Synthesis of selenium derivatives of 3-hydroxy-2-substituted-2,3- dihydroisoindol-1-ones

Article abstract of DOI:10.1080/10426500902947849

Regiospecific transformation of 3-hydroxy-2-substituted-2,3- dihydroisoindol-1-ones into their aryl and alkyl 7-selenium derivatives, via metallation and subsequent reaction with diselenides, is described.

Full text of DOI:10.1080/10426500902947849

Phosphorus, Sulfur, and Silicon, 184:1502–1507, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902947849
Synthesis of Selenium Derivatives of
3-Hydroxy-2-substituted-2,3-dihydroisoindol-1-ones
1
1
´
´ ´
Magdalena Ciechanska, Andrzej Jozwiak, and Jacek
Scianowski
2
´
1Department of Organic Chemistry, Faculty of Chemistry, University of
Lꢀ o´dz´, Lꢀ o´dz´, Poland
2Department of Organic Chemistry, Faculty of Chemistry, Nicolaus
Copernicus University, Torun´, Poland
Regiospecific transformation of 3-hydroxy-2-substituted-2,3-dihydroisoindol-1-
ones into their aryl and alkyl 7-selenium derivatives, via metallation and sub-
sequent reaction with diselenides, is described.
Keywords Diselenides; isoindolinones; ortho-lithiation; selenides
INTRODUCTION
The dihydroisoindolin-1-ones are central building blocks in a very large
number of biologically active products,1,2 and moreover they are regios-
electively deprotonated with organolithium compounds3,4 or lithium
amides.5,6 The reaction of lithium reagents with diselenides is known
as a method for preparing disymmetric selenides.7–14 The synthesis
and reactivity of compounds containing a disubstituted selenide moiety
also have been studied, due to their biological activities and chemical
properties.15–18
Recently we have described a convenient methodology of the synthe-
sis of optically active dialkyl diselenides, their properties, and applica-
tions in asymmetric synthesis.19–22
Received 9 January 2008; accepted 7 February 2008.
Dedicated to Professor Marian Mikolꢀajczyk, CBMiM PAN in Lꢀ o´dz´, Poland, on the
occasion of his 70th birthday.
The authors are grateful to the Rector of the University of Lꢀ o´dz´ for financial sup-
port (Grant No. 505/684).
Address correspondence to Andrzej Jo´z´wiak, Department of Organic Chemistry, Fac-
ulty of Chemistry, University of Lꢀ o´dz´, Narutowicza 68, 90-136 Lꢀ o´dz´, Poland. E-mail:
ajozwiak@uni.lodz.pl
1502

Selenium Derivatives of Some Dihydroisoindol-1-ones
1503
Herein, we wish to present our findings a one-pot procedure for the
conversion of isoindol-1-ones 1 into corresponding aryl and alkyl sele-
nium derivatives 2 (Scheme 1).
SCHEME 1
RESULTS AND DISCUSSION
The compounds 1 were initially treated with sec-butyllithium (sec-
BuLi, THF, TMEDA, −78◦C) and followed by the reaction with dis-
elenides 3–6 (Figure 1) were transformed to corresponding selenides
2a–2e (Figure 2).
Products 2c–2e, after the reactions, were separated by means of col-
umn chromatography as a mixture of diastereomers. The structures
1
of compounds 2a–2e were confirmed on the basis of the H, 13C, 77Se
NMR, and IR spectra analysis. In all cases, formation of small amounts
of 3-sec-butyl-2-(methyl or phenyl)-2,3-dihydro-isoindol-1-ones were
observed.
In summary, we have shown a regiospecific synthetic method for the
preparation of 7-selenium derivatives of 3-hydroxy-2-substituted-2,3-
dihydroisoindolinones such as 2a–2e.
FIGURE 1 The structures of diselenides 3–6.

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M. Ciechan´ska et al.
FIGURE 2 The structure of selenium derivatives of 2,3-dihydroisoindolinones
2a–2e.
EXPERIMENTAL
Melting points were determined using a Boetius hot-stage apparatus
and are uncorrected. 1H, 13C, and 77Se NMR spectra were recorded
on a Bruker Avance 300 and Varian Gemini 200 spectrometers at 300
and 200 MHz, respectively (J values are given in Hz). IR spectra were
recorded on a FT-IR NEXUS apparatus. High resolution mass spec-
tra were recorded on a Finnigan MAT 95. Reactions were carried out
under an argon atmosphere. Thin layer chromatography was carried
out on Merck silica gel plates (Kiselgel 60 F254, layer thickness 0.2)
and visualized using a UV lamp at 254 nm. Column chromatogra-
phy was performed on silica gel 60 (70–230 mesh) from Merck, us-
ing 30 g of silica gel per 1 g. sec-Buthyllithium (s-BuLi, Aldrich) and
diphenyl diselenide (3, Aldrich) were used without further purifica-
tion. Tetrahydrofuran (THF) was distilled from sodium benzophenone
prior to use. N, N, Nꢀ, Nꢀ-Tetramethylethylenediamine (TMEDA) from
Aldrich was distilled before use and stored over potassium hydrox-
ide pellets. 3-Hydroxy-2-methyl-2,3-dihydro-1H-isoindol-1-one (1a),23
5-chloro-3-hydroxy-2-phenyl-2,3-dihydro-1H-isoindol-1-one (1b),24 (+)-
dineomenthyl diselenide20 (4), (+)-dimenthyl diselenide20 (5), and (−)-
bis(cis-myrtanyl) diselenide19 (6) were prepared according to previously
used procedures.

Selenium Derivatives of Some Dihydroisoindol-1-ones
1505
Typical Procedure for the Preparation of Selenium Derivatives
of 3-Hydroxy-2-substituted-2,3-dihydroisoindol-1-ones
To a solution of (1) (0.002 mole) and TMEDA (0.004 mole) in THF (70 ml)
at –78◦C, s-BuLi (0.004 mole) was added. The solution was held at –78◦C
for 1.5 h, then diselenide (0.002 mole) in THF (20 mL)◦. The reaction
was warmed up to room temperature, and water was added (10 mL).
The mixture was adjusted to pH∼ 2 with hydrochloric acid. The organic
layer was separated and dried with magnesium sulfate. After evapora-
tion of solvents, a product was separated by column chromatography
(2a, 2c, 2d, 2e) or by precipitation 2b by addition of toluene.
3-Hydroxy-2-methyl-7-phenylselanyl-2,3-dihydro-isoindol-1-
one (2a)
The title compound was separated by column chromatography (chlo-
roform:acetone, 9:1; Rf = 0.15), yield 38%, mp 223–225◦C, (ethyl ac-
etate); IR (KBr) ν 1686 and 1675 cm−1 (C O); 1H NMR (200 MHz,
DMSO-d6): δ 7.80–7.20 (7H, m, H-Aryl), 6.65 (1H, dd J = 2.4 Hz, J =
6.1 Hz, H-Aryl), 6.59 (1H, d, J = 9.0 Hz, OH), 5.72 (1H, d, J = 9.0 Hz,
3-H), 2.95 (3H, s, NMe); 13C NMR (50 MHz, DMSO-d6): δ 166.1 (C),
145.9 (C), 137.1 (2x CH), 132.4 (CH), 131.7 (C), 130.1 (2x CH), 129.5
(CH), 128.3 (C), 127.1 (CH), 125.6 (C), 120.2 (CH), 82.1 (CH), 25.7 (Me);
77Se NMR (38 MHz, CDCl3): δ 425.9; HRMS Calcd for C15H13NO2Se:
319.0111, found: 319.0112.
5-Chloro-3-hydroxy-2-phenyl-7-phenylselanyl-2,3-dihydro-
isoindol-1-one (2b)
The title compound was precipitated by the addition of toluene, yield
42%, mp 262–264◦C (methanol); IR (KBr) ν 1697 and 1679 cm−1 (C O);
1H NMR (200 MHz, DMSO-d6): δ 7.84–7.38 (10H, m, H-Aryl), 7.30–7.19
(1H, m, H-Aryl), 6.99 (1H, d J = 9.7 Hz, OH), 6.62–6.48 (2H, m, 3-H and
H-Aryl); 13C NMR (50 MHz, DMSO-d6): δ 164.7 (C), 147.2 (C), 138.2
(C), 137.2 (2x CH), 136.9 (CH), 135.5 (C), 130.4 (2x CH), 130.1 (CH),
128.7 (2x CH), 126.7 (C), 126.6 (CH), 124.9 (CH), 124.8 (C), 122.1 (2x
CH), 120.4 (CH), 81.5 (CH); 77Se NMR (38 MHz, DMSO-d6): δ 444.9;
HRMS Calcd for C20H14ClNO2Se: 414.9878, found: 414.9877.
3-Hydroxy-2-methyl-7-neomenthylselanyl-2,3-dihydro-
isoindol-1-one (2c)
The title compound was separated as a mixture of diastereomers by
column chromatography (chloroform:acetone, 95:5; Rf = 0.14), yield
32%, mp 215–225◦C (decompose); IR (KBr) ν 1686 and 1671 cm−1
1
(C O); H NMR (200 MHz, DMSO-d6) δ 7.50–7.22 (3H, m, H-Aryl),

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M. Ciechan´ska et al.
6.50 (1H, d, J = 9.0 Hz, OH), 5.63 (1H, d, J = 9.0 Hz, 3-H), 4.00 (1H,
br.s, CH), 2.90 (3H, s, NMe); 2.00–0.95 (9H, m), 0.90 (3H, d, J = 6.6
Hz, Me), 0.83 (3H, d, J = 6.6 Hz, Me), 0.81 (3H, d, J = 6.6 Hz, Me); 13
C
NMR (50 MHz, DMSO-d6): δ 166.1 (C), 146.5, 146.4 (C), 132.4 (CH),
129.9, 129.8 (C), 129.4 (C), 127.5, 127.4 (CH), 119.8 (CH), 81.6, 81.5
(CH), 48.3, 48.2 (CH), 42.7, 42.3 (CH), 41.0, 40.8 (CH2), 34.6 (CH2),
31.2 (CH) 27.9, 27.8 (CH), 27.4, 27.3 (CH2), 25.7 (Me), 22.0 (Me), 20.9
(Me), 20.3 (Me); 77Se NMR (38 MHz, DMSO-d6): δ 288.5; HRMS Calcd
for C19H27NO2Se: 381.1207, found: 381.1208.
3-Hydroxy-2-methyl-7-menthylselanyl-2,3-dihydro-isoindol-1-
one (2d)
The title compound was separated as a mixture of diastereomers
by column chromatography (chloroform:acetone, 95:5, Rf = 0.15), yield
40%, glass-oil, IR (KBr) ν 1679 cm−1 (C O); 1H NMR (200 MHz, DMSO-
d6): δ 7.52–7.28 (3H, m, H-Aryl), 6.50 (1H, br.s, OH), 5.64 (1H, br.s, 3-H),
3.60–3.40 (1H, m, CH), 2.90 (3H, s, NMe), 2.35–2.05 (2H, m), 1.80–0.90
(7H, m), 0.88 (3H, d, J = 6.8 Hz, Me), 0.84–0.68 (6H, m, 2x Me); 13C
NMR (50 MHz, DMSO-d6): δ 166.1, 166.0 (C), 146.5, 146.4 (C), 132.2
(CH), 130.1, 130.0 (C), 129.7, 129.6 (C), 128.5, 128.4 (CH), 120.0, 119.9
(CH), 81.6, 81.5 (CH), 46.6, 46.5 (CH), 44.6, 44.6 (CH2), 42.8, 42.7 (CH),
34.3 (CH2), 33.2, 33.1 (CH), 28.8 (CH), 25.8, 25.7 (Me) 24.6 (CH2), 22.1
(Me), 21.2 (Me), 15.3 (Me); 77Se NMR (38 MHz, DMSO-d6): δ 377.4;
HRMS Calcd for C19H27NO2Se: 381.1207, found: 381.1208.
3-Hydroxy-2-methyl-7-myrtanylselanyl-2,3-dihydro-isoindol-1-
one (2e)
Title compound was separated as a mixture of diastereomers by
column chromatography (chloroform:acetone, 95:5; Rf = 0.08), yield
1
30%, mp 183–186◦C, (toluene), IR (KBr) ν 1675 cm−1 (C O); H NMR
(200 MHz, DMSO-d6): δ 7.50–7.27 (3H, m, H-Aryl), 5.65 (1H, d, J = 9.0
Hz, 3-H), 5.22 (1H, d, J = 9.0 Hz, OH), 3.08–2.92 (2H, m, CH2), 2.89
(3H, s, NMe), 2.36–2.20 (2H, m), 2.12–1.73 (5H, m), 1.68–1.50 (1H, m,
CH), 1.17 (3H, s, Me), 1.05 (3H, s, Me), 0.084 (1H, d, J = 9.8 Hz, CH);
13C NMR (50 MHz, DMSO-d6): δ 166.3 (C), 146.2 (C), 132.3(CH), 130.4
(C), 129.1 (C), 127.1 (CH), 119.6 (CH), 81.8 (CH), 45.8, 45.7 (CH), 40.7
(CH), 40.3 (CH), 38.3 (C), 32.9 (CH2), 30.4 (CH2), 27.8 (Me), 25.8(Me),
25.7 (CH2), 23.1 (Me), 22.6, 22.5 (CH2); 77Se NMR (38 MHz, DMSO-d6):
δ 286.7; HRMS Calcd for C19H25NO2Se: 379.1050, found: 379.1051.

Selenium Derivatives of Some Dihydroisoindol-1-ones
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