated. It should be noted that
compounds with Se–Cl, Se–O and Se–S bonds are
susceptible toward hydrolysis producing 2,20-diselenobis-
(benzoic acid) (7) or its carboxyesters.
A solution of chloride (1) (0.51 g, 2 mmol) in dry
acetonitrile (15 mL) was added dropwise at room tempera-
ture over a period of 30 min to a stirred solution of alcohol
(2 mmol) (and triethylamine 0.7 mL, in the case of product
5) in dry acetonitrile (45 mL) and the reaction was
continued for an additional 2 h. When the reaction
was completed, acetonitrile was evaporated in vacuo and
the crude products were recrystallized from acetonitrile.
4.1.1. Ethyl 2-(chloroseleno)benzoate (2a). Yellow tiny
needles (0.32 g, 61%), mp 85–888C; [Found: C, 41.30; H,
3.70; Cl, 13.32. C9H9O2SeCl requires C, 41.01; H, 3.44;
Cl, 13.45%]; nmax (KBr) 1616, 2983, 2939 cm21; dH
(300 MHz, DMSO-d6) 1.46 (t, 3H, J¼7.2 Hz, CH3), 4.51
(q, 2H, J¼7.2 Hz, CH2), 7.34–7.39 (m, 1H, Ar-H ), 7.65–
7.70 (m, 1H, Ar-H), 8.02–8.07 (m, 2H, Ar-H ); dC (300
MHz, DMSO-d6) 13.89, 64.21, 124.03, 125.97, 126.84,
131.6, 135.26, 142.60, 172.00.
4.1.2. Dodecyl 2-(chloroseleno)benzoate (2b). Yellow tiny
needles (0.45 g, 56%), mp 43–458C; [Found: C, 56.22;
H, 6.95; Cl, 8.54. C19H29O2SeCl requires C, 56.52; H, 7.19;
Cl, 8.80%]; nmax (KBr) 1635, 2855, 2927, 2955 cm21; dH
(300 MHz, DMSO-d6) 1.45 (t, 3H, J¼7.3 Hz, CH3), 4.30–
4.55 (m, 22H, CH2), 7.30–7.45 (m, 2H, Ar-H ), 8.05–8.10
(m, 2H, Ar-H ).
Among N, O and S nucleophiles, a primary amino group is
the most susceptible towards selenenylation and acylation.
Although it is difficult to predict which reaction proceeds
initially, the final result is ring closure. Thus aminothiols,
aminoalkanols and aminophenols form 2-thioalkyl-,
2-thioaryl-, 2-hydroxyalkyl- and 2-(hydroxyaryl)benziso-
selenazol-3(2H )-ones. Since this reaction is highly chemo-
selective it opens a way for the synthesis of new biological
response modifiers of this class starting from aminopolyols,
aminosugars and nucleosides. We hope that the results
presented in this work will be useful to those seeking new
bioactive structures based on selenium-containing
heterocycles.
4.1.3. Benzyl 2-(chloroseleno)benzoate (2c). Yellow
powder (0.36 g, 55%), mp 66–698C; [Found: C, 51.36; H,
3.94. C14H11O2SeCl requires C, 51.61; H, 3.38%]; nmax
(KBr) 1629, 3030 cm21; dH (300 MHz, DMSO-d6) 5.47 (s,
2H, CH2), 7.30–7.55 (m, 6H, Ar-H ), 7.69 (t, 1H, J¼7.5 Hz,
Ar-H ), 8.06 (t, 2H, J¼7.6 Hz, Ar-H).
4.1.4. 4-Hydroxybutyl 2-(chloroseleno)benzoate (2d).

M. Osajda, J. Młochowski / Tetrahedron 58 (2002) 7531–7537
7535
Yellow tiny crystals (0.35 g, 57%), mp 60–628C; [Found:
4.3. Reaction of chloride (1) with hydroxylamine and
aminoalkanols
C, 45.14; H, 4.93; Cl, 12.12. C11H13O2SeCl requires C,
45.30; H, 4.50; Cl, 12.68%]; nmax (KBr) 1630, 2874, 2942,
3067, 3358 cm21; dH (300 MHz, DMSO-d6) 1.59–1.92 (m,
8H, CH2), 4.49 (s, 1H, OH ), 7.36–8.03 (m, 4H, Ar-H ).
A solution of chloride (1) (0.51 g, 2 mmol) (and 6 mmol
CaO in case 9) in dry acetonitrile (15 mL); (in case of 11,
15 mL DMF) was added dropwise at room temperature over
a period of 30 min to a stirred solution of hydroxylamine
hydrochloride and aminoalkanol or aminophenol (2 mmol)
in dry acetonitrile (45 mL) (in case 11, 45 mL DMF) and
the reaction was continued for additional 2 h. When the
reaction was completed, acetonitrile (DMF in case 11) was
evaporated in vacuo. Product 8b was recrystallized from
water; product 9 from acetonitrile. Water (100 mL) was
added to the residue, the mixture was stirred for 12 h and the
product 10 was filtered off, dried in air and recrystallized
from DMSO/acetonitrile (4:1). Product 11 was extracted
with ethanol (30 mL) and recrystallized from the same
solvent; the compounds 8a, 8c were extracted with
dichloromethane (30 mL) and recrystallized from
acetonitrile.
4.1.5. 2-[(2-Hydroxyethyloxy)selena]benzoyl chloride
(4). White prisms (0.29 g, 52%), mp 128–1298C; [Found:
C, 38.50; H, 3.31; Cl, 12.72. C9H9O3SeCl requires C,
38.62; H, 3.25; Cl, 12.68%]; nmax (KBr) 1698, 2878, 2948,
3285 cm21; dH (300 MHz, DMSO-d6) 3.76 (t, 2H, J¼
4.7 Hz, CH2), 4.38 (t, 2H, J¼4.8 Hz, CH2), 4.38 (s, 1H,
OH), 7.41 (t, 1H, J¼7.4 Hz, Ar-H ); 7.54 (t, 1H, J¼7.3 Hz,
Ar-H ), 7.69 (d, 1H, J¼4.0 Hz, Ar-H ), 8.14 (d, 1H, J¼
4.0 Hz, Ar-H ).
4.1.6. 2-[(2-Hydroxyphenyl)selena]benzoyl chloride (5).
Yellow powder (0.45 g, 72%), mp 173–1748C; [Found: C,
50.22; H, 2.70; Cl, 11.28. C13H9O2SeCl requires C, 50.10;
H, 2.89; Cl, 11.40%]; nmax (KBr) 1605, 3368 cm21; dH
(300 MHz, DMSO-d6) 7.03 (d, 2H, J¼4.4 Hz, Ar-H), 7.66
(t, 1H, J¼7.7 Hz, Ar-H ), 7.89 (d, 2H, J¼4.4 Hz, Ar-H ),
7.96 (t, 1H, J¼7.7 Hz, Ar-H ), 8.33 (d, 1H, J¼4.0 Hz,
Ar-H ), 8.38 (d, 1H, J¼3.9 Hz, Ar-H ), 10.78 (s, 1H, OH ).
4.3.1. 2-(4-Hydroxyphenyl)benzisoselenazol-3(2H )-one
(8a). White powder (0.54 g, 93%), mp 94–968C; [Found:
C, 53.80; H, 3.10; N, 4.85. C13H9O2NSe requires C, 53.81;
H, 3.13; N, 4.83%]; nmax (KBr) 1639, 3260 cm21; dH
(300 MHz, DMSO-d6) 6.84–6.79 (m, 2H, Ar-H ), 7.31–
7.35 (m, 2H, Ar-H ), 7.44 (t, 1H, J¼7.5 Hz, Ar-H ), 7.64 (t,
1H, J¼7.6 Hz, Ar-H ), 8.06 (d, 1H, J¼3.9 Hz, Ar-H ), 8.86
(d, 1H, J¼3.9 Hz, Ar-H), 9.57 (s, 1H, Ar-OH ).
4.1.7. 2-[(2-Hydroxyphenoxy)selena]benzoyl chloride
(6). Beige powder (0.66 g, 71%), mp 159–1618C; [Found:
C, 47.80; H, 2.87; Cl, 10.80. C13H9O3SeCl requires C,
47.66; H, 2.77; Cl, 10.82%]; nmax (KBr) 1715, 3422 cm21
;
dH (300 MHz, DMSO-d6) 6.16–8.33 (m, 8H, Ar-H ), 9.67
(bs, 1H, OH ).
4.3.2. 2-(4-Hydroxyethyl)benzisoselenazol-3(2H )-one
(8b). Yellow tiny crystals (0.30 g, 85%), mp 142–1458C;
[Found: C, 44.52; H, 3.64; N, 5.87. C9H9NO2Se requires C,
44.67; H, 3.72; N, 5.79%]; nmax (KBr) 1593, 2842, 2921,
3224 cm21; dH (300 MHz, DMSO-d6) 3.58–3.63 (m, 2H,
CH2), 3.79 (t, 2H, J¼5.4 Hz, N–CH2), 5.07 (s, 1H, OH ),
7.39 (t, 1H, J¼7.4 Hz, Ar-H), 7.58 (t, 1H, J¼7.5 Hz, Ar-H ),
7.80 (d, 1H, J¼7.8 Hz, Ar-H ), 8.01 (d, 1H, J¼7.8 Hz,
Ar-H ).
4.2. Acid hydrolysis of esters (2) and compounds (4, 6, 9,
12, 13)
The hydrolyzed compound (2 mmol) was poured into water
(30 mL), the reaction mixture was stirred for 24 h
and formed solid was filtered off. Diselenides (3a–3d) or
2,20-diselenobis(benzoic acid) (7) thus obtained were dried
in vacuo and recrystallized from hexane–ethyl acetate.
4.3.3. 2-(4-Hydroxyethoxyethyl)benzisoselenazol-3(2H )-
one (8c). White needles (0.39 g, 68%), mp117–1198C;
[Found: C, 46.12; H, 4.58; N, 5.10. C11H13NO2Se2 requires
C, 46.00; H, 4.55; N, 4.89%]; nmax (KBr) 1578, 2902,
3486 cm21; dH (300 MHz, DMSO-d6) 3.64–3.67 (m, 2H,
CH2), 3.73–3.83 (t, 4H, J¼5.4 Hz, CH2–O–CH2), 4.12 (t,
2H, N–CH2), 7.39–7.44 (m, 1H, Ar-H ), 7.56–7.64 (m, 2H,
Ar-H ), 8.06 (d, 1H, J¼7.8 Hz, Ar-H ).
4.2.1. Diethyl 2,20-diselenobisbenzoate (3a). Beige powder
(0.86 g, 94%), mp 1328C;24 1328C.
4.2.2. Didodecyl 2,20-diselenobisbenzoate (3b). Yellow
powder (1.18 g, 80%), mp 728C;24 728C.
4.2.3. Dibenzyl 2,20-diselenobisbenzoate (3c). White
powder (0.95 g, 85%), mp 1088C; [Found: C, 57.80; H,
3.84. C28H22O4Se2 requires C, 57.95; H, 3.79%]; nmax
(KBr) 1690 cm21; dH (300 MHz, DMSO-d6) 5.42 (s, 4H,
CH2), 7.20–7.52 (m, 12H, Ar-H ), 7.65–8.05 (m, 6H,
Ar-H ).
4.3.4. Compound 9. Orange powder (0.37 g, 47%), mp 85–
868C; [Found: C, 42.27; H, 2.30; N, 3.20. C14H9NO3Se2
requires C, 42.31; H, 2.27; N, 3.52%]; nmax (KBr) 1654,
1705, 3433 cm21; dH (300 MHz, DMSO-d6) 4.42 (bs, 1H,
OH ), 7.35–8.37 (m, 8H, Ar-H).
4.2.4. Di(4-hydroxybutyl) 2,20-diselenobisbenzoate (3d).
Yellow powder (1.00 g, 92%), mp 125–1278C; [Found: C,
48.11; H, 4.35. C22H26O6Se2 requires C, 48.55; H, 4.78%];
nmax (KBr) 1686, 3330 cm21; dH (300 MHz, DMSO-d6)
1.45–1.80 (m, 16H, CH2), 4.45 (s, 2H, OH ), 7.30–8.09 (m,
8H, Ar-H ).
4.3.5. 2-[2-(3-Hydroxypyridyl)]benzisoselenazol-3(2H )-
one (10). Beige powder (0.22 g, 74%), mp 199–2018C;
[Found: C, 49.32; H, 2.77; N,9.39. C12H8N2O2Se requires
C, 49.50; H, 2.75; N, 9.63%]; nmax (KBr) 1624, 2573,
3056 cm21; dH (300 MHz, DMSO-d6) 7.18–7.26 (m, 1H,
Ar-H ), 7.36 (d, 1H, J¼4.0 Hz, Ar-H ), 7.49 (t, 1H, J¼
7.5 Hz, Ar-H ), 7.71 (t, 1H, J¼7.6 Hz, Ar-H ), 7.92–8.03
(m, 2H, Ar-H ), 8.09 (d, 1H, J¼4.0 Hz, Ar-H ), 12.15 (s, 1H,
4.2.5. 2,20-Diselenobisbenzoic acid (7). White powder
(84–90%), mp 2958C;25 296–2978C.

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M. Osajda, J. Młochowski / Tetrahedron 58 (2002) 7531–7537
OH ); dC (300 MHz, DMSO-d6) 123.70, 126.26, 126.73,
127.59, 128.53, 129.78, 133.43, 138.87, 140.89, 142.87,
145.11, 165.59.
Ar-H ), 8.07–8.15 (m, 1H, Ar-H ), 8.26–8.35 (m, 1H,
Ar-H ).
4.4.5. S-Propyl 2-[(propylthio)seleno]benzoate (16).
Yellow oil (59%); [Found: C, 46.82; H, 5.09; S, 19.11.
C13H18OS2Se requires C, 43.28; H, 4.59; S, 19.23%]; nmax
(KBr) 1694, 2929, 2961 cm21; dH (300 MHz, DMSO-d6)
0.95 (t, 6H, J¼15 Hz, CH3), 1.55–1.68 (m, 4H, CH2), 2.76
(t, 2H, J¼7.2 Hz, S–CH2), 3.07 (t, 2H, J¼7.2 Hz, S–CH2),
7.47 (t, 1H, J¼4.0 Hz, Ar-H ), 7.72 (d, 1H, J¼4.0 Hz,
Ar-H ), 8.15 (t, 1H, J¼4.0 Hz, Ar-H ), 8.24 (d, 1H, J¼
4.0 Hz, Ar-H ).
4.3.6. 2-(4-Carboxy-3-hydroxyphenyl)benzisoselenazol-
3(2H )-one (11). White powder (0.39 g, 45%), mp 190–
1958C; [Found: C, 50.26; H, 2.74; N, 4.41. C14H9NO2Se
requires C, 50.30; H, 2.69; N, 4.19%]; nmax (KBr) 1605,
1651, 3055, 3421 cm21; dH (300 MHz, DMSO-d6) 7.26–
7.29 (m, 1H, Ar-H ), 7.43–7.52 (m, 2H, Ar-H ), 7.69 (t, 1H,
J¼7.5 Hz, Ar-H ), 7.83 (d, 1H, J¼4.1 Hz, Ar-H ), 7.91 (d,
1H, J¼4.0 Hz, Ar-H ), 8.07 (d, 1H, J¼4.0 Hz, Ar-H ),
10.43–14.00 (m, 2H, OH; COOH ).
4.5. Reaction of chloride (1) with aminothiol and
aminothiophenols
4.4. Reaction of chloride (1) with thiols and thiophenol
A solution of chloride (1) (0.51 g, 2 mmol) in dry
dichloromethane (15 mL) were added stepwise at room
temperature over a period of 30 min to a stirred mixture of
thiol (2 mmol) and BaO (0.31 g, 4 mmol) in dry dichloro-
methane (45 mL) and the reaction was continued for
additional 2 h. The insoluble Ba(OH)2 and BaCl2 were
filtered off. From the filtrate, dichloromethane was evapo-
rated in vacuo. Products 12 and 13 were recrystallized
from dichloromethane; 14 from toluene; 15 and 16 from
acetonitrile.
A solution of chloride (1) (0.51 g, 2 mmol) in dry
acetonitrile (15 mL) was added dropwise at room tempera-
ture over a period of 30 min to a stirred solution of
aminothiol or aminophenol (6 mmol) in dry acetonitrile
(45 mL) and the reaction was continued for additional 2 h.
When the reaction was completed, acetonitrile was
evaporated in vacuo. Water (100 mL) was added to the
residue, the mixture was stirred for 12 h and the precipitate
solid was filtered off and dried in air. The products 17–19
were recrystallized from DMSO/acetonitrile (3:1).
4.4.1. 2-[(2-Hydroxyethylthio)seleno]benzoyl chloride
(12). Yellow tiny prisms (0.31 g, 59%), mp 94–968C;
[Found: C, 36.02; H, 3.10; S, 11.04. C9H9O2SSeCl requires
C, 36.56; H, 3.05; S, 10.83%]; nmax (KBr) 1635, 2950,
3055, 3436 cm21; dH (300 MHz, DMSO-d6) 2.86 (s, 1H,
OH ), 3.16–3.26 (m, 2H, CH2), 4.48–4.62 (m, 2H, CH2),
7.37 (t, 1H, J¼7.5 Hz, Ar-H ), 7.47 (d, 1H, J¼3.6 Hz,
Ar-H ), 7.67 (d, 1H, J¼3.6 Hz, Ar-H ), 8.22 (t, 1H, J¼
7.5 Hz, Ar-H).
4.5.1. 2-(2-Mercaptoethyl)benzisoselenazol-3(2H )-one
(17). Bright beige powder (0.44 g, 75%), mp 150–1528C;
[Found: C, 39.16; H, 3.45; N, 5.55. C8H9NOSeS requires C,
39.04; H, 3.66; N, 5.69%]; nmax (KBr) 1630, 2925 cm21; dH
(300 MHz, DMSO-d6) 2.07 (s, 1H, SH), 2.98–3.16 (m, 2H,
CH2), 3.19–3.32 (m, 2H, CH2), 7.35–8.23 (m, 4H, Ar-H ).
4.5.2. 2-(2-Mercaptophenyl)benzisoselenazol-3(2H )-one
(18). Brown powder (0.47 g, 80%), mp 179–1818C;
[Found: C, 51.51; H, 2.58; N,4.60. C13H9NOSe requires
C, 51.00; H, 2.94; N, 4.58%]; nmax (KBr) 1621, 3055 cm21
;
dH (300 MHz, DMSO-d6) 7.22–7.93 (m, 8H, Ar-H ), 10.67
(s, 1H, SH).
4.4.2. 2-(2-Propylthioseleno)benzoyl chloride (13). Beige
powder (0.39 g, 66%), mp 67–688C, [Found: C, 40.90; H,
3.80; S, 10.95; Cl, 12.11. C10H11OSSeCl requires C, 40.90;
H, 3.78; S, 10.92; Cl, 12.07%]; nmax (KBr) 1636, 2872,
2931, 2964, 3060 cm21; dH (300 MHz, DMSO-d6) 1.04
(t, 3H, J¼7.2 Hz, CH3), 1.76 (t, 2H, J¼7.2 Hz, CH2), 3.16–
3.19 (m, 2H, CH2), 7.38 (d, 1H, J¼3.4 Hz, Ar-H ), 7.68
(d, 1H, J¼3.4 Hz, Ar-H ), 8.12 (t, 2H, J¼8.0 Hz, Ar-H ). dC
(300 MHz, DMSO-d6) 13.21, 22.22, 22.31, 64.20, 126.61,
126.72 129.82, 131.60, 133.96, 144.97.
4.5.3. 2-(4-Mercaptophenyl)benzisoselenazol-3(2H )-one
(19). Yellow powder (0.40 g, 66%), mp 139–1418C;
[Found: C, 51.22; H, 3.16; N, 4.70. C13H9NOSe requires
C, 51.00; H, 2.94; N, 4.58%]; nmax (KBr) 1646, 3286 cm21
;
dH (300 MHz, DMSO-d6) 7.27–8.03 (m, 8H, Ar-H ), 10.67
(s, 1H, SH ); dC (300 MHz, DMSO-d6) 122.00, 122.40,
126.80, 127.84, 129.41, 130.24, 130.64, 131.50, 132.54,
133.00, 134.04, 136.45, 174.00.
4.4.3. S-Phenyl 2-[(phenylthio)seleno]benzoate (14).
Yellow powder (0.34 g, 55%), mp 278–2798C; [Found: C,
56.00; H, 3.39; S, 16.05. C19H14OS2Se requires C, 56.87; H,
3.49; S, 15.93%]; nmax (KBr) 1745 cm21; dH (300 MHz,
DMSO-d6) 7.27–7.43 (m, 4H, Ar-H ) 7.59 (t, 1H, J¼7.7 Hz,
Ar-H ), 7.66 (d, 2H, J¼4.0 Hz, Ar-H ), 7.73 (d, 1H, J¼
4.0 Hz, Ar-H ), 8.03 (t, 2H, J¼7.8 Hz, Ar-H ), 8.17 (d, 1H,
J¼4.0 Hz, Ar-H ).
Acknowledgments
This work was supported by the Polish State Committee for
Scientific Research (grant No 3T09A 097 17).
4.4.4. 1,2,5-Selenadithiabenzcyclooctan-6-one
(15).
White prisms (0.33 g, 45%), mp124–1268C; [Found: C,
39.30; H, 3.00; S, 23.66. C9H8OS2Se requires C, 39.27; H,
2.91; S, 23.27%]; nmax (KBr) 1661 cm21; dH (300 MHz,
DMSO-d6) 2.96–3.09 (m, 2H, CH2), 3.36–3.43 (m, 2H,
CH2), 7.30 (t, 1H, J¼8.0 Hz, Ar-H ), 7.60 (t, 1H, J¼8.0 Hz,
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