Synthesis and structure determination of some monothio- and dithioimides derived from succinic and glutaric acids

Article abstract of DOI:10.1080/10426500902856404

A series of novel 5-thioxopyrrolidin-2-ones and 6-thioxopiperidin-2-ones was synthesized using Lawesson's reagent in thionation of the appropriate imides. The NMR data were determined, and in one case the structure assignment was additionally supported by

Full text of DOI:10.1080/10426500902856404

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Synthesis and Structure
Determination of Some
Monothio- and Dithioimides
Derived from Succinic and
Glutaric Acids
Michał Pawłowski a , Anna Lendzion a , Joanna
Szawkało a , Andrzej Leniewski a , Jan K. Maurin b c
& Zbigniew Czarnocki a
a Faculty of Chemistry , Warsaw University , Warsaw,
Poland
b National Medicines Institute , Warsaw, Poland
c Institute of Atomic Energy , Otwock-Świerk, Poland
Published online: 28 Apr 2009.
To cite this article: Michał Pawłowski , Anna Lendzion , Joanna Szawkało , Andrzej
Leniewski , Jan K. Maurin & Zbigniew Czarnocki (2009) Synthesis and Structure
Determination of Some Monothio- and Dithioimides Derived from Succinic and Glutaric
Acids, Phosphorus, Sulfur, and Silicon and the Related Elements, 184:5, 1307-1313,
DOI: 10.1080/10426500902856404
To link to this article: http://dx.doi.org/10.1080/10426500902856404
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Phosphorus, Sulfur, and Silicon, 184:1307–1313, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902856404
Synthesis and Structure Determination of Some
Monothio- and Dithioimides Derived from Succinic
and Glutaric Acids
Michal Pawlowski,1 Anna Lendzion,1 Joanna Szawkalo,1
ꢀ
ꢀ
ꢀ
Andrzej Leniewski,1 Jan K. Maurin,2,3
and Zbigniew Czarnocki1
1Faculty of Chemistry, Warsaw University, Warsaw, Poland
2National Medicines Institute, Warsaw, Poland
3
´
Institute of Atomic Energy, Otwock-Swierk, Poland
A series of novel 5-thioxopyrrolidin-2-ones and 6-thioxopiperidin-2-ones was syn-
thesized using Lawesson’s reagent in thionation of the appropriate imides. The
NMR data were determined, and in one case the structure assignment was addi-
tionally supported by X-ray crystallography.
Keywords Lawesson reagent; regioselectivity; thioamides; thionation reaction
INTRODUCTION
Thiocarboxoamides and thiocarboxoimides are still the subject of in-
tense investigations by organic chemists. They proved to be valuable
intermediates in agriculture and medicine.1,2 Their sophisticated and
rich reactivity3 make them important intermediates in several aspects
of synthetic organic chemistry. Thioamides undergo a broad spectrum
of chemical transformations, for example the oxidation to carbonyl
compounds,4 the reduction to amines,5 or conversion to nitriles.6 De-
protonation of thioamides produces highly reactive anions capable of a
variety of condensation reactions7 as well as Michael-type additions
to unsaturated ketones.8 Thioamides also undergo several types of cy-
clization reactions, including electrophile-induced additions to olefins9
Received 14 January 2008; accepted 29 January 2008.
Dedicated to Professor Marian Mikolajczyk, CBMiM PAN in Lo´dz´, Poland, on the
ꢀ
ꢀ
occasion of his 70th birthday.
Financial support from grants PBZ-KBN-126/T09/2004/13 and 501/68-BW-175610 is
gratefully acknowledged.
Address correspondence to Zbigniew Czarnocki, Faculty of Chemistry, Warsaw Uni-
versity, Pasteura 1, 02-093 Warsaw, Poland. E-mail: czarnoz@chem.uw.edu.pl
1307

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M. Pawlowski et al.
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and the Rh(II)-catalyzed reaction of α-diazomethyl vinyl ketones bear-
ing a thioamido substituent.10 Remarkable chiral memory effect was
observed upon a photochemical asymmetric synthesis of a phenyl-
bearing quaternary chiral center.11 In this article, we present the syn-
thesis of a series of thioimides derived from succinic and glutaric acids,
along with some spectroscopic and single crystal X-ray data.
RESULTS AND DISCUSSION
In continuation of our ongoing interest in reactivity of amides and
imides and the influence of the Ingold–Thorpe effect on tautomeric
equilibria, we have recently studied the regioselectivity of the reac-
tion of phenyllithium with differently substituted succinimides and
glutarimides.12 Interestingly, we observed some unexpected differences
in the products distribution and their structures in the case of five- and
six-membered ring system. Since the thionation reaction, upon treat-
ment of imides with the Lawesson’s reagent (LR),2 is an important
method for thioimides formation, we decided to investigate the pro-
cess for a series of differently substituted imides. Thus, we reacted an
equimolar amount of the Lawesson’s reagent and appropriate imides in
boiling toluene. After completion of the reaction and subsequent column
chromatography, the products were recrystallized from the appropriate
solvent (see Table I). It is already known that 3,3-dimethylsuccinimide
1 exhibits a high degree of regioselectivity, and under analogous condi-
tions, it produces only 3,3-dimethyl-5-thioxopyrrolidin-2-one 3 in 51%
yield13 (Scheme 1).
SCHEME 1
Since the replacement of the hydrogen atom in the NH moiety in
succinimides sometimes caused a change in regioselectivity,12 we sub-
jected compound 2 to the thionation reaction. Apparently, steric con-
straints caused by α-dimethyl group constituted the major factor that
affected the mechanism of this reaction, and, as a consequence, the
sulfur atom was introduced at the less-hindered side of the molecule
to afford exclusively compound 4 in 47% yield. In the glutarimide

Thionation of Cyclic Imides
1309
series, a similar effect was observed. Thus, 3-methylglutarimide 5,
3,3-dimethylglutarimide 6, and 3,3,4,4-tetramethylglutarimide 7 were
thionated at the C-6 position, giving mono-thioimides 8, 9, and 11 in
moderate yields (Scheme 2).
SCHEME 2
Surprisingly, in the case of compound 6, the double thionation was
also observed, and compound 10 was formed in 23% yield together with
the monothio derivative 9 (52% yield).
The structures of all new compounds were derived on the basis of
their NMR (1H and 13C) spectra and MS measurements. The differen-
tiation between possible regioisomers of monothio compounds is based
on the strong deshielding effect of the C S group seen in the 13C NMR
spectra.13 Moreover, in the case of the tetramethylderivative 11, we
were able to grow single crystals suitable for an X-ray study that served
as unambiguous proof for its structure (Figure 1).
As is shown in the Figure 1, the independent part of the unit cell con-
sists of two molecules differing slightly in their conformation and molec-
ular geometry. The centrosymmetry-related molecules denoted with
“un-primed” numbers are bonded through N-H· · ·O hydrogen bonds to
form dimers, which are arranged in sheets perpendicular to the a-axis
and intersecting it at 0, 0, 0 and 1, 0, 0. They are separated by sheets
of “primed” molecules, which form N-H· · ·S hydrogen bonds with the
neighbor “un-primed” molecules. The crystal packing is depicted in Fig-
ure 2.
EXPERIMENTAL
The NMR spectra were recorded with a Varian Unity Plus spectrom-
1
eter operating at 200 MHz for H NMR and at 50 MHz for 13C. The
spectra were measured in CDCl3 and are given as δ values (in ppm)

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M. Pawlowski et al.
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FIGURE 1 Molecular structure of compound 11 in the crystal, independent
part of the unit cell; thermal ellipsoids are drawn at 50% probability level.
relative to TMS. Mass spectra were recorded with a LCT Micromass
apparatus. TLC analyses were performed on silica gel plates (Merck
Kiesegel GF254) and visualized using UV light or iodine vapor. Column
chromatography was carried out using Silica Gel 60 (230–400 mesh,
FIGURE 2 The crystal packing of compound 11.

1311

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M. Pawlowski et al.
ꢀ
Merck) using mixtures of chloroform/methanol or hexane/ethyl acetate
as eluents. Melting points were determined on a Boetius hot-plate mi-
croscope and were uncorrected. All solvents used in the reactions were
anhydrous. The single crystal X-ray measurements were done with a
KUMA KM4 CCD κ-axis diffractometer with point scintillation counter
using MoKα radiation. After initial corrections and data reduction, in-
tensities of reflections were used to solve and consecutively refine struc-
tures using the SHELXS9714 and SHELXL9715 programs. In the final
structure refinement, the analytical absorption correction was applied
to the collected reflections.
Thionation of Imides 2, 5–7: General Procedure
2.5 mmol of the appropriate imide12 and 2.5 mmol (1.01 g) of the Lawes-
son’s reagent in 200 mL of toluene were refluxed under argon atmo-
sphere for ca. 1.5 h. The progress of the reaction was monitored by
TLC. The solution was cooled to ambient temperature and evaporated
to dryness. The residue was subjected to column chromatography on
silica gel, and the crude product thus obtained was recrystallized (see
Table I). The spectroscopic data and physical properties of the products
were collected in Table I.
X-ray crystallographic data for 11: crystal dimensions: 0.6 × 0.6
× 0.6 mm3,C9H15NOS, M = 185.28, P21/c monoclinic space group, a =
13.211(3), b = 12.463(3), c = 12.365(3) Å, β = 101.53(3)◦, Z = 8, ρ = 1.234
g/cm3, T = 293(2) K, λ(MoKα) = 0.71073 Å, µ(MoKα) = 0.280 mm−1
,
F(000) = 800. 5228 reflections were collected. The final R1 = 0.0495 and
wR2 = 0.1447, for 3160 reflections with I > σ(I). The detailed structural
data were deposited with the Cambridge Crystallographic Data Center
under the deposition number CCDC 674008.
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